On 2020-07-11 21:13:11, user Tim W wrote:

Not sure whether this is a typo, but is the NaCl concentration in the droplet buffer really 150 nM, and not 150 mM?

On 2023-01-24 01:17:12, user Rory O'Keeffe wrote:

The DOI of the published version in IEEE Journal of Biomedical Health and Informatics: https://doi.org/10.1109/JBH....

On 2023-10-11 03:38:39, user Pietro Roversi wrote:

The paper has appeared in https://doi.org/10.1016/j.i...

On 2019-06-25 06:47:33, user JJ wrote:

It would be better to have the tested versions of these tools.

On 2021-11-08 16:42:36, user Nicolas wrote:

The current Preprint has been accepted for publication and a revised version can be accessed here: https://doi.org/10.1111/nph...

On 2025-04-24 16:46:53, user Aaron Feller wrote:

Hello! I have a few suggestions for the manuscript, likely noted by reviewers assuming this was submitted to a journal. First, include the metric used on each dataset for Tables 2 & 3. And second, try using splits that are not randomly selected for evaluation -- KMeans clustering can be done on embeddings or clustering by sequence with MMSeqs2 is another option. This will give a better idea of model generalization to unseen sequences.

On 2020-06-08 12:23:39, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2021-01-14 07:07:41, user Alessandro Stern wrote:

Very interesting preprint! However, where can I download the supplementary table files? Couldn't find them anywhere? Many thanks in advance!

On 2018-04-05 14:43:14, user Perry Evans wrote:

Great paper. Thanks for making the data public. When you build the combined variant deleteriousness scores (MPC, etc) using ClinVar and ExAC as training data, did you remove variants used to train PolyPhen-2 (HumDiv and HumVar3)? If not, could PolyPhen-2's inclusion and weight in the final MPC classifier result in part from some ClinVar and ExAC variants being present in PolyPhen-2's training data?

On 2018-11-27 13:09:02, user wint wrote:

cool

On 2019-10-01 16:21:31, user James Albert wrote:

This is a fascinating study in several regards. One thing that caught my eye is the big red dispersal vector in Fig. 5 from the Amazon to Atlantic Forest at about 10 Ma. Although paleogeography is not discussed in this paper, this dispersal event is coeval with the origin of the modern transcontinental Amazon river, an epochal event that allowed the diverse biota of the Western Amazon to colonize the Eastern Amazon and it's major tributaries on the Brazilian Shield and Dry Diagonal.

See e,g. Albert, J.S., Val, P. and Hoorn, C., 2018. The changing course of the Amazon River in the Neogene: center stage for Neotropical diversification. Neotropical Ichthyology, 16(3): e180033[1]

On 2017-10-27 20:31:08, user David Pitt wrote:

Will, thanks for pointing out the typos (rs7665090 not rs7665080). Will put up a corrected version

On 2020-03-31 15:43:46, user David A.Carlson wrote:

This work was done without using gas chromatography (GC) to find which actual sugars were present. I don't understand why not. So much more detail is possible using GC.

On 2021-03-08 13:00:57, user Rick Sheridan wrote:

Great work - really glad to see attention on natural plant extracts against SC2 replication such as the study of artemisia annua. I hope the comments below will be seen in that light - 80% supportive, 20% constructive critical review to support it becoming even better:

My lab would be very happy if the relevant active phytochemicals in a. annua or a. afria for potency against SARS-CoV-2 replication were identified, whatever they are. That said, I feel that members of the flavonoids class haven't been ruled out yet: While valuable to recognize and assay flavonoids as a monolithic class, there are still very different flavonoid molecules among them that cluster to make up the different classes of flavonoids (flavans, flavanones, etc.). Then there are the glycosidic states of each flavonoid - i.e. does it have one or two sugars attached via a glycosidic linkage? Our in silico modeling shows that these states can have profound effect on limiting SARS-CoV-2 replication. (Note this critique doesn't apply to the statements made with regards to artemisinin, being one single unambiguous molecule)

It would be very easy for a an operative flavonoid molecule to show up more in one cultivar of a. annua than another, such that even while no association could be shown to total flavonoids, rather that individual flavonoid species vary across the cultivars in such a way that studying a correlation of "flavonoids" collectively against viral inhibition would mask. Our posted work provides justification for just such flavonoid candidates specific to a.annua, and I would be happy to direct these diligent authors toward it with accompanying context.

Rick Sheridan<br /> EMSKE Phytochem

On 2025-04-11 21:41:10, user Omer Faruk Gulban wrote:

This work is now published with a slightly different title "Selective attention sharpens population receptive fields in human auditory cortex" at: https://doi.org/10.1093/cercor/bhac427

On 2024-02-01 18:30:26, user Plough Jogger wrote:

Is this paper real, as in, has anyone replicated it and gotten it to work? I ask because it was posted in 2017 and this group usually follows up with a peer-reviewed version, yet, I don't think there is a peer-reviewed version and its been 6 years.

On 2017-05-02 14:56:24, user Peter Doshi wrote:

I very much enjoyed reading this proposal. I agree with the need for dramatic improvements in the way journals handle the post-publication modification to articles.

Some general reactions/thoughts:

1. Newspapers vs. Scientific Journals. I find it difficult to pinpoint the key difference between newspaper articles and scientific journals, making me wonder why the simple approach many newspapers have taken to amending articles cannot work for scientific journals, or at least be the basis for the approach journals take? I think the key would be that journals would do a better job at allowing an audit trail. The audit train would make transparent the nature and timing of the changes, make obvious to the reader which version they are viewing at any given time, and add on electronic features such as the ability to compare any two versions a reader wants to compare, showing tracked-changes version between those two versions.

2. What to call it. I agree with the authors that terms like “correction” and, in particular, “retraction” are problematic in that they are perceived to necessarily convey more than the straightforward act of a post-publication change to an article. I agree that the term “amendment” is neutral, but I have trouble with it. My trouble is that one dictionary definition of “amendment” is a “minor change in a document”, whereas you are conceiving this as an overarching term including changes that may be large. My second difficulty is that it suggests adding something to the document, as in an appendix, not necessarily changing the document itself (albeit in ways that are transparent). Did you consider “alteration”, “version”, or “revision”? Journals generally use “revision” to characterize different version of a manuscript in the pre-publication phase. Is there any good reason not to use it post-publication? There can be minor revisions and major revisions, insubstantial, substantial, and complete revisions… so the term has the flexibility I think you’re looking for.

3. In terms of contextualizing the topic, I think something needs to be said describing the old world of print only vs. the new world of print and online. With print, there was a clear ORIGINAL publication. No matter how flawed, once printed on paper, one couldn’t amend the true original in the library stacks, but only issue further statements ABOUT the article (corrections, editorials, notices of concern, retraction NOTICES). With online comes the possibility of editing the original – or at least what appears to be the original (i.e. the version people will see when they attempt to access the publication from the publisher’s website). This added complexity can help reduce the propagation of errors (small or large) that may have existed in a publication.

4. This point is not just stylistic. I think it gets at the heart of whether or not the first published version should means anything special. We are used to thinking it does. But the authors discuss protocols (under “A proposal for the future”) which raises the question of publishing documents that have mostly not undergone editorial processes. So when does the first version start, and what does it represent? Is it the first version that the authors ever drafted or is it the version accepted for publication i.e. the culmination of many revisions pre-publication? Is the idea that once a document is made public (i.e. published), then thereafter, all changes, big or small, will be tracked?

5. What does one do in the event that editors are convinced of an error that needs correcting but the author(s) adamantly refuse? I know the correction notice can carry words to the effect that the editors are fixing what they deem to be an error but if the authors disagree, will the actual article be amended yet still carry the authors names in the byline? That seems highly problematic as it attributes words to them that they do not stand by. The only way I can see to deal with this is to issue, depending on severity of error, a retraction against authors will or, alternatively, a linked ‘expression of concern’ but not change the actual text of the article. Any kind of modification of the original where even one author dissents seems problematic. It would get even more complex if some authors agree with the amendment yet others do not. Do we get version forking with editors to decide which version is served up as “current”?

6. I would avoid introducing protocols into the single-stream publication proposal. Protocols are one of many essential documents involved in research. A research paper another one of those essential documents – but again there are many important documents with research. Protocols often go through their own many revisions and, practically speaking, are different files on one’s computer that may exist simultaneously to a manuscript that is in preparation. It seems to me your proposal should track the versioning of a single document – e.g. the journal-destined research report – possibly pre-, but definitely post-publication in a journal.

7. Stylistically, the concept the authors put forward (of conceptualizing the amendment process as containing two distinct elements of (1) editing articles and (2) publishing a notice about the edit) is important and I think can be made clearer earlier on, perhaps giving it its own heading “The amendment model: publish a notice and edit the article itself”.

8. Also stylistically, I would put more emphasis on the point that in the case of a correction, irrespective of the size of the correction, articles available online will be edited so that by default, the version served up to a reader when they visit the article on the web will be the CURRENT version (reflecting all edits/corrections to date), not the version that appeared when the article was first published (with a notice that a correction exists). I think this is a big break from current practices at many journals.

9. The authors note that every publisher has their own strategy for content delivery, and do not make specific recommendations for or against how to display amendments. But it seems to me that display strategies are part of what has got many people feeling uncomfortable about corrections. Many authors probably would prefer to avoid a big bold all caps notice that THERE HAS BEEN A CORRECTION TO THIS ARTICLE at the top of their published article? I think therefore that a specific recommendation for how the reader should be alerted about the existence of amendments should be made. The authors suggest a difference in display between minor vs. other amendments, but I wonder if there should just be one approach in line with the notion of de-stigmatizing amendments.

10. As far as locations for noting the existence of post-publication amendments, newspapers are doing it below the article, often set apart with italicized text. Where will this flagging occur in scholarly publishing? What about proposing certain article meta-data become standard. Just the way Acknowledgements and COI declarations are now fairly standard elements of articles, could a “Current version: X (version history)” line become standard, with a link to a separate document that contains the explanation of the corrections? Or perhaps all articles should contain a "Version history (up to [YYYYMMDD]): On YYYYMMDD, we fixed a typo. On YYYYMMDD, we removed an author for reasons described here (DOI-to-editorial-note-about-research-misconduct)..."

On 2018-06-11 17:44:42, user Terry Oas wrote:

This paper has been accepted for publication in Journal of Molecular Biology.

On 2018-09-08 18:57:48, user PTRRupprecht wrote:

Dear Carrillo-Reid et al.,

Thanks for sharing this preprint on bioRxiv, it is a very interesting read! I have one quick question for you.

