On 2019-07-01 05:17:30, user Gal Haimovich wrote:

This is very interesting, and a cool method, but the authors should verify that CYP3A4 protein is not secreted as well in their mice, e.g. as suggested here: https://bpspubs.onlinelibra...<br /> Also, in fig 1B, there are very faint bands of CYP3A4 protein in ScA and VsA which the authors ignore. This could explain the 5EU-RNA in adipose tissue.<br /> There is also clear HD5EU staining in adipose tissue at level similar to kidney(fig 2C). Perhaps a quantitative analysis of these images (instead of showing a single image example) will show clear differences.<br /> I am not convinced that the 5EU-RNA from adipose tissue originated from Liver, or that the differences seen are a result of the ccfRNA and not the change in diet that changes transcriptional or RNA decay programs.

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

We at the Evolutionary Health Group ( https://evoheal.github.io/) "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 2022-11-19 13:38:52, user Mahad AZAM wrote:

Though the work has been conducted on quite basic aspects of hematology, however such validations are a need of time for resource poor countries.

On 2020-12-17 08:52:05, user Priyanka Kadam wrote:

Congratulations to Kartik and team for this very important paper. Great to see the new species of Krait named after Rom Whitaker :)

On 2025-10-06 12:17:30, user Alex Cope wrote:

This was published earlier this year under a new title: https://doi.org/10.1126/science.ads2658

On 2015-01-11 14:10:18, user Owen Petchey wrote:

In Version 1 the name of Dylan Childs has first name and surname swapped. This is corrected in Version 2.

On 2019-07-14 20:50:17, user Aleksandar Jeremic wrote:

A creative and very innovative approach that will advance cell biology field. Excellent paper.

On 2020-02-09 15:49:43, user ResearchGuy wrote:

I see several commenters have asked about the COMPOUND probability of ALL FOUR sequences occurring naturally in what would seem to be a section of nCoV that affects what kind of cells that can infect. I have seen no answers to that question. Someone, preferably several someone's, please answer it. If I had the skills I would do so myself, but I don't think any of the posts have even stated the exact individual probabilities so I can't multiply them together for myself.

On 2020-02-01 07:05:39, user Anon wrote:

I noticed that several people have pointed out that QHR63300.1 has all of the same insertions and is from Bat. Can anyone explain why this is the only Bat CoV with these insertions?

If you search for matches to QHR63300.1 the best hit by far is the Wuhan Seafood Market CoV, which infects humans.

It's also hard to understand why QHR63300.1 was uploaded 4 days ago (Jan 27, 2020) from Wuhan Institute of Virology.

On 2021-05-15 20:43:02, user Vicente Velasquez wrote:

This was overall a really good read, and great evidence is presented to demonstrate a connection between leptin and the canoncial WNT pathway.

Strengths:<br /> - Methodologies on zebrafish and mice feeding and measuring are well described and easily replicable. <br /> -Staining images are high resolution and can be clearly read and analyzed by the reader.

Some critiques I have with the paper include:

-Figure coloring choices are not color-blind friendly. The use of bright reds and yellows are not comfortable to the above listed. I suggest choosing colors that would not be this way ( such as less bright/more subdued colors).

-Figure 3B's grey boxes look less like data and more like formatting errors. Please use another method to demonstrate what the grey boxes are saying, so it can stand out more.

-For your immunohistochemistry, please cite your antibodies/techniques. While you do cite the papers that you used for the protocol, this is incredibly inconvenient as the cited papers are not clear and specific as well. It would be fine to just list what antibodies you used, and just cite the protocol from the papers.

-Figure 5A has an odd break in weight recordings, and this break is not explicity stated. Is there a reason for this? Please state it in the figure or in your results section.

-Zebrafish pictures in 3A should be moved to a supplemental figure. <br /> -Figure1A-D zebrafish pictures should be moved to better allow room for E and F elaboration.<br /> -Consider getting more data points or using more for E and F to establish a stronger significance.

-Figure 2A-D also has data from female fish, even though you state that males were only used due to variances in female weight due to eggs. If this is the case, the female data should not be present in your main figures; either move female data to a supplemental figure or do not include the female data.

• A potential direction I recommend ( especially for mice/mammalian systems) is to analyze fat levels via radiolabeling. This can also be done in the zebrafish, as you did see a weight change in circumstances of extreme nutrient surplus.

On 2021-08-17 16:08:17, user Graham Hitman wrote:

This MS is now published in BMC endocrine disorders <br /> The link is<br /> https://rdcu.be/ct4S2

On 2023-02-02 09:25:55, user Sebastian Van Blerk wrote:

Dear authors,

There seems to be a mistake with the primers described in the methods section.<br /> The 515F-806R primer pair only amplify the V4 region. They do not amplify V3-V4.

If these primers were indeed the ones used for sequencing then this is a comparison of V1-V3 vs V4.

Kind regards,<br /> Sebastian Van Blerk

On 2016-09-19 02:22:21, user DeboraMarks wrote:

Great paper Hugh, Adam and Jesse !<br /> Looking forward to digging into the data.

On 2024-01-12 11:41:56, user Miquel wrote:

Summary Twitter thread can be found here<br /> https://twitter.com/MiquelSendra/status/1745766466282979662

On 2015-01-17 16:18:04, user Guest wrote:

We have already issued a detailed response refuting these claims.

1) See comment by Hanna at the bottom: http://www.nature.com/natur...

2) Link for response: https://www.dropbox.com/sh/...

Please also see a copy of correspondence pasted below (from May 2014).

On 2023-09-21 08:42:03, user Diego del Alamo wrote:

This is a comment about version 5 of the manuscript.

These results are thorough, compelling and persuasive. They also stand in contrast with other papers, published in the aftermath of alphafold's release, that argue the opposite.

The main concern for me is the absence of any testing or discussion surrounding the relax step of the pipeline - the manuscript never uses the words "relax", "minimization", and "openmm" (the package used by alphafold for all-atom minimization), and I did not find details in the accompanying github repo. It is therefore unclear how much of the results should be attributed to the neural network itself and how much should be attributed to the minimization step following structure prediction. We can't rule out the possibility that the strain being measured results from this second step. Were that the case, it would cast doubt on the role of the alignment and templates as the authors suggest in the discussion.

On 2019-04-23 12:47:59, user Brian Levine wrote:

In this study, the researchers assessed concurrent validity of questionnaires against established measures in a sample of 217 participants. There is a strong motivation for this kind of study, which provides useful information for researchers assessing memory, imagery/scene construction, navigation, and future thinking. The researchers are commended for a comprehensive study reflecting many hours of effort in order to execute these measures. My comments will be largely focused on the measures of autobiographical memory (AM), some of which were developed by my group. This comment grew out of a discussion with my trainees who also read the article, including Nick Diamond, Carina Fan, Raluca Petrican, Stephanie Simpson, and Lynn Zhu. I thank the authors for posting this preprint, open to community commentary.

A major contribution of this paper is an emphasis on subjective experience, which, although impossible to assess directly, is important to the consideration of episodic memory. This paper supports the view that subjective and objective instruments do not assess the same thing. As stated by the authors, the use of these instruments depends on the goals of the study. Where we disagree is the premise that seems to be implied in the title, which is that questionnaires (and to some extent, the objective tests) are measuring something different than what they purport to measure.

My main critique of the approach is that it lacks nuance in terms of levels of analysis within AM, which is itself a multifaceted construct. The authors took a strictly univariate approach in which each criterion measure is treated as a unitary measure of a latent construct. Normally, multiple measures would be deployed in a latent construct approach because no single measure is process-pure.

A main finding of the present study is that overall, subjective ratings (either on questionnaires or self-/other ratings of laboratory test performance) correlate with each other to a greater degree than the subjective/objective comparison. This is interesting though not surprising given that subjective measures do not measure the same thing as objective measures, and that they share measurement error bias. This is also the case for the scene construction measure which is held as objective, but in fact takes subjective ratings into consideration in the scoring.

In the Autobiographical Interview (AI), internal details are treated as a measure of a person’s capacity to recover contextual information from past events; external details reflect content not specifically related to the defined event and are therefore considered to be inversely related to cognitive control over memory retrieval. A recovered detail is neutral with respect to subjective/conscious experience. Patient M.L., who had a specific impairment in conscious re-experiencing of the past due to frontotemporal disconnection, showed only marginal reductions in internal detail production, even though his “remember” ratings for the same events suggested a profoundly reduced conscious experience (Levine, Svoboda, Turner, Mandic, & Mackey, 2009). He also showed reduced activation of the AM network when presented with rich retrieval cues for these events. Even more to the point, patients with severe medial temporal lobe amnesia, including H.M. (Steinvorth, Levine, & Corkin, 2005) have produced events with substantial internal details (see also Cermak & O'Connor, 1983).

