DOI: 10.1002/advs.202519586

Resource: (RRID:CVCL_6602)

Curator: @scibot

SciCrunch record: RRID:CVCL_6602

What is this?

DOI: 10.1002/adhm.202600001

Resource: RRID:Addgene_17843

Curator: @scibot

SciCrunch record: RRID:Addgene_17843

What is this?

DOI: 10.1002/adhm.202600001

Resource: RRID:Addgene_22036

Curator: @scibot

SciCrunch record: RRID:Addgene_22036

What is this?

DOI: 10.1002/adhm.202600001

Resource: RRID:Addgene_19068

Curator: @scibot

SciCrunch record: RRID:Addgene_19068

What is this?

DOI: 10.64898/2026.01.30.702552

Resource: None

Curator: @dhovakimyan1

SciCrunch record: RRID:MMRRC_031180-UCD

What is this?

DOI: 10.48610/b58aac1

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:SCR_016728

What is this?

DOI: 10.48610/b58aac1

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:SCR_014519

What is this?

DOI: 10.48610/b58aac1

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:SCR_002881

What is this?

DOI: 10.48610/b58aac1

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:SCR_001622

What is this?

DOI: 10.1101/2025.08.15.666880

Resource: None

Curator: @evieth

SciCrunch record: RRID:IMSR_JAX:035764

What is this?

DOI: 10.1101/2025.08.15.666880

Resource: None

Curator: @evieth

SciCrunch record: RRID:IMSR_JAX:020505

What is this?

DOI: 10.1101/2025.08.15.666880

Resource: None

Curator: @evieth

SciCrunch record: RRID:IMSR_JAX:014175

What is this?

DOI: 10.1101/2025.08.07.669049

Resource: None

Curator: @evieth

SciCrunch record: RRID:CVCL_0063

What is this?

DOI: 10.1021/acs.jmedchem.5c03704

Resource: None

Curator: @dhovakimyan1

SciCrunch record: RRID:SCR_022379

What is this?

DOI: 10.1016/j.xcrm.2026.102616

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:024234

What is this?

DOI: 10.1016/j.neuron.2025.11.028

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_66794

What is this?

DOI: 10.1016/j.neuron.2025.11.028

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_61463

What is this?

DOI: 10.1016/j.neuron.2025.11.028

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_136552

What is this?

DOI: 10.1016/j.isci.2026.114983

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:MMRRC_032108-UCD

What is this?

DOI: 10.1016/j.isci.2026.114820

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:AB_2737024

What is this?

DOI: 10.1016/j.isci.2026.114720

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:030323

What is this?

DOI: 10.1016/j.isci.2026.114707

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:AB_2251304

What is this?

DOI: 10.1016/j.isci.2026.114707

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:AB_10806644

What is this?

DOI: 10.1016/j.isci.2026.114647

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:000664

What is this?

DOI: 10.1016/j.immuni.2026.01.003

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:AB_313705

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207224

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @evieth

SciCrunch record: RRID:Addgene_207216

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207205

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207202

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207200

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207198

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207197

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207193

What is this?

DOI: 10.1016/j.immuni.2025.08.001

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:Addgene_207192

What is this?

DOI: 10.1016/j.devcel.2026.01.011

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:028342

What is this?

DOI: 10.1016/j.devcel.2026.01.011

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:017860

What is this?

DOI: 10.1016/j.celrep.2026.116961

Resource: None

Curator: @areedewitt04

SciCrunch record: RRID:IMSR_JAX:005557

What is this?

explanation and conceptualization of Aristotle and his ethics focusing on happiness

This is saying that even the best farming method in Europe and Asia Chinese rice farming could only feed about one person per acre. This comparison helps show how productive American farming could be during the same period.

This shows that Native peoples in the Americas were able to build large, successful cities once they had steady food supplies, just like people in other parts of the world. The Maya are a good example they created a complex society with impressive buildings and cities. Their way of life changed over time, but that doesn’t mean their civilization suddenly collapsed. Instead, they may have simply chosen to live differently. Overall, this shows that American societies were advanced and capable long before Europeans arrived.

In 1500, Europe, Africa, and the Americas all had millions of people. They weren’t the same in number, but they were closer than most people expect. This shows the Americas were already full of Indigenous peoples before Europeans arrived.

eudaimonia and seeking and attaining true peak happiness, yet does not define happiness.

Analyzing the good in life and finding place in nature

Est ce que vous sous entendez qu'il en est de même pour l'architecture ? La proximité que vous défendez au troisième stade du récit pourrait être explicitée.

J'invite les auteurs à découvrir (ou redécouvrir) les travaux de Jacques Fontanilles sur "les plans d'immanence".

FONTANILLE, , J. (2015). Formes de vie. In Formes de vie. Presses universitaires de Liège. FONTANILLE, J. (2008). Pratique sémiotique, Presses Universitaires de France. FONTANILLE, J. (2006). Textes, objets, situations et formes de vie. Les niveaux de pertinence du plan de l’expression dans une sémiotique des cultures. In J. Alonso Aldama, D. Bertrand, M. Costantini, & S. Dambrine (éds.), La Transversalité du sens (1 ). Presses universitaires de Vincennes. https://doi.org/10.4000/books.puv.5828 FONTANILLE, J., & ZINNA, A. (2005). Les objets au quotidien. Presses Univ. Limoges.

