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

On 2017-09-22 13:44:57, user technicalvault wrote:

The link to HLA*IMP:03, http://imp.mcri.edu.au/ now forwards to http://imp.science.unimelb.... and which is kir imp. It should probably be updated to: http://imp.science.unimelb....

On 2022-09-15 15:36:04, user Foster Birnbaum wrote:

The difference between Figures 4 and 5 is striking. In Figure 4, UniRep/BO is clearly superior to the other versions, whereas in Figure 5, even a random sequence performs well until higher iterations and there is never a clear difference between UniRep/BO and the other methods. You highlight that this task is very specific and is convex as explanations for why UniRep/BO is not clearly better, but I am still wondering why the performance for any method is not much better than random. Also, you also state that the sequence length is fixed at thirteen residues. In part A of the results, you mention that an advantage of BO is that the sequence length can change during optimization. Have you experimented with letting BO run with a variable length sequence on the unknown target matching problem? In addition, can you perform the AlphaFold task using the two ablated methods? I think including the ablation results for all three tasks would be helpful.

I think Figure 1 could be made clearer if the sequences and labels proposed from the logits went directly to the train step, instead of being directed first to a separate shape. This would make Figure 1 have a more triangular structure, with the logits at the top, the UniRep vector in the bottom left, and the prediction plot in the bottom right. I think this could help make the flow of information clearer.

On 2022-11-28 15:06:35, user Lladser Research Group wrote:

The pre-print has been revised after receiving input from several people.

On 2020-01-28 21:51:23, user Cyborg Gabe wrote:

A 14% daily probability of death if hospitalized vs only 1.5% daily recovery probability if hospitalized? That means ~90% of hospitalized cases will die. Can that be correct?

On 2021-02-24 23:21:11, user Ziyan Wu wrote:

I really appreciated this paper and I think it did a nice job in showing the accuracy and precision of the TIFF method. At the same time, I think a couple of edits could be made to help the clarity.

For example, figure 2(c) includes the proteins that had more than two valid values. These proteins, shown blue and red in figure 2(b), are shown red in figure 2(c). Therefore, changing the color scheme may be helpful to prevent misunderstanding.

Also, I really like the Venn Diagram, while can be a little confusing when considering what the “98%” in the overlapped part means.

Besides, figure 3(b) includes some data from previous research. And I noticed the standard method used in that paper is LC-MS. Since the one for the other figure is MS-MS, I think it will be nice to label LC-MS directly in figure 3(b).

In the end, personally, I hope there can be a distinct color scheme for figure 3(d), which shows the different pair-wise coefficients in different colors so that the comparison can be easier.

In general, my colleagues and I believe your research is really important, and that is also why we chose it for our journal club. Overall, the work was very exciting and intriguing to read. I hope this feedback helps in strengthening your paper.

On 2022-10-21 20:26:49, user Thierry Rebetez wrote:

This article "SARS-CoV-2 Main Protease: a Kinetic Approach" has been published in the peer-review Journal of Physical Chemistry & Biophysics at the following URL:

https://www.longdom.org/ope...

On 2024-08-05 16:25:30, user Ra Hel wrote:

Hi, thank you for the thorough article. I would like to comment on : "We then employed GB classifiers in subsequent studies and utilized them to exclude studies that cannot discriminate the disease phenotype based on microbial profile."<br /> It would be really useful to have information on what percentage of studies for each disease passed this criterion - did you need to screen 10 studies per disease to have one that would be able to discriminate the phenotype based on microbial profile or rather vice versa that there were very few odd studies that didn't pass this selection.

On 2020-12-21 11:54:11, user Shi Huang wrote:

The same pattern is also found for rs73621775, which has 9 reads coverage. Impossible for sequencing or calling errors to explain.

On 2021-02-23 20:47:09, user Guillaume Mas wrote:

Stimulating work with Skp and SurA that do confirm current hypothesis that chaperones are able to expand their client proteins even in the absence of source of energy such as ATP.

