Guido Mazzoni’s terracotta Lamentation tableau created for the Duke of Ferrara, biblical characters perform their sorrow over Christ’s death in ways that reflect expectations for gendered emotional experience: the women are collectively far more violent than the men in their expressions of grief.
And men still have expectations to hide their emotions for the delusions of masculinity to this very day.
German artist Albrecht Dürer’s engraving of Adam and Eve includes numerous symbols associated with the four humors: a rabbit (blood), an ox (phlegm), a cat (yellow bile), and an elk (black bile)
But what do those symbols mean, and why were these specific animals chosen?
Notice that she does not look at the angel but is almost frightened. She knew that it was an angel…What would she have done had it been a man! Take this as an example you maidens!
The tale of the Virgin Mary.
Eve was the temptress who led the first man, Adam, into breaking God’s law, sentencing humankind to toil and death. Every woman thereafter was thought to live in the shadow of Eve’s sin, justly sentenced to the pains of childbirth, the labors of motherhood, and submission to her husband.
Is that why women don't get that much respect, unlike men, because of what Eve did? That's messed up.
gender refers to the social role that a person plays based upon individual and collective ideas about identity as it relates to being a man or a woman. Different cultures define masculinity and femininity differently. These social roles are constructed by multiple factors including medical understandings of the body and mind, as well as cultural and religious ideas about the sexes.
Society will always judge you when you do something the majority doesn't agree on. That's why prejudice and racism are still around, no matter how hard we fight back.
While he stands erect and linear, she sits, swathed in copious folds of costly fabric that suggest the rounded forms of her body. While he is active, she is passive, her containment within the domestic sphere affirmed by the window to her right. Eleonora’s bodily comportment is a far remove from her husband’s thrusting fist that intrudes upon the audience’s space. The small dog and the costly clock that rests upon the table beside her remind us of her loyalty and patience in reservedly awaiting her husband whose military pursuits often kept him abroad.
This was probably the norm that most men viewed women as. Their looks, alluring body, and physique rather than the inside of who they are.
Francesco Maria’s prominent codpiece and piercing stare emphasize his aggressive masculinity, while his dark beard and ruddy complexion mark him as a mature man of action.
His stance and presentable figure are what led men to believe he is the alpha and the omega.
Y recuerdo que después de esa reunión entre Cámpora y Perón le dije al General: “El proceso termina con usted en el balcón y de uniforme militar, como el símbolo de la unidad nacional”. Pero bueno, Cámpora creyó que era peligroso resaltarlo, que podían los militares reaccionar mal. Porque había habido todo tipo de condicionantes durante febrero. Entre otras cosas, un discurso de Lanusse, teóricamente ante mandos militares pero que había trascendido, en el que dijo que a pesar de todo él podía asegurar que el señor Perón nunca iba a volver a ser presidente de Argentina. Textual. En las Actas de la Junta hay cosas sensacionales. Por ejemplo, en la reunión de la Junta del 17 de noviembre (de 1972), por la tarde, Lanusse dice que el regreso ha sido una gran derrota de Perón. Que está prácticamente terminado como sujeto pensante.
!
Great work! I particularly appreciated the integration of comparative genomics, metabolomics, phenotypic assays, macrophage interactions, and in vivo infection models across multiple strains of both A. fumigatus and A. fischeri. The observation that several A. fischeri strains overlap with A. fumigatus in both macrophage assays and murine virulence models provides strong evidence that pathogenic potential may be better understood at the strain level rather than strictly at the species level.
I also found the proposed framework of "ecological fitting" and "environmental filtering" especially valuable, as it highlights the importance of considering both fungal traits and host susceptibility when studying opportunistic infections. The finding that no single virulence gene, biosynthetic gene cluster, or metabolite consistently explains pathogenicity reinforces the idea that virulence is a complex phenotype resulting from multiple interacting factors rather than a single genetic determinant.
To further strengthen the impact of these findings, it would be valuable to address how they translate to clinical realities. Since the conclusions are mainly based on murine models, the actual frequency of human infections caused by highly virulent environmental A. fischeri strains remains unclear. Additionally, because routine clinical identification heavily relies on morphology, cryptic species are likely underreported. Beyond addressing this potential misidentification in clinical settings, a compelling next step for this research would be to employ transcriptomic analyses (RNA-seq) during host-pathogen interactions. Since the authors found no statistical correlation based on the presence of genomic elements, investigating the differential expression of these genes under immune pressure could unveil the regulatory mechanisms driving the observed strain-level virulence. Overall, I believe this work provides an important contribution to our understanding of opportunistic fungal pathogenicity and opens several exciting directions for future research.
The authors are to be commended for the breadth and coherence of their multi-platform experimental design. The integration of PacBio HiFi genome assemblies, Iso-seq long-read transcriptomics, Illumina RNA-seq, and mass spectrometry proteomics across multiple species and tissues produces a robustly triangulated dataset that is difficult to dismiss. The use of independent lines of evidence to support each major claim; confirming venom gland expression of the hemostatic F10 paralog by both long-read isoform sequencing and short-read mapping, and then further validating protein presence by mass spectrometry,reflects commendable scientific rigor.
The comparative genomic framework is also well-constructed. By selecting outgroup species at carefully chosen phylogenetic distances; a non-venomous colubrid, an Asian elapid, an Australian elapid lacking vF5, and multiple sea snake species; the authors establish a clear evolutionary backdrop against which each genomic event can be contextualized. The synteny-based approach to tracing segmental duplications is particularly elegant, allowing the authors to reconstruct the order and boundaries of duplication events with high confidence.
Nevertheless, the study presents several methodological and inferential limitations that temper the strength of its conclusions. First, the argument for the temporal ordering of co-option and duplication rests on a most parsimonious basis rather than direct evidence. The authors propose that co-option preceded duplication for both F10 and F5 because residual expression of the liver-expressed paralogs is detectable in the venom gland today. However, this residual expression could equally reflect incomplete subfunctionalization after duplication or other post-duplication phenomena. The study cannot definitively exclude these alternatives, meaning the proposed sequential model remains a well-supported inference rather than a proven pathway.
Second, the study lacks functional experimentation for several of its key toxin candidates. This is most evident in the case of the procoagulant PLA₂ in O. microlepidotus, which the authors themselves describe as a "candidate" whose biochemical activity "has yet to be functionally validated". Similarly, the entire case for coagulation factor VII as a venom toxin is built exclusively on expression data and mass spectrometry protein detection, with no enzymatic assay provided to confirm its biological role in prey envenomation.
Third, the study draws broad conclusions about the evolutionary history of the entire Australian elapid radiation while only generating new genome assemblies for two in-group species: Pseudonaja textilis and Oxyuranus microlepidotus. Given the considerable diversity of the Hydrophiinae, deeper taxonomic sampling would be necessary to robustly support the proposed stepwise co-option model across the clade.
Fourth, the comparative analysis relies partly on a N. scutatus genome reassembled using ONT long-read sequencing, which is known to have accuracy limitations in homopolymeric regions. The authors acknowledge having to manually correct exonic indels where the F10 locus was initially absent, introducing a degree of subjectivity into a key outgroup comparison.
Finally, despite the introduction explicitly recognizing the importance of cis-regulatory mutations as the primary mechanism driving gene co-option in animal evolution, the study never characterizes how F10 and F5 came to be expressed in the venom gland at the molecular level. This omission represents a significant open question in an otherwise mechanistically detailed study.
4.7.1: Nested loops.
This last part was annoying. It was difficult to follow the numbers.
L'Évolution des Masculinités et l'Adaptation des Rapports de Domination
L’analyse des travaux de l'anthropologue Alix Boireau et de la chercheuse Laura Verkeré révèle que les masculinités contemporaines, bien qu'en apparence plus diverses ou « déconstruites », demeurent intrinsèquement liées à des rapports de pouvoir et de domination.
Que ce soit à travers le « tourisme festif » des jeunes hommes de classes populaires ou la figure de l'« homme nouveau » des classes supérieures, la masculinité fonctionne comme un système adaptatif.
Les points clés à retenir sont :
La plasticité de la domination : Le système patriarcal s'adapte aux critiques féministes en produisant de nouveaux modèles (l'homme pro-féministe, le père investi) qui, sans modifier les pratiques réelles, permettent aux hommes de maintenir une position sociale dominante.
L’entre-soi et l’instrumentalisation : Dans les contextes de loisirs, les femmes sont souvent réduites à un rôle instrumental, servant de « capital séduction » pour valider le statut d'un homme auprès de ses pairs.
Le mécanisme de distinction sociale : La revendication de modernité ou de « déconstruction » est souvent l'apanage de classes sociales favorisées, servant à stigmatiser les hommes des classes populaires (jugés « sexistes » ou « beaufs ») tout en s'exonérant de toute remise en question profonde.
La masculinité ne doit pas être perçue comme une essence biologique, mais comme une construction sociale et relationnelle.
On parle de « masculinités » au pluriel pour souligner qu'il existe une infinité de manières d'incarner le masculin, toutes inscrites dans des rapports de pouvoir, tant vis-à-vis des femmes qu'entre les hommes eux-mêmes.
Le document s'appuie sur le modèle de la sociologue Raewyn Connell pour structurer la hiérarchie des masculinités :
| Type de Masculinité | Caractéristiques | | --- | --- | | Hégémonique | Modèle normatif dominant, considéré comme la "bonne" façon d'être un homme dans un contexte donné. | | Complice | Hommes qui ne correspondent pas parfaitement au modèle hégémonique mais en tirent profit et le soutiennent. | | Subalterne | Masculinités marginalisées, notamment en raison de l'orientation sexuelle (ex: masculinités gay). | | Marginalisée | Masculinités dévalorisées par des critères de classe sociale ou de race. |
Il convient de distinguer l'étude des masculinités du masculinisme.
Le masculinisme est décrit comme :
Un mouvement de réaction aux avancées féministes.
Une idéologie de défense des droits des hommes, prétendant que l'ordre des genres se serait inversé en leur défaveur.
Une culture diffusée en ligne (notamment via les communautés d'incels) et hors ligne, imprégnant l'ensemble de la société.
L'enquête menée par Alix Boireau à Lloret de Mar (Espagne) met en lumière les dynamiques des jeunes hommes (18-23 ans) issus de milieux populaires ou ruraux en vacances.
Le tourisme de « beuverie » est vendu comme un espace de transgression où les femmes seraient « absolument disponibles ».
En réalité, le terrain révèle une omniprésence masculine (le marketing et les codes de ces vacances étant dévalorisants pour les femmes).
Dans cet entre-soi, l'objectif réel est moins la rencontre sexuelle que la socialisation entre hommes.
Les femmes sont instrumentalisées :
Elles servent d'objets de comparaison et de hiérarchisation.
Séduire une femme devient un moyen de prouver sa valeur aux autres hommes du groupe.
Les rapports de force se jouent sur le « capital corporel » (taille, muscles, mâchoire).
La fête ne suspend pas les dominations, elle les renforce :
Hommes blancs hétérosexuels : Leur lâcher-prise est perçu comme ludique et autorisé par le cadre des vacances.
Hommes racisés : Leurs comportements festifs sont souvent interprétés par les observateurs extérieurs comme une « nature turbulente », basculant dans la stigmatisation.
Laura Verkeré et Mélanie Gourarier interrogent la figure de l'homme moderne, pro-féministe et investi.
La figure de l'homme déconstruit est souvent une stratégie de repositionnement.
En se revendiquant « progressiste », l'homme se place « du bon côté de la ligne » pour échapper à la critique féministe sans pour autant transformer l'ordre social.
Cette figure est socialement située : elle concerne majoritairement des cadres urbains des classes supérieures.
Le lexique de l'innovation et de la modernité est utilisé pour créer une distinction morale.
L'invocation de la modernité permet de désigner un bouc émissaire : le sexisme serait le fait exclusif des « autres » (les « beaufs », les hommes de classes populaires, ou les « masculos » radicalisés).
Cela fait diversion et permet d'occulter les violences et dominations qui persistent au sein même des milieux dits progressistes.
Certains hommes adoptent les codes esthétiques du féminisme (vernis à ongles, consommation de produits labellisés « féminins ») sans que cela ne se traduise par un changement dans les pratiques réelles de partage des tâches ou du pouvoir.
Le changement reste alors purement individuel et autocentré.
Le document conclut sur la nécessité de dépasser les postures individuelles pour engager une transformation profonde.
La vision d'un changement par la « révolution » ou la « rupture spectaculaire » est elle-même empreinte de valeurs masculines de performance.
Le changement réel est décrit comme :
Buissonnant et modeste : Il se loge dans des espaces moins spectaculaires et moins valorisés médiatiquement.
Infrapolitique : Composé de petites résistances quotidiennes et de pratiques concrètes plutôt que de labels.
Relationnel : Il nécessite d'accepter l'inconfort, les contradictions et de développer une empathie réelle envers ceux qui subissent les inégalités.
Une véritable transformation féministe ne peut être une « table rase » opérée par de grandes figures masculines.
Elle doit se construire collectivement, en retissant des liens avec les luttes existantes et en se focalisant sur les pratiques sociales plutôt que sur la mise en scène de soi.
tions. It also removes the archivistand his or her records manager ally from their traditional, reactive, ad hoc, servant rela-tionship with records creators - and with researchers - and substitutes instead a strategic,functions-oriented, research-based sta
As more information is created by institutions over time the value of each individual piece of information goes down. Whereas when dealing with scarce medieval documents one must extrapolate the context from the scant information which can be divined from the records, now the broader context must be established first in order to limit the vast quantity of information available to what is actually relevant. If the archive contains everything, it becomes as useless as if it contained nothing. And if the role of the archivist is merely to hoard everything the institutions that create records produce rather than critically evaluating which possible records best reflect the reality of what is being documented, then archival studies cannot really be a field in its own right, because it merely collects rather than studying. Cook is right that archivists must record the forest rather than getting lost in the trees.
Gerade bei
Bei
weil
da
Sie eignet sich als täglicher Sonnenschutz fürs Gesicht und sollte großzügig aufgetragen und bei längerem Aufenthalt in der Sonne nachgecremt werden.
Die Relief Sun eignet sich ideal als täglicher Sonnenschutz für das Gesicht. Tragen Sie sie großzügig auf und cremen Sie bei längerem Aufenthalt in der Sonne regelmäßig nach.
Am meisten lohnt sich der Kauf bei Douglas: als autorisierter Händler führt Douglas die komplette Beauty-of-Joseon-Sonnenpflege an einem Ort, dazu geprüfte Originalware, derzeit Gratis-Proben ab 10 € Bestellwert, Beauty-Card-Punkte und versandkostenfreie Lieferung ab 34,95 €.
Besonders praktisch ist der Kauf bei Douglas. Als autorisierter Händler erhalten Sie dort geprüfte Originalprodukte von Beauty of Joseon. Außerdem profitieren Sie aktuell von Gratis-Proben ab 10 Euro Bestellwert, Beauty-Card-Punkten und einer versandkostenfreien Lieferung ab 34,95 Euro.
Damit LSF 50+ auch wirklich schützt, sollten Sie die Relief Sun großzügig auftragen, fürs Gesicht etwa zwei Fingerlängen, und bei längerem Aufenthalt in der Sonne nachcremen.
Sounds more like human:
Damit der Lichtschutzfaktor 50+ zuverlässig schützt, sollten Sie die Relief Sun großzügig auftragen. Für das Gesicht gelten etwa zwei Fingerlängen als Richtwert und bei längerem Aufenthalt in der Sonne sollten Sie regelmäßig nachcremen.
Als autorisierter Beauty-Händler bezieht Douglas die Relief Sun über offizielle Vertriebswege und steht damit für geprüfte Originalware, bei einem Sonnenschutz, den Sie täglich auftragen, zählt diese Verlässlichkeit mehr als ein kleiner Preisunterschied.
Douglas bezieht die Relief Sun über offizielle Vertriebswege. So können Sie sicher sein, ein Originalprodukt zu erhalten.
Gerade bei einem so gefragten Produkt tauchen im Netz immer wieder Nachahmungen auf.
Vor allem tauchen im Netz bei einem so gefragten Produkt immer wieder Nachahmungen auf.
ist längst breit verfügbar:
ist bereits breit verfügbar.
, weil
Der Grund dafür ist, dass
erste
beste
Genau diese
We dont use the word: Genau, hier.
Diese
Dass hinter dem Hype Substanz steckt, bestätigen die vielen begeisterten Kundenstimmen bei Douglas: Gelobt werden vor allem die leichte Textur, der fehlende weiße Film und das angenehme Hautgefühl über den ganzen Tag.
Sounds very unnatural, better:
Die vielen positiven Bewertungen bei Douglas zeigen, dass der Hype nicht unbegründet ist. Besonders häufig werden die leichte Textur und das angenehme Hautgefühl gelobt. Viele Nutzerinnen und Nutzer freuen sich außerdem darüber, dass die Sonnencreme keinen weißen Film hinterlässt.
Genau dieses
Dieses
Die Beauty of Joseon Relief Sun ist zum viralen Liebling geworden, weil sie ein altes Sonnencreme-Problem löst: den weißen Film.
Sounds more like human:
Die Beauty of Joseon Relief Sun ist in den sozialen Medien zum echten Liebling geworden. Sie hinterlässt keinen weißen Film auf der Haut und löst damit ein Problem, das viele von Sonnencremes kennen.
aufträgt wie eine leichte Feuchtigkeitspflege
wie eine leichte Feuchtigkeitspflege auftragen lässt.
gemacht ist
geeignet ist
über
mit
sind: Die
sind. Die
Beauty of Joseon Relief Sun: die Reis-Sonnencreme, die diesen Sommer in keiner Routine fehlt
More natural:
Beauty of Joseon Relief Sun: Die Reis-Sonnencreme für den Sommer
(e.g., MIT or Apache for code; CC BY for data).
Temos alguma explicação sobre essas licenças e que cenários eu uso um ou outro?
Once you accept emergence, you can explain any result.
Once you accept emergence, you can explain any result.
Account
Need to look at this broken out by issuer, country, etc.
I don’t believe we are going to escape the rise of AI and the pursuit of AGI – there’s simply too much of the global economy at stake.
"Most people's fear of the AI-induced automation economy is that of technology running amok and eliminating human jobs. However, that's not really what's here. The biggest threat posed by the AGI economy is that it has zero financial incentive to preserve the world's languages. The world's most expensive machinery to date has been created to automatically scale human labor as efficiently as possible. And the commercial bias of said machinery to render to scale, will by commercial necessity default to English. Escaping from AGI is impossible. The real battle is therefore to somehow escape the machinery's default indifference to small languages.
Through my work with Global Voices, I know a lot of people who are working to preserve small languages
So, if the hypothesis is correct, these individuals and groups are not merely preserving artifacts and old texts. Rather, they are proving that a language does not need to have native speakers in large numbers in order to be kept alive from generation to generation. The language can be kept alive by people of modern times, adapting it to the many forms of modern communication to bring awareness of its existence. The ultimate test of all of this will be to see whether or not the language’s increased presence on the web leads to increased use between generations in people’s homes.
4.4.2: Looping N times.
I got all of these wrong.. study before taking quiz
Suppose the first input was 0. Would (1.0 * valuesSum / numValues) be 0? Yes No
answer == no Why? valuesSum and numValues would both be 0. valueSum is multiplied by 1.0, converting from integer to float. numValues is then implicitly converted to float. 0.0 / 0.0 results in a "not a number", as 0.0 / 0.0 is mathematically undefined.
Suppose the first input was 0. Would (1.0 * valuesSum / numValues) be 0? Yes No
end value = "not a number" undefined.. 0.00/0.00
4.3.2: GCD program.
This section was a bit tricky...
The Third Gender/Other category included one participant whose sex was male (23 years, 1.60 m, 73 kg) and two participants whose sex was female (22 years, 1.63 m, 68 kg; and 21 years, 1.60 m, 45 kg).
please make this as a footnote in docs file.
3.1 Participants and environmental conditions
I think its better to move this section to "Methodology".
Les Pionniers de l'Infographie pour les Applications Médicales : Synthèse et Perspectives
Ce document de breffage synthétise les interventions du panel « Pionniers de l'infographie pour les applications médicales », explorant l'évolution technologique, les applications cliniques et l'impact social de l'imagerie numérique dans le domaine de la santé.
