On 2025-12-09 23:05:23, user Harrison Lee wrote:

Is Figure 2C mislabeled? Based on the lysis assay described in the methods section, it does not make sense that there should be such strong lysis (as evidenced by the dark plaques / clearing zone on the bacterial lawn) for the empty vector control.

Also, the word induction is misspelled as "inductuion" in this figure.

On 2025-12-09 21:06:51, user Etter wrote:

This paper has been accepted as scientific paper in Ticks and tick-borne diseases,16, 102569. https://doi.org/10.1016/j.ttbdis.2025.102569

On 2025-12-09 20:57:00, user Prof. T. K. Wood wrote:

Should cite the seminal work that discovered the most-prevalent defense system, toxin/antitoxins by showing Hok/Sok is related to T4 phage defense and by determining the mechanism, transcription shutoff: doi: 10.1128/jb.178.7.2044-2050.1996

On 2025-12-09 19:07:03, user Gabriel Rocklin wrote:

I think these experimental results are consistent with a model where all the domains do fold in the full length construct, but have somewhat different individual melting temperatures, so the DSC and CD results do not show a high level of cooperativity. Each domain is cooperatively folded within itself (even in the full length construct), but there is low or no cooperativity across domains. I would expect the domains are actually stably folded in the full length construct.<br /> Gabriel Rocklin

On 2025-12-09 09:57:47, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

The authors test the popular idea that humans prefer partners with dissimilar HLA genotypes in order to increase the immunological diversity of their offspring. Instead of urban populations - where it is extremely difficult to disentangle social and biological drivers of mate choice - they analyze a small, endogamous community of Himba pastoralists in Namibia. This community includes both “purely romantic” unions and marriages arranged by families (and the anthropological record on Himba marital categories is considered a well-validated and reliable source of information).<br /> This elegant design gives the authors a rare opportunity to directly compare HLA similarity between “chosen” and “arranged” partnerships within a single culture while carefully controlling for genome-wide relatedness, using a relatively large dataset (about 250 partnerships).<br /> The results show NO significant differences in HLA diversity between arranged and chosen pairs. Likewise, the authors find no advantage of chosen unions in the predicted breadth of pathogen-peptide binding repertoires. Instead, they observe very frequent sharing of long HLA haplotypes - a pattern clearly consistent with recent episodes of fluctuating positive selection, which appears to be the main driver of HLA representational patterns in the population.<br /> In a global sense, there is good reason to believe that Himba genotype data can yield rich insights into selection in human populations, helping to separate biological evolution from cultural processes.

On 2025-12-08 23:51:39, user Anna wrote:

This work has been updated, peer reviewed and published.<br /> See: https://pubmed.ncbi.nlm.nih.gov/41188644/

On 2025-12-08 15:37:15, user Damien F. Meyer wrote:

Please take into account this paper https://doi.org/10.3389/fcimb.2017.00535 showing that tr1 is coregulated with the T4SS by ErxR in Ehrlichia ruminantium

On 2025-12-08 14:56:28, user Erica Newman wrote:

I enjoyed this article. You might be interested in a related article we wrote a few years ago, which is a study about a forest under succession: https://onlinelibrary.wiley.com/doi/abs/10.1111/geb.13711

On 2025-12-08 10:21:44, user mossab1hax wrote:

wonderful and helpful

On 2025-12-07 22:47:33, user Sam Aroney wrote:

Now published: Aroney, S.T.N., Newell, R.J.P., Tyson, G.W. et al. Bin Chicken: targeted metagenomic coassembly for the efficient recovery of novel genomes. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02901-1

On 2025-12-07 17:32:03, user José Meléndez wrote:

This paper has been published at https://ami.info.umfcluj.ro/index.php/AMI/article/view/1191

MELÉNDEZ-GALLARDO, J., & PLADA-DELGADO, D. (2025). Serotonergic Modulation of Motoneuronal Excitability and Its Impact on Muscle Force Generation: A Computational Study. Applied Medical Informatics, 47(3). Retrieved from https://ami.info.umfcluj.ro/index.php/AMI/article/view/1191

On 2025-12-07 06:13:20, user Zeyuan (Johnson) Chen wrote:

Dear Biorxiv,

Please link this preprint to the final publication: <br /> https://link.springer.com/article/10.1186/s13059-025-03776-3

Thanks

On 2025-12-06 18:02:31, user zhengt wrote:

doi: https://doi.org/10.1101/2024.01.27.577582 had been published by mBio https://journals.asm.org/doi/10.1128/mbio.03172-24

On 2025-12-06 17:59:22, user zhengt wrote:

https://doi.org/10.1101/2024.02.01.578320 had been published by eLife https://elifesciences.org/articles/102681

On 2025-12-06 11:00:44, user GC wrote:

great work, thaks for sharing! Have you tried to use gapTrick for scoring your predictions? It would be very interesting to see if removing pairing and training set bias would improve the tpr.

On 2025-12-06 05:54:26, user trankos_89 wrote:

Thank you for this excellent study.

I wanted to bring to your attention what I believe is an important missing citation: PMID: 32513799. This reference appears highly relevant to your findings and closely aligns with the data presented in your work.

I hope this feedback is helpful for strengthening your study.

On 2025-12-05 14:49:26, user LaDarrius wrote:

This was a great read!

On 2025-12-05 14:17:55, user Inna Volynkina wrote:

Now, this work is published under DOI: https://doi.org/10.1134/S0006297925603740

On 2025-12-05 04:37:32, user Alan Cotter wrote:

Please download the supplementary material to obtain the ECOLPS software and the Trials.txt files for parameters of the trial simulations. You'll need R and, I recommend, Tinn-R to run the trials. Instructions for running ECOLPS are in Annex 3 and, more extensively, in the ECOLPS text file itself.

On 2025-12-04 20:04:45, user Sean Johnson wrote:

You should compare to:<br /> https://elifesciences.org/articles/91415 (ESM2 3B directly to 3Di)<br /> https://academic.oup.com/nargab/article/6/4/lqae150/7901286 (ProtT5 directly to 3Di)<br /> and<br /> https://academic.oup.com/bioinformatics/article/40/11/btae687/7901215 <br /> (longer structure embeddings claimed to be more sensitive than 3Di)

Can you combine with one of the first two approaches to produce TEA and 3Di embeddings in a single pass through a ESM2 or ProtT5?

In the first work above, I tried making hmms from 3Di, but it didn't give better results, and the search was really slow. I wonder if 3Di/TEA/Reseek embeddings are already approaching some kind of limit it terms homology search sensitivity.

I'm very interested to hear how your efforts to make TEA-hmms will turn out.

On 2025-12-04 15:57:07, user Jill Zeilstra wrote:

Do the authors have any information regarding the tRNA used in translating the arginine codons? Since the mito genome does not encode an arginine tRNA for AGR codons, wouldn't translation involve an imported tRNA?

On 2025-12-04 14:19:00, user Zhi-Ming Zheng wrote:

doi: https://doi.org/10.1101/2020.06.25.171959 had been published officially by mBio 2024 https://journals.asm.org/doi/full/10.1128/mbio.00729-24 . Thank you for your attention! Zhi-Ming Zheng

On 2025-12-04 09:03:46, user Joris de Wit wrote:

This preprint is now published in Science Advances: 10.1126/sciadv.adx5140

On 2025-12-03 09:37:45, user FS wrote:

Very Cool!

On 2025-12-03 04:29:43, user Susan wrote:

This study introduces a NanoLuc-based Sec-signal reporter to assess whether the Type IVa pilus system (T4aPS) contributes to non-pilin protein secretion in Synechocystis. The reporter itself is a valuable methodological advance, offering markedly improved sensitivity over traditional secretion assays. However, several experimental and presentation issues limit the strength and generalizability of the authors’ biological conclusions.<br /> The central claim that T4aPS components are dispensable for secretion is based entirely on a single engineered substrate, the TfAA10A–NanoLuc fusion. Because endogenous secreted proteins may use distinct Sec signal or rely on alternative export mechanisms. Many of the T4aPS mutants display regulatory and envelope abnormalities, yet the study does not quantify NanoLuc expression across strains. Consequently, differences in luminescence may reflect altered expression rather than true differences in export efficiency. Normalization of secretion output to OD750 complicates interpretation. The authors note that aggregation affects OD measurements, and aggregation varies considerably among the mutants. <br /> Despite RbcL being present in supernatants, this cannot rule out subtle lysis, selective leakage, or extracellular degradation of NanoLuc, leaving open the possibility that luminescence does not strictly represent secreted protein. The subcellular fractionation experiments are promising but lack purity markers, loading controls, and quantitative analysis, making mechanistic conclusions uncertain. The statement that the PilQ secretin is unnecessary for secretion is weakened by the absence of functional validation demonstrating loss of PilQ activity in the ΔpilQ strain. Similarly, the proposed mechanism for enhanced secretion in ΔpilA1 remains speculative without supporting measurements of Sec-pathway components or alternative Sec substrates.<br /> Presentation issues also reduce clarity. Several figures lack color and contrast, limiting interpretability, and some figure descriptions have methodological information. Typographical inconsistencies and minimal statistical reporting, combined with reliance on a single 24-hour endpoint, further detract from the manuscript’s rigor. Overall, the NanoLuc reporter represents a promising tool for cyanobacterial secretion studies, but the biological interpretations require additional controls, expanded substrate testing, more robust normalization, and clearer data presentation. The study supports only the conclusion that this Sec-signal NanoLuc reporter does not depend on the T4aPS under the tested conditions, it does not justify broader claims about cyanobacterial non-pilin secretion pathways.

On 2025-12-03 03:45:39, user Sandro Santillan wrote:

Your study is important because it explores a classic question in evolutionary biology: whether humans share certain acoustic preferences with other animals. You also use a new comparative approach by testing sounds from many species, which makes the work original and valuable.<br /> An introduction should be added to generally speak about the topic of bioacoustics, and the reasoning behind the similarities in acoustic preference.<br /> Regarding the methodology, the design is appropriate to establish the correlation , however a main limitation is that the sounds used for the study don't reflect the natural context of the source. Digitally editing them and isolating them from their natural environment, could make the subject’s preferences biased. Also, because they came from different sources, it is difficult to ensure the uniformity of the quality and volume, which could also add a bias towards the preferences. Finally, the study doesn't control for a possible familiarity with the sounds in the participants, which could also add to the bias of the results. This should be added in your discussion.<br /> Concerning the results and their interpretation, there is a risk of overestimating the conclusion about the shared acoustic preferences between humans and non-human animals. This is because the percentage of agreement between the two was 56.4%. Even though this was statistically significant, it's still a very limited effect size. Moreover, the mechanisms of decision between humans and non-human animals when choosing a more “beautiful” sound should be supported by the fact that both groups prefer a certain acoustic feature. However, the results show the contrary, proving that specific acoustic features have no effect in sharing the same auditory taste. Finally, the group of sounds from species used in the study is small and not very diverse), which could undermine the generalization that humans share acoustic preferences with animals. <br /> The overall idea of the study is very interesting and it's not that well researched, showing great potential. Also, the main points made were communicated effectively in a way that is understandable. As a final suggestion, a short summary of the methodology employed could be added to the abstract.

On 2025-12-03 01:12:35, user Marcelo Salas wrote:

The manuscript addresses relevant protein targets associated with Parkinson’s disease and explores a set of phytocannabinoids with potential therapeutic implications. This integrative approach, combining docking, ADMET prediction, and molecular dynamics, is conceptually valuable and could provide meaningful preliminary insights. However, several methodological aspects require clarification or refinement to ensure that the conclusions presented are scientifically robust and reproducible.

From a methodological perspective, the docking section would benefit from substantial improvement. The study does not report a redocking of the co-crystallized ligand nor provide RMSD values, making it impossible to determine whether the docking protocol can accurately reproduce known binding poses. Furthermore, several essential parameters—such as exhaustiveness, number of runs or modes, pose-selection criteria, and software version are not specified, limiting reproducibility. Although the grid box dimensions are reported, their rationale is not explained, particularly for α-synuclein, an intrinsically disordered protein that lacks a stable binding pocket. Using a rigid docking protocol for such a target requires additional justification or alternative strategies.

The ADMET analysis also presents inconsistencies. Several LD₅₀ values appear implausible, suggesting potential issues with molecular input files or prediction settings. Moreover, some interpretations, such as characterizing compounds as “non-toxic if ingested", are too strong for in silico predictions, which should be framed as preliminary and subject to experimental validation.

The molecular dynamics section exhibits additional methodological ambiguities. The simulation box is reported with units incompatible with atomistic MD, and essential parameters such as ionic concentration, thermostat and barostat conditions, NVT/NPT equilibration steps, and time-step are not described. Only a single trajectory is presented without replicates, and the structural analyses are limited to basic RMSD and RMSF plots, without energetic evaluations such as MM-GBSA. These omissions hinder assessment of the stability and reliability of the proposed protein–ligand complexes.