The SAM episodic subscale, on the other hand, was developed specifically to probe the subjective experience of recollection at the trait level. As noted by the authors, we found that these were unrelated in our original SAM paper in healthy young adults (Palombo, Williams, Abdi, & Levine, 2013; see also Hebscher, Levine, & Gilboa, 2018 for a similar finding), nor were people with Severely Deficient Autobiographical Memory (SDAM) impaired on AM for recent events using the AI. Considering these findings, the above-described patient findings, and the more general findings of dissociation between subjective recollection and recognition performance, as illustrated in the Remember/Know technique, a strong relationship between these two measures should not be expected.

Nonetheless, some relationship between recovered details and self-reported episodic autobiographical re-experiencing at the trait level could be expected. I believe the lack of relationship is owing to the fact that the AI was designed to elicit the richest possible event descriptions from participants. As the authors note, internal details are scored liberally for the sake of reliability (i.e. the “benefit of the doubt” rule where any detail that could reasonable be considered internal was classified as such). However, there was another purpose in eliciting rich episodic autobiographical memories, which was to avoid a false positive classification of memory impairment based on incidental factors, such as misunderstanding instructions, which is of particular importance in studies of aging and clinical samples. Accordingly, under the most commonly used administration method, the subject selects an event for each time period that is highly accessible and likely well-rehearsed. The resulting score therefore reflects the participant’s best possible narrative production. This is why M.L. and H.M. could produce seemingly normal autobiographical narratives.

The SAM, on the other hand, is explicitly designed as a measure of trait mnemonics, not cognitive function as assessed by performance on a given test. The instructions for the episodic questions are “When answering, don’t think about just one event; rather, think about your general ability to remember specific events.” Even assuming that the SAM and the AI are designed to assess the same construct (which as I argue above is not the case) there is a difference between asking how one performs in general versus assessing how they perform when asked to give their best possible narrative by the examiner. By analogy, an introverted person may appear extroverted if required in certain social situations. There is no requirement to cue 5 lifetime period events as originally specified in our 2002 aging study. The AI scoring system has been applied to memories cued in different ways. Harvesting unrehearsed events from significant others may be a more effective way to estimate one’s typical retrieval abilities as opposed to their best possible performance.

The present paper used a sample of young adults. The AI as implemented in our 2002 study was developed for use in older adults and in patients. The internal detail measure is very sensitive to medial temporal lobe integrity. While this has been demonstrated in neuroimaging studies of healthy young adult samples (Hebscher et al., 2018; Palombo et al., 2018), its sensitivity to individual differences in a homogeneous sample of young adults is limited relative to individuals with compromised medial temporal lobe function, especially at the behavioral level. Nonetheless, the proportion of internal/total details or internal details/word count should be examined rather than the raw count of internal details, as the latter is confounded with verbosity. A comprehensive test of this relationship should also examine detail subcategories and time period effects. Given the foregoing I do not expect that this would change the results substantially, but it should be done for completeness.

It is intriguing that the parallel analysis on subjective vs. objective measures of spatial memory yielded significant relationships. This speaks to the complexity of AM relative to spatial memory. In navigation, the criteria for success are clearer than for AM. If someone arrives at the correct location (or gets lost), their subjective and objective experience are consonant. But if someone recalls an episode, it is unclear if the correct criterion is subjective experience or imagery or quantity of detail. As noted above, I agree with the authors that there is a distinction between subjective and objective measures, and that one’s selection of measures should be governed by the goals of the study. I would not agree that the present findings call into question whether or not internal details “is actually a good measure of recall ability” given that this measure (or its variants) has been used in over 170 studies (for table of studies, see AutobiographicalInterview.com), with good evidence for the validity of the internal/external distinction, including associations to brain structure and function. I also disagree that the findings of this study justify the use of vividness ratings alone as proxies for memory recall ability, especially in patients, who may show greater variability and less reliability in their introspective ratings than healthy adults. In any case, generalization to aging or clinical samples from a homogenous sample of younger adults is not justified.

There is great richness to these data that could be exploited in a multivariate data-driven approach. I recognize that this was not the goal of this study, but a multivariate approach such as Canonical Correlation Analysis (CCA) would allow the researchers to detect latent variables and patterns of association across these measures opaque to a series of bivariate correlations and linear regressions. This feels like a lost opportunity in favor of an assumption-laden approach that results in a flat, protracted series of individual analyses that is difficult to follow. In fact, much of the analyses here are already exploratory in that they assess the ability of questionnaires to predict performance on constructs other than the one they were hypothesized to measure. Data driven multivariate approaches are well-suited for such goals.

Finally, I had difficulty understanding the justification for proposing a single sentence test of any psychological construct. Classical test theory dictates that the reliability of a composite is better than the reliability of a single item. While single items may be useful as a screening technique, for pathognomonic signs, or when doing mass testing, they should not be used for assessment of complex traits, where interpretations of individual items may vary across individuals. A brief questionnaire for each construct would be more stable and does not pose an undue burden on participants. There are no psychometric data presented here to support the use of a single item measure aside from the fact that they showed sensitivity in this sample of healthy adults. These overfitted coefficients will shrink if tested in a separate sample. The composite test of all 15 single items could be subjected to psychometric analysis, but it is unclear if this is of interest.

Cermak, L. S., & O'Connor, M. (1983). The anterograde and retrograde retrieval ability of a patient with amnesia due to encephalitis. Neuropsychologia, 21(3), 213-234.

Hebscher, M., Levine, B., & Gilboa, A. (2018). The precuneus and hippocampus contribute to individual differences in the unfolding of spatial representations during episodic autobiographical memory. Neuropsychologia, 110, 123-133. doi:10.1016/j.neuropsychologia.2017.03.029

Levine, B., Svoboda, E., Turner, G. R., Mandic, M., & Mackey, A. (2009). Behavioral and functional neuroanatomical correlates of anterograde autobiographical memory in isolated retrograde amnesic patient M.L. Neuropsychologia, 47(11), 2188-2196.

Palombo, D. J., Bacopulos, A., Amaral, R. S. C., Olsen, R. K., Todd, R. M., Anderson, A. K., & Levine, B. (2018). Episodic autobiographical memory is associated with variation in the size of hippocampal subregions. Hippocampus, 28(2), 69-75. doi:10.1002/hipo.22818

Palombo, D. J., Williams, L. J., Abdi, H., & Levine, B. (2013). The survey of autobiographical memory (SAM): a novel measure of trait mnemonics in everyday life. Cortex, 49(6), 1526-1540. doi:10.1016/j.cortex.2012.08.023

Steinvorth, S., Levine, B., & Corkin, S. (2005). Medial temporal lobe structures are needed to re-experience remote autobiographical memories: evidence from H.M. and W.R. Neuropsychologia, 43(4), 479-496.

On 2018-06-19 17:07:21, user Ryan S Gray wrote:

We welcome comments. Enjoy.

On 2022-04-13 20:17:21, user Chouheao wrote:

This antibody 76E1 also targets to the fusion peptide. https://www.researchsquare....

On 2022-01-17 17:11:18, user Martin R. Smith wrote:

If you wanted a more systematic way to identify which specific fossil (or indeed extant) taxa might be acting as rogues, you might be interested in the approach I've recently proposed in Systematic Biology: https://doi.org/10.1093/sys...

On 2020-06-22 19:44:23, user Giulia Raimondi wrote:

An outstanding work introducing new perspective to improve oncolytic virotherapies thruough codon optimization. Extremely interesting!

On 2024-01-17 14:11:41, user Boris Hedtke wrote:

This paper was published in February 2023 in Plant Physiology with the modified title <br /> "Two isoforms of Arabidopsis protoporphyrinogen oxidase localize in different plastidal membranes" <br /> Plant Physiology, Volume 192, Issue 2, June 2023, Pages 871–885

https://doi.org/10.1093/plp...

On 2020-12-18 10:07:47, user disqus_32giU6NoIA wrote:

Really nicely written and helpful paper. It would be good if you stated in the paper what PacBio technology you used. Is it correct in assuming you used CLR data, rather than CCS/HiFi?

On 2017-11-21 21:40:08, user Timo van Kerkoerle wrote:

Congratulations on the great paper! Very impressive work.

There are some inaccuracies which I thought would be good to point out. I can imagine that some people thought this represents the first 'solid evidence' about the brain mechanisms of alpha because it is stated in the manuscript that previous papers use a global reference? This is not the case for our 2014 PNAS paper. For the laminar recordings we referenced to the metal shaft of the probe, which is right next to the contact sites, giving something like a bipolar LFP. We compared this with a silver/silver chloride wire in the recording chamber (as also noted in the paper), which didn't change the results. Furthermore, the crucial finding that implicated the involvement of layer 5 in the alpha rhythm (figure 4 of the PNAS paper) are based on CSD and MUA signals, for which the reference is not relevant. The V1-V4 data (not V2 as mentioned in the discussion) used bipolar LFP signals as well.

Also, it might be good to note that only in early visual areas alpha has been shown to be strongest in the deep layers. In particular, Bollimunta, Chen, Schroeder and Ding J. Neuroscience 2008 showed that alpha was only strongest in the deep layers for V1 and V4, but in the superficial layers in IT.