Qu'est ce que cache ce terme ? Eléments = du physique, du matériel ? du relationnel ? de l'ambiance ? tous ?

Peut-être poursuivre ce "listing" en mentionnant les travaux autour du rapport affectif à la ville

https://shs.cairn.info/habiter-le-propre-de-l-humain--9782707153203-page-171?lang=fr

Il serait utile de mentionner les questionnements et/ou hypothèses de ce travail de thèse, cela pourrait aider à cerner le "pourquoi ces questions sont revenus avec force"

Qu’est-ce qu’on va faire de toi ? : Synthèse des perspectives enfantines sur le monde

Ce document de synthèse analyse les échanges et les réflexions de jeunes enfants au sein d'un cadre scolaire, tels que rapportés dans le documentaire d'ARTE.

Il explore la manière dont ces enfants perçoivent, interprètent et s'approprient des concepts complexes tels que l'identité, la politique, la justice sociale et les relations humaines.

Résumé Exécutif

L'analyse du contexte source révèle une porosité frappante entre le monde des adultes et l'univers enfantin.

Les enfants ne sont pas de simples observateurs passifs ; ils intègrent les discours médiatiques, politiques et familiaux pour construire leur propre compréhension de la société.

Les thématiques centrales incluent la remise en question des normes de genre, une conscience aiguë des inégalités socio-économiques et une appréhension palpable des tensions géopolitiques mondiales (guerre en Ukraine, immigration).

Le document souligne également l'importance de la vie démocratique à l'échelle de l'école (élections de délégués) comme laboratoire de la citoyenneté, tout en mettant en lumière les peurs existentielles des enfants face à la violence et au changement.

--------------------------------------------------------------------------------

I. Identité, Genre et Structures Familiales

Les discussions enfantines révèlent une phase de déconstruction et de négociation des normes sociales traditionnelles.

La perception de la diversité et de l'altérité

• Représentation physique : À travers des jeux comme le "Qui est-ce ?", les enfants interrogent la représentation des couleurs de peau et des caractéristiques physiques, notant parfois l'absence de diversité dans les supports de jeu ("Tout le monde est blanc").

• Identité divine : Une distinction est opérée entre les humains et les figures divines ou mythologiques (Athéna, Cerbère), avec des débats sur l'existence physique de Dieu, confrontée à la réalité scientifique (l'astronaute Neil Armstrong ne l'a pas vu).

Évolution des rôles de genre

• Répartition des tâches ménagères : Les enfants contestent l'idée que la cuisine est réservée aux femmes, citant des exemples paternels faisant la vaisselle ou l'aspirateur.

• Expression de soi : La distinction entre filles et garçons est remise en question par l'usage du vernis à ongles ou des paillettes par les garçons, certains affirmant que "les hommes peuvent se vernir".

• Force et autorité : Les enfants discutent de la brutalité ou de la force, parfois attribuée aux sœurs ou aux filles, brisant les stéréotypes de douceur féminine.

Schémas familiaux et procréation

• Homoparentalité : Le concept de deux mères est abordé.

Les enfants débattent de la nécessité biologique d'un homme (spermatozoïdes) pour concevoir un enfant, tout en reconnaissant la possibilité pour deux femmes d'élever un bébé ensemble grâce à une aide extérieure.

II. Conscience Politique et Enjeux Sociaux

Les enfants manifestent une connaissance surprenante de l'actualité et des structures de pouvoir.

Manifestations et figures politiques

• Le droit de grève : Les enfants associent la grève à une colère contre le Président et à l'utilisation d'affiches pour manifester dans la rue.

• Perception des dirigeants : Les noms d'Emmanuel Macron, de Marine Le Pen et de Vladimir Poutine apparaissent dans les discussions.

Les avis sont partagés sur la "méchanceté" ou le rôle de ces figures, certains suggérant même un mariage (erroné) entre Macron et Le Pen.

Géopolitique et conflits

• Guerre en Ukraine : Le conflit est perçu comme une lutte pour le territoire et le pouvoir.

Les enfants critiquent l'absurdité de détruire un pays que l'on souhaite récupérer ("Ils sont un peu bêtes parce que s'ils veulent récupérer un pays, ils cassent tout").

• Immigration et frontières : La question des réfugiés et des contrôles aux frontières (notamment en Italie) est évoquée, liée à la nécessité de parler la langue et de travailler pour être accueilli.

Inégalités économiques

• Pauvreté vs Richesse : Les enfants expriment le désir d'être "blindés d'argent" pour mieux soigner leurs proches ou accéder à de meilleures écoles.

• Écoles privées : Certains perçoivent l'école privée comme une injustice ou un moyen de "voler de l'argent", créant une séparation entre amis.

III. La Vie Scolaire comme Micro-Société

L'école est le lieu où s'expérimentent la démocratie, la justice et les émotions liées à la collectivité.

L'expérience démocratique : Les élections de délégués

Les enfants organisent des élections et proposent des programmes électoraux centrés sur l'amélioration du quotidien et la justice sociale :

| Candidat / Thème | Propositions et Idées | | --- | --- | | Protection | Protéger la planète, protéger les filles. | | Partage | Partager l'argent avec ceux qui n'en ont pas. | | Règlement | Arrêter les bêtises, interdire les punitions. | | Bien-être | Plus de fêtes, plus de glace à la cantine. |

Instabilité et attachement

• Transience : Le départ de camarades en cours d'année (dû à des déménagements ou des changements de situation sociale comme l'hébergement en hôtel) suscite une tristesse profonde et une peur de la solitude pour ceux qui partent.

