On 2020-01-22 16:28:23, user Saad Khan wrote:

Very cool paper. What would happen if you tested both tavaborole and norvaline at the same time? Would the effects shown here cancel out, or would you have a net loss in e. coli population relative to control, or could it even lead to selection for tavaborole resistance that is not susceptible to norvaline? <br /> I also think in a therapeutic context, it's important that a combination therapy involving simultaneous or alternating doses of the antibiotic should result in a faster elimination of the pathogen than antibiotic alone. ie. the growth in wild type population that occurs due to norvaline supplementation should be less than the amount of elimination that you get from antibiotic.

On 2020-01-21 14:39:45, user Serguey Melnikov wrote:

All your feedback is very welcome!

On 2020-01-22 15:09:50, user Momo Vuyisich wrote:

Your description of the sequencing method is incorrect. You are not sequencing the 16S rRNA. You are sequencing a small portion of the 16S rRNA gene.

On 2020-01-22 10:04:40, user Dirk Jochmans wrote:

Pure theoretical study. We need to be careful with conclusions. From the speed of the current outbreak I doubt that 2019-nCoV is less infectious in humans than SARS. We need in vitro/in vivo data before making these claims. Also more data from the clinic would be very informative. These viruses do weird things sometimes. NL63 CoV also binds ACE2 but in a very different way, maybe this should be included in the paper.

On 2020-01-22 08:08:13, user Shillah Simiyu Mangwa wrote:

Yesterday, the Chinese Health authorities reported that human-to-human infection is possible, and the virus has killed slightly more than 6 people. How then do your findings suggest that the virus " does not readily transmit between humans and should theoretically not cause very serious infection"?

On 2020-01-22 09:59:57, user Alexandre Kitching wrote:

The software can be found here: <br /> https://github.com/lumevr/vLume/releases

(Please make sure you read the SI and User Manual first)

We really hope it will help you see your data in a light and analyse it more intuitively!

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

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

On 2020-01-21 13:20:09, user Anastasia Stefanaki wrote:

What a nice paper! We had similar findings on rare and threatened plants in Greece. Species with zygomorphic flowers appeared to be more vulnerable. See https://journals.plos.org/p...

On 2020-01-21 12:05:26, user Gennady Afanasiev wrote:

I’d like to inform you that in 2015, during the excavation of the Sarmatian burial mound located in the central part of the historical Khazaria (Rostov district), a later inlet burial was discovered in the burial mound (Kamyshevakhsky burial ground X, burial mound 2, burial 2). The authors of the excavation (P. Uspensky and R. Mimohod) very tentatively dated it to the 12th-14th century. This date appears in Damgaard's article "137 ancient human genomes.." (DA142). Recently there was information that this sample is dated 618-918 years.

https://www.theapricity.com...

That is, we have two important arguments: the Khazar time and the geographic center of the Khazar Khaganate. And here it is especially interesting that this sample has R1a1a1b2a2 Y-DNA and J1c5a1 mtDNA. If I am not mistaken, this female subclade is often found in Ashkenazi.

http://open-genomes.org/ana...

On 2020-01-21 01:57:04, user Hazard wrote:

Happy to share our study on endothelial to haematopoietic stem cell transition. Up to date, the precisest identification and the most comprehensive interpretion of Haemogenic Endothelial Cells at the Transcriptomic, Immunophenotypic and Functional levels (tif-HEC).

On 2020-01-20 23:39:58, user Sebastian Aguiar Brunemeier wrote:

The rationale behind this study is convincing, and thankfully someone is doing the duty of publishing 'negative' results, i.e., a dose of reality on what does *not* work. This is valuable to the community.

On 2020-01-20 23:30:43, user Dylan Glubb wrote:

I'm a bit surprised that the largest endometrial cancer GWAS study to date (Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7) wasn't included in the analysis.

On 2020-01-20 23:04:52, user Peter Sorger wrote:

This paper has now appeared in Elife as follows:<br /> 2019 Nov 19;8. pii: e50036. doi: 10.7554/eLife.50036.