On 2024-01-20 00:06:45, user Pamela Bjorkman wrote:

This paper was published as: Cohen, AA, Gnanapragasam, PNP, Lee, YE, Hoffman, PR, Ou, S, Kakutani, LM, Keeffe, JR, Wu, H-J, Howarth, M, West, AP, Barnes, CO, Nussenzweig, MC, Bjorkman, PJ (2021) Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science 371: 735-741. PMCID: PMC7928838 doi:10.1126/science.abf6840

On 2017-06-01 07:45:51, user David Colquhoun wrote:

This is a first draft. Please tear it to pieces.

On 2020-04-23 16:03:43, user Rusty wrote:

Good study! I'm wondering is it published?

On 2018-03-27 08:04:39, user S. R. wrote:

Great work, looking forward to the future applications!

On 2016-05-09 14:17:55, user Giannis Tamvakis wrote:

Your Medicago truncatula SoPIN1 (Medtr7g106430) is annotated in Phytozome as "TatD-related deoxyribonuclease" and not MtPIN10 (different geneID).

On 2017-09-07 15:01:21, user Alexander J. Shackman wrote:

These are exciting new data, but you should show/discuss the recording locations. Amygdala and "dACC" are heterogeneous regions.

On 2018-01-22 03:30:20, user BenjaminSchwessinger wrote:

Thanks for posting this preprint. The detail of analysis and the availability of all code is great. it is excellent to see more plant pathogenic obligate biotrophic fungi sequenced. My 'feel' is that these genomes may well look pretty different to some of the better studied non-obligate oomycetes and fungi e.g. 'two speed' genome with effectors clustering to TEs. I could conceived that at least a subset of effectors may well be required in obligate biotrophs as they have to infect the host to complete the life-cycle.

Some thoughts and questions:

• Would be great to see some read length statistics on your PacBio sequencing to get a better understanding why the genome is still in a good number of contigs.

l. 146 Instead of beginning and end of contig I would use 5' and 3' prime of the sequence.

l. 185 ff. I got confused here as the numbers didn't add up for me 6039 single-copy groups give rise to 6,844 one-to-one mappings? I think I get it after reading it several times, yet some rephrasing may well help. Else proteinortho with the synteny flag may have also been an option for doing this analysis.

l. 223ff: The observation of smaller parts of the genome being reshuffled in DH14 vs. RACE1 is pretty interesting. We saw something similar comparing the two haploid genomes in wheat stripe rust fungus (see Figure 2, https://www.biorxiv.org/con... "https://www.biorxiv.org/content/early/2017/12/07/192435)"). Wonder how this all happens. Else http://assemblytics.com/ may also be a useful too in future to compare two genomes with each other in regards to structural variations.

l. 265ff: Great analysis on paralogous. We still need to do this for our candidate effectors, yet we saw an overall 'clustering' of candidate effectors. I liked the part of looking if SPs are enriched on certain contigs. Does this also hold true if you consider gene content and not only contig length?

Figure 4A would be easier to interpret if it were normalized to the number of genes analyzed and n given within the figure.

l. 353 ff: Mirrors what we found in wheat stripe rust and others in P. coronata, where candidate effectors do not reside close to TEs in general and not in gene sparse regions. We also see that candidate effectors such as CEPS in Figure S2 C have no really close neighbours. This is pretty intriguing to me. Any thoughts on this? Have you tested if CSEPs are somewhat linked to BUSCOs following the idea that some effectors are necessary in obligate biotrophs. If that is the case for you guys as well, i would be happy to look into if the BUSCOs or effectors tor which this is true are conserved.

l. 380 ff: The analysis of a TE burst in Bgh is very interesting indeed. I think it would profit from a bit more detail on what kinds of TEs were found and how much each family covered. Figure 5 also lacks some details about the usage of all these acronyms used in the figure eg. BOTR? Increasing font size and including a key in the legend would be great.

What I wonder with BGH is where did all the old TEs go? Wouldn't you expect to have some of the older TEs still present around the same age/%id as in the other Blumeria? Within the Blumeria how many TE families were specific to each species? Could it be that your database does not include the most recent TEs from other fungi?

Supplemental figure[:-3]: Not sure that joyplots are the best representation here. A circos plot maybe a better visualization.

Great work. Gave me some good pointers for my own work.

On 2019-01-25 15:09:07, user sudheer kumar wrote:

Amazing work..!! Very exciting....

On 2018-05-12 16:41:11, user Raghu Parthasarathy wrote:

The final, published version of this paper is here:<br /> https://doi.org/10.1073/pna...<br /> (It's almost identical to the preprint.)

On 2015-11-19 22:01:43, user Peter Frost wrote:

I agree that Europeans became light-skinned relatively late in time. Beleza et al. (2013) estimate that the derived alleles at SLC45A2 and SLC24A5 originated between 19,000 and 11,000 years ago. Canfield et al. (2014) suggest a time range of 19,200 to 7,600 years ago for the derived allele at SLC24A5. These are estimates, and the exact dates will remain unknown until we can retrieve ancient DNA from the late Upper Paleolithic / early Holocene. Most likely this change took place during the second half of the last ice age.

I disagree with the conclusion that these derived alleles originated among early European farmers. Yes, these alleles are absent from late hunter-gatherers in Spain, Luxembourg, and Hungary, but they are present in late hunter-gatherers from Sweden (Motala), Karelia, and Russia (Samara) (see discussion at: http://www.eupedia.com/foru... "http://www.eupedia.com/forum/archive/index.php/t-30957.html)")

The authors acknowledge this point towards the end of their text:

"We find a surprise in six Scandinavian hunter-gatherers (SHG) from the Motala site in southern Sweden. […] A second surprise is that, unlike closely related western hunter-gatherers, the Motala samples have predominantly derived pigmentation alleles at SLC45A2 and SLC24A5."

This seems to undermine the argument that light European skin originated in Neolithic farmers from Anatolia, and then spread into Europe through migration. Such an argument fails to account<br /> for the presence of the same alleles in northern and eastern Europeans at the same time, if not earlier. Again, we won’t be able to resolve this problem until we can retrieve earlier ancient DNA, particularly from the hunter-gatherers of northern and eastern Europe.

References

Beleza, S., Murias dos Santos, A., McEvoy, B., Alves, I., Martinho, C., Cameron, E., Shriver, M.D., Parra E.J., & Rocha, J. (2013). The timing of pigmentation lightening in Europeans. Molecular Biology and Evolution, 30, 24-35.

Canfield, V.A., Berg, A., Peckins, S., Wentzel, S.M., Ang, K.C., Oppenheimer, S., & Cheng, K.C. (2014). Molecular phylogeography of a human autosomal skin color locus under natural selection, G3, 3, 2059-2067.

On 2015-08-22 15:38:45, user Edouard Debonneuil wrote:

content suggestion: there is actually already aging, or rather senility, in ICD-10 : http://apps.who.int/classif...

On 2018-06-08 03:49:42, user Roland wrote:

Published in PLOS Computational Biology, April 27, 2018

http://journals.plos.org/pl...

On 2021-09-26 17:35:58, user Fernando Barroso wrote:

More experimental data to support our theoretical predictions: https://doi.org/10.1101/202...

On 2023-11-25 17:04:50, user Omid Karami wrote:

Dear bioRxiv team,<br /> This manuscript has been published in The Plant Journal (https://doi.org/10.1111/tpj... "https://doi.org/10.1111/tpj.16024)"). Please add a link to the published version

On 2021-09-23 09:05:28, user Dr. Nagarajan wrote:

Interesting article looks Amoxicillin has effect in gut ecology and provide beneficial effect in metabolic syndrome

On 2015-11-17 16:59:33, user Ian Derrington wrote:

Dear authors. This work is stellar! I must comment, as I have been doing recently on Minion related publications. It seems in nearly all ONT-related publications, there is an apparent blatant neglect of citing any work from Prof. Jens Gundlach's group, who has peer reviewed publications on the *initial* successes of nanopore sequencing (doi:10.1038/nbt.2171) as well as more extended publications showing species identification etc with nanopores (doi:10.1038/nbt.2950). Given that every one of ONT's patent they are using the nanopore MspA, which Gundlach et al (Including myself, Ian Derrington) pioneered the use of, it is essential that this work be cited in academic fairness. Please consider this for future publications.

On 2016-06-15 12:52:58, user Jean Manco wrote:

Unfortunately, this study, by limiting itself to mtDNA, was incapable of picking up the genetic signals of a third major migration - that from the European steppe in the Copper Age, with deeper origins in Siberia. MtDNA has proved very effective in distinguishing between Mesolithic hunter-gatherers in Europe and incoming farmers from the Near East over most of Europe. However by the late Neolithic, all the mtDNA haplogroups common in Europe today had already arrived. The most obvious differences between the Late Neolithic and subsequent populations lie in the arrval of new Y-DNA haplogroups and a genome-wide component, both found earlier on the European steppe. See Allentoft et al. 2015, Haak et al. 2015, Jones et al., 2015, Lazarides et al. 2014, Mathieson et al 2015, full citations for which can be found in the recent review Montgomery Slatkin and Fernando Racimo, Ancient DNA and human history, PNAS, June 7, 2016, vol. 113, no. 23, pp. 6380–6387.