• Valeurs républicaines : La devise "Liberté, Égalité, Fraternité" est citée comme un idéal de droits communs et de lien fraternel.

IV. Imaginaires, Peurs et Violences

L'univers mental des enfants est peuplé de références culturelles et de craintes liées à la violence réelle ou fictive.

• Peurs médiatiques : Les informations télévisées ("Le malheur du monde") et certains clips (comme Thriller de Michael Jackson) génèrent des cauchemars impliquant des monstres électroniques ou des morts-vivants.

• Terrorisme et sécurité : La notion d'attentat est comprise comme une attaque surprise.

Les enfants imaginent des systèmes d'alerte pour se protéger des "méchants" qui s'introduiraient dans l'école.

• Définition de la torture : Les enfants débattent de la cruauté, citant la guillotine ou l'arrachage d'organes comme exemples de torture, tout en distinguant la méchanceté pure de la violence physique extrême.

V. Verbatim : Paroles d'Enfants

« Si j'étais président, je dirais que les gens ils peuvent faire ce qu'ils veulent sauf voler de l'argent. »

« Marine Le Pen... elle veut pas qu'on accueille des gens du tout en France... moi je pense qu'elle va être présidente, elle est méchante. »

« Ce qui est important dans la vie c'est d'être heureux. »

« La devise de la France c'est liberté, égalité, fraternité. Ça veut dire nous sommes tous frères, nous avons les mêmes droits. »

« Ils sont un peu bêtes parce que s'ils veulent récupérer un pays, ils cassent tout le pays, du coup quand ils vont le récupérer ils vont devoir tout reconstruire. »

The definition of bad faith-pretending to hold views or feelings one does not genuinely possess, whether through intentional deception or self-deception-is both precise and nuanced.

This definition is clear, precise, and theoretically grounded. It effectively captures the core of authenticity by linking presentation and reality, making the abstract concept concrete and easy to understand.

This is a very good way to transformation. I think the people in that time are very smart

It starts with a straightforward, intuitive definition—"Metadata is information about some data"—which avoids overly technical jargon and immediately grounds the concept in a relatable way.

an isolated new phenomenon, but as a continuation of humanity's long-standing process of mediatization.

Soutenir les compétences socio-émotionnelles chez les jeunes enfants : Approches et Dispositifs

Résumé Exécutif

Ce document synthétise les interventions de Sylvie Richard (Université de Genève / HP Valais) concernant le soutien aux apprentissages socio-émotionnels durant les premières années de scolarité.

La recherche scientifique identifie deux leviers complémentaires : l'approche directe (structurée et dirigée par l'enseignant) et l'approche indirecte (développementale, centrée sur le jeu de faire semblant).

Les données probantes, issues notamment de méta-analyses incluant plus d'un million d'élèves, démontrent que le renforcement des compétences socio-émotionnelles améliore non seulement le bien-être et les comportements sociaux, mais aussi les résultats académiques à long terme.

La transition vers une pédagogie intégrant le jeu accompagné nécessite toutefois une formation approfondie des enseignants (plus de 20 heures) et un travail réflexif sur leurs propres compétences émotionnelles.

--------------------------------------------------------------------------------

1. Cadre Conceptuel des Compétences Socio-Émotionnelles

Les compétences socio-émotionnelles sont définies selon le modèle de l'organisation Casel, qui regroupe trois grands domaines d'apprentissage :

• Conscience de soi et des autres : Identifier ses propres émotions et comprendre celles d'autrui.

• Gestion des émotions et des relations : Établir et maintenir des relations sociales positives.

• Prise de décision responsable : Apprendre à agir de manière éthique et constructive.

--------------------------------------------------------------------------------

2. L'Approche Directe : Programmes Structurés et Dirigés

L'approche directe repose sur des activités planifiées où l'enseignant cible des savoirs spécifiques via des supports dédiés (jeux de plateau, fiches, lectures).

Preuves d'Efficacité et Recherche

La littérature scientifique internationale (méta-analyses de 2022 et 2025) souligne des bénéfices majeurs :

• Impact scolaire : Amélioration significative des résultats académiques comparativement aux élèves ne bénéficiant pas de ces programmes.

• Impact comportemental : Réduction des comportements problématiques et de la détresse émotionnelle.

• Impact à long terme : Diminution de la consommation de drogues à l'entrée de l'âge adulte.

Programmes en Contexte Francophone

Il existe un manque de programmes francophones validés par rapport aux modèles anglo-saxons. La simple traduction est jugée insuffisante ; une adaptation socio-culturelle est nécessaire. Deux outils se distinguent :

| Programme | Origine | Compétences Ciblées | Accessibilité | | --- | --- | --- | --- | | Emotimat | France (Grenoble) | Identification, compréhension et expression des émotions. | Libre d'accès (en ligne). | | Emoti | Suisse (Genève) | Reconnaissance émotionnelle, besoins et régulation. | Payant (coût d'impression des cartes). |

--------------------------------------------------------------------------------

3. L'Approche Indirecte : La Pédagogie par le Jeu de Faire Semblant

Le jeu de faire semblant est une activité où les objets, les paroles et les actions représentent autre chose que leur réalité immédiate. C'est une fonction mentale de haut niveau mobilisant l'imagination.