Finally, several presentation issues affect clarity. Some tables lack units or clear column descriptions, and the selection criteria for the four compounds included in the interaction tables are not explained, despite docking fifteen molecules.

In summary, the manuscript addresses an interesting question and uses relevant targets, but significant methodological clarification and refinement are necessary before the results can support the conclusions drawn.

On 2025-12-02 23:22:28, user Jimena Patricia Giraldo Flores wrote:

We are undergraduate students from the Biology program at the Universidad Peruana de Ciencias Aplicadas (UPC). As part of our academic training, we are analyzing recent preprints and publications to strengthen our critical understanding of genomics. In this context, we would like to share our observations.

We recognize the important advances achieved in your zebrafish genome study, particularly the closure of gaps and the integration of third-generation sequencing technologies. Nevertheless, we believe certain methodological aspects require further consideration.

First, the figures presented in the preprint aren’t of the highest quality, making it difficult to see the graphics and plot names. Since figures are a central element in communicating scientific results, the image resolution is crucial to fully appreciate the data and conclusions.

Second, the exclusive reliance on Verkko as the assembler reduces reproducibility and methodological robustness. While Verkko is powerful, particularly for Telomere-to-Telomere projects, benchmarking against widely adopted assemblers such as Flye or Canu, or even Wengan is essential. Without such comparisons, it is difficult to determine whether the reported improvements in contiguity and gap closure are genuine biological advances or artifacts of the chosen software. We suggest doing further analysis and comparison of assemblers in order to have a more robust pipeline.

Third, we note the absence of detailed controls and verifications that would strengthen confidence in the assembly. These include: (1) confirmation of the absence of paternal contribution through comparative genotyping of TU mothers, AB sperm, and doubled-haploid adults; (2) verification of ploidy and mosaicism by karyotyping (3) cell culture controls such as reporting passage number, mycoplasma testing, and fibroblast karyotyping to ensure genomic stability.

The pangenome analysis, while mentioned, is not fully aligned with the study’s main objective of generating a gap-free reference. Broader and more systematic characterization of genetic diversity would be required before extending conclusions to the whole pangenome.

In conclusion, we recognize the importance of your work and its contribution to zebrafish genomics. Incorporating benchmarking, and systematic controls would further enhance the reproducibility, credibility, and long-term impact of this valuable resource.

On 2025-12-02 20:25:03, user MB wrote:

Fascinating findings and lovely work- congratulations to all the authors! One point of concern- as of 02 December none of the data/material sharing links provided (e.g. NCBI or Github) are available or return any information.

On 2025-12-02 14:42:29, user Deepak Modi wrote:

The manuscript is published and available at https://www.nature.com/articles/s41420-025-02799-w

On 2025-12-02 10:54:18, user Babür Erdem wrote:

This article was published in a peer-reviewed journal. Citation:<br /> Babur Erdem, Ayben Ince, Sedat Sevin, Okan Can Arslan, Ayse Gul Gozen, Tugrul Giray, Hande Alemdar,<br /> Api-TRACE: A system for honey bee tracking in a constrained environment to study bee learning process and the effect of lithium on learning,<br /> Computers and Electronics in Agriculture,<br /> Volume 241,<br /> 2026,<br /> 111236,<br /> ISSN 0168-1699,<br /> https://doi.org/10.1016/j.compag.2025.111236. <br /> ( https://www.sciencedirect.com/science/article/pii/S0168169925013420)

On 2025-12-02 02:52:36, user Anthony Gerber wrote:

This well done new work was in part anticipated by work from the Stallcup lab published in 2017 in 2017, which should be cited in the final publication.

On 2025-12-01 15:42:06, user Sherif wrote:

Great job

On 2025-12-01 13:50:34, user Abdelrahman Osman wrote:

congratulations Omar on publishing your impressive paper, you truly did a great work.

On 2025-12-01 02:54:02, user hibiscustea wrote:

Hi, thank you for sharing this preprint, it’s really bold work, and I enjoyed reading it. A couple of things you might consider for the next version: the Introduction would really benefit from explicit hypotheses, just so readers know what the expected contrasts were between phenology and morphology. Some of the modeling assumptions (equal evolutionary variances, missing environmental forcing) could use a clearer justification too. And the transition to the empirical motifs comes a bit abruptly, the Doñana system is very seasonal, so V+ motifs might appear for several reasons besides coevolution.<br /> But overall, really interesting work. Looking forward to seeing where it goes next. I'm a PhD student and we are reviewing a preprint paper for a class, I chose yours, thank you for your work.

On 2025-11-30 12:31:56, user David Greening wrote:

Please note this article has now been published in full: https://www.nature.com/articles/s41556-025-01795-7

Rai, A., Huynh, K., Cross, J. et al. Multi-omics identify hallmark protein and lipid features of small extracellular vesicles circulating in human plasma. Nat Cell Biol (2025). https://doi.org/10.1038/s41556-025-01795-7

On 2025-11-30 07:11:24, user Misha Koksharov wrote:

I presume the final version of this paper was published in 2024: <br /> Vedalankar, P., Tripathy, B.C. Light dependent protochlorophyllide oxidoreductase: a succinct look. Physiol Mol Biol Plants 30, 719–731 (2024). https://doi.org/10.1007/s12298-024-01454-5

On 2025-11-29 18:12:35, user Agata Leszczuk wrote:

The paper is currently published in Plant Science: https://doi.org/10.1016/j.plantsci.2025.112906

On 2025-11-28 21:08:51, user Andre Rendeiro wrote:

The manuscript from Pyne et al. develop a computational framework<br /> to predict potential trajectories of bone mineral density for<br /> particular individuals using generative adversarial networks (GANs).<br /> The manuscript is well written (despite being quite technical for<br /> an aging-specific audience) and the method is interesting, but the<br /> need for the application of GANs to this problem is not fully justified.<br /> In addition, the evaluation of the model's performance is as rigorous<br /> as it could be,<br /> and it is not clear whether the model is truly capable of generalizing<br /> to unseen timepoints of specific individuals or is simply learning to<br /> interpolate/extrapolate at the population level.

Major comments

1. It is known that several aging phenotypes are shared across a population<br /> with fairly moderate reproducibility/variability - which is what enables<br /> the establishment of population-level aging clocks which are mostly linear<br /> models. Therefore a baseline to compare to could be a linear regression model<br /> which accounts for individual-specific differences such as a linear mixed model that<br /> is trained on the same covariates as input, but seeing only a fraction of the timepoints<br /> and simply inter- or extrapolates to a held out timepoint. Another benchmark to beat<br /> could be a gaussian process regression model, which is well suited to modeling temporal<br /> data and supports irregular timelines and missing data. These models would be important<br /> baselines to assess the generative model's ability to capture individual-level trends<br /> rather than simply population-level trends.

2. The evaluation of the generated timepoints for various individuals is not rigorous<br /> enough. The simple quantification of a score with an arbitrary threshold is too<br /> lenient as it does not capture individual-specific trends,<br /> but can report inflate performance simply by capturing population-level trends.<br /> A more quantitative assessment of the model's ability to capture individual-level<br /> trends is needed.<br /> This could be done by evaluating the mean square error, mean absolute error,<br /> Pearson correlation and R^2 between predicted and true<br /> values at the held-out timepoint, as well as evaluating<br /> the ability of the model to rank individuals according to their predicted<br /> phenotype values at the held-out timepoint. Another approach could be to<br /> perform a clustering analysis of the predicted vs true values to see if<br /> the model can capture subgroups of individuals with similar aging trajectories.

3. I am not sure the model is truly capable of generalizing across time because it<br /> always sees timepoints 2 and 4 as inputs and predicts timepoints 5 and 8 as targets.<br /> So it may not necessarily ever learn to generalize to an unseen time index as it<br /> could simply learns the mapping of 2,4 to 5,8. What is being evaluated is therefore<br /> only a test of whether the model can inter- and extra-polate across individuals for<br /> these fixed visit times. In addition, the conditioning timepoints are assymetric<br /> (2 and 4 are both early). Related to my previous point, if the cohort shows<br /> predictable average decline between t4 to t5 and t5 to t8, then a simple<br /> baseline (like a linear mixed model or gaussian process) should capture this well.<br /> It would be interesting to see how the model performs when trained and evaluated<br /> on different timepoints. The hold out timepoint (7) does provide some evidence<br /> but is not sufficient to demonstrate generalization across time as the performance<br /> of predicting that one timepoint could be easily interpolated from the others<br /> at the population level and not at the individual level.

Minor comments

1. Some abbreviations need to be defined at first use (e.g. SIR).

2. The methods section could more explicitly describe that the timepoint 7 is<br /> held-out during training and only used for evaluation.

3. The specification of the various 'strata' is really not clear.

On 2025-11-28 12:37:29, user Jörg Klug wrote:

This preprint was published in 2023 already.<br /> DOI: 10.15252/embr.202357064<br /> Is this information not updated automatically?

On 2025-11-27 20:45:13, user Mucahit wrote:

Preprint Review of the Article Titled

‘’Immune Profiling of the Axilla with Fine Needle Aspiration is Feasible to Risk-Stratify Breast Cancer’’

doi: https://doi.org/10.1101/2025.10.22.683956

The research conducted by Naidoo et al shows that immune profiling of axillary lymph nodes (ALN) samples taken by fine needle aspiration (FNA) would be an efficient method to predict breast cancer (BC) prognosis. As FNA is a less invasive method for obtaining samples from patients, the article's findings would provide new insights for researchers and clinicians. Another important result of the article is that the immune cell profile of a single reactive ALN appears to reflect the patient's entire immune status in the axilla.

The article has explained that FNA itself has sufficient leukocytes for comprehensive cell immunophenotyping of reactive ALN.

The research question was well explained, and the results were presented clearly. The results of the study have given significant and novel information about the concept.

All conclusions are well-supported by the results. Results obtained from different directions have backed each other up. Results might be supported more effectively by using control groups more in experiments. Yields of the animal study might be stronger if it were applied to animals with breast cancer.

The quality of writing is fine. It seems to be accessible to both experts and semi-experts. Figures in the text were well presented, and legends provided enough information.

The publication appears to attract a lot of interest from clinicians and researchers in different areas.

The authors’ contributions were fairly explained. It was a remarkable point to know that samples were de-identified in the study before being released to researchers to ensure blinded data analysis.<br /> Increasing the number of patients participating in the study would lead to an improvement in the statistical significance of the results.

Using only the results of the article is not sufficient to make a generalized conclusion about BC diagnosis. Results need to be confirmed by further studies to change the current approach to BC diagnosis.

On 2025-11-27 20:34:42, user Paola Murgas PhD wrote:

This is an interesting manuscript showing the non-inflammatory function of STING, confirming our previously published data ( https://doi.org/10.1186/s40659-025-00624-3) .

We found that STING deficiency results in increased body weight, independent of alterations in locomotor activity or food consumption.

Moreover, STING-null mice exhibited markedly elevated circulating triglyceride and total cholesterol levels. Furthermore, histological and morphological analysis demonstrated augmented fat accumulation in adipose and hepatic tissues, despite the lack of nutritional or genetic metabolic stress.

These findings indicated a crucial function for STING in the control of lipid homeostasis across the lifespan ( https://doi.org/10.1186/s40659-025-00624-3) .

Although we did not test in other species, it is important to note that STING is an evolutionarily conserved regulator of lipid metabolism beyond its well-known inflammatory role.

On 2025-11-27 15:35:01, user Manuel Mendoza wrote:

Peer-reviewed version available in JCB https://doi.org/10.1083/jcb.202502014

On 2025-11-27 06:01:48, user Merlyn wrote:

Romiumeter: An Open-Source Inertial Measurement Unit-Based Goniometer for Range of Motion Measurements<br /> Basinepalli Kothireddy Gari Diwakarreddy, S Abishek, Amal Andrews, Lenny Vasanthan, View ORCID ProfileSivakumar Balasubramanian<br /> doi: https://doi.org/10.1101/2024.05.29.596353

Brilliant article !is it published or still under peer review.

On 2025-11-26 05:26:36, user Prof. T. K. Wood wrote:

Please cite the seminal paper that initiated research on the impact of bacteria-derived indole on human physiology: http://www.pnas.org/cgi/doi/10.1073/pnas.0906112107 <br /> This manuscript was the first to find indole tightens epithelial cell junctions.

On 2025-11-26 05:03:47, user Oded Beja wrote:

Our preprint is now published in Nature https://www.nature.com/articles/s41586-025-09656-x

On 2025-11-26 02:46:52, user Tania Perroux wrote:

This article is now published in Journal of Zoology<br /> https://doi.org/10.1111/jzo.13017

On 2025-11-26 02:44:40, user Tania Perroux wrote:

Now published in Royal Society Open Science https://doi.org/10.1098/rsos.250379

On 2025-11-25 23:52:27, user Huigang Shi wrote:

Please note: The author name “Wuchun Ling” appears incorrectly in the preprint metadata and PDF.<br /> The correct name is “Chunling Wu,” as shown in the published journal version.

