1. Last 7 days
  2. www.nature.com www.nature.com
    Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors
    24
    Visit annotations in context

    Tags

    Annotators

    URL

    nature.com/articles/s41467-025-64255-8
  3. www.nature.com www.nature.com
    The astrocytic ensemble acts as a multiday trace to stabilize memory
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    nature.com/articles/s41586-025-09619-2
  4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesis
    6
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12533196/
  5. www.nature.com www.nature.com
    The formation of the ‘footprint of death’ as a mechanism for generating large substrate-bound extracellular vesicles that mark the site of cell death
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    nature.com/articles/s41467-025-64206-3
  6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Co-Conservation of synaptic gene expression and circuitry in collicular neurons
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12528736/
  7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Microglia-specific regulation of lipid metabolism in Alzheimer’s disease revealed by microglial depletion in 5xFAD Mice
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12528747/
  8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Effects of deep brain stimulation of the nucleus accumbens and anterior limb of the internal capsule on heroin addiction: Over five years of long-term follow-up in a prospective open-label pilot study
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12534431/
  9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12532598/
  10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12532699/
  11. pubs.acs.org pubs.acs.org
    Cascade Mechanochemical Transformation of a Benzobarrelane Polymer
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/jacs.5c14494
  12. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    The Mechanism of Mineral Nucleation and Growth in a Mini-Ferritin
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12532284/
  13. pubs.acs.org pubs.acs.org
    Interfacial Polymerization at a Nonaqueous Acid Interface for the Fabrication of Structurally Unusual Polymer Thin Films
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acs.macromol.5c01953
  14. pubs.acs.org pubs.acs.org
    Voltage-Induced Degradation of PTB7 with Atmospheric Exposure and the Contributions of Simultaneous Exposure to Light
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acs.jpcc.5c05633
  15. pubs.acs.org pubs.acs.org
    Modular Supramolecular Assembly through Clickable Hemilabile Ligands via the Weak-Link Approach
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acs.inorgchem.5c04131
  16. pubs.acs.org pubs.acs.org
    Cobalt(II) Phthalocyanine Substituents Tune the Electrocatalytic CO2 Conversion to Methanol
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acs.inorgchem.5c02279
  17. pubs.acs.org pubs.acs.org
    Comparative Evaluation of Low-Melting Metals (Bi, Sn, In) for Intensified Ethylene Production
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acs.energyfuels.5c04062
  18. pubs.acs.org pubs.acs.org
    Effect of Inertial Cavitation by Ultrasound Active Silica Nanoparticles on 2- and 3D Cellular Systems
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    pubs.acs.org/doi/full/10.1021/acsanm.5c04443
  19. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes
    6
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12533590/
  20. www.sciencedirect.com www.sciencedirect.com
    Sleep modulation via Nucleus Accumbens A2AR neurons to probe cognition and behavior in mice
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    sciencedirect.com/science/article/pii/S0306452225008516
  21. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Loss of postnatal Arx transcriptional activity in parvalbumin interneurons reveals non-cell autonomous disturbances in CA1 pyramidal cells
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC11381180/
  22. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Functional dissection of the zDHHC palmitoyltransferase 5–golgin A7 palmitoylation complex
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12528901/
  23. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Inflammasome-independent IL-1β activation via staphopain A protease of Staphylococcus aureus[image]
    11
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12528902/
  24. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Dissecting the Neuroprotective Interaction Between the BH4 Domain of BCL-w and IP3 Receptor
    9
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC11490406/
  25. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Biophysically constrained dynamical modelling of the brain using multimodal magnetic resonance imaging
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12533546/
  26. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances in Ddx3x Haploinsufficient Mice
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12524031/
  27. link.springer.com link.springer.com
    [18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s11307-025-02056-7
  28. link.springer.com link.springer.com
    CPT1A facilitated ferroptosis by forming feedback loop with Nrf2 via PI3K/AKT pathway in colorectal cancer
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s10495-025-02171-4
  29. link.springer.com link.springer.com
    Effect of an acute bout of endurance eccentric exercise on exerkines production in healthy males
    5
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s00421-025-06015-6
  30. link.springer.com link.springer.com
    Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s00213-025-06917-5
  31. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Platelet‐Macrophage Aggregates in Remodeled Vessels of Patients With Pulmonary Arterial Hypertension
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12521612/
  32. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Mettl14 Deficiency Promotes Fam32a Expression via m6A Modifications to Facilitate the Hepatocyte G1/S Transition
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/full/10.1002/jcp.70102
  33. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Mechanistic Insights Into METTL1/WDR4-Mediated m7G Modification in Prostate Cancer Progression and Its Potential as a Therapeutic Target
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/full/10.1002/jbt.70546
  34. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Organization of the Auditory Brainstem in a Lizard, Gekko gecko. II. Afferent and Efferent Projections of Nuclei of the Lateral Lemniscus and the Torus Semicircularis
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12534725/
  35. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Characterizing Evoked Movement Patterns and Connectivity in Sensorimotor Cortex After Sensory Loss in Squirrel Monkeys
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12531938/
  36. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Head Color Morph‐ and Sex‐Specific Differences in Follistatin Gene Expression in the Gouldian Finch Brain
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12534724/
  37. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Immunohistochemical Profile of a Conspicuously Organized Structure in the Dorsal Forebrain of the Peacock Gudgeon, Tateurndina ocellicauda
    8
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/10.1002/cne.70097
  38. onlinelibrary.wiley.com onlinelibrary.wiley.com
    The Distribution of Nitric Oxide-Synthesizing Neurons and Soluble Guanylate Cyclase in Relation to Dopaminergic Systems in the Pigeon Brain
    7
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/10.1002/cne.70095
  39. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Synergistic Reduction of Breast Cancer Cell Viability and Aggressiveness Through Dual Inhibition of APE1 Redox Function and STAT3 Signaling
    4
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/10.1002/cbin.70094
  40. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Biotechnological Potential of Seaweeds from Bahia, Brazil: Metabolomic insights, Photoprotection and Antioxidant Activity
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/10.1002/cbdv.202502708
  41. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Early Postnatal Infection With Human Cytomegalovirus Has Long‐Term Consequences on Brain Structure of Former Preterm Born Children
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12528545/
  42. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Chemically Recyclable and Tunable Polyolefin‐Like Multiblock Copolymer Adhesives
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12535384/
  43. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com
    Gold Nanoturf-Mediated Wireless Photothermal Upregulation of Human Adipose-Derived Stem Cell Spheroids for Synergistic Skin-Wound Closure
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202515490
  44. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com
    Punicalagin Enhances Autophagy Through Sirtuin 1/FoxO3a Axis to Inhibit Intracellular Mycobacterium Abscessus Infection
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202511734
  45. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com
    Synergistic Anti-Cancer Therapy Through Ultrasound-Induced Piezocatalytic Therapy and Tumor Treatment Fields
    3
    Visit annotations in context

    Tags

    Annotators

    URL

    advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202511604
  46. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com
    Pseudo-Solid-State Polymer Materials for QD-Sensitized NIR-I and NIR-II Upconversion Beyond the Silicon Bandgap
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202512741
  47. febs.onlinelibrary.wiley.com febs.onlinelibrary.wiley.com
    A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.70127
  48. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Transcriptomic and Metabolomic Insights into Benzylisoquinoline Alkaloid Biosynthesis in Goldthread (Coptis trifolia)
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12525506/
  49. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Glia Cells Are Selectively Sensitive to Nanosized Titanium Dioxide Mineral Forms
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12524891/
  50. www.biorxiv.org www.biorxiv.org
    Persistence of vestibular function in the absence of glutamatergic transmission from hair cells
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/content/10.1101/2025.10.15.682551v1
  51. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A histone methyltransferase-independent function of PRC2 controls small RNA dynamics during programmed DNA elimination in Paramecium
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC12529928/
  52. academic.oup.com academic.oup.com
    eEF2K promotes immune evasion in melanoma via Cyclin D1–mediated stabilization of PD-L1
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    academic.oup.com/jimmunol/advance-article-abstract/doi/10.1093/jimmun/vkaf278/8287776
  53. 54.241.53.176 54.241.53.176
    gotthardt-et-al-2025-cysteine-reactive-covalent-chloro-n-acetamide-ligands-induce-ferroptosis-mediated-cell-death-html.html
    2
    Visit annotations in context

    Tags

    Annotators

    URL

    54.241.53.176/63994eedfd6c98b86dee1f70deb73962649e18d0/gotthardt-et-al-2025-cysteine-reactive-covalent-chloro-n-acetamide-ligands-induce-ferroptosis-mediated-cell-death-html.html
  54. www.biorxiv.org www.biorxiv.org
    Bora Bridges Aurora-A Activation and Substrate Recognition of PLK1
    4
    1. EMBOpress 21 Oct 2025

      Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

      Learn more at Review Commons

      Reply to the reviewers

      We appreciated the positive, detailed and helpful feedback from all three reviewers.

      Reviewer 1.

      Minor comments.

      1. In the introduction, on page 2, the authors seem a little confused about the Plk1 Polo-box domain - text as written: "...kinase domain linked to tandem Polo-box domains (PBD)", and cite a review paper. Actually, there is only a single Polo-box domain in these kinases, which contains both Polo-boxes and a bit of the upstream linker region. The "PBD" terminology denotes his 2-Polo-box +linker structure. Perhaps it would be better here to cite the PBD structure (Elia et al., Cell, 2002) as a primary citation here.