On 2020-01-20 11:52:35, user Moritz Graeff wrote:

Very intresting work with promising applications. There seems to be a little error in Figure 1a, or is there an amino-group in IAA I so far overlooked?

On 2020-01-20 11:47:22, user Robert King wrote:

Is there an estimate when the genome will be available from NCBI so can compare with what the paper is saying?

On 2020-01-20 11:27:49, user Jubin Rodriguez wrote:

Many thanks for your responses. I look forward to testing out URMAP

On 2020-01-15 12:08:23, user Jubin Rodriguez wrote:

How does URMAP compare to BBMap in terms of speed?

On 2020-01-20 08:06:33, user Mazher Farid Iqbal wrote:

Respected reviewers. Kindly review it and give your valuable suggestions please,

On 2020-01-20 08:03:27, user Mazher Farid Iqbal wrote:

Kindly review the paper and give valuable suggestions please

On 2020-01-20 02:35:47, user Jonathan Gent wrote:

It's in press: https://genome.cshlp.org/co...

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 2020-01-19 07:59:42, user Qi Zhao wrote:

Good job! I think a comparison should be made between ideal and IDEA in the manuscript. <br /> Plz see my previous manuscript of another differential expression analysis tools kit and R package. https://www.biorxiv.org/con... and https://github.com/likelet/...

On 2020-01-18 17:42:08, user Patrick Griffin wrote:

Has anyone attempted this protocol? I have and would like to compare notes. It would be very nice if the authors would provide some of their supplementary methods and details, though I understand the paper may be under review.

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

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

On 2020-01-18 00:13:20, user Rodney Savidge wrote:

Is the full potential for ethylene production by Citrus being given recognition? See Plant Physiol. (1970) 45, 533-534

On 2020-01-17 13:54:38, user Erika H wrote:

Hi! This is an awesome study, and a great read. Cool to see more and more studies published using ASVs/ESVs in lieu of traditional OTUs.

However, there was one mistake in the pre-print that sort of jumped out at me. In this line: "Briefly, the V3-V4 region was amplified using primers 515F-Y/926R (Parada et al. 2016) followed by library preparation (2 × 300 bp) and sequencing on a MiSeq Illumina platform."

If the primers being used are from 515/926, the region amplified is actually V4-V5 not V3-V4.

Best,

E

On 2020-01-17 10:47:51, user Sergiy Korol wrote:

Hello, Proud to announce that the article is published today, 17th of January 2020 on the International Journal of Molecular Sciences web site with DOI https://doi.org/10.3390/ijm....

On 2020-01-17 09:44:08, user Thomas Haverkamp wrote:

Hey, nice paper, but which assembler did you used to generate the assembly graph that is used by SCAPP? and why did you use that assembler?

Best<br /> Thomas Haverkamp

On 2020-01-16 19:55:30, user Tom Radivoyevitch wrote:

In Figure S4, patient 15, did the TKI start at month 0 or did it start at month ~40?

On 2020-01-16 19:47:17, user Guy G wrote:

Gotta love the tweet storm around this article. How many universities around the globe are downloading the code?

On 2020-01-16 18:37:02, user Peter Frost wrote:

Calcidiol levels are higher in redhaired people because the level of calcidiol, like the incidence of red hair, is increased by estrogen, i.e., women have higher calcidiol levels and a higher incidence of red hair. In both cases, we are looking at an estrogen-induced effect.

There is good evidence that calcidiol levels differ between men and women. In their review of the literature, Epstein and Schneider (2005) concluded that “the majority of studies have found a positive effect of estrogen on calcitriol levels.” Testosterone has no effect. Similarly, Barnes et al. (2007) noted this sex difference when they studied people with multiple sclerosis and people without MS.

The sex difference reverses with age. In fact, vitamin D levels are lower in elderly women than in elderly men. At that age the sex difference seems to be explained entirely by differences in body fat (van Dam et al. 2007).

Why, then, did your study not find a significant sex difference? A big reason is the age difference between your male participants and your female participants (6.6 years). There seems to be an interaction between age and sex, i.e., the sex difference in vitamin D levels decreases with age and then reverses.