On 2025-11-25 21:14:55, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/ ) really enjoyed this paper.

Here are our highlights:

Including nutrient availability shifts the focus of antibiotic control from "more drug vs less drug" to how the population's vulnerability state can be altered as a mechanism driving extinction.

The reinforcement learning (RL) agent discovers strategies that humans would be unlikely to design, such as giving nutrients before antibiotics and pausing drug application until cells return to a susceptible state, illustrating how machine learning-guided therapy can find hidden leverage points.

It's unlikely that clinicians will have access to "full-state" information like subpopulation composition or proteome sector fractions. By restricting the agent's observations to the population growth rate, the authors demonstrate that RL-based population control is feasible even with severely limited observability.

Rigorously testing the generalizability of the RL method shows that it can discover principles of susceptibility that are broadly applicable. Uncovering such principles enables RL to propose treatment strategies that leverage fundamental cellular physiology, rather than simply fitting a training scenario.

On 2025-11-25 15:00:15, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

This work evaluates the potential for oral microbiome sequencing to predict esophageal squamous cell carcinoma. The authors transparently evaluate the potential for their model to generalize to external, held-out datasets.

We like how the formulation of the method is clearly articulated, beginning with simpler descriptive statistics and culminating in the final model.

The authors compute and visualize SHAP values, revealing that some of the top predictive features are microbes already putatively associated with disease incidence. While the biological properties of these features are described in detail, the authors are also careful to emphasize that causality has not been robustly assessed (in this work, or more broadly).

We like how the authors emphasize that the oral microbiome is relatively stable over time compared to other body sites. We are excited by the possibility that, in principle, this stability could support individual longitudinal surveillance efforts that could lead to the discovery of predictive signatures with greater generalizability (accounting for individual baseline variability).

On 2025-11-25 11:41:10, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper. Here are our highlights:

This study provides a clear and thoughtful evaluation of whether modern deep generative models can meaningfully improve ancestral sequence reconstruction (ASR). The authors explore a compelling idea: that variational autoencoders (VAE), trained on homologous protein families, might capture epistatic interactions that classical site-independent evolutionary models omit.<br /> A key highlight is the demonstration that VAE latent spaces do recover meaningful phylogenetic structure. The authors show that relationships among sequences are encoded coherently in the latent representation, suggesting that deep models can learn informative global organization from sequence data - an encouraging insight for future machine-learning approaches to molecular evolution.Another important contribution is the comparison across simulated evolutionary scenarios, with and without epistasis. Across all cases, classical maximum-likelihood ASR methods outperform the VAE-based approach.<br /> Finally, the study identifies the decoder as a key bottleneck, offering a constructive direction forward for the field. Even when the latent space contains strong phylogenetic signal, reconstructing accurate ancestral sequences remains challenging. The authors highlight a concrete opportunity for model development and for integrating phylogenetic constraints more explicitly into deep generative architectures.

On 2025-11-25 09:07:03, user Layue wrote:

Unbelievable，do immune cells also display “associative learning” like brain?

On 2025-11-25 08:53:39, user Kris wrote:

The topic of the manuscript is conceptually intriguing.....

On 2025-11-24 17:41:36, user Andrew Castonguay wrote:

This is very nice work! Looks like the image files were maybe compressed prior to submission; would the authors kindly re-upload with high DPI?

On 2025-11-24 13:12:26, user Stefano Busti wrote:

Nice follow-up of the 2019 paper. One thing it's unclear to me: for NIRFPs, how did you provide biliverdin ? Were the proteins expressed in a bioengineered strain to slef-produce chromophore?

On 2025-11-24 08:18:05, user Mikhail Kutuzov wrote:

Dear authors,

it was a great interest to read the article «Nucleosome unwrapping and PARP1 allostery drive affinities for chromatin and DNA breaks» devoted to study of PARP1 interaction with DNA and nucleosome providing at a single molecule level. It’s really exciting to see “the molecular face”. You made a very intriguing experiment with the partially NCP unwrapping and received a hopeful result on it. One more interesting feature is relative to PARP1 trapping mode in the presence of different inhibitors that is a direct demonstration of protein holds-on on DNA.<br /> However, after discussion your paper on a lab seminar I have got several questions that probably arise due to I am not a specialist in optical tweezer and confocal microscopy fields. I hope that you could clarify it for me.<br /> 1. I couldn’t find in the text how the dwell and gap times were converted to k(off) and k(on app). Is it just the reciprocal value of the projection of the inflection point of the sigmoid approximation onto the time axis? Additionally, is it correct the kon app = k(on)/C(PARP1)? How did you estimate the DNA concentration under single molecule conditions? I also could not find the PARP1 concentration used in the experiments. Is that 0.1 nM?<br /> 2. The time resolution of microscope used in the work is 1/10s. One of the basic assumptions for result interpretation was the absence of association/dissociation acts of the DNA-protein complexes during this time period. As far as spontaneous collisions are limited by diffusion and can happen 10^9 times/s, how do you estimate the probability of reassociation of dissociated complexes during the dwell periods? To exclude the reassociation did you try to transfer the trapped DNA with bounded PARP1 molecules to the channel without PARP1 (with buffer) with keeping the flow? In my opinion it could allow to avoid PARP1 reassociation events from the calculation.<br /> 3. In the text you do not discuss potential dimerization of PARP1 and PARP2 under DNA/nucleosome bounding. Although, it seems to me that it is important for Kd calculations.<br /> 4. According to your data, the binding manner of PARP1 with nick-sites is different in frames of one DNA molecule. Part of tracks demonstrate a long dwell and gap periods; another part is characterized short dwell and gap periods. Did you take it into account in any way at the constant calculations or results interpretation?<br /> Moreover, on the kymograph of PARP2 binding there are only two nick sites from seven were found in association, and due to long dwell periods, it led to low Kd calculated value. Could you somehow comment your interpretation of the obtained result and the feasibility of using calculation method?<br /> 5. I didn't find in the text and references what kind of plasmids did you use for the transient overexpression of the fluorescent-tagged proteins.<br /> I will be very grateful for clarification these questions for me.

Thanks in advance,<br /> Mikhail

On 2025-11-23 04:39:09, user Ainsley wrote:

In Figure 3, the inconsistency between the usage of triangles to represent pulses or constancy between A/B and C/D is harmful to the efficacy of the figure’s data presentation. Picking one shape for pulses and one for constancy would be better. Additionally, the colors chosen for pulse 2 and pulse 3 in C/D are too close together in color and make the figure more confusing to read. Otherwise, the figures are very well made and effectively present the dense information from this complex research.

On 2025-11-22 23:05:01, user SF wrote:

Overall, I thought that this manuscript provided an interesting look into the diet of the Reunion Island free-tailed bat and its implications. However, compared to the rest of the text, I thought that the Discussion section could benefit from more integration with the overarching ideas addressed towards the beginning of the Introduction. Tying the conclusion back to the big picture (i.e. potential applications of understanding bat diets on pest management, agriculture, and disease vector control in modified landscapes) could help re-establish the importance of this study beyond Reunion Island and create cross-disciplinary connections with other fields such as agricultural science, economics, and public health. It may also be helpful to reiterate a few points from the first paragraph of the Introduction (lines 44-56) to emphasize the importance of understanding ecological dynamics in highly-modified landscapes that are often major sites of human settlement/ interest.

On 2025-11-22 18:00:08, user Michael wrote:

Extremely cool work, well done!

On 2025-11-22 11:27:20, user Néstor de la Visitación wrote:

This preprint has been published in Circulation research. DOI: https://doi.org/10.1161/CIRCRESAHA.124.324068

On 2025-11-22 02:22:59, user Sandy Emery wrote:

The blanket descriptor of rhizobacterial inoculated plants gets used in earlier sections while in later situations you specify the specific rhizobacteria. This got confusing because at one point it seemed like all three were in one group because of the generalized statement; however, it is just grouping the three treatments together. I think you should think about changing your phrasing from the general statement to “the three rhizobacterial inoculated plants” for ease of understanding. As I read further, it was easily understood, but in the beginning when its not as clear of all the aspects of the experiment specifying its for all three groups would have be nice.

On 2025-11-22 01:36:22, user Birdie wrote:

L77-81: “As forests grow in age and complexity, they are able to sustain stable microclimates that are on average cooler than in deforested areas during the day and in the summer, and warmer at night and in winter, as a result of changes in the vertical and horizontal structure of forest canopies and understories. These cooler microclimates buffer many species from extreme temperatures and can facilitate local persistence” [italics added]). This is one of many instances in the manuscript where I am left unsure whether it is the coolness per se of the plots for which microclimates are valuable habitats or whether it is because of their bufferedness/stability. In the first sentence bufferedness seems to be the important quality, but in the latter sentence coolness seems to be. This lack of clarity regarding bufferedness versus coolness recurs throughout the manuscript. Early in the introduction, the manuscript should clearly outline the relationship among microclimates, coolness, and bufferedness and their relative uses in the text.

On 2025-11-21 20:26:09, user Anita Salamon wrote:

Thank you for sharing this exciting work. In addition to empagliflozin, have you tested any other SGLT2 inhibitors for binding to PANK1? I’m particularly interested in bexagliflozin.

On 2025-11-21 18:49:01, user Max Seldes wrote:

To the authors, I very much enjoyed reading this manuscript! I found the introduction and discussion sections to be particularly well structured and were very logical in their progression. I wanted to know if you have any way of retrieving or calculating the specific locations of calls or relative density of calls along your transects? I think this project could really grow from investigating the correlation of call frequency/density with canopy cover as an explanatory variable in something like a GLMM or ANOVA. If you were able to do this, I think it would be really cool to create some additional layers like percent road coverage within a 1km buffer or percent surface water to test some of the suggested explanations for the shift in overall abundances. You could even quantify stuff like distance to forest patch or something like that to really hone in on patch effects. I think this project has a really great direction and could really easily be expanded upon! Best of luck to the authors on your future endeavors and I hope to see more from you!

On 2025-11-21 18:43:34, user AzC919 wrote:

A key issue that substantially limits the strength of this manuscript is the decision to pool three bee guts into a single microbiome sample for each microcolony. While pooling can reduce sequencing costs and simplify workflow, it also eliminates all variation at the individual level. This variation is essential for understanding how thermal stres and pathogen infection can impact hosts differently. Individual bees vary in microbiome composiiton, immune status, body size, and infection intensity, and these variations are biologically meaningful. When you average individuals inot a singular pooled sample, it blurs whether observed microbial shifts reflect consistent responses across bees or the cominance of a single/few outlier(s). This loss of clarity can affect nearly every analysis presented in the manuscript, including alpha and beta diversity estimates, infection quantification, and the interpretation of taxa associated with particular treatments. <br /> Even though the manuscript briefly acknowledges this limitation, they frame it mainly as a reduction in sequencing resolution rather than a core biological constraint. The manuscript would benefit from a clearer justification for pooling, whether it was due to logistics, cost, survivorship, or colony level focus. Also a more explicit discussion of how pooling influences the interpretation of microbiome patterns would greatly clarify this inconsistency. Overall, addressing this issue directly in the manuscript would improve the transparency in the study’s results, and strengthen the conclusions.

On 2025-11-21 17:10:10, user Liz Cramer wrote:

Hi authors! I really enjoyed this paper! The topic is very relevant and important to be researching. I also thought you did and excellent job of setting up the novelty of the study and justification of why you chose to study these factors. However, when I was reading your methods I may have found something you might want to look into. I will say I am not an expert in statistical analyses, but based on my knowledge, these are my suggestions. First, you assigned distance to forest patch as a fixed effect, but I think this effect would be more accurately described as random. Since there is a range of possibilities for distance to forest patch I believe this should be a random effect because there are not a fixed number of possibilities for this variable. Unless you predetermined and intentionally chose certain distances to forest patches. Additionally, I think orchard ID should be a fixed effect, not random. Since orchard ID was predetermined and there is a fixed number of possibilities for this variable, I think it should be treated as a fixed effect rather than random.

On 2025-11-21 16:57:05, user Troy Kervin wrote:

Hi all, overall an excellent manuscript. There are a few things I would like to mention.

We have already resolved the question you pose: "But we are unsure which came first: is it the proteins that bring these ordered lipids with them, or do the lipids form domains into which the proteins partition?" Indeed, we built a theoretical framework where one of the central theories is that lipids do not form stable subregions that subsequently recruit proteins ( https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-024-01849-6 ). The answer lies with lipid fingerprints ( https://pubs.acs.org/doi/10.1021/acscentsci.8b00143) .