Les Composantes du Jeu Mature

Pour qu'un jeu génère des apprentissages, il doit tendre vers la maturité, caractérisée par plusieurs éléments :

• Substitution d'objets : Utiliser un bâton pour représenter une fusée (inhibition de la fonction réelle de l'objet).

• Attribution de rôles : Endosser une identité (docteur, pirate) et respecter le registre de comportement associé.

• Méta-communication : Planifier et négocier le scénario avec les pairs ("On dirait que tu étais...").

• Raisonnement par hypothèses : Utiliser la logique "Et si..." pour explorer des mondes possibles et des relations de cause à effet.

Un Laboratoire de Développement

Le jeu de faire semblant permet à l'enfant :

1. De s'autoréguler : En s'imposant des règles de comportement liées au rôle choisi.

2. D'expérimenter sans risque : Tester des situations sociales complexes dans un cadre "pour de faux", sans enjeu de performance.

3. De traiter le réel : Mettre en scène sa compréhension du monde (ex: jeux liés à la pandémie ou aux soins médicaux) pour réguler ses frustrations ou ses peurs.

--------------------------------------------------------------------------------

4. Rôle et Posture de l'Enseignant

Le passage d'un "jeu libre" à un "jeu accompagné" est crucial. L'enseignant ne doit pas être un simple spectateur, mais un acteur capable d'adopter plusieurs postures :

• Régisseur de scène : Fournir les accessoires et l'espace nécessaires.

• Co-joueur ou Joueur : Entrer dans le scénario pour enrichir le contenu et proposer des défis émotionnels.

• Observateur-Évaluateur : Identifier le niveau de maturité du jeu pour intervenir au bon moment.

L'Importance de la Formation

Les recherches indiquent que l'efficacité de ces dispositifs dépend de la préparation de l'adulte :

• Formation technique : Un minimum de 20 heures de formation est recommandé pour maîtriser l'accompagnement du jeu et les concepts socio-émotionnels.

• Dimension réflexive : L'enseignant doit évaluer ses propres compétences émotionnelles et sa capacité à jouer, car il sert de modèle par imitation pour les jeunes enfants.

--------------------------------------------------------------------------------

5. Conclusions et Recommandations

La littérature scientifique actuelle récuse l'idée que le temps alloué au développement socio-émotionnel serait une "perte de temps" au détriment du scolaire. Au contraire :

• Complémentarité : Il est impératif de combiner les séances structurées et les temps de jeu accompagné.

• Enjeu de santé publique : Le déclin de l'engagement des enfants dans le jeu de faire semblant fait de son soutien à l'école une priorité de développement psychologique.

• Apprendre à jouer pour jouer pour apprendre : Le jeu de faire semblant n'est pas inné à un niveau mature ; il doit être enseigné pour devenir un outil d'apprentissage efficace.

Steady growth

USD weaking affects !

Non-US still MA edge on V

Among the top 5

Strong YoY growth for a mature business

primary

secondary

Tertiary

opinion

opinion

fact

All of this is the equivalent of guessing what a gift is based on its shape and the sound it makes when you open it. The bulletin entries are also very emotionally charged. It should be noted that nobody is saying they have DID, that a lot more of what is speculated has to do with Tumblr's queue system (more than you think), that people can influence each others' messages in ways that explain the conspiracy theories described, that supporting presumption of guilt as with the fourth bullet isn't a good look, and that getting to the bottom of the DeviantArtDramaHub history and analyzing it with word-finding functionality will prove the bits about who has what lingo and who is willing to ask the subject questions wrong.

Source?

Also, not historically accurate. Spanish was the first European language spoken in the land that would become the US, as Spain was the first to colonize. French was the dominant language in the large French colony of Louisiana. Dutch was widely spoken in New York. German spoken by large populations in Texas.

Reference to common conservative view that the American Civil War was over "state's rights" and not slavery. What does this have to do with the topic of illegal immigration?

Context? Which media companies do they own? Also, antisemitic undertones -- choosing two Jewish media owners to single out, using Yiddish term.

(Googling revealed Sulzberger controls the New York Times, and Newhouse family controls several publications such as Vogue, The New Yorker, partial owner of Reddit, etc)

Source? Relevance to topic of illegal immigration?

After research, apparently there is an entity called "Black Lives Matter Global Network Foundation" that is a separate entity from the overall Black Lives Matter movement, and it seems they may have been profiting off the name.

https://www.npr.org/2022/04/07/1091487910/blm-leaders-face-questions-after-allegedly-buying-a-mansion-with-donation-money

Another thinly veiled antisemitic comment, and again, relevance to the topic of illegal immigration?

Relevance to topic of illegal immigration? Almost 90% of the Somali population in MN are US citizens or permanent residents.

Relevance to topic of illegal immigration?

Misleading implication - English proficiency is a requirement to become a US citizen, and only US citizens can vote. This article is about illegal immigrants, who are not eligible to vote.

Sources? Extremely provocative language with no supporting evidence.

Overtly sexist/misogynistic, inflammatory language. Again, source? What report/article is the author referencing?

Source? Relevance to topic of illegal immigration?