The experiments at different Skp concentrations (Fig. 2) are particularly interesting as you have chosen to work at near physiological concentrations. In our recent Skp publications, we have shown that in this concentrations range Skp populates an equilibrium between an inactive disordered monomeric state and the canonical active folded trimeric state (PMID: 33087350). This equilibrium being shifted toward Skp3 in presence of OmpX/tOmpA.

Would integrating the fact that Skp exist as a mix of inactive/active species explain why only ~80% of uOmpX molecules were in a Skp3–uOmpX complexed state even at the highest concentration of Skp (2.5 uM)?

Guillaume

On 2021-05-04 17:48:43, user Science Girl wrote:

Very nice and significant work. I loved the creative experiments and the cool results. The results are clearly a significant leap for plant biology, especially the unexpected findings.

On 2024-01-05 14:30:56, user Chris Schadt wrote:

The peer reviewed article been published in ASM journal mSystems in October 2023, but link to online version never updated. The mSystems version also doesnt show up in google scholar so Im not sure what is going on.<br /> https://journals.asm.org/do...

On 2023-07-20 09:35:16, user Dmitrii Kriukov wrote:

Amazing, clear and precise work! Thank you!

On 2025-02-17 21:53:40, user Alessandro Hernández wrote:

Are you thinking on use this tool for alleles that has been under natural selection? For example LCT (lactase persistance allele) which are very common in european populations and some parts of Africa. Do you hypothesize that they could be restricted to certain populations and obtain an ADS >0?

On 2020-12-15 10:36:24, user Julian Marchesi wrote:

Can anyone answer me this<br /> 1: what % of singletons i.e. 1 read in one sample are real and what % are due to sequencing errors and bioinformatic artefacts? It always amazes me how people grab the latest idea like it must be right, so ASVs are in and OTUs are out. Well if you missed the memo, we don't even have a robust definition of what a bacterial species is, so anything we use is always a compromise and biases out analysis.<br /> 2: if you don't sample to the same read depth how can you create comparable alpha diversity indices? Won't a sample with a read depth of 20,000 reads have a different Shannon index to one with 1500 reads?

On 2017-11-25 22:47:05, user SC4649 wrote:

L128-137: 'While other researchers had hit upon similar notions throughout the early 1980s (e.g., Clutton-Brock and Harvey, 1980; Mace et al., 1981; Ridley, 1983; Stearns, 1983; Cheverud et al., 1985), none of these had the pervasive impact that Felsenstein’s presentation did [...] And while of course his proposed solution, “independent contrasts” (IC), was widely adopted, we suspect it is the clarity with which Felsenstein articulated the problem that has kept his paper a hallmark of biological education and a testament to the importance of tree-thinking...'

...Isn't it simply because Felsenstein's IC was the first statistically viable solution (Felsenstein 1985; Purvis and Garland, 1993. Syst Biol 42: 569-57)?

On 2019-07-08 04:08:39, user Fraser Lab wrote:

This work describes the implementation of a data processing pipeline for acquiring high-resolution maps of microtubules (MTs) from cryo-electron microscopy (cryoEM) data using the RELION software. As in other pipelines for processing microtubule EM data, this implementation requires extensive custom processing because of the pseudosymmetric nature of most MTs assembled in vitro (also observed in vivo): a "seam" down the length of the assembly disrupts the otherwise helical symmetry. The broken symmetry means that existing methods for processing purely helical particles equate nonequivalent positions and produce low-quality reconstructions. The authors implement a treatment of these particles that accounts for the seam and produces high-resolution structures of the MT ? and ? asymmetric units. It builds on implementations of similar pipelines for the same purpose using other software, with the key advantage of conducting all steps in a single program that most cryoEM users are already familiar with. The pipeline consists of a set of scripts and a series of steps the user should complete in the RELION graphical user interface (gui) in order to obtain the asymmetric unit reconstructions. The authors test their pipeline on three example datasets with different decorators on the ? or ? subunits that aid in initial alignment and discrimination between the two, and note that they have successfully (with minor modifications) applied the pipeline to a more challenging dataset with both subunits decorated.