Depuis les premières visualisations moléculaires des années 1960 jusqu'aux prothèses bioniques gamifiées d'aujourd'hui, l'infographie médicale a transcendé la simple illustration pour devenir un outil essentiel de diagnostic, de traitement et d'éducation.
Les points clés incluent :
Évolution de la Fidélité Visuelle : Le passage de représentations filaires rudimentaires à des modèles organiques complexes (ZBrush, Maya) et des simulations en temps réel.
Gamification de la Rééducation : L'utilisation de jeux vidéo actifs pour améliorer l'adhésion aux soins, notamment pour les patients souffrant de paralysie cérébrale, de sclérose en plaques ou d'amputation.
Démocratisation par la Technologie : L'impression 3D et les logiciels open-source permettent de créer des dispositifs médicaux abordables (bras bioniques) et des formations accessibles.
L'Ère de la Réalité Étendue (XR) et de l'IA : L'intégration de la VR/AR pour la formation chirurgicale, le traitement des phobies et la gestion du stress, avec l'intelligence artificielle comme futur moteur de la création de scénarios cliniques.
L'histoire de l'infographie médicale s'enracine dans la nécessité de visualiser l'invisible, comme les structures moléculaires et cellulaires.
Avant cela, les chercheurs devaient construire des modèles physiques complexes.
Algorithmes de Rendu : Nelson Max a introduit des techniques d'ombrage quadratique en 1977 (programme Atom LLL) pour simuler des modèles de remplissage d'espace (sphères de Van der Waals) avec des reflets et des ombres portées, atteignant une vitesse de rendu alors inédite de 1,5 microseconde par pixel.
Applications Biologiques : Ces technologies ont permis de visualiser l'interaction de médicaments contre le cancer avec l'ADN, la structure des virus icosaédriques et les réactions biochimiques comme la photosynthèse ou la contraction musculaire (modélisation des ponts transversaux de myosine).
Le passage à l'animation 3D a révolutionné la conception des dispositifs médicaux et la planification chirurgicale.
Le flux de travail moderne combine des outils de conception mécanique et de sculpture organique :
SolidWorks : Utilisé pour la modélisation précise de dispositifs « rigides » (stents, neurotransmetteurs, électrodes).
ZBrush et Maya : Employés pour le modelage de tissus mous, comme le cortex cérébral ou le système cardiovasculaire, souvent à partir de données de tomodensitométrie (CT scans).
XGen (Maya) : Un générateur de fibres utilisé pour modéliser des structures microscopiques détaillées comme les bactéries (E. coli, peste bubonique) et les virus (Marburg).
| Projet | Description Technologique | Impact Clinique | | --- | --- | --- | | Stimulation Cérébrale Profonde | Modélisation du subcortex et placement d'électrodes de précision. | Précision accrue dans le ciblage des zones problématiques cérébrales. | | Anévrisme Aortique Abdominal | Stents modélisés et simulés à partir de scans CT. | Aide à la sélection du dispositif et éducation du patient. | | Ablation Rénale | Visualisation de l'irrigation pour refroidir l'artère pendant l'ablation. | Réduction des risques de perforation des parois vasculaires. |
L'intégration de la technologie EMG (électromyographie) et du jeu vidéo transforme l'expérience des patients.
L'organisation se concentre sur la création de moments d'autonomisation pour les enfants nés avec des différences de membres.
Accessibilité : Utilisation de l'impression 3D pour réduire drastiquement les coûts des prothèses pour enfants.
Entraînement par le Jeu : Les enfants pratiquent la flexion musculaire via des jeux vidéo (ex: Smash Bros, Bionic Bash) avant de recevoir leur bras physique.
Cela garantit une meilleure adoption et évite les blessures musculaires.
Ce système de jeux actifs cible les troubles neuromoteurs (paralysie cérébrale, sclérose en plaques).
Découplage Mouvement-Action : Une bibliothèque logicielle permet de lier n'importe quel mouvement corporel (coude, torse, jambe) à une commande de jeu, permettant une personnalisation totale selon les capacités du patient.
Suivi à Distance : Les thérapeutes peuvent ajuster les paramètres du jeu et surveiller les progrès via un portail cloud.
La simulation numérique permet un apprentissage sécurisé et répétable pour le personnel soignant.
Cela permet aux experts médicaux de modifier les scénarios sans coder. - Exemples : Transfusion sanguine, cathétérisme urinaire, identification de patients critiques.
Réalité Étendue (XR) pour les Infirmières : Des plateformes comme Olive et Fora Systems permettent des entraînements de masse (jusqu'à 40 avatars) pour des interventions d'urgence (bombes sales, victimes de masse).
Avantages : Les études montrent que l'apprentissage en monde virtuel est comparable à la formation en personne, tout en permettant un déploiement rapide et global.
L'utilisation de l'électroencéphalographie (EEG) ouvre des voies vers la communication non-verbale et la santé cognitive.
Brain Chat : Technologie permettant de collecter et de transmettre les motifs d'ondes cérébrales en temps réel sur Internet pour visualiser la communication interactive.
Gamma Time : Application utilisant des battements binauraux et de la lumière gamma (40 Hz) pour stimuler le liquide céphalorachidien, visant à « nettoyer » les plaques amyloïdes associées à la maladie d'Alzheimer.
Les experts identifient plusieurs vecteurs de croissance pour la prochaine décennie :
Intelligence Artificielle :
Automatisation des tâches « cléricales » de l'art 3D (nettoyage de scans, conversion de formats).
Interface entre les données complexes et la compréhension humaine.
Haptique et Multisensoriel : Intégration du toucher (force-feedback) dans les simulations chirurgicales et de rééducation pour une immersion totale.
Défis d'Adoption : Malgré 10 000 articles de recherche publiés par an sur la XR médicale, l'adoption à grande échelle reste freinée par le coût du contenu et la complexité de l'intégration dans les systèmes de santé existants.
« La technologie peut être intimidante... notre objectif est de la rendre aussi accessible, amusante et créative que possible. » — Matt Dumbrossski, Limitless Solutions
Iterate until cVal equals 15 (tricky; think carefully).
I got this wrong..
cVal != 15
Briefing : Le e-parcours de Promotion Santé Île-de-France
Ce document de synthèse détaille le dispositif "e-parcours", une plateforme d'auto-formation en ligne développée par l'association Promotion Santé Île-de-France.
Conçu pour pallier les lacunes du système de formation classique, ce parcours innovant vise la montée en compétence des professionnels de santé et des acteurs territoriaux.
Structuré en trois modules progressifs (fondamentaux, déterminants de santé, et santé dans toutes les politiques), le dispositif repose sur une pédagogie interactive, réflexive et ancrée dans la pratique francilienne.
Avec plus de 2 300 inscrits en 2024, le e-parcours s'impose comme un outil de référence pour harmoniser les pratiques et favoriser l'intersectorialité, malgré le défi persistant que représente le manque de temps des utilisateurs.
Le e-parcours est le fruit d'une collaboration amorcée en 2018-2020 par Promotion Santé Île-de-France (association financée principalement par l'ARS Île-de-France).
Le projet répond à une analyse précise du paysage de la formation professionnelle.
Une étude menée en 2018 a révélé "deux trous dans la raquette" concernant l'offre de formation en promotion de la santé :
D'un côté, une pléthore de formations courtes (1 à 4 jours).
De l'autre, des formations universitaires longues (Masters, DU). L'objectif était de créer une offre intermédiaire, numérique et flexible.
Le dispositif s'inscrit dans les missions de Promotion Santé Île-de-France, notamment :
Fournir une plateforme numérique de ressources référentes.
Accompagner la montée en compétence des référents franciliens.
Contribuer au développement d'environnements capacitants (ex: projet Acte 77).
Le e-parcours a été conçu avec l'appui d'un comité de pilotage pluridisciplinaire et d'environ 40 partenaires experts.
Sa pédagogie refuse le modèle purement "descendant".
Le tableau suivant synthétise les principes directeurs de la plateforme :
| Principe | Description | | --- | --- | | Approche par compétences | Basée sur un référentiel européen (2011) accessible et solide. | | Adéquation aux besoins | Alignée sur les besoins identifiés des coordinateurs (ASV, CLS, CLSM, CPTS). | | Interactivité et réflexivité | Utilisation de la plateforme Moodle pour des exercices ludiques et dynamiques. | | Autonomie de l'apprenant | Liberté totale dans le rythme et la scansion de l'apprentissage. | | Ancrage territorial | Utilisation systématique d'exemples et d'outils issus du contexte francilien. |
Le parcours est structuré en trois focales d'apprentissage complémentaires.
Ce module dresse la "toile de fond" de la pratique. Il s'adresse aussi bien aux novices qu'aux professionnels souhaitant mettre à jour leurs connaissances.
Contenus clés : Concepts de base, enjeux des inégalités de santé, principes de la Charte d'Ottawa.
Exemples d'activités : Diaporamas sonorisés avec études de cas (ex: éducation à la vie affective et sexuelle, nutrition).
Témoignage d'usage : Mathilde Mendisco (Saint-Denis) souligne que ce module permet de faire le lien entre théorie et pratique, servant de véritable "boîte à outils" mobilisable au quotidien.
Ce module propose une focale méthodologique pour identifier les leviers d'action sur un territoire.
Méthodologie : Analyse d'une situation, identification des déterminants, sélection des leviers (compétences, milieux) et stratégies.
Supports : Documents de synthèse, modèles conceptuels interactifs et études de cas sur la périnatalité.- Outils : Mise à disposition d'une grille d'analyse pour la pratique professionnelle.
Lancé en janvier 2024, ce module explore l'intégration de la santé dans des secteurs a priori non-sanitaires (urbanisme, logement, culture).
Culture commune : Activités basées sur la précarité énergétique pour apprendre à travailler avec des services logement.
Analyse de contexte : Jeu d'enquête pour identifier comment les politiques locales (culture, enfance) contribuent à la santé mentale sans le savoir.
Partenariat et Plaidoyer : Utilisation de l'outil "Guidup" pour cartographier les partenariats et apprentissage du "pitch dans l'ascenseur" pour influencer les décideurs.
Urbanisme favorable à la santé (UFS) : Analyse des impacts des projets d'aménagement sur le bien-être des populations.
En 2024, une évaluation quantitative et qualitative a permis de mesurer l'efficacité du parcours.
Volume : Plus de 2 300 inscrits.
Géographie : Un inscrit sur deux est francilien (ouverture nationale).
Diversité : Acteurs associatifs, coordinateurs territoriaux, agents de collectivités, étudiants et quelques élus.
Les points forts identifiés par les utilisateurs incluent l'aspect ludique, la qualité des vidéos et l'utilité des études de cas.
L'évaluation révèle des usages inattendus :
Usage collectif : Environ 11 % des utilisateurs suivent le parcours en équipe pour créer une "vision commune" au sein d'un service.
Légitimation : Le parcours renforce le sentiment de compétence et la confiance des professionnels dans leurs cadres conceptuels.
Le principal obstacle à la complétion du parcours est le manque de temps (cité par 95 % des personnes n'ayant pas terminé les modules).
Certains utilisateurs ont également jugé le module 2 parfois trop dense ou répétitif en raison de sa structure itérative.
Le document conclut par des conseils pratiques pour optimiser l'apprentissage en autonomie.
Organisation : Il est conseillé de consacrer des plages de temps dédiées (demi-journées) plutôt que de tenter de tout réaliser d'un bloc.
Flexibilité : Les utilisateurs sont encouragés à naviguer selon leurs besoins spécifiques plutôt que de viser une lecture exhaustive de chaque ressource.
Valorisation : Bien que non certifiant (au sens universitaire), le parcours permet l'obtention de "badges" numériques pour chaque module terminé.
Ces badges constituent un outil de valorisation auprès des employeurs dans le cadre de la formation continue.
e-parcours Promotion de la santé : Synthèse du dispositif d'auto-formation de Promotion Santé Île-de-France
L'e-parcours "Promotion de la santé" est un dispositif d'auto-formation en ligne conçu par l'association Promotion Santé Île-de-France pour répondre à un besoin de montée en compétences des professionnels franciliens.
Développé depuis 2018 en collaboration avec une quarantaine de partenaires experts, ce parcours gratuit et ouvert à tous se structure en trois modules complémentaires : les fondamentaux, l'approche par déterminants et la "Santé dans toutes les politiques".
Basé sur un référentiel de compétences européen, l'outil privilégie une pédagogie interactive et réflexive, ancrée dans des cas pratiques territoriaux.
Avec plus de 2 300 inscrits, l'évaluation souligne une forte utilité pour légitimer les pratiques et créer une culture commune au sein des équipes.
Le principal défi identifié pour les apprenants demeure la gestion du temps, nécessitant une planification rigoureuse pour une appropriation optimale des contenus.
Le projet est né d'un constat réalisé en 2018 par Promotion Santé Île-de-France (anciennement Instance Régionale d'Éducation et de Promotion de la Santé) concernant l'offre de formation en Île-de-France.
L'analyse a révélé un "trou dans la raquette" entre les formations courtes (1 à 4 jours) et les formations longues de type Master.
Le e-parcours a été conçu pour remplir plusieurs missions essentielles :
Alternative de formation : Offrir un format numérique souple, complémentaire aux dispositifs existants (comme le DU de l'Université Sorbonne Paris Nord).
Transfert de connaissances : Transformer des dossiers de connaissances théoriques en outils opérationnels et interactifs.
Appui aux réseaux : Soutenir les coordinateurs territoriaux (ASV, CLS, CLSM) et les nouveaux acteurs (CPTS, MSP) dans leur pratique quotidienne.
Légitimation : Permettre aux acteurs de se réapproprier les concepts pour conforter leur posture professionnelle.
Le dispositif repose sur cinq piliers fondamentaux qui guident sa conception :
Approche par compétences : Utilisation du référentiel européen de 2011 (Commission européenne), choisi pour son accessibilité et sa précision.
Adéquation aux besoins : Contenus basés sur des études de besoins menées auprès des référents en promotion de la santé.
Interactivité et réflexivité : Structure favorisant l'autonomie et la mise en lien constante entre théorie et pratique de terrain.
Flexibilité : Liberté totale dans le rythme et la modalité d'apprentissage.
Ancrage territorial : Utilisation d'exemples et d'outils spécifiquement adaptés au contexte francilien.
Le parcours se compose de trois modules progressifs, bien qu'il soit possible de les suivre de manière indépendante :
| Module | Thématique | Focalisation | | --- | --- | --- | | Module 1 | Fondamentaux | Concepts, enjeux, Chartes d'Ottawa, inégalités sociales de santé. | | Module 2 | Déterminants de santé | Méthodologie : identifier les déterminants, les leviers et les stratégies d'action. | | Module 3 | Santé dans toutes les politiques | Intersectorialité, plaidoyer, partenariats et urbanisme favorable à la santé. |
Sorti en janvier 2024, ce module explore comment intégrer la santé dans des secteurs qui n'en ont pas l'étiquette primaire (urbanisme, logement, prévention de la délinquance).
Analyse de contexte : Utilisation d'un "jeu d'enquête" pour identifier comment les politiques locales (culture, enfance, social) contribuent à la santé mentale et au lien social sans toujours le conscientiser.
Culture commune et partenariat : Étude de cas sur la précarité énergétique.
Utilisation de l'outil "Guidup" pour cartographier les partenariats et structurer des stratégies intersectorielles.
Plaidoyer et influence : Apprentissage des techniques de "pitch dans l'ascenseur" et utilisation d'un jeu de l'oie pour illustrer les hauts et les bas d'une stratégie de plaidoyer à long terme.
Urbanisme favorable à la santé (UFS) : Sensibilisation à la planification urbaine et à la caractérisation des impacts en santé des projets d'aménagement.
Le dispositif compte plus de 2 300 inscrits.
La répartition géographique est équilibrée (50% de Franciliens, 50% hors région).
Les profils sont variés :
Acteurs associatifs et coordinateurs territoriaux.
Agents de collectivités locales et élus.
Étudiants en santé publique ou éducation.
Enseignements de l'évaluation (2024)
L'évaluation qualitative et quantitative souligne que le parcours permet de "conforter les connaissances" et de "se sentir plus légitime".
"C’était mes attentes par rapport à ce module : que ça fasse vraiment ce liant entre théorie et pratique." — Mathilde Mendisco, chef de projet.
Un usage inattendu a émergé : l'utilisation collective. Bien que conçu pour l'autonomie individuelle, environ 11% des utilisateurs s'approprient l'outil en équipe pour créer une "culture commune" et harmoniser les pratiques au sein d'un même service ou avec des partenaires.
Une simplification est prévue pour 2025.
L'association préconise de sanctuariser des créneaux d'une demi-journée plutôt que de tenter de tout suivre d'un bloc.
Bien que le e-parcours ne soit pas une formation diplômante ou certifiante au sens académique, il bénéficie de la crédibilité institutionnelle de Promotion Santé Île-de-France et de ses partenaires (ARS, PSYCOM, SFSP, etc.).
Badges numériques : Un badge est délivré à l'issue de chaque module terminé pour valoriser l'investissement.
Gratuité : Le dispositif est entièrement gratuit et accessible via une inscription sur la plateforme Moodle de l'association.
Temporalité : L'investissement total est estimé entre 3 et 6 jours pour l'ensemble du cycle, selon la profondeur de lecture souhaitée par l'apprenant.
AI technology is not inherently good or bad
Disagree! The motivations and intentions of its creators do make it (and its' use) inherently good or bad. These tools are intended to result in profit for the few and are made possible through hidden costs to the many (water, energy, intellectual property, reduced human skills, etc.)
La Crise de la Misogynie Adolescente dans les Écoles Australiennes : Analyse de l'Influence de la « Manosphère »
Le milieu scolaire australien traverse une crise profonde caractérisée par une normalisation alarmante de la misogynie, des blagues sur le viol et des comportements sexistes.
Ce phénomène, qui touche tous les codes postaux et des enfants dès l'école primaire, est largement alimenté par la « manosphère » — un écosystème numérique de contenus toxiques promus par des influenceurs comme Andrew Tate ou Milo Yiannopoulos.
Les algorithmes des grandes entreprises technologiques sont pointés du doigt pour leur rôle dans la radicalisation des jeunes garçons, transformant des recherches initialement innocentes sur le fitness ou le développement personnel en une rhétorique de haine et de domination.
Les conséquences sont graves : un environnement d'insécurité pour les élèves filles et un exode des enseignantes, confrontées à des agressions verbales et sexuelles systématiques.
La résolution de ce problème complexe exige une réponse sociétale globale, allant de la régulation technologique à une éducation proactive impliquant parents, écoles et gouvernements.
Le contexte scolaire actuel est marqué par une montée de comportements perturbateurs et violents à l'égard des femmes, perçus non plus comme des incidents isolés mais comme une norme culturelle.
Normalisation de la violence verbale : Les blagues et menaces de viol sont devenues courantes dans les salles de classe.
Défiance envers l'autorité féminine : Les garçons refusent de suivre les instructions des enseignantes, remettant activement en question leur autorité, tout en obéissant aux enseignants masculins.
Harcèlement sexuel et sonore : Des comportements tels que des gémissements sexualisés au passage des enseignantes ou le tournage de vidéos sans consentement sont rapportés.
Déshumanisation des élèves filles : Création de groupes de discussion (ex: Snapchat) pour classer les filles selon leur physique et prendre des photos d'elles à leur insu en classe.
De nombreuses enseignantes témoignent d'un sentiment d'insécurité permanent.
Certaines rapportent des agressions verbales extrêmes (« chienne », « pute »), des simulations d'actes sexuels ou de violence physique (simulations de coups de ciseaux sur des enseignantes enceintes).
Ce climat toxique pousse des professionnelles qualifiées à quitter le métier, se sentant incapables de protéger leurs élèves ou elles-mêmes.
La radicalisation des adolescents ne se produit pas de manière isolée ; elle est le résultat d'une exposition constante à des récits toxiques via les réseaux sociaux.
Le parcours de radicalisation suit souvent une progression logique exploitée par les algorithmes :
Phase initiale : Recherche de conseils sur le fitness, la confiance en soi ou comment parler aux filles (contenu apparemment utile comme « range ta chambre »).