Suppose lipid-lipid interactions were strong enough to form platforms large enough to accommodate proteins (the evidence for this is very poor, by the way). It wouldn't matter. The idea that the proteins and lipids are collectively present in the final structure suggests that the proteins have preferential interactions with the lipids, so there would have to be a very good reason why the lipids would "ignore" the proteins such that they cluster and then recruit the proteins in a sequential manner. If this is insufficient to cover all cases (for example, if the proteins are not initially present in the membrane when the lipids supposedly cluster), there are many other reasons why this cannot occur. For example, if the lipid platforms are ordered, one would expect there to be a free energy barrier for protein entry. I could go on and on, but there is really no need. It is a thermodynamically absurd notion.

This sequential mechanism was popularized by the original lipid raft theory. Since it was false, lipid rafts underwent many ad hoc modifications and should now be regarded as pseudoscience ( https://www.researchgate.net/publication/397646378_Lessons_from_pseudoscience_in_biology ). I should also mention that the phase separation narrative (which I debunk here: https://doi.org/10.5281/zenodo.17201253 ), and Kusumi et al.'s picket fence/tiered mesoscale domain model are also wrong. I think you will understand why after reading lipid fingerprints ( https://pubs.acs.org/doi/10.1021/acscentsci.8b00143) and the proteolipid code ( https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-024-01849-6 ).

Since I am challenging so many of their beloved theories, the lipid raft people, who still run the place, do not want you to know that the proteolipid code exists. I hope that this excuses my somewhat aggressive promotion ( https://proteolipid.org ).

Best of luck with this.<br /> Troy

On 2025-11-21 14:42:48, user ARB wrote:

I am writing this comment as an assignment for a graduate-level class.

I thoroughly enjoyed the overall conceptualization of this manuscript, and I believe it effectively addresses the current gap in eco-evolutionary studies. I also appreciated the manuscript's approach to connecting empirical studies with the theoretical model to evaluate eco-evolutionary dynamics in real communities. However, I think the manuscript can benefit from a writing review. For instance:<br /> Line 243: The whole paragraph from Line 243 to Line 247 is an exact copy of the previous paragraph.<br /> Line 261: The usage of linear regression analysis to examine the relationship between warming rate and different stabilities is mentioned several times in different paragraphs. It is also the case for the next paragraph from Line 268 to Line 274.

On 2025-11-21 08:40:17, user Catherine Etchebest wrote:

This paper is now published in J. Chem. Inf. Model. 2025, 65, 20, 11454–11472

On 2025-11-21 01:22:49, user Aline Machado wrote:

This study explores how Pheidole bergi colonies are distributed across habitats and spatial scales in the Monte desert, and how natural and anthropogenic environmental variation affects colony density and spatial structure. Long-term data reveal strong preference for protected algarrobal habitat; major density declines through drought years; density-dependent shifts from aggregation to more dispersed patterns; consistent microhabitat selection toward inter-patch borders and open patches.<br /> This is a promising and well-executed spatial ecology study, but several issues must be addressed for clarity and robustness. The largest concerns involve justification of biological assumptions, narrative organization, overinterpretation of environmental drivers, and insufficient integration of the anthropogenic component.

MAJOR ISSUES<br /> 1. The assumption that each nest corresponds to a separate colony must be justified<br /> This is the main flaw of this study. The analyses assume that each nest entrance represents an independent colony, but this assumption is never justified. Many Pheidole species are polydomous, meaning that multiple nests may belong to the same colony. If P. bergi is polydomous, nest counts may not correspond to colony counts, spatial clustering may reflect intra-colony nest structure rather than interactions among colonies, observed “repulsion” could represent spacing among satellite nests, and density declines may reflect contraction of colony structure rather than colony mortality. This has direct implications for all spatial analyses. Given that the authors note that little is known about the natural history of P. bergi, this issue needs to be addressed explicitly. The manuscript should clarify whether P. bergi is known to be monodomous or polydomous, how this was assessed in the field, and what implications this uncertainty may have for interpreting spatial patterns.

1. The manuscript does not explicitly link its predictions to its results and discussion<br /> The Introduction presents several detailed, scale-specific predictions regarding habitat-level differences in aggregation, drought-induced density-dependent thinning, mosaic-driven microhabitat selection, predicted shifts in inter-colony interactions, and responses to anthropogenic disturbance. However, these predictions are not revisited consistently in the Results or Discussion. In several sections it is unclear which prediction a given result addresses, or whether a result supports or contradicts the authors' expectations. Reorganizing the Results and Discussion using a clear prediction–finding–interpretation structure would substantially improve narrative clarity and help readers understand how each analysis addresses the study’s questions.

2. Anthropogenic variation is stated as a major objective but receives insufficient analysis <br /> The Introduction frames the study as examining abundance, habitat associations, and spatial arrangement across both natural and anthropogenic sources of environmental variation. Yet the anthropogenic component receives very limited treatment. The “grazed algarrobal” appears only in a single 2021 sampling, with no information provided about the intensity or history of grazing, and anthropogenic predictions are not explicitly stated. In the Discussion, the potential effects of grazing and dirt-road disturbance are mentioned only briefly, without deeper engagement or clear linkage back to the stated objectives. Clarifying the expected ecological effects of grazing and dirt roads, showing how those expectations were tested, and revisiting these comparisons explicitly in the discussion would bring the manuscript into better alignment with its claims.

3. A spatial overview map is essential but missing<br /> An important limitation is the absence of a spatial overview map. Because spatial scale and spatial context are central to the study, a map showing the locations of all dirt-road transects, he positions of dirt-road transects (D, F, D1, D2, F1, T, L, P1, P2, M), and the two permanent grids (J, V), habitat boundaries such as algarrobal, sand dunes, and grazed lands, and approximate distances among sites is essential for interpreting habitat comparisons and understanding how environmental heterogeneity relates to the observed patterns. Without such a map, it is difficult for readers to evaluate the spatial independence of sampling areas or the relevance of local heterogeneity. Including a map would greatly improve the clarity of the manuscript.

4. Environmental drivers underlying heterogeneous intensity patterns are inferred but not measured<br /> Along the dirt-road transects, for example, environmental attributes such as soil texture, moisture, or vegetation structure are invoked to explain variation in colony distribution, but these variables were not measured. Thus the interpretations rely on assumptions rather than data. The manuscript would benefit from acknowledging more explicitly that interpretations of road-scale heterogeneity are speculative unless environmental covariates are incorporated into the analyses.

5. Gibbs point-process model interpretation requires additional clarification<br /> These models are a strength of the manuscript, but their biological meaning is not always clear. The significance of positive versus negative interaction parameters may not be obvious to readers unfamiliar with point-process modeling. In addition, the first-order and second-order terms operate at similar spatial scales, leading to partial confounding that complicates interpretation. Although this confounding is acknowledged late in the Discussion, it would be more helpful to flag it earlier, so that readers can interpret the model results with appropriate caution. Providing more biological explanation of what the model components represent would enhance accessibility.

6. The long-term population decline is compelling but causality is overstated <br /> The manuscript describes a greater than fifty percent decline in colony density between 2001 and 2019, and an additional approximately forty percent decline between 2019 and 2025. These changes are attributed largely to drought. While this is plausible, causal claims are currently too strong given the absence of direct soil moisture data, prey availability measurements, reproductive output data, or queen survival data. Phrasing should be adjusted to reflect that the observed pattern is consistent with drought effects rather than demonstrating causality, and alternative explanations such as detectability changes, nest dormancy, or colony relocation should be acknowledged.

MINOR ISSUES<br /> 1. The introduction overextends and lacks a clear conceptual framework<br /> The introduction reviews many ecological processes (competition, habitat heterogeneity, disturbance, droughts) but does not clearly articulate which mechanisms the authors expected to dominate at each scale (macro vs micro), or how these mechanisms generate distinct predictions.<br /> Explicitly state what processes are expected to drive spatial patterns at macro scale (abiotic heterogeneity vs density-dependent thinning) vs micro scale (territoriality, vegetation mosaic), and indicate which predictions are tied to drought, habitat type, or population density.

1. The macro-scale interpretation equates heterogeneous intensity with ecological responses, but the ecological drivers remain untested<br /> Along dirt roads, the intensity of colonies is strongly heterogeneous in algarrobal but not in grazed or dune habitats. However, the manuscript interprets these heterogeneities as linked to soil or vegetation structure, but these environmental variables were not quantified. The interpretation of “inverse density-dependent thinning” from 2019–2025 is plausible but speculative without a formal test.<br /> Acknowledge explicitly that without measured habitat covariates along the roads, the environmental interpretation is inferential. Clarify limitations of attributing density changes to specific drivers.

2. Visual presentation of spatial results needs improvement<br /> Several figures (especially 2, 3, and 4) are extremely dense. Overlapping confidence envelopes make interpretation difficult. Lack of legends for symbols or shading in some subpanels. Figure 5 has too many components on a single page.<br /> Simplify or divide composite figures. Ensure that interpretation of Ripley’s L and pair-correlation graphs is clearly explained in captions. Highlight key distances at which patterns deviate from CSR.

WRITING QUALITY<br /> The manuscript is written in generally clear and grammatically correct English, and the overall academic tone is appropriate. However, the prose is often excessively dense, with very long paragraphs and sentences that embed multiple ideas at once. The abstract is longer than necessary and would benefit from reduction. Parts of the Introduction are dense and could be streamlined. Important predictions, results, and conceptual transitions are sometimes buried within complex constructions, which makes the narrative harder to follow. Key terms and modeling approaches would benefit from brief explanatory context. In addition, the Discussion section is unusually long and occasionally repetitive, with several arguments stated multiple times across different paragraphs, while others are presented with more certainty than the data justify. This dilutes the impact of the key findings and makes it harder for readers to follow the logical flow of the authors’ interpretations. Overall, the manuscript would benefit from substantial stylistic polishing aimed at improving clarity, structure, and readability for organization and flow. Reference formatting should be checked for consistency.

CONCLUSION<br /> In conclusion, the manuscript is based on a strong dataset with considerable potential. Addressing the issues outlined above, especially the need for clear hypothesis integration, fuller treatment of anthropogenic variation, inclusion of a spatial map, justification of assumptions about colony structure, and more cautious interpretation of environmental drivers, will substantially strengthen the scientific clarity and impact of the work.

On 2025-11-20 22:10:54, user ML wrote:

Hi Finand & Kotze,

I really enjoyed reading this paper! I liked how this manuscript was framed. However, I have a few comments/criticisms:

I think there is an opportunity to discuss the metapopulation model here. Dispersal is highlighted heavily in this manuscript, but the metapopulation model isn't mentioned at all.

Perhaps more a personal preference, but I would like you to define want a "specialist" is. This term is NOT adequately defined in the introduction. "Specialist” refers to a lot of things. Are we studying diet specialists, habitat specialists, or something else? I assume we are studying habitat specialists, but that’s based in context clues.

The use of PCA and PERMANOVA is appropriate, however, the "vegan" package in R makes certain assumptions that you may NOT want. I would highly recommend using the PRIMER-E software to double check your analyses.

The axes aren't grounded, also! They should start at zero. that being said, I enjoyed the color selection here.

Overall, I thought this was a great manuscript, with a really robust dataset.

ML

On 2025-11-20 20:55:07, user SB wrote:

Peer reviewed and published October 24, 2025 in Vaccine<br /> https://www.sciencedirect.com/science/article/pii/S0264410X25010813 <br /> https://doi.org/10.1016/j.vaccine.2025.127784

On 2025-11-20 19:31:12, user Rodrigo Santibanez wrote:

Please find the accepted paper here https://www.cell.com/cell-systems/fulltext/S2405-4712(25)00284-4

On 2025-11-20 18:54:11, user Vanja Klepac-Ceraj wrote:

This work was published in January 2025: https://www.nature.com/articles/s41467-025-56072-w

On 2025-11-20 15:34:33, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper. Here are our highlights:

This work demonstrates that metagenomes contains a vast layer of “not yet genome-resolved” biodiversity. According to the results, up to ~80% of putative species-level clusters are not represented by genomes of cultivated organisms or by MAGs.

The study quantitatively shows that species discovery is far from saturation and strongly habitat-dependent. Human gut samples and anthropogenic environments are already densely sampled and contribute few new lineages per additional metagenome, whereas soils, aquatic ecosystems, the rhizosphere, and non-mammalian hosts remain true hotspots of unexplored diversity.

A separate and fundamentally important result - confirmed numerically- is the observation that the structure of prokaryotic diversity follows the same universal statistical laws (the power-law Willis-Yule / Yule-Simon distributions) as that of eukaryotes. In other words, the authors demonstrate that the same simple macroevolutionary regularities operate across the entire Tree of Life.