As a main asset of your method, you describe that it offers advantages compared to more established methods based e.g. on cross-correlation or mutual information. I think it would be good idea to test this directly. One way to do so (the following is probably not the best way to test this!) would be to use e.g. a correlation matrix of neuronal activities and sum over the columns to get an approximative measure of the respective "neuron's node strength"; and also correlate this neuron's activity with the visual stimuli to get the neuron's predictive performance. Then you could select a cortical core ensemble as in Fig. 2D also based on model-free cross-correlation measures (or something similar) using the two dimensions "node strength" and "predictive performance", which would allow to compare the ensembles selected by the CRF-based selection process and the ones based on a model-free procedure. Right now, the ensembles selected using your method is compared to randomly selected ensembles, but a comparison with ensembles selected using a model-free approach would be much more informative, if I am not mistaken.

Or any other more direct comparison with model-free methods would be really appreciated and would help to better understand the usefulness of the presented method.

I hope that I did understand your method correctly and that you find my comments helpful.

Best,<br /> Peter

On 2023-05-02 16:06:52, user Zach Hensel wrote:

Exploration of these interactive plots shows that it takes a great deal of cherry picking of parameter combinations to put any plausibly infectable hosts at the top of the list of species whose mitochondrial material is most correlated with the abundance of SARS-CoV-2.

I am curious what parameter combinations were attempted and how reasonable it is to call them "cherry picking." Sampling on 1/Jan was biased to locations known to be linked to humans recently infected with SARS-CoV-2 and is expected to show correlation between SARS-CoV-2 RNA and nucleic acids from both humans and species sold at these locations.

Sampling on 12/Jan was biased towards locations known to be linked to wildlife sales without, as far as I know, reason to expect a positive SARS-CoV-2 result by PCR or sequencing.

In my hands, the only "cherry picking" that is required is including samples negative for SARS-CoV-2 and not including sampling from 1/Jan when it was focused on locations of human COVID-19 cases. The result is that samples with reads for "Amur hedgehog" and "Malayan porcupine" consistently rank highly with any choice of parameters otherwise. This is also true if examining correlation between species reads and positivity by PCR.

It is difficult to say it's "cherry picking" to focus on the one day with sampling not biased to locations expected to have reads mapping to SARS-CoV-2. However, I agree with comments by Débarre and Crits-Cristoph that this type of correlation analysis is problematic. In the end, in pointing to multiple species it points to one location. That location and locations and animal carcasses linked to it were subsequently sampled hundreds of times, so clearly investigators saw correlation in this data and acted on it.

On 2019-04-26 22:15:24, user Joylynn Woodruff wrote:

I'm curious as to the names of the specific birds that are migratory and threatened birds. The migratory path should include at least the area north of the Dallas/Ft. Worth area.

On 2021-01-14 13:33:59, user Alex wrote:

Interesting discovery highlighting the interplay between epigenetic proteins and metabolic reprogramming. Great wok by Jamia Millia Islamia University researchers!

On 2025-11-11 14:11:18, 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 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 2018-06-20 16:17:52, user Atul Butte wrote:

Great preprint! You might be interested in our related paper from back in 2010<br /> Extreme Evolutionary Disparities Seen in Positive Selection across Seven Complex Diseases<br /> http://journals.plos.org/pl...

and 2012<br /> Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases<br /> http://journals.plos.org/pl...

On 2020-02-23 11:46:49, user Ben Berman wrote:

I really like this extensive and very comprehensive analysis of DNA methylation changes in normal B-cell development and B-cell derived cancer. The fact that epiCMIT-hypo and epiCMIT-hyper were often correlated is reminiscent of the strong correlation we found between hypomethylation of late-replicating heterochromatin and hypermethylation of PcG-CpG Island promoters in colon cancer (https://www.nature.com/arti..., Figure 6B). Your finding that these two can be de-coupled in several of the B-cell derived cancers including ALL and MM, is fascinating and opens up a new avenue to understand the mechanism. Great work!

On 2023-03-07 20:01:07, user Andy wrote:

Really impressive work!<br /> I'd suggest citing the work of Betsuyaku et al - it's a really cool paper looking at ETI in Arabidopsis and the area of SA response surrounded by a JA response ring -- this is during incompatible reaction (vs your work in susceptible interaction), but is a cool example of spatial response <br /> https://pubmed.ncbi.nlm.nih...

On 2020-03-30 13:50:05, user Laura Uelze wrote:

Dear Shaoting Li, Shaokang Zhang and Xiangyu Deng,

Thank you for your thorough re-analysis of our data!<br /> We agree that the GC-bias has a major impact on serotyping results and should<br /> be taken into account when analyzing WGS data. We have addressed this issue in<br /> our publication and we will continue to promote these findings based on your<br /> preprint as well. As stated in our publication, we encourage the use of<br /> low-bias library prep kits such as the Illumina Flex kit.

We noticed that you were wondering which version of<br /> SeqSero2 was used in our study. Information about all programs and versions can<br /> be found in the supplementary material, Table S1 (https://aem.asm.org/content/aem/suppl/2020/02/06/AEM.02265-19.DCSupplemental/AEM.02265-19-s0001.pdf). As<br /> stated, all analyses were performed with SeqSero2 version v.1.0.0, as version<br /> v.1.0.2 was not released before 30th of September 2019 and we<br /> submitted our manuscript to AEM on 2nd of October 2019.

In regard to the nomenclature, we used k-mer mode<br /> and allele-mode as these are the terms used in the official documentation of<br /> SeqSero2 on GitHub (latest version of the readme, current commit: e599e82).

Please do not hesitate to contact me if you have any<br /> further questions.

Best Regards,

Laura Uelze

On 2019-12-14 01:23:56, user Jeffrey Ross-Ibarra wrote:

Some random thoughts from journal club today:

Overall we thought this was a cool experimental approach to ask some neat questions about inbreeding depression. We're also big fans of the nematode system in that it is both fast and tractable while still being a "real" diploid organism. We did have some places where we were a bit confused or thought things could be clearer, however:

Perhaps we missed it, but would be nice to mention that E464 is a single isofemale line. People were initially very confused by the SFS in Figure 5.

The X-chromosome arguments confused us. Our a priori thought was that selection in natural pops should zap any recessive deleterious variants on the X because males are hemizygous, so that should allow for rapid homozygosity on the X during inbreeding. A bit more depth here explaining the thinking about why we might expect otherwise would help.

We didn't buy the argument (on line 507) that inbreeding == environmental change. This might be true under a scenario in which there is no standing genetic variation, but seems unlikely to be true for an outcrossing population.

It was not clear to us how differences in dominance in MA lines vs natural pops (L440) translates to effect sizes (L445). Is this assuming a correlation between dominance and effect size?

It seemed to us that, given the small size of the genome, population, and number of generations, there was a lost opportunity to compare the results to simulations. Seems like either simulations in something like SLIM or even simulations using the allele freqs in the Ancestor could have been useful to get a better idea of expectations. In several places (e.g. paragraph starting L335) having some expectations of what we think should happen would have been helpful. For example, while impressive, the simple 0.5^X generations of inbreeding expectation (L317) is not particularly realistic given linkage.

I liked the discussion of mating system, especially how trans polymorphisms are harder to select on in an outcrosser. But given that the experiment started with an isofemale line that was then inbred, these don't seem that important here (as you note at the end of the paragraph). I'd be tempted to axe this paragraph.

Fig4 parts C-E look awfully similar because of the huge peak at 0. Why not separate into %polymorphic and the SFS of polymorphic?

Fig5 Needs more explanation and/or redoing. It took us a while to figure out what the lines were, and our interpretation is that runs of homozygosity are literally the white space between lines? Why not make a histogram of the number of ROH in a given window size along the genome? Or the cumulative distribution of ROH as you move along the genome?

Figure 6/7 could benefit from having some expectation of 1) how many SNPs should follow each pattern and 2) how likely the changes in allele frequency are. Both could be achieved (I think) by some simualtions.

L448 Given the known high nucleotide diversity in remanei, it seems like there is a strong a priori expectation that you'd have a lot more mutations than in an MA experiment.

L41 We were confused by this. Our intuition was that larger mutational target size = more sites = higher input of new mutations. Why does a larger mutational target size lead to a limitation of new mutations?

L481: the phrase "positive directional selection" confused some folks. I think "fitness" would be clearer.

L433 and L448 both purport to explain the most likely explanation.

L119 Would clarify to say these are MA lines. This is made clear later on, but I initially thought "populations" meant natural or experimental populations, not MA lines.

On 2020-10-05 10:23:10, user Surajit Chakraborty wrote:

Study by Ghosh et al indicates the role of lysosome as a player of MHV egress. As per data presented in the study, viruses enter the ER-secretory pathway, proceed to Golgi and then gets shuttled back to lysosomes for release. Simultaneous with its participation in virus release, deacidification of the lysosomal milieu has been demonstrated to hamper the antigenic presentation via MHC-dependent antigenic presentation hence dampening the immune response against beta-coronavirus. It would be interesting to investigate whether viral entry from ER-secretory pathway to lysosome is directly associated with the deacidification of lysosomes, or at earlier time points (6hpi, 9hpi) deacidification already gets started as a result of virus-mediated activation/deactivation of host signaling thus setting up a platform for virus egress.

On 2021-12-31 00:05:55, user Greggory Heller wrote:

This is really neat! I've been trying to think about ways to better align datasets across days/across mice, and this looks like a great method to consider.

I noticed that for your examples the two datasets seem to largely overlap - there are members of all cell types in each. Perhaps this would be obvious if I understood the theoretical framework better, but I'm curious - How well would you expect this to work if this weren't the case? If one dataset was missing some cell types? for example extracellular recordings that sample slightly different subpopulations? or even from two different visual areas?

On 2024-11-19 16:24:35, user Jesus Valencia wrote:

An exhaustive analysis of viral diversity in blackflies collected from Onchocerciasis-endemic areas is presented. While it provides valuable data, the study has limitations that affect the coherence between its main objective and results. The title and introduction suggest a focus on neurotropic viruses associated with epilepsy linked to Onchocerca volvulus (OAE), but the results primarily describe viral diversity without providing evidence of these viruses. Possible explanations for the absence of neurotropic viruses are not discussed, nor are methodological alternatives proposed to address this issue. To improve the narrative, it is recommended to reframe the title and present the work as an exploratory study on viral diversity in blackflies.