      Response: Thank you for finding this error, the text has been updated and the new citation included within the text on line 65.

      1. Similarly, the line "...during the G2/M transition following successful DNA damage repair" cites the Seki et al paper, but those findings are shown in the Macurek et al paper, not the Seki et al paper.

      _Response: _Thank you for finding this error, the new citation included within the text on line 69.

      1. Using the model of the ternary complex as shown in Figure 1B, deletion constructs of Bora missing regions within the disordered loops, but still retaining the residues that bind the PBD, FW pocket and Aurora A, can be modeled and tested to see if such deletions can improve the ipTM scores and binding affinity.

      Response: ____AlphaFold3 modelling was attempted with shorter regions of Bora to see the effect on the ipTM scores. Unfortunately, when Bora was reduced to shorter sequences, such as 18-88 or 18-45 modelled with 68-120, the models became inconsistent and of a low quality. Models were also created including the short region of Bora surrounding Ser252 that interacts with the polo box domain as well as Bora 18-120, but this had minimal effect on the calculated iPTM scores.

      1. On page 5, "S112A" within the sentence "Unexpectedly, the F56A/W58A Bora was less efficiently phosphorylated on S112A (Supplementary Figure S11, F compared to H and Supplementary Table S4)." This should be "S112".

      Response: ____Thank you for spotting this, the error has been corrected.

      1. In the assays shown in Figure 2D, the presence of excess F56AW58A Bora that remained unphosphorylated on S112 may complicate the interpretation of the results. Can the authors show that the S112-phosphorylated F56AW68A Bora is predominantly bound to Aurora A in such a mixture, perhaps by NMR using labelled pS112 F56AW58A Bora and unlabeled S112 F56AW58A Bora?

      _Response: _15N13C labelled of Bora 18-120 F56A W58A was produced and assigned. We then phosphorylated a sample using ERK2, tracking with NMR, and when the reaction had progressed to a 50:50 mixture of pSer112 and Ser112 (based on peak intensities) the kinase activity was quenched by addition of EDTA to sequester Mg2+. This produced a solution containing both pS112 and unphosphorylated S112 Bora species with marker peaks in HSQC spectra that could be used to directly compare Aurora-binding to the two species. Aurora-A was introduced to the sample and the peak intensities were monitored. Although both species are affected, there is much greater peak loss from the pS112 related peaks than those for unphosphorylated S112. This indicates that Aurora-A still preferentially binds pS112 Bora over S112 Bora when the F56A W58A mutation is present. This data has been included in Supplementary Figure S11.

      1. Please expand Figure 3A to better show the FW pocket-forming residues on Plk1.

      Response: ____Figure 3 has been amended to reduce the size of the sequence alignments so that 3A could be made slightly larger.

      1. It would be helpful to label the peaks in the mass spectra in Fig. S11 with the phospho-species that they correspond to.

      Response: ____This information has been added to the mass spectra in Fig. S11 (now supplementary Figure S14) to make them easier to view.

      1. In the last paragraph on page 7, "see we" in the sentence "As well as a decrease in intensity around pSer112 in Bora, see we an overall effect with decreased intensity across most of the Bora sequence." Should be corrected to "we see".

      Response: ____Thank you for spotting this, the error has been corrected.

      1. While not required, it would be helpful if binding or Bora to Aurora A after Erk2 phosphorylation could be shown using fluorescence polarization or ITC to lend additional support to the NMR data for S112 and S59 phosphorylation and for CEP192 and TPX2 competition.

      Response: ____This question has been partially answered in previous work by Tavernier et al. (2021), who showed improved binding of Aurora-A to Bora after Erk phosphorylation (by SPR), and they used labelled-TPX2 for a series of competition FP assays in that and the recent parallel study (Pillan et al. 2025).

      We made initial efforts to perform additional FP assays using longer sections of Bora with different phosphorylation states but without success (perhaps due to the multisite-binding nature of the Bora–Aurora interaction, and difficulties with directly expressing phosphorylated Bora). The revised manuscript now includes some additional NMR data to show improved Bora–Aurora-A interaction after phosphorylation at Ser59 (Supplementary Figure S12).

      1. The Aurora A phosphorylation motif has been further defined beyond that reported by the Pinna lab in 2005. Notably, the Ser-59 sequence on Bora (F-R-W-S-I), has, in addition to dominant selection for AR in the -2 position, both favorable -1 (W) and +1 (I) positions based on peptide library measurements (Alexander et al., Science Signaling 2011), further arguing that it may be an excellent Aurora A phosphorylation site.

      Response: ____Thank you for highlighting this publication and how it further reinforces the likelihood of Ser59 being an effective substrate for Aurora-A, this should have been included in the original manuscript. This citation has now been included.

      1. Have the authors tried to model the Drosophila melanogaster Aurora A-Bora-Polo complex to see if the Asn substitution of Bora Ser59, and the expected loss of the interactions between Bora pSer59 and Plk1 Arg59 and Aurora A Arg205 are compensated by other features?

      Response: ____A ternary complex between the Drosophila melanogaster orthologues was modelled using AlphaFold3 (Uniprot code PLK1 (Q9VVR2 72-165), Aurora-A kinase (Q9VGF9) 151-411 and PLK1 (P52304 21-280)). This model was analysed using PDBe PISA to identify potential interactions between the three proteins, focusing on residues that are not conserved between the human and Drosophila sequences. From this model a potential salt bridge was identified between Drosophila Bora Lys120 and PLK1 Glu93 that would not occur in the human ternary complex given Lys120 is replaced with an asparagine. This could be an alternative (kinase-independent) method for improved Bora-PLK1 interaction. When comparing the Bora:Aurora-A side of the predicted interface and focusing on the short region of Bora in between Aurora-A and PLK1, there were no clear differences seen in the residues predicted to bind to Aurora-A. This modelling has been included in Supplementary Figure S10 C and D.

      1. Given the relevance of the recent publication from Zhu et al. to this study, the authors may want to comment on, or test, the relative importance of PKA and Aurora A as a potential kinase for Bora S59. While those authors argue that PKA phosphorylates Bora on Ser-59, one could easily imagine a model in which either PKA or Aurora A could initially phosphorylate that site followed by a propagation step after initial Aurora A activation, in which Aurora A phosphorylation of Bora Ser-59 is the dominant process.

      Response: ____A brief discussion of this recent publication has been added to the discussion, highlighting the similarities between the two publications and the importance of pSer59, as well as suggesting that in cellulo this modification could be achieved via more than one pathway. We also include some additional NMR data to show improved Bora–Aurora-A interaction after phosphorylation at Ser59 (Supplementary Figure S12).

      Reviewer 2.

      Minor comments.

      Page 5: '... a K82R PLK1 mutant was used to increase the stability of the protein' - It is not clear how this mutation confers increased stability of the protein. The authors do not show any data to support this. Isn't the PLK1 K82R an ATP-binding-deficient, kinase-inactive mutant?

      Response: ____Thank you for spotting this, the text has been updated to clarify that this version of PLK1 was used as it is acting as a substrate in the in vitro assay as we didn’t want to see any PLK1 activity within this assay.

      All panels showing the Alphabridge diagram - it would be helpful if pictorial definitions of the colour codes were provided with corresponding score ranges (in addition to the description in the figure legend).

      Response:____The AlphaBridge images have been updated to include details about the plDDT scores each of the different colours refer to.

      Fig 2B - The Fluorescence anisotropy assay curves do not reach a plateau. Though the effect of mutation on binding affinity is pretty clear, if possible, I suggest including more data points at higher concentrations and estimating apparent Kd values.

      __Response:____The direct binding assay was repeated with a higher concentration of PLK1 in order to try and see a top plateau. This was successful and has been included in Figure 2B (shown in black). The measured Kd was 24 ± 3 µM. __

      The cartoon representation of the structures and molecular interfaces - better to avoid shadows, as they compromise the clarity of the figures, particularly the ones where side chains are shown in stick representation.

      Response:____The structural images have been remade to remove the shadows and improve the clarity of the images.

      It is important to discuss how the parallel studies by Verza et al. and Pillan et al. complement this study, highlighting similarities and differences.

      Response:____References to these two publications and details on the similarities and differences seen are now included in the discussion.

      Reviewer 3.

      Major comments

      It would be helpful to measure the level of pThr210 PLK1 in some experiments and graph the data. The current presentation is Fig. 2D-E is qualitative rather than quantitative.

      Response:____Graphs displaying the levels of pThr210 produced in the assay are now shown in Supplementary Figure S4.

      Have the authors measured the binding affinity of the F/W mutant Bora for PLK1 using the assay in Fig. 2B? Likewise, for Fig. 7 the S59 mutant could be tested to see if it affects PLK1 binding or activation.

      Response:____The direct binding assay has been repeated with the use of a FAM-Bora peptide that incorporates the F56A W58A mutation which shows reduced binding (Figure 2B, shown in blue). A version of the Bora peptide phosphorylated on Ser59 was also tested in the direct binding assay and this shows a similar affinity for PLK1 to the wild-type sequence (Figure 2B, shown in red compared to the wild-type shown in black).