Phase de glissement : Recommandation de vidéos suggérant que les difficultés sociales des garçons sont la faute des femmes ou de la société.
Phase de toxicité : Adhésion à des discours prônant la domination masculine, la soumission biologique des femmes et le rejet du féminisme (qualifié de « cancer »).
Des influenceurs comme Andrew Tate et, auparavant, Milo Yiannopoulos, servent de modèles à des jeunes garçons souvent anxieux ou en quête de repères.
Ils diffusent des mythes (comme l'inexistence de l'écart salarial) et promeuvent une masculinité traditionnelle rigide pour masquer des insécurités personnelles.
| Concept | Description dans la Manosphère | | --- | --- | | Féminisme | Perçu comme un échec ou un « cancer » qui détruit les femmes. | | Rapports de force | Idée que les femmes désirent biologiquement être dominées par les hommes. | | Objectif 666 | Contenu viral prônant qu'un homme doit avoir un salaire à 6 chiffres, un corps sculpté (6-pack) et mesurer 6 pieds pour avoir de la valeur. |
Les industries technologiques pesant des milliards de dollars sont accusées de « militariser » le système limbique des enfants.
Leurs algorithmes sont conçus pour capter l'attention en poussant des contenus de plus en plus extrêmes, sans égard pour les dommages causés dans le monde réel.
Le concept de « sécurité dès la conception » (safety by design) est jugé essentiel pour tenir ces plateformes responsables.
L'accès précoce et massif à la pornographie (56 % des garçons de 15 ans en regardent chaque semaine) déforme radicalement la perception des relations sexuelles.
Normalisation de la violence : Des pratiques comme la strangulation (« choking ») sont devenues courantes chez les jeunes, influencées par les scripts pornographiques.
Manque d'empathie : La pornographie n'enseigne pas le consentement ni la préoccupation pour l'expérience du partenaire.
La résolution de cette crise ne peut reposer uniquement sur les épaules des enseignants ou des parents.
Programmes éducatifs proactifs : Des éducateurs comme Daniel Principe interviennent pour déconstruire les stéréotypes et encourager les garçons à rejeter les modèles de masculinité toxiques.
Régulation gouvernementale : Nécessité d'une reddition de comptes pour les plateformes numériques et d'une réglementation plus stricte des contenus poussés vers les mineurs.
Dialogue et imagination morale : Encourager les garçons à exprimer leurs insécurités sans passer par la haine, et aider les filles à identifier les signes avant-coureurs de violence (sortir des « zones oranges » dans les relations).
« Ce n'est pas le problème des influenceurs masculins. C'est la question de savoir pourquoi ces messages sont si séduisants pour les jeunes garçons. » — Jefferson, ancien adepte de la manosphère.
« Les enfants ont ces industries de plusieurs milliards de dollars qui militarisent leur système limbique contre eux. » — Source Contextuelle.
« Si nous voyons une augmentation des commentaires sexistes et des blagues misogynes, ce sont tous des éléments qui contribuent à un environnement où la violence contre les femmes est plus susceptible d'être tolérée. » — Holly Cooper, ancienne enseignante.
Le document souligne que la misogynie en milieu scolaire est un problème multifacette.
Ce n'est pas simplement une question de « mauvais comportement », mais le symptôme d'une exposition systémique à une culture numérique qui déshumanise les femmes.
La lutte contre ce fléau nécessite une mobilisation générale : parents, écoles, clubs sportifs et gouvernements doivent collaborer pour offrir aux adolescents une voie de passage vers l'âge adulte qui ne soit ni dégradante pour eux-mêmes, ni déshumanisante pour autrui.
“quia sicut per crucem non sine gravi dolore ad exitum pervenitur, ita illa natura (the old man) sine dolore non extinguitur.
"Because just as one does not come to death by crucifixion without severe pain, so that nature (the old man) is not extinguished without pain."
Figure 0.1
in the the picture the word lossy merges with लौकिक.
data compression
开销降低，但精度同样可能损失且压缩及错误避免的计算可能带来额外开销
问题：Imerge是否可能同样带来精度损失，实验部分没有展示精度
two approaches
增加单服务器中的聚合节点或多层扩展聚合 或多服务器、物理多层架构：增加了同步开销和维持一致性的复杂度
strong serialization
应该是客户端训练->上传->同步->下拉
问题：传统串行调度使计算和通信资源利用没有达到最优
deployed with minimaloverhead in PyTorch
这句话啥意思，单纯能直接作为pytorch组件接入吗
All-Reduce
去中心训练在大量细粒度梯度(我估计是通信十分频繁场景)和大规模网络场景下失去优势
PS architecture [23]–[25] adoptsa centralized parameter management paradigm, offering ad-vantages in fault tolerance, system flexibility, and adaptabilityto heterogeneous computing environmen
ps架构有这些好处所以应用比较广泛
core
准确建模模型每个layer的通信开销，以知道自适应的梯度融合，使 梯度同步和向后计算的重叠更加明智 问题：是否真的准确，梯度融合是什么；重叠是在干什么
对straggler的梯度传输采用客户端间的interleaved传输，有效减少传输拥塞和链路瓶颈 问题：这个interleaved在干什么，拥塞和瓶颈减少在实验中是否体现
I found it in an old Italian typewriting course that I’m studying, it says translated “on olivetti machines both manual and electric , if you press the margin release key while performing line return, the carriage will stop ten spaces before the set left margin. This creates a fix indentation useful for starting new paragraphs”
https://www.reddit.com/r/typewriters/comments/1upt285/did_you_know_about_this_hidden_feature_on_the/
[GRIND] (<35%) — the last of which is banned from ever being shown.
Really? Please explain.
greedy multi-candidate
what is this?
unified JSON ships in
Normalized Postgres database tables?
preservice
relating to the period before a person takes a job that requires training, especially in teaching:
Calibration anchors are a small set of real example papers that teach The Unjournal's AI prioritization scorer what “value of evaluation” looks like in each area — including the boundary cases where a good paper is not a good candidate. Each anchor's rating is the team's real prioritization rating; the proposed lesson is an AI inference about the calibration takeaway. Use this page to confirm or correct each rating and lesson, suggest new anchors, and track the discussion.
This anchoring page should allow people to specify the different dimensions of quality, that is, the different ratings.
And the form should be more quantitative rather than "too high, too low." -- or maybe I'm missing the point?
To be honest, I'm not sure what was intended by the question "not by the answer", "not a good anchor". ... What is the " lesson" here? That's confusing.
If you need parts, hit me up. I have nearly an entire disassembled QDL (same vintage as your machines) in good condition that I will not be using.
u/typercito has a 50s Royal Quiet De Luxe that is a parts machine if necessary.
https://www.reddit.com/r/typewriters/comments/1ua62rl/comment/osohxex/?context=1&screen_view_count=2
eLife Assessment
This important study establishes a robust live-imaging toolkit to characterize excitatory and inhibitory synaptic dynamics during neuronal development, advancing our mechanistic understanding of synaptic homeostasis and neural circuit maturation. The core findings clarify how stable E/I balance is maintained despite persistent synaptic turnover, with broad implications for developmental neurobiology and neurodevelopmental disorders. The methodology and quantitative data are convincing and well validated, and this work represents a significant advance that will be of significant interest to researchers in synaptic biology, cell imaging and neuroscience.
Reviewer #1 (Public review):
[Editors' note: all three reviewers confirm that all initial concerns have been fully resolved through comprehensive revisions and supplementary analyses.]
Summary:
By imaging the dynamics of synaptic proteins in cultured neurons, this study presents significant findings regarding the dynamics of excitatory and inhibitory synaptic proteins during development. The evidence shows that the ratios of excitatory and inhibitory synaptic proteins are stable during synapse development. This discovery advances our understanding of the complex mechanisms governing synapse formation. The strength of the evidence is robust, as it is supported by a combination of biological assays and endogenous labeling.
Strengths:
This research sheds light on the dynamics of the excitatory and inhibitory synapses during development. It is crucial to understand that while excitatory synapses and inhibitory synapses are developed independently, the ratio of their number is relatively stable during development, maintaining a stable excitatory/inhibitory ratio.
Important findings and implications in the research include:
(1) Persistent Synapse Dynamics: Excitatory and inhibitory synapses remain highly dynamic even in mature neurons (DIV12-14), challenging the dogma that synaptic structures are stable after the synaptogenesis stage.
(2) Maintained E/I Balance: Despite ongoing synapse turnover (formation/elimination) and presynaptic terminal reduction, the overall density and ratio of excitatory-to-inhibitory synapses remain relatively stable during circuit maturation (Figure 7).
(3) Developmental Shifts: While presynaptic compartments decrease over time, postsynaptic sites increase, suggesting independent regulation of pre- and postsynaptic elements within a stable E/I framework.
Weaknesses:
This study focuses on specific synaptic proteins within synapses, which may not fully represent the dynamics of other synaptic machinery; also, whether similar observations exist in vivo is still unknown. Further research is needed to explore the implications of these findings in more complex neuronal environments.
Comments on revised version:
The authors have addressed all my questions/comments. No further questions for this manuscript.
Reviewer #2 (Public review):
Summary:
The Garbett et al. identified a critical need to begin to understand the interplay between the assembly, maturation, and elimination of excitatory and inhibitory synapses. They also detail the lack of reliable tools to address this gap in knowledge. Here, the authors developed synaptic reporters expressed by lentiviruses (mClover3-Homer1c, HaloTag-Syb2, and tdTomato-Gephyrin). They combined these reporters with resonance scanning confocal imaging to measure synapses over a 15-hour period during neuron development and in mature neurons in primary hippocampal cultures. Using these reporters in the same neuron, the authors compared the ratios of postsynaptic excitatory and inhibitory specializations that co-localize with presynaptic terminals during development and in mature neurons and found that they are stable across time points. Finally, the authors developed CRISPR/Cas9 tools (TKIT) to knock-in endogenous fluorescent tags (GFP/tdTomato-Gephyrin) or epitope tags (HA-Bassoon and HA-Homer1) to begin to study synapse dynamics using endogenous proteins. I believe this paper highlights an important gap in knowledge and begins to offer methodologies to determine the dynamic coordination between excitatory and inhibitory synapses.
Strengths:
(1) The experiments are well-designed and carefully controlled.
(2) The authors carefully validated the reporter and TKIT constructs.
(3) The authors provide strong proof-of-principle for the use of the reporter constructs to track synapse formation, maintenance, and elimination over a 15-hour period.
(4) Ingenious use of technologies (reporters, TKIT, and resonance scanning confocal microscopy) to develop a platform for future studies of synapse dynamics.
(5) Strong evidence supporting that the ratio of excitatory and inhibitory synapses (those that oppose syb2) stays constant through development.
Overall, this is a well-executed study that develops tools to simultaneously image excitatory and inhibitory synapse dynamics and represents an important first step to address the fundamental question regarding the coordination between these two types of synapses.
Comments on revised version:
The authors addressed all my questions and comments. Their edits have made this paper significantly stronger. I believe that this is an important paper for the field.
Reviewer #3 (Public review):
In the present study, the authors describe the development of new tools and imaging strategies to assess the concomitant development of excitatory and inhibitory synapses in dissociated neuron cultures. To this end, they generate fluorescently tagged constructs of excitatory and inhibitory synapse marker proteins using either conventional overexpression or CRISPR-based strategies. They then image these marker proteins over a timespan of 15 hours to assess synaptic dynamics at different developmental timepoints. Based on their data, they conclude that excitatory and inhibitory synapse development occur in concert to maintain a functional balance despite individual synapse turnover.
Overall, this study addresses an interesting question, i.e., the interplay between the development of excitatory and inhibitory synapses, which has important implications, particularly for neurodevelopmental disorders in which the balance of excitation and inhibition is disrupted. The experiments are technically solid and well-executed, and the individual images are highly compelling.
Comments on revised version:
The authors have fully addressed my concerns, and this is now a strong manuscript for the synaptic field.
Author response:
The following is the authors’ response to the original reviews.
eLife Assessment
In this valuable study, the authors developed long-term imaging tools to simultaneously monitor the temporal and spatial dynamics of excitatory and inhibitory synapses and reported that excitatory and inhibitory synapses need to develop synergistically during synaptogenesis to maintain balance. While the analysis and quantification of the imaging data are incomplete, there is convincing evidence that the developed tools are feasible. If these tools can function stably in vivo, their applications will be much broader.
We have completely overhauled our analysis and quantification methods and generated custom-made drift correction and tracking pipelines. Also, we have tested these tools ex vivo.
Public Reviews:
Reviewer #1 (Public review):
Summary:
By imaging the dynamics of synaptic proteins in cultured neurons, this study presents significant findings regarding the dynamics of excitatory and inhibitory synaptic proteins during development. The evidence shows that the ratios of excitatory and inhibitory synaptic proteins are stable during synapse development. This discovery advances our understanding of the complex mechanisms governing synapse formation. The strength of the evidence is robust, as it is supported by a combination of biological assays and endogenous labeling.
Strengths:
This research sheds light on the dynamics of the excitatory and inhibitory synapses during development. It is crucial to understand that while excitatory synapses and inhibitory synapses are developed independently, the ratio of their number is relatively stable during development, maintaining a stable excitatory/inhibitory ratio.
Important findings and implications in the research include:
(1) Persistent Synapse Dynamics: Excitatory and inhibitory synapses remain highly dynamic even in mature neurons (DIV12-14), challenging the dogma that synaptic structures are stable after the synaptogenesis stage.
(2) Maintained E/I Balance: Despite ongoing synapse turnover (formation/elimination) and presynaptic terminal reduction, the overall density and ratio of excitatory-to-inhibitory synapses remain relatively stable during circuit maturation (Figure 7).
(3) Developmental Shifts: While presynaptic compartments decrease over time, postsynaptic sites increase, suggesting independent regulation of pre- and postsynaptic elements within a stable E/I framework.
We thank the Reviewer for their positive feedback and careful review of our study.
Weaknesses:
This study focuses on specific synaptic proteins within synapses, which may not fully represent the dynamics of other synaptic machinery; also, whether similar observations exist in vivo is still unknown. Further research is needed to explore the implications of these findings in more complex neuronal environments.
We also thank the Reviewer for their insights and suggestions. We have added discussion of this important point to the Discussion section. Furthermore, we have tested the applicability of our tools ex vivo (new Figures 1, 4, and 6). While using these tools in vivo for live imaging is the eventual goal, we started in a reduced culture system given the relative simplicity. Our current study now provides a framework for future experiments applying these approaches in more complex in vivo systems.
Reviewer #2 (Public review):
Summary:
The Garbett et al. identified a critical need to begin to understand the interplay between the assembly, maturation, and elimination of excitatory and inhibitory synapses. They also detail the lack of reliable tools to address this gap in knowledge. Here, the authors developed synaptic reporters expressed by lentiviruses (mClover3-Homer1c, HaloTag-Syb2, and tdTomatoGephyrin). They combined these reporters with resonance scanning confocal imaging to measure synapses over a 15-hour period during neuron development and in mature neurons in primary hippocampal cultures. Using these reporters in the same neuron, the authors compared the ratios of postsynaptic excitatory and inhibitory specializations that co-localize with presynaptic terminals during development and in mature neurons and found that they are stable across time points. Finally, the authors developed CRISPR/Cas9 tools (TKIT) to knock-in endogenous fluorescent tags (GFP/tdTomato-Gephyrin) or epitope tags (HA-Bassoon and HAHomer1) to begin to study synapse dynamics using endogenous proteins. I believe this paper highlights an important gap in knowledge and begins to offer methodologies to determine the dynamic coordination between excitatory and inhibitory synapses.
Strengths:
(1) The experiments are well-designed and carefully controlled.
(2) The authors carefully validated the reporter and TKIT constructs.
(3) The authors provide strong proof-of-principle for the use of the reporter constructs to track synapse formation, maintenance, and elimination over a 15-hour period.
(4) Ingenious use of technologies (reporters, TKIT, and resonance scanning confocal microscopy) to develop a platform for future studies of synapse dynamics.
(5) Strong evidence supporting that the ratio of excitatory and inhibitory synapses (those that oppose syb2) stays constant through development.
We thank the Reviewer for their positive assessment of our study.
Weaknesses:
Overall, this is a well-executed study that develops tools to simultaneously image excitatory and inhibitory synapse dynamics and represents an important first step to address the fundamental question regarding the coordination between these two types of synapses.
Minor weaknesses of the manuscript include:
(1) The lack of a characterization of endogenous Homer1-positive excitatory synapses using TKIT.
We attempted to perform live imaging of endogenous Homer1-positive synapses using the TKIT approach by tagging endogenous Homer1 with mClover3 but encountered low signal/noise while live imaging. This prompted us to focus our current study on live imaging endogenous Gephyrin. Future studies using more robust tags (e.g. StayGold, HaloTag) for TKIT tagging of endogenous Homer1 will likely help circumvent this issue.
(2) Discussion about other approaches to study excitatory and inhibitory synapses using endogenous proteins (e.g., intrabodies - FingR or nanobodies) should be included.
This important point was also raised by other Reviewers. We have now significantly expanded the Discussion section, including discussion of this point.
(3) The activity state of a neuron and/or a synapse might alter the dynamic properties (formation, maintenance, and/or elimination). A discussion on whether the overexpression of Homer1 and/or gephyrin might alter synapse/neuron activity would provide greater interpretability of the results. A discussion of the potential limitations and benefits of the reporter and TKIT approaches would be beneficial.
We agree and have added discussion of these points to the Discussion section.
(4) A description and interpretation of the computational approach to calculate particle tracking would be helpful. I found that particle tracking figures, while elegant, are difficult to interpret.
As discussed in more detail below, we have generated drift correction and particle tracking approaches for the revised manuscript. We now elaborate on these new approaches in the paper.
We thank the Reviewer again for their very helpful input and suggestions.
Reviewer #3 (Public review):
In the present study, the authors describe the development of new tools and imaging strategies to assess the concomitant development of excitatory and inhibitory synapses in dissociated neuron cultures. To this end, they generate fluorescently tagged constructs of excitatory and inhibitory synapse marker proteins using either conventional overexpression or CRISPR-based strategies. They then image these marker proteins over a timespan of 15 hours to assess synaptic dynamics at different developmental timepoints. Based on their data, they conclude that excitatory and inhibitory synapse development occur in concert to maintain a functional balance despite individual synapse turnover.
Overall, this study addresses an interesting question, i.e., the interplay between the development of excitatory and inhibitory synapses, which has important implications, particularly for neurodevelopmental disorders in which the balance of excitation and inhibition is disrupted. The experiments are technically solid and well-executed, and the individual images are highly compelling.
We thank the Reviewer for their positive assessment of our study.
However, a number of aspects remain to be addressed in order for the study to support the claims made by the authors. First, the novelty aspect of the development of the fluorescently tagged synaptic proteins is unclear, since reporters of this nature are in routine use in many labs. Second, the analysis of the acquired images often seems incomplete, with only example images but no quantification shown, or the distinction between spatial and temporal dynamics appearing unclear. Third, given this incomplete analysis, the interpretations of the authors are not always convincingly supported by the data presented. In conclusion, substantial improvements are required to render the main messages of the study clear and compelling.
We agree and have incorporated all of the Reviewer’s suggestions in the revised manuscript (please see below).
Recommendations for the authors:
Reviewer #1 (Recommendations for the authors):
This is an interesting study. This reviewer has the following questions/comments for the authors:
(1) Please provide evidence that the gRNAs targeting each gene of synaptic protein have no offtarget effects.
We now include analysis of off-target effects for the TKIT tools (new Figure S6).
(2) While structural E/I balance is shown, functional electrophysiological validation (e.g., mEPSC/mIPSC ratios) is absent. It is interesting to know whether the balanced functional structural changes translate to functional?
We thank the Reviewer for this insightful suggestion and now include these recordings in the revised paper (new Figure 8).
(3) In lines 217-218, please define thresholds for "stable" vs. "dynamic" puncta (e.g., temporal and spatial criteria).
We more clearly define our categorization parameters (e.g. new Figure 2).
(4) In Figure 5B: The low co-localization between endogenously tagged Bassoon and antibodystained Bassoon is likely due to the low TKIT efficiency. Quite a few HA-tagged Basson signals are insensitive to Basson-antibody. The authors are suggested to explain those.