On 2016-06-30 20:50:46, user Marius Pachitariu wrote:

see some example multi-plane data with >10,000 neurons here https://www.youtube.com/wat...

On 2020-11-10 01:02:40, user DHelix wrote:

A very interesting paper! I was wondering if you had removed duplicate fragments when you calculated FRiP and FRiTSS (Figure 1f)? Thanks!

On 2020-05-11 07:48:24, user Wiep Klaas Smits wrote:

Great idea to benchmark the different tools. I don't know though how generalisable the results are when using only E.coli as a testcase. I can imagine that other phylogenetic groups (e.g. gram positives) will show significant differences? Would it be possible to run this on for instance B. subtilis as well to see if this conforms to the E.coli results?

On 2025-06-26 18:47:54, user Fatemeh Delavari wrote:

This paper has now been published in Cognitive Neurodynamics. You can access the final published version here: https://doi.org/10.1007/s11571-025-10280-8

On 2019-10-25 22:44:48, user Bryan Ivan Ruiz wrote:

The manuscript by Xu et.al proposes a post-transcriptional mechanism required to maintain mitochondrial dynamics modulated by Clock. Using both in-vitro and in-vivo experiments, the authors clearly show a novel role of the Clock in regulating mitochondrial morphology, specifically in the post-transcriptional regulation of Drp1. This post-transcriptional model is novel and has not been previously characterized in hepatocytes. The investigators have conducted a significant amount of biologically relevant experiments to test and validate to validate their conclusions. Through a combination of assays, immunofluorescence, rt-PCR and western blots, the data shows that Clock modulates Drp1 activity via mRNA degradation thus controlling mitochondrial fission. Further the authors provide a potential new roll for mitochondrial fission repressor Mdivi-1 through the evident mitigation of ROS production, the reduction of NAFLD and the recovery of the membrane potential of Clock?19 mitochondria. This is a novel and significant mechanism in regulating mitochondrial homeostasis in a circadian context. However, despite the amount of work that has been done in this manuscript, there are important issues that must be addressed. <br /> Minor Issues<br /> • In line 135-137 the authors state that the mitochondrial matrix of Clock?19 mice hepatocytes was deeply stained implying a pH change may observed in the mitochondria (Figure 1B). This is inaccurate observation as Figure 1A displays less stained mitochondria in the Clock?19 hepatocytes vs Wt hepatocytes. In order to remediate this pH levels should be quantified and more representative images should be utilized. <br /> • In Figure 3 the authors state that in Clock?19 mice display a smaller mitochondrial surface ranging approximately 0.1-0.3 um2 However the bar plot displays the majority of Clock?19 mice have a slightly larger mitochondrial surface ranging from 0.3-0.5 um2. The overall conclusion is still sound however changes in the manuscript must be made to report finding this accurately.<br /> Major Issues<br /> • In Figure 1E The authors use ATP6 as a marker to observe mitochondrial morphology. The use of ATP6 is supported since the authors show the relative protein concentrations of ATP6 are equivalent in both Wt and Clock?19 mice mitochondria (Fig 3C). However due to the differences in fluorescence intensity a change in mitochondrial morphology is difficult to support. In order to remedy this the authors could report two images of similar fluorescence intensity.

• Line 214 the authors claim mitochondrial fusion genes (Opa1, Mfn1 and Mfn2) display decreased mRNA expression in Clock?19 vs Wt. This is untrue as Mfn1 was shown to have higher mRNA expression in the Clock?19 sample (Figure 3D). The authors can consider in situ hybridization to verify their claims. <br /> • The authors further claim fission protein DRP1 expression was increased in Clock?19 mice (Figure 3E). However in the results reported this is untrue, when observing the blot both DRP1 and phospho-DRP1’s do not appear to show increased band density. This claim must be redacted or band density must be calculated and show significant difference. However, the claim that FIS1 is elevated in expression is supported.<br /> • In Figure 5E mtDNA proteins are used to demonstrate the inhibition of mitochondrial fission by Mdivi-1. This is an indirect way to demonstrate inhibition of mitochondrial fission. In order to further support this point the investigators can consider blotting for Fis1 in tandem with the mitochondrial proteins reported in Figure 5E.

On 2021-01-11 03:30:48, user Daniel Isenegger wrote:

Would be good if this paper compared promoter activity relative to ZmUBI not 35S in monocots.

On 2019-08-02 13:33:37, user Michael Jeltsch wrote:

Last time when I checked - a few years back -, the extracellular domain of human VEGFR2 consisted of 7 IgG-like domains (and not of 8). This part of the Results section are not results but the results of previous research, correct? When I started to read it, it was not clear to me that you are talking about VEGFR-2 in general and not about the results of your work (that becomes clear only later when you switch to the real results with the sentence "In case of HyVEGFR-2..."). It is difficult to evaluate your analysis about the domain structure since you do not show the complete alignment of the whole EC domain of hydra VEGFR2 with the other VEGFR2 sequences, but only a partial alignment. I think you need to show the complete alignment and (to show which domains are equivalent and what the intervening sequences are).

On 2020-04-27 06:28:50, user Noah Dolev wrote:

Hi all,

Thank you for having a look at Segment2P. Our AWS credits are expiring this month, so we are shutting down the website www.segment2p.co.il. However, the Github repository is still available to anyone who wants to use the model on Amazon's platform. In the coming weeks, I will release an additional repository with a model that can run locally.

All the best,<br /> Noah Dolev

On 2019-03-28 19:21:25, user Sónia Melo wrote:

One of the best discussions I've ever seen in a paper. An unbiased approach that questions a paradigm with data. "...one cannot help but wonder whether the prevailing paradigm is based on anything more than a circular argument in which exosomes are believed to arise by endosomal budding for the sole reason that exosomes have been defined in that manner."<br /> Hope to see this out there soon!

On 2021-04-29 17:51:43, user Jay wrote:

It seems like the difference in MPRA results may be due to the ATRA differentiating the progenitors to neurons--> the difference of MPRA results (ATRA MPRA vs DMSO MPRA) may be due to different cell types and not the added ATRA itself. How did yall account for this? It would be really great if yall could do this MPRA in differentiated neurons without adding ATRA to compare the two (ATRA progenitors vs neurons).

On 2019-12-10 00:49:13, user elonnrot wrote:

A valuable addition to the growing number of passerine genomes. May I point out the barn swallow genome published this year is missing? it's one of the most contiguous ever published. Formenti et al. 2019 GigaScience https://academic.oup.com/gi...

On 2025-07-23 15:41:21, user VIKRAM GANESAN wrote:

Hello, is the data for this preprint available anywhere? We are developing a machine learning method for spatial data that might suit this dataset very well.

On 2020-05-22 07:46:35, user Lien Decruy wrote:

The current title and pdf for this paper was uploaded by mistake. The correct title is: "Evidence for enhanced neural tracking of the speech envelope underlying age-related speech-in-noise difficulties" and the correct preprint is 489237v1 is still accessible through the Info/History tab. Please look at the final version of this paper via the doi link in the Journal of Neurophysiology.

My apologies,

Kind regards,<br /> Lien

On 2022-01-21 16:11:10, user Julia Drube wrote:

We were able to publish this great piece of work in International Journal of Molecular Sciences: <br /> Please check out that revised version here: https://www.mdpi.com/1422-0...<br /> https://doi.org/10.3390/ijm...

On 2016-04-13 15:46:19, user Maria Kalyna wrote:

This is very interesting work. It definitely changes our perception of frequency and landscape of alternative splicing, and consequently of its importance, in unicellular organisms.

You introduce “intron in exon” category to analyse alternative splicing events. Recently, we used a similar term, “exonic introns” (abbreviated to “exitrons”), to describe an alternative splicing event that either includes or removes internal regions of annotated protein-coding exons: http://genome.cshlp.org/con...

Our definition is narrowed to exonic introns within the protein-coding exons that allowed us to analyse functional significance of such events at the protein level and their evolution. By analysing orthologs, we could show that almost all tested exitrons originate from protein-coding sequences. We also obtained evidence that intron loss/retroposition played a role in exitron evolution as at least some exitrons correspond to a single or multiple exons in orthologs and/or paralogs.

Though there are obvious differences in definitions of “intron in exon” and “exitron”, it appears that at least some Sch. pombe introns in exons are exitrons. Since Sch. pombe underwent extensive intron loss, we are wondering whether you see any evidence of intron loss at the borders of such introns in exons (aka exitrons); meaning that such introns correspond to protein-coding exons in orthologous genes bordered by canonical/regular introns?

On 2018-07-26 18:18:13, user Kenji Sugioka ~ wrote:

The paper including many data from this preprint, but basically rewritten and with new data has been published at Dev Cell. <br /> https://www.cell.com/develo...