      It would be helpful if measurements of pThr210 PLK1 for all conditions were shown in the graph Fig. 7F.

      Response:____This graph has been updated to include the levels of phosphorylation seen for PLK1 in all of the conditions tested.

      Minor comments

      I found Figure S1B easier to understand than Fig S1A and Fig 1A-B. Some of the supplemental data Fig. S1C-E could be moved to a revised Figure 1, dropping the current Fig. 1A-B. Can the interaction plots (Fig. S1C-D) be rotated to have the same original at the top and order of proteins (i.e. Bora > Aurora A > {plus minus} PLK1 depending on the plot).

      Response:____Figure 1 and S1 have been rearranged to hopefully make them easier to understand, with all AlphaFold3 models of the full-length sequences kept in the supplementary figure and the focus in 1B just on the truncated model. The AlphaBridge plots have been rotated as suggested.

      Figure 3F. Typo "Strongyl" not "Strongly".

      Response:____Thank you for spotting this, this has been corrected in the updated manuscript.

      Figure 3 could be supplemental material.

      Response:__Thank you for your suggestion, but we have decided to keep this as a main figure.

      Fig. 7E. Run a positive control reaction +ERK2 on the second gel to allow direct comparison of pThr210 across all the conditions tested.

      Response:____These samples have been rerun on the same membrane and the levels of phosphorylation have been quantified and included in Figure 7F.

      PeerReviewed
    2. EMBOpress 21 Oct 2025

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #3

      Evidence, reproducibility and clarity

      Summary.

      Miles and co-workers have carried out a careful and high-quality study of the activation mechanisms of the mitotic kinase PLK1. Multiple proteins have been implicated in PLK1 activation and localisation as cell enter and pass through mitosis. Initial activation of PLK1 is promoted by a complex of Bora with another kinase Aurora A. Later in mitosis, this activated PLK1 associates with mitotic spindle and centrosome proteins regulating different aspects of mitosis and cytokinesis. In this study, Miles et al. extend previous work on this question by proposing and testing detailed models for Bora/Aurora A-mediated activation of PLK1 to elucidate the mechanism of this reaction.

      Using the latest Alphafold they generate a series of models of the PLK1/Bora/Aurora A complex to home in on the key regions mediating interactions of the three proteins. This approach suggests an arrangement where the first ~120 amino acids of Bora wrap Aurora A and create an interaction surface for the N-terminal kinase domain of PLK1. This orients Thr210 in PLK1 towards Aurora A creating a situation likely favourable for phosphorylation, although has the authors discuss there are some caveats to this. A further prediction of the modelling helps explain the requirement for Bora phosphorylation to promote the interaction with Aurora A. This data is presented in Fig. 1 and Fig. S1-S3.

      In the subsequent figures the details of this model are tested using biochemical assays and structural biology methods to validate key predictions. First the PLK1 interaction with Bora was shown to require the conserved F/W motif of Bora and a conserved pocket close to R106 on PLK1 (Fig. 2 and 3). In reconstituted PLK1 activation assays the F/W motif mutant Bora showed greatly attenuated pThr210 phosphorylation. This reaction also required phosphorylation of Bora at S112, presumably due to the interaction with Aurora A. An R106A mutant PLK1 showed reduced binding to Bora and reduced kinase activation. This data is clear and provides compelling support for the model.

      Using NMR the authors then investigate the interaction between Bora and Aurora A, and more specifically the requirement for Bora phosphorylation at Ser112. The NMR data in Fig. 4 and Fig. 6 provide good support for the Alphafold model. A helpful comparison with known Aurora A binding proteins is also shown to highlight the way CEP192, TPX2 and TACC3 contact a series of conserved pockets on the surface of Aurora A which are common to the Bora interaction. S59 phosphorylation by Aurora A is also shown to play an important role in contacting PLK1 and is required for pThr210 phosphorylation.

      In summary, the authors have made valuable progress in working out details of the PLK1 activation mechanism, that extends previous work in the field.

      Major comments.

      It would be helpful to measure the level of pThr210 PLK1 in some experiments and graph the data. The current presentation is Fig. 2D-E is qualitative rather than quantitative.

      Have the authors measured the binding affinity of the F/W mutant Bora for PLK1 using the assay in Fig. 2B? Likewise, for Fig. 7 the S59 mutant could be tested to see if it affects PLK1 binding or activation.

      It would be helpful if measurements of pThr210 PLK1 for all conditions were shown in the graph Fig. 7F.

      Minor comments.

      I found Figure S1B easier to understand than Fig S1A and Fig 1A-B. Some of the supplemental data Fig. S1C-E could be moved to a revised Figure 1, dropping the current Fig. 1A-B. Can the interaction plots (Fig. S1C-D) be rotated to have the same original at the top and order of proteins (i.e. Bora > Aurora A > {plus minus} PLK1 depending on the plot). Figure 3F. Typo "Strongyl" not "Strongly". Figure 3 could be supplemental material. Fig. 7E. Run a positive control reaction +ERK2 on the second gel to allow direct comparison of pThr210 across all the conditions tested.

      Significance

      Timely and orchestrated activation of multiple mitotic protein kinases is crucial for the alignment and segregation of chromosomes, and for the process of cell division. In this study the authors explore how activation of the mitotic kinase PLK1 is triggered by another mitotic kinase Aurora A, and the role played by a scaffold protein Bora.

      Strengths: Detailed analysis of mechanism using biochemical and structural approaches.

      Limitations: The study is focussed on the biochemical and structural mechanisms rather than the cellular outcomes. Some data would benefit from additional quantitative measurement.

      Relevance: Cancer and cell biology due to the role of Aurora A in many cancers.

      Reviewer expertise: Biochemistry, molecular and cell biology.

      PeerReviewed
    3. EMBOpress 21 Oct 2025

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #2

      Evidence, reproducibility and clarity

      Summary:

      PLK1 is one of the master regulators of cell division. The activation of PLK1 requires the activation loop phosphorylation at T210, mediated by Aurora A kinase. However, Aurora A phosphorylation of PLK1 T210 requires Bora, one of the several activators of Aurora A kinase. While the molecular requirement of Aurora A kinase and Bora for PLK1 activation is well established, the mechanistic understanding of how Bora facilitates PLK1 activation by Aurora A has remained an important open question for a long time. Exploiting the latest development in AI-driven structure prediction, three independent studies provide a structural and mechanistic basis for PLK1 activation by Aurora A and Bora. Here, Miles et al. have generated AlphaFold models, further characterised some of the interfaces using NMR, and validated the contribution of intermolecular interactions at suggested interfaces in vitro using recombinant proteins in kinase assays. Overall, this is a well-executed work providing important new insights into our understanding of the activation of the critical regulator of cell division, PLK1. However, as the authors have highlighted in the discussion section, one limitation of this modelling study is that the models still do not entirely explain how these interactions facilitate the phosphorylation of Thr210ur, as this residue is oriented far away from Aurora A's active site for the reaction to take place. Despite this limitation, I believe this is an important work that advances our understanding significantly.

      Comments:

      Experimental data satisfactorily support claims. Hence, most of my comments are minor in nature.

      Points to consider during revision:

      Page 5: '... a K82R PLK1 mutant was used to increase the stability of the protein' - It is not clear how this mutation confers increased stability of the protein. The authors do not show any data to support this. Isn't the PLK1 K82R an ATP-binding-deficient, kinase-inactive mutant?

      All panels showing the Alphabridge diagram - it would be helpful if pictorial definitions of the colour codes were provided with corresponding score ranges (in addition to the description in the figure legend).

      Fig 2B - The Fluorescence anisotropy assay curves do not reach a plateau. Though the effect of mutation on binding affinity is pretty clear, if possible, I suggest including more data points at higher concentrations and estimating apparent Kd values.

      The cartoon representation of the structures and molecular interfaces - better to avoid shadows, as they compromise the clarity of the figures, particularly the ones where side chains are shown in stick representation.

      It is important to discuss how the parallel studies by Verza et al. and Pillan et al. complement this study, highlighting similarities and differences.

      Significance

      As highlighted in the summary, a mechanistic understanding of how PLK1 is activated by Aurora A kinase and its activator Bora has remained a long-standing open question. As PLk1 is one of the major regulators of cell division, which exerts its function (via phosphorylating numerous substrates) during different stages of mitosis, understanding its activation mechanism is of critical interest for those working on the cell cycle in general and cell division in particular. A key limitation of this study is the lack of any cellular functional evaluation of the interaction interfaces.

      PeerReviewed
    4. EMBOpress 21 Oct 2025

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #1

      Evidence, reproducibility and clarity

      Miles et al. used a combination of AlphaFold modeling, biochemical assays of mutant constructs and NMR spectroscopy to model the ternary complex of Aurora A, Bora and Plk1, and elucidate how Bora can act as a molecular bridge that facilitates the phosphorylation of the activation loop Thr210 within Plk1 by Aurora A. Their studies identified an interaction between residues 52-73 within Bora and the 'FW' pocket on the N-terminal lobe of Plk1, which binds Phe56 and Trp58 of Bora. Additionally, Ser59 of Bora was identified as a good Aurora A substrate using a Bora peptide array, and pSer59 was predicted to form bridging interactions with Aurora Arg205 and Plk1 Arg59. This was supported by NMR and biochemical assays. In addition, the authors validate that phosphorylation of Ser-112 on Bora enhances stabilization of the Aurora A-Bora complex Overall, the model revealed novel details of the interactions within the Aurora A-Bora-Plk1 ternary complex that are supported by the biochemical and NMR data. The work will be of significant interest to basic scientists whose work involves protein kinase signaling, cell division/mitosis, signal transduction, and cancer biology. We recommend publication of this manuscript with the following minor changes and additions.