We thank the Reviewer for identifying this and add discussion to the Results section.
(5) For the data analysis. If each n represents an independent neuronal culture, should the authors are suggested to provide the number of neurons/dendrites analyzed for each independent culture?
We have added these important details to the manuscript.
(6) Regarding the title, the author used the term "coordinated dynamics". This reviewer finds it is a bit over-claim because the stable ratios of the number of excitatory synapses and inhibitory synapses are likely an association, not actively "coordinated". I suggest that the authors rephrase this.
We agree that we cannot argue that excitatory and inhibitory synapses are causally coordinated in our current study. Their levels are likely associated by either association or direct coupling, which we now discuss further in the first paragraph of the Discussion. We have rephrased the title accordingly.
Reviewer #2 (Recommendations for the authors):
I have only minor suggestions that I think will improve the manuscript:
(1) Please define Syn1/2 on line 129.
We have defined this in the revised paper.
(2) For Figures 2B, C, and 4B, C: are the puncta in panel C from the dendrites in panels B? If so, it would be helpful to identify the ROIs selected in panels C.
We now include this in new Figure 2.
(3) For the particle tracking figures, while the ability to track all synaptic puncta is very impressive, it is sometimes difficult to clearly track the lifespan of a synaptic puncta from the current figures. I believe that it would be helpful if the authors selected specific examples of synapses formed, maintained, and eliminated.
We agree and now include more examples.
(4) I believe that more detail about the computational approach and analysis for the particle tracking (Figs 2E and 4E) would help the interpretability of the figure.
This important point was also raised by the other Reviewers. We generated custom tools during the revision that significantly expand the capabilities of our tracking approaches and more clearly describe them in the revised manuscript.
(5) Similar to the rigorous gephyrin TKIT analysis (Fig. 6), did the authors perform a similar analysis for Homer1c TKIT? This might be valuable to confirm that overexpression of the Homer1 reporter does not indirectly alter synapse dynamics.
We attempted to perform live imaging of mClover3 TKIT-tagged endogenous Homer1 but encountered low signal/noise with live imaging. We now add discussion that optimization of more robust tags (e.g. StayGold, HaloTag) will likely be necessary for live imaging of different target proteins.
(6) The tools developed by Garbett et al. have the potential to be broadly utilized in the field to provide new insight into the coordination of excitatory and inhibitory synapses. It would thus be helpful for the authors to include a discussion about the strengths and limitations of the reporter and TKIT methods relative to other approaches used to live image synapses (e.g., intrabodies (FingR and nanobodies)).
We have now significantly expanded the Discussion to include these important points.
(7) In the discussion, can the authors elaborate on whether it is experimentally feasible to apply their TKIT labeling of gephyrin and Homer1c in the same neuron to assess the endogenous excitatory and inhibitory synapse dynamics from the same neuron?
We have added discussion of this point and also proof-of-concept data supporting tagging of two postsynaptic targets within the same neuron (new Figure S5D).
Reviewer #3 (Recommendations for the authors):
(1) While the new tools described in the current manuscript can undoubtedly be used for the described purposes, the novelty of these tools is unclear to me. Viral vectors expressing fluorescently tagged versions of Homer1, synaptobrevin, and gephyrin are commercially available, e.g., via Addgene, and they are in routine use in many labs. CRISPR-mediated strategies for this purpose have also been previously reported (e.g., Willems et al. 2020, PLOS Biology; Fang et al. 2021, eLife). It is not clear to me how the tools reported here present a significant improvement over existing resources, other than that they use different fluorescent tags. If this aspect is a central part of the current manuscript, it should be expanded on in the discussion, including a direct comparison with available tools to highlight the novel aspects.
We agree and have significantly expanded the Discussion to include these important points. Also, rather than argue that our tools are superior to pre-existing approaches, we adjust the text to argue that our tools and analytical approaches have been designed and optimized for the purposes we apply them to.
(2) In addition to generating new tagged constructs, the authors also state that they have developed new imaging and analysis strategies to facilitate long-term assessment of synaptic dynamics. However, in many figures, they present only sample images, with little quantification to allow assessment of the wider relevance of the imaged synapses. For example, in Figures 2C and 4C, they present one example each of, e.g., a stable, nascent, transient, or eliminated synapse. However, they do not provide any quantification on how frequently any of these events occur, or whether they can be reliably quantified at all. These quantifications (i.e., percentage of each event type across a large population of synapses) would be necessary and should be added to demonstrate that this tool can be used for more than single example images.
We have generated custom-made drift correction and particle tracking approaches for the revised manuscript. Based on the reviewer’s suggestion, we have quantified the relative frequencies of stable, nascent, transient, and eliminated synapses (Fig 2B-G, Fig3A-F, Fig 5A-F, Fig 7B-C). These metrics greatly enhance the biological interpretation of our results. We have also added a supplemental movie with an example image with corresponding categorized tracks for each puncta type (Movie S3)
(3) The authors do present an automated visual representation of spatial track length across the neuron, e.g., in Figure 2E and 4E, although this is also not quantified. Moreover, the track lengths appear surprisingly short, despite the authors' claims that their analyses 'highlight the dynamic nature of excitatory synapses over these timescales'. It is not clear to me whether these short tracks are more than just jitter, either in the synapses themselves or in the images due to technical limitations. E.g., in panel 2E, I see very few examples in which the track is not simply centered around one point, but actually expands over a distance. Quantification of the distance between start and end points of the tracks would be important to support the claim that these synapses are dynamic in terms of spatial translocation (if that is what the authors meant). Or if the 'dynamic nature' of the synapses referred to temporal dynamics, it is unclear to me how this information can be gained from the represented tracks.
We thank the reviewer for these excellent points. To accurately access spatial motion, we drift-corrected our images with a custom correction algorithm to eliminate stage or microscope drift as a source of contaminating motion (See Methods, Movie S2), in addition to collecting time-lapse imaging with Nikon perfect focus. We noticed heterogeneity in our cultures such that some areas contained very mobile neurites, while other remained stationary (Fig. S1). We binned movies into either moving or still neurites and assessed spatial metrics as suggested (Fig. S1A). Consistent with our binning, puncta on moving neurites showed larger net displacement (distance between start and end points), but puncta on still neurites also showed ~1 µm net displacement (Fig. S1D). We also quantified puncta speed and found that puncta on moving neurites generally moved faster (Fig. S1C). We appreciate the reviewer’s insight that track length were surprisingly short, and after employing our drift correction and revised tracking methods, we now see substantially longer track lengths (Fig 2E, Fig 3C & F, Fig S2B & C). We additionally see a large fraction of tracks that persist throughout the imaging session (Fig 2E, Fig S2B & C).
(4) In Figure 3, the authors now quantify track length, but in this case in the unit 'minutes', from which I would interpret that this is now meant to assess the temporal dynamics rather than the spatial dynamics. The lack of a clear distinction between spatial dynamics and temporal dynamics is very confusing to me, since these are entirely independent measures. 'Track length' to me indicates spatial dynamics, and I would expect the units to be a measure of distance. 'Track duration', which the authors also use in some places, but inconsistently as far as I can tell, makes sense to me for the assessment of temporal dynamics, with the units being a measure of time. I would strongly recommend being very clear about this distinction, since the current representation of the data is very difficult to follow and interpret.
In addition to new spatial metrics, we have clarified in the text when we are referring to spatial dynamics (distance) versus temporal dynamics (time). As suggested, we use duration when referring to time, and speed or distance when referring to spatial metrics.
(5) The images from the newly generated CRISPR-based tags in Figures 5-7 are striking and very compelling - these will be very useful tools. However, here too, it seems that the interpretation of the data does not really match the results. All quantification indicates that there is very little change in synapse density or other assessed parameters over the time course of the imaging, and yet the authors emphasize the dynamic nature of visualized synapses. More compelling quantification would be needed to support this claim.
We have quantified spatial and temporal metrics for live neuron culture imaging for all tools developed including CRISPR-based tags (Figure 7).
(6) The discussion is extremely short and provides almost no integration of the results of the study into the framework of existing knowledge. Instead, it focuses almost exclusively on unanswered questions and future perspectives, which are also important, but not helpful in interpreting the findings from the current study. The latter aspects should be added to provide essential context for the current findings.
We agree and have added additional discussion of our current findings to help contextualize their significance.
We thank the Reviewers again for their positive feedback and insightful input, which has undoubtedly strengthened our study.
Module 1: Emerging Trends in Business
Need a link to the Playbook on this page
Explore the forces reshaping modern business administration and examine how emerging trends influence strategy, leadership, and organizational decision-making.
This text and the Module Focus checklist basically duplicate the Introduction. Can we delete and just have a smaller header with the title?
- imposto sobre a propriedade predial e territorial urbana progressivo no tempo;
Progressividade extrafiscal do IPTU aplicável ao imóvel que não cumpre a sua função social.
ser progressivo em razão do valor do imóvel
Progressividade Fiscal do IPTU em razão do valor do imóvel
Finance is not a major player in this model of the economy. Corporations in the industrial technostructure seek to optimize for retained earnings, the only kind of capital that they can use completely flexibly, rather than for equity or debt, both of which come with (sometimes quite costly) obligations. Galbraith quips that no banker would presume to know more than a General Motors engineer about the design of a new combustion engine—and the banker would lend anyway, because who would doubt a GM engineer, an “organization man”? The barrier to economic development in Galbraith’s time is no longer any scarcity of capital; rather, it is the concentration of expertise—which the industrial corporation is uniquely able to organize and shape to its ends.
How things have changed
Select the List Objects radio button to run a test before creating the actual transport. This test run shows which objects will be included and helps estimate processing time (the longer the system takes to list the objects, the longer the processing time). No transport request is created at this stage. If you're happy with the test result, change the radio button back to Create Language Transport.
These need to go after the current step 8
Show detailed scoring rubrics & methodology
"Show" --> SHOW/HIDE ... and make it clearer that this is the 'toggle to open the content below' ... it's not shared or offset or boxed, so that's hard to see
March
need a 'fold all/unfold all' button here
Scores are calibrated against 353 actual human prioritization decisions from the Unjournal team. The AI scores are systematically compared to human assessor ratings, and field-specific corrections are applied. Read more about UJ’s prioritization process.
Link a page on 'how this was 'calibrated' here'
For prominent work (NBER, CEPR, World Bank, top journals), decision-relevance dominates. For less-prominent work, methodology becomes the tie-breaker—our evaluation could boost neglected but rigorous research.
clarify this -- see note abobe
Methodological potential
this needs more discussion and thinking. Even for prominent work the strength of the data/approach may be weighted somewhat. E.g., all else equal, real world measured outcome data is usually preferred to recall data, which might be preferred to hypothetical choice data. However, for prominent work we don't weight/rate the 'methodological correctness' of the work in rating its potential for impact. If it's prominent and ~influential already, if it has major flaws that makes it perhaps _ more_ important, to be publicly evaluated. In contrast, for less prominent work, clear methodological, logical, contextual, and communications flaws make it less likely to have potential for impact, and thus less valuable to commission for evaluation.
Prominence
Not sure we want a 'prominence' rating/weighting for less-prominent work -- that seems confusing and contradictoru
The list can be scored and sorted through either of two transparent weightings of the six sub-scores — toggle Evaluation-relevance weighting in the controls, and unfold What is this score? to see the live weights:
(Tooltip?) We may want to ask users to specifically rate papers by these multiple categories, in part to help refine the model
We welcome both team and public feedback.
Explain how we are also soliciting human ratings, and these wil be incorporateed into this tool, both in the direct prioritization, and informing the AI model.
Quick-rate mode
A tooldtip should explain 'quick rate mode'. And we should have a folding box (and or a link on 'get involved') explaining how we want direct ratings -- either quick +/- ratings, or detailed discussion input on prioritizing these research objects according to their potential for impact
Für den ersten Test aber in Ordnung.
Finde ich auch!
Die vier Darstellungen sollen dann durch H5P-Elemente wie einem Accordion mit weiterführenden Informationen zu den jeweiligen Erkenntnissen aus den Darstellungen ergänzt werden. Dadurch werden die Darstellungen auch für fachfremde Menschen, die die Webseite besuchen, verständlich und bieten nicht nur Fachpersonal einen Mehrwert. Die Darstellungen und Informationen können dann auf der Webseite durch iframes eingebettet werden.
Ich vermute, dass du in einem H5P-Akkordeon die Grafana-Zellen nicht einbetten kannst.
Daher schlage ich vor, hier schon mal nach anderen Akkordeon-Lösungen zu schauen, die mit HTML/CSS/JavaScript funktionieren und mehr Freiraum bieten.
Ich bin jedoch zum einen dankbar, dass ich die ID 0 an Unknown vergeben habe und die Daten so nicht verloren sind, und zum anderen sehr zuversichtlich, dass der Index durch schrittweise Erweiterung sehr gut funktionieren wird.
Wie willst du damit umgehen, wenn Vogelarten nicht im Training vorgekommen sind?
Whoop whoop!
HAMMER!, wie Dieter sagen würde.
Module Complete Key Takeaways This module introduced concepts and practices that will serve as a foundation for your work throughout the DBA program.
We will not need this page.
Evaluate an emerging business trend and analyze its implications for organizational strategy, managerial decision-making, and global business practice.
Can we trim this - repeats what's in the overview.
As with the discussion and the faculty live session, this page will focus on student action - just the minimum needed to submit. Assignment istructions will go into the Playbook.
Seminar Focus Topics Covered During the Live Session
This information will go into the Playbook.
Connect with your instructor and classmates to discuss course expectations, academic success strategies, and the skills needed to thrive in the DBA program.
If we delete this sentence, can we make the header a bit smaller?
Overall the page is useful, but - as with other pages - we'd like this to be focused on student actions rather than content.
Discussion Reading, Thinking, and Introducing Yourself Introduce yourself and reflect on the skills and habits that will support your success in the DBA program. Jump to Reply
This page should be focused on just the task of posting to the discussion board, with the overview, prep, and prompts in the Playbook. So again, maybe this page is scaled down just to facilitate the conversation?
1.1 Required Reading
Let's chat about whether we need this page. We can't put resources into Scholar Source, and are instead including the full (linked) list in the course Playbook.
They not only choose to discon-tinue the conversation but are morelikely to turn to someone who willunderstand their perspective.”
I have an interesting situation in my classroom and my school (elementary K-5) in which kids are kind of figuring out things about race and identifying their own race in a really innocent way. Many students have more than one race and they haven't given it a thought until 2-3rd grade. This seems like a perfect time for us to have open conversations about race that seem really casual and not anxious.
t’simportant that we talk about i
I think that when we rely on people of color to discuss race and racism we give up our responsibility to reflect on our own. If we only hear from people of color, we aren't reflecting on other areas in our lives in which we benefit from racism.
reflection is distorted byracism.
I think that this can sometimes come across as teachers who have a hard time engaging with students of color or are hesitant to engage with them. I went to a workshop about teaching students of color and I learned so much about how students of color do have cultural differences, but teachers have to learn about them and engage with them to fight racism.
Welche API´s?
Kein React, kein Vue, reines HTML und CSS im ersten Durchlauf. Bei jedem Aufruf deiner Webseite holt Flask Daten aus InfluxDB und rendert die Seite frisch. Alles Elegante kann später kommen.
Wie fängt man jetzt am besten an, wenn man noch keine Website gebaut hat?
Ich schlage dir vor, zunächst mit HTML und CSS eine Website zu gestalten, die visuell Antworten auf deine obigen Fragen liefert. Weil sie ein Lernprodukt aus der Veranstaltung ist, muss sie nicht funktionieren. Stattdessen kannst du den Zinnis mit diesem Mockup hinweise geben, wie sie im Rahmen ihres Relaunches mit den Daten umgehen können.
In InfluxDB findest du unter "Load data" eine Anleitung für Python mit Beispielen, wie du einen Query auf dein Bucket absetzt. Denkbar wäre nun, mit Flask und diesem Ansatz Daten aus deinem Bucket abzufragen und in dem Mockup anzuzeigen.
```python query_api = client.query_api()
query = """from(bucket: "my-bucket") |> range(start: -10m) |> filter(fn: (r) => r._measurement == "measurement1")""" tables = query_api.query(query, org="jonas-draussen")
for table in tables: for record in table.records: print(record) ``` Zusammengefasst:
Würdest du empfehlen, die Website lokal auf dem gleichen Raspberry Pi zu hosten, auf dem auch Node-RED und InfluxDB laufen, oder eher getrennte Systeme zu verwenden (z.B. wegen Ressourcen oder Ausfallsicherheit)?
Unser 24/7 Node-RED und InfluxDB sowie Chirpstack und Grafana laufen alle auf einem VPS bei IONOS. Da könnten wir auch deine Website hinlegen.
Zunächst ein einfaches Grafana-Dashboard aufsetzen, um schnell erste Ergebnisse zu sehen und die InfluxDB-Abfragen zu testen und im zweiten Schritt eine eigene, kleine Webseite drumherum bauen, die diese Daten mit den gewünschten Zusatzinformationen anreichert.
Genau so solltest du vorgehen!
Oberfläche mit Grafana
Missverständlich hier, dass das nicht ein Dashboard deiner Daten ist.
Weiter Ideen
Überleg mal, welche dieser Ideen leicht zu haben sind (DWD-Vergleich z. B.) und welche vielleicht auch erst nach einer Weile Sinn machen.
Willst du eigentlich nach dem Ende der Veranstaltung weiter daran arbeiten?
Die Idee dahinter ist, nicht nur nüchterne Daten zu zeigen, sondern sie in einen Kontext zu setzen, der auch für Laien sofort verständlich und unterhaltsam ist und einen Mehrwert für den Hof und die Anwohner in der Nähe schafft.
Ich finde deine Ideen und Fragen alle sehr gut!
ise ne, to increase reliability is to be careful notmuch.
This is crucial, but so challenging for educators!
essential for tr
I actually wanted to highlight the next paragraph but it wouldn't let me. I think that the warmth piece is immediately recognizable, where as the competence piece sometimes comes with time and trust and experience with a person.
imitmenttoservice”(Pp.xx).MEE
This is something that I want to embody as a mentor. I cannot help someone grow by only serving my own interests!
Giver,generous without*EngagesotherseEngagesotherstoget theirstringsattache
I was trying to just highlight "giver, generous without strings attached." I think this is so important for people who work thankless jobs. There are plenty of us in education.
Show loyaltyinvolves|twoq°arealtoothers,andspeakingabout peopleasthougtheywerepresent”(p.166)
I think that it's powerful to model this, especially speaking about people as if they were there, but it is also something I want to explicitly require of my staff (at least effort) at the beginning of the school year!
This is great work! I am wondering about a part in Sup Fig 7 where figure legend and method description do not detail how the values plotted are derived: "Dot plots representing significance of differences in H3K27ac (B and D) or H3K27me3 (C and E) signal across each tumor sample relative to ISCs (one-sided Kolmogorov-Smirnov p-value) at stemness and growth enhancers" Can the authors comment on how this was calculated to make the numbers easier to interprete?\
Also, the references are missing - can the authors share them?
Think about the purpose of your research and whether the keywords you are using closely align with your research question. You can use the tips you learned in Chapter 1 to make sure you’re using the best keywords for your research question.
The alignment of your keywords with your research question can help you know whether you are using the right search terms. I am on the right task through what i read.
Make it a habit to check your emotions and ensure that they aren’t affecting the choices you make in your research or life
Just like Figure 4.1 Headline misinforms public most times we can just allow our emotions to have the better part of our reasoning. before we realize it, we have damage ours or someone else's reputations by passing misinform information to the public without investigating and tracing the source.
Article is now published: https://doi.org/10.1523/ENEURO.0212-18.2018
Article is now published: https://doi.org/10.3389/fnins.2023.1175629
Article is now published: https://doi.org/10.1371/journal.pone.0348018
JRC repo
forgejo repo's by the EU institutions.
I don't know if you'll see this but I need to tell at least one person. When you've been holding on to something like this as long as I have. I have officially and verifiably solved The Theory of Everything. This is 100% true. Keep on doing your thing.
This is an interesting and potentially important paper. However, I recommend the authors reconsider their model assumptions and conclusions based on the following points after a first read:
1) The model is basically based on one paper, Forrest (1971), but this paper collected data for a "tundra" peatland ecosystem at Sike Hill (extreme conditions are outlined in the paper); biomass and vegetation heights are, therefore, unsurprisingly small by comparison to other temperate systems. This data represent a very extreme environment and should not be generalised.