Methodologically, the sample size (10 blackflies per pool) and the lack of information about the genus of the collected blackflies compromise the representativeness of the data. Additionally, the criteria for excluding incomplete sequences are inconsistent, as incomplete Riboviria sequences were retained, potentially biasing abundance results.

Regarding the figures, Figure 2 lacks a clear description of its columns, hindering interpretation. Figure 3 presents phylogenetic trees with barely distinguishable details, complicating analysis. In Figure 4, the point corresponding to Blackfly flavivirus does not clearly cluster with invertebrate hosts, weakening conclusions about its specificity. Analyses based on PCA and dinucleotide composition are interesting but insufficient to infer viral tropism without experimental validation. The supplementary files, although relevant, lack proper descriptions, and the main text does not specify which supplementary figure to consult, limiting their utility.

Although the study does not successfully address its main objective, it provides an important starting point for future research on the viral diversity of blackflies and highlights the need for further investigation into their relationship with human diseases in endemic areas.

On 2020-10-27 16:34:10, user Kamran Kadkhoda wrote:

What about cross-reacting memory cells from past CoV infections and also what about HLA compatibility issue? These two, among others, will cast doubt on the usefulness of this approach...

On 2019-06-07 14:25:21, user Giorgio Scita wrote:

A revised version of this manuscript has been accepted for publication in Nature Materials.

On 2022-10-31 15:52:49, user Daniel Lüdke wrote:

Figure S3/Line 200: “Moreover, under LL, Pst grew to levels similar to Pst hopM1-/avrE1- (h-/a-), which cannot induce water-soaking (Fig. S3).”<br /> - Pst and the Pst mutant line levels are markedly different

On 2020-05-28 00:39:15, user Elizabeth Molnar wrote:

A novel approach to fundamentals of neurogenesis, one must work for smell and taste satisfaction.

On 2015-10-29 22:28:11, user pandolfatto wrote:

This paper may also be relevant: <br /> Andolfatto P, Wall JD. 2003. Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster. Genetics 165(3):1289-1305

On 2016-04-07 15:33:30, user Ben Ewen-Campen wrote:

My post-pub, pre-print, pro-bono review of this paper is: accept without revisions.

This paper presents a very useful set of tools for the Drosophila CRISPR community, all of which are immediately made publicly available, with detailed protocols - a model for how such work should be presented! In particular, I believe that pCFD5 plasmid for expressing multiple gRNAs will be very useful to many in the field, as well as the ability to do tissue-specific knock-outs using the UAS:gRNA plasmid. I hope that such robust tissue-specific knockouts are generally applicable for other genes.

I was also happy to see that Port & Bullock published their work on the Cpf1 system, showing that while it is functional in flies, it does not appear to be quite as robust as Cas9, and has a relatively high failure rate (which I have also observed myself). I am glad to see such "negative results" (well, not exactly negative) made public, as this will undoubtedly save others much time.

On 2020-03-08 21:35:20, user Saad Khan wrote:

Interesting paper. I think this is an important next step in how we should do microbiome studies. I'm wondering how do you quantify the accuracy and validity of inferred causal relationships? The statistical problem is very high dimensional and probably admits many solutions, so how do you evaluate that?

On 2020-04-29 19:21:27, user Joseph Christian Daniel wrote:

In the 2019 paper "Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica)" it was mentioned 11 dead pangolins and from 2 of them Coronaviridae families were identified. But in the current paper, "Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ?" it was mentioned that "In March of 2019, we detected Betacoronavirus in three animals from two sets of smuggling Malayan pangolins (Manis javanica) (n=26) intercepts by Guangdong customs [11]." Which number is correct?

On 2020-04-22 07:36:48, user jeremiahsky801204 wrote:

Just curious, does anyone have the same problem with not finding the extended data. QQ

On 2021-08-05 09:34:08, user William Martin wrote:

This is really interesting. Life on geochemical H2, geochemical formate and geochemical glycine. Just barely possible, but possible, and taking place.

On 2023-11-16 14:40:43, user disqus_46DQBV9D4A wrote:

Dear Wenderson,

thank you very much for the thorough feedback on our manuscript. We are very happy that you enjoyed the read! I think the preprint club in your lab is a great initiative!

As our manuscript was under review and ultimately accepted in the meantime (https://rdcu.be/drgAc) "https://rdcu.be/drgAc)"), we did not manage to address all the issues you mentioned for the peer-reviewed version.

With respect to PC vs NMDS: we have adopted the method of doing both analysis since PC plots are limited to two variables in each iteration and this can cause statistical limitations with smaller sample sizes (as is the case here). NMDS collapses the variability to two dimensions and does not assume normal distribution. We use these two analyses in a complementary manner (one does not influence the outcome of the other, they are two independent methods). As our interest here was limited to inspect if the data is powerful enough to distinguish expression patterns at the respective time points, we did not focus on further discussion of these tests.

With respect to identifying secreted proteins, we used SignalP5 and TMHMM to identify candidate secreted soluble proteins. This was only mentioned int he methods section and we could have added this in the results section, as well.

We used the pipeline detailed in Figure 4 to identify the transcripts as noncoding. The tool CPC with a cutoff of an ORF length of 200 bp was used for that.

Once again, thank you for your feedback!<br /> Best regards,<br /> Stefan Kusch

On 2017-01-13 21:04:38, user nickloman wrote:

A small suggestion - when talking about 'between run' carry-over, I think you should say 'between wash' carry-over. I would consider a separate run to be one with a new flowcell, where of course no carry-over should be detectable.

On 2020-12-08 14:48:43, user Follicle Thought.com wrote:

Dr. Paus seems to have his hand in most of the important hair research going on. I wonder if there is an early stage therapy in the works for this. The grey hair cure market has been quiet for a long time.

On 2021-09-13 13:06:04, user Gianluca Sigismondo wrote:

Holistic view on chromatin dynamics during the DDR

On 2018-10-21 21:44:01, user George Pamboris wrote:

Reference 56 in the document is refering to dynamic and not static stretching. Please correct.

On 2021-01-29 05:33:26, user Jeff Bowles wrote:

The clocks aren't even the mos timportant part of this paper.....It is the fact that aging is "indeed conserved by evolutona and related to development" This throws a huge money wrench into the Selfish gene theory of aging-theose evolutionary biology professors gonna have some splainin' to do!! ANBd teh second most importna thing abotu this paper are the genes identified involved in he aigng process!! he clocks are rally just a side show compared to these two earth shaking findings!

On 2020-08-13 17:42:59, user Leo wrote:

Place cells are not "only selective to one location". They usually have multiple fields in environments that are of a more naturalistic size than those used in the original place cell experiments. See for example this paper published on 2011: https://journals.plos.org/p...

On 2019-07-15 15:26:12, user Claire Lonsdale wrote:

Very interesting work. I'd suggest that you try an alternative method for inactivating your non-viable RNA control culture using something other than hypochlorite which is well known for destroying nucleic acids

On 2017-08-04 18:24:09, user Sandra Porter wrote:

In figure 4, there's a clear difference between the number of people that say S3 Statistics is important and the number of syllabi that provide evidence that this concept is taught. I wonder if this could happen because faculty might not call out statistical analysis of results as a separate item on a syllabus. For example, I identify blast in my syllabus, but I don't list e values separately. We include using and understanding blast statistics as a part of understanding how to use blast.

On 2024-09-13 15:32:48, user Ibrahim, Tarhan E wrote:

Chung et al. (2024) identified a physical interaction between ERC1 and ATG8e, leading them to explore potential ATG8-interaction motifs (AIMs) in ERC1. Using the iLIR database (Jacomin et al., 2016) for AIM prediction, they found the results irrelevant to the ERC1-ATG8e interaction, indicating a false prediction. Through truncated ERC1 variants, they identified a non-canonical AIM undetectable by current prediction tools, which focus on the canonical [W/F/Y]-[X]-[X]-[L/I/V] sequence. They validated this motif with AlphaFold2-multimer (AFM), a method we previously demonstrated (Ibrahim et al., 2023) to accurately predict non-canonical AIMs, as shown with ATG3. Our findings were later confirmed in humans by Farnung et al. (2023) via X-ray crystallography. Despite their similar approach, Chung et al. (2024) did not acknowledge our prior work

On 2019-01-26 05:30:13, user Andre wrote:

This is a link to my bipolar experiences and background that accompanies this paper: in a LinkedIn article https://www.linkedin.com/pu...

On 2020-12-10 09:45:18, user Sam Andre wrote:

Since there is a lot of debate about whether clathrin plaques/ flat lattices are artefacts of interactions with the coverslip, it would be interesting to see the dynamic lifetimes of plaque vs. pit assembly, and whether they are, at least in part, specific to coverslip facing surfaces. The authors have previously used diSPIMs to observe clathrin and EGFRs (10.1016/j.bpj.2018.11.545). Do they observe distinct modes of clathrin assembly in both coverslip facing and dorsal free surface of the cell? That would be crucial to absolve the clathrin flat lattices of being artefacts. They may be specific to cell-cell adhesion, dependent on alternative splicing. That concept again, needs further experimentation and is probably best done in live organisms as demonstrated by Kirchhausen.

On 2019-09-23 15:47:09, user Edward Musinski wrote:

David, how do you plan to make the adoption of your technologies?

WIthout awareness there is no demand!

On 2018-05-02 15:12:51, user ARB & SILVA wrote:

This pre-print by Robert C. Edgar has the intention to measure differences in the<br /> taxonomic framework of ribosomal RNA databases. For this purpose, he compares<br /> the taxonomic annotations and guide trees of the SILVA, Greengenes and RDP<br /> databases to estimate their annotation error rates. His results show that<br /> overall RDP has an error rate of 10-15% while SILVA and Greengenes both have<br /> 17% (page 2 and 21). He claims that the better performance of RDP vs. SILVA and<br /> Greengenes is due to the fact that RDP uses a fully-automated annotation system<br /> while SILVA and Greengenes are based on a semi-automated procedure involving<br /> manual curation by taxonomic experts (page 21).

First, with respect to the SILVA database there are a couple of errors in the paper:

Page: 9:<br /> SILVA is not only based on LPSN but, like RDP, uses the Bergey’s Manual as the<br /> main source of taxonomy (see https://academic.oup.com/na... and https://www.arb-silva.de/do... "https://www.arb-silva.de/documentation/silva-taxonomy/)"). The SILVA team is even an<br /> associate member of Bergey’s Trust https://www.bergeys.org/tru... and well informed about any upcoming changes in taxonomy.