On 2020-09-17 14:05:48, user Diana Duarte wrote:

Dear all, this is the link of the published version!!<br /> https://bmcplantbiol.biomed...

On 2021-06-30 07:02:22, user Joshua Mylne wrote:

This is now published (title has changed) at Pest Management Science https://doi.org/10.1002/ps....

On 2017-07-09 20:31:42, user AdamMarblestone wrote:

-"Structure Learning in Motor Control: A Deep Reinforcement Learning Model" https://arxiv.org/pdf/1706....<br /> -"Deep learning in the brain. Deep learning summer school. Montreal 2017. Blake Richards." https://drive.google.com/fi...

On 2017-03-14 14:26:22, user AdamMarblestone wrote:

-"Improved multitask learning through synaptic intelligence" https://arxiv.org/abs/1703....

On 2019-10-18 16:28:23, user °christoph wrote:

The cumulative GC skew is a valuable tool to verify correct assembly of bacterial genomes but there are caveats. Cyanobacteria frequently lack clear GC skews (not the Synechococcus/Prochlorococcus group which have clean GC skews). Also, while most GC skews show a "V" shaped minimum region, others have rather a "U" shape, which make pinpointing the minimum difficult. Also "W" shapes are not uncommon, and it is difficult to pinpoint the minimum among several "secondary minima" although the "minimum region" seems clear. Lastly, I would suggest that you rather talk of "origin region" because *the origin* should be reserved for oriC (origin for DnaA-dependent replication from oriC). In my experience, the GC skew minimum locates close to oriC but can be up to 20 kb away.<br /> Thanks for considering!

On 2017-04-13 08:59:41, user Muriel Lobier wrote:

Interesting results but I would like to know what are the N for each group (pre-modern, transitioning and modern)?

On 2017-10-27 01:25:54, user None wrote:

So are you planning to sell these?

On 2021-11-22 14:56:37, user William Matchin wrote:

This manuscript does not cite Goucha & Friederici (2015 - NeuroImage) or Matchin et al. (2017 - Cortex), papers that replicated core aspects of Pallier et al. (2011). Namely, these two papers both found selective jabberwocky structure effects in posterior STS and anterior inferior frontal regions extremely similar to Pallier et al. (2011), not finding these effects in anterior temporal cortex or inferior angular gyrus/temporal-parietal junction. These papers also used a within-subjects design, remedying one of the deficits cited by this manuscript that Pallier et al. (2011) only used a between-subjects design. Given that the results of Goucha & Friederici and Matchin et al. are congruent with Pallier et al. and bolster the same claims, these papers must be cited by the present work.

On 2021-04-16 09:55:19, user Nathalie Balakina-Vikulova wrote:

The part "3.1.2 Simulation of the physiological mode of contraction-relaxation cycles" of the 1st Version of the article "Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model" was not included in the final version of the article published in the The Journal of Physiological Sciences (doi: 10.1186/s12576-020-00741-6). This results were sent as a conference paper for «IEEE Ural-Siberian Conference on Computational Technologies in Cognitive Science, Genomics and Biomedicine (CSGB)» csgb.ieeesiberia.org in 2021.

On 2021-01-16 19:09:46, user Nicholas Markham wrote:

McAllister et al. have generously posted their excellent C. difficile physiology manuscript on bioRxiv. This careful investigation of how selenophosphate synthetase governs metabolism exemplifies the power of CRISPR-Cas9-mediated bacterial gene deletion and restoration. Thank you to the authors for sharing their work. It has introduced me to Strickland metabolism, and I expect the reviews will be positive. I wonder if referees will ask for more discussion on what molecular mechanisms are responsible for the difference in phenotype between plasmid complementation and gene editing. They might wish to see how protein levels are similar or different. It’s understandable one wouldn’t speculate on how atmospheric hydrogen makes a striking difference in phenotype, but I’m very curious to think about how this variable affects the whole field!

On 2016-05-01 13:53:47, user Thang Truong wrote:

I have similar ideas and the theory would be investigated soon

On 2025-01-07 19:02:17, user Thomas Munro wrote:

This is an ingenious idea. The name azo-morphine will likely cause confusion, however, given that the scaffold used is naltrexamine. The name is already in use for azo-substituted morphine derivatives. A full semi-systematic name would be unwieldy, but could be used to derive a distinctive acronym like IBNtxA, which would make literature searches much easier.

On 2025-01-25 16:41:10, user Rouf Banday wrote:

This study provides fundamental insights into how interactions between mutational processes contribute to carcinogenesis. Meticulous and terrific work!

On 2021-05-13 19:53:48, user Felipe wrote:

This paper is now published ! https://www.frontiersin.org...

On 2018-07-16 10:32:49, user John Thompson wrote:

No conflict of interest. I do not work for nor have any financial interest in any DTC genetic testing company. No affiliation listed because work was not done in association with any current or past employer.

On 2021-02-09 09:28:30, user Hansi Weißensteiner wrote:

Paper published on Genome Research - 2021-01-15: https://genome.cshlp.org/co...

On 2020-08-07 17:18:38, user E. Laurel wrote:

This is really interesting work. Have you subtyped the cell lines and PDX models you're using? I'd be interested in seeing if classical and basal lines responded differently or had different base levels of DDR1 or NETs. Perhaps this is one targetable difference between the subtypes or maybe it would work on all patients.

On 2021-02-01 17:20:59, user Cornelis Grimmelikhuijzen wrote:

35 years ago, I published this paper in Cell and Tissue Research:

Organization of the nervous system of physonectid siphonophores<br /> C. J. P. Grimmelikhuijzen, A. N. Spencer & D. Carré <br /> Cell and Tissue Research volume 246, pages463–479 (1986)

We investigated several siphonophores, including Nanomia biuga, stained their nervous systems (with peptide antibodies) as well as the muscle fibers (with rhodamine-labeled phalloidin). Did the authors ever read it?

On 2016-11-17 14:56:31, user Fabian Staubach wrote:

Is table 1 for illumina/nanopore hybrid? It would be interesting to know how minion alone performed to judge its usefulness.

On 2016-12-05 17:15:04, user Geraint Duck wrote:

This is an interesting idea. However, I wonder about some other "hidden costs" of review that may also need to be considered. For example, the cost of access to both data, software, and *other papers*. Would a "full-time reviewer" have access to the array of non-OA journal subscriptions needed for a complete review? Some publishers will provide access to their own journal collections should you agree to review, but how often is (just) this sufficient? And related, access to software and/or equipment (which you do allude to in your article already) to properly assess and/or run supplied code (especially code that uses proprietary programs, e.g. Matlab and the like).

On 2017-09-11 18:26:52, user Biswapriya Biswavas Misra wrote:

Hello,

Nice data and work.

The Proteomics and Transcriptomics data are archived.

But, why not also archive the Metabolomics CE-ToF-MS and Lipidomics data somewhere in these Metabolomics Databases, Metabolights, UK: http://www.ebi.ac.uk/metabo... and/ or MetabolomicsWorkbench: http://www.metabolomicswork... or GNPS/Massive: https://gnps.ucsd.edu/Prote...

Thanks,<br /> Biswa

On 2018-03-20 15:06:43, user Hannes Almgren wrote:

Code for reproducibility is available at https://github.com/halmgren...

On 2024-11-20 14:47:46, user MD Devignes wrote:

This is a preliminary version of our study on HLA epitope recognition. A more advanced and peer-reviewed version is about to get published in Bioinformatics Advances (DOI: 10.1093/bioadv/vbae186).

On 2019-09-11 19:38:29, user Jing Yong wrote:

Updated version is now available at: <br /> https://elifesciences.org/a...<br /> Jing

On 2019-08-22 14:55:56, user Kathleen wrote:

Cellular pH rules insulin secretion. Important finding!

On 2025-10-08 15:32:30, user M.A. wrote:

Great work. It would seem that the "baseline setting" (Figure 2) is unfairly favoring the semi-supervised methods. The same labels are used as input to guide integration AND for performance evaluation; this allows ss-methods to overfit the data, especially scGen and scDREAMER, which have many parameters. Wouldn't it make sense to report the rankings based on a more realistic scenario, such as one with partial annotation or partially incorrect labels?<br /> On another note, silhouette coefficients have been reported to be suboptimal for this kind of benchmarks, and more appropriate metrics have been proposed, see e.g. https://www.nature.com/articles/s41587-025-02743-4

On 2021-01-27 22:50:46, user Timothy En Haw Chan wrote:

It is published on https://doi.org/10.1016/j.c...

On 2016-07-29 19:24:16, user David Suter wrote:

Interesting paper; the formaldehyde fixation artifact for mitotic chromosome binding of TFs has been described before and methanol/acetic acid fixation seems to do the job:

http://www.sciencedirect.co...

http://www.molbiolcell.org/...

On 2017-06-06 15:10:19, user Vivek Das wrote:

must say it was a pleasure reading this pre-print! Something I would like to try if our lab again invests on cancer exomes and I am big fan of driver mutational analysis.