2) The harsh tundra conditions reflect the historically much colder (~5°C mean temp at the time - now much warmer) and frequently high winter snow packs together with high winds and thus frost killing of shoots. The vegetation was shaped by those conditions for hundreds of years (and notably a very cold 10-year period before sampling in the 1960s); especially the "Big Freeze" in 1962/63 needs to be considered when interpreting or using those data. Basically, the growth/age data represent regrowth responses and recovery under those (past) extreme conditions.
3) Since then, the climate changed considerably. The information from Forrest (1971) basically does not currently apply to any significant blanket bog habitat in the UK (certainly not in England) - I think it already did not apply to much at the time of the paper. Basically, the data do not relate to blanket bog overall and certainly not under current or future climate.
4) Layering of heather under such conditions (heavy snow pack) is normal and to be expected (a growth strategy to tundra conditions). The actual ages of the heather plants are therefore much older, but this was not determined by Forrest (only the recent vertical shoots were measured) - but the recorded mass of such horizontal shoots is considerable.
5) Therefore, the histogram of the (vertical) stem numbers versus age is only representative of such a highly disturbed system - not a system in a 'normal' steady state (it is recovering from extreme conditions - certainly of the "Big Freeze"); moreover, the heather ages are almost certainly way out as only vertical stems were measured, ignoring the much older horizontal stems (which can be more than a meter long at that site - evidence is in a freezer available for age determination) from which those shoots resprouted. Therefore, it should not be used to inform a model for generic blanket bog heather ages, where stems are growing without this killing off during winter and flattening from snow - it clearly will be very different (and there are data on this growth/age from other, more relevant studies).
Some other observations:
Defra has not banned burning (although in effect they have - but they do not like seeing such statements it seems).
Quite a few important studies seem to have been overlooked (e.g., MacDonald, 1995; Harris et al., 2011 - and many references therein; Glatzel et al., 2024).
Sub-optimal growth conditions of heather are not defined - this is clearly a complex issue as heather has a wide range of adapted 'ecotypes', even growing quite massive under very wet conditions (our Mossdale site is one example; Heinemeyer et al., 2019; 2023).
Past vegetation needs to consider past climate (Little Ice Age!) - more Sphagnum and less heather are unsurprising under wetter and colder conditions but things warmed up since the ~1750s (and continue to get much warmer and drier).
Mowing has many more issues (smoldering brash risks, perfect tick habitat, ..., but also clearly has some benefits on soil moisture but not necessarily net, long-term carbon storage) but key studies and related papers are, unfortunately, not cited/considered (including Peatland-ES-UK ones). Heinemeyer et al. 2019/23 study is not a chronosequence study as stated and, unfortunately, our cited 2023 report is not listed in the reference list and it provides much more relevant information in addition to our papers on various claims about burning, cutting, rewetting etc.).
It is important not to confound papers/studies from topogenous bogs (e.g., valley and raised bogs) with hill blanket bogs (e.g., I think many Wallen 1980s papers are as such) - ecohydrological conditions (wetness and thus vegetation potential) need to be considered and comparable.
Formatting etc. issues in the reference list.
eLife Assessment
This important study shows that regions of the human auditory cortex that respond strongly to human voices are also sensitive to vocalizations from closely related primate species. The evidence is convincing and methodologically strong. The work offers significant insight into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.
Reviewer #1 (Public review):
Summary:
This study investigates how human temporal voice areas (TVA) respond to vocalizations from nonhuman primates. Using functional MRI during a species-categorization task, the authors compare neural responses to calls from humans, chimpanzees, bonobos, and macaques while modeling both acoustic and phylogenetic factors. They find that bilateral anterior TVA regions respond more strongly to chimpanzee than to other nonhuman primate vocalizations, suggesting that these regions are sensitive not only to human voices but also to acoustically and evolutionarily related sounds.
The work provides important comparative evidence for continuity in primate vocal communication and offers a strong empirical foundation for modeling how specific acoustic features drive TVA activity.
Strengths:
(1) Comparative scope: The inclusion of four primate species, including both great apes and monkeys, provides a rare and valuable cross-species perspective on voice processing.
(2) Methodological rigor: Acoustic and phylogenetic distances are carefully quantified and incorporated into the analyses.
(4) Neuroscientific significance: The finding of TVA sensitivity to chimpanzee calls supports the view that human voice-selective regions are evolutionarily tuned to certain acoustic features shared across primates.
(4) Clear presentation: The study is well organized, the stimuli well controlled, and the imaging analyses transparent and replicable.
(5) Theoretical contribution: The results advance u
Comments on revised version.
I thank the authors for having carefully considered and implemented my remarks on the first version.
Reviewer #2 (Public review):
Summary:
This study investigated how the human brain responds to vocalizations from multiple primate species, including humans, chimpanzees, bonobos, and rhesus macaques. The central finding-that subregions of the temporal voice areas (TVA), particularly in the bilateral anterior superior temporal gyrus, show enhanced responses to chimpanzee vocalizations-suggests a potential neural sensitivity to calls form phylogenetically close nonhuman primates.
Strengths:
The authors employed three analytical models to consistently demonstrate activation in the anterior superior temporal gyrus that is specific to chimpanzee calls. The methodology was logical and robust, and the results supporting these findings appear solid.
Weakness:
The authors only tested vocalizations from three non-human primate species other than humans. In this case, the species specificity of the effect does not fully represent the specificity of evolutionary relatedness.
Comments on revised version.
I have no further comments.
Reviewer #3 (Public review):
Summary:
Using fMRI, the authors demonstrate that human temporal voice areas (TVA) respond not only to human vocalizations but also to those of other primates, particularly chimpanzee calls, which share acoustic features with human voices. These findings provide compelling evidence for cross-species vocal processing in the human auditory system and carry important theoretical implications for understanding the evolutionary underpinnings of speech perception.
Strengths:
The study offers a valuable comparative design, rigorous acoustic and phylogenetic modeling, and consistent evidence that bilateral anterior TVA regions respond more strongly to chimpanzee vocalizations than to other species' calls. The inclusion of both great apes and monkeys provides a rare cross-species perspective.
Weaknesses:
Minor limitations include the acoustic-phylogenetic confound (which the authors partially address with additional analyses), the lack of non-vocal controls to establish true selectivity.
Overall, the methods, data, and analyses broadly support the claims, with only minor weaknesses that do not undermine the main conclusions. The findings are valuable for the subfield of auditory neuroscience and comparative cognition, with solid evidence supporting the primary claims.
Comments on revised version.
After revision, this work has shown great improvement in data analysis, figure organization, and writing. I have no further suggestions.
Author response:
The following is the authors’ response to the original reviews.
Public Reviews:
Reviewer #1 (Public review):
Summary:
This study investigates how human temporal voice areas (TVA) respond to vocalizations from nonhuman primates. Using functional MRI during a species-categorization task, the authors compare neural responses to calls from humans, chimpanzees, bonobos, and macaques while modeling both acoustic and phylogenetic factors. They find that bilateral anterior TVA regions respond more strongly to chimpanzee than to other nonhuman primate vocalizations, suggesting that these regions are sensitive not only to human voices but also to acoustically and evolutionarily related sounds.
The work provides important comparative evidence for continuity in primate vocal communication and offers a strong empirical foundation for modeling how specific acoustic features drive TVA activity.
Strengths:
(1) Comparative scope: The inclusion of four primate species, including both great apes and monkeys, provides a rare and valuable cross-species perspective on voice processing.
(2) Methodological rigor: Acoustic and phylogenetic distances are carefully quantified and incorporated into the analyses.
(4) Neuroscientific significance: The finding of TVA sensitivity to chimpanzee calls supports the view that human voice-selective regions are evolutionarily tuned to certain acoustic features shared across primates.
(4) Clear presentation: The study is well organized, the stimuli well controlled, and the imaging analyses transparent and replicable.
(5) Theoretical contribution: The results advance understanding of the neural bases of voice perception and the evolutionary roots of voice sensitivity in the human brain.
Weaknesses:
(1) Acoustic-phylogenetic confound: The design does not fully disentangle acoustic similarity from phylogenetic proximity, as species co-vary along both dimensions. A promising way to address this would be to include an additional model focusing on the acoustic features that specifically differentiate bonobo from chimpanzee calls, which share equal phylogenetic distance to humans.
(2) Selectivity vs. sensitivity: Without non-vocal control sounds, the study cannot determine whether TVA responses reflect true selectivity for primate vocalizations or general auditory sensitivity.
(3) Task demands: The use of an active categorization task may engage additional cognitive processes beyond auditory perception; a passive listening condition would help clarify the contribution of attention and task performance.
(4) Figures and presentation: Some results are partially redundant; keeping only the most representative model figure in the main text and moving others to the Supplementary Material would improve clarity.
We thank the reviewer for contributing to the improvement of the present study and for the extremely constructive criticism. Concerning the identified weaknesses of our work, we provide here some general answers while the detailed review (below) addresses point-by-point the reviews in high detail.
(1) We totally agree that acoustics and phylogeny cannot be disentangled in our study, which is a limitation. We now provide the suggested analysis on the acoustic specificities of chimpanzee and bonobo calls.
(2) This point on selectivity vs. specificity is indeed crucial, and we now provide a more careful viewpoint and phrasing on this aspect, since our study can only provide partial arguments for this important distinction.
(3) Task demand following species categorization might rightfully yield to the engagement of distinct brain network compared to merely listening to the stimuli. We discuss this aspect and put forward the argument that, while we cannot control for this aspect, our attentional control study performed by an independent sample, N=28 provides clear evidence that no species triggered an attention bias. In other words, task demand might play a role, but at least in the study we know that attentional resources were not biased towards one species in particular since no effects were observed.
(4) We agree that results were not articulated in a clear fashion and that figures were redundant. We addressed this aspect and regrouped the figures where appropriate while we include the rest in the supplementary material now.
Reviewer #2 (Public review):
Summary:
This study investigated how the human brain responds to vocalizations from multiple primate species, including humans, chimpanzees, bonobos, and rhesus macaques. The central finding - that subregions of the temporal voice areas (TVA), particularly in the bilateral anterior superior temporal gyrus, show enhanced responses to chimpanzee vocalizations - suggests a potential neural sensitivity to calls from phylogenetically close nonhuman primates.
Strengths:
The authors employed three analytical models to consistently demonstrate activation in the anterior superior temporal gyrus that is specific to chimpanzee calls. The methodology was logical and robust, and the results supporting these findings appear solid.
Weaknesses:
The interpretation of the findings in this paper regarding the evolutionary continuity of voice processing lacks sufficient evidence. A simple explanation is that the observed effects can be attributed to the similarity in low-level acoustic features, rather than effects specific to phylogenetically close species. The authors only tested vocalizations from three non-human primate species, other than humans. In this case, the species specificity of the effect does not fully represent the specificity of evolutionary relatedness.
We want to thank the reviewer for the constructive criticism and for evaluating the manuscript.
Concerning the principal weakness highlighted, we provide new analyses behavioral, acoustics, model-based fMRI that improve our understanding of the influence of both phylogeny and bioacoustics in our data. We argue that the explanation proposed by the reviewer cannot explain our results, as also observed in several other research from us and others. We discuss this aspect and emphasize that including stimuli from more species would greatly improve the understanding of phylogeny and bioacoustics in this context.
Reviewer #3 (Public review):
Summary:
Ceravolo et al. employed functional magnetic resonance imaging (fMRI) to examine how the temporal voice areas (TVA) in the human brain respond to vocalizations from different nonhuman primate species. Their findings reveal that the human TVA is not only responsible for human vocalizations but also exhibits sensitivity to the vocalizations of other primates, particularly chimpanzee vocalizations sharing acoustic similarities with human voices, which offers compelling evidence for cross-species vocal processing in the human auditory system. Overall, the study presents intellectually stimulating hypotheses and demonstrates methodological originality. However, the current findings are not yet solid enough to fully support the proposed claims, and the presentation could be enhanced for clarity and impact.
Strengths:
The study presents intellectually stimulating hypotheses and demonstrates methodological originality.
Weaknesses:
(1) The analysis of the fMRI data does not account for the participants' behavioral performance, specifically their reaction times (RTs) during the species categorization task.
(2) The figure organization/presentation requires significant revision to avoid confusion and redundancy.
We thank the reviewer for evaluating our manuscript and for the constructive criticism as well as the many suggestions. Concerning the weaknesses of the study, we provide here some quick answers while more detailed responses can be found below.
(1) We now include behavioral data analysis (accuracy data controlled for reaction times and acoustics of existing Model 3, using mixed-effects logistic regression) in addition to a new, 4th model for fMRI data. This 4th model was computed in a model-based fashion by modeling the probability of correct categorization within the TVA (fitted regression coefficients, per Participant, Species, Trial) and revealing the neural correlates of this modulator.
(2) We totally agree that figure redundancy was a problem and we now reduced confusion by combining congruent aspects while pushing other results to the supplementary material.
Recommendations for the authors:
Reviewing Editor Comments:
With additional analyses and discussions, the work has the potential to offer important insight into the evolutionary continuity of voice processing.
We thank the Reviewing Editor for this additional motivation and for offering us the possibility to revise our manuscript. We will now provide our point-by-point reviewing, referring to manuscript modifications by section and/or line number(s). All modifications are also highlighted in light grey in the text.
Reviewer #1 (Recommendations for the authors):
The manuscript is clearly written and addresses an important comparative question about the specificity of human TVA responses. The acoustic analyses are well designed, and the imaging work is careful and thorough. However, several conceptual and methodological issues need clarification or tempering of claims, particularly regarding (i) the distinction between sensitivity and selectivity, (ii) the confounding of acoustic and phylogenetic factors, and (iii) the interpretation of "chimpanzee-specific" TVA activity.
(1) Introduction
Line 48: cite more recent infant EEG evidence for early voice sensitivity (Calce, Curr Biol).
The reference and explanation were added, lines 46-48.
Line 53: mention recent data on voice processing in marmosets (Jafari, Cell Rep; Dureux, Curr Biol).
We added the references and the mention of these interesting studies on common marmosets, lines 53-54.
Line 59: Fecteau et al. (2004) already explored cross-species selectivity; please integrate and discuss.
We now mention here the work from Fecteau and colleagues and its relevance, see lines 57-59.
Line 70: clarify that in [27] (Bodin et al., 2021) human TVA responded similarly to human nonverbal vocalizations and macaque coos, likely due to acoustic similarity.
We added this important aspect, thank you for this precision. See lines 71-72.
Clarify why an active species-categorization task was chosen instead of passive listening, which is standard in TVA research. Were participants familiarized with stimuli beforehand?
We added a sentence on this aspect, but basically to summarize it here: we wanted to be able to test human recognition of nonhuman primate species’ calls. From the start, we wanted to test the frontal mechanisms related to decision-based processes of humans when categorizing non-human primate calls hence the 2023 article we published. See lines 75-77 and we also added information on familiarization to the stimuli in the Methods, lines 679-682.
The 16 acoustic features mentioned should be briefly defined earlier, as they are central.
We feel like describing 16 acoustic parameters in the introduction would be heavy on the reader, so we instead added a reference to the supplementary table (Table S1) in which these are named and described. See line 80.
Explain why only chimpanzees and bonobos were selected among the great apes, and discuss the value of including both, given their equal phylogenetic proximity but largely dissimilar acoustics.
The stimuli were obtained by Thibaud Gruber and his team and through collaborations with Katie Slocombe and Zanna Clay. Unfortunately, at the time we could only use chimpanzee and bonobo calls for the great apes. Therefore, it was mainly a material constraint rather than a deliberate choice to exclude other great apes. We now discuss this aspect and present the absence of other great apes as a limitation (lines 587-591).
Rephrase references to "recruitment" of TVA - this term implies general activation, while the key question concerns selectivity (stronger responses to voices vs. non-vocal controls).
We rephrased throughout the manuscript, thank you for this suggestion.
The hypothesis section should more clearly separate the acoustic and phylogenetic predictions, and clarify which earlier data motivate each.
We now explicitly categorize the hypotheses according to either Bioacoustics or Phylogeny to clarify. We also added references motivating each hypothesis. See lines 114-120.
(2) Methods
Clarify whether stimuli were RMS-normalized or otherwise balanced for energy (line 128).
Sound pressure level was kept constant but the stimuli were not normalized, specifically to avoid a negative impact on their naturality. We added a sentence (lines 131-132) including a reference on this aspect.
The task design could benefit from reporting accuracy in addition to reaction times for the 4AFC species classification task.
We agree this aspect was missing. We now report accuracy data (controlled for reaction times and acoustics of Model 3) for the species categorization task (lines 147-165; Fig.1B), and in the Methods (lines 769-786). The fitted regression values of this analysis are also used for a new fMRI model (Model 4), to uncover within-TVA correlates of the probability of correct species categorization (lines 309-325; Fig.4).
Please note that previously, the behavioral data of the species categorization task were completely absent (N=23), and the reaction times data previously part of Fig.1 were for the species attentional bias task (independent sample of N=28). Since this aspect was not clear at all (same remark by all reviewers—apologies for that), we now include a clear separation in Fig.1, with newly added panels D & E part of a distinct figure area named: “Control task: Testing for Species attentional bias (N=28)”. Panel D illustrates the control task paradigm (each species as exogenous cue; “dot-probe” paradigm) while panel E shows the results (target sine wave tone or “bip” detection reaction times), showing that no species triggered more attentional capture than the others (Species effect non-significant).
The acoustic parameters used in Models 2 and 3 should be explicitly listed in the Methods (even if already published elsewhere).
In addition to their description in Table S1, we now include the 16 acoustic parameters used to calculate acoustic distance between the species in the Methods, see lines 828-844.
Consider simplifying the presentation of the three models: a figure summarizing their relationships would help.
We now include only one figure (Fig.2) for Model 3, and we pushed model 1&2 to the supplementary material. We also simplified Fig.3 for a clearer view of the overlaps between the 3 models within the TVA.
The description of “systematic and thorough control of phylogeny” (line 119) is overstated, given that only three nonhuman species were included.
We agree with the reviewer and we suppressed both “systematic” and “thorough” from the sentence.
Provide rationale for not including a nonvocal control category (e.g., scrambled vocalizations or environmental sounds) to assess TVA selectivity.
The main objective of the study was to uncover whether human participants could recognize the vocalizations from nonhuman primates—from both great apes and monkeys—as compared to the human voice. We therefore did not include nonvocal or noise stimuli. We added this point as a limitation in the Discussion (lines 593-596 and 609-611).
Even though we did not include such stimuli for the reason mentioned above, the delineation of subtypes of nonvocal material within the TVA of our participants (Fig.2) are, in our opinion, clarifying the message: chimpanzee-selective activations are fully within ‘voice vs. animal’ and ‘voice vs. nature’ TVA subareas, while it is not the case in ‘voice vs. music’ and ‘voice vs. noise’ TVA subareas.
Clarify if participants were trained or had a practice session to recognize the four species before scanning.
The participants were indeed trained on 3 stimuli per species before entering the MRI scanner. These stimuli were discarded from the species categorization task. We added a sentence about this aspect, see lines 131-132.
Specify what is meant by "no good or bad response" in the attentional control task (line 724).
We suppressed this wording as it was highly confusing.
(3) Results
Behavioral accuracy should be reported to complement reaction times.
We now added behavioral data for the species categorization task as well as the neural correlates of accurate species categorization. See our previous response above (‘‘‘).
Figures 2-4 largely overlap; consider merging or simplifying to reduce redundancy.
We agree and this point was raised by the other reviewers as well. Task-based results are now presented only for Model 3 as Fig.2, while Fig.3 (previously Fig.5) summarizes the overlap between the three models. Figures for Models 1 & 2, previously labelled Fig.3 and Fig.4, were moved to the supplementary material.
Figure 2: Please indicate more clearly where "chimp-selective" areas are located (perhaps with zooms).
We agree, we now modified Fig.2 with zoomed-in panels and a clearer outline of chimp-selective areas (solid blue outline). This outline is also referenced in the text (lines 236-237).