The major success of this paper is the clear and thorough description of the steps necessary to produce high-resolution ? and ? subunit reconstructions, complete with clear justification for each step and descriptions of expected results so that an advanced user can intervene when intermediate results deviate from expectations. This tool meets an immediate need in the structural biology community for analysis of MTs, which are inadequately reconstructed from cryoEM data by existing helical or strictly single-particle methods, and which play an important role in the cell interacting with a variety of other molecular machines. Ideally, it would be benchmarked against the other pipelines mentioned in the paper (e.g. https://github.com/nogalesl... from: https://www.ncbi.nlm.nih.go... "https://www.ncbi.nlm.nih.gov/pubmed/26424086)") but as one of us (JSF) knows from personal experience that it can be tricky to set up the necessary EMAN and frealign environments correctly to do such benchmarking properly. Here, the ability to complete this analysis without exporting steps to other programs could be a major boost in accessibility. Moreover, as the authors have built upon a popular cryoEM image processing program that has a gui highly accessible to novice and intermediate users as well as command-line tools that expert users may use for more advanced customizations and interventions, we anticipate this pipeline will be enthusiastically adopted by many users.

We also applaud the authors' choice to make the scripts open-source and publicly available on github, which will facilitate the active conversation between users and developers (and sometimes software developers who did not author the original work) that lead to major breakthroughs and advancements in later versions. However, we cannot comment on the scripts themselves yet as a full path to the source code is not provided in the manuscript and a search for “MiRP relion github” didn’t yield anything informative. We would like to request the authors include it in the revised manuscript and also provide it to us during the review process so we may evaluate this important component of the work. We recommend using Zenodo (https://zenodo.org/) "https://zenodo.org/)") to generate a DOI for a snapshot of the repository, which will also produce a timestamp and facilitate formal versioning.

We identify a few major weaknesses in the manuscript in its current form, all of which we hope the authors can address in a revision. First, the final, high-resolution reconstruction is the ?? dimer, not the C1 reconstruction of a full helical turn, which may not serve the goals of all users. The authors identify the final averaging step that disrupts the density for all but the ?? dimer directly opposite the seam and describe alternative approaches, including one implemented by the Carter group while the manuscript was in preparation. We would strongly encourage them to implement one of these approaches so that biological questions that require examination of the whole MT can also be addressed. We are also unclear on how the present implementation would preocess both the microtubule and fiducial protein for datasets with dynein or EB3 bound, and would like to see this explicitly discussed (or better, tested if EMPIAR datasets are available).

Second, at times the authors describe what they expect from data they have not processed, for example on page 14 lines 1-4. Given that they have the necessary tools in-hand and this work describes the method, we would press them to test this type of claim and describe the supporting evidence. They have also described processing a dataset with fiducial markers on both ? and ? monomers but not described the modifications they had to make to the pipeline for this dataset, and they have not yet (to our knowledge) used the method to process undecorated MTs. As they cite successful processing of undecorated MTs by the Nogales group, proof-of-concept processing of undecorated MTs would be an important component of making this pipeline at least as useful as existing methods. The other case where we would strongly prefer to see the authors test their claims is on page 12 lines 46-48, where they speculate on the effects of excluding some MTs from further analysis, and although the authors do not make any claims about performance using automated MT picking, we would be very interested to see this tested (even if the result is that it is discouraged).

Third, while we agree with the statement: “strikingly, although application of MiRP compared to standard helical processing has a negligible effect on the reported reconstruction resolution by FSC (Fig. 6c), the structural details are clearly superior in quality,” based on the snapshots of density shown at a specific contour in Fig 6 and Supp Fig 3, it is possible to use tubulin model refinement and other quantitative evaluations of the map to validate this statement. For example, compared to the standard helical map we would expect a higher quality reconstruction to have a smaller convergence rmsd when multiple independent models are rebuilt into the map (as in: https://www.ncbi.nlm.nih.go...; "https://www.ncbi.nlm.nih.gov/pubmed/30449687);") a better EMRinger score (https://www.ncbi.nlm.nih.go... "https://www.ncbi.nlm.nih.gov/pubmed/26280328)") when evaluated with the same starting model rigid body fitted into the map; and lower B-factors/better model geometry when an atomic model is refined.