On 2023-05-09 07:22:54, user Cedric Maurange wrote:

Beautiful work really, congrats! Would be nice to acknowledge the previous work on Chinmo and Broad in the neuroepthelium:<br /> - Dillard C, Narbonne-Reveau K, Foppolo S, Lanet E, Maurange C. Two distinct mechanisms silence chinmo in Drosophila neuroblasts and neuroepithelial cells to limit their self-renewal. Development. 2018 Jan 25;145(2):dev154534. doi: 10.1242/dev.154534. PMID: 29361557.<br /> - Zhou Y, Yang Y, Huang Y, Wang H, Wang S, Luo H. Broad Promotes Neuroepithelial Stem Cell Differentiation in the Drosophila Optic Lobe.<br /> Genetics. 2019 Nov;213(3):941-951. doi: 10.1534/genetics.119.302421. Epub 2019 Sep 17. PMID: 31530575; PMCID: PMC6827381.

On 2017-06-06 03:57:37, user count0interrupt wrote:

In abstract, there is singular-plural subject to verb disagreement that should be corrected: "estimates dramatically increases".

On 2017-07-03 05:19:14, user sandeep chakraborty wrote:

Please see the comments section of the original version of this paper for a debate on the validity of the TEP-paper.

http://www.biorxiv.org/cont...

On 2022-10-23 03:08:24, user Alex Crits-Christoph wrote:

Genomic and phylogenetic evidence proves this preprint false for a very simple reason: the 'endonuclease fingerprint' observed in SARS-CoV-2 is also present in the bat coronaviruses most closely related to SARS-CoV-2. Thus, any hypothetical engineer of the RE sites would have to go to enormous lengths to purposefully mimick natural bat coronaviruses that have only been discovered in the past 2 years: a very dubious proposition. The far simpler alternative is that the sites evolved via natural recombination from natural bat coronaviruses.

Further, if one examines the genomic regions around each restriction enzyme sites, we find that SARS-CoV-2 shares general genetic similarity with the virus(es) it shares the RE site (or lack therefore) with. This would further indicate that they were inherited via recombination. For example, two BsaI sites missing in SARS-CoV-2 are also missing in the RpYN06 batCoV, which follows naturally from the phylogenetic prediction that RpYN06 is the nearest neighbor in that region. Correspondingly, SARS-CoV-2 shares not just the lack of the BsaI sites in this region, but several other mutations as well: a signal entirely inconsistent with engineering and entirely consistent with natural recombination. The same is true with other natural batCoVs if you examine any of the RE sites described in this work.

For the engineering hypothesis, this would have to imply that someone not only modified the RE sites to match natural viruses, but also unrelated nearby sites as well - an even more ludicrous proposition that I do not think even these authors can defend.

Finally, this sort of analysis can be be done systematically by reconstructing a recombinant ancestor of SARS-CoV-2, as the two papers below did:<br /> https://www.nature.com/arti...<br /> (See Fig 2)<br /> https://www.science.org/doi...<br /> (See Fig 6)

The recombinant ancestor is a reconstruction of the common ancestor of SARS-CoV-2 and other known bat viruses in each region of the genome. The recombinant ancestor of SARS-CoV-2 indeed shares the exact BsaI/BsmBI RE pattern of SARS-CoV-2, minus a signal synonymous mutation: thus further proving that these sites were naturally acquired via recombination. This follows intuitively from the observation that different bat viruses each have some of the RE sites described in this work, and that each bat virus that shares an RE or lack therefore with SARS-CoV-2 is the most recent common ancestor of that genomic region.

For more, please read:<br /> https://twitter.com/flodeba...<br /> https://twitter.com/acritsc...<br /> https://twitter.com/K_G_And...<br /> https://twitter.com/zhihuac...

And the data described in my comment is fully available at:<br /> https://github.com/alexcrit...<br /> In particular, the file with 'alignment-with-RpYN06.fasta' which includes a comparison with several batCoVs ignored in this preprint.

Let us be clear, this is firm phylogenetic proof that the RE pattern in this work is natural. I would not use the word 'proof' lightly in science, but if we cannot use it in such a clear circumstance, we cannot use it at all. If the authors have any integrity they should gracefully retract their work here.

On 2022-06-17 09:46:09, user N van Hilten wrote:

The peer reviewed version of this paper is now published in the Journal of Chemical Theory and Computation (JCTC). https://pubs.acs.org/doi/fu...

On 2017-01-28 12:37:12, user Ratnesh Tripathi wrote:

Good and interesting findings.<br /> Canu is a haploid assembler, so it did fairly good assembly for a homozygous clone in nile tilapia. <br /> Please include the stats of alternate assembly (a_ctg.fa) obtained in FALCON assemblies to have insights for persistence of heterozygosity in homozygous clones, if any.

On 2020-10-07 09:42:53, user David Peters wrote:

Unfortunately, genomic studies too often recover false positives in deep time studies when compared to phenomic studies, the only studies that include a wide array of fossil taxa. In an online phenomic study Vulpavus, Protictis and Nandinia are basalmost Placentalia, the outgroups to the Carnivora, the basal-most of the placental clades. Talpa is an overlooked extant member of the Carnivora. Ursus arises apart from dogs and cats, which find last common ancestors in Tremarctos, Speothos and Borophagus. Arctodus, the short-faced bear, is a giant wolverine (Gulo). Seals and sea lions have separate terrestrial ancestors and became aquatic by convergence. Online cladogram here: http://reptileevolution.com...

On 2019-09-12 07:30:00, user Prof. Calum Semple wrote:

Effective shunt fraction - eGFR for the lung will be included as a secondary outcome measure in the @BESStudy where we will trial endotracheal surfactant in infants with life threatening #Bronchiolitis

On 2020-01-18 17:34:02, user Sirius wrote:

Very great insight into what's in these dangerous vaporizers. One question though, is it not possible that all those siloxane compounds come from column bleed? Also, it would be useful to see a table with the match qualities, and an example chromatogram. It's also useful to highlight that making an identification of a compound based on comparison with a mass spectrum from the NIST library qualifies as a tentative identification, not a full identification.

On 2019-09-20 10:33:38, user Julie Tucker wrote:

A great read - modelling as it should be done; informed by and informing biological insight and mutational studies. Would be good to see some statistical significance statistics on Figure 5. And are the suppressor mutants still responsive to cytokine stimulation? Perhaps this information is in the supplemental, which I have yet to find on biorxiv.

On 2022-03-22 18:03:56, user Emily wrote:

Hello authors,

Thank you for posting this excellent article on the gut microbiome in adult gars. I do, however, have a few comments and questions on your study.

First, you mention that you are studying the GMB of the fish. You describe this acronym as the gut emicrobiome; however, when I researched this acronym, I was unable to find anything. Is this a typo? Where could I find this information?

Second, I was confused about the sample collection of the gar. How did the fishermen catch the fish, specifically what bait was used? Would this affect the gut microbiome of the gar? What food was fed to the fish grown in the lab? Were there significant differences in the GMB based on the collection method? Following that, you state that you squeeze the GMB; I am confused about how you obtained the feces. How did you squeeze the gut microbiome? Would this affect a change in the location? Would you be able to elaborate further on this?

Next, while investigating your methods sections, I found some missing information in your PCR step. To improve your study and help end the replication crisis, I would add the PCR cycle number and temperature for this amplification. Thank you for including the variable region and specific primers you used.

Finally, I read your sections on bioinformatics and phylogenetic analysis and had a suggestion. When I first read the paper, I could not find your Good’s coverage and how you clustered the OTUs. I would move the information on how many clustered sequences and the similarity percentage right after removing the chimeras. Moreover, I was curious about an internal standard for sequencing and clustering analysis. I suggest adding a known strain you grew in the lab to the sample as to confirm that your sequences and binning are correct. Another suggestion would be to elaborate on why you adjusted the identity percentage to 99% with a coverage of 70%. Did this help with the phylogenetic analysis? Is this a quality control for the phylogenetic analysis similar to chimera removal?

Overall, this study highlighted the gut microbiome of tropical gar and allowed for further research questions to be asked. I appreciate the amount of information on the method section and implore you to add my suggested feedback. Thank you for your time.

SHSU5394

On 2019-12-16 15:00:23, user Thomas Munro wrote:

I think it would be of interest to give the proportion of mutants that fall into a given category (e.g. constitutively active, loss of function, etc). Also, for readers from other disciplines, a brief description of how to interpret the activity values in Supplementary Table 1 might be helpful, i.e. "a value greater than 1 represents ..."

On 2017-09-29 21:48:33, user darachm wrote:

I don't see the supplementary files in the PDF. Is there another file?

On 2019-02-04 09:48:36, user M B wrote:

Published version now available in Ecology and Evolution under new title: 'Effects of model choice, network structure, and interaction strengths on knockout extinction models of ecological robustness'<br /> https://doi.org/10.1002/ece...

On 2019-11-27 23:46:02, user John Bowman wrote:

Can confirm archaea have negigible presence in Atlantic salmon (based on direct Q-PCR - coming manuscript). Most (but not all) of the taxa from hatcheries will replaced after smolt undergo marine insertion (see https://www.nature.com/arti... and https://sfamjournals.online... "https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/jam.12514)").