      1. In the introduction, on page 2, the authors seem a little confused about the Plk1 Polo-box domain - text as written: "...kinase domain linked to tandem Polo-box domains (PBD)", and cite a review paper. Actually, there is only a single Polo-box domain in these kinases, which contains both Polo-boxes and a bit of the upstream linker region. The "PBD" terminology denotes his 2-Polo-box +linker structure. Perhaps it would be better here to cite the PBD structure (Elia et al., Cell, 2002) as a primary citation here.
      2. Similarly, the line "...during the G2/M transition following successful DNA damage repair" cites the Seki et al paper, but those findings are shown in the Macurek et al paper, not the Seki et al paper.
      3. Using the model of the ternary complex as shown in Figure 1B, deletion constructs of Bora missing regions within the disordered loops, but still retaining the residues that bind the PBD, FW pocket and Aurora A, can be modeled and tested to see if such deletions can improve the ipTM scores and binding affinity.
      4. On page 5, "S112A" within the sentence "Unexpectedly, the F56A/W58A Bora was less efficiently phosphorylated on S112A (Supplementary Figure S11, F compared to H and Supplementary Table S4)." This should be "S112".
      5. In the assays shown in Figure 2D, the presence of excess F56AW58A Bora that remained unphosphorylated on S112 may complicate the interpretation of the results. Can the authors show that the S112-phosphorylated F56AW68A Bora is predominantly bound to Aurora A in such a mixture, perhaps by NMR using labelled pS112 F56AW58A Bora and unlabeled S112 F56AW58A Bora?
      6. Please expand Figure 3A to better show the FW pocket-forming residues on Plk1.
      7. It would be helpful to label the peaks in the mass spectra in Fig. S11 with the phospho-species that they correspond to.
      8. In the last paragraph on page 7, "see we" in the sentence "As well as a decrease in intensity around pSer112 in Bora, see we an overall effect with decreased intensity across most of the Bora sequence." Should be corrected to "we see".
      9. While not required, it would be helpful if binding or Bora to Aurora A after Erk2 phosphorylation could be shown using fluorescence polarization or ITC to lend additional support to the NMR data for S112 and S59 phosphorylation and for CEP192 and TPX2 competition.
      10. The Aurora A phosphorylation motif has been further defined beyond that reported by the Pinna lab in 2005. Notably, the Ser-59 sequence on Bora (F-R-W-S-I), has, in addition to dominant selection for AR in the -2 position, both favorable -1 (W) and +1 (I) positions based on peptide library measurements (Alexander et al., Science Signaling 2011), further arguing that it may be an excellent Aurora A phosphorylation site.
      11. Have the authors tried to model the Drosophila melanogaster Aurora A-Bora-Polo complex to see if the Asn substitution of Bora Ser59, and the expected loss of the interactions between Bora pSer59 and Plk1 Arg59 and Aurora A Arg205 are compensated by other features?
      12. Given the relevance of the recent publication from Zhu et al. in https://doi.org/10.1038/s41467-025-63352-y to this study, the authors may want to comment on, or test, the relative importance of PKA and Aurora A as a potential kinase for Bora S59. While those authors argue that PKA phosphorylates Bora on Ser-59, one could easily imagine a model in which either PKA or Aurora A could initially phosphorylate that site followed by a propagation step after initial Aurora A activation, in which Aurora A phosphorylation of Bora Ser-59 is the dominant process.

      -Dan Lim and Michael Yaffe

      Significance

      The work is well done and clearly presented.

      PeerReviewed
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/lookup/doi/10.1101/2025.08.08.668882
  55. social-media-ethics-automation.github.io social-media-ethics-automation.github.io
    8.9. Bibliography
    3
    1. Scxrlett 21 Oct 2025
      Greg Miller. Researchers are tracking another pandemic, too—of coronavirus misinformation. Science, March 2020. URL: https://www.science.org/content/article/researchers-are-tracking-another-epidemic-too-misinformation (visited on 2023-12-05).

      This article by researchers at UW discuss the mass wave of misinformation in regards to the coronavirus. In this article, one of the researchers reveals that often, misinformation during massive events such as the Covid 19 out break are due to people's growing fear and anxiety. Because of the uncertainty, people are often seeking solutions, which therefore help exhilarate information they may find shocking or comforting. This is why its important to always fact check data before fully believing what you see online.

    2. Scxrlett 21 Oct 2025
      Jordan Pearson. Your Friends’ Online Connections Can Reveal Your Sexual Orientation. Vice, September 2014. URL: https://www.vice.com/en/article/gvydky/your-friends-online-connections-can-reveal-your-sexual-orientation (visited on 2023-12-05).

      This article talks about how even if profiles may not share much information about themselves, their sexual orientation can still be deduced by their contact list, or "friends" list online. This that simple things like your network of who you know can reveal about yourself. It was revealed in the article that researches were also able to build bots which can collect information just like this to keep tabs on people. This goes for show that although you may think you are protected, you're online data can reveal things you may not want to share.

    3. yfeng33 21 Oct 2025
      Catherine Stinson. The Dark Past of Algorithms That Associate Appearance and Criminality. American Scientist, January 2021. URL: https://www.americanscientist.org/article/the-dark-past-of-algorithms-that-associate-appearance-and-criminality (visited on 2023-12-05).

      I found Catherine Stinson’s “The Dark Past of Algorithms That Associate Appearance and Criminality” especially compelling — it highlights how seemingly neutral data-mining efforts (for example facial recognition or risk scoring) embed deep historical biases and reinforce harmful associations. It makes me reflect: when we apply mining methods in social-media contexts, it’s not just about data quality but also which associations we’re willing to carry forward.

    Visit annotations in context

    Annotators

    URL

    social-media-ethics-automation.github.io/book/bsky/ch08_data_mining/09_bibliography.html
  56. www.google.com www.google.com
    Google
    1
    Visit annotations in context

    Tags

    Annotators

    URL

    google.com/webhp
  57. d2l.ai d2l.ai
    2.4. Calculus — Dive into Deep Learning 0.16.3 documentation
    1
    Visit annotations in context

    Annotators

    URL

    d2l.ai/chapter_preliminaries/calculus.html
  58. Local file Local file
    Untitled document
    6
    1. TibangLiu 21 Oct 2025
      This framework goes beyond just meetingregulatory limits; it is about fostering a nighttime acoustic environment that contributes to the serenity of thecommunity.

      I like this part. The author says we should not just follow the minimum rules. We should try to create a city that feels peaceful for everyone. It's not just about avoiding fines; it's about making the community a better place to live.

    2. TibangLiu 21 Oct 2025
      Additionally, the pub (or bar) owner should ensure that their external walls should be a minimum of 100 mmconcrete precast panels, and double glazed windows and doors (say 8 mm to 10 mm laminated glasses with a75 mm to 100 mm air gap) should be closed.25 This type of design can have an acoustic insulation of around 40dB.

      This is a very useful and specific solution. It explains a technical way to reduce noise—using special windows. It even says how much noise it can block (around 40 dB).

    3. TibangLiu 21 Oct 2025
      In the US, the number of noise complaints about bars and clubs increased by over 100 percentfrom 38,000 in 2010 to 93,000 in 2015 in New York City.

      This statistic is very powerful. It shows that in just five years, the number of complaints in New York City more than doubled. This proves that the problem is not getting better; it is getting much worse. It is a clear trend.

    4. TibangLiu 21 Oct 2025
      The survey results showed that 41% of respondents suffered from anxiety while 35% ofrespondents suffered from disturbed sleep due to noise

      This is a direct link between bar noise and health problems. It's not just about being annoyed. The noise causes real mental health issues like anxiety and sleep problems for many people. This is very strong evidence for my research.

    5. TibangLiu 21 Oct 2025
      Pubs (a short form of public houses) and bars are an integral part of cities across the globe. They serveimportant social functions and are recognized as a tourist attraction in many places.

      This part is important because it explains why we can't just close all the bars. They are important for the city's culture and for tourism. This shows that the problem is not simple; we have to find a balance between nightlife and quiet for residents.

    6. TibangLiu 21 Oct 2025
      Previousresearch showed that the average measured noise level in Hong Kong’s pubs and bars was 80 dBA in peakhours (with peak measured value up to 97 dBA) and 75 dBA in happy hours.

      This is a important statistic from the study. It gives specific numbers for how loud bars are. 80 dBA is very loud, like a garbage disposal. This is solid data I can use to show how big the problem is.