Correction for multiple contrasts: With many pairwise tests, adjustments (Bonferroni or FDR) should be mentioned explicitly.
We now specify ‘FDR correction at the voxel level’ at the beginning of the Results section (lines 195-198) as well as in each figure.
Replace "specific to chimpanzee" with "selective for chimpanzee" to avoid implying exclusivity.
We made the suggested replacement throughout the manuscript.
Discuss whether the small macaque-related clusters might simply reflect acoustic overlap rather than true category selectivity.
We added a section on this important aspect, including results that support the role of mid-STG/STS regions for more noise-like stimuli, including the use of macaque coos. See lines 450-461.
(4) Discussion
The discussion overstates claims of "chimpanzee-selectivity" in TVA. The evidence shows relative preference, not absolute selectivity.
We now specify from the start of the Discussion that we are not interpreting the results as absolute selectivity but rather as more relative preference, see lines 371-373.
The authors repeatedly conflate acoustic and phylogenetic factors; this should be explicitly acknowledged as a limitation.
We agree, and we completed the limitations section already dedicated to this aspect by a more explicit account of the confound, see lines 609-611.
Clarify what is meant by "recruitment" and "selectivity" (lines 411-419, 577). TVA activity often reflects enhanced responses to voices compared to non-vocal sounds, not exclusive activation.
We clarified this wording in the Discussion (lines 377-378) and replaced another instance by “activated the […]” to make it clearer what we imply, namely enhanced activity triggered by chimpanzee calls within human TVA.
The lack of non-vocal control conditions should be discussed as a major interpretive limitation.
We added this point as a limitation in the Discussion (lines 593-596).
The statement that "chimpanzee-selective activity" arose in humans who have never been exposed to chimp calls (line 450) invites evolutionary speculation but should be more cautiously phrased.
We agree, and we rephrased by: “[…] with chimpanzee calls triggering responses in the anterior STG/TVA of our human participants […]”. See lines 432-433.
The comparison to recent macaque data (Giamundo et al., 2024 PNAS) is crucial: these findings of human-voice-selective neurons in macaques directly parallel the present human-chimp result.
We agree with the reviewer, and we are hopeful to read similar results for other apes/great apes in the future.
Reviewer #2 (Recommendations for the authors):
(1) The primate vocalizations used in this study were recorded in diverse social and emotional contexts, which may have contributed to the observed differences in TVA activation. Since the temporal voice areas are known to be sensitive to affective and socially relevant cues, these contextual differences could confound the interpretation of species-specific neural responses. Therefore, I suggest that the authors conduct a post-hoc analysis to quantify and compare the affective valence, arousal levels, and social contexts associated with each stimulus set.
We agree that the TVA are sensitive to social—or socially relevant—cues, motivating the very thorough work of the expert reserve personnel on-site to accurately categorize the calls according to the very specific context they were produced in. If the reviewer meant presenting these stimuli to non-expert participants and asking them to categorize the context or valence, we think it would make no sense since the ratings would be completely below chance level and therefore uninformative. The newly added behavior—and model-based fmri—data include this crucial point, a factor that we named ‘Context’ in our analyses. In fact, for each species’ 18 stimuli, we control for agonistic and affiliative production context—split evenly, per species. Also, computing an additional posthoc analysis by splitting the stimuli according to Context would result in too few trials to get sensible and reliable fMRI results.
That being said, our study targets this specific aspect by extracting the acoustic features that characterize our stimulus set the best, across context-species-valence-arousal, which is exactly what we want. Through the three types of modeling we used—from more simplistic to more elaborate the results converge only for one species: chimpanzee calls.
We think the addition of behavioral data, model-based fMRI data, and the specific analysis on acoustic differences between chimpanzee and bonobo calls strengthens the message and the validity of our findings.
(2) Although the author mentioned that the behavioral effects triggered by these vocalizations have been reported previously, the behavioral responses of the participants in the current study are also crucial for our understanding of the results. If the MRI data can be combined with the participants' behavioral responses for comprehensive analysis, the conclusions of this study will be more compelling.
We agree with the reviewer, and we added the behavioral data—controlling for reaction times, production context and acoustics of interest—and we also included a model-based fMRI modeling of the probability of correct species categorization as Model 4, Fig.4. See, respectively: lines 147-165, Fig.1B; Methods, lines 769-786; Neuroimaging results, lines 309-325.
(3) I am still not convinced that phylogenetic proximity drives the observed neural selectivity. While chimpanzee vocalizations do elicit stronger responses in anterior STG, the claim that this reflects evolutionary relatedness lacks evidence. If the acoustic features of a certain call from a particular species are similar to those of human voices, it may also lead to similar effects.
We agree with the reviewer that generalizing our results in terms of phylogenetic proximity alone is not a viable option. Including many more primate species including other great apes would be necessary, and we mention this crucial aspect in the limitations section. We also insist in the Discussion on the interdependence between phylogeny and acoustics in our data, since: 1) we cannot fully disentangle these factors here, 2) we cannot attribute our results to either one or the other. See lines 387-390, 410-411, 473-477, 587-591.
If the acoustic features of a certain call from a particular species are similar to those of human voices, it may also lead to similar effects.
We agree, and nobody could disagree: if an auditory object is extremely similar to the human voice in terms of acoustics, it would therefore potentially activate the TVA. This is exactly our message: in the natural ‘auditory world’, the calls from chimpanzees seem to be among the very few animal auditory signals that are sufficiently close, acoustically, to the human voice and therefore trigger TVA activity. They also happen to be the calls from a species which is phylogenetically the closest to humans with minimal differences with other great apes. Our results are in that sense very aligned with work from the laboratory of Pascal Belin, namely on ‘voice patches’ in the primate brain located in the (anterior) TVA, cited in our manuscript.
We therefore think our interpretation does not exclude that in the near future, similar results within the TVA could be observed for other auditory objects, and if animal, from a species potentially much more distant phylogenetically or from vocal signals of other great apes.
We added a key limitation point in the Discussion on the absence of auditory control stimuli in our design, such as scrambled or spectrum shifted per-species stimuli, which would have made the interpretation clearer identical acoustics but alteration/destruction of the species auditory object. See lines 593-596 and 609-611.
Reviewer #3 (Recommendations for the authors):
While the manuscript presents intriguing results, several concerns are raised for further consideration, detailed below.
We thank the reviewer for evaluating the manuscript and for the constructive criticism and suggestions.
Major concerns:
(1) This study claims that bilateral anterior superior temporal gyrus (aSTG) in humans can be specifically activated by chimpanzee vocalizations rather than all other primate species after regressing out relevant acoustic parameters using three distinct analyses. I am wondering if a control stimulus (e.g., scrambled chimpanzee vocalizations) were presented, would the activation patterns in these same temporal voice areas (TVA) exhibit significant differences compared to the natural chimpanzee vocalizations?
We completely agree with the reviewer, and this point was also raised by the other reviewers. We therefore added a key limitation point in the Discussion on the absence of auditory control stimuli in our design, such as per-species scrambled or spectrum shifted stimuli, which would have made the interpretation clearer—identical acoustics but alteration/destruction of the species auditory object. See lines 609-611.
(2) The figure organization/presentation requires significant revision to avoid confusion and redundancy. E.g:
Figure 1C is the same as Figure S1. In addition, Figure 1C lacks a figure legend and descriptive label.
The scatter plots in Figures 2D, 2H, 3D, 3H, and 4D, 4H are same as those in Figures S2, S3, and S4. However, some of these duplicate plots even have inconsistent axis labels.
In several panels, the main figures appear to be summaries derived from the supplementary figures. The authors should organize these figures well to eliminate redundancy.
Please double-check all the figures to make sure of accuracy.
We agree that the figures were badly organized and were too crowded and redundant. We now suppressed the redundancy between Fig.1 and Fig.S1, and we reduced fMRI results to one figure for statistical Model 3 while the other models are in the supplementary data—we also justify this decision in the text by highlighting that model 3 is the most elaborate and sensitive one. Fig.3 (previously ‘Fig.5’) shows the overlaps between models and was simplified and clarified as well.
(3) The analysis of the fMRI data does not account for the participants' behavioral performance, specifically their reaction times (RTs) during the species categorization task. It is possible that processing vocalizations from certain species requires more cognitive effort or induces higher decision uncertainty. Could the observed neural effects be confounded by the decision-making process itself?
We now include behavioral data analysis (accuracy data controlled for reaction times and acoustics of existing Model 3, using mixed-effects logistic regression) in addition to a new, 4th model for fMRI data. This 4th model was computed in a model-based fashion by modeling the probability of correct categorization within the TVA (fitted regression coefficients, per Participant, Species, Trial) and revealing the neural correlates of this modulator. We now display these results in Fig.4 and we introduce the motivation factor for including a categorization task rather than more traditional passive listening (lines 75-77), as well as limitations, lines 595-596.
(4) One interesting attempt of this study is to dissociate biologically salient information in animal vocalizations from their low-level acoustic properties. This presents a fundamental conceptual challenge: how to rigorously disentangle a vocalization's species-specific attributes from its inherent acoustic correlates. More precisely, what essential biological information persists in a species' vocal signal after statistically accounting for all quantifiable acoustic features? I recommend that the authors address it in the discussion.
We thank the reviewer for this very important comment, and for suggesting we discuss it in the manuscript. We completely agree: we cannot fully orthogonalize species and acoustics, and this aspect relates also more broadly to cognitive and affective neuroscience studies involving vocal material. Namely: “What is an auditory object without acoustics?”
We included a full paragraph on this aspect, see Discussion, lines 570-584.
(5) If a brain region, such as TVA, is responsive to both acoustic parameters and biological meanings of animal vocalizations, the method used in this study might be inadequate by setting covariates to zero. It is possible that species information is embedded within a specific acoustic pattern. The current modeling approach may not capture such complex information and could potentially introduce bias when estimating the species effect. I recommend that the authors address this issue in the discussion.
We thank the reviewer for this point once again, we addressed it in the Discussion, lines 581-584, and also in the section dedicated to study limitations, lines 609-613.
(6) In the discussion, non-human primate vocalizations are "unreadable" to humans. If this is the case, what is the fundamental perceptual difference between these vocalizations and those from the other animal species? An alternative and highly plausible explanation for the findings is the differential familiarity of the participants with the various species, driven by media exposure (e.g., documentaries) or zoo visits and interactions. The authors need to provide a stronger justification for their control stimuli and directly address, either through discussion or additional analysis, how the factor of familiarity might explain their results better than the proposed "evolutionary distance" hypothesis.
We now discuss this important aspect, see lines 560-569.
We thought about doing additional analyses on this aspect but we concluded that we did not have any reliable indicators of familiarity for our participants, and additionally they were all recruited for being ‘unfamiliar’ with great apes or old-world monkeys’ vocalized communication.
Also, frequent mismatches in the media between images of apes and the associated vocal signals (for instance, the depiction of a chimpanzee but with background audio of macaque coos) are not helping this cause.
Minor:
(1) No figure legend and result description for Figure 1.
Figure 1 has a legend, maybe it was cut out during the uploading process, but it is present and verified now.
(2) In the main text, three statistical models were referenced. Was the data used in each subsequent statistical model derived from the processed data of the preceding model? Please clearly explain this in the main text.
We now specify this aspect in the Methods and the Results section to clarify that each model is independent from the others (lines 964-966 and 189-191, respectively).
(3) In Figure 5, the two dashed lines representing Model 1 and Model 2 are confusing for readers.
We modified the figure (now Fig.3) and simplified it by removing some outlines and clarifying the colors, therefore improving readability.
(4) Lack of reaction times in the species categorization task.
We clarified behavioral data, including the results for the species categorization task and for the control, exogenous cueing task, see modified Fig.1 and behavioral results section of the Results.
(5) Figures 2, 3, 4, 5, Please keep the font size of the figure title consistent.
Figure title font size were uniformized.
(6) Line 201, Line 224, and so on, (EFG) → (E, F, G).
We modified this aspect in every figure legend, including the supplementary material.
eLife Assessment
Argunşah et al. investigate the mechanisms underlying the differential response dynamics of barrel vs septa domains in shaping the responses to single vs multiple whiskers. Based on the observation of a higher density of SST+ interneurons in the septa, the authors investigate the hypothesis that Elfn1-dependent short-term plasticity shapes these responses. This important study is, however, supported by incomplete evidence; factors restricting the strength of evidence are the limited spatial resolution of the multi-unit activity, as well as the lack of a mechanistic explanation. This provocative and intellectually stimulating hypothesis provides a contribution to work on how different cell types shape cortical representation.
Reviewer #1 (Public review):
Summary:
Argunşah et al. describe and investigate the mechanisms underlying the differential response dynamics of barrel vs septa domains in the whisker-related primary somatosensory cortex (S1). Upon repeated stimulation, the authors report that the response ratio between multi- and single-whisker stimulation increases in layer (L) 4 neurons of the septal domain, while remaining constant in barrel L4 neurons. The authors attribute this divergence to differences in short-term synaptic plasticity, particularly within somatostatin-expressing (SST⁺) interneurons. This interpretation is supported by 1) the increased density of SST+ neurons in L4 of the septa compared to barrel domain, 2) the stronger response of (L2/3) SST+ neurons to repeated multi- vs single-whisker stimulation and 3) the reduced functional difference in single- versus multi-whisker response ratios across barrel and septal domains in Elfn1 KO mice, which lack a synaptic protein that confers characteristic short-term plasticity, notably in SST+ neurons. Consistently, a decoder trained on WT data fails to generalize to Elfn1 KO responses. Finally, the authors report a relative enrichment of S2- and M1-projecting cell densities in L4 of the septal domain compared to the barrel domain, suggesting that septal and barrel circuits may differentially route information about single vs multi-whisker stimulation downstream of S1.
Strengths:
This paper describes and aims to study a circuit underlying differential response between barrel columns and septal domains of the primary somatosensory cortex. This work supports the view these two domains contribute distinctly to the processing single versus multi-whisker inputs and highlight the role of SST+ neuron and their short-term plasticity. Together, this study suggests that the barrel cortex multiplexes whisker-derived sensory information across its domains, enabling parallel processing within S1.
Weaknesses:
Although the divergence in responses to repeated single- versus multi-whisker stimulation between barrel and septal domains is consistent with a role for SST⁺ neuron short-term plasticity, the evidence presented does not conclusively demonstrate that this mechanism is the critical driver of the difference. The lack of targeted recordings and manipulations limits the strength of this conclusion: SST⁺ neuron activity is not measured in L4, nor is it assessed in a domain-specific manner. The Elfn1 knockout manipulation does not appear to selectively affect either stimulus condition, domain or interneuron subtype. Finally, all experiments were performed under anesthesia, which raises concerns about how well the reported dynamics generalize to awake cortical processing.
Reviewer #3 (Public review):
Summary:
This study investigates the functional differences between barrel and septal columns in the mouse somatosensory cortex, focusing on how local inhibitory dynamics (particularly involving SST⁺ interneurons) may mediate temporal integration of multi-whisker (MW) stimuli in septa. Using a combination of in vivo multi-unit recordings, calcium imaging, and anatomical tracing, the authors propose a model in which Elfn1-dependent synaptic facilitation onto SST⁺ interneurons contribute to the distinct sensory responses to MW input in barrels and septa, enabling functional segregation between these domains.
Strengths:
The study presents a thought-provoking and useful conceptual model for understanding sensory processing in the somatosensory cortex. While barrel columns have been widely studied, septal regions remain relatively understudied in mice. If septa indeed act as selective integrators of distributed sensory input, this would suggest a novel computational role for cortical microcircuits beyond the classical view focused on barrels. Although still hypothetical, the proposed model in which SST⁺ interneurons contribute to domain-specific sensory responses between barrel and septal domains is intriguing and opens new avenues for investigating inhibitory circuit mechanisms.
Weaknesses:
The primary limitation of this study lies in the spatial and cellular specificity of the recording techniques. The physiological data rely predominantly on unsorted multi-unit activity (MUA) recorded with low-channel-count silicon probes. Because MUA aggregates signals from multiple neurons over a radius of approximately 50-100 µm (comparable to or larger than the width of septal domains in mice), it remains difficult to confidently attribute the recorded activity exclusively to septal versus barrel populations. The authors have now addressed this concern more carefully by reframing their interpretation in terms of "septal-enriched" populations and by providing additional threshold-based analyses suggesting that the principal effects are more robust in Layer 4. These additions substantially improve the manuscript and support a more cautious interpretation of the findings. Nevertheless, the proposed Elfn1/SST⁺ mechanism remains supported primarily by indirect evidence. Although the calcium imaging data provide useful support for stimulus-dependent SST⁺ recruitment, these experiments were restricted to L2/3 interneurons and therefore do not directly test the Layer 4 circuit mechanism proposed to underlie the electrophysiological observations. Direct in vivo cell-type-specific recordings and manipulations in Layer 4 would ultimately be required to establish the proposed mechanism more conclusively.
Comments on revised version.
I have read the revised manuscript and overall, I think the authors have addressed my major concerns appropriately. I appreciate the substantially moderated interpretation of the findings and the additional analyses clarifying the limitations of the MUA recordings.
Author response:
The following is the authors’ response to the previous reviews
Public Reviews:
Reviewer #1 (Public review):
Summary:
Argunşah et al. describe and investigate the mechanisms underlying the differential response dynamics of barrel vs septa domains in the whisker-related primary somatosensory cortex (S1). Upon repeated stimulation, the authors report that the response ratio between multi- and single-whisker stimulation increases in layer (L) 4 neurons of the septal domain, while remaining constant in barrel L4 neurons. The authors attribute this divergence to differences in short-term synaptic plasticity, particularly within somatostatin-expressing (SST<sup>+</sup>) interneurons. This interpretation is supported by
(1) The increased density of SST+ neurons in L4 of the septa compared to barrel domain,
(2) The stronger response of (L2/3) SST+ neurons to repeated multi- vs single-whisker stimulation and
(3) the reduced functional difference in single- versus multi-whisker response ratios across barrel and septal domains in Elfn1 KO mice, which lack a synaptic protein that confers characteristic short-term plasticity, notably in SST+ neurons.
Consistently, a decoder trained on WT data fails to generalize to Elfn1 KO responses. Finally, the authors report a relative enrichment of S2- and M1-projecting cell densities in L4 of the septal domain compared to the barrel domain, suggesting that septal and barrel circuits may differentially route information about single vs multi-whisker stimulation downstream of S1.
Strengths:
This paper describes and aims to study a circuit underlying differential response between barrel columns and septal domains of the primary somatosensory cortex. This work supports the view these two domains contribute distinctly to the processing single versus multi-whisker inputs and highlight the role of SST+ neuron and their short-term plasticity. Together, this study suggests that the barrel cortex multiplexes whisker-derived sensory information across its domains, enabling parallel processing within S1.
Weaknesses:
Although the divergence in responses to repeated single- versus multi-whisker stimulation between barrel and septal domains is consistent with a role for SST<sup>+</sup> neuron short-term plasticity, the evidence presented does not conclusively demonstrate that this mechanism is the critical driver of the difference. The lack of targeted recordings and manipulations limits the strength of this conclusion: SST<sup>+</sup> neuron activity is not measured in L4, nor is it assessed in a domain-specific manner. The Elfn1 knockout manipulation does not appear to selectively affect either stimulus condition, domain or interneuron subtype. Finally, all experiments were performed under anesthesia, which raises concerns about how well the reported dynamics generalize to awake cortical processing.
We thank the reviewer for their careful reading of the manuscript and their balanced assessment of both its strengths and limitations. We acknowledge the reviewer’s concerns regarding the lack of direct, layer- and cell-type–specific recordings and manipulations of SST<sup>+</sup> interneurons, as well as the use of anesthesia. As noted in the Discussion, these factors limit the extent to which causal mechanisms can be established and the degree to which the reported dynamics can be generalized to awake cortical processing. For this reason, we intentionally frame the Elfn1–SST mechanism as a working model supported by converging anatomical, developmental, physiological, and genetic evidence, rather than as definitive proof. We believe this conceptual framing appropriately reflects the scope of the current data while highlighting clear directions for future work.
Reviewer #2 (Public review):
Summary:
Argunsah and colleagues demonstrate that SST expressing interneurons are concentrated in the mouse septa and differentially respond to repetitive multi-whisker inputs. Identifying how a specific neuronal phenotype impacts responses is an advance.