After researching, it seems that his wife briefly flew an upside down flag at their home in Jan 2021, and several democrats accused them of supporting the "stop the steal" movement, calling into question his ability to hear election fraud cases without bias.

What is this in reference to? Classic word-salad of liberal buzz words. Relevance to topic of illegal immegration?

Source?

Source? Relevance to topic of illegal immigration?

The only reference I could find of the US being mocked for flying the rainbow flag at embassies was of Putin mocking the US Embassy in Moscow.

Source?

After my own research, this appears to originate with a New York Post article, which the New York State Court system claims is full of errors, and sent a letter to the New York Post requesting they correct the errors (linked below), and the Post agreed to correct them, but doesn't seem to have followed through.

https://www.nycourts.gov/legacyPDFS/press/pdfs/AV26_02.pdf

Relevance of race and sex of judge?

Scapegoating - aside from the lack of evidence of this being a real issue, this shifts the blame in any situation where an illegal immigrant is employed to the immigrant, instead of where it belongs -- on the company exploiting cheap labor.

Inflammatory - Source?

Inflammatory - Source? Evidence? How does the author claim to know this?

eLife Assessment

This study offers important methodological advances for CRISPR-based mutagenesis in mice, highlighting the potential of founder animals for early phenotypic characterization. The authors present convincing evidence, supported by rigorous experimental design, that "crispant" (F0) analysis in mice, despite prior concerns about genetic mosaicism, can be utilized to assess protein function.

Reviewer #1 (Public review):

Summary:

This study evaluates the feasibility of using crispant founder mice, first-generation animals directly edited by CRISPR/Cas9, for initial phenotypic assessments. The authors target seven genes known to produce visible recessive traits to test whether mosaicism in founder animals prevents meaningful phenotype-genotype interpretation. Remarkably, they observe clear null phenotypes in founders for six of the seven genes, with high editing efficiencies. These results demonstrate that crispant mice can, under specific conditions, display recessive phenotypes that are readily interpretable. However, this conclusion should be moderated, as the study addresses only one biological context, visible Mendelian traits, and may not generalize to quantitative, subtle, or late-onset phenotypes. The report also examines attempts at multiplex CRISPR targeting, which reduce viability, underscoring limits for concurrent gene disruptions. Finally, the detailed description of diverse alleles generated by CRISPR provides valuable insight into how allelic series can be exploited to investigate protein function.

Strengths:

(1) The manuscript provides a comprehensive and technically rigorous description of CRISPR/Cas9‑induced mutations across several loci. The accompanying genotyping, sequencing, and analytical approaches are sound, complementary, and well-detailed, providing a resource that will be valuable to researchers using genome editing beyond the specific application of genetic screening.

(2) By documenting a wide diversity of alleles and mutation types, the study contributes to understanding how allelic series generated by CRISPR can be leveraged for dissecting protein function, a perspective that has been less systematically presented in prior literature and could be compared to targeted strategies such as those described by Cassidy et al. (2022, DOI: [10.1016/bs.mie.2022.03.053]) or other relevant studies addressing CRISPR-based allelic series generation.

(3) The work demonstrates technically solid editing and validation workflows, setting a methodological reference point for similar projects across species or trait categories.

Weaknesses:

(1) There is a disconnect between the abstract/introduction and the discussion. While both the abstract and introduction focus on the potential use of crispant founders for phenotypic assessment in the context of genetic screening, with the introduction notably emphasizing this framework through a detailed section on ENU-based screens, the discussion devotes relatively little attention to this aspect. Instead, it primarily examines CRISPR mutagenesis outcomes, mutation detection, and allele characterization. Overall, the study's aims are not clearly or explicitly defined, which contributes to the lack of alignment across sections.

(2) Important limitations of the approach are not sufficiently discussed. For instance, the paper does not address how applicable the findings are beyond visible Mendelian traits, such as for quantitative, late-onset, or more subtle phenotypes, including behavioral ones, or how to interpret wild-type appearing founders. There is little consideration of appropriate experimental controls (e.g., wild-type or mock-edited animals) or of how many animals might be required to robustly establish genotype-phenotype associations.

(3) The conclusion that this strategy will "dramatically reduce time, resources, and animal numbers" is not quantitatively supported by the data presented and should be expressed more cautiously.

Reviewer #2 (Public review):

Summary:

The authors sought to validate the use of genetic screening pipelines that assess phenotypes in founders (F0, referred to as "crispants") obtained from CRISPR/Cas9 gene editing in 1-cell zygotes. The application of this approach in mice has generally been avoided due to concerns that results would be confounded by genetic mosaicism, but benefits to this approach include reducing animal numbers needed to achieve goals of identifying knockout phenotypes, as well as improved efficiency in the use of time and resources. The authors targeted seven genes associated with visible recessive phenotypes and observed the expected null phenotype in up to 100% of founders for each gene. Although mosaicism was common in the crispants, the various alleles were generally all functional null alleles and, in fact, some in-frame deletions with null phenotypes revealed critical functional motifs within the gene products. The rigorous data presented support using crispants to assess knockout phenotypes when guide RNAs with strong on-target and low off-target scores are used for gene editing in 1-cell mouse embryos.

Strengths:

By targeting multiple genes with existing, well-characterized mutations, the authors established a robust system for validating the analysis of crispants to assess gene function.

Cutting-edge technologies were used to carefully assess the spectrum of mutations generated.