Why should sex have a stronger effect on hair redness than on vitamin D levels? Women need more vitamin D only when they are pregnant or lactating (Kumar et al. 1979). In contrast, red hair has a selective advantage over a longer time span, i.e., when women are sexually mature (Frost et al. 2017) .

References

Barnes, M.S., M.P. Bonham, P.J. Robson, J.J. Strain, A.S. Lowe-Strong, J. Eaton-Evans; et al. (2007). Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers. Multiple Sclerosis Journal 13(5): 670-672.

Epstein, S., and A.E. Schneider. (2005). Drug and hormone effects on vitamin D metabolism. In: D. Feldman, J.W. Pike, F.H. Glorieux (eds). Vitamin D. San Diego: Elsevier.

Frost, P., K. Kleisner, and J. Flegr. (2017). Health status by gender, hair color, and eye color: Red-haired women are the most divergent. PLoS ONE 12(12)

Kumar, R., W.R. Cohen, P. Silva, and F.H. Epstein. (1979). Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. The Journal of Clinical Investigation 63(2): 342-344.

Van Dam, R.M., M.B. Snijder, J.M. Dekker, C.D.A. Stehouwer, L.M. Bouter, R.J. Heine, and P. Lips. (2007). Potentially modifiable determinants of vitamin D status in an older population in the Netherlands: the Hoorn Study. American Journal of Clinical Nutrition 85: 755-761.

On 2020-01-16 15:16:01, user David Ron wrote:

The theme of co-evolution, as it relates to the recognition of JDP and Hsp70 is nicely developed in this scholarly paper. It might be interesting to consider the suppression of the DnaJ D35N mutation by DnaK R167H, alluded to in the discussion as a case of co-evolution affecting the mechanistic step. It might be helpful were the authors to digress further on the basis of the functionality of the R167H mutation in DnaK? Does it maintain the interaction with D517-SBD and D429-linker? How does it suppress the HPD>HPN mutation? Could this pair serve as fodder for an MD simulation such as the one presented for the wildtype DnaK/DnaJ pair in figure 2b?

On 2020-01-16 03:00:34, user David Ron wrote:

The theme of co-evolution, as it relates to the recognition of JDP and Hsp70 is nicely developed in this scholarly paper. It might be interesting to consider the suppression of the DnaJ D35N mutation by DnaK R167H, alluded to in the discussion, as a case of co-evolution affecting the mechanistic step. It might be helpful were the authors to digress further on the basis of the functionality of the R167H mutation in DnaK? Does it maintain the interaction with D517-SBD and D429-linker? How does it suppress the HPD to HPN mutation? Could this pair serve as fodder for an MD simulation such as the one presented for the wildtype DnaK/DnaJ pair in figure 2b?

On 2020-01-16 15:04:39, user Axel Loewe wrote:

Published conference proceedings article: 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)<br /> doi:10.1109/EMBC.2019.8857573

On 2020-01-16 09:10:48, user Gabriele Giachin wrote:

This paper has been accepted now on Biophysical Journal: https://www.cell.com/biophy...

On 2020-01-16 02:12:22, user Adeline Boettcher, PhD wrote:

A finalized version of this manuscript can be found at: https://www.frontiersin.org...

On 2020-01-15 19:00:39, user Joshua Shaevitz wrote:

Please not that there is a typo in the URL for the source code. It should be: https://github.com/talmo/leap

On 2020-01-15 16:40:50, user laschp13@gmail.com wrote:

The software, LC-MS¹ test data and the in silico database can be obtained from the following web addresses:<br /> Software: https://wiki.microbe-ms.com<br /> in silico database: /10.5281/zenodo.3573996(Zenodo)

Peter Lasch

On 2020-01-15 10:33:10, user qx jiang wrote:

This paper is now published by JBC with a different, more informative title. <br /> https://www.ncbi.nlm.nih.go...

On 2020-01-15 10:32:04, user Bas E. Dutilh wrote:

This paper has now been published in Genome Biology doi: 10.1186/s13059-019-1817-x

On 2020-01-15 05:55:44, user Vladimir Seplyarskiy wrote:

Signatures track <br /> https://drive.google.com/dr...