On 2025-11-20 03:10:28, user osedaxMucofloris wrote:

This is a really interesting study, and I'm happy to see Darlingtonia featured so prominently as it gets less attention than many other carnivorous plant taxa. that being said, I believe that the framing of this paper around mutualism is not accurate to the biology of the system involved. A true mutualistic interaction is one in which both partners benefit from the interaction. While there may be some cheating involved, the basis of the relationship must be mutually beneficial to both organisms involved. In the case of pitcher plants and insects, there can only be a single benefactor to any interaction. If the plant benefits from consuming an insect, the insect does not benefit. If the insect benefits from consuming pitcher extrafloral nectar, then that insect must not fall into the plant's trap and thus the plant does not benefit. There cannot be a true mutualism here. For the same reason, the sentiment of a "reciprocal nutrient exchange between carnivorous plants and local insect populations" (line 235) is misleading, as the insects which obtain nutrients from the carnivorous plants in question are, by necessity, not the same insects which provide nutrients to the carnivorous plants.

The most appropriate framing device for this paper in my opinion would be to simply focus on whether any insects are able to obtain a significant portion of their nutritional requirements from carnivorous plants, which would make Darlingtonia not a strict predator; instead, it would occupy a less straightforward place in the trophic web of the serpentine fen. The manuscript does mention this concept several times, but never as the driving concept or overall thrust of the paper. I think reframing the paper, including the title, around questioning whether carnivorous plants are always strict predators of insects would improve the manuscript. To further the potential novelty of this paper, reframing could focus on the fact that it is already known that specialist insects benefit from interactions with pitcher plants (often in an actually mutually beneficial manner, sensu detritivorous pitcher plant inquilines) but far less is known about whether any generalist insects may benefit from interactions with the plants.

Darlingtonia's focal status in this study is more or less self-explanatory, but the use of Vespula specifically is far less so. At no point in the introduction are yellowjackets set up to be a good candidate for the study at hand, nor do the methods explain why Vespula was chosen. It is my belief that the use of Vespula wasps is a strength of this study's design, and the manuscript should make that clear. There are several reasons why Vespula is an ideal choice here. For example, it is stated that wasps rarely fall prey to pitchers despite visiting them regularly, thus they are good candidate insects for an investigation of nitrogen isotopes which originate from pitcher nectar. Studies which investigate compounds that are found in higher concentrations at higher trophic levels (i.e., are biomagnified) might benefit from first looking at the highest trophic levels; if no signature is detected at the greatest point of biomagnification, then it is likely that lower trophic levels will likewise show no difference in bioaccumulated material. Vespula wasps occupy a high trophic level in this ecosystem, making them a good candidate for this study in this aspect as well. Yellowjackets are also easy to selectively capture in great numbers due to the availability of specialized traps, meaning there are cheap, effective, passive methods for sampling a large number of them. This paper does address that these wasps forage in localized patches, and thus can be more reliably assigned to either "fen" or "forest" patches, but this is brought up in passing. Any number of these points can and should be addressed, as it stands there is no explicit justification given for using these wasps as opposed to any other group of insects.

On 2025-11-19 21:19:50, user Daniel Vásquez-Restrepo wrote:

This preprint already received a “major revision” decision. Unfortunately, the original reviewers were not available to evaluate it again, and the process stalled. Despite sending 15 additional peer-review invitations, no one agreed to take it on. Although the manuscript has now entered a new review process, I am attaching the previous reviewers’ comments.

Reviewer 1

This isn’t a finding as not only is it already available information, the use of the available IUCN maps and statuses was part of the methodology.

R/ We rephrased the sentence to clarify that it refers to the underlying data itself and not to our results.

I like the approach they’ve taken, but none of this is novel information or unexpected.

R/ Although it is well known that mountains promote diversity and endemism at a global macroevolutionary scale, this information has not been explicitly tested in Colombian squamates in conjunction with threat categories. We consider that clearly stating the result of hotspots of diversity and endemism in Colombian squamates can help local environmental policies. Therefore, while our results are consistent with theoretical expectations, this alignment does not diminish the novelty of our findings, as we provide the first quantitative analysis supporting these patterns in the local context.

This is the main novel finding of the work and I’d recommend reorganising the text to stress this.

R/ We modified several sections of the text to emphasize the finding highlighted by the reviewer, also in accordance with comments made by the other reviewer.

Unclear what this means in the context of this paper.<br /> R/ We rephrased the section for clarity.

This is just the existing EDGE list, so I’m not sure it warrants mentioning as an output here.

R/ In accordance with a comment from Reviewer 2, we acknowledge that this is a local rather than a global list, and that species rankings may differ between the two. Therefore, we believe it is an output worth highlighting. Nevertheless, we have clarified in the text the differences between the local and global scores and their implications.

This entire paragraph seems superfluous, and this work has nothing to do with the latitudinal gradient so it’s a strange thing to focus discussion on.

R/ While we briefly mention the latitudinal gradient, the main purpose of this introductory paragraph is to provide general context on biodiversity, leading into the key argument of the subsequent sections: the need to understand biodiversity and extinction risk as multidimensional phenomena. We have made minor adjustments to better integrate the role of the latitudinal gradient in promoting tropical diversity, thereby reinforcing the importance of prioritizing conservation efforts in regions of exceptionally high biodiversity.

Suggested added context as this was unclear as worded.

R/ We accepted the reviewer’s suggestion and revised the text accordingly.

I’m not sure this follows - more that, as the paragraph goes onto say, it results in a lack of understanding of the impacts and vulnerability of the species.

R/ We rephrased the idea to make it clearer.

This seems to be an inappropriate reference, as Paez et al. 2006 focused on turtles rather than squamates. Please check and reword as needed.

R/ We double-checked the reference and confirmed that it is correct, as it covers not only turtles but all Colombian reptiles (including squamates, crocodiles, and turtles).

This seems inconsistent with the earlier statement that “a local assessment is lacking” - should this rather say a recent local assessment? Though as the paper goes on to reference a 2015 ‘local assessment’, it’s unclear what this section means.

R/ We agree with the reviewer and revised the text to clarify that we refer to a recent assessment that also considers different facets of biodiversity, not just species richness (i.e., taxonomic diversity).

The figure given later is 597, and that was used as the basis for the analysis. This may be a discrepancy due to a later update, but the same Reptile Database update should be cited throughout the paper for consistency.<br /> R/ In the Introduction, we refer to the most recent estimate of 620 reptile species for Colombia, based on the latest update of the Reptile Database (2024). However, the analyses in this study were based on the 2023 version of the database, which listed 597 species at that time. Given that the analyses were conducted using the 2023 data, and a complete reanalysis would be required to incorporate the updated figures, we chose to retain the original dataset to ensure consistency and reproducibility. We have clarified this point in the text to avoid confusion.

Better to use the term ‘squamates’ rather than ‘reptiles’ if crocs and turtles are to be excluded.

R/ Done, we have consistently replaced "reptiles" with "squamates" throughout the text where appropriate.

Once again, this could benefit from clarity. The data in the Reptile Database should be reviewed with reference to available material and literature to be used as a formal checklist, but it should be ‘complete’ - it’s more likely to erroneously list species from a country than to miss ones that actually occur there.

R/ We agree with the reviewer and rephrased the sentence to make the idea clearer.

Are the authors able to explain the discrepancy between this figure and the maps (which represented 81% of the dataset)? Most IUCN assessments will have maps, but no IUCN maps will be associated with species that don’t have assessments.

R/ The figures were validated against the information provided in Table S1. As the reviewer correctly points out, there are more assessments than polygons, consistent with the supplementary material. The figure of 77% corresponds to 461 species (excluding DD and NE categories) out of 597 species in our dataset (461/597 = 0.77). Meanwhile, the figure of 81% refers to 481 species with available geographic information, including species categorized as DD (481/597 = 0.81). The discrepancy arises because DD species were included when considering geographic data but excluded from threat category analyses. We have revised the Methods and Results sections to clarify this distinction explicitly. Also, we updated the previous 77% figure to include DD species too, increasing it to 92%.

This is not a sufficient way to evaluate whether the assessments are likely to need updating - the Criteria take account of the distribution and extent of threats to each species, not simply its distribution. The ‘needs update’ tag is applied by the Red List only to assessments more than 10 years old, which is all that should be mentioned here.

R/ We understand the reviewer’s concern and acknowledge that a mismatch between EOO and threat classification is not sufficient by itself to determine if an update is needed. We have separated these ideas in the text: first, we highlight species whose assessments are formally tagged as “needs update” after 10 years; second, we discuss species whose EOO does not align with their current threat classification. We moved the second point to the 3.2 Geographic patterns section, and expanded the Discussion to better explain these observations.

See above. The authors didn’t ‘show’ this, they interpreted the Criteria incorrectly.

R/ See previous answer. We further expanded the Discussion section to better frame this point.

I would consider it suitable for the manuscript to be more fully revised as a shorter paper, as the region-scale analysis within Colombia and the phylogenetic results are of more interest than the well-trodden path of identifying the Andes as an area of greater endemism than Amazonia and the additional analyses included in the paper render its main findings somewhat opaque in places.

R/ We consider that highlighting the Andes as an area of high endemism is necessary to provide context for interpreting the patterns of phylogenetic diversity. While it may be a well-known topic, not all readers will have the same background. Although the manuscript is extensive because it covers taxonomic, geographic, and phylogenetic patterns, its current length (ca. 6,300 words, excluding references) is well within the 9,000-word limit for Original Research articles in Biodiversity and Conservation and only slightly above the typical 5,000-word range. Nevertheless, we made an effort to shorten unnecessary sections to improve focus and clarity. For example, we removed some analysis related to diversification rates and extinction risk, since as the Reviewer 2 pointed out, some metrics depending on branch lengths may be biased.<br /> <br /> Reviewer 2

L393-405: it is important to acknowledge the phylogenetic incompleteness of a national-level analysis, and how that might be affecting these results – divergence times are influenced by phylogenetic coverage and structure, removing >90% of squamate species from the phylogeny will give you divergence times between Colombian species, not true lineage age/divergence time information. This could be addressed with sensitivity analyses to explore how lineage age varies between pruned and complete trees, or with stronger discussion of the pitfalls of this approach in the methods and discussion, with clearer wording in the results.

R/ We appreciate the reviewer’s insightful comment and fully agree. We performed additional calculations to assess sensitivity, and indeed, the age of some lineages can be severely affected, while others remain largely unchanged. Following the reviewer’s recommendation, we revised the Methods and Discussion sections to place greater emphasis on the limitations of using evolutionary metrics derived from pruned trees and on the considerations needed when interpreting these results. As the reviewer also notes, these results are not necessarily incorrect, since global conservation priorities do not always align with local ones. Additionally, we introduced local and global subscripts to our metrics to explicitly distinguish between them.

407-418: Distinction is needed between EDGE scores and national EDGE scores (literally just saying ‘national EDGE scores’ would suffice). It may also be useful to identify national-specific priorities – i.e. high ranking national EDGE species that are not highly ranked in global context. There are EDGE scores available for all vertebrates at the global level here ( https://www.nature.com/articles/s41467-024-45119-z) . There are endemic Colombian squamates that are high EDGE in this study and also high EDGE at the global scale (e.g. Lepidoblepharis miyatai) but also species that are high EDGE nationally because of the phylogenetic diversity they are solely responsible for in Colombia, but the responsibility for which is shared beyond Colombia’s borders. These key cases can be instrumental in ensuring species that are globally ‘safe’ but locally important do not fall through the cracks.

R/ Please refer to the previous response. We now explicitly distinguish between national EDGE scores and global EDGE scores throughout the text and highlight cases where species are locally important but not necessarily globally prioritized.

L41 and throughout: “threatenedness” = “extinction risk” or “level of threat”.

R/ Done.

Throughout: It’s the IUCN Red List, not IUCN, particularly when referring to versions of the Red List database.

R/ Done.

L145: make it clear you’re referring to national endemics.

R/ The Resolución 0126/2024 from Colombia’s Ministry of Environment (MADS) covers not only national endemics but all species occurring within the country’s administrative boundaries.

L167: ensure it’s clear that its imputation based on taxonomy alone.

R/ Done.

L182: check references.

R/ We reviewed the references cited at this point and confirm they are correct.

L222-224 and throughout: phylogenetic diversity == Faith’s PD – the other measures are indices of phylogenetic distance/relatedness that are calculated in same units as PD, but are not phylogenetic diversity – that should be clarified.

R/ Done. We clarified that Faith’s PD refers specifically to phylogenetic diversity, while the other metrics represent measures of phylogenetic relatedness or distance.

L393: extinction risk should not be though of as a trait evolving but as the manifestation of extrinsic and intrinsic factors.

R/ Agreed. We rewrote the sentence.<br /> L393-397: unclear what the relationships discussed are, and what they infer.

R/ We have removed this section from both the Methods and Results. Given that the correlations discussed involved metrics dependent on branch length — and, as the reviewer previously pointed out, branch lengths can be affected by pruning the phylogenetic trees — we decided to eliminate this section. Overall, it did not substantially contribute to the text or to the discussion.