Fourth, reiterating that this is a methods paper, we find it critical that the raw data be made available on EMDB for all datasets described in the manuscript, not just the C1 reconstructions and symmetrized asymmetric units. This is important for reproducibility, open science, and the development of exciting new methods like this one using publicly available test data.

In sum, we find this an important piece of work that will immediately improve the ability of groups working on MTs to recover high-resolution structures, pending our several major reservations that we hope the authors will resolve in a revision. We also identify several minor points that could be improved, mostly regarding readability, and a few suggestions for alternative implementations of some steps in this or a future version of the pipeline. As the line numbers do not appear to be spaced the same as the text, for these points, we have indicated the closest line number to the line when printed.

Some figures or tables referenced in the main text are not referenced correctly, such as on page 9 line 31, Fig. 6aii (referencing a panel that does not exist).

Table 1 should include accession codes in the EMDB.

The authors might comment on the biological relevance of MTs with seams, given that these are more often encountered in vitro and much less often in vivo, preferably in the introduction.

We suggest a figure that visually highlights the symptoms of misalignment of the seam and/or helical averaging of MTs with seams. Including correlation coefficients with this figure could help illustrate the challenge this pipeline overcomes. This could also illustrate the signal boost of the superaverage and the symptoms of out-of-register units. The figure could be referenced at several points later in the text to explain why certain steps are necessary.

At the end of the first paragraph on page 6, the authors describe "structural constraints of MT polymers" but apply restraints in orientational and translational searches. It would be helpful to expand on the rigidity of these restraints and whether it varies with distance to further neighbors, if applicable. Ideally (or possibly in a future version), the authors could consider restraining each ? or ? monomer relative to its immediate neighbors and using this approach in combination with variable restraint rigidity to aid in reconstructions of monomers at the seam and in distorted regions.

Several points regarding resolution starting at the end of page 6 and continuing in the first paragraph on page 7 describe increments of resolution or changing pixel size by binning, which have no meaning in isolation (e.g. a difference of 0.2 Å or binning x 4). The starting or ending absolute quantities should be included (e.g. improvement of the resolution to 3.2 Å or a final pixel size of 3 Å). This is repeated on page 11 lines 11-12.

The authors describe that "there is a clear bias towards a certain range of Rot angles" on page 8 line 16, but as this is the expected behavior and not a ground truth, it should be described as such.

Similarly, on page 9 line 19, the authors intermix behavior on their test data ("As expected") with description of the method, and should more clearly separate these.

On page 8 lines 18-22, the authors describe their approach for using the bias toward one Rot angle to select the correct seam location. We recommend testing the alternative method of a grid search over correlation coefficients, or describing how this is effectively accomplished during the global search step.

On page 8 lines 21-22, the result of the Rot search is described as an approximation. It would be helpful to clarify whether this result is precise but sometimes inaccurate, or accurate but known to be imprecise.

On page 8 in the section on X-Y shift smoothing, the authors describe a remedy for out-of-register asymmetric units involving resetting excessively large shifts to zero and re-refining. We propose an alternative method by analysis of the distribution of X-Y shifts that identifies the out-of-register shift vector and adjusts excessively large shifts by modulo arithmetic. This would reduce the error in the reset shifts.

As part of the same description on page 8 lines 47-48, the authors describe enforcing all X/Y shifts in a MT to follow a single slope and intercept, and should clarify whether this is constrained or restrained.

The authors could expand on the process of 'segment average' image generation on page 4 line 29 and the source of known helical parameters on page 4 line 33.

The sample preparation for cryoEM section starting on page 3 could include greater detail, e.g. Vitrobot parameters during blotting and freezing.

The authors could clarify the difference between defects and switches in PF number on page 7, lines 27-28.

The description of a 'clean' seam on page 10 line 48 is confusing. Describing this as a MT with no seam might be clearer, if that is the correct interpretation.

There are a couple creative uses of the word "allocation" — on page 9 line 6 we suggest substituting with "positioning" and on page 13 line 22 we suggest substituting with "assignment".