On 2020-01-15 05:42:01, user Prashant Mishra wrote:

Novel discovery in the field of imaging. Will have solution for high resolution microscopy in simple way.

On 2020-01-15 00:54:57, user Dai Mitsushima wrote:

Now I fixed graphic errors in Figures 2 and 3. PDF version 5 or later is OK. I am sorry for the inconvenience.

On 2020-01-14 17:57:58, user Charles Warden wrote:

I'm sorry, but I think your title has a typo:

Do you mean "non-coding" instead of "non-doding"?

On 2020-01-14 16:35:39, user Anne-Catherine Prats wrote:

This paper is now published in eLife 2019 Dec 9;8. pii: e50094. doi: 10.7554/eLife.50094.

On 2020-01-14 14:23:28, user Arnaud Martin wrote:

Great paper! Quick suggestion:<br /> Use the unified terminology : DWnt4 is actually Wnt9 (doi:10.1186/1471-2148-10-374).<br /> This matters because Wnt9 is a clustered paralog that groups with Wnt1/6/10<br /> (DOI: 10.1093/molbev/msq052), and that could be co-regulated. There is no true Wnt4 in insects (doi:10.1186/1471-2148-10-374)

On 2020-01-14 13:34:08, user Ying-Chi Chan wrote:

We have made revisions to the abstract and the content of the article. For the newest version, please refer to the published article in Global Ecology and Conservation (open access). Thanks!

On 2020-01-14 10:53:12, user Fernando Meloni wrote:

This paper is published in Physica A.

https://www.sciencedirect.c...

https://doi.org/10.1016/j.p...

On 2020-01-14 09:25:29, user Silas Kieser wrote:

Dear Authors, <br /> thank you for identifying the difficulties in the quality estimation of many eukaryotic clades.

Have you seen, that BUSCO 4.0 was just released? It has more fine-grained marker sets than BUSCO 3. I wonder if the mentioned shortcomings still persist. <br /> Also, do have you the data of the running time / resource usage for the different tools in your benchmark?<br /> Kind regards<br /> Silas Kieser

On 2020-01-14 08:06:01, user Eran Elhaik wrote:

My response to this study is now available on BioRxiv: https://www.biorxiv.org/con...

On 2019-12-19 10:19:40, user Gennady Afanasiev wrote:

An article of interest, but a lot of fundamentally important mistakes. Firstly, there is no comparison of the Khazar samples with the population of the same region of the Sarmatian time (although the data are published). Secondly, there is no comparison of the Khazar samples with the sample of Don Alans (this is the same time and the same culture, data published). Thirdly, there is no comparison of the Khazar samples with the samples of the North Caucasian Alans (at the same time, data published). General impression: a good laboratory analytical part, but the comparative analysis and historical interpretation leaves much to be desired.

On 2019-12-17 05:52:26, user kevinbrook wrote:

When I wrote my first comment today, I didn't realize that the <br /> Khazarian mtDNA haplogroups in this study have already been summarized <br /> in the supplementary file: C4, C4a1, C4a1c, D4e5, D4b1a1a, H1a3, H5b, <br /> H13c1, and X2e. I had just seen where the preprint said they "will be released upon publication."

On 2019-12-17 05:37:31, user kevinbrook wrote:

This is a very important study and many of us are eagerly anticipating the release of the final version of the paper, including its set of mtDNA data that will appear in Table S3.

I found it odd, however, that this preprint cites Eve Krakowski's positive review of the 2nd edition of my book "The Jews of Khazaria" rather than citing my book directly, especially the 3rd edition (written in 2017 and published in February 2018) which was the first Khazar history book to discuss DNA data from medieval Khazars (albeit not from this study, obviously).