    Annotators

  59. www.biorxiv.org www.biorxiv.org
    Bilateral equalization of synaptic output in olfactory glomeruli of Xenopus tadpoles
    3
    1. Public_Reviews 21 Oct 2025

      eLife Assessment

      This manuscript investigates inter-hemispheric interactions in the olfactory system of Xenopus tadpoles. Using a combination of electrophysiology, pharmacology, imaging, and uncaging, the transection of the contralateral nerve is shown to lead to larger odor responses in the unmanipulated hemisphere, and implicates dopamine signaling in this process. The study uses a rich and sophisticated array of tools to investigate olfactory coding and uncovers valuable mechanisms of signaling. However, the data is incomplete, with a few of the conclusions not being well-supported by the data; the interpretation should be adjusted with some caveats, or additional experiments should be done to support these conclusions.

      Summary
    2. Public_Reviews 21 Oct 2025

      Reviewer #1 (Public review):

      In this study, the authors investigate LFP responses to methionine in the olfactory system of the Xenopus tadpole. They show that this response is local to the glomerular layer, arises ipsilaterally, and is blocked by pharmacological blockade of AMPA and NMDA receptors, with little modulation during blockade of GABA-A receptors. They then show that this response is translently enlarged following transection of the contralateral olfactory nerve, but not the optic lobe nerve. Measurement of ROS- a marker of inflammation- was not affected by contralateral nerve transection, and LFP expansion was not affected by pharmacological blockade of ROS production. Imaging biased towards presynaptic terminals suggests that the enlargement of the LFP has a presynaptic component. A D2 antagonist increases the LFP size and variability in intact tadpoles, while a GABA-B antagonist does not. On this basis, the authors conclude that the increase driven by contralateral nerve transection is due to DA signaling.

      Overall, I found the array of techniques and approaches applied in this study to be creatively and effectively employed. However, several of the conclusions made in the Discussion are too strong, given the evidence presented. For example, the authors state that "The observed potentiation was not related to inflammatory mediators associated to inury, because it was caused by a release of the inhibition made by D2 dopamine receptor present in OSN axon terminals." This statement is too strong - the authors have shown that D2 receptors are sufficient to cause an increase in LFP, but not that they are required for the potentiation evoked by nerve transection. The right experiment here would be to get rid of the D2 receptors prior to transection and show that the potentiation is now abolished. In addition, the authors have not shown any data localizing D2 receptors to OSN axon terminals.

      Similarly, the authors state, "the onset of LFP changes detected in glomeruli is determined by glutamate release from OSNs." Again, the authors have shown that blockade of AMPA/NMDA receptors decreases the LFP, and that uncaging of glutamate can evoke small negative deflections, but not that the intact signal arises from glutamate release from OSNs. The conclusions about the in vivo contribution of this contralateral pathway are also rather speculative. Acute silencing of one hemisphere would likely provide more insight into the moment-to-moment contributions of bilateral signals to those recorded in one hemisphere.

      Review 1
    3. Public_Reviews 21 Oct 2025

      Author response:

      Thank you for your time and for considering our manuscript as a Reviewed Preprint. We also would like to thank Reviewer 1 for their evaluation of our manuscript.

      Here, we present a provisional response to reviewer comments and following their suggestions we will make an effort to: i) increase evidence for the role of dopamine in olfactory glomeruli and ii) delineate the circuit involved mediating the observed potentiation. Next, we briefly describe the set of experiments that are in progress or will be performed to improve our paper.

      We will carry out immunostainings for tyrosine hydroxylase to certify that dopamine can be released on the genetically labelled glomerulus. There is a lack of good commercial antibodies for Xenopus (we already tried one and did not work, PA1-4679, Thermofisher scientific), but we will look for alternatives. In a previous set of experiments, we attempted to measure dopamine release in the glomerular layer by electroporating olfactory sensory neurons or olfactory bulb neurons with the dopamine sensors dLight1.1 (Addgene #111053) or dLight1.3 (Addgene # 111056). In our hands, fluorescence signals were extremely weak, barely undetectable. Similar results were obtained after electroporating the tectum or the rhombencephalon. We propose to repeat experiments using a more sensitive sensor such as GRAB_DA2m. Other approaches, such as performing single cell transcriptomics of olfactory sensory neurons might be considered to confirm the expression of D2 receptors.

      We agree with the reviewer that we should obtain more lines of evidence in support for a presynaptic inhibition mediated by D2 receptors.To gain insight on the bilateral circuit mediating the observed potentiation of glomerular responses we are currently investigating the role of dorsolateral pallium neurons. In Xenopus tadpoles the lateral pallium plays an analogous role to the olfactory cortex in amniotes. Preliminary observations show that neurons located in this pallial region respond to ipsilateral stimulation of the olfactory epithelium and if damaged, a contralateral potentiation of glomerular output occurs. We aim to conclude this set of experiments and include it in the paper as we believe it clarifies the circuitry involved.

      AuthorResponse
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/content/10.1101/2025.06.25.661605v1
  60. www.biorxiv.org www.biorxiv.org
    Twice as nice: Boosts in adolescent reinforcement learning from Pavlovian bias and age-related prioritization of reward-motivated incidental memory
    4
    1. Public_Reviews 21 Oct 2025

      eLife Assessment

      This valuable developmental study provides intriguing but incomplete evidence suggesting that, relative to adults, the enhancement of instrumental learning by Pavlovian bias is most pronounced in adolescence, while reward-induced memory enhancements are strongest in childhood. Although the authors tackle a key aspect of learning and motivation with rigorous experimental methods and sophisticated modeling techniques, there are substantial concerns about the absence of relevant analyses, the lack of accord between model-based and exploratory analyses, and the lack of an explanation for how the results cohere with inconsistent findings in the literature.

      Summary
    2. Public_Reviews 21 Oct 2025

      Reviewer #1 (Public review):

      In this study, the authors aim to elucidate both how Pavlovian biases affect instrumental learning from childhood to adulthood, as well as how reward outcomes during learning influence incidental memory. While prior work has investigated both of these questions, findings have been mixed. The authors aim to contribute additional evidence to clarify the nature of developmental changes in these processes. Through a well-validated affective learning task and a large age-continuous sample of participants, the authors reveal that adolescents outperform children and adults when Pavlovian biases and instrumental learning are aligned, but that learning performance does not vary by age when they are misaligned. They also show that younger participants show greater memory sensitivity for images presented alongside rewards.

      The manuscript has notable strengths. The task was carefully designed and modified with a clever, developmentally appropriate cover story, and the large sample size (N = 174) means their study was better powered than many comparable developmental learning studies. The addition of the memory measure adds a novel component to the design. The authors transparently report their somewhat confusing findings.

      The manuscript also has weaknesses, which I describe in detail below.

      It was not entirely clear to me what central question the researchers aimed to address. They note that prior studies using a very similar learning task design have reported inconsistent findings, but they do not propose a reason for why these inconsistent findings may emerge nor do they test a plausible cause of them (in contrast, for example, Raab et al. 2024 explicitly tested the idea that developmental changes in inferences about controllability may explain age-related change in Pavlovian influences on learning). While the authors test a sample of participants that is very large compared to many developmental studies of reinforcement learning, this sample is much smaller than two prior developmental studies that have used the same learning task (and which the authors cite - Betts et al., 2020; Moutoussis et al., 2018). Thus, the overall goal seems to be to add an additional ~170 subjects of data to the existing literature, which isn't problematic per se, but doesn't do much to advance our theoretical understanding of learning across development. They happen to find a pattern of results that differs from all three prior studies, and it is not clear how to interpret this.

      Along those lines, the authors extend prior work by adding a memory manipulation to the task, in which trial-unique images were presented alongside reward outcomes. It was not clear to me whether the authors see the learning and memory questions as fundamentally connected or as two separate research questions that this paradigm allows them to address. The manuscript would potentially be more impactful if the authors integrated their discussion of these two ideas more. Did they have any a priori hypotheses about how Pavlovian biases may affect the encoding of incidentally presented images? Could heightened reward sensitivity explain both changes in learning and changes in memory? It was also not clear to me why the authors hypothesized that younger participants would demonstrate the greatest effects of reward on memory, when most of the introduction seems to suggest they might hypothesize an adolescent peak in both learning and memory.

      As stated above, while the task methods seemed sound, some of the analytic decisions are potentially problematic and/or require greater justification for the results of the study to be interpretable.

      Firstly, it is problematic not to include random participant slopes in the regression models. Not accounting for individual variation in the effects of interest may inflate Type I errors. I would suggest that the authors start with the maximal model, or follow the same model selection procedure they did to select the fixed effects to include for the random effects as well.

      Secondly, the central learning finding - that adolescents demonstrate enhanced learning in Pavlovian-congruent conditions only - is interesting, but it is unclear why this is the case or how much should be made of this finding. The authors show that adolescents outperform others in the Pavlovian-congruent conditions but not the Pavlovian-incongruent conditions. However, this conclusion is made by analyzing the two conditions separately; they do not directly compare the strength of the adolescent peak across these conditions, which would be needed to draw this strong conclusion. Given that no prior study using the same learning design has found this, the authors should ensure that their evidence for it is strong before drawing firm conclusions.

      It was also not clear to me whether any of the RL models that the authors fit could potentially explain this pattern. Presumably, they need an algorithmic mechanism in which the Pavlovian bias is enhanced when it is rewarded. This seems potentially feasible to implement and could help explain the condition-specific performance boosts.