The wording on page 5 line 52 seems to imply the RELION nomenclature preceded the Euler angle nomenclature used in many other applications, so we recommend dropping the modifier "former".

The wording on page 7 line 5 implies the previously implemented approaches are lacking in some way, and we recommend dropping the modifier "albeit". This is repeated on page 12 line 42.

The authors could describe which of the operations through the gui could alternatively be run on the command line on page 5, lines 59-60.

On page 13 line 21, the authors claim their implementation is "the only way to avoid introducing artefacts." This may be an overly bold claim.

We are unsure what the authors mean to do with the "41 Å shifted positions" on page 9 line 7.

Some of the word choices could be made more accessible to all readers, for example by using the more common and equivalent "while" instead of "whilst" in several instances.

The sentence "Initial Tilt ... picking coordinates" on page 6 lines 54-56 is unwieldy and could be rephrased.

We find the sentence beginning "In other words" on page 8 lines 2-4 redundant and unnecessary.

The qualifier "data collection parameters" should not accompany ice thickness on page 9 line 42.

We would prefer sticking to one set of units on page 10 line 1 and substituting "sub-10 Å" for "subnanometer".

The abbreviation "(DQE)" on page 9 line 43 is not used again and may be omitted.

There are several spacing errors throughout the text. Between a numeral and a unit, there should be no space, except where the next character is º or %.

On page 8 line 4 and in several other instances, where "however" is an interjection, it should also be preceded by a comma, e.g. "this register is, however, very error prone".

There is a typo on page 3 line 52 (1 mg/ml --> 1 mg/mL), an incorrect abbreviation on page 4 line 6 (sec --> s), an overly dense abbreviation on page 4 line 59 (4xbin), a typo on page 4 line 53 (smoothened --> smoothed), a typo on page 5 line 14 (psi/tilt/ranges --> Psi/Tilt ranges), use of redundant "around" and "~" modifiers on the same quantities on page 6 line 53, incorrect pluralisation on page 7 lines 33-34 (confidence --> confidences), an unnecessary word "score" on page 8 line 7, a missing word "good" in "good signal to noise and good angular distribution" on page 9 line 33, an unnecessary hyphen in "ice-thickness" on page 9 line 42, and an unnecessary comma in "reconstructions, remains" on page 9 line 56.

We review non-anonymously, Iris Young and James Fraser (UCSF).

On 2020-08-18 03:16:44, user Jink wrote:

Where can I get the codes? I want to try it..!!

On 2014-10-08 01:32:23, user Casey Brown wrote:

This paper by Wen, Luca, and Pique-Regi presents a novel statistical approach to eQTL mapping. This work builds upon a series of recent methods for association mapping in a Bayesian framework, by applying a meta analysis to a trans population eQTL cohort, modeling the effects of allelic heterogeneity under causal variant uncertainty, and incorporating regulatory element annotation data as an informative prior. This method also improves the interpretability of loci that appear to have subgroup specific effects that are actually caused by multiple, independent, linked causal variants. In general, this is an important topic that will be of broad interest, the paper is generally well written, and the author’s conclusions follow logically from the stated analyses.

I have the following concerns:

1. Improvement in power with joint analysis across groups. The authors note multiple times (including in the abstract) that meta analysis across groups improves power for eQTL detection relative to single group analyses. While it is clearly true that

the meta analysis identifies more associations than the union of the single group analyses, I don’t think this is a particularly meaningful comparison. Given the difference in samples sizes, it seems obvious that the multi group analysis would have much greater power than the single group analyses. The authors need a better way to make this point.

1. PIP clusters. At several points in the manuscript (e.g., Figure 3), the authors discuss SNP sets that fall into ‘clusters’ based on their pattern of inclusion in the model sampling. These clusters of SNPs appear to represent groups of SNPs in high LD that cannot be differentiated statistically. Because of the fact that, within each of these clusters, there is likely one causal variant, the delineation of the clusters is extremely important. If I understand correctly, these clusters cannot by identified from the PIPs alone, but rather must be extracted from the sampling results (e.g., a collection of 8 SNPs in perfect LD could have a summed PIP of ~1, but each individual SNP would only have a PIP of ~0.12). It is not clear from the text if these clusters of SNPs are annotated automatically or if this requires manual intervention. Users of the software would certainly benefit if this annotation was automated.