The preprint found that "none of the identified [Khazarian] mitochondrial haplotypes are present in present-day Ashkenazi Jews". I correctly predicted this on page 207 of the 3rd edition of my book where I wrote: "None of those [Ashkenazic] mtDNA haplogroups are identical to the ones identified to have been present among medieval inhabitants of Khazaria and Hungary (see chapters 1 and 9), and, although the number of DNA samples from Khazaria is currently limited, there is no reason to believe that any additional samples from Khazaria would include them either."

The paper's co-author Vladimir Klyuchnikov is a contributing writer at my website, Khazaria.com

On 2020-01-13 17:30:31, user Ingeborg Zehbe wrote:

Dear Dr. Lou,

Thank you for sharing your interesting results with the scientific community. Would it be possible to get a breakdown of the samples mentioned in Figure 1? Could you provide some metrics in terms of numbers to complement your data reported in percentage (%): how many A1, D2 and D3 cases did you find in each group of the total samples size n=96 and likewise, how many in each group were integrated?

Thank you so much for considering to answer my questions.

Sincerely, Ingeborg Zehbe

On 2020-01-13 12:16:02, user Phil wrote:

Seems like this paper is now published in Nature Structural & Molecular Biology<br /> https://www.nature.com/arti...

On 2020-01-13 09:46:00, user Lera Sulejmanovski wrote:

Looks like there could be some errors in the "Percent of views, by OA type" and "Percent of papers, by OA type" sections. The numbers in the OA columns (green, gold, hybrid, etc.) don't always add up to the number in the "all OA" column.

On 2020-01-13 04:58:41, user Alex wrote:

The paper refers to supplementary data, but the data doesn't appear to be available

On 2020-01-12 23:28:09, user yochannah wrote:

Hey - just FYI - I went to the GitHub link in the preprint - the link doesn't work for <br /> github.com/optimusmoose/xflow - is it possible it's set to be a private repo? :)

On 2020-01-12 15:25:23, user Heba Ibrahim wrote:

This is an interesting paper. Although it is not in my field of expertise, it is important to understand the mechanistic regulation of the pathogen system we are working with. However, I have few comments that might be of interest to you.

• As I understand from the presented results, the pathogen here performs somewhat better under constant light condition than in constant darkness. Therefore I expected that the infection rate would be higher at dawn than at dusk, based on the other findings with the biomass, sporulation, and germination rate. Maybe what is missing here is to link these results with another experiment testing the plant immunity (similar to the one you performed with the transgenic PR1-GUS lines) but in this case it would be during dusk and in dawn. This would be to confirm that the difference in the inoculation rate is due to the circadian clock of the pathogen and not due to the reduced defense response of the plant to pathogens at dusk.

• Related to this, the abstract reads “Contrastingly, exposure to constant light or constant dark suppressed sporulation. Exposure to constant dark suppressed spore germination, mycelial development and oospore formation. Interestingly, exposure to constant light stimulated spore germination, mycelial development and oospore formation.”. This sounds contradictory since according to this, first constant light suppresses, then stimulates spore formation.

• For the data representation, the data is shown in bargraphs with SE. I think these data should be presented in box plots, showing all data points, since they are quantitative data. Bar plots misrepresent such data often, especially given the rather low number of data points, which doesn’t allow to judge the data point distribution (see for example here: doi:10.1371/journal. pbio.1002128).

Thanks for the nice paper. I enjoyed reading it and I hope my comments are useful.

On 2020-01-11 22:41:39, user Martin Collinson wrote:

Like this, and thanks for citing our paper (6 - Findlay et al). If it helps to get this through review, we have also published on role of Vangl2 in apical/basal polarity (Panzica et al. <br /> https://doi.org/10.1111/joa.... On a science point, that paper (and previous ones e.g.

Dor?a NJ et al. (2014) Hemizygous Le-Cre transgenic mice have severe eye abnormalities on some genetic backgrounds in the absence of LoxP sites. PLoS One 9, e109193.) showed that Cre itself may produce a phenotype in corneal epithelia independent of floxed genes. In practice that means that if we are studying phenotype of [Cre-positive/active, Gene flox/floxed] mice, the appropriate controls are [Cre-positive/active, Gene +/+]] mice. [Cre-negative/inactive, Gene flox/flox] mice, as apparently used here, are not controls.