Weaknesses:

There could have been some discussion regarding how this approach would be impacted if mutations are dominant or embryonic lethal (for the latter, for example, F0 can be examined as embryos).

Reviewer #3 (Public review):

Summary:

The study assesses whether CRISPR-generated founder (F0) "crispant" mice can be reliably used for initial phenotypic assessment and screening. By targeting seven genes with known visible recessive phenotypes, the authors show that, despite genetic mosaicism, the expected null phenotypes were observed in all targeted genes. These findings demonstrate that the phenotyping and screening of F0 "crispant" mice is a valid (and efficient) approach to selecting candidate alleles for follow-up studies, thereby streamlining mouse breeding and animal husbandry-related costs.

Strengths:

The study is comprehensive, carefully executed, and provides deep insight into the utility of F0 "crispant" mice for phenotypic screening. The authors evaluated the CRISPR/Cas9 editing outcomes across seven genes using multiple sequencing modalities, providing a robust framework for determining and interpreting complex founder genotypes. Importantly, the study examines/highlights the biological insight gained from compound heterozygous founders and naturally arising allelic series, enabling genotype-phenotype associations and functional inferences about protein domains.

More broadly, the authors' thorough evaluation of the CRISPR/Cas9-based gene editing events in the founders can serve as a benchmark for others in the field, engineering their own mouse "crispants."

Weaknesses:

The relationship between the sgRNA/Cas9 concentrations delivered to the zygotes and the resulting editing efficiencies are not explicitly investigated.

Author response:

We would like to thank the reviewers for their detailed reading of our manuscript and for the constructive comments they have provided.

We plan to make structural changes to the introduction and the discussion. Reviewer #1 describes the “disconnect between the abstract/introduction and the discussion”. We agree that “the study's aims are not clearly or explicitly defined”. We will edit the introduction to state our aim of investigating the factors that affect using “crispants” in mouse functional genomics. In the discussion, we described how our findings inform sgRNA choice to ensure biallelic gene disruption in founders and how our extensive genotyping methods enabled us to determine the molecular basis for the observed phenotype (explaining why some founders showed the expected recessive trait and why it was partial or absent in others). We also concluded from our attempts of multiplexing that this had too great an impact on viability to be useful. We will edit the discussion to better address our aim and to elaborate on several points raised by the reviewers (discussed in more detail below). Specifically, we will provide examples of screening situations where generating crispant mice may be useful, e.g. preliminary in vivo studies to follow up candidates identified in large-scale cellular screens. We will also provide more context about our assumptions underlying our statement that the use of crispants will “dramatically reduce time, resources, and animal numbers” compared to ENU mutagenesis (where recessive traits require breeding of G2 females with G1 males to achieve homozygosity of de novo mutations in G3 offspring) and the work needed to validate this. We will more clearly acknowledge that our proof-of-principle study used visible phenotypes that can be assessed in individual animals and then discuss how the use of crispants could be extended to the investigation of quantitative or late-onset traits using cohorts of crispants (discussed further below). We will also discuss the assessment of non-null alleles to dissect protein function, building on our unexpected finding that a single round of CRISPR/Cas9mediated mutagenesis can generate an allelic series.

Reviewer #1 asked us to address “how to interpret wild-type appearing founders”. We have discussed the mechanisms underlying the wild-type appearing founders generated in this study. This is linked with concerns in the field that incomplete editing, transcripts escaping nonsense-mediated decay, and/or the presence of in-frame mutations that don’t disrupt protein function may lead to founders that appear wild-type or have a partial phenotype. We have shown that our electroporation protocol results in very high levels of editing, but that this must always be assessed during genotyping. We found that by using an sgRNA that targets a critical protein domain, you can ensure that short in-frame indels also disrupt protein function. In future studies that determine how strain background modifies a phenotype that has been established on one strain (e.g. C57BL/6J), wild-type appearing founders would suggest that the new strain background rescues the null phenotype. In future studies that determine the consequence of targeting a second gene on a mutant background, wild-type appearing founders would indicate that the second mutation supresses the phenotype associated with the mutant background. We will add this to the discussion section where we describe possible screening situations in which crispant mice would be useful.

Reviewer #3 states that “the relationship between the sgRNA/Cas9 concentrations delivered to the zygotes and the resulting editing efficiencies are not explicitly investigated.” Members of The Centre for Phenogenomics (TCP) Transgenic Production Core who co-author this study (Lauryl Nutter, Marina Gertsenstein and Lauri Lintott) have published detailed protocols on mouse model production, which we cite in this paper (PMID: 30040228; PMID: 33524495; PMID: 39999224). In PMID: 33524495, they tested a two-fold difference in Cas9 RNP concentrations for generating knock-out alleles. Using their optimised protocols for electroporation of one cell zygotes with RNPs, we achieved an extremely high editing rate. We did not vary the sgRNA/Cas9 concentrations as part of this study as our goal was to assess the ability to generate “complete” null animals. We do note, however, that by targeting two genes simultaneously whilst keeping the total RNP concentration constant (to avoid reagent toxicity), we halved the amount of each sgRNA and this did not lead to a decrease in editing efficiency. We will highlight this in the results/discussion section (as appropriate).