2. Characteristics of PIP clusters. I’d be curious to know about the relative distance to the TSS of SNPs that from multiple clusters. In other words, if a gene has two independent clusters of SNPs with high summed PIPs, I’d be interested to know if the cluster with the greater PIP is more often closer to the TSS than the second cluster.

3. Resolution. The authors demonstrate very clearly that the use of multi population cohorts for eQTL fine mapping improves resolution by ~50%. This is a subject of great interest to the disease mapping community. I think the authors have a very interesting collection of analyses and data that they could explore a bit more deeply. Perhaps these data warrant a display item as opposed to just the limited treatment in the text?

4. Model incorporating TFBSs. How were SNPs classified into not overlapping DHSs, footprint SNPs, and binding variants? More detail or a reference is needed. What is the relative importance TFBS overlap vs. distance to the TSS? Is it possible for the authors to quantify the fraction of the PIP that is overlaps footprint or binding variants? Or conversely, can the authors estimate what fraction of eQTLs do not appear to overlap a TFBS?

5. Fig 6. The authors state that the multi SNP model yields an even greater enrichment of eSNPs about the TSS. However, this conclusion is neither directly quantified nor visualized. For example, figure 6 could be changed to present the results from both the multi SNP analysis and the single SNP analysis, which might make this very interesting result much more intuitive. I also wonder if this increased resolution could be used to ask if the distribution SNP enrichment is symmetrical about the TSS?

6. Direction of effects at multiple-eQTL loci. The example presented in figure 3 depicts a gene with multiple independent eQTL effects. At this particular locus, the minor allele at the largest effect SNP cluster is associated with an increase in expression while the minor allele at the 2nd, 3rd, and 4th clusters is associated with a decrease. I’d be interested to know how often the data fit this pattern, as opposed to the situation where the independent effects have concordant effect directions.

7. ‘Functional analysis of eQTLs’. While I understand that it is common practice to refer to SNP enrichment analyses as ‘functional’ analyses, it does not seem appropriate to me. Simply calling it ‘Enrichment analysis of eQTLs’ would be more accurate.

8. Minor and Grammatical errors:

a. “We thank…our funding agency for support,” should probably be changed.

b. Abstract: i) *joint* analysis

c. Section 2.1.1: Such *an* indicator? ... This is because most previous studies only *identified* small numbers…

d. Section 2.1.3: …of corresponding null

*hypotheses* …

e. Section 2.1.4: …and we give the details in *the

Methods* section.

f. Section 2.2.2: Nevertheless, for a non-trivial proportion of genes, there *is* strong evidence…

g. Section 2.2.3: “…*their* enrichment in eQTLs is statistically highly significant…”

h. Discussion: “…it is clear that in most cases, even *if we* are relatively certain about the number…”

j. Discussion: …evaluate the enrichment of certain functional *features* in eQTLs…

k. Section 4.2: …we tested the null hypothesis *that* asserts no cis-eQTLs.

l. Section 4.4: …whereas the other parts of the Bayesian model *remain* intact.

m. Figure 1 legend: …the SNP *exhibits* a strongly consistent…

n. Figure 5 legend. The opposite effects of rs6006800 *are* clearly explained by…

Christopher Brown, University of Pennsylvania

On 2018-02-09 08:44:58, user Wiep Klaas Smits wrote:

This is an interesting paper, linking the presence of tetracyclin resistance determinants to the emergence of the epidemic C. difficile PCR ribotype 078. The data here are in line with previous findings reported by the Lawley lab (WTSI/UK) and Kuijper lab (LUMC, NL). Unfortunately, this prior body of work is not very well acknowledged or discussed in the paper. For instance, Bakker et al have reported a link between Tet resistance and Tet resistance in human and animal isolates (DOI: 10.1128/JCM.01171-10). Recently, Knetsch et al. have shown the presence of tet40 in RT078 already (unlike the claim in the abstract) - doi:10.1128/JCM.01384-17. I also find it surprising that though fluoroquinolone resistance is mentioned as a driver of epidemicity, the recent Nature paper from the Britton group (which also deals with RT078) is not discussed - DOI: 10.1038/nature25178. I hope the authors will provide a more balanced view in an updated version of this manuscript.