On 2020-01-10 15:55:35, user PMI Journal Club at MPIPZ wrote:

We recently reviewed this paper in our pre-print journal club at the Max Planck Institute for Plant Breeding Research. The review can be found here: https://www.authorea.com/41...

On 2020-01-10 11:38:26, user jvkohl wrote:

ICYMI: Their significance statement links natural selection for food energy-dependent codon optimality from the physiology of pheromone-controlled reproduction to biophysically constrained viral latency and healthy longevity via epigenetically effected microRNA-mediated sympatric speciation in all mammals.

Fixation of the EDAR V370A amino acid substitution is the example I used in my mouse-to-human model.

On 2020-01-10 05:33:46, user Saurabh Gayali wrote:

I would suggest correcting title and adding affiliations.

On 2020-01-09 23:34:55, user Gary Stacey wrote:

A related paper overlooked by these authors that presents a somewhat different view

Dongqin Chen, Nagib Ahsan, Jay J. Thelen, Gary Stacey. 2019. S-Acylation<br /> of plant immune receptors mediate immune signaling in plasma membrane nanodomains<br /> BioRxiv doi: https://doi.org/10.1101/720...

On 2020-01-09 23:29:46, user Nilesh Banavali wrote:

I enjoyed this paper because I have recently published reactant, intermediate, and product models for drosophila hedgehog along with the SRR region (by hypothesizing it to be similar to cholesterol-bound cryptogein). These pdb format files are part of the supplementary material, and are available for download at https://onlinelibrary.wiley.... It would be informative to make specific comparisons of the present results with the 3D models to see if they are consistent, or if the models can be improved using restraints derived from these results. Best regards, Nilesh

On 2020-01-09 18:49:08, user Hannah Takasuka wrote:

Under the "SHIELD Processing" section under methods, I believe that the first reference should be 13 and not 3.

On 2020-01-09 17:37:50, user George Weiblen wrote:

The preprint is based on a genome described in 2018 and the authors could improve the manuscript by acknowledging the original source of the data.

Grassa, C. J., J. P. Wenger, C. Dabney, S. G. Poplawski, T. Motley, T. P. Michael, C. Schwartz, J., and G. D. Weiblen. 2018. A complete Cannabis chromosome assembly and adaptive admixture for elevated cannabidiol (CBD) content. bioRxiv 458083.

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

On 2020-01-09 13:01:06, user Sabyasachi Rakshit wrote:

This is now published in Febs J.

https://doi.org/10.1111/feb...

On 2020-01-09 12:59:35, user Sabyasachi Rakshit wrote:

This is now published in Biochem J.<br /> https://doi.org/10.1042/BCJ...

On 2020-01-09 09:51:03, user Begossi Alpina wrote:

The manuscript is shortened and more objective. All the parts of CS _Citizen science will be part of a introduction to the book Garoupas e Pescadores (Brasil) (Groupers and Fishers Brazil). The part with the results about groupers in Copacabana is submitted to Environment, Development and Sustainability as: "A sustainable fishing of dusky grouper (Epinephelus marginatus) in the small-scale fishery of Copacabana, Rio de Janeiro, Brazil". Alpina Begossi, January 9, 2020.

On 2020-01-08 23:06:56, user PZM Diagnostics wrote:

This article has been accepted for publication in Fetal & Pediatric Pathology, published by Taylor & Francis"

On 2020-01-08 17:41:04, user Thomas Weitzel wrote:

IMPORTANT UPDATE: The most abundant chigger morphotype found in our study was re-classified as Herpetacarus species. For more information, please see the upcoming article.<br /> Thomas Weitzel

On 2020-01-08 13:41:35, user Peter Prudon wrote:

Hi Daniel et al.,<br /> I think you will do well to have a look at the work of Reuven Dar on the use of "proxies" by OCD patients. Latest study: Dar, R., Eden, T., Dongen, M. van, Hauschild, M., & Liberman, N. (2019). Obsessive-compulsive tendencies predict seeking proxies for understanding. Journal of Behavior Therapy and Experimental Psychiatry, 64, 87-91. https://doi.org/10.1016/j.j...<br /> Referring to it should not be missed in the article.<br /> Regards,<br /> Peter