L428-429: This is higher than, or at least comparable to, the global % of DD/NE squamates I think, so might not be considered relatively low for squamates.

R/ We rewrote the sentence to clarify that it is comparable to or higher than the global percentage, as the reviewer correctly pointed out.

L429-432: it might be worth highlighting how taxonomists and others can contribute to rapid reassessment of species with basic information in ecological publications see: https://doi.org/10.1016/j.biocon.2018.01.022

R/ Done. We incorporated the reviewer’s suggestion.

L442-444: Unclear what is meant here? A species can be assessed as CR with a wide range if its under population decline criteria, and a small-ranged species can be assessed as not-threatened if there is no evidence of decline/ongoing degradation.

R/ This comment was also raised by Reviewer 1. We addressed it accordingly by revising the text to clarify that species can indeed have wide distributions and still qualify as Critically Endangered if facing significant threats, and vice versa. Please refer to our responses to Reviewer 1.

On 2025-11-18 22:59:11, user Marco Wu wrote:

Well written article!

On 2025-11-18 16:20:18, user Jan Graffelman wrote:

This article is now published in Molecular Ecology Resources:

Graffelman, J. (2026) A Logratio Approach to the Analysis of Autosomal Genotype Frequencies Across Multiple Samples. Molecular Ecology Resources 26(1) e70072. <br /> doi: https://doi.org/10.1111/1755-0998.70072

On 2025-11-18 02:18:11, user paula_mj wrote:

Authors might want to consider citing the following recent paper PMID: 39612916; PMCID: PMC11896817 as it is highly relevant to their findings.

On 2025-11-17 16:00:24, user Logan Suits wrote:

I'm so glad to be able to share this story with the world!

On 2025-11-17 07:38:21, user Jadwiga Śliwka wrote:

I read this preprint with great interest. We also found Rpi-vnt1.1 in a CIP line, in our case it was a line derived from S. phureja and S. stenotomum. We called the gene Rpi-phu1 https://link.springer.com/article/10.1007/s00122-006-0336-9 but later revealed that it was identical to Rpi-vnt1.1 (Foster et al. 2009). Could you say anything more about your line C1848?

On 2025-11-16 23:03:46, user Patricia Hunter wrote:

Single cell transcriptomics is a useful experimental approach for this work but are there is a missed opportunity to make progress in understanding and treating preeclampsia because neutrophils are absent from the analysis. Neutrophils are the most abundant immune cells in the body, outnumbering all other immune cells combined, so any analysis of tissue needs to identify them or explain why they are absent. It has already been demonstrated using single cell transcriptomics that neutrophils are not functioning properly in preeclampsia:<br /> Xiao S, Ding Y, Yu L, Deng Y, Zhou Y, Peng M, Lai W, Nie Y, Zhang W. Maternal-Fetal Interface Cell Dysfunction in Patients With Preeclampsia Revealed via Single-Cell RNA Sequencing. Am J Reprod Immunol. 2025 Sep;94(3):e70101. doi: 10.1111/aji.70101. PMID: 40924867.<br /> In pregnancy, the neutrophil fraction increases to 70% of all white blood cells (two neutrophils for every one other type). They are involved in all activities of the uterus including the build-up of the endometrium, spiral artery formation, the break down and expulsion of the endometrium, placental vascularization, cervical remodelling to enable the passage of the newborn, the expulsion of the placenta, the coagulation and diversion of the uterine arteries and the remodelling of the uterus back to its pre-pregnancy size and shape. I would go as far as to say that from an evolutionary point of view, the whole reason that primates have and make so many neutrophils is to support reproduction.<br /> The main issues with this work follow:<br /> 1. PBMC should not be used as a control for immune cells in single cell transcriptomics of tissue as mononuclear cells do not represent the full identity or functionality of immune cells.<br /> 2. In figure 1f, it should be possible to identify all of the clusters on the UMAP more precisely. For example, there are 2 clusters of “myeloid cells”. What are they? I don’t believe that they are both monocytes/macrophages. Monocytes and macrophages differ by only a small number of transcripts. The most widely accepted distinguishing surface protein is CD68. Why is this not used?<br /> 3. Why is the UMAP for a preeclampsia sample not shown?<br /> 4. CD16 should not be used to identify NK cells or CD16+ monocytes without additional markers. All neutrophils express CD16.<br /> 5. Neutrophils, monocytes and macrophages are phagocytic and phagocytosis is key to their function. If a maternal phagocyte phagocytoses a fetal cell, the phagocyte will then contain both genotypes. Could this explain some of the observations in Figure 1?

I hope that a more enlightened version of this manuscript – one that considers rolls of immune cells in placental development and function more broadly – will be published. Research in women’s health is stagnating and needs to discard some of its current paradigms to enable discovery and progress.

On 2025-11-16 07:07:24, user Lucian Parvulescu wrote:

A paper that may be of interest to you: http://doi.org/10.7717/peerj.18229

On 2025-11-16 01:19:07, user Robert Marvin wrote:

I was glad to have a chance to help test the Reproducibility Packet, even if only in a modest way compared to the other contributors. What impressed me most was Dr. Stumpf’s innovative use of knowledge graphs to organize such a vast amount of mitochondrial data. The way he connected palindromic motifs into a scalable framework really shows how graph-based approaches can reveal patterns that might otherwise remain hidden. It’s exciting to see this kind of structural thinking applied to genetics, and I’m grateful to have had even a small part in supporting the effort.

On 2025-11-15 03:01:19, user Brian Swann wrote:

You need to get this work evaluated by the Crick, for example. If they say it is credible, it will go somewhere. It needs an institution with bioinformatics folk and statisticians to look at this. I just wonder where this is all going - do we end up proving that unless we are identical twins we are all different. We know that already by looking in our faces. What difference does it make to human disease in the long term, if anything. There is crosstalk between the nuclear and mitochondrial genomes. How is that organised.

On 2025-11-14 16:06:36, user Wesley Johnston wrote:

Full disclosure: I am one of three people who have reacted to Dr. Stumpf's empirical analysis and his conclusions for the past 3 years. We have advised him, and we have significantly challenged him. He has diligently sought every possible way in which he might be wrong - he is his own most significant challenger. No one would be more pleased to see a solid data-driven disproof of any of his conclusions than he would.

The fundamental difference in his bottom-up, data-driven no-hypothesis exploration of mitochondrial DNA versus prior analyses (such as in population genetics and genetic genealogy) is that those have been primarily based on point comparisons of mutations and indels. His consideration is based on the biology of the 3D structure of the mtDNA, specifically in how the palindromes that make up so much of the mtDNA shape that structure and thus the function of the mtDNA. All point mutations are not the same: for example, a point mutation in a palindrome can have either a non-viable result or else result in a mitochondrial DNA disease.

He has sought and believes he has provided an objective reproducible method to explore mitochondrial DNA without preconceptions. If his method is valid, this alone is a major contribution, independent of what he has found about mtDNA.

What the data has revealed and the conclusions he has made from the data very definitely challenge major beliefs about mtDNA. In genetic genealogy discussions I have seen, the reaction is defense of the status quo, with no real examination of the data discoveries underlying Dr. Stumpf's conclusions. This is not surprising but also not of any real help in verifying or refuting his conclusions. I hope that serious examination of his methods and data and analytical results and whether or not they support his conclusions will be presented here.

On 2025-11-13 17:50:18, user Coker wrote:

Nice to see your paper published at last. I look forward to reading the final version.

On 2025-11-15 05:00:10, user Borkronzilla wrote:

Cool paper!

On 2025-11-14 19:47:05, user Elmira wrote:

This is a very interesting study, thank you for sharing your findings! I noticed that the manuscript mentions that Alpha-1-acid glycoprotein is being identified for the first time in stool samples from IBD patients. I just wanted to point out that, according to the following studies published in Feb 2024, this protein has actually been previously reported in this context:

https://www.mdpi.com/2227-9059/12/2/333 <br /> This doesn’t diminish the value of your work, but I thought it might be helpful for clarification and for readers who are tracking prior discoveries.

On 2025-11-14 14:59:21, user M.J. Naughton wrote:

This paper is now published in Scientific Reports:<br /> https://doi.org/10.1038/s41598-025-23364-6

On 2025-11-14 09:31:57, user Frederik Stein wrote:

I recommend providing a more detailed description of the field design, ideally supported by a map showing the sampling sites and the spatial arrangement of treatment and control areas. This would greatly help readers understand how the sites were selected and how spatial structure may influence the results.

From the current description, it appears possible that treatment plots are located inside outbreak areas while control plots are situated outside of them. If this is the case, the design may risk pseudoreplication, as outbreak and non-outbreak areas can systematically differ in environmental conditions independent of the treatment. Clarifying this aspect, and discussing how such spatial structure was accounted for in the analysis, would strengthen the robustness of the study.

For reference, see also the discussion of pseudoreplication issues in:<br /> https://www.sciencedirect.com/science/article/pii/S0378112725006772

On 2025-11-14 08:48:27, user 鄭凱陽 wrote:

Many thanks for your help. That's also a great work. I am now trying to integrate your results into this study.

On 2025-10-19 13:28:31, user Graeme Nicol wrote:

This looks like an interesting and valuable study. There are a couple of additional recent AOA virus publications that might be relevent for your analyses ( 10.1038/s41396-022-01341-5; 10.1093/ismejo/wrae205):9vwgVhwzm4g0ZJPkZ57D2ZprShg "http://doi.org/10.1093/ismejo/wrae205)") . Also just wanted to mention it is ammonia-oxidizing archaea.

On 2025-11-14 02:24:01, user Ken Field wrote:

I wonder if you can comment on how SCINKD would work on an organism with an XO sex-determination system?

On 2025-11-14 01:02:43, user Kavli Neuroscience wrote:

Readers should be aware that an increasing number of recent studies have successfully employed tartrazine for both in vivo and ex vivo tissue clearing and imaging:

https://opg.optica.org/optica/fulltext.cfm?uri=optica-12-1-24&id=566618

https://opg.optica.org/ol/fulltext.cfm?uri=ol-50-7-2282&id=569527

https://opg.optica.org/boe/fulltext.cfm?uri=boe-16-6-2504&id=572320

https://onlinelibrary.wiley.com/doi/full/10.1002/jbio.202500297

https://www.worldscientific.com/doi/10.1142/S1793545825400024

https://www.biorxiv.org/content/10.1101/2024.10.28.620537v1

https://opg.optica.org/prj/fulltext.cfm?uri=prj-13-10-2757

https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-29/issue-12/120501/Optical-clearing-with-tartrazine-enables-deep-transscleral-imaging-with-optical/10.1117/1.JBO.29.12.120501.full

https://pubs.acs.org/doi/10.1021/acssensors.5c02046

The upcoming Photonics West '26 meeting has many talks and posters demonstrating using tartrazine for in vivo clearing:

https://spie.org/photonics-west/presentation/Advancements-in-OCT-structural-and-functional-imaging-for-in-Utero/13850-9

https://spie.org/photonics-west/presentation/Assessing-tartrazine-mediated-optical-clearing-for-enhanced-macroscopic-fluorescence-lifetime/13841-17

https://spie.org/photonics-west/presentation/Tartrazine-based-optical-clearing-to-enable-deep-imaging-of-murine/13850-15

https://spie.org/photonics-west/presentation/Enhancement-of-NMB-PDT-against-anaerobic-bacteria-by-a-skin/13829-16

https://spie.org/photonics-west/presentation/Permeation-enhanced-biocompatible-tissue-clearing-for-improving-OCT-imaging-depth/13837-55

https://spie.org/photonics-west/presentation/Comparative-study-of-optical-clearing-agents-and-mechanical-compression-effects/13850-34

https://spie.org/photonics-west/presentation/Investigating-optical-transparency-in-real-biological-samples-by-engineering-the/13852-25

https://spie.org/photonics-west/presentation/Optical-clearing-with-absorbing-dyes-enables-non-invasive-OCT-characterization/13837-54

https://spie.org/photonics-west/presentation/Refractive-Index-Modulated-Spectral-Near-Infrared-Diffuse-Optical-Breast-Imaging/13850-42

On 2025-11-13 21:20:40, user gabe wrote:

A shortsighted proposal has been made by some to "manage" barred owls by murdering them. This presents a major issue for spotted owls too, as one cannot make a quick differentiation between the two species. Many spotted owls would be shot by mistake.

I wonder if the authors of this study are familiar with this issue. I also wonder about the timber company employees who contributed to this study - did their contribution have anything to do with their employers' plan to kill barred owls?

On 2025-11-13 18:28:02, user SolveSaint wrote:

Thank you for your research. I am using it in my biolectrics model that explains a stress-cortisol-glutamate-ROS axis that is passed transgenerationally through methylation patterns. It explains most disease as ROS driven, cancer as an ROS avoidance survival program locked in through methylation, and excitatory methylation patterns that are passed transgenerationally, predisposing offspring to heightened excitatory load and disease. This excitatory state is also called autism. https://solvesaint.github.io/Biolectrics-Wiki/

On 2025-11-13 03:25:39, user HJ w wrote:

This is a very beautiful work, but the authors have released it prematurely, which will inadvertently help their competitors copy the discovery.