On 2020-08-24 15:35:54, user UAB BPJC wrote:

Review by University of Alabama at Birmingham Bacterial Pathogenesis & Physiology Summer Journal Club:

This paper begins to elucidate the role of GumB, an IgaA ortholog in a S. marcescens rabbit<br /> keratitis model. Overall, we feel this paper is well written and begins to demonstrate the role of GumB on the Rcs system in S. marcescens. We found all experiments to be insightful and straightforward. We especially appreciate the complementation experiments that were performed as we feel these types of experiments are lacking in many animal infection models.

Below are our critiques:<br /> 1. Introducing the roles of wecA and wza in context with the Rcs system sooner in the introduction of the paper would allow us to understand why these mutants were used in early experiments in the manuscript.

1. More introduction for shlBA would also be useful.

2. The experiments presented in this manuscript utilize double mutants without single mutant controls. Including these experiments would improve the clarity of the manuscript.

3. Including a cartoon of the Rcs system and its associated roles along with its regulation by GumB would allow for the reader to understand the system much quicker and easier than what is currently presented.

4. Throughout the manuscript, many between comparisons are made in the figures that we feel may be unnecessary when there are controls present. Performing more comparisons of mutants to controls may be more informative

On 2020-02-01 17:25:30, user Prashant Pradhan wrote:

This is a preliminary study. Considering the grave situation, it was shared in BioRxiv as soon as possible to have creative discussion on the fast evolution of SARS-like corona viruses. It was not our intention to feed into the conspiracy theories and no such claims are made here. While we appreciate the criticisms and comments provided by scientific colleagues at BioRxiv forum and elsewhere, the story has been differently interpreted and shared by social media and news platforms. We have positively received all criticisms and comments. To avoid further misinterpretation and confusions world-over, we have decided to withdraw the current version of the preprint and will get back with a revised version after reanalysis, addressing the comments and concerns. Thank you to all who contributed in this open-review process.<br /> : Authors of the Manuscript

On 2020-01-19 15:33:08, user George Diallinas wrote:

Very interesting article! See also in relationship to our work

Kourkoulou A, Grevias P, Lambrinidis G, Pyle E, Dionysopoulou M, Politis A,<br /> Mikros E, Byrne B, Diallinas G. Specific Residues in a Purine Transporter Are<br /> Critical for Dimerization, ER Exit, and Function. Genetics. 2019<br /> Dec;213(4):1357-1372. doi: 10.1534/genetics.119.302566. Epub 2019 Oct 14. PubMed <br /> PMID: 31611232; PubMed Central PMCID: PMC6893392.

Pyle E, Kalli AC, Amillis S, Hall Z, Lau AM, Hanyaloglu AC, Diallinas G, Byrne<br /> B, Politis A. Structural Lipids Enable the Formation of Functional Oligomers of<br /> the Eukaryotic Purine Symporter UapA. Cell Chem Biol. 2018 Jul<br /> 19;25(7):840-848.e4. doi: 10.1016/j.chembiol.2018.03.011. Epub 2018 Apr 19.<br /> PubMed PMID: 29681524; PubMed Central PMCID: PMC6058078.

On 2020-02-11 07:06:29, user PE DI wrote:

Question from a layman: So in reference to the RaTG13 genome found in the 2019-nCoV means that this virus is 96.3% similar to the SARS-CoV ? Also if RaTG13 is not the exact genome that caused the outbreak in humans then does that mean that there is another bat like genome that needs to be identified as the cause ?

On 2020-04-21 22:09:05, user Charles Warden wrote:

Thank you very much for posting this.

While I am not sure exactly when I will get around to testing GLIMPSE on my own data, I am adding this comment as a reminder to myself (since it does relate to the content of this post, where I tested STITCH and Gencove).