Page 11: Edgar implies that only for RDP the history of genesis of the datasets is available. This is not true since also SILVA provides all datasets and guide trees back to<br /> 2015 in its archive on the website https://www.arb-silva.de/do....

Second, it is questionable if the comparison as it is presented are justified. The general<br /> idea of comparing taxonomic frameworks is not new and the SILVA team has<br /> already made attempts to quantify and eliminate them see https://academic.oup.com/na.... It is also a general misconception<br /> that we know the “true gene/phylogenetic tree” as stated on page 5, 13, 14 and<br /> 20. Consequently it is impossible to give a clear answer what is correct and<br /> what is wrong with respect to different taxonomic annotations. Taxonomy is<br /> never static, but rather a moving target influenced by the constant insertion<br /> of new sequences in the tree as well as substantially faster the tree<br /> calculation algorithms that allow to reconstruct trees with many more<br /> sequences. Consequently, for each SILVA release the SILVA team spends a<br /> significant amount of time to manually go through the guide tree to provide the<br /> best compromise between the phylogenetic tree and taxonomy. A guideline<br /> describing the “technical” problems in phylogenetic inference has even been<br /> published by the SILVA team in 2008 see https://doi.org/10.1016/j.s....

Keeping this in mind that taxonomy is not necessarily monophyly and any reconstructed<br /> tree is just an approximation of the “true tree” it is rather the rule than the<br /> exception to locate differences in the taxonomic annotations between databases.<br /> Recalling this, the added value of taking the five years old Greengenes<br /> annotations into account for the comparisons can be questioned. If a comparison<br /> is necessary, it would make more sense to correlate the intraspecific<br /> differences of the guide trees over time with the interspecific differences<br /> between the three annotations. My best guess would be that the changes in<br /> taxonomy over time are almost in the same range as the differences between RDP,<br /> Greengenes and SILVA.

In summary the results provided are neither new nor unexpected. It is even a feature of<br /> the three databases to provide different views on the “true tree” of life.

The SILVATeam

On 2019-11-13 14:34:27, user Pietro Pichierri wrote:

Interesting work. I would suggest reading also:

https://doi.org/10.1371/jou...

On 2015-10-07 10:40:23, user Daniel Bader wrote:

Now also avilable here:<br /> http://journals.plos.org/pl...

On 2022-11-07 20:26:55, user George Orwell wrote:

This sentence is ambiguous enough it seems nonsensical: "In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs."<br /> I think I know what the authors are trying to say and not say.<br /> Against BA.2 (the latest, most common variant tested), Sotrovimab (VIR-7831) and VIR-7831 do NOT demonstrate potent in vitro and in vivo activity: Table 1 shows IC50 and IC90 values for Sotrovimab need to be about a thousand and ten thousand times higher than against the Wuhan strain. But everything is being done to avoid making that clear.

To call the oldest strain "wild-type" is inappropriate, as the preponderance of the evidence indicates a lab origin, so there is no wild type.

On 2020-08-14 22:38:02, user Vectorman wrote:

This is a very interesting article and a promising approach. However, the authors should more directly acknowledge prior work on this concept. They cite a Nature Communications manuscript by Maselko et al. yet do not mention that it was a demonstration of the same idea. A Scientific Reports manuscript by Waters et al. is also cited but it is once again not acknowledged that those researchers were working on the very same approach.

Furthermore, the authors should be aware that there is a Maselko et al. bioRxiv preprint (link below) that has demonstrated 100% reproductive isolation in D. melanogaster using this same mechanism which was posted in April 2020 and should be cited if the current work is published in a journal that accepts preprint citations.

https://www.biorxiv.org/con...

On 2022-01-06 01:37:06, user Jacob Roberson wrote:

Hi everyone. I see you've gotten accepted. Two last minute suggestions for the acc ver: First "While researchers have long sought..." sounds like a contrast but it's really two agreeing ideas. I suggest "While researchers have long sought to understand short-term adaptation, decreasing sequencing costs in recent years have made it increasingly practical." instead. --- And secondly: "As a further check for contamination, we checked IBD..." seems to need a "whether" between "checked IBD".

On 2023-12-10 01:55:58, user Bernie Taylor wrote:

Rising Star Cave Engravings – Part II: The Terrestrial Plane https://beforeorion.com/cav...

On 2019-02-26 12:09:58, user Eliécer E. Gutiérrez wrote:

A bit dissapointed not to see our article (see below), which seems highly relevant to this awesome research, cited:

Gutiérrez EE, Boria RA, Anderson RP. 2014. Can biotic interactions cause allopatry? niche models, competition, and distributions of South American mouse opossums. Ecography 37: 741–753. DOI: 10.1111/ecog.00620

On 2019-07-19 12:40:54, user Melissa Andrews wrote:

This is quite the approach to use ordinary optical microscopy for such detailed imaging!

On 2020-04-27 11:24:04, user Vijay Veer wrote:

In India another source major was people returned from middle East after Umra (Haz). Southi Arabia and other gulf countries got the virus from European counties including Italy. Other wise this analyse seems highly relevant.

On 2022-12-01 23:39:27, user Blake Williams wrote:

My name is Blake Williams and I am an undergraduate student in the Biomedical Research Minor at UCLA. I selected your paper for a journal club presentation this quarter and I really enjoyed learning from it and sharing it with my class. We all appreciated how thorough and well-designed these experiments were, the claims made in the paper were all supported by multiple strong lines of evidence. As my group and I read the paper, we had a few suggestions to share with you.

In Figure 2B, protein abundance of the kidney derived and brain derived pre-pro-vasopressin would have been helpful to quantitatively compare the vasopressin levels from each organ.

In Figure 4, I would have appreciated some quantitative analysis of the amount of colocalized Rab3 and pre-pro-vasopressin relative to pre-pro-vasopressin on its own in order to compare the difference between the basolateral, mid-section, and apical levels of the IMCDs.

The methods used in Figure 5 were very creative and the results were compelling and interesting to read!

A figure legend or explanation of the 5 different wells in the Western blot conducted in Figure 8A would make these data more clear.

On a broader scale, I think this paper would be strengthened with a more thorough examination of pre-pro-vasopressin made in human kidneys. The sequence of mature vasopressin is the same between humans and mice, so the same assay used in Figure 5 could also be used to detect if vasopressin synthesized by human kidneys is also active. Additionally, using female mice in addition to male mice would increase the power and scope of these experiments.

I’m excited to see future studies on this topic and the physiological impact and relevance of kidney-derived vasopressin! Looking forward to reading more work from your lab!

On 2017-09-18 19:10:06, user Christoph Nowak wrote:

May consider power calculation (as far as possible as not much published on it in MR)

On 2021-06-08 11:20:16, user Damien wrote:

Thank you for this nice paper ! I think "changes in N (28,880 GAT>CAT, D3L)" should read 28280

On 2019-07-05 11:35:18, user Carolyn Lawrence-Dill wrote:

It's submitted and under review! Comments here would also help, so please do give us some feedback if you have ideas.

On 2020-10-16 07:18:46, user Pablo Carbonell wrote:

Nice tool! I think that it would be great to integrate genome-scale models and dFBA (dynamic flux balance analysis) with the fermentation model. Those models can provide a better picture about having estimates on maximum theoretical yields, performing sensitivity analysis and strain engineering.

On 2025-09-05 10:52:12, user Daniel Paluh wrote:

The peer-reviewed version of this manuscript is now available: https://royalsocietypublishing.org/doi/10.1098/rsos.251196

On 2022-10-12 11:44:01, user Lily Fogg wrote:

Please note that upon peer review, this manuscript was divided into two related papers which were published back-to-back in the Journal of Experimental Biology:

1) Development of dim-light vision in the nocturnal reef fish family Holocentridae. I: Retinal gene expression <br /> Link: https://journals.biologists...

2) Development of dim-light vision in the nocturnal reef fish family Holocentridae. II: Retinal morphology<br /> Link:<br /> https://journals.biologists...

On 2020-09-02 19:29:52, user Nicholas Wu wrote:

Thanks a lot for catching the typo. You are absolutely correct, L490 should actually be L492!

Nicholas Wu

On 2023-11-24 14:55:11, user Guest wrote:

https://journals.plos.org/p...

On 2017-08-09 21:51:03, user Gert Wörheide wrote:

Nice work, congratulations!<br /> However, you might want to reconsider your taxonomy: the species occurring on the Great Barrier Reef is not Acanthaster planci. We know since 2008 (Vogler et al. 2008, Biology Letters) that the crown-of-thorns seastar actually is a species complex of at least four species, and the Pacific one likely is Acanthaster solaris (also called like this in the COTS genome paper). A. planci occurs in the northern Indian Ocean only.

I suggest to consult the following papers:<br /> Vogler, Catherine, John Benzie, Harilaos Lessios, Paul Barber, and Gert Wörheide. 2008. “A Threat to Coral Reefs Multiplied? Four Species of Crown-of-Thorns Starfish.” Biology Letters. doi:10.1098/rsbl.2008.0454.<br /> Haszprunar, Gerhard, and Martin Spies. 2014. “An Integrative Approach to the Taxonomy of the Crown-of-Thorns Starfish Species Group (Asteroidea: Acanthaster): a Review of Names and Comparison to Recent Molecular Data.” Zootaxa 3841 (2): 271–84. doi:10.1098/rsbl.2008.0454.<br /> Haszprunar, Gerhard, Catherine Vogler, and Gert Wörheide. 2017. “Persistent Gaps of Knowledge for Naming and Distinguishing Multiple Species of Crown-of-Thorns-Seastar in the Acanthaster Planci Species Complex.” Diversity 9 (2) doi:10.3390/d9020022.

Furthermore, COTS is not a fish, so better not use "starfish" but seastar ...

On 2018-11-20 00:10:02, user Lauz Bradfield wrote:

Interesting paper. In our rat study (in references) we also found that lesions/inactivations of mOFC left rats with the ability to predict up to about 20-30 seconds in the future intact (in outcome-selective reinstatement and contingency degradation tasks, for example), but unable to draw upon their memory of action-outcomes to drive decision-making when outcomes had not been experienced in the last 20-30 seconds. So that is pretty consistent with the findings here I think.

On 2020-09-24 14:48:15, user Phil wrote:

If they had a camera to observe the test, where are the photos?

On 2019-01-18 20:17:50, user vox_populi wrote:

I will read this, Henry.

On 2017-01-15 16:43:09, user Debbie Kennett wrote:

An alternative method for identifying kinship from ancient DNA was developed by Fernandez et al for the identification of the remains of Thomas Kent, the Irish rebel who died in the Easter Uprising: http://biorxiv.org/content/...