On 2025-11-12 17:13:41, user Leslie Sanderson wrote:

The links for "View current version of this article" and "Now published in Microbial Biotechnology...." are incorrect and instead link to a different article by the same authors. This article has been published in Microbiology ( https://doi.org/10.1099/mic.0.000997 )

On 2025-11-12 16:33:28, user Paul Macklin wrote:

Where are the methods, the mathematical model, and supplementary information?

On 2025-11-12 14:08:47, user Muhammad Sufyan wrote:

not enough validation for example Gene ontology results are not explained well. pathways are not li ked with AD in the text. Docking 2D and 3D figures are not provided for the interation analysis. compound target netwrok is not constructed. discussion is not strong, comparison is missing. Molecular dynamics simulation must be included. why the specific targets were selected I mean criteria for selction either they are more relevant to AD or you just pickedup based on their hub connectivity

On 2025-11-12 13:57:04, user Prof. T. K. Wood wrote:

For the novel TAs you designed, there are two missing references:

1. We discovered that the physiological role toxin-antitoxin systems is phage defense in 1996 and deduced how some of them function (transcription shutoff), so this seminal ref should be added (1996, doi: 10.1128/jb.178.7.2044-2050.1996). I note TAs have since been found to be the most prevalent-phage defense system in bacteria and archaea.

2. We were the first to create both novel toxins and novel antitoxins, through DNA shuffling, so that should be added, too (2014, DOI: 10.1038/srep04807).

On 2025-11-11 17:59:30, user Erin Sauer wrote:

This manuscript is now published:<br /> https://doi.org/10.1093/icb/icaf086

On 2025-11-11 16:11:40, user Aya Ludin wrote:

This paper is now published in Cell. <br /> DOI: 10.1016/j.cell.2025.09.021 <br /> Link: https://www.cell.com/cell/fulltext/S0092-8674(25)01089-X <br /> Please refer to the published Cell paper for the accurate description of CD8 construct and reporter fish production.

On 2025-11-11 15:45:49, user Jaroslav Nunvar wrote:

Congratulations on your nice results. I suggest some points to discuss:<br /> You should definitely state if the three SOS inhibitors are located in the leader region of ICEBs1 (i.e. are among the first genes to enter recipient). If so, these would confirm the general phenomenon in conjugative elements, detailed in https://doi.org/10.1038/s41586-024-07994-w Also, if this is the case, leader-located genes tend to have ssDNA promoters. Can you observe such promoter preceding ramSTA?

On 2025-11-11 14:24:19, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

Inefficient intron splicing is repurposed as a regulatory mechanism. What might seem like a limitation, instead becomes something functional, an idea that might apply to a diversity of signaling pathways with a prominent rate limiting step.

Identifying other genes with similar "IntP-like" introns shows that the tim mechanism likely isn't a one-off, but part of a post-transcriptional regulatory strategy that could apply to development and stress response as well.

Classic models of circadian regulation focus heavily on proteins and transcriptional feedback. This paper argues that RNA processing can be an intrinsic timing mechanism, revealing a new method for clock control.

The effects of intron splicing are shown, not only in a reconstituted system, but in the whole-organism behavior of live, freely moving flies

On 2025-11-11 14:11:18, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

This work models viral adaptation not as isolated mutations but as evolutionary escape trajectories constrained by both protein viability and antibody pressure. The authors show that escape proceeds through narrow and predictable “escape funnels”, consistent with convergent mutations observed in SARS-CoV-2 variants.

Combining generative RBM models with mean-field trajectory analysis enables quantitative estimates of path entropy and fitness cost. The model captures the direction of antigenic drift and enables prospective prediction of antibody escape, including for therapeutic cocktails: anti-correlated escape profiles force viruses onto longer, costlier routes.

The model shows impressive predictive power. It demonstrates that, despite the potentially vast mutational landscape, the virus tends to follow a limited set of evolutionary routes, many of which are already observed in Omicron variants.

The approach is broadly applicable and offers a principled route to rational therapeutic design for rapidly evolving pathogens - for instance, for HIV and influenza.

On 2025-11-11 03:27:09, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

The authors build alignments of human and great-ape Telomere-to-Telomere genome assemblies across multiple individuals. This allows them to separate true lineage-specific divergence from ordinary human polymorphism, a long-standing limitation in studies of human accelerated regions.

They identify ~1,600 “Consensus HAQERs” (human ancestor quickly evolved regions) -regions that diverged rapidly between the human-chimpanzee ancestor and the ancestral node of modern humans. These loci mark only 0.05% of the genome but carry signatures of elevated mutation rate and ancient positive selection.

HAQERs are enriched in "bivalent chromatin states" - regions poised between repression and activation. The same regions overlap GWAS loci for psychiatric, endocrine, and cancer-related traits, suggesting that the sequence changes shaping human-specific evolution also underlie modern disease susceptibility.

By combining T2T genomics with probabilistic ancestral reconstruction, this study reframes human-specific evolution as a process concentrated in dynamic, regulatory DNA rather than protein-coding change. It exemplifies how complete genome assemblies and population variation can refine our understanding of the genetic basis of human uniqueness.

On 2025-11-11 03:17:07, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) really enjoyed this paper.

Here are our highlights:

As rates of chronic inflammatory and metabolic diseases rise, the variance partitioning framework used here can isolate how much of microbiome variance can be attributed to specific factors.

Including historically underrepresented populations with limited exposure to industrialization presents a truer picture of what parts of the microbiome are ancestral, variable, and adaptive.

This paper highlights a lack of cross-population model transferability and emphasizes the need for inclusive data. If microbiome science only reflects industrialized populations, we can't design context-appropriate interventions for rapidly industrializing regions.

The chain of influence from environment to microbiome to physiology shows that industrialization-driven microbiome changes have real physiological costs, even in the absence of overt disease.

On 2025-11-10 16:12:23, user Ben Auxier wrote:

The work presented in Tan et al. is provocative, suggesting that during asexual spore dispersal Neurospora crassa segregates its chromosomes across multiple nuclei, instead of the nuclei being mitotic copies of each other as previously assumed. While similar to the results that some of these authors have presented in Botrytis and Sclerotinia, showing this in a genetic model organism would provide the genetic tools to dissect this phenomenon.

However, the results presented here lack definitive proof. The evidence presented can be summarised as follows:

1) relatively low measured DNA per spore, based on DAPI fluorescence, compared to yeast

2) chromosome specific probes show patchy distribution across nuclei, compared to probes that target all chromosomes.

The first line of evidence suffers from an apples-to-oranges comparison, because the comparison is across species. The compound DAPI binds to the AT regions of DNA, and so differences between species in both AT% as well as those that affect general fluorescence, will influence this measurement. For instance, yeast has 62% AT genome, while Neurospora has 46%. Highlighting the futility of such comparisons, the data in Figure 1C shows clearly that while N. crassa has a haploid genome that is 4 times as large as yeast (compare 1st and 3rd columns), the fluorescence signal is equal (compare 6th and 4th column). Even assuming the authors’ hypothesis, there is still "too little" fluorescence given the genome size of N. crassa. Clearly, while within a species there is a strong correlation between genome size and fluorescence, when compared across species such correlation disappears.<br /> The second evidence is from fluorescent hybridisation. Here the authors show that a FISH probe specific to chromosome 1 is never found in more than one nuclei, while a telomere probe that targets all chromosomes is more often found in multiple nuclei. The main issue is that the claims rely on negative evidence, that is to say the absence of signal. However, the absence of signal is not a strong signal of absence. FISH is a very sensitive process, and differences in probe design and washing steps can greatly affect the process. Highlighting this, in 14% of spores, the authors' own chromosome 1 specific probe does not bind to either nucleus. If this data was to be taken at face value, this would indicate 14% of spores lack Chr1, which would be inviable. Extrapolating across all chromosomes, we would only expect 36% of spores to have all chromosomes and be viable ((1-0.14)^7). Such low viability is inconsistent with observed spore viability of N. crassa, which generally exceeds 95%. An alternative explanation is that the probe binding is not very efficient. This is supported by the telomere probe, where it remained undetected in 10% of conidia , despite this probe targeting 14 different chromosomal regions! Again, taken at face value this would indicate that a significant fraction of spore nuclei lack chromosomes entirely. Notably, only 64% of spores had all nuclei with signal from this telomere probe.

Aside from inconclusive data, the claims here are also inconsistent with the basic empirical genetics of this fungus. It has been known for decades that when one wishes to isolate loss-of-function mutants in N. crassa, like the auxotrophic mutants used to demonstrate the "one gene - one enzyme" principle, regular macroconidia do not work. Instead, microconidia prove useful, allowing for the easy isolation of such mutants (Catcheside, 1954). This provides powerful evidence that macroconidia have redundant nuclei, which compensate for loss-of-function mutations (See Gross and Lester 1958 for further discussion). One only needs to read the experimental methods of Beadle and Tatum to see the effort in isolating auxotrophic mutants in this organism. Instead of simply mutagenizing conidia to obtain auxotrophs, they needed to use the extremely labour intensive purification process of individually crossing mutagenized conidia to a wild-type background, to be able to isolate homokaryotic ascospores (Beadle and Tatum; 1954). This is also true of genetic transformations, which are performed on macroconidia. Transformants always need to be purified, as the original colony that grows on selective medium generally contains a mix of transformed and untransformed nuclei. If the macroconidia would contain a single haploid genome, divided over multiple nuclei, as suggested by Tan et al, there would be no need to purify induced mutations.

Further, the claims here are also inconsistent with the evolutionary dynamics of this fungus. This fungus is the foundation of the studies in heterokaryosis, the presence of multiple distinct genotypes within a single mycelia. Arising from either de novo mutations, or from fusion of two mycelial hyphae, such heterokaryons in Neurospora are quite stable. It is well-described that conidia can be heterokaryotic, meaning a single conidium inherits two distinct genotypes. This has been studied in detail for the soft mutation, where up to 40% of conidia are heterokaryotic, containing both the wild type and mutant alleles of the soft gene (Figure 2A; Grum-Grizmaylo et al. 2021). This is not due to specific dynamics of the soft mutation, as similar ratios of homokaryotic and heterokaryotic macroconidia have been observed in auxotrophs (Atwood and Mukai, 1955), which were used to form the current model of random segregation into multiple mitotic nuclei in Neurospora. A recent example of such evidence has been shown by Mela and Glass, who inserted either green or red fluorescence into the his3 locus in different genotypes, and using fluorescent microscopy they readily recover ±40% of conidia with both colors (Figure 1f; Mela and Glass, 2023).

The claims made by Tan et al. are strong and in my opinion the evidence does not rise to the level needed. Measures like fluorescence intensity or hybridisation can never be definitive and therefore are at most a start of further experimentation. However, the predictions of incomplete chromosome sets per nuclei can be definitively tested through single nucleus sequencing. The technology has advanced to the level that single nuclei can be reliably processed for whole genome sequencing, which is the most reliable way to determine if these claims ultimately reflect reality.

References:<br /> Beadle G.W. & Tatum E.L. 1945. American Journal of Botany. https://doi.org/10.2307/2437625 <br /> Mela A.P. & Glass N.L. 2023. Genetics. https://doi.org/10.1093/genetics/iyad112 <br /> Grum-Grzhimaylo, et al. 2021. Nature Communications. https://doi.org/10.1038/s41467-021-21050-5 <br /> Lester H.E. & Gross S.R. 1959. Science. https://doi.org/10.1126/science.129.3348.572 <br /> Catcheside D.G. 1954. Microbiology. https://doi.org/10.1099/00221287-11-1-34 <br /> Atwood K.C. & Mukai F. Genetics. https://doi.org/10.1093/genetics/40.4.438

On 2025-11-08 21:44:47, user Eugene F. Baulin wrote:

The best read I had this year.

On 2025-11-07 21:29:04, user Katie Schaefer wrote:

Looking forward to the paper, but I can't help but notice multiple typos in the abstract.

On 2025-11-07 14:48:23, user Sofia Peressotti wrote:

Peer-reviewed version available at Advanced Functional Material: https://doi.org/10.1002/adfm.202522306

On 2025-11-07 11:28:23, user Uri Bertocchi wrote:

Now published in ACS NANO!<br /> https://doi.org/10.1021/acsnano.5c12530

On 2025-11-07 10:51:52, user Tatsuya Yamashita wrote:

Dear authors,

at first, congratulations to this important findings. This data, paired with other ancient DNA evidence, can further clarify the demographic patterns of the peopling of Eastern Eurasia and Oceania, as well as their interactions with archaic human groups. Different deeply branching Denisovan components can be very useful data points for possible migration routes and or population substructure scenarios.