Reviewer #1 asks about whether the use of crispants is applicable for “quantitative, late-onset, or more subtle phenotypes, including behavioral ones”. We are hopeful that this is possible and it is a priority for future studies. Crucially, cohorts of crispants can be generated in a single round of mutagenesis. Starting an experiment with ten donor females will produce ~100 zygotes, resulting in ~40 crispants. Power calculations must be performed to determine the size of the cohort required for the effect size and variability of the phenotype being studied, but many neurobehavioural studies use ~10 mutants vs ~10 controls. We note that sex and/or background genotype may mean that only some of the ~40 crispants produced can be used for phenotypic testing. This reviewer also raises the point about whether wild-type animals or mock-edited animals serve as the best controls. From work carried out by Lauryl Nutter and her colleagues from the IMPC (PMID: 37301944), we know that “wild-type” controls should ideally be from the same embryo pool as the crispants to avoid differences due to genetic drift within inbred colonies. This study also found that possible off-target mutations from CRISPR/Cas9-mediated mutagenesis is not an issue (despite a lot of attention in the literature). The suggestion of using mock-edited controls, resulting from zygotes that have gone through electroporation without RNP, addresses a possible need to control for the stress of undergoing the electroporation process. Our study shows that additional stress is caused by inducing and repairing a break in a neutral locus (EGFP). Controlling for these stressors may be particularly important when assessing behavioural phenotypes in crispants vs controls.

Reviewer #2 states that “there could have been some discussion regarding how this approach would be impacted if mutations are dominant or embryonic lethal (for the latter, for example, F0 can be examined as embryos).” Our manuscript discusses how crispants could help with the study of genes that may be essential. Specifically, we stated that when CRISPR/Cas9-mediated mutagenesis fails to produce live pups, phenotypic assessment of crispant embryos could reveal whether targeting the gene impacts embryogenesis. Crispants can only be used to screen for recessive traits since both alleles are edited. The assessment of dominant traits is not addressed in our study and remains a challenge in the field. We note that CRISPRi screens in cultured cells reveal candidates that when partially downregulated lead to the desired phenotype. One possibility is to employ this set up in vivo using dCas9-KRAB transgenic mice (JAX stock #030000). We could add this point to the discussion section.

let us not mention the version. instead link to create payment reference

no version

Let us add vertical navigation on the right for the items in the current page

Let us move the Payload to the top , so that the user gets immediate knowledge on landing on the apge.

Our doc is primarily concentrated around the workflow. But most of the competitor documentation is based on events. Example -- https://docs.wise.com/guides/developer/webhooks/event-types https://docs.trustly.com/api/credit-notification

Should we think restructuring our docs also to be aligned with competitor structure

Present when provided

We should explain the user what Third party Payment is . In api guide, if we have something, then we should point the user there

Please link it to an api for creating the session.

General comment about the article as a whole:

1. Cited sources are numerous, reliable, and relevant
2. The article sticks almost exclusively to direct quotes and verifiable facts
3. Descriptions of the judges are limited to which administration appointed them, which helps with transparency around potential political bias of the judges in the article.
4. The article stays on topic all the way through.

Detail included to increase emotional impact of this example.

Headline meant to evoke feeling - using term "whisks" instead of "moves"

The article focuses heavily on controlled trials where food was sometimes provided. My "Critical Question" for the review is: Can these results be replicated in a "free-living" environment where an EMT has to buy their own food at a gas station at 2 AM? This "access" issue is a major limitation I need to discuss.

The article mentions improvements in "insulin resistance." This bridges the gap between my primary source on hospital workers (Kahleova) and the general biology. It explains why the hospital workers in the COVID study saw their glucose drop—it wasn't magic, it was insulin sensitivity returning.

Savchuk cites a study where participants saw a "36% drop in deep abdominal fat." I’m highlighting this not for the vanity aspect, but because visceral fat is a key driver of the metabolic syndrome I’m investigating. This provides the physiological mechanism for why the diet works, which I need for my "Findings" section.

This article is published by Stanford Medicine, which lends it immediate institutional weight. The author uses this prestige to validate the idea of "metabolic psychiatry" linking diet to mental health. This is crucial for my paper because it supports the argument that what we eat affects how we handle high-stress trauma in the ER.

The author uses the phrase "food as medicine" to describe reversing illness. I annotated this because it shifts the paradigm from "diet for weight loss" to "diet for survival." For my audience (healthcare workers), framing nutrition as a clinical tool rather than a lifestyle choice is a stronger rhetorical angle.

I notice this is from NutritionFacts.org, which has a clear plant-based bias. While the data is compelling, I need to be careful in my discussion section to balance this with unbiased primary studies (like EPIC-Oxford) to ensure I’m not just cherry-picking pro-vegan data.

Greger notes that meat-eaters were "sorer" after exertion. This connects directly to my theme of "Physical Recovery." For healthcare workers, chronic soreness leads to burnout and injury; finding a dietary intervention that acts as a "natural NSAID" would be a massive finding for my final paper.

While the text mentions "recovery times" being faster for plant-based athletes, it doesn't specify what exact nutrients drive this. I need to cross-reference this with my primary sources to see if it's the antioxidants or the lack of inflammatory arachidonic acid (found in meat) that is actually reducing the soreness.

The article highlights that vegetarian athletes had "significantly higher endurance" than meat-eaters. In the context of my literature review, I need to define "endurance" not just as running a marathon, but as the ability for a nurse or EMT to maintain cognitive and physical focus during hour 11 of a 12-hour shift.