On 2020-04-10 03:01:43, user Xin Wang wrote:

Our paper has already been published online https://www.cell.com/iscien...

On 2024-07-21 16:01:56, user Min Zhu wrote:

The full version of this manuscript is online in Science Advances. https://www.science.org/doi/10.1126/sciadv.adl6366

On 2025-05-01 20:46:20, user Ohad wrote:

This paper was published: https://doi.org/10.1016/j.cub.2025.01.009

On 2014-10-06 19:16:49, user Heather Lander wrote:

Sounds interesting and I will read it in full when I can, but at quick glance an editor would be helpful. For example, in the Abstract, 4th line down, the word "diseases" should instead be "disease". Also in the first line of the intro you have "Transmissible infectious diseases", but by definition, infectious diseases are transmissible so that's redundant. Best of Luck!

On 2019-01-13 12:38:21, user Tim Fenton wrote:

Exciting development @HarrisLabUMN - not an easy task to get a specific antibody for A3B, to say the least and will be a valuable tool!

On 2020-11-22 12:04:47, user Alon Sela wrote:

Very similar conclusions to this work: <br /> Asher, E., Ashkenazy, Y., Havlin, S., & Sela, A. (2020). Optimal COVID-19 infection spread under low temperature, dry air, and low UV radiation. arXiv preprint arXiv:2007.09607.?

On 2023-11-05 08:37:13, user Manuela Giovannetti wrote:

Dear Olga and co-authors,<br /> I have just read your paper and I want to compliment for the high level of your study. Your data are very interesting and worth of depth consideration. I have only a doubt, concerning the retrieval of bacteria other than endobacteria in your spore. As you may know, we have retrieved many bacteria strictly associated with AMF spores (after 15 washings). Actually, you performed a de-contamination of spores, with H2O2 and chloramine T, so you assumed that the retrieved bacteria were endobacteria. As our previous works described the occurrence of bacteria within the different layers of spore walls, I wonder whether they may have been protected from de-contaminating agents in such a peculiar niche. This is why we defined them as "stricty associated". With all my best wishes and regards, Manuela Giovannetti

On 2020-06-20 17:32:01, user stoyan denev wrote:

"The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones"

Detected: https://genetiker.wordpress...

On 2020-04-01 08:45:54, user Liz Miller wrote:

This paper was the subject of the Miller lab weekly journal club and, following a fun discussion of the findings, we have the following comments to make. Please bear in mind that we do not study mRNA regulation or decay, but enjoyed reading the manuscript which was somewhat out of our normal area of expertise.

This paper uses a synthetic mRNA library to examine how changes in a 10 nucleotide sequence preceding an upstream open reading frame (uORF) can alter translation and mRNA stability of both the uORF and downstream ORF. The main findings are that translation of the main ORF is protective to the mRNA, whereas improved translation of the uORF is detrimental to the stability of the mRNA. Additionally, sequences are found that prevent translation entirely, whilst others are shown to enable cap-independent translation of the main ORF. Finally, the degradation pathways that these types of messages might follow are identified. Overall, this seems a powerful tool to study the sequence landscape that is possible for modulating uORF and ORF translation and the effects on subsequent mRNA decay. We were excited to think about how the information in this study could be mapped onto the human genome to understand how frequent the different classes of modulatory sequences are and whether any of these have actually been selected for in evolution (one example, that of an RG4 upstream of NRAS is an exciting first step for this!).

We have some short points of note following our group discussion:

1. The text relating to Fig 1b states that there is a reciprocal relationship between tracer peptide (uORF) and GFP (main ORF) abundance (ie. if tracer peptide is translated, GFP is not). This relationship wasn’t apparent to our eyes in the flow cytometry of Fig 1b, which showed that with the AUG condition, increased tracer peptide was generally accompanied by increased GFP. This is probably due to the plasmid-based system used for expression, since in Supplemental Figure 1b. that used RNA transfection, the effect was clear. We spent quite some time puzzling over this (and some of the other flow cytometry plots), so for a naive reader, additional explanation here might be good.

2. In some experiments presented as violin plots (eg. Figure 2B and C), n is clearly very large and the p-value presented is impressive, but we wondered if it would be more useful to plot effect size rather than p-value for these data. With such large datasets, effect size can be more meaningful in understanding how two populations vary. On a similar note, we thought it would be valuable to include the p-values (and effect size) for the in vitro comparisons of mRNA stability to support the claim that the stability is only different between the populations in vivo.

3. Finally, on a stylistic note, we felt that there was a lot of important data in the supplementary figures, in particular the various experiments that follow up on the potential decay mechanisms for these reporters. The short format does not do justice to the full story!

Thank you for sharing your work on BioRXiv and we hope our comments might be useful

On 2013-11-20 18:24:30, user Aaron Berdanier wrote:

This is exciting work. I have a few quick comments.

It seems like an important aspect of this is that you are getting a much more nuanced picture of water use. I agree that this will be relevant for efforts to predict water use responses to the environment. I'm wondering if you could include some discussion about other efforts to do this (e.g., with time lags, etc.). I think that this will provide definite mechanistic improvements, but it seems like relevant literature to discuss.

Also, I like how you used light sensors for individual leaves. I wonder how many hysteresis analyses use light data that is not representative of the canopy. I would imagine that most light sensors are either on the ground or on top of a tall tower (above canopy), which could be biased indices of what a tree actually experiences. What are the implications of this 1:1 (sap flow to light) connection (and its potential absence in other studies) for your findings?

On 2021-02-04 03:36:46, user Sara Sims wrote:

Reviewer #3 (Minor Comments):

P2, ?3. The authors cite To et al. (2011) for the claim that foveal magnification is greater than peripheral magnification. However, to make this claim, To et al. rely on a number of other citations which would be more appropriate here (?2 of their introduction). A clear example of this is Horton and Hoyt (1991). Additionally, it might be more appropriate to describe cortical magnification as having units of square-mm/square-degree rather than only mm/degree. <br /> We appreciate reviewer 3 for her/his suggestion, we cited Horton and Hoyt, 1991; Azzopardi and Cowey 1993 in the third paragraph of Introduction on Page 3.

P2, ?3. Additionally, the final line of this paragraph addresses receptive field size. It might be of interest to review the finding of Harvey and Dumuolin (2011) [10.1523/JNEUROSCI.2572-11.2011], that the product of the pRF size and the cortical magnification factor are approximately constant across human V1 and nearby visual cortex. <br /> We added the information regarding how receptive field size and cortical magnification factor changes as eccentricity increases through V1 constantly in human V1 and near visual areas in the third paragraph of Introduction on Page 3.

P4, continued ?1. in order to understand what the FEF's inclusion in the Dorsal Attention Network means, it might be useful to introduce the Dorsal Attention Network briefly when discussing the DMN and the FPN. <br /> This sentence was reworded for clarity, including removing reference to the Dorsal Attention Network since it was not relevant to the sentence’s main point.

P4, full ?1. Given the amount of work that has been done on the fronto-occipital and inferior longitudinal fasciculi, the following sentence should probably include a citation or three. "Major white matter tracts that connect to the occipital lobe such as the inferior fronto-occipital fasciculus (connects occipital lobe to lateral prefrontal cortex) and the inferior longitudinal fasciculus (connects occipital lobe to anterior temporal lobe) have been well documented using tractography methods in humans." <br /> We have added this citation to the text in the introduction: “Major white matter tracts that connect to the occipital lobe such as the inferior fronto-occipital fasciculus (connects occipital lobe to lateral prefrontal cortex) and the inferior longitudinal fasciculus (connects occipital lobe to anterior temporal lobe) have been well documented using tractography methods in humans (Wu et al., 2016).” <br /> Here is the full citation: Wu, Y., Sun, D., Wang, Y., & Wang, Y. (2016). Subcomponents and Connectivity of the Inferior Fronto-Occipital Fasciculus Revealed by Diffusion Spectrum Imaging Fiber Tracking. Frontiers in Neuroanatomy, 10, 88.

P4, full ?2. This paragraph is a bit hard to follow and might be improved by breaking it up into shorter sentences. In particular, I'm not 100% sure what the authors mean by "direct and indirect structural connections". Additionally, I'm not sure why the end of this sentence follows from its beginning: "Since functional connectivity between two brain regions could come from both direct and indirect structural connections, we used DWI to examine direct connections between regions (Adachi et al., 2012; Honey et al., 2009) that were previously found to show functional connections." <br /> We have changed the wording of this paragraph to the following:<br /> “The goals of the current study are 1) to assess the reproducibility and generalizability of retinotopic effects on functional connections between V1 and functional networks that were found in prior work (Griffis et al., 2017). We aim to extend these findings in a new dataset collected under different task conditions (previous work used blocks of rest during a task with central fixation and the current data was collected as part of a resting-state only scan). 2) Extend prior work on the retinotopic connectivity difference to structural connections between V1 and functional networks. 3) Examine the relationship between functional and structural connections. Since functional connectivity between two brain regions could be derived from measurable structural connections, we used DWI to examine connections between regions (Adachi et al., 2012; Honey et al., 2009).”

P4, full ?3. Again, the concept of a "direct connection" versus an "indirect connection" appears prior to being introduced. Given that this paragraph marks the concept as critical to the point of the paper, the introduction needs to explain what these are. Additionally, it seems that the paper separates the idea of a direct/indirect "structural connection" from that of a direct/indirect "functional connection". This should all be clearer. <br /> In addition to the text added in response to the above comment the following text has been added to the paragraph referenced in this comment: “the pattern of structural and functional connections is similar, suggesting that this lateral frontal functional connection pattern arises from a direct (uni-synaptic) structural connection.” for additional clarification.

P6, ?3. "Previous work has shown that cortical anatomy is a reliable predictor of the retinotopic organization of V1 (O. Hinds et al., 2009; O. P. Hinds et al., 2008) so that the more posterior parts of the visual cortex represent more central portions of the visual field." At the risk of splitting hairs, the publications by Oliver Hinds show mainly that the V1 *boundaries* are reliably predicted by anatomy. A better citation for the V1 *retinotopic organization* is Benson et al. (2012) [10.1016/j.cub.2012.09.014], wherein we actually assessed the retinotopic maps and not just the boundaries. <br /> This citation has been added.