On 2020-01-08 06:33:29, user VIJAY LAKHUJANI wrote:

Spelling mistake 'Signifiacantly'

On 2020-01-07 22:49:15, user Donal Hickey wrote:

WJR (Walter J. Remine?) states that we have biased the simulation results in favor of the sexual population by choosing a large population size combined with strong selection. In order to address this concern, we reduced both the population size and the selection coefficient. As expected, we found that reducing the selection coefficient merely slows the process, but does not change the outcome. The reduction in population size increases the amount of genetic drift in both populations. Asexual populations are subject to genetic drift because of the stochastic variance in the number of offspring per individual. Apart from genetic drift, the reduction in population size has a major negative effect on the asexual population only. This is because the lower population size reduces the probability of finding a chromosome carrying more that one favorable allele in the initial asexual population.

Reducing the starting frequency would also be disadvantageous to the asexual population because it also reduces the probability of finding chromosomes carrying more than one favorable allele. For example, when the starting frequency is 0.05, the chance of finding a chromosome carrying two favorable alleles is 1 in 400. But if we reduce the starting frequency to 0.01, the chance of finding two favorable alleles is reduced to 1 in 10,000. Again, this proposed change would have a negative impact on the asexual population rather than on the sexual population.

WJR seems to be deliberately obfuscating the mutational rates. They note a rate of 100 per individual which is obviously radically different from our assumption of 1x10^-8. But WJR should know that that 100 mutations per individual is the rate for the entire genome rather than the rate for individual nucleotides. Since a diploid human genome contains 2 x 3.234 x10^9 base pairs, then the rate of 100 mutations per the entire genome corresponds to a rate of 1.5 x 10^-8 per nucleotide, which is quite close to the rate assumed by us. In any case, WJR is deliberately bringing up a red herring and pretending to land a whale. Mutations of any kind happen at such a low rate that they have negligible effects on the results. The main effect is due to the sorting of the existing selectable genetic variation through recombination in the sexual population.

Our main focus was on the selection of beneficial alleles, following the scheme used in Haldane’s original papers. Since we were testing Haldane’s dilemma, it was important to follow his model. We did not consider deleterious mutations because the effect of recombination on such mutations has been described many years ago by H.J. Muller. The effect is known a Muller’s ratchet.

Increasing the recombination rate does not change the outcome. Indeed, free recombination between all 100 genes gives the same result. A little recombination goes a long way!

Epistasis is defined as the deviation from multiplicative fitness. We used multiplicative fitness in the simulation. Therefore, the level of epistasis in the simulation is by definition zero.

Doubling the reproductive rate of the asexual population would not change the results because it would have no significant effect on that population’s ability to produce new combinations of favorable alleles through recombination.

I have attended a number of horse races, but I have yet to witness a case where the fastest horses combined to produce an even faster super-horse. Neither have I seen new horses added during the course of the race. Are they added at start line or near the finish line? This analogy needs more work.

On 2020-01-07 21:32:26, user Matthew Borchers wrote:

Did you run BUSCO on your final genome assembly?

On 2020-01-07 21:16:33, user Howard Junca wrote:

Extremely happy for this proposal continuing the work on this model strain 1dBTEX2 that I isolated 18 years ago! Back then we finally found a naturally evolved type able to handle monoaromatics from typical polyaromatic mechanisms with few mutations in key enzymes. As suggestion, the original references of isolation and first insights at: https://sfamjournals.online... https://www.microbiologyres... https://aem.asm.org/content... https://www.sciencedirect.c...

On 2020-01-07 13:46:55, user João Saraiva wrote:

When do you expect to have this out in press?

On 2020-01-07 00:25:42, user Guofeng Meng wrote:

Comments are appreciated to improve this manuscript.