      I also have major concerns about the computational model-fitting results. While the authors seemingly follow a sound approach, the majority of the fitted lapse rates (Figure S10) are near 1. This suggests that for most participants, the best-fitting model is one in which choices are random. This may be why the authors do not observe age-related change in model parameters: for these subjects, the other parameter values are essentially meaningless since they contribute to the learned value estimate, which gets multiplied by a near-0 weight in the choice function. It is important that the authors clarify what is going on here. Is it the case that most of these subjects truly choose at random? It does seem from Figure 2A that there is extensive variability in performance. It might be helpful if the authors re-analyze their data, excluding participants who show no evidence of learning or of reward-seeking behavior. Alternatively, are there other biases that are not being accounted for (e.g., choice perseveration) that may contribute to the high lapse rates?

      Parameter recovery also looks poor, particularly for gain & loss sensitivity, the lapse rate, and the Pavlovian bias - several parameters of interest. As noted above, this may be due to the fact that many of the simulations were conducted with lapse rates sampled from the empirical distribution. It would be helpful for the authors to a.) plot separately parameter recoverability for high and low lapse rates and b.) report the recoverability correlation for each parameter separately.

      Finally, many of the analytic decisions made regarding the memory analyses were confusing and merit further justification.

      (1) First, it seems as though the authors only analyze memory data from trials where participants "could gain a reward". Does this mean only half of the memory trials were included in the analyses? What about memory as a function of whether participants made a "correct" response? Or a correct x reward interaction effect?

      (2) The RPE analysis overcomes this issue by including all trials, but the trial-wise RPEs are potentially not informative given the lapse rate issue described above.

      (3) The authors exclude correct guesses but include incorrect guesses. Is this common practice in the memory literature? It seems like this could introduce some bias into the results, especially if there are age-related changes in meta-memory.

      (4) Participants provided a continuum of confidence ratings, but the authors computed d' by discretizing memory into 'correct' or 'incorrect'. A more sensitive approach could compute memory ROC curves taking into account the full confidence data (e.g., Brady et al., 2020).

      (5) The learning and memory tradeoff idea is interesting, but it was not clear to me what variables went into that regression model.

      Review 1
    3. Public_Reviews 21 Oct 2025

      Reviewer #2 (Public review):

      The authors of this study set out to investigate whether adolescents demonstrate enhanced instrumental learning compared to children and adults, particularly when their natural instincts align with the actions required in a learning task, using the Affective Go/No-Go Task. Their aim was to explore how motivational drives, such as sensitivity to rewards versus avoiding losses, and the congruence between automatic responses to cues and deliberate actions (termed Pavlovian-congruency) influence learning across development, while also examining incidental memory enhancements tied to positive outcomes. Additionally, they sought to uncover the cognitive mechanisms underlying these age-related differences through behavioral analyses and reinforcement learning models.

      The study's major strengths lie in its rigorous methodological approach and comprehensive analysis. The use of mixed-effects logistic regression and beta-binomial regression models, with careful comparison of nested models to identify the best fit (e.g., a significant ΔBIC of 19), provides a robust framework for assessing age-related effects on learning accuracy. The task design, which separates action (pressing a key or holding back) from outcome type (earning money or avoiding a loss) across four door cues, effectively isolates these factors, allowing the authors to highlight adolescent-specific advantages in Pavlovian-congruent conditions (e.g., Go to Win and No-Go to Avoid Loss), supported by significant quadratic age interactions (p < .001). The inclusion of reaction time data and a behavioral metric of Pavlovian bias further strengthens the evidence, showing adolescents' faster responses and greater reliance on instinctual cues in congruent scenarios. The exploration of incidental memory, with a clear reward memory bias in younger participants (p < .001), adds a valuable dimension, suggesting a learning-memory trade-off that enriches the study's scope. However, weaknesses include minor inconsistencies, such as the reinforcement learning model's Pavlovian bias parameter not reflecting an adolescent enhancement despite behavioral evidence, and a weak correlation between learning and memory accuracy (r = -.17), which may indicate incomplete integration of these processes.

      The authors largely achieved their aims, with the results providing convincing support for their conclusion that Pavlovian-congruency boosts instrumental learning in adolescence. The significant quadratic age effects on overall learning accuracy (p = .001) and in congruent conditions (e.g., p = .01 for Go to Win), alongside faster reaction times in these scenarios, convincingly demonstrate an adolescent peak in performance. While the reinforcement learning model's lack of an adolescent-specific Pavlovian bias parameter introduces a slight caveat, the behavioral and statistical evidence collectively align with the hypothesis, suggesting that adolescents leverage their natural instincts more effectively when these align with task demands. The incidental memory findings, showing younger participants' enhanced recall for reward-paired images, partially support the secondary aim, though the trade-off with learning accuracy warrants further exploration.

      This work is likely to have an important impact on the field, offering valuable insights into developmental differences in learning and memory that could influence educational practices and psychological interventions tailored to adolescents. The methods, particularly the task's orthogonal design and probabilistic feedback, are useful to the community for studying motivation and cognition across ages, while the detailed regression analyses and reinforcement learning approach provide a solid foundation for future replication and extension. The data, including trial-by-trial accuracy and memory performance, are openly shareable, enhancing their utility for researchers exploring similar questions, though refining the model-parameter alignment could strengthen its broader applicability.

      Review 2
    4. Public_Reviews 21 Oct 2025

      Author response:

      We thank both reviewers for their thoughtful and constructive comments. To address this feedback, we plan to do the following:

      Questions/Hypotheses: We will clarify the study’s motivation, central questions, and our hypotheses, with a particular focus on the integration across learning and memory.

      Methods: To improve clarity and transparency, we will expand the Methods section and modify relevant figures to provide more explanation of the task, our decisions regarding data analysis approaches, and how they address our questions and hypotheses.

      Learning Behavioral Analysis: As suggested by reviewers, we will fit and compare mixed-effects models with the maximal random effects structure for the within-subject variables and their interactions. We may simplify this structure as the data justify (i.e., if we encounter convergence problems or the random effects explain minimal variance). In the revision, we will also directly compare the adolescent peaks in performance across the conditions to support our conclusion that adolescents outperform people of other ages in the Pavlovian-congruent conditions.

      Computational Modeling: We appreciate the reviewers’ close attention to the computational modeling methods, as it identified a small error in the reporting of the formulas we implemented. Specifically, the preprint’s softmax function had an error and should be printed as:

      This correct parameterization can be seen in the Huys, 2018 public repository on line 48 here. As such, rather than indicating random choices, the lapse rates with estimated solutions close to one represent expected goal-directed behavior. That said, we acknowledge that parameter recovery indicated potential identifiability issues for some parameters, especially those with extreme values. We appreciate the reviewer’s suggestion to examine “learners” separately from “non-learners,” as has been done in prior work with adults (Cavanagh et al., 2013; Guitart-Masip et al., 2012). In this revision, we will investigate whether behavioral differences in learners vs. non-learners, among other potential explanations, accounts for the relatively poor parameter recovery. We will also explain more about why we selected these RL models, including how the Pavlovian policy works and why it adequately captures participants’ behavior.

      Memory Behavioral Analysis: At the reviewers’ suggestion, we will expand our analysis of the learning-memory trade-off to fully explore this possible explanation. We will also explore the additional analyses that the reviewers suggested (e.g., ROC curves accounting for confidence ratings, analysis of correct vs. incorrect responses).

      We are confident that these revisions will strengthen the work, and we are grateful to the reviewers for their thorough, insightful feedback. In the coming revision, we will provide a detailed point-by-point response to all comments and questions.

      References

      Cavanagh, J. F., Eisenberg, I., Guitart-Masip, M., Huys, Q., & Frank, M. J. (2013). Frontal Theta Overrides Pavlovian Learning Biases. The Journal of Neuroscience, 33(19), 8541–8548. https://doi.org/10.1523/JNEUROSCI.5754-12.2013

      Guitart-Masip, M., Huys, Q. J. M., Fuentemilla, L., Dayan, P., Duzel, E., & Dolan, R. J. (2012). Go and no-go learning in reward and punishment: Interactions between affect and effect. NeuroImage, 62(1), 154–166. https://doi.org/10.1016/j.neuroimage.2012.04.024

      Huys, Q. J. M. (2018). Bayesian Approaches to Learning and Decision-Making. In Computational Psychiatry (pp. 247–271). Elsevier. https://doi.org/10.1016/B978-0-12-809825-7.00010-9

      AuthorResponse
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/content/10.1101/2025.07.11.664442v1
  61. gutenberg.org gutenberg.org
    The Grand Inquisitor
    14
    1. Emersondawes 21 Oct 2025
      hey will destroy the temples and raze them to the ground, flooding the earth with blood. But the foolish children will have to learn some day that, rebels though they be and riotous from nature, they are too weak to maintain the spirit of mutiny for any length of time. Suffused with idiotic tears, they will confess that He who created them rebellious undoubtedly did so but to mock them. They will pronounce these words in despair, and such blasphemous utterances will but add to their misery—for human nature cannot endure blasphemy, and takes her own revenge in the end.

      man is too weak to even maintain the spirit of mutiny, needs to be whipped into submission

    2. Emersondawes 21 Oct 2025
      Thou judgest of men too highly here, again, for though rebels they be, they are born slaves and nothing more

      Christ thinks too highly of men whose nature condemns them to slavery

    3. Emersondawes 21 Oct 2025
      rather than live without, he will create for himself new wonders of his own making; and he will bow to and worship the soothsayer's miracles, the old witch's sorcery, were he a rebel, a heretic, and an atheist a hundred times over.

      man will create other mysteries -find soothsayers, sorcery, heresy, atheism -- atheism here a miracle? miracle of rationality's triumph over mystery?