P6, ?3. "The average eccentricity of each segment was estimated from Benson and colleagues' probabilistic retinotopy template (Benson et al., 2012)..." The correct citation for the retinotopic template is Benson et al. (2014) [10.1371/journal.pcbi.1003538], along with Benson and Winawer (2018) [10.7554/eLife.40224] assuming you are using a recent version of the template, which appears to be the case based on Figure 2 (though given that you are using the FreeSurfer V1 boundary also, I can't really tell). Additionally, it isn't technically correct to call this a probabilistic template (such as might be said correctly of the visual area atlas by Wang et al., 2015). The retinotopic template is more accurately a model of retinotopic organization fit to the average retinotopic organization across many subjects-it does not explicitly express or depend on probabilities. <br /> Wording has been changed to retinotopic template.

P6, ?3. "These ROIs were defined in the gray matter on the cortical sheet for the freesurfer template, then moved into the individual anatomical space for each participant." I believe that the authors' intent here is to state that ROIs were defined on FreeSurfer's fsaverage brain using the eccentricity of the retinotopic template (which is also defined on the fsaverage brain) then were interpolated over to individual subject cortical surfaces using FreeSurfer's anatomical registration. However, I don't have a good prior for what the "freesurfer template" is here or what the "gray matter on the cortical sheet" of it might be, so this may all be wrong. Perhaps the implication is that the ROIs were hand-drawn in the voxels of the fsaverage subject's "ribbon," but if so, is the interpolation back to the individual subject done on the surface or using FreeSurfer's newish diffeomorphic volumetric alignment? <br /> The following text has been revised to further clarify for the reviewer: “These V1 eccentricity segment ROIs were defined on FreeSurfer's fsaverage brain using the eccentricity of the retinotopic template then were interpolated to individual subject cortical surfaces using FreeSurfer's anatomical registration. To avoid the potential for artifacts due to differences in ROI size when comparing probabilistic tractography results, the number of vertices were kept similar (on the Freesurfer fsaverage brain) between eccentricity segments.”

P6, ?3. "To avoid the potential for artifacts due to differences in ROI size, the number of segments per eccentricity region were assigned to more evenly distribute ROI size." Again, this is not at all clear. Earlier text in this paragraph implies that the segments *are* eccentricity regions. Does this sentence indicate that the segments were adjusted in each individual subject to be of a similar size? Or that the ROIs were split into several segments each before interpolation? Is there a material difference between what was done and simply starting with a larger number of segments? It's not clear to my why the process is described in terms of three segments whose eccentricities are reported then redescribed in terms of more segments whose eccentricities are not reported. <br /> We acknowledge that the reporting of the V1 ROI eccentricity segments was unclear. We have simplified the text to be more clear so that it now reads: “Based on this template, 3 retinotopic regions were identified: central vision (mean eccentricity estimates of 0-2.2 degrees visual angle), mid-peripheral vision (mean eccentricity estimates of 4.1-7.3 degrees visual angle) and far-peripheral vision (mean eccentricity estimates of 14.1-25.5 degrees visual angle) (Figure 2).”

P7, ?1. "... voxels within the white matter corresponding to the network ROIs were used as track seeds." I found this initially confusing as immediately prior to this section, "ROI" refers to the ROIs of V1, which should have no truck with the white-matter (i.e., a white-matter voxel predicted to be in an ROI derived from the FreeSurfer's V1 label or the retinotopic template must by definition be erroneous). However, I suspect that this is intended to be about a separate set of network ROIs? This should be clearer. <br /> Yes, there are two sets of ROIs, the V1 ROIs and the Network ROIs. The “network ROIs” has been changed to “network-ROIs” to emphasize this point further. Also, whenever the term “ROI” is used, the name of the set of ROIs being referred to is now stated.

P7, Data Analysis. Again, citing the analysis methods is well and good, but this section should make very clear up front which data were collected/analyzed by the authors and which data were collected/analyzed by the HCP. I should be able to easily tell both what analysis steps were performed *and* which set of authors performed each step. <br /> See response to Reviewer #3 Major Comment #2.

P7, ?2. "Next, right-to-left and left-to-right acquisitions were concatenated into a single 4D volume for the functional connectivity analysis." While I understand from this sentence that the preprocessed images were transformed into single 4D volume files, I do not follow the significance of "right-to-left" and "left-to-right" in this context. <br /> The text of the article has been changed to clarify this: “Next, both the acquisitions (those collected right-to-left and those collected left-to-right) were concatenated into a single 4D volume for the functional connectivity analysis.”

P8, ?4. The text references a "2mm2 Gaussian kernel". Is this supposed to be 2 mm (not squared)? If so, does it refer to the FWHM or to the HWHM or to the parameter ?? It says the "surface maps" were smoothed, but was this done on the FreeSurfer cortical sphere (in which case, mm is a curious unit)? Volumetrically? Something else? <br /> This was a typo it has been changed to “2mm” and the text now reads “Surface maps of the track termination probabilities were smoothed using a 2mm FWHM Gaussian filter and averaged across all subjects.”. This was done with mri_glmfit “fwhm” flag.

P9, ?1. More information is needed about the t-tests that were used. Were these tests one-tailed or two-tailed? Corrected for multiple comparisons or not? How was mri_glmfit used to perform these tests? The help-file for mri_glmfit mentions t-tests only in the context that a certain use-case reduces to a t-test in some circumstances. <br /> We have added “two-tailed” to the text. The mri_glmfit function can be used as a t-test under one sample group mean test with the --osgm flag. We did not correct for multiple comparisons due to the analysis’s design with specific, planned comparisons.

P9, Comparison of Functional and Structural Connectivity. Was only one correlation coefficient calculated? Were the authors not interested in these correlations for the non-central V1 regions? It seems irregular that only one of these would be examined given the experimental setup and the hypotheses of the manuscript. <br /> We have now included dice coefficients, per the reviewer’s suggestion, as well as adding non-central V1 regions in this new analysis.

Methods, generally. In a couple of places, the authors refer to commands like "mri_vol2surf" (P8, ?1). It would be ideal if the command lines or scripts were also provided with the manuscript. <br /> The code has now been added to the code repository.

P9, ?4. "The t-test comparing functional connectivity to different eccentricity segments in V1 revealed significant effects (p<.001) and brain regions belonging to FP, CO, and DMN functional networks (Figure 3)" is the "and" here supposed to be "in"? <br /> This edit has been made.

P9, ?4. It's not clear to me how "preference" was evaluated here. For example, "central representing V1 was preferentially connected (over mid-peripheral and far-peripheral V1) to regions associated with the FP network". Was this assessed by visual inspection? A good quantitative metric would be nice to have here, such as the dice coefficient for each ROI-network pair. <br /> We have added dice coefficients to the analysis. See Tables 1 & 2.

P9, ?4. "Those previous results had also shown differences in connectivity between mid-peripheral-representing regions and far-peripheral representing regions, which were not observed here, (Figure 3)" <br /> This text has been reworded for clarity: “However our results differ in that mid-peripheral-representing regions and far-peripheral representing regions differences were not observed here (Figure 3).”

P10, Figure 3. "There, vertices in yellow showed stronger (z>3) connectivity to central V1 than to both Far peripheral and mid-peripheral regions." I do not understand the significance of "(z>3)" in this caption. Additionally, what is the significance of the gray color shown on all brains in the bottom row? <br /> Clarification has been added to the Figure legend, including “The grey regions indicate the location of the other networks.”

P11, ?1. "... we performed pairwise comparisons of functional connections... Results indicate that ... there are preferential connections between central V1 ..." Again, I'm not clear how preference is being assessed here, or what is being compared pairwise. Pairwise comparisons between segments and networks? What values exactly were compared? If these are referring to visual inspection, that is fine, but the language seems to suggest something more programatic, and what that might be is not clear. <br /> The text has been clarified to now state “We performed statistical comparisons (t-test) of functional connections between central vs far-peripheral eccentricity segments of V1 and the FPN (Figure 4).”

P11, Figure 4. Please tell us what exactly is being plotted. What value minus what value? <br /> The values being subtracted have now been added to all figures.

P14, ?2. "A comparison between structure and function showed overall agreement, indicating that the functional connections are likely mediated by direct structural connections (Figure 6, right column)." Depending on what the authors mean by "mediate" I'm not sure that this follows. Please elaborate. <br /> We acknowledge that this wording is unclear. We have therefore changed the wording of this statement to the following: “These relationships indicate that the overall pattern of connectivity of central V1 greater than far peripheral V1 is consistent across modalities with an especially high overlap within the FPN.”

P14, Figure 6. "Far-peripheral and central V1 are statistically different within the FPN..." How was statistical difference within the FPN assessed? <br /> Please refer to the following section:<br /> “Tractography Analysis <br /> To test the hypothesis that patterns of functional connections previously found in V1 (Griffis et al., 2017) are similar to patterns of structural connections, comparisons were made between the central and far-peripheral eccentricity segments of V1 connectivity patterns to the FPN. Differences in track probabilities corresponding to V1 eccentricity segments connections were compared by paired, two-tailed t-test (using Freesurfer’s mri_glmfit with a one sample group mean test). “

Style/Aesthetic Comments <br /> Throughout the manuscript, starting on P3, full ?1, there are several mismatched parentheses that are distracting. These typically look like this: "some claim is made here (e.g., (Someone et al., 2010) then continues here". Almost all of these could be fixed by removing the "(e.g. ". That said, the use of "e.g., "makes me think that there are other citations that *should* appear here, but haven't been filled in yet, especially given that many of these are broad statements somewhat outside my particular expertise, such as "The fronto-parietal network (FPN) directs attentional control (e.g., (Zanto & Gazzaley, 2013)".

P4, L8. "Markov et. al," should be "Markov et al.," <br /> This edit has been made.

P4, full ?2-3. The authors mix the style "Something listable: (1) first thing, (2) second thing..." and the style "Something listable: 1) first thing, 2) second thing." <br /> This formatting has been changed.

P7, ?1. The acronyms "FP" and "CO" were previously reported as "FPN" and "CON". This needs to be fixed throughout. I get that at times the intention is to represent the deduplication of the word "network," i.e., "the fronto-parietal and default mode network" becomes "the FP and DMN". I think this usage is less clear to readers than "the FPN and DMN" and, besides, the text sometimes says "the FP and DMN networks" (P8?3L3, P9?4L4). Alternately, introduce FP et al. as separate acronyms on P7: "Fronto-parietal (FP), cingulo-opercular (CO), and default mode (DM) networks...". <br /> Abbreviations have been edited for consistency.

Reviewer #3 (Additional data files and statistical comments):

As mentioned in the Major and Minor comments, most if not all of the statistical tests need to be more explicitly described. I could not currently reproduce the exact tests from the manuscript, even if I had the data.