On 2020-12-02 12:26:25, user Elin Sørhus wrote:

Article is now published in Science of the total environment: Doi: 10.1016/j.scitotenv.2020.143896<br /> https://authors.elsevier.co...

On 2025-07-17 03:49:26, user Mike Kalwat wrote:

published: https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00605-9

On 2021-02-19 09:18:00, user Stéphane Ory wrote:

Hi, nice work. I was wondering why you looked at Dyn2 and not Dyn1 which is expected to be the major form of Dynamin in neurons?

On 2023-05-06 15:50:59, user Marcelo Kauffman wrote:

Do you have a github repository with the scripts and data used for training and validating?

On 2024-12-26 20:12:49, user Huy Le wrote:

Now has been published in Advanced Science: https://onlinelibrary.wiley.com/share/GRXAEZQFHDVMNTTIKBN8?target=10.1002/advs.202406751

On 2020-03-23 03:32:41, user ppgardne wrote:

Looks like a very interesting preprint. Is there a supplementary material? In particular, where is Table S5 available?

On 2024-04-09 16:42:36, user Michelle Meyer wrote:

This article has been published:<br /> https://doi.org/10.1371/jou...

On 2020-04-16 12:20:55, user Mukesh Mahajan wrote:

A recent article on "Paratope prediction and its application to ab-ag docking" is really very nice work by Bonvin group. This article will significantly guide researchers about structural understanding of HV regions in the antibodies. However, I was unable to understand how to select the probable residues involved in the ab-ag interaction from the probability plot (output)?

On 2020-08-10 14:43:33, user Renzo Huber wrote:

The manuscript entitled “Estimation of laminar BOLD activation profiles using deconvolution with physiological point spread functions” promotes the usage of layer-dependent GE-BOLD models to account for venous drainage effects in laminar fMRI signals. <br /> The described study uses previously acquired data and a previously developed laminar vascular model to show that the model can be inverted for the removal of unwanted vein effects ini GE-BOLD data.

The research field of layer-fMRI is gaining a lot of interest these days. And the effect of draining veins is one of its major limitations. Thus, the proposed solution in this manuscript will be very relevant for a wide readership.

There are more than a handful of layer-dependent vascular models published out there. The one described here stands out in its elegant simplicity, user-friendly applicability, and careful validation with experimental results.

I enthusiastically support the publication of the study in it’s present form. <br /> Though, if time constraints permit, I believe the manuscript could be further improved by considering the following specific point.

1.) <br /> There are quite a bit of parallel efforts to model (and ultimately remove) venous drainage in layer-fMRI. While the authors (rightfully?) ignore most of these efforts that are not from their own group or the Uludag group, I would find it appropriate to acknowledge all of them to some degree somewhere in the manuscript:

Heinzle J, Koopmans PJ, den Ouden HEM, Raman S, Stephan KE. A hemodynamic model for layered BOLD signals. Neuroimage. 2016;125:556-570. doi:10.1016/j.neuroimage.2015.10.025

Puckett AM, Aquino KM, Robinson PA, Breakspear M, Schira MM. The spatiotemporal hemodynamic response function for depth-dependent functional imaging of human cortex. Neuroimage. 2016. doi:10.1016/j.neuroimage.2016.06.019

Lacy TC, Robinson PA, Aquino KM, Pang JC. Cortical Depth-Dependent Modeling of Visual Hemodynamic Responses. bioRxiv. 2020. doi:10.1101/2020.03.16.993154

Corbitt PT, Ulloa A, Horwitz B. Simulating laminar neuroimaging data for a visual delayed match-to-sample task. Neuroimage. 2018;173(February):199-222. doi:10.1016/j.neuroimage.2018.02.037

Merola A, Weiskopf N. Modelling the laminar GRE-BOLD signal: integrating anatomical, physiological and methodological determinants. In: Proc Intl Soc Mag Reson Med. ; 2018:2299. https://cds.ismrm.org/prote....

If the authors find it appropriate, they could even refer to a recent layer-fMRI analysis suite that uses the author’s P2T-PSF model to deconvolve the GE-BOLD data one a column-by-column basis with user-defined P2T values as described here: https://layerfmri.com/devein/

Huber L, Poser BA, Bandettini PA, et al. LAYNII: A software suite for layer-fMRI. bioRxiv. 2020:1-20. doi:10.1101/2020.06.12.148080

2.) <br /> If I understand the model correctly, the appropriate P2T-values depend on the number of layers that the data are binned into. Maybe the manuscript would benefit from a discussion about this and maybe the authors could add an extra Table of how the reported values of P2T values in the range of 5-9 for 16 layers refers to any other commonly used number of layers.

3.) <br /> I am not sure if I fully agree with the simplified statement of lines 63-67 that tries to disregard all sequences (but GE-BOLD) as “low-sensitivity”. I would recommend the authors to expand a bit on what they mean here. Maybe it would even be appropriate to add an entire paragraph in the discussion section about the “sensitivity” of their proposed model too.

I think it would be appropriate to discuss whether the “sensitivity” of GE-BOLD and its alternatives is referring to the desired laminar signal or instead if it refers to the sensitivity of unwanted artifacts. In fact, I believe most of the large GE-BOLD sensitivity is coming from low spatial frequencies. Whereas the detection power at high-spatial frequencies (at the laminar scales), however, is rather low: even lower than some non-BOLD methods. Thus, I would like to encourage the authors to rephrase the above referred statement.

In this context, I find that it would be appropriate to also discuss the “sensitivity” of the laminar signals upon the deconvolution. E.g. I happen to know that the strong GE-BOLD sensitivity with 8-10% signal change is reduced to weaker 4%, when going from GE-BOLD to VASO. This is a dramatic sensitivity loss of approx a factor of two.

With the proposed deconvolution model, however, the original BOLD sensitivity of 8-10% at the surface is reduced to 3% at the surface (compared Fig. 2a and 2b). This is an even stronger sensitivity loss; more than a factor of two.

I would recommend to the authors to comment on their view of the sensitivity in the manuscript.

4.) <br /> The two datasets that were chosen here have been previously somewhat criticised in the field about the risk of double-dipping. I think, the manuscript would benefit from a brief discussion about this:

The underlying assumption behind the “leakage free” profiles from Fracasso et al., should be explicitly mentioned. I would believe that there is a class-5 principle diving vein every 400-500 micrometer (Duvernoy). Thus, it is surprising that the flat profiles extracted from 0.5mm data are considered to be leakage-free. In my opinion, as long as there is noise present in a collection of several thousand profile samples, one can always find and pick a subsample of profiles that match the expectation. One could even do so with experimental data that are acquired without excitation pulses :-) Selecting the profiles based on the same features that are of interest might be considered double-dipping by some people.

The underlying assumptions behind the vertical alignment (lines 353-354) of layer-fMRI profiles in the Koopmans et al. data has been criticised in the field. Aligning many noisy profiles based on laminar features that are later used for the analysis might be considered double dipping by some people.

Maybe the authors can comment, why the current study is not at the risk of double dipping.

5.) <br /> I believe the statement about the baseline hemodynamic condition (line 309) could be extended. In the neuroscience application community (e.g. recent de Hollander paper) there might have been a bit of a confusion about the sensitivity to baseline physiology in the combination of layer-dependent vascular deconvolution. Maybe the authors can extend the discussion with the following points.

Does the deconvolution still allow applications that assume linearity? <br /> -> E.g. is the deconvolved signal difference of task A and task B the same as the difference between the deconvolved signal of task A and the deconvolved signal of task B? <br /> -> E.g. is the deconvolution applicable to task modulations that happen on top of a non-baseline background activity.<br /> -> E.g. what happens if my inter-stimulus intervals are too short for the signal to go back to baseline? Can I still apply the deconvolution signal, then? <br /> -> E.g. If I just add a 1% offset on the y-axis of Fig 2a, the neuroscientific conclusion about the relative difference of the layers would be unchanged. However, would the shape of the devonvolved signal in Fig. 2b still look the same? Would the neuroscientific interpretation still be the same for the devonvolved layer profile with such an additive offset?

6.) <br /> Maybe the authors can briefly mention the existence of blooming effects of large pial veins and whether they are accounted for in the model.

7.) <br /> I found it a bit hard to interpret the similarity of the multiple TEs in Fig. 3b. However, normalizing the profiles on the y-axis would help. Maybe the authors might consider including an additional panel like they showed it in their 2016 ISMRM presentation (minute 1:50): https://youtu.be/7s2o2I0QrW... I found that figure very informative.

The above comments are submitted to BioRxiv and the journal in the same form.

On 2025-07-07 07:47:13, user Pietro Roversi wrote:

Pioneering work that pushes the boundaries of human PPI hypothesis making and fully realises the promise of many earlier pieces of work such as https://doi.org/10.1073/pnas.0805923106 and https://doi.org/10.1126/science.abm4805 . As the signal underpinning the hypothesis on novel PPIs is harvested from MSAs - this tool also enables novel hypothesis making on the interactomes of most Eukaryotic proteomes!