    4. Emersondawes 21 Oct 2025
      But Thou knewest not, it seems, that no sooner would man reject miracle than he would reject God likewise, for he seeketh less God than "a sign" from Him.

      man doesn't want God but wants signs, wants miracles, wants proof

    5. Emersondawes 21 Oct 2025
      Thy hope was, that following Thy example, man would remain true to his God, without needing any miracle to keep his faith alive

      blessed are those who have not seen, and yet have believed

    6. Emersondawes 21 Oct 2025
      There are three Powers, three unique Forces upon earth, capable of conquering for ever by charming the conscience of these weak rebels—men—for their own good; and these Forces are: Miracle, Mystery and Authority.

      man are weak 'rebels'; can only be conquered by Miracle, Mystery and Authority

    7. Emersondawes 21 Oct 2025
      Without a clear perception of his reasons for living, man will never consent to live, and will rather destroy himself than tarry on earth, though he be surrounded with bread

      man needs more than bread but will to live

    8. Emersondawes 21 Oct 2025
      man has no greater anxiety in life than to find some one to whom he can make over that gift of freedom with which the unfortunate creature is born.

      man only desires to renounce his freedom

    9. Emersondawes 21 Oct 2025
      For the chief concern of these miserable creatures is not to find and worship the idol of their own choice, but to discover that which all others will believe in, and consent to bow down to in a mass.

      men chiefly desire to submit to collective will, not follow their own desires

    11. Emersondawes 21 Oct 2025
      while the remaining millions, innumerable as the grains of sand in the seas, the weak and the loving, have to be used as material for the former?

      order of might makes right, despair of the meek forced to serve the mighty

    12. Emersondawes 21 Oct 2025
      Command that these stones be made bread—and mankind will run after Thee, obedient and grateful like a herd of cattle.

      first temptation: miracle -- turn stones into bread to seduce men to follow

    13. Emersondawes 21 Oct 2025
      Thou hast rejected the only means which could make mankind happy; fortunately at Thy departure Thou hast delivered the task to us....

      Christ rejected the means that could make man happy (ie by limiting their freedom)

    Visit annotations in context

    Annotators

    URL

    gutenberg.org/cache/epub/8578/pg8578-images.html
  62. moderndive.com moderndive.com
    Chapter 7 Sampling | Statistical Inference via Data Science
    3
    2. ygchoi.stat 21 Oct 2025
      The distribution of a list of numbers is the set of the possible values in the list and how often they occur.

      The distribution of X: is the set of the possible values that X can take, and how often they occur

    3. ygchoi.stat 21 Oct 2025
      ince we returned the observed balls to the bowl before getting another sample, we say that we performed sampling with replacement

      No, the experiment did sampling withOUT replacement, because 50 balls were drawn simultaneously.

    Visit annotations in context

    Annotators

    URL

    moderndive.com/v2/sampling.html
  63. social-media-ethics-automation.github.io social-media-ethics-automation.github.io
    8.1. Sources of Social Media Data
    1
    1. Scxrlett 21 Oct 2025
      Online advertisers can see what pages their ads are being requested on, and track users [h1] across those sites. So, if an advertiser sees their ad is being displayed on an Amazon page for shoes, then the advertiser can start showing shoe ads to that same user when they go to another website.

      This type of tracking has always been something I've been curious about. I often notice that when I search something into google, or look for specific things on TikTok/Instagram, I soon will get ads, or posts about that thing I searched recommended to me. While I know that this is the apps taking my data and pumping out content related to it in order to get me more hooked to the app, I find this type of tracking invasive and weird. I also notice that I've been getting a lot of UW related content on my social media apps recently. So this makes me think that these apps track more then your searches, but things like your location, etc. as well.

    Visit annotations in context

    Annotators

    URL

    social-media-ethics-automation.github.io/book/bsky/ch08_data_mining/01_data_sources.html
  64. www.androidcentral.com www.androidcentral.com
    MediaTek beats Qualcomm to the punch with powerful Dimensity 9500 chipset
    1
    1. SuperPauly 21 Oct 2025
      MediaTek emphasized AI performance gains in its announcement. The new NPU 990 uses Compute in Memory (CIM), which MediaTek says is an industry-first that allows low-powered AI models and applications to run continuously on-device.While MediaTek argues that the Dimensity 9500 is closer to delivering an "agentic AI," you can tangibly expect twice-as-fast token generation, on-device 4K image generation, and 50% reduced power consumption for on-device tasks. Practically, AI models like Gemini should run on-device applications much faster.

      Ai

    Visit annotations in context

    Annotators

    URL

    androidcentral.com/phones/mediatek/mediatek-dimensity-9500-is-android-powerhouse-with-major-performance-gains
  65. www.pewresearch.org www.pewresearch.org
    Writing Survey Questions
    1
    1. cyk817 21 Oct 2025
      Accurate random sampling will be wasted if the information gathered is built on a shaky foundation of ambiguous or biased questions.

      I totally agree with this sentence because for some surveys even as a responder, I feel like the question is somehow swaying me in a certain direction to an answer. For example, when surveys are coming from school, but are not anonymous, I feel guided to say something good or only given certain choices of answer to choose from when I have other things I wish to answer as. But overall I think the idea is that it's really important to focus on creating a place where everyone feels safe and comfortable to truly express themselves.

    Visit annotations in context

    Annotators

    URL

    pewresearch.org/writing-survey-questions/
  66. medium.com medium.com
    A Guide to Competitive Analysis for UX Design
    1
    1. cyk817 21 Oct 2025
      Who is currently trying to solve this problem?How are they trying to solve the problem?What their main differentiator or unique value-add is for their business and productsDid anyone try to solve it in the past and fail?Why did they fail?

      I think these questions that are listed are all highly valuable questions. The reason why I think that is because I had been put in a lot of situations where I had to solve a problem in some kind of a way and many times I look over these factors. These are the most critical base of the solution process but I think are also very easy to miss and overlook them. Especially for "did anyone try to solve it in the past and fail?", I think this is really a strong question that needs to be pondered on and requires a lot of thinking/research based off other questions like "am I copying other person's solution/method?" "Can I learn out of their failures? Can I try it on my own?" and so on.

    Visit annotations in context

    Annotators

    URL

    medium.com/design-bootcamp/a-guide-to-competitive-analysis-for-ux-design-1ddafeb9a3e7
  67. social-media-ethics-automation.github.io social-media-ethics-automation.github.io
    8.7. Data Poisoning
    1
    1. yfeng33 21 Oct 2025
      Datasets can be poisoned unintentionally. For example, many scientists posted online surveys that people can get paid to take. Getting useful results depended on a wide range of people taking them. But when one TikToker’s video about taking them went viral, the surveys got filled out with mostly one narrow demographic, preventing many of the datasets from being used as intended.

      I found the discussion of unintended versus intentional data poisoning especially striking — it reminded me of how a viral trend on a platform can distort a research survey in ways the authors likely never anticipated. One thing I’m wondering though: given that many social-media datasets are collected passively and opportunistically, how can researchers realistically detect when the data has already been poisoned by normal platform usage (rather than a malicious actor)?

    Visit annotations in context

    Annotators

    URL

    social-media-ethics-automation.github.io/book/bsky/ch08_data_mining/07_data_poisoning.html
  68. www.biorxiv.org www.biorxiv.org
    The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot
    3
    1. Public_Reviews 21 Oct 2025

      eLife Assessment

      This study provides a valuable contribution to understanding the functional and molecular organization of the medial nucleus accumbens shell in feeding. Using in vivo imaging, optogenetics, and genetic engineering, the authors present solid evidence for a rostro-caudal gradient in D1-SPN activity that refines earlier pharmacological models. The identification of Stard5 and Peg10 as molecular markers and the creation of a Stard5-Flp line represent meaningful advances for future circuit-specific studies. While stronger integration of molecular and functional results and additional analyses of other Stard5-expressing cell types (e.g., D2-SPNs, interneurons) would enhance completeness, the overall methodological rigor and convergence of findings make this a well-executed and informative study. This will be of interest to those interested in brain circuits, reward, emotion, and feeding behavior.

      Summary
    2. Public_Reviews 21 Oct 2025

      Reviewer #1 (Public review):

      Summary:

      This study examines how different parts of the brain's reward system regulate eating behavior. The authors focus on the medial shell of the nucleus accumbens, a region known to influence pleasure and motivation. They find that nerve cells in the front (rostral) portion of this region are inhibited during eating, and when artificially activated, they reduce food intake. In contrast, similar cells at the back (caudal) are excited during eating but do not suppress feeding. The team also identifies a molecular marker, Stard5, that selectively labels the rostral hotspot and enables new genetic tools to study it. These findings clarify how specific circuits in the brain control hedonic feeding, providing new entry points to understand and potentially treat conditions such as overeating and obesity.