Greger starts by citing historical studies from Yale (Fisher) and Belgium to build a foundation of credibility before introducing modern data. By anchoring the argument in century-old research, he rhetorically suggests that the "endurance advantage" of plant-based eating isn't a new fad, but a long-forgotten biological fact.

Highlight: To understand how to

Highlight: Crowd work is typically

The action of swearing to or affirming.

The body of statements, analysis, opinions, etc

To stand over ( a place) with the legs

Romeo's yearning for Juliet is very deep.

In a way Benvolio calls Romeo delusional about his view on love.

This shows that obesity is not just about personal choices, but is strongly connected to income and social inequality. It suggests that people with higher incomes may have more access to healthy food, safe places to exercise, and healthcare, while lower-income groups may face more barriers that increase their risk of obesity. This also makes me think about how society often blames people for their weight without considering the economic and environmental factors that shape their daily options.

This shows that changing laws and policies can have a bigger impact on public health than just telling people to change their behavior. It suggests that focusing on larger structural changes, like raising taxes or limiting advertising, may be more effective than placing all the responsibility on smokers themselves.

This comment shows how different each person can be and the fact that we do not know everything about every person. Each member in a community has their own wants, needs, and stories that make them who they are.

This is a great detail to add that builds her character. It shows the strengths she has had from a very early age, and that could be why she is so confident in other areas.

I think that social media platforms showing the users content its interested is a fair assumption of what the user wants, but it can create echochambers where the user is only seeing the same kind of content. I think it should also push content that the user might be interested, emphasis on the might, leaving more room for the users to decipher and decide instead of keeping them in tunnel vision.

It is important for me to keep my position in all this in mind so that I don't leave anything out.

What if the observation sites only consists of online sites? I'll keep these in mind along with ethical consideration. I think it is also important for me to consider what type of interview I am going to do in the future, along with the format of the interview I am going to conduct.

This is 100% important for me to keep in mind. Notes need to be written down in order for me to be able to expand on them later on. Using descriptive notes in the beginning will only distract me and lead to weaker observations.

love #true #play w me

I think that posting a gif and considering it 'Copying" is a stretch. I think that the internet is so vast and connected that it is very easy to find information on where the gif came from. Also, considering virality, people are not focused on citing sources with things like gifs or videos, the way that our social media platforms are set up, there is no need to put down or care about that information.

ALOT OF PATIENCE

Do not over do it

Make sure you are specific about what you want your paper to be about.

Just how you would if you were reading something boring ang not so interesting to you.

MAKE SURE INTRO IS NOT GIVING THIS

make sure you are not just repeating yourself

It usually takes me re-reading about 3 times to catch the mistakes.

It sure can make me feel stressed.

Household labor created influence.

Push for marital equality.

Cultural shift toward romantic marriage.

Women gained bargaining power.

Love and practicality combined in marriage.

Defines marriage’s multiple roles.

Wife openly rejected marital expectations.

Court recognized women’s individual identity.

Refusal of marital sex used in divorce case.

Legal views of marriage were changing.

Women's refusal became more recognized and taken more serious

Verbal cruelty increased between 1860 and 1880 and emotional abuse is on a gradual rise.

main legal reason for seperation

Women challenged marital sexual control.

Divorce pressured men’s behavior.

Verbal abuse became the main complaint.

Abuse grew as a divorce reason.

Emotional connection became more important than economics.

Mobility and abandonment caused divorce.

Conflict over authority could end marriages.

Spending used as leverage in marriage.

Example of resistance to male control.

Gender conflict over spending priorities.

Recognition of women’s economic importance.

Sewing machine symbolized personal authority.

Technology gave women autonomy.

technology began changing women’s labor.

Men still held final financial authority.

Legal action used to defend women’s rights.

Separate finances increased women’s power.

Money caused marital tension.

Movement toward marital equality.

Women used subtle power rather than open control.

Conflict over women’s spending and value.

Patriarchal control declined across generations.

Women exercised personal freedom.

Male dominance was increasingly questioned.

Women gained more household authority.

Growing sensitivity to women’s equality.

Authority reframed as responsibility, not power.

Financial readiness seen as a moral duty

tradional provider role continued

Marriage combined love and economics.

Remaining single became more acceptable

Women raised standards for husbands.

Marriage choices still limited by reality.

Cultural advice promoted love-based marriage.

Shift from practical to emotional marriage.

Love was becoming important in marriage.

Women were urged to choose for themselves.

Idea that women didn’t need marriage for value.

Marriage became more of a personal choice.

Views on marriage became more diverse.

Cultural influence from the East shaped behavior.

early views of management were heavily oriented toward efficiency, at the expense of attention to the manager-as-leader. 

This is actually really funny because this is exactly what was happening when I was in middle school. There were always pictures that had some sort of "repost this for good luck" or "share this with someone else or you'll get bad luck." I think this is still pretty prominent on platforms that mostly host older users because I still see my aunts and uncles reposting things like that on Facebook.

I have the same question. If the observation site is online how do you substitute for things like comfortability or feeling left out? If we can't substitute then what do we do? This all makes me wonder if there is a disadvantage when doing online sites.

Noticing that some trials are being collected under fasting condition while others are not. This comparison will have identify the differences in fasting status.