One detail: as the authors have already acknowledged in full, some of the complexes in Figure 5 can be easily improved if tools to detect self-association are brought to bear on stoichiometry, and models are built that allow for multiple copies of certain subunits that are oligomeric or present in more than one copy in the complex.

In particular, the TZC complex in Figure panel 5I likely misses additional copies of B9D1, B9D2, TMEM216, TMEM107, TMEM218 and TMEM231. TMEM67 and TMEM237 are also likely dimeric across the interface to neighbouring complexes - giving the TZC the ability to polimerise.

I am looking forward to the final published version of the paper.

On 2018-12-30 00:57:31, user José Feijó wrote:

Maurice MJ Martens from Nijmegen Univ made wonderful studies on the acoustics of plants e.g. https://asa.scitation.org/d... "https://asa.scitation.org/doi/10.1121/1.385313)"), you guys should check it, to my knowledge he has not done anything like this, but he was a true pioneer and should be acknowledged by that

On 2019-05-08 11:43:44, user FEGraf wrote:

Where can I access the supplementary data?

On 2017-12-12 07:33:39, user Robyn Hall wrote:

This is now peer-reviewed and available at: 10.1111/tbed.12779

On 2022-08-27 15:52:20, user Mark A. Hanson wrote:

The first version of this article was accidentally missing its Acknowledgements section. This has been rectified in v2. To ensure this information is present regardless of manuscript version, we would like to additionally post this information here:

We would like to thank Samuel Rommelaere, Jean-Philippe Boquete, Emi Nagoshi, Lukas Neukomm, Kausik Si, and Anzer Khan for helpful discussion. We would also like to thank Brian McCabe, Mariann Bienz, Barry Ganetzky, Steven Wasserman and Lianne Cohen, the Vienna Drosophila Resource centre, and the Bloomington Drosophila Stock Centre for fly stocks requested over the course of this research. This research was supported by Sinergia grant CRSII5_186397 and Novartis Foundation 532114 awarded to Bruno Lemaitre.

On 2020-02-14 18:42:43, user Arthur Jenkins wrote:

Inadmissible evidence in obesity genetics

Background<br /> My initial interest in this area came out of an interest in adiposity and the various well-recognized failings of existing phenotypes as proxies of the underlying pathophysiology and genetics of obesity. Our initial report of familial segregation was an unexpected result of testing a new rationally constructed phenotype against diabetes family history in a small convenience sample [1]. We saw that result as generating an hypothesis requiring further testing and identified the NHANES data set as the most powerful available to us. We conclude that we have replicated and extended our original finding in the NHANES data [2].

I provide this history, which is implicit in our preprint [2], to emphasise that we did not arrive at our current position through any pre-conceived model of the genetics of obesity. At the time of publication of our initial study (2013) the claims for polygenes with small effect sizes were modest (1-2% of variance) and did not conflict with our results. Since that time the claims for polygenes have grown to the extent that the strongest of those claims are now in conflict with our analyses and interpretations.

Feedback<br /> Journals<br /> I expected that in attempting to publish our findings I would engage with reviewers familiar with obesity genetics and at least come away with a better scientific understanding of the apparent discrepancies between our findings and those coming out of genomics. Far from it. A first attempt in a specialist obesity journal made clear in a very helpful way that our audience was elsewhere and we decided that we must approach geneticists.

The results were at first just disappointing – rapid editorial rejection by the first two genetics journals tried ("not a good fit", "unlikely to receive favourable reviews") – but then quite startling - the third genetics editor rejected without review on the basis of a mis-statement of the hypothesis tested ("that BMI has a strong, single gene effect detectable in a segregation analysis"). It requires more than ignorance to describe our hypothesis of individually rare, but collectively common, variants as a single gene and we finally got the message that evidence against polygenic small-effects explanations for obesity is inadmissible in the genetics literature.

Preprint<br /> Early tweets visible on the preprint site along the lines of "what do you think?" produced few responses. More recently one directed explicitly at geneticists produced an offsite response from an eminent obesity geneticist "Inconsistent with the direct empirical evidence" (unidentified but presumably GWAS) which led me to an offsite discussion. In that discussion the eminent obesity geneticist defended the strongest claims of the small-effects polygene model using, among other things, an intuition that our results are more consistent with a single gene model, which could then be definitively excluded on lack of genomic evidence: our result must therefore have other unspecified, and presumably artifactual, explanations. My attempts to engage with this discussion have so far (14/02/20) not been successful. Other partly overlapping discussions focus on our lack of genomic data in the context that only genomic evidence is relevant to this area. I have questioned this faith and hope for some response.

Conclusions<br /> The geneticists' responses to our work support the proposition that a polygenic small-effects explanation for obesity is one of those entrenched under-performing big ideas that currently permeate the biomedical literature [3]. It is certainly under-performing in terms of both mechanistic insights into the problem and effective applications, but perhaps not so much in terms of interests vested in the genomics industry, broadly defined. It appears to be entrenched behind a strategy of oxygen-denial to conflicting evidence and the faith of some genomicists in the omnipotence of their methods. It is time to ignore the antagonism of the vested interests and faith-based dismissals and assess our work on other more objective criteria. Perhaps by the epidemiologists?

References<br /> 1. Jenkins AB, Batterham M, Samocha-Bonet D, Tonks K, Greenfield JR, Campbell LV. Segregation of a latent high adiposity phenotype in families with a history of type 2 diabetes mellitus implicates rare obesity-susceptibility genetic variants with large effects in diabetes-related obesity. PLoS One. 2013;8:e70435.<br /> 2. Jenkins AB, Batterham M, Campbell LV. Segregation of Familial Risk of Obesity in NHANES Cohort Supports a Major Role for Large Genetic Effects in the Current Obesity Epidemic. Preprint https://www.biorxiv.org/con...<br /> 3. Joyner MJ, Paneth N, Ioannidis JP. What Happens When Underperforming Big Ideas in Research Become Entrenched? JAMA. 2016;316:1355-1356.

14/02/20

On 2023-02-08 14:37:20, user Mégane wrote:

Very interesting and exciting results !! You might be interested in our recent work about the formation of invadosomes by IPF fibroblasts: https://www.mdpi.com/1422-0...

Congratulations!!

On 2019-07-14 09:02:45, user Cyril wrote:

great work - quick review here https://publons.com/review/...

On 2025-11-03 09:49:04, user ??? wrote:

Hello. This preprint has now been published. Here is the DOI of the publication: [ https://doi.org/10.1002/advs.202501661 ]. Could you please update the status of this study? Thank you!

On 2023-07-10 09:22:24, user Ramon Crehuet wrote:

Now published in J. Chem. Theory Comput.: https://pubs.acs.org/doi/10...

On 2020-01-21 21:46:33, user Trina McMahon wrote:

Hi everyone! The link to the figshare archive in the PDF doesn't work. The current link can be found under "Data/Code" near the top of the page here. Direct link: https://figshare.com/projec...

On 2021-02-08 20:11:04, user Nicholas Markham wrote:

Outstanding manuscript by Pruss and Sonnenburg! Thanks to the authors for posting on bioRxiv. These elegant experiments show how C. difficile toxin-mediated host inflammation alters the metabolic phenotype of C. difficile itself. In particular, the authors identified an inflammation-associated upregulation of the sorbitol utilization locus responsible for permitting increased C. difficile growth in the presence of sorbitol. By altering the host's ability to produce sorbitol, including the use of an aldose reductase knockout, they show differential severity of C. difficile infection. This novel work is exciting because it reveals multiple potential therapeutic targets. I imagine the reviews will be kind. I wonder if looking more at the infected ARKO mice would be helpful: fecal CFUs, fecal toxin amounts, and histopathology.

On 2015-04-08 19:27:33, user Mostly Greek islands ancestry wrote:

Perhaps the EDGAR gene prevalent in East Asian may have contributed to the high cheek bones and straight hair of Scandinavians and many East Europeans compared to my relatively flat cheekbones and curly brown hair from my mostly Mediterranean origins?

On 2021-03-15 14:45:33, user Ron K wrote:

Can the compounds be ingested or do they need to be inhaled?

On 2024-06-17 06:37:44, user Sebastian Gregoricchio wrote:

Now published on Genome Research:<br /> https://www.genome.org/cgi/doi/10.1101/gr.278680.123

On 2025-07-27 22:27:49, user Paul Macklin wrote:

Article is now published in Cell as:

Johnson et al., Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories. Cell (2025). DOI: 10.1016/j.cell.2025.06.048

https://doi.org/10.1016/j.cell.2025.06.048

On 2022-10-20 21:34:50, user Moshe Tsvi Gordon wrote:

In the third and fourth panel of Figure 2F it looks like the low FRET <br /> states might be a result of photobleaching. In those traces did you see <br /> recovery to the higher FRET state or was the transition to a low FRET <br /> state permanent?