      Strengths:

      (1) Conceptual advance: The work convincingly establishes a rostro-caudal gradient within the medNAcSh, clarifying earlier pharmacological studies with modern circuit-level and genetic approaches.

      (2) Methodological rigor: The combination of fiber photometry, optogenetics, CRISPR-Cas9 genetic engineering, histology, FISH, scRNA-seq, and novel mouse genetics adds robustness, with complementary approaches converging on the central claim.

      (3) Innovation: The generation of a Stard5-Flp line is a valuable resource that will enable precise interrogation of the rostral hotspot in future studies.

      (4) Specificity of findings: The dissociation between appetitive and aversive conditions strengthens the interpretation that the observed gradient is restricted to feeding.

      Weaknesses and points for clarification

      (1) Role of D2-SPNs: Since D1 and D2 pathways often show opposing roles in feeding, testing, or discussing D2-SPN contributions would provide an important control and context. Since the claim is that Stard5 is expressed in both D1- and D2MSNs, it seems to contradict the exclusive role of D1R MSNs in authorizing food intake.

      (2) Behavioral analyses:

      a) In Figure 2, group differences in consumption appear uneven; additional analyses (e.g., lick counts across blocks and session totals) would strengthen interpretation.

      b) The design and contribution of aversive assays to the main conclusions remain somewhat unclear and could be better justified.

      c) The scope of behavior is mainly limited to consumption; testing related domains (motivation, reward valuation, and extinction) could broaden the significance.

      (3) Molecular profiling:

      a) Stard5 expression is present in both D1- and D2-SPNs; comparisons to bulk calcium signals and quantification of percentages across rostral and caudal cells would be helpful. The authors should establish whether these cells also express SerpinB2, an established marker of LH projecting neurons.

      b) Verification of the Stard5-2A-Flp line (specificity, overlap with immunomarkers) should be documented more thoroughly.

      c) The molecular analysis is restricted to a small set of genes; broader spatial transcriptomics could uncover additional candidate markers. See also above.

      Review 1
    3. Public_Reviews 21 Oct 2025

      Reviewer #2 (Public review):

      Summary:

      Marinescu et al. combine in vivo imaging with circuit-specific optogenetic manipulation to characterize the anatomic heterogeneity of the medial nucleus accumbens shell in the control of food intake. They demonstrate that the inhibitory influence of dopamine D1 receptor-expressing neurons of the medial shell on food intake decreases along a rostro-caudal gradient, while both rostral and caudal subpopulations similarly control aversion. They then identify Stard5 and Peg10 as molecular markers of the rostral and caudal subregions, respectively. Through the development of a new mouse line expressing the flippase under the promoter of Stard5, they demonstrate that Stard5-positive neurons recapitulate the activity of D1-positive neurons of the rostral shell in response to food consumption and aversive stimuli.

      Strengths:

      This study brings important findings for the anatomical and functional characterization of the brain reward system and its implications in physiological and pathological feeding behavior. It is a well-designed study, technically sound, with clear and reliable effects. The generation of the new Stard5-Flp line will be a valuable tool for further investigations. The paper is very well written, the discussion is very interesting, addresses limitations of the findings, and proposes relevant future directions

      Weaknesses:

      At this stage, identification and characterization of the activity of Stard5-positive neurons is a bit disconnected from the rest of the paper, as this population encompasses both D1- and D2-positive neurons as well as interneurons. While they display a similar response pattern as D1-neurons, it remains to be determined whether their manipulation would result in comparable behavioral outcomes.

      Review 2
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/content/10.1101/2025.05.24.655907v4
  69. www.biorxiv.org www.biorxiv.org
    Subtle methodological variations can substantially impact correlation test performance in ecological time series
    3
    1. Public_Reviews 21 Oct 2025

      eLife Assessment

      This study presents a valuable in-depth comparison of statistical methods for the analysis of ecological time series data, and shows that different analyses can generate different conclusions, emphasizing the importance of carefully choosing methods and of reporting methodological details. The evidence supporting the claims, based on simulated data for a two-species ecosystem, is solid, although testing on more complex datasets could be of further benefit. This paper should be of broad interest to researchers in ecology.

      Summary
    2. Public_Reviews 21 Oct 2025

      Reviewer #1 (Public review):

      Summary:

      The manuscript investigates methods for the analysis of time series data, in particular ecological time series. Such data can be analyzed using a myriad of approaches, with choices being made in both the statistical test performed and the generation of artificial datasets for comparison. The simulated data is for a two-species ecosystem. The main finding is that the rates of false positives and negatives strongly depend on the choices made during analysis, and that no one methodology is an optimal choice for all contexts. A few different scenarios were analyzed, including analysis with a time lag and communities with different species ratios.

      Strengths:

      The paper sets up a clear problem to motivate the study. The writing is easy to follow, given the dense subject matter. A broad range of approaches was compared for both statistical tests and surrogate data generation. The appendix will be helpful for readers, especially those readers hoping to implement these findings into their own work. The topic of the manuscript should be of interest to many readers, and the authors have put in extra effort to make the writing as clear as possible.

      Weaknesses:<br /> The main conclusions are rather unsatisfying: "use more than one method of analysis", "be more transparent in how testing is done", and there is a "need for humility when drawing scientific conclusions". In fact, the findings are not instructions for how to analyze data, but instead highlight the extreme dependence of the interpretation of results on choices made during analysis. The conclusions reached in this study would be of interest to a specialized subset of researchers focused on the biostatistics of ecological data. Ending the article with a few specific recommendations for how to apply these conclusions to a broad range of datasets would increase the impact of the work.

      Review 1
    3. Public_Reviews 21 Oct 2025

      Reviewer #2 (Public review):

      Summary:

      This manuscript tackles an important and often neglected aspect of time-series analysis in ecology - the multitude of "small" methodological choices that can alter outcomes. The findings are solid, though they may be limited in terms of generalizability, due to the simple use case tested.

      Strengths:

      (1) Comprehensive Methodological Benchmarking:

      The study systematically evaluates 30 test variants (5 correlation statistics × 6 surrogate methods), which is commendable and provides a broad view of methodological behavior.

      (2) Important Practical Recommendations:

      The manuscript provides valuable real-world guidance, such as the superiority of tailored lags over fixed lags, the risks of using shuffling-based nulls, and the importance of selecting appropriate surrogate templates for directional tests.

      (3) Novel Insights into System Dependence:

      A key contribution is the demonstration that test results can vary dramatically with system state (e.g., initial conditions or abundance asymmetries), even when interaction parameters remain constant. This highlights a real-world issue for ecological inference.

      (4) Clarification of Surrogate Template Effects:

      The study uncovers a rarely discussed but critical issue: that the choice of which variable to surrogate in directional tests (e.g., convergent cross mapping) can drastically affect false-positive rates.

      (5) Lag Selection Analysis:

      The comparison of lag selection methods is a valuable addition, offering a clear takeaway that fixed-lag strategies can severely inflate false positives and that tailored-lag approaches are preferred.

      (6) Transparency and Reproducibility Focus:

      The authors advocate for full methodological transparency, encouraging researchers to report all analytical choices and test multiple methods.

      Weaknesses / Areas for Improvement:

      (1) Limited Model Generality:

      The study relies solely on two-species systems and two types of competitive dynamics. This limits the ecological realism and generalizability of the findings. It's unclear how well the results would transfer to more complex ecosystems or interaction types (e.g., predator-prey, mutualism, or chaotic systems).

      (2) Method Description Clarity:

      Some method descriptions are too terse, and table references are mislabeled (e.g., Table 1 vs. Table 2 confusion). This reduces reproducibility and clarity for readers unfamiliar with the specific tests.

      (3) Insufficient Discussion of Broader Applicability:

      While the pairwise test setup justifies two-species models, the authors should more explicitly address whether the observed test sensitivities (e.g., effect of system state, template choice) are expected to hold in multi-species or networked settings.

      (4) Lack of Practical Summary:

      The paper offers great insights, but currently spreads recommendations throughout the text. A dedicated section or table summarizing "Best Practices" would increase accessibility and application by practitioners.

      (5) No Real-World Validation:

      The work is based entirely on simulation. Including or referencing an empirical case study would help illustrate how these methodological choices play out in actual ecological datasets.

      Review 2
    Visit annotations in context

    Tags

    Annotators

    URL

    biorxiv.org/content/10.1101/2024.10.11.617506v1
  70. Local file Local file
    Untitled document
    3
    1. Calvinrw9 21 Oct 2025
      He said he always viewed the American dream as the aspirational middle-class life, but also as the manifestation ofthe country's foundational values of liberty, equality and justice.''I like to say that these are America's professed values. It is the task of each successive generation to make ourprofessed ideals real for everyone,''

      Mijuel Johnson: Could the American Dream be different for each generation or ethnic/racial community?

    2. Calvinrw9 21 Oct 2025
      For the first time, she questioned if the American dream was sustainable. ''Ihave always felt that if I worked hard enough, I could achieve the American dream. I was able to buy a house on myown,'' said Ms. Burke, who describes herself as fiscally conservative and socially liberal

      Malinda Burke's experience: Fiscally conservative as in modern republican? Neo-liberalist view?

    Annotators