Additionally, because the project is a reanalysis of a large dataset, it would be particularly valuable to have the source code used for analysis. It is nearly impossible to reproduce or assess a project like this without such code.

The code for the analysis has now been added to a repository and it is referenced in the paper.

On 2020-04-24 03:04:22, user Maddy wrote:

Hi. Good paper. I have one suggestion: CtBP1/2 does not interact with LSD1 directly, but via RCOR1 (Corest). CoIP evidence here and elsewhere keep suggesting as if they interact directly. But, they don't. There are several papers and reviews that clearly mentions that they interact indirectly. And in the absence of CtBP, LSD1 may still function as an efficient demethylase. I recommend mentioning it in your text and graphical abstract.

On 2015-12-08 18:06:44, user Aaron Liston wrote:

In Figure 5B, shouldn't there be two different M. peregrinus (green) mt haplotypes? In Figure 5A I would expect more divergence between the two M. peregrinus cp haplotypes.

On 2017-10-04 17:30:45, user Jan Homann wrote:

It looks like you might need to download the Supplementary Videos with a right click, at least in Safari. Otherwise they won't show.

On 2019-02-22 17:01:14, user Rocío Deanna wrote:

Now published in American Journal of Botany:<br /> https://bsapubs.onlinelibra...

On 2024-04-12 15:15:07, user Alaina wrote:

I really enjoyed reading this paper. Very exciting results! I am wondering how the results differed between the cultured genomes and the MAGs? MAGs only represent a population average of a genome, lacking that individual-level genome variability which defenses tend to exhibit. Were the results different between MAGs and cultured genomes? Also if available, I'd recommend including SAGs as well to recover that variability / microdiversity.

On 2025-10-31 14:56:58, user Remi Dulermo wrote:

I think that Fig 1b is not complete since we can not see anything between archaea to asgard. Moreover, you could also more talk about RDR using publication in Hvo (Hawkins et al, 2013), T. barophilus (Mc Teer et al, 2024) and T. kodakarensis (liman et al., 2024) that proposed and proove that RadA is involved into DNA replication. This will be complementary to the biochemical study that you cite in the present paper (Hogrel et al., 2020).

On 2019-02-07 15:55:21, user UMass microbial ecology jclub wrote:

Thank you for this paper. It does a nice job of demonstrating that priming effect is in the eye of the beholder. We read it for journal club today, and I am summarizing some comments and suggestions we came up with, primarily related to the display of the data. This is because the objective set out for the paper (see if bacteria can grow on NOM) is not in line with much of the introduction, experimental design, or interpretation of the results. We suggest 1. see if bacteria grow on NOM, and 2. how the presence of LOM affects this. Figure 1 should then be just NOM minus C-free controls, and a separate figure for just the composite and mix samples were plotted (as figure 2). Even better, just plot the priming effect through time by subtracting the composite from the mix. At present, figure 1 is complete information overload, and making everything divided by or subtracted from some control will go a long way to remedying this. And hopefully also getting rid of the ANOVA tables. We would also suggest plotting the respiration data as a rate rather than cumulative respiration to enable figure 1 and 2 to be viewed more comparably could also be useful.

A strength of your paper is that it shows that whether priming effect exists depends on whether you look at respiration or growth. However, what we are usually interested in when we think of priming is how much of the native organic matter will be lost. If you have any measures of the remaining LOM or NOM to indicate whether more was lost overall under priming, this would be a great addition. Including in particular LOM data from the different components to show if the crash and burn growth was a response to depleting the LOM or whether LOM became limiting would also be very useful in interpreting the priming results.

Finally, a strong theoretical basis for why time matters for priming effect is much needed; is a priming effect real if it is not consistent? What does it mean? How does growing the cells on acetate and then switching them to NOM affect results compared to another source? Do bacteria undergo batch culture in estuaries, or is it more like chemostats? Physiology is very different during different growth phases and this may ultimately change the conclusions made in the paper.

On 2019-07-02 18:41:34, user Wyllian Schartchter wrote:

I was impressed with the effect of CDNF on the transient calcium. Could CDNF have any effect on Ryanodine receptors?<br /> Could the activation of the KDEL receptor act on the Ryanodine receptor?<br /> Great job.Your research tells a story from beginning to end.<br /> WS

On 2020-11-20 22:41:14, user Gunes Parlakgul wrote:

Supplemental videos can also be reached here: <br /> https://www.youtube.com/pla...

On 2020-11-04 16:14:40, user Marie wrote:

Peptides numbers 2, 3 and 4 give homology with Sodium-coupled neutral amino acid transporter 1 isoform X2 (ref|XP_011537088.1|) and Dynein heavy chain 2, axonemal isoform X10 (ref|XP_011521972.1|) from Homo sapiens

On 2019-04-25 07:50:38, user Axel Thielscher wrote:

The results shown in this paper should be contrasted with the findings published in: https://doi.org/10.1101/611962. There, the value and the limitations of intracranial recordings for validating electric field modeling for transcranial brain stimulation are also investigated in more detail.

On 2020-09-01 16:08:29, user carlos wrote:

Figures are rendered in very bad quality. It is not possible to read the text within.<br /> Can you please reupload figures?

On 2024-08-19 04:14:33, user Gray Shaw wrote:

Very interesting observations. Any experiments done as yet to see if a blocking anti-VISTA antibody reduces the luminescence signal generated by the cis interaction of VISTA-SmBiT and PSGL-1-LgBiT at pH6?

On 2020-09-04 02:53:28, user Boas Pucker wrote:

Very interesting study! Are you sure that the enrichment of GC-AG splice sites in lnc genes is not due to an annotation issue? I got the impression that the splice site analysis is "only" based on the available annotation(s). Is there actually RNAseq support for these splice sites? For example, previous reports (e.g. https://dx.doi.org/10.3390%... "https://dx.doi.org/10.3390%2Fcells9020458)") suggest that some non-canonical splice sites could be due to annotation of genes on the opposite strand. I would assume that lnc genes are more likely to have annotation errors than protein encoding genes, because there is no ORF for validation.

On 2019-12-17 17:24:41, user Venkataraman Sriram wrote:

In addition to the gut and skin analyses, it would be nice to also check alveolar immune composition in the rewilded vs. lab mice. Also, wondering if the 12 remaining rewilded mice are now accounted for?

On 2017-11-10 16:23:55, user AdamMarblestone wrote:

-"Sparse Attentive Backtracking: Long-Range Credit Assignment in Recurrent Networks" https://arxiv.org/abs/1711....

On 2024-09-22 19:30:05, user Subha Kalyaanamoorthy wrote:

The paper has been published in Nature Machine Intelligence. Here is the citation: Reeves, S., Kalyaanamoorthy, S. Zero-shot transfer of protein sequence likelihood models to thermostability prediction. Nat Mach Intell 6, 1063–1076 (2024). https://doi.org/10.1038/s42256-024-00887-7

On 2020-01-23 19:04:19, user Nejc Stopnisek wrote:

A revised version of our manuscript #727461 on the identification of the common bean core microbiota. It includes additional spatial and temporal data supporting the relevance of identified microbial core taxa.

On 2024-05-03 21:47:59, user Michael L. wrote:

This manuscript has now been combined with https://www.biorxiv.org/con... and published as https://pubmed.ncbi.nlm.nih...

On 2018-02-03 15:36:36, user Anshul Kundaje wrote:

Very nice work.

I'm curious. How many steps of random walk did you use for GenomeDisco. You will likely need more steps than the default we set for bulk HiC data.

Also did you try MDS with 3 dimensions. Do you see even better separation?

On 2021-03-25 21:31:09, user Sophia wrote:

Something you might want to keep in mind: it is not logical to compare this algorithm to Seurat 3 because Seurat 3 is not intended for deconvolving mixtures, rather it provides cell type enrichment scores to "deconvolve" capture spots. Is seems as though you used their integration feature (which leverages the MNN-classifier) to evaluate its performance (given how the R^2 value is); the intended use of this integration feature is to integrate two single-cell resolution datasets (e.g. scRNA-seq and MERFISH), not for trying to align a mixture to a single scRNA-seq cell type.

On 2025-06-12 04:20:37, user Saswat K. Mohanty wrote:

This publication has now been published at: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-025-03635-1

On 2020-03-29 18:25:52, user Andrew Crowley wrote:

Very informative! Will you be depositing the model that you created for figure 3 anywhere? Figure 1 appears to be missing a branched marker at N801.

On 2020-07-16 15:43:10, user Rebecca Goldstein Zitnay wrote:

Have the methods here described by the reference "Tatler, 2016" been published? Here it is cited as a personal communication yet forms the primary motivation for this article. This technique would be widely applicable for mechanical studies in the lung. A detailed understanding of how these experimental studies are conducted and their outcomes as compared to the modeling results is necessary to understand the impact of this work and should be described here or as a separate publication.

On 2016-04-03 20:01:40, user Bob wrote:

Nice!! Finally!

On 2018-02-05 23:06:08, user Jin Li wrote:

The website URL of SFMetaDB is updated to be http://SFMetaDB.yubiolab.org.

On 2021-09-13 01:49:05, user nimrat chatterjee wrote:

This preprint just got accepted at BBRC journal and a link to the accepted and published version will be available soon!

On 2018-09-05 08:10:52, user baj09 wrote:

Great work and nice read. <br /> It is a bit unfortunate that I developed something very similar in parallel (https://github.com/baj12/sc... "https://github.com/baj12/scShinyHub)"). I guess when I started on scShinyHub it wasn't clear what could become of your tool. Anyhow, since we have a lot in common I would appreciate very much a short reference to our project in your paper and would like to suggest to try to coordinate our efforts. If you are interested in talking please don't hesitate to contact me. Thanks for the consideration.<br /> Bernd

On 2017-07-03 15:20:51, user Donald R. Forsdyke wrote:

The final version of this paper is in Gene Reports 8, 45-48. I was somewhat surprised to see that the “pregenomics era” refers only to the last two decades. But entire genomic sequences, often from viruses, became available much earlier. Furthermore, Grantham made enormous strides in the 1970s and 1980s with his first database of sequences that preceded the emergence of GenBank. Many of Grantham’s sequences were incomplete, but you do not need an entire dictionary to work out how a dictionary functions! Tear out a page and that suffices! So just because we now have more entire genomic sequences, does not mean that the former era was “pregenomic.”