Strengths:
(1) Careful physiological and imaging studies.
(2) Novel result showing the role of SST+ neurons in shaping responses.
(3) Good use of a knockout animal to further the main hypothesis.
(4) Clear analytical techniques.
Comments on revisions:
The authors have effectively responded to my initial critiques - I have no further concerns.
We thank the reviewer for their positive evaluation of our work and for recognizing the novelty of the findings, the careful physiological and imaging approaches, the use of the Elfn1 knockout model, and the clarity of the analytical framework. We are pleased that the reviewer has no further concerns and appreciates the contribution of this study to understanding the role of SST<sup>+</sup> interneurons in shaping sensory processing in the barrel cortex.
Reviewer #3 (Public review):
Summary:
This study investigates the functional differences between barrel and septal columns in the mouse somatosensory cortex, focusing on how local inhibitory dynamics (particularly involving SST<sup>+</sup> interneurons) may mediate temporal integration of multi- whisker (MW) stimuli in septa. Using a combination of in vivo multi-unit recordings, calcium imaging, and anatomical tracing, the authors propose a model in which Elfn1-dependent synaptic facilitation onto SST<sup>+</sup> interneurons contributes to the distinct sensory responses to MW input in barrels and septa, enabling functional segregation between these domains.
Strengths:
The study presents a thought-provoking and useful conceptual model for understanding sensory processing in the somatosensory cortex. While barrel columns have been widely studied, septal regions remain relatively understudied in mice. If septa indeed act as selective integrators of distributed sensory input, this would suggest a novel computational role for cortical microcircuits beyond the classical view focused on barrels. Although still hypothetical, the proposed model in which SST<sup>+</sup> interneurons contribute to domain-specific sensory responses between barrel and septal domains is intriguing and opens new avenues for investigating inhibitory circuit mechanisms.
Weaknesses:
The primary limitation of this study lies in the spatial and cellular specificity of the recording techniques. The physiological data rely predominantly on unsorted multi-unit activity (MUA) recorded with lowchannel-count silicon probes. Because MUA aggregates signals from multiple neurons over a radius of approximately 50-100 µm (often wider than the typical septal width in mice), this approach makes it difficult to confidently isolate activity originating strictly from within septal domains. The manuscript would benefit from additional analyses to validate the spatial specificity of these recordings, such as systematically varying spike detection thresholds to test the robustness of domain attribution, as suggested by the reviewer. Furthermore, although the authors now appropriately frame their findings in the Elfn1 knockout mice as indirect evidence, it is worth emphasizing that the study lacks direct in vivo, cell-type-specific recordings and manipulations to more definitively test the proposed mechanism.
We thank the reviewer for their thorough and constructive evaluation of the manuscript and for highlighting both the conceptual strengths of the study and its technical limitations. We agree that the spatial and cellular specificity of unsorted multi-unit recordings imposes inherent constraints on the interpretation of domain-specific activity, particularly given the narrow width of septal compartments in mice. As now clarified in the manuscript, we do not claim absolute cellular specificity of “septal” recordings but rather interpret them as septal-enriched populations. To directly address this concern, we performed additional threshold-based analysis demonstrating that the key domain-specific effects persist selectively in Layer 4 under stricter spike-detection criteria, supporting a local circuit origin of the critical findings. Further, the more stringent detection criteria (Suppl Fig 3A) collapse the divergence seen in Layer2/3 (Suppl Fig 4C), suggesting that this divergence arises in Layer 4, where SST+ interneuron distributions diverge between barrel and septa.
We further agree that the Elfn1 knockout results provide indirect, rather than definitive, evidence for causal involvement of SST<sup>+</sup> interneurons and therefore intentionally frame the Elfn1–SST mechanism as a working model supported by converging anatomical, physiological, developmental, and genetic observations. We believe this explicitly moderated interpretation appropriately reflects the scope of the current data while establishing a clear conceptual framework and motivation for future studies employing cell-type-specific recordings and manipulations to directly test the proposed mechanism.
Recommendations for the authors:
Reviewer #3 (Recommendations for the authors):
Major comments
(1) Interpretation of "septal" recordings: The authors claim that the activity recorded from electrodes placed in the septa can be confidently attributed to septal neurons. In my previous review, I raised a major concern that such "septal" recordings likely include spikes from adjacent barrels, given the broad spatial resolution of MUA and the narrowness of the septa in the mouse S1. In fact, the intermediate properties observed in septal recordings from wild-type mice could be explained by a mixture of activity from principal and neighboring barrels-an interpretation that contrasts with the authors' conclusion. Upon reviewing the probe model used (A8x8-Edge-5mm-100-200-177), I noticed a discrepancy between the manufacturer's design and the schematic provided in the manuscript. The electrodes are located near the right edge of the probe rather than the center, suggesting that neurons in adjacent barrels could easily be sampled. In my previous review, I therefore suggested alternative approaches, such as calcium imaging, to more convincingly support the authors' claims. However, the revised manuscript does not include new experiments or additional analyses addressing this issue. Instead, the authors argue that using a high spike detection threshold (SD > 7.5) ensures that recorded activity originates from septal neurons, even though this value does not appear particularly conservative, as it was merely adopted from a previous study without justification in the present context. While I agree that a higher threshold may reduce contamination from distant sources, it does not guarantee that only septal neurons contribute to the signal. By nature, MUA reflects activity from multiple neurons within a radius of at least 50-100 µm. To more rigorously support the claim of spatial specificity, I strongly encourage the authors to reanalyze their existing dataset by systematically varying the spike detection threshold and quantifying how the properties and selectivity of detected units change. If neurons closer to the electrode indeed exhibit distinct domain-specific properties, they should become more prominent as the threshold increases. Such an analysis would strengthen the authors' interpretation and improve the manuscript's impact, even in the absence of new experimental data. Alternatively, the authors could revise their claims to acknowledge that the "septal" electrodes likely record from a population that includes septal neurons as well as neurons located at the periphery of principal and adjacent barrels.
We agree with the reviewer that, by nature, MUA reflects the activity of multiple neurons within a spatial radius and that recordings obtained from electrodes positioned in the septa may include contributions from neurons located at the periphery of adjacent barrels. This concern is further compounded in superficial layers by probe geometry and orientation: given the narrow width of septa and the lateral spread of processes in upper cortical layers, recordings in L2/3 are inherently more susceptible to spatial mixing than those in layer 4, where columns are more compact and cytoarchitecturally distinct. To directly address these issues, we reanalyzed the same dataset using a more stringent spike detection threshold (SD > 9.5), compared to the originally reported SD > 7.5. Importantly, increasing the threshold selectively reduced or eliminated effects in L2/3, while the key domain-specific differences in L4 responses both the differential MW/SW dynamics in wild-type animals and their attenuation in Elfn1 knockout mice remained robust (the new Supp. Fig. 3. In the manuscript). This threshold-dependent dissociation is consistent with the interpretation that the critical effects reported in L4 arise from neurons spatially closer to the electrode and are less influenced by probe orientation or distant sources, rather than reflecting simple mixing of barrel signals. While this analysis does not claim absolute cellular exclusivity of septal neurons, it provides empirical support that the principal conclusions of the study are robust to stricter spatial sampling criteria and are particularly anchored in L4 circuitry. Accordingly, we now explicitly acknowledge in the manuscript that “septal” recordings likely represent septal-enriched populations rather than purely septal neurons, while emphasizing that the persistence of L4 effects under higher spike-detection thresholds strengthens the conclusion that local L4 inhibitory dynamics underlie the reported functional differences between barrel and septal domains.
The greater sensitivity of L2/3 results to spike-detection threshold is also expected based on both anatomical considerations and probe geometry. Neurons in L2/3 possess broader horizontal dendritic and axonal arbors and participate in more laterally distributed integration across columns, making population signals in these layers intrinsically less spatially focal. As a result, conservative spike-detection criteria preferentially suppress L2/3 effects, particularly when recordings are obtained with probes optimized for deeper layers. Importantly, our two-photon calcium imaging data while similarly limited to L2/3 demonstrate that SST<sup>+</sup> interneurons show locally measurable and stimulus-specific responses at the single-cell level, providing independent support that L2/3 SST<sup>+</sup> activity is stimulus-modulated rather than artifactual. Taken together, these observations suggest that L2/3 results reflect more distributed and integrative network activity, whereas the L4 effects that persist across thresholds are more directly attributable to local circuit mechanisms. This layer-specific dissociation further supports our interpretation that the central findings of the study are driven by local inhibitory dynamics in L4, with L2/3 activity reflecting downstream integration rather than primary domain-specific computation.
(2) Interpretation of the Elfn1 KO data: The authors' interpretation that Elfn1-dependent facilitation of SST<sup>+</sup> interneurons underlies the differential sensory responses between barrel and septal domains is conceptually appealing and supported by several converging, albeit indirect, lines of evidence. Specifically, the consistent correspondence among the differential activation of SST<sup>+</sup> neurons upon SWS and MWS, the late development of the barrel-septa differences in the responses to SWS and MWS, and the attenuation of this difference in Elfn1 knockout mice lends plausibility to the proposed model. However, it should be emphasized that the data remain indirect: the study does not include direct recordings of SST<sup>+</sup> neuronal activity from the knockout mice, nor cell-type- specific manipulations to demonstrate causal involvement. The mechanistic explanation therefore represents a hypothesis rather than definitive proof. That said, the authors clearly acknowledge these limitations in the Discussion and appropriately moderate their claims by presenting the SST-Elfn1 mechanism as a working model. Given this careful framing, the current manuscript can be regarded as a valuable conceptual contribution that advances our understanding of how inhibitory dynamics may shape temporal processing in the barrel cortex. Further experiments, as mentioned above, will be essential to test the causal role of this mechanism directly.
We thank the reviewer for this thoughtful and balanced assessment. We fully agree that the Elfn1 knockout experiments provide indirect rather than definitive evidence for a causal role of SST<sup>+</sup> interneurons in mediating the domain-specific MW/SW response dynamics between barrels and septa For this reason, throughout the revised manuscript we explicitly frame the Elfn1–SST mechanism as a working model rather than a proven mechanism.
Minor comments:
The authors have adequately addressed my previous minor comments. In this round, I carefully reviewed the revised manuscript and identified several issues related to references. I would also like to add a brief comment regarding the Discussion section:
(1) Stachniak et al., 2021 is included in the reference list but is not cited anywhere in the main text. Please either remove this entry or cite it appropriately in the manuscript.
Removed.
(2) Yamashita et al., 2018 is cited in the main text (Line 767), but it is not included in the reference list.
Fixed.
(3) Sylwestrak and Ghosh, 2012 is cited at Line 261 and Line 270, but likewise absent from the reference list.
Fixed.
(4) At Line 497, Chen et al., 2015 is cited, but, the appropriate and original reference would be Chen et al., 2013 (PMID: 23792559), which should either replace or precede the 2015 citation.
Added.
(5) At Line 221, El-Boustani et al., 2018 is cited. However, this study is based on the visual cortex, whereas the manuscript concerns the barrel cortex. A more relevant citation (e.g., Lefort et al., 2009 [PMID: 19186171]) would better support the discussion of cellular organization in the barrel cortex. Please consider updating the citation.
Thank you for this suggestion. We agree with the reviewer and now we have changed El-Boustani with Lefort et al. 2009 as suggested by the reviewer.
(6) Furthermore, Chakrabarti & Alloway (2006) performed tracer-based mapping of projections from barrel and septal columns in rat S1 and similarly suggested differential organization of M1- and S2projection neurons in the barrel and septal regions.
Although the current study thoroughly analyzed the layer-specificity of the location of these projection neurons, the lack of explicit discussion of this relevant prior work is a notable omission.
The authors should incorporate a comparison with these results to better contextualize their findings.
The following text is added to the discussion: “Our retrograde labeling data supports and expands on previous work proposing similar models (Alloway, 2008; Chakrabarti and Alloway, 2006).”
鬼斧神工
高富帅的官方分公司个
Since toxin/antitoxin systems (TAs) are the most-prevalent phage defense and Ishtar uses an HEPN-based toxin (part of type VII TAs that is inactivated by ampylation, doi: 10.1093/nar/gkaa855), seems both the discovery of TAs as phage defenses (doi: 10.1128/jb.178.7.2044-2050.1996) and the HepT/MntA TAs should be cited.
abbraccia
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amore
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arsi
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ardor,
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desiderj
desiderio
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name
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I never really thought about annotation as something people do together. I've always highlighted or written notes for myself, so this changes how i think about reading in a classroom.
NO_CUDA_EXT=1
不编译所有C++扩展（Redis、文件系统、存储管理器）。 对应代码在: https://github.com/LMCache/LMCache/blob/v0.4.3/setup.py#L16
详细说明参见 LMCache - setup_extensions/build_profiles/init.py#L64
直到 0.5.1 也没有见到昇腾相关支持： https://github.com/LMCache/LMCache/tree/v0.5.1/setup_extensions/build_profiles
To use LMCache-Ascend on the NPU hardware
从目前(0.4.3)总结到的信息: - 尚不支持MP模式 (https://github.com/LMCache/LMCache-Ascend/issues/212 ) - ?? 也不支持LMCache的任何其它后端（比如mooncake, s3等）——确实不能编译成功?? - 只支持CANN 8.2 - 8.5，不支持 CANN 9.0 - 尚不支持A5
実行タイミングによっては結果が異なる場合があります。
nits: 直前に同じ文章が出てきます。どちらかを言い換えてもいいかもしれないです
以下などはどうでしょうか？ ・そのため、実行する日によって対象になるリビジョンが変わることがあります。 ・実行日が変わると経過日数の計算結果も変わるため、更新対象のリビジョンが変わる可能性があります。
場面ついて
nits: 場面ついて → 場面について 「に」がぬけてますかね？
SKILL.mdが作成
感想です：整えてあるのが今っぽいですね
(सम्, totality, completion) + kṛta (कृत, past participle of the kṛ dhātu कृ,
You might need to add the extra S after M, as you mentioned the other day
eLife Assessment
This potentially valuable study aims to investigate neural correlates of spatial attention in whisker somatosensory cortex (S1) in mice, finding increased sensory-evoked spiking when the mice appear to be attending to the contralateral whiskers. Although some of the results appear to be robust despite relatively small effect sizes, overall the findings are incompletely supported, because attentional modulation is insufficiently distinguished from learning of stimulus-response contingencies, and because the analyses do not adequately consider orofacial movements that may contribute key confounds.
Reviewer #1 (Public review):
The paper uses a passive whisker detection task in mice to identify a behavioral phenomenon that can reasonably be interpreted as spatial attentional capture. The attentional effect occurs transiently after a successful whisker stimulus detection yields reward, and lasts for a few trials before subsiding. The attentional effect is to the right or left whiskers, depending on whether right or left whiskers are rewarded; no finer spatial resolution for attention was tested. By recording whisker-evoked spiking from single units in S1, the authors show that this form of spatial attention increases the gain of whisker-evoked neuronal responses in S1 for a large subset of S1 units. In contrast, neural responses are not modulated by overall task engagement. Together, these findings show a neural signature of spatial attention in S1 cortex. Because whisker or facial movements were not tracked, it is not clear whether this represents covert attention or whisker movement in response to previously rewarded stimuli, which would be a form of overt attention.
Substantial attentional modulation of neural responses was observed for a subset of whisker-responsive S1 units, but the effect size was small on average for the total unit population. The top 25% of units showed a ~12% attentional response modulation (relative to firing rate range for each unit), but the median unit showed only a 1.3% response modulation. It would have been useful to analyze the magnitude or prevalence of attentional modulation across layers or in fast-spiking vs. regular spiking units, but this was not reported.
Major
(1) It is hard to interpret the underlying causes of the attentional modulation of neural activity without having measured whisker and facial movement. This is a particular issue in S1, where whisker movement against the stimulation grid can alter the mechanical efficiency of stimulus delivery. Such movements would represent overt attention, which would engage an entirely different neural mechanism than covert attention.
(2) An interesting debate is whether the behavioral phenomenon is best described as attention or as dynamic learning of the stimulus-response association for that block. In Posner-type cued attention tasks, and also in many block-type attention tasks in rodents, animals receive reward for successfully detecting either cued or uncued stimuli, and thus attention (higher response probability or improved psychometric sensitivity for cued stimuli) is at least partially dissociated from the stimulus-reward contingency. That is not the case here. The fact that mice have difficulty learning the contingency reversal suggests that the phenomenon is better explained by attention than by learning the contingency; however, to prove this clearly, the existence of the attentional effect on neural activity in Block 1 vs. Block 2 would have to be shown.
(3) Some of the graphical representations of the attentional modulation of neural activity are unclear. The single-unit example of attentional modulation is quite strong (Figure 3d). The mean response for the top 25% of units is also visually clear (Figure 3f). But the effect is not apparent at all in Figure 3e, which the figure legend says shows every unit. What is the yellow point and line in this figure? Why isn't the attentional effect visible in this panel? Perhaps I am misunderstanding Figure 3e, but it is not clear to me why it compares Pref>0.5 to Pref<0.5, when the intended analysis suggests it should be Pref>0 to Pref<0? Also in Figure 3, it is critical for the reader to know whether panels 3g-3h represent the top 25% of units or all units. Neither the results text nor the legend is clear on this.
(4) There is a missed opportunity to quantify attentional modulation across cortical layers, since laminar probes and Neuropixels probes were used for the recordings. In addition, there is no separation of fast-spiking from regular-spiking units, and no quantitative metrics are provided to assess the quality of single units. This could reveal key aspects of cortical processing of attentional signals.
Reviewer #2 (Public review):
Summary:
Dyce et al investigate the modulation of sensory responses in the somatosensory 'barrel' cortex during a novel whisker vibration detection task in head-fixed mice, aiming to find correlates of spatial attention in both the animals' behavior and their neuronal activity.
Strengths:
The authors produced an extensive and parameterized dataset of both behavioral responses and neuronal activity, with >3000 single units of which >1400 were responsive.
Weaknesses:
In my view, the main conclusions of the manuscript are not currently well supported by the data.
The authors effectively define "spatial attention" as a state where an animal responds more to a stimulus that gives more rewards (out of two possible stimuli presented on different sides of the snout, i.e., segregated spatially). If one defines spatial attention purely in these terms, then their findings do show neuronal correlates of spatial attention. However, those neuronal correlates can be explained by known aspects of neuronal responses in the barrel cortex.
This plays out in several different ways:
From the behavioral point of view, greater attention may correlate with an increased hit rate to stimuli on the rewarded side, but in the absence of other supporting measurements, the relationship could well be the opposite: an animal could pay more (rather than less) attention to the stimulus delivered on the unrewarded side, to make sure it suppresses the incorrect response. It is impossible to tell, as the data don't provide an independent measurement of whether the animal is paying greater attention to, or is more aware of, one side than the other, nor do they provide an independent measurement of neuronal tuning on either side. There is no separate measurement of arousal either (e.g., via pupillometry or locomotion).
The experimental design involved two blocks on each daily task session, with the second block reversing the side on which rewarded stimuli were delivered. Reinforcing one's doubts about the behavior and its interpretation, mice had much poorer performance on each day's second block, to the extent that perceptual sensitivity (d') was the same for both sides: d' did not increase after reward reversal for stimuli on the initially unrewarded side. This further emphasizes the lack of a separate demonstration of focused "spatial attention".
Much of the data (both behavioral and neuronal) could be accounted for, e.g., by a strategy where the mouse keeps a token in working memory of what side seems to be driving rewards, while maintaining equally strong sensory drive on both sides, but with no attentional shift at all. The policy would be to respond more whenever the stimulated side matches the token in memory (thus also reinforcing the token, thus enhancing performance next time). This would be easily implemented with a disinhibitory reward-modulation signal such as the one multiple researchers have found carried by VIP neurons (e.g., Szadai et al DOI: 10.7554/eLife.78815).