In your pre-print, you argued for a possible earlier southern route into Oceania, followed by a later wave of the ancestors of South Asians (AASI) and East Asians, with East Asians via a possible northerly route: "This supports an early migration of the ancestors of Oceanians through South Asia followed by the later arrival of the ancestors of present-day South Asians. East Asians do not share this Denisovan component in their genomes, suggesting that their ancestors arrived independently, perhaps by a northerly route".

One major problem with this scenario is the observed genetic affinity between the different "basal Asian" populations (e.g. Tianyuan, Önge, Hoabinhian, Xingyi_EN, Jōmon/Shiraho_27k, AASI, and Australasians/Oceanians such as Papuans); also known as "eastern non-Africans" (ENA) or "East Eurasian Core" (EEC). The aDNA data strongly suggest a single dispersal route and subsequent rapid diversification into multiple basal Asian lineages (presumably in the South-Southeast Asia region via a single Southern route).

E.g. Oceanians/Papuans can successfully be modeled (qpAdm/qpWave) as simply Önge-like + additional Denisovan; or alternatively as Tianyuan-like + additional Denisovan. They do not fit as outgroup to "West/East Eurasians" either, but are nested within the "Eastern" clade (e.g cluster with Önge, Tianyuan, or present-day East Asians).

Although it is possible to reproduce a signal affilated with a distinct earlier southern coastal route (proxied by ZlatyKun_45k); this wave however left only minor ancestry among present-day Oceanians/Papuans (and or South Asians), with the majority ancestry of them being derived from the same source as Önge or Tianyuan: e.g. ZlatyKun + Önge-like + extra Denisovan, in a 3–5%, 92–95%, and 2–3% ratio respectively. (qpGraph models allow higher "early ancestry" for Oceanians/Papuans: 12–24% when splitting before or at around the same time as ZlatyKun/Ranis, or up to 44% when splitting at the same time as Ust'Ishim.)

Beyond that, a northern route entry for the ancestors of East Asians seems to be only partially possible, as the majority ancestry of East Asians seems to be from an Önge-like source (except Önge also used a northern route entry).

This means that present-day eastern non-Africans (ENA) descend primarily from a single migration wave eastwards, presumably via a route South of the Himalayas; and which possibly absorbed an earlier less successfull wave, at least regionally (Oceania and South Asia).

This may also have happened via a more substructured wave: e.g. both a southern coastal route (along the coast of the Indian subcontinent) and a southern interior route (via an interior route along the southern Himalayan mountain range) into Southeast Asia and beyond. – It is however well possible that the southern coastal wave pre-dated the southern interior wave, and thus display different Denisovan signals. E.g. timely separated migrations waves of a shared clade.

Regional Denisovan admixture events (or their partial absence as in the case of Jōmon HGs [see the recent paper by Jiaqi Yang et al. 2025 "An early East Asian lineage with unexpectedly low Denisovan ancestry"]) can be explained that way, without needing several different distinct waves, which would contradict the observed genetic affinities of the different Basal Asian lineages. The low Denisovan ancestry of Jōmon hunter-gatherers may or may not be affilated with the Shiraho_27k specimen, who appearently contributed some ancestry to later Jōmon. For more information on the Shiraho_27k specimen, please contact your co-author Svante Pääbo or Hideaki Kanzawa-Kiriyama.

Note that Tianyuan40k can successfully be modeled as Önge-like + IUP-affilated admixture (BachoKiro_IUP); which fits the presence of IUP material sites in nearby NW China and Mongolia. Such IUP admixture has also been noted to explain the observed affinity to the GoyetQ116-1 specimen in Europe, which similarly can be modeled as Kostenki14/Sunghir_UP + BachoKiro_IUP (see Hajdinjak et al. 2021 "Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry").

It is possible that this Siberian IUP group absorbed the EA-specific Denisovan component and via its admixture into Tianyuan, contributed it to other Eastern Asians in lesser amount. – Present-day East Asians in turn can be successfully modeled as Tianyuan-like (c. 25%) + Önge-like (c. 75%); (see McColl et al. 2018 "The prehistoric peopling of Southeast Asia" for example). – Via Tianyuan-like or Denisovan-admixed IUP groups, this archaic ancestry may have also reached regions further West (as with the supposed Denisovan signal in Sunghir etc.).

You can also review Bennett et al. 2024 "Reconstructing the Human Population History of East Asia through Ancient Genomics", a recent summary paper on the peopling of Eastern Asia and beyond; as well as Tianyi Wang et al. 2025 "Prehistoric genomes from Yunnan reveal ancestry related to Tibetans and Austroasiatic speakers".

A summary of my points regarding your postulated "earlier southern route" for Oceanians and a possible "northerly route" for East Asians:

• The available genetic data strongly suggests a single shared migration wave for the primary ancestral source of all eastern non-Africans (Papuans, AASI, East Asians, Önge/Hoabinhian, and Tianyuan). The presence of multiple deeply branching EEC lineages in Southeast Asia and southern China suggest it to be a major place of diversification from a shared ancestral source.<br /> • Papuans/Oceanians (and AASI) may have limited amounts of admixture from an earlier wave, but primarily share ancestry with Önge and Tianyuan.<br /> • Tianyuan can be modeled as either an admixture between Önge-like (61–67%) and BachoKiro_IUP-like (33–39%) ancestries; or represents a deep split from the rest of eastern non-Africans; although with some geneflow into later East Asians.<br /> • Ancient and present-day East Asians can be modeled as primarily Önge-like (c. 75%) with Tianyuan-like admixture (c. 25%).<br /> • The different Denisovan introgression events, if not shared, may have happened regionally to explain the observed affinities, but the differences in Denisovan components among each group.

Below some qpAdm results on this (AADR v.62 + Ranis dataset); allsnps=TRUE:

Model1<br /> target: Papuan<br /> left: Hoabinhian, ZlatyKun, Denisovan<br /> right: Mbuti, Ranis13, Ust'Ishim, BachoKiro_IUP, Tianyuan, Önge, Kostenki14, Sunghir_UP<br /> Results: Hoabinhian: 93,9%; ZlatyKun: 3,2%; Denisovan: 2,9%;<br /> p-value: 0.061

Model2<br /> target: Papuan<br /> left: Japan_Jōmon, ZlatyKun, Denisovan<br /> right: Mbuti, Ranis13, Ust'Ishim, BachoKiro_IUP, Tianyuan, Kostenki14, Sunghir_UP<br /> Results: Japan_Jōmon: 94,1%; ZlatyKun: 2,4%; Denisovan: 3,5%;<br /> p-value: 0.094

Model3<br /> target: Tianyuan<br /> left: Önge, BachoKiro_IUP<br /> right: Mbuti, Ranis13, Ust'Ishim, Oase1_IUP, Papuan, Hoabinhian, Kostenki14, Sunghir_UP<br /> Results: Önge: 65,5%%; BachoKiro_IUP: 34,5%%;<br /> p-value: 0.170

Model4<br /> target: Japan_Jōmon<br /> left: Önge, Amur33k<br /> right: Mbuti, Ranis13, Ust'Ishim, BachoKiro_IUP, Tianyuan, Papuan, Hoabinhian, Kostenki14, Sunghir_UP<br /> Results: Önge: 79,0%%; Amu33k: 21,0%;<br /> p-value: 0.053

Model5<br /> target: Han_Chinese<br /> left: Önge, Amur33k<br /> right: Mbuti, Ranis13, Ust'Ishim, BachoKiro_IUP, Tianyuan, Papuan, Hoabinhian, Kostenki14, Sunghir_UP<br /> Results: Önge: 73,6%%; Amu33k: 26,4%;<br /> p-value: 0.090

Etc.

(Önge = ONG Mondal; Jōmon = JpOd181/274/282).

E.g. it is not likely that Oceanians were part of a distinct earlier wave into Oceania, separate from other mainland Asian groups, nor that East Asians reached East Asia along a distinct northern route (independently of Önge-like groups etc.). Next to qpAdm/qpWave or qpGraph models, f3/f4 statistics are quite clear on this. Papuans are (beyond their extra Denisovan ancestry and possible minor "earlier group" admixture) nested in eastern non-African diversity (e.g. EEC).

It is plausible that after the OoA exit, and the IUP/EEC dispersals from a Hub on the Persian plateau, Eastern non-Africans (ENA/EEC) shared a secondary Hub somewhere in Northwest India, from which Oceanians expanded first, via a coastal route towards Oceania. Along the coast of the Indian subcontinent (South India?), they absorbed the Deep Denisovan ancestry and continued to expand to Oceania. – Some time afterwards, the remainder ENA/EEC group (residual) expanded along an interior route South of the Himalayas into Southeast Asia and Southern China; not admixing with the Deep Denisovan group. – There, one branch split and head towards Japan (low Denisovan), while another group headed northwards coming into contact with IUP groups & the EA-specific Denisovan (Denisovan3-like) component (=Tianyuan_40k); while the remainder absorbed a local Denisovan group in Southern China or Southeast Asia (=Önge-like). – This Önge-like groups expanded back into South Asia/India, absorbing the group with Deep Denisovan introgression (becoming the AASI). The Önge-like groups staying in Southeast Asia became the Hoabinhians, while early East Asians formed along a cline of Tianyuan-like and Önge-like ancestries.

Of course the above scenario is just one of many possibilities; it is well possible that Oceanians used a southern route, while the ancestors of both East Asians and Önge used as northerly route. – Or any other scenario which can explain the aDNA data and genetic affinities.

My suggestion is to define a model which alignes with both aDNA data and archaic components (for ancient and present-day populations), as well as, if possible, archaeologic and paleoenvironmental evidence.

E.g. including a set of ancient and present-day groups to test on their Denisovan components and their overall genetic affinities (not just modern groups to prevent bias from ancient geneflow events): For South Asians: AASI-rich tribal groups from Southern India, such as Irula and Paniya; for SEA: Önge, Hoabinhians; for EA: the newly analyzed Xingyi_EN samples, Jōmon, Longlin, Amur14k, Qihe3, Tianyuan and Amur33k, as well as present-day East/Southeas Asians; for Oceania: Papuans, Australians, and Aeta. Maybe a chart comparing shared/distinct Denisovan components and f3/f4 statistics of each test group to each other would help clarify the exact affinities, shared routes or geneflow events. Perhaps, your co-author Svante Pääbo can share informations on the Shiraho_27k specimen and its Denisovan components.

A strong model should explain the genetic data/affinities of ancient/present-day populations, their different Denisovan components, and in best case also include archaeologic and paleoenvironmental data. To determine the influence of ancient geneflow, comparison between ancient specimens could help (Tianyuan vs Önge vs Jōmon vs Longlin vs Amur14k etc.).

I hope this information can help to tangle out some possible scenarios on the dispersal, contact and introgression events for the different deeply branching Denisovan components and present-day Asian populations. Or maybe inspire future studies on this topic.

I am looking forward for the publication of your paper and more exciting findings!

Thank you.

Yours sincerely,<br /> Yamashita Tatsuya

On 2025-11-07 06:51:31, user Christian M wrote:

Pahvantia has been demonstrated to not be a suspension feeder (Caron and Moysiuk, 2021). The "appendage" previously used to calculate mesh size represents the setal blade gills, while the true portion of the appendage obscured alongside it has a Hurdia-like morphology. If possible, Pahvantia should be removed from the analysis.

On 2025-11-07 02:15:47, user Mailang Ouyang wrote:

This research truly defined the real hematopoiesis in zebrafish. Gorgeous work！！！

On 2025-11-06 19:00:54, user Joyce Lee wrote:

https://www.nature.com/articles/s41467-022-31238-y

On 2025-11-06 18:29:12, user Jonathan Rondeau-Leclaire wrote:

Hi,<br /> I'm on the fence about consensus methods for DA, because these tools are statistical models that do not estimate the same thing (e.g. Aldex measures fold-differences in proportions whereas deseq and edgeR model changes in sequence counts). Also, each model makes different assumption about the data, since they are statistical models. What does the consensus between two tools that target different estimand and have different null hypotheses really mean?

On 2025-11-06 17:50:58, user Prof. T. K. Wood wrote:

Seems like another toxin (MisA)/antitoxin (MisB) system.

On 2025-11-05 16:14:22, user NA wrote:

https://doi.org/10.1016/j.ard.2025.07.019

On 2025-11-05 10:13:41, user Gregory Ehx wrote:

This article is now published in Methods in Molecular Biology https://link.springer.com/protocol/10.1007/978-1-0716-4430-0_17

On 2025-11-05 08:42:19, user Anastas wrote:

May be cite this one too?<br /> https://pubmed.ncbi.nlm.nih.gov/38301362/

On 2025-11-04 18:29:17, user Leonardo Salmena wrote:

This study has now been published https://rdcu.be/eOaYe