The paper states: “Since position 3 is not constrained by the amino acid frequencies, it is the best reflection of selection pressure in mRNA interaction dynamics. If the Politeness Hypothesis were true, position 3 should have been the major contribution of the purine rich pattern of mRNAs, but actually its average purine content is less than 50% in most species.” In fact, third positions have to respond to numerous non-amino acid pressures other than that of purine-loading (RNY-pressure, GC pressure, etc. ), so it is not the best reflection of selection pressure on mRNA interaction dynamics (see: http://post.queensu.ca/~for... ).

On 2019-12-07 10:34:41, user Timothy D Craggs wrote:

We would like to encourage comment and discussion of this work - either here, or following the Twitter thread @Craggs_Lab #smfBox

Our aims are to promote open science explicitly through our open source microscopy platforms, bring smFRET to the non-specialist scientific community.

Any suggestions will be critically considered, to help us to improve our manuscript and most importantly, the accessibility of our method.

Thanks!

Tim

On 2021-08-26 23:28:45, user Laura Sanchez wrote:

Dear Willems et al, this preprint was discussed in a lab meeting and we would like to offer the following for review. Thank you for posting this very interesting manuscript. Best, The Sanchez Lab:

The manuscript by Willems et al. presents an overview of a new software, AlphaTims, which allows for fast indexing and retrieval of LC-TIMS-MS/MS data. The authors present a clear explanation of how software indexing and data matrix construction works, along with an example of how their software is used to simplify the accession of data from complex samples. This open-source program has the potential to make data more accessible without proprietary software, and has many possible applications in conjunction with further data processing software. Overall, AlphaTims looks to be an impressive piece of software, and figure 1 especially did a great job of visualizing and explaining the difficult concept of data indexing in 4 dimensions. This was a great, polished read, and very informative in elucidating the experimental process for those who are less familiar with the LC-TIMS-MS/MS workflow. It was also appreciated that the data was publicly available on PRIDE! Below please find a list of critiques that may improve the accessibility of some of the concepts and better illustrate the software’s utility.

? Figure 1 is very well done and all the terms are well-explained. It may add further clarity if the authors were to add a part (d) to help visualize what the data looks like once indexed, perhaps with number values. Additionally, the color palette is difficult to interpret when printed in black and white; the authors may wish to consult ColorBrewer.

? Some of the data on the speed of the software is difficult to conceptualize without benchmark data for comparison. There’s a brief comparison between the program and Bruker’s DataAnalysis on two different systems (one local and one Github VM) with different specifications, which doesn’t provide a lot of context as these do not seem to be directly comparable. While the speed of the software compared to others is not necessarily a major focal point, as AlphaTIMS carries out different processes to DataAnalysis, it’s still a little difficult to conceptualize the relevance of the times in figure 2, as these events are somewhat decontextualized. With that being said, it was apparent that both systems used solid state drives. Therefore, even if runtimes cannot be directly compared, it may be helpful to note whether the code is CPU-bound, storage speed bound, etc. and suggest what hardware upgrades may help increase performance.

? The documentation in general is very good! The accessibility and the included explanations for all of AlphaTims’ reading, writing, slicing, and visualization workflows are impressive. However, more examples for other included processing functions (i.e. centroiding) would be helpful.

? Some more broad data visualizations in figures 3 and 4 would be helpful. Seeing an overall LC-MS and/or TIMS-MS spectrum in figure 3 could help contextualize the complexity of the data, beyond the quality control purposes expressed in the figure. This would also help to visualize the described “polygon filter” - again, not an expressed priority of the paper, but helpful for readers to connect the software to data. Additionally, in figure 4, showing a comparison of the selected peptides between the 6 sample conditions could help to visualize the utility of the software for determining sample optimization. There’s also a slight disconnect in the captions for figure 4 - “cell 24” could refer to In [24] or Out[24]. This is worth clarifying with traditional a, b, c, d, e, f labels.

? The forward looking statement in the conclusion may provide a great opportunity to expand on future possible applications. For instance, do the authors see this being developed with additional data processing/analysis functionalities, or integrated into new/existing data analysis programs? Is there possible functionality to visualize and compare multiple datasets at once?

On 2023-01-21 23:37:14, user Donovan Parks wrote:

Hi,

I much enjoyed reading your preprint and look forward to playing with skani. Do you have results showing how alignment fraction (AF) compares between skani, FastANI, ANIu, and/or ANIm? AF is a key criteria for applications such as assigning genomes to species clusters. An application dear to me as a maintainer of the GTDB.

Thanks,<br /> Donovan

On 2020-04-17 12:31:23, user UAB Bacteriology Journal Club wrote:

Review of “Boosting Toll-like receptor 4 signaling enhances the therapeutic outcome of antibiotic therapy in pneumococcal pneumonia” Casilge et al.

University of Alabama at Birmingham<br /> Bacterial Pathogenesis and Physiology Journal Club

Summary<br /> This manuscript is well written. The authors showing that in TLR4 agonist MPLA can be improved Streptococcus pneumoniae (Spn) clearance with a combination treatment of sub-inhibitory doses of amoxicillin in a mice model. Moreover, the authors found that MPLA enhances host immune response for invasive Spn via inducing the pro-inflammatory cytokines and up-regulating the granulocyte related genes. This paper is very reasonably demonstrated, but we have a few comments and clarifications.

Major Comments<br /> • The authors analyzed Spn titer on lung and spleen and analyzed gene expression or protein expression by RT-PCR or ELISA assay in lung or blood, respectably. Why you didn’t check Spn titer on blood and gene expression on spleen?

• The authors used 30ug AMX for “high-dose AMX monotherapy”. However, some of the other experiments 350 ug used. If the authors have a reason, please explain in the manuscript. It will be helpful to understand.

• The authors used one antibiotic “AMX”. How are other antibiotics? The title of this manuscript is “antibiotic therapy”. If you can, please check other antibiotics also. It will give a more powerful story.

• How is the AMX-resistant Spn (?-lactam resistant strains) strains and other pathogens? It clearly lowers the effective MIC of AMX in these experiments, but we wonder whether that extends to the possibility of overcoming at least moderate levels of AMR. These experiments are probably beyond the scope of this paper, but I would be interested to hear the authors’ opinion on whether this might be the case.

• The authors used three different mice. However, the authors did not explain why different mice were chosen and used. If the authors have some reasons, please explain in the manuscript.

Minor Comments<br /> • In Fig. 2, it would be very helpful to include treatment labels on each panel (A to E)

• In Fig. 3B and 3C, please explain which gene used for normalization. In Fig. 3D, this panel is difficult to read. It might be more clearly expressed as a table, or possibly by using color instead of greyscale. Please broadly explain the function of genes in microarray data.

• In Fig 4A, the time point is not matched with Fig 4B. Moreover, What is the difference between “untreated”, “uninfected”, “naïve”, and “reference”??

On 2019-11-09 13:44:29, user Anil wrote:

Congratulations on a nice work on delineating the transcriptional architecture of enhancers.

But, terms like "promoter", "core promoter" and "TSS" in our collective understanding have been etched in our minds to reflect gene-proximal elements necessary for gene transcription. Our knowledge of widespread intergenic transcription is only a decade old, and we are getting to learn deeper about how these transcriptional units function, and this paper is a great contribution towards that. Now, calling the similar elements within gene-distal enhancers by the very same name creates confusion. I believe there is a strong need to distinguish enhancer-embedded promoter elements from the classical meaning of such terms that normally refer to such elements at the 5' end of genes.

I suggest the authors, instead, use "ePromoter", "core ePromoter" and "eTSS" to reflect such elements that are embedded within enhancers and that primarily initiate enhancer transcription - a prefix "e" signifying the elements' location at/within enhancers.

On 2023-04-03 12:09:44, user Alexis Darras wrote:

Dear bioRxiv members ( @biorxivpreprint ), please note that this research has now been peer-reviewed and published in Biophysical Journal https://doi.org/10.1016/j.b...

On 2021-04-07 17:34:05, user Otakar Mach wrote:

Considering the fact, that the report under review is a preprint, this paper is not to be accepted as peer review publication.<br /> Early immune response in mice immunized with a semi-split inactivated vaccine against SARSCoV-2 containing S protein-free particles and<br /> subunit S protein. Marek Petráš, Petr Lesný, Jan Musil, Radomíra Limberková, Alžbeta Pátíková, Milan Jirsa, Daniel Krsek, Pavel Brezovský,<br /> Abhishek Koladiya , Šárka Vaníková, Barbora Macková, Dagmar Jírová, Matyáš Krijt, Ivana Králová Lesná, Vera Adámková<br /> The authors set themselves a goal – to design a vaccine prototype using the protein of an inactivated virus. As a source of the virus they<br /> used a supernatant from the cell-culture of Vero E6 cells. In this place I rebuke the authors for not including detailed information about the<br /> virus origin. The virus is completely new. The reference saying that it was taken from the SZÚ archive can lead to a conclusion that the SZÚ<br /> employees isolated the virus and stocked it in the archives, the virus should be identified and named according the taxonomic rules.<br /> As a second the scale is absent in the electron microscope images. The proof of the capture of S protein is missing, only authors have<br /> supposed this capture. The authors must support their claim with using e.g. an immunochemical assay. The authors consistently worked<br /> with a low-speed supernatant of the tissue media. They used 300 g and 1800 g only.. Under these circumstances only the cells and larger<br /> parts of the cell detritus are removed from the tissue culture meidum. The virus together with a rich spectrum of the cell detritus are<br /> present in the supernatant. The authors never tried to prepare a virus specimen using differential or density gradient centrifugation.<br /> The precise data about the concentration of the protein is not present in the study, not even in the paragraph regarding the preparation<br /> thickening . The purity of the virus fraction - how much contaminants it contains- can’t be found in the study. Saying this, it makes no sense<br /> to employ ourselves with the remaining paragraphs of the preprint any further. Very much useless work was done here. Mice have been<br /> dosed a rich spectrum of protein, glycoproteins and low-molecular substances. This mixture of very immunogenic substances can never be<br /> used as a vaccine. It does not matter when used in a mouse, but one cannot envisage using it as a vaccine for human beings.<br /> If the authors intended to use their experiment as a prototype for people, they should have thought of a suitable adjuvant. Aluminium<br /> compounds are only suitable for a laboratory use.<br /> The way in which the lab work has been done brings the following result: a low-speed tissue media supernatant of undefined nature<br /> containing inactivated unspecified virus, its protein structures and also containing unspecified antigen originating from the cell culture<br /> caused an immune response in mice.<br /> The preprint can in no respect be considered a sound prototype for a human vaccine.<br /> Otakar Mach 22.3.2021