You include a lot, so you don't necessarily have to add something about the minimum amount of reads needed for an application like self-identification. However, at least within the window where you are able to do so, I think some readers may be interested in seeing a comparison to Gencove.

Thanks again!

On 2020-02-11 22:40:05, user Lindsay Wu wrote:

The updated, peer reviewed version of this paper is out at Cell Reports - enjoy!

https://www.cell.com/cell-reports/pdf/S2211-1247(20)30083-8.pdf

On 2021-02-27 01:33:37, user Lorenzo Calviello wrote:

Nice paper and idea!<br /> Did you try using random forest regression (using feature importance as a predictor for gene-set relevance) as an alternative to regularized regression?

On 2022-02-17 01:12:41, user Marta wrote:

Thank you for uploading the article. I'm not an specialist in evolution and can't critisize the methods. But I detected some problems in the ontology table. Lgals7 is not a Channel and Plagl1 does not codify for monoamine oxidase. Maybe I´m missing the point. Can you explain the table?

On 2017-10-10 08:05:18, user Peter Joshi wrote:

Nice paper and very nice idea. I like figure 1, but suggest a couple of things - firstly can you be clear on the bases of the logarithm, secondly could you show the slope explicitly. I have a more fundamental issue with interpretation - extrapolating this fit would see the men and women lines cross: you know this doesn't happen. So beyond age 50, it looks like ageing behaves differently than before age 50. As you recognise mortality causes are different between men and women, but also by age. In particular many younger men die due to risky behaviour, which diminishes as they age (or grow up!) To what extent can your findings be explained as reverse ageing in men due to this effect, rather than differences in the acceleration of morbidity between men and women?

Good luck with the manuscript!

On 2020-12-01 18:03:57, user Daniel Himmelstein wrote:

I reviewed this preprint (version 1) for a journal and have posted my review online.

Copying my conclusion below:

The study addresses an important problem. A unified dataset of gene-trait associations based on GWAS would be valuable resource. However, the manuscript is lacking details and intermediate results regarding the crucial steps of variant-to-gene mapping and association integration. Furthermore, the methods for association integration appear suboptimal, although more discussion of the reasons behind the design decisions might sway my opinion.

Integration into DISEASES and PHAROS suggest the TIGA data will make a lasting impact.<br />

On 2015-04-27 22:47:48, user Jeffrey Ross-Ibarra wrote:

Cool analysis and comparison of TEs among these taxa. I wondered why a simple model of drift wasn't more seriously considered? Couldn't this explain similar numbers of fixed differences (since substitution of neutral copies would be independent of Ne) between D. sim and D. mau, but a lower Ne in D. mau would lead to fewer total polymorphic TEs and fewer TEs at low frequency?

On 2016-07-09 09:07:16, user David Colquhoun wrote:

I left a comment on the Nature commentary on this paper. Probably it should have been left here, so I'll repeat it.

Congratulations to Curry et al for managing to have an impact on what I now like to call the legacy publishing industry. It's taken far too long. It was 1997 when Seglen et al pointed out that the number of citations that an article gets is not detectably correlated with the impact factor of the journal in which it appears. I emphasized it again in 2003, in this journal [Nature].

After 20 years of pressure, it seems that something may, at last, be done about it. Not enough, of course. The impact factor has had such a corrupting effect on science that it should be forgotten altogether. Perhaps, when citation distributions are published, it will become so obvious that its mean is such an absurd measure that will happen. Expect that to take another 20 years.

The really interesting question, though, is whether Nature or Science will still be publishing original research 20 years hence. By then I expect they will be reduced to news journals, and research will be published in far cheaper journals, with fully open access. Even if that doesn't happen for good scientific reasons, it may well happen because universities can no longer afford the huge cost of Elsevier, Cell Press and NPG journals.

On 2020-04-19 12:13:22, user Saurabh Gayali wrote:

Url shows error:<br /> DNS_PROBE_FINISHED_NXDOMAIN

On 2023-12-21 04:29:43, user roshan.nepal wrote:

The intra-host evolutionary landscape and pathoadaptation of persistent Staphylococcus aureus in chronic rhinosinusitis

https://www.microbiologyres...