Similarly, the fact that "attended trials" (Pref > 0) produced greater responses than "unattended trials" appears to be explainable as follows. Here, "attended" trials are those where the contralateral stimulus is presented (and, if responded to, is rewarded), "unattended" trials are those where the stimulus is ipsilateral (and not rewarded). The animal responds more (at least in the first block) to stimuli delivered to the contralateral pad - i.e., rewarded as opposed to unrewarded ones. Beyond the knowledge mentioned above that cortex-wide VIP sensitivity to rewards can drive disinhibition in general, activity modulation dependent on rewards and outcomes (and stimulus value) has been established specifically in the barrel cortex (e.g., Lacefield et al DOI: 10.1016/j.celrep.2019.01.093, Bale et al DOI: 10.1016/j.cub.2020.10.059, Banerjee et al DOI: 10.1038/s41586-020-2704-z, Chereau et al 10.1038/s41467-020-17005-x). The reward- and value-evoked activity demonstrated in those papers would suffice to predict more activity at the contralateral electrode on "attended" trials, along the lines of the findings in Ramamurthy et al (DOI: 10.1038/s41467-025-60592-w) and consistent also with the enhanced "attentional modulation" on hit trials.
Other aspects of the analysis and terminology lead to confusing outcomes. For example, in the analysis in Figure 3, Performance averaged in a set of trials around a given trial is defined as the mean rate of responses to stimulation on either side - regardless of whether those responses are correct (since the stimuli can be on either side, but only one side is correct and gets rewarded and putatively reinforced). Thus, this definition of "Performance" can increase with the rate of incorrect licks to the wrong side and is at odds with the normal use of the word. On trials where this Perf = 1 and the stimuli are balanced on either side, this corresponds to a true performance (and reward rate) of only 0.5 - what one would normally consider random discrimination between the sides. Thus, Perf = 1 trials may still give a low reward rate and, if responses scale with reward, a small effect of reward. Hence, based on known properties of reward dependence, greater correlation of neuronal activity with "Preference" than with "Performance" would be expected, rather than reflecting a new aspect of "spatial attention". A definition of performance more in line with established practice and measuring side-to-side discrimination (corresponding more closely to the authors' "Preference" parameter) would have shown this more clearly.
Author response:
(1) Introduction & Roadmap
We are grateful to the Reviewers for engaging with outstanding questions relating to our findings’ connections to multiple subdisciplines of cognitive neuroscience. Noting that Reviewers 1 and 2 interpreted our findings differently, we welcome the opportunity to engage in what Reviewer 1 characterised as “an interesting debate”. To promote a shared understanding and discussion of our findings, we have organised our response to address more technical comments first.
Our provisional response is organised as follows: Section 2 addresses selected technical comments relating to our Results. Section 3 addresses comments related to the design of our behavioural paradigm. Section 4 focuses on the broader interpretation of our findings. Section 5 concludes our provisional response with potential future directions and a summary of the significance of our findings.
(2) Selected technical comments related to our Results
We apologise to Reviewer 2 for the confusion in relation to the meaning of “attended” and “unattended” trials. What we said was “Positive Pref values indicate a higher response rate to the contralateral side than the ipsilateral side (relative to the electrode)” (Figure 3c caption), “we indexed all contralateral whisker vibrations according to their associated Perf and Pref” (Results text), and “we divided trials into (contralaterally) attended (Pref<sub>C/L</sub>: Pref>0) and unattended (Pref<sub>I/L</sub>: Pref<0) groups” (Results text). We can confirm that we defined an “unattended trial” (Pref<0) as a contralateral stimulus trial in the centre of an epoch (10-15 trials) within which the mouse responded (licked) more frequently to ipsilateral stimuli. Critically, we did not define an unattended trial as an ipsilateral stimulus trial. Furthermore, attention thus defined (i.e. Pref>0) can vary independently of the whisker stimulus associated with rewards. Indeed, while we initially did not include this result in our paper for the sake of brevity, even unrewarded “attended” trials (Pref>0) evoked significantly greater neuronal responses than unrewarded “unattended” (Pref<0) trials. We note that this is an analysis suggested by Reviewer 1, and we will include and discuss this result in our revised manuscript (e.g. in relation to literature suggested by Reviewer 2). For additional clarity, we use “Performance” (Perf) in relation to overall stimulus detection, consistent with the analysis of Lee et al. (2020), which found this measure was correlated with pupil diameter in a vibrissal target detection task.
We thank Reviewer 1 for noticing that the axes on Figure 3e should be labelled “Pref>0” (Y axis) and “Pref<0” (X axis), as suggested by the figure caption. We will correct this in our revised submission. The yellow point on Fig 3e shows the unit from Fig 3d, while the yellow line in Fig 3e shows the magnitude of that unit’s (non-normalised) gain modulation. While this is alluded to in the Results text (“The example unit in Figure 3d is in the 93rd percentile of units for raw modulation depth (ΔHits(attended – unattended) = 3.3 spikes/second; yellow line in Fig.3e)”, this should be explained in the Figure caption, and it will be in our revised manuscript. We would also like to clarify that Figures 3g–3h display results for all units, not just the top 25%. We agree this is not sufficiently clear and we will rectify this in our revised manuscript. Addressing Reviewer 2, while we acknowledge that mice responded less to both stimuli in the second block, they also meaningfully adjusted their behaviour to the reversal in reward contingencies: their responses to the previously rewarded stimulus reduced significantly more than those to the previously unrewarded stimulus.
(3) Design of the behavioural paradigm
We made a deliberate design choice to maximise the ecological validity of our behavioural paradigm, and note that there are advantages to doing so. For example, our paradigm can be used to show that even unrewarded “attended” trials (Pref>0) evoke significantly greater neuronal responses than unrewarded “unattended” (Pref<0) trials (see Section 2, above). Indeed, it is precisely this finding that makes our paradigm uniquely suited to the investigation of value-driven attentional capture (Anderson et al., 2011): in this instance attention directed to stimuli that are no longer rewarded despite equal availability of rewarded stimuli. This finding also demonstrates that our paradigm dissociates attention from stimulus-reward contingency at least as well as other paradigms which have been successfully used to study spatial attention in mice. As noted in Section 2, we will discuss this result in relation to other relevant research (e.g. Ramamurthy et al., 2025) in our revised manuscript.
Briefly, the direct manipulation of reward contingencies is one of two noteworthy methodological distinctions between our own paradigm and that of Ramamurthy and colleagues (2025). The task of Ramamurthy et al. (2025) associated all whisker stimuli with rewards and delivered stimuli to different whiskers on a single whisker pad. These methodological distinctions may have reduced the relevance of the spatial differences between stimuli to the mice undertaking the task. Indeed, it is not certain that a mouse would treat the unilateral variation in whisker stimulation Ramamurthy and colleagues delivered as primarily spatial or featural. The psychophysical and neural differences between spatial and featural attention in humans suggest dissociable underlying mechanisms, and the same may be true in mice. Thus, our own paradigm may more effectively isolate spatial attention from featural attention. Conversely, to the extent that the findings of Ramamurthy and colleagues do reflect spatial attention, our combined findings and paradigms help elucidate the associated mechanisms across spatial scales in mice.
We acknowledge that spatial cueing is well-suited to isolating the effects of covert attention from other forms of attention. However, it should be noted that spatial cueing in rodents is subject to its own challenges, including limitations in trial numbers due to the required manipulation of stimulus intensity (Reynolds et al., 2000; Herrmann et al., 2010), cue validity and associated trial probabilities (Peterson & Gibson, 2011; Girardi et al., 2013). Such experiments are further complicated by the duration and efficacy of training (i.e. the number of mice that learn the task; Wang & Krauzlis, 2018; Hu & Dan, 2022). It is also worth noting that trial probability manipulations introduce the same limitation in trial numbers with block-type attention tasks (You & Mysore, 2020; Kanamori & Mrsic-Flogel, 2022).
While there are clear differences between our own paradigm and those mentioned above, there are also important similarities. First, these tasks are all goal-directed, stimulus-driven, and reliant on learned task contingencies (e.g. Peterson & Gibson, 2011; Girardi et al., 2013). Furthermore, these paradigms are all operant conditioning protocols which leverage learned stimulus-reward contingencies to train attention-related behaviours in mice. A noteworthy similarity between our findings and those of authors using block-type attention tasks in particular (e.g. You & Mysore, 2020; Kanamori & Mrsic-Flogel, 2022) is the observation of apparent attentional biases in behavioural responses independent of the experimental manipulations (i.e. stimulus probability / reward contingency).
(4) Comments relating to the broader interpretation and discussion of our findings
Fundamentally, attention involves dedicating limited processing resources to some stimulus events at the expense of others. The design of our behavioural paradigm was informed by existing literature on spatial attention in humans, non-human primates, and mice. Our choice of behavioural and neuronal measures as proxies for attention in mice is consistent with this literature. It is technically possible “an animal could pay ‘more’ (rather than less) attention to the stimulus delivered on the unrewarded side, to make sure it suppresses the incorrect response”, but this seems unlikely given what is known about how attention is typically allocated in such tasks, based on the previously mentioned literature.
With respect to the interpretation and discussion of our findings, Reviewer 1 describes them as “a behavioral phenomenon that can reasonably be interpreted as spatial attentional capture” but suggests they do not clearly distinguish whether this attentional capture is covert or overt. We respectfully disagree for three reasons. First, as discussed in our paper, whisker motion during detection tasks has consistently been associated with reduced detection performance (Ollerenshaw et al., 2012; Kyriakatos et al., 2017; Vandevelde et al., 2023), suggesting that a “receptive” strategy (Diamond & Arabzadeh, 2013) of whisker immobilisation is more applicable to the current data than a “generative” strategy of asymmetric whisker movement (O'Connor et al., 2010; Dominiak et al., 2019). Second, if our behavioural and neuronal findings were due to the mice moving their whiskers to maximise contact with the meshes, we would expect increased evoked neuronal responses to be associated with greater Perf, not just with greater Pref. This pattern was not observed. Of course, the mice might have employed different whisker movement strategies during epochs of high Pref and Perf, but this seems unlikely and is not a parsimonious explanation for our findings. Third, as noted in the Methods section of the paper, we deliberately positioned the meshes close to the base of the whiskers, limiting the impact of whisker movements on stimulus detectability and the incentive to make them.
In contrast, Reviewer 2 questions the interpretation of our findings as evidence of spatial attention and suggests they might reflect working memory instead. Current research suggests attention and working memory are intimately related integrative brain functions. Indeed, some researchers have even proposed that working memory might be a form of internally directed attention (Awh & Jonides, 2001; Chun, 2011; Gazzaley & Nobre, 2012; Kiyonaga & Egner, 2013; or vice versa: Libedinsky & Fernandez, 2019). Consistent with the comments of Reviewer 2, more recent work seems to emphasise the coordination of attention and working memory (e.g. Joe & Kim, 2023; Zhu et al., 2026; for reviews see Huynh Cong & Kerzel, 2021; van Ede & Nobre, 2023), along with shared mechanisms (Kiyonaga et al., 2021; Panichello & Buschman, 2021), and nuanced dissociations (Liu et al., 2025). Attention is difficult to dissociate from working memory partly because there are multiple definitions (and/or types) of attention. We did not discuss the various definitions and/or forms of attention at length in our paper, but we will briefly discuss this in the revised manuscript.
The “interesting debate” to which Reviewer 1 refers could also be described as vigorous, despite approximately three decades of research. This debate broadly relates to the degree to which attentional control is driven by exogenous (e.g. colour contrast) versus endogenous factors (e.g. the focus of spatial attention, see Fig.2 in Belopolsky et al., 2007; see also: Liesefeld & Mueller, 2020; Manini et al., 2021; Beffara et al., 2022), and the degree to which this is a function of experimental context. The review article by Luck et al. (2021) entitled “Progress toward resolving the attentional capture debate” provides a striking illustration of this debate, as do the twenty-two commentaries (and three commentary responses) associated with it. Admittedly, this debate largely revolves around human attention experiments, and human cognition may be more complex than mouse cognition. However, the complexity of human cognition may also be easier to study and appreciate because complex behavioural experiments can be explained to, understood, and performed by human participants with relative ease.
(5) Comments relating to future directions and the significance of our findings
The complexity of the attentional capture debate underscores the importance of developing accessible and scalable animal experiments which can be used to provide mechanistic insights. If the human attention literature is any indication, a diversity of rodent experimental paradigms will be necessary to thoroughly map the neuronal implementation of spatial attention. Returning to our paradigm, Reviewer 1 noted that valuable insights into the mechanisms of vibrissal spatial attention might be obtained from comparing the magnitude of attentional modulation we observed between putative regular and fast-spiking categories of units, and between units located in different cortical layers. We agree it is important to understand spatial attention with cell-type and circuit (including laminar) specificity. However, because we could not persuasively cluster our units based on waveform width, and because of the lack of histological data, segregating units on the basis of such variables is not feasible. Despite our assertion that our findings reflect the effects of covert attention (contra Reviewer 1), we agree that future experiments will be required to conclusively rule out overt attention. Noting the proximity of the meshes to the base of the whiskers in our paradigm, and the difficulty of tracking whiskers in this context, Botulinum toxin injections (as in Ramamurthy et al., 2025) might be a means of achieving this.
The above notwithstanding, our findings provide multiple contributions to the literature on spatial attention (and perhaps working memory). We detected significant attentional gain modulation across a population of 1461 responsive units. While the gain modulation exhibited by the median unit was modest (albeit statistically significant), the top 25% of responsive units showed a ~12% response modulation (relative to firing rate range for each unit), and ~21% of responsive units were suppressed by the average vibrissal stimulus in the unattended state. Our experimental framework offers an accessible platform for future studies leveraging genetic and circuit-level interventions to dissect the cell-type specific mechanisms of spatial attention. Our work is timely, noting the recent focus of human research on the nexus of attention, selection history, and valence (e.g. Serences, 2008; Della Libera & Chelazzi, 2009; Della Libera et al., 2011; van den Berg et al., 2014; Kim & Anderson, 2019, 2023). Our work is also uniquely poised to stimulate new interdisciplinary research into the circuit mechanisms of value-driven attentional capture, with translational relevance to psychopathologies such as ADHD, addiction, and depression; where value-driven attentional capture is altered (for a review see Anderson, 2021).
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eLife Assessment
This valuable study compares hippocampal-cortical functional connectivity to various other brain measures and examines their development across youth. It uses sophisticated analyses replicated in multiple datasets, but provides incomplete evidence to support the primary claim that hippocampal-cortical connectivity relates to cognitive maturation. The manuscript would benefit from a more nuanced consideration of the biological basis of some of the derived imaging measures and the limitations of the cross-sectional design. This work will be of interest to neuroimaging specialists and cognitive neuroscientists.
Reviewer #1 (Public review):
Summary:
The authors studied the development of hippocampal connectivity gradients based on open datasets and performed correlation analyses with other MRI features as well as gene expression information from other datasets. Although the main findings are correlational and cross-sectional, the analyses are overall sophisticated and replicated in several datasets.
Strengths:
The hippocampus is a key region in understanding large-scale brain organization and cognition, and the authors applied advanced and suitable analytics to study its development. The paper is overall well-organized and well-written, and the findings are relevant for studying large-scale brain development.
Weaknesses:
While sophisticated, several of the analyses appear mainly correlational, cross-sectional, and rely on cross-dataset contextualization, which should also be stated as a limitation of the current work.
Reviewer #2 (Public review):
Summary:
In this manuscript, the authors aim to assess how the functional organisation of the hippocampus is related to the geometry and neurobiological differences of the hippocampus. In particular, the authors focus on the first three eigenvectors of hippocampal-cortical functional connectivity, based on non-linear dimensionality reduction on resting-state functional MRI data. Furthermore, the work aims to describe changes in these functional axes and their relation to other factors throughout youth and evaluate whether they are predictive of individual variations in cognition.
Strengths:
A major strength of this study is the attempt to replicate key findings across multiple developmental cohorts.
Weaknesses:
The major weaknesses of the manuscript center on gaps in technical transparency and several conceptual inaccuracies. The machine learning methodology used for cognitive prediction is scarce, leaving little means to evaluate whether the behavioral results suffer from data leakage or overfitting. The introduction sets up an oversimplified historical premise regarding the field's understanding and appreciation of hippocampal connectivity, and contains several incorrect references that throw doubt on the argumentation. Additionally, T1w/T2w signal intensity is incorrectly used as synonymous with myelin, despite gold-standard histological validation showing a non-significant correlation between T1w/T2w and myelin staining (Sandrone et al., 2013).
Appraisal of Aims and Conclusions:
The authors partially achieve their aims by illustrating certain age-related changes in hippocampal function; however, the correlative study design is not equipped to examine how these changes are "shaped" by geometry, myelination, or gene expression (especially the latter two). Furthermore, conclusions were often overstated based on small effect sizes.
Context and Field Impact:
This work adds to a growing body of literature focused on gradient-based representations of hippocampal topology. By applying these methods across a wide developmental age bracket, it provides a useful reference point for how the hippocampus and wider cortex interact during maturation. To improve utility to the neuroimaging and cognitive neuroscience communities, the nesting of subfields within the eigenvector topology should be addressed, too.
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ATCC, #CCL-61
DOI: 10.64898/2026.06.25.734451
Resource: (IZSLER Cat# BS CL 15, RRID:CVCL_0214)
Curator: @dhovakimyan1
SciCrunch record: RRID:CVCL_0214
RRID: #168510
DOI: 10.64898/2026.06.25.734451
Resource: RRID:Addgene_168510
Curator: @dhovakimyan1
SciCrunch record: RRID:Addgene_168510
30143
DOI: 10.64898/2026.06.25.734451
Resource: RRID:Addgene_30143
Curator: @dhovakimyan1
SciCrunch record: RRID:Addgene_30143
30144
DOI: 10.64898/2026.06.25.734451
Resource: RRID:Addgene_30144
Curator: @dhovakimyan1
SciCrunch record: RRID:Addgene_30144
30146
DOI: 10.64898/2026.06.25.734451
Resource: RRID:Addgene_30146
Curator: @dhovakimyan1
SciCrunch record: RRID:Addgene_30146
30137
DOI: 10.64898/2026.06.25.734451
Resource: RRID:Addgene_30137
Curator: @dhovakimyan1
SciCrunch record: RRID:Addgene_30137
RRID: CVCL C9CB
DOI: 10.34133/research.1315
Resource: RRID:CVCL_C9CB
Curator: @evieth
SciCrunch record: RRID:CVCL_C9CB
HTB-38
DOI: 10.3390/nu18132125
Resource: (RRID:CVCL_0063)
Curator: @dhovakimyan1
SciCrunch record: RRID:CVCL_0063
RRID: CVCL_0062
DOI: 10.3390/nu18132125
Resource: (RRID:CVCL_0062)
Curator: @dhovakimyan1
SciCrunch record: RRID:CVCL_0062
Zebrafish International Resource Center
DOI: 10.3390/ani16020249
Resource: Zebrafish International Resource Center (RRID:SCR_005065)
Curator: @Apiekniewska
SciCrunch record: RRID:SCR_005065
RRID: AB_3532145
DOI: 10.1210/jendso/bvag141
Resource: (IBL - America Cat# IB59131, RRID:AB_3532145)
Curator: @evieth
SciCrunch record: RRID:AB_3532145
RRID: AB_395870
DOI: 10.1158/2767-9764.CRC-25-0749
Resource: (BD Biosciences Cat# 555478, RRID:AB_395870)
Curator: @evieth
SciCrunch record: RRID:AB_395870
RRID: AB_2536840
DOI: 10.1158/2767-9764.CRC-25-0749
Resource: (Thermo Fisher Scientific Cat# MA1-134, RRID:AB_2536840)
Curator: @evieth
SciCrunch record: RRID:AB_2536840
RRID: Addgene_12259
DOI: 10.1158/2767-9764.CRC-25-0749
Resource: RRID:Addgene_12259
Curator: @evieth
SciCrunch record: RRID:Addgene_12259
RRID:SCR_002338
DOI: 10.1136/bmjonc-2025-001031
Resource: dbSNP (RRID:SCR_002338)
Curator: @evieth
SciCrunch record: RRID:SCR_002338
RRID:SCR_000560
DOI: 10.1136/bmjonc-2025-001031
Resource: Pindel (RRID:SCR_000560)
Curator: @evieth
SciCrunch record: RRID:SCR_000560
RRID: AB_259529
DOI: 10.1126/sciadv.aee5417
Resource: (Sigma-Aldrich Cat# F3165, RRID:AB_259529)
Curator: @evieth
SciCrunch record: RRID:AB_259529