On 2020-01-06 14:26:39, user Diethard Mattanovich wrote:

The research summarized here was recently published in Nature Biotechnology:<br /> Gassler, T., et al. The industrial yeast Pichia pastoris is converted from a heterotroph into an autotroph capable of growth on CO2.<br /> Nat Biotechnol (2019) doi:10.1038/s41587-019-0363-0<br /> https://doi.org/10.1038/s41587-019-0363-0

On 2020-01-05 20:01:48, user Douglas Silva Domingues wrote:

Very nice tool...really recommend you to mantain it.

On 2020-01-05 08:53:18, user sunburnt wrote:

This is great news.

Am I right in observing that it took a while to go from the original Yaminaka research from what.. the mid 2000s to now.. over 10 years later & we are just now trying to in vivo epigenetic resets?

What was the hold up? Was there a general assumption that all in-vivo resetting would cause teratomas?

Also, now that Lu, & Sinclair has shown it may be possible, can we now expect a global tidal wave of research into this area?

On 2020-01-04 22:25:11, user Leonardo wrote:

Yeah I've always said that about "genome-wide association studies" - so is there a stupid patient-level explanation of this?

On 2020-01-03 13:42:02, user Alexey Guzey wrote:

A response to this paper was posted by Lee et al (authors of the original study): https://www.biorxiv.org/con...

On 2020-01-03 05:05:47, user Pavel Prosselkov wrote:

The title does not sound right, it is actually wrong. Better to "Heritability of the FR NTW"

On 2020-01-03 03:04:45, user Adam Yates wrote:

What definition of Brevirostres are you using? You state that Alligatoridae is the crown of Brevirostres but I've always thought that Brochu's definition (Alligator + Crocodylus) is the only working definition of Brevirostres. Perhaps you are inadvertently using Brevirostres in place of Globidonta ?

On 2019-12-28 19:49:18, user David Marjanović wrote:

This is a manuscript submitted for review to the Timetrees topic of Frontiers in Genetics under constraints of both time and space. This is why the discussion is a little short, and why I accidentally applied the calibration of Node 108 to Node 107 (although that's not likely to have any noticeable effect on the results).

My name contains a "nonstandard character" because the standard bioRχiv [sic] is on is still ASCII!

On 2020-01-02 18:29:46, user Richard McKenney wrote:

The work presented in this manuscript confirms published observations from our own lab (Tan et al. Nat. Cell Biol. 2019), in which we found that tau molecules cannot bind as densely along GMP-CPP (a GTP-like state) microtubules, as compared to taxol or native GDP microtubule lattices. Both our earlier work, and the current manuscript, support previous observations from the Goodson lab showing that tau has a higher affinity for GDP, versus GTP-like microtubule lattices (Duan et al. J. Mol. Biol. 2017). It should also be noted that work from the Berger lab has previously shown that tau does not have the same effects on processive kinesin transport depending the nucleotide state of the microtubule lattice (McVicker et al. J. Biol. Chem. 2011). Together, these studies lead to the picture that the tau molecule intrinsically recognizes the nucleotide state of the microtubule lattice, an effect likely mediated by changes in the spacing of tubulin dimers within the assembled microtubule. Further support for this conclusion comes from earlier observations that tau preferentially binds highly curved regions of microtubules in living cells (Samsonov et al. J. Cell Sci. 2004, Ettinger et al. Curr. Biol. 2016, and this manuscript), and in vitro (Tan et al. Nat. Cell Biol. 2019). It will be interesting to further delineate the molecular mechanism of tau’s intrinsic ability to distinguish different conformations of the microtubule lattice.

On 2020-01-02 07:53:49, user StreuthCobber wrote:

"The collar rot causing oomycete, Phytophthora agathidicida, threatens the long-term survival of the iconic New Zealand kauri." Have we got a reference for that foundation statement. Black & Dickie Independent Kauri Dieback Review described Phytopthora Agathidicida being the sole causal agent as a "hypothesis." It was found in 1972 on Great Barrier where Kauri are still thriving. IN the largest and most recent testing done by Auckland Council, significantly more of the soil samples in Waitakere came back positive for Cinnamomi than PTA when symptomatic trees were tested, and an equal number came back for P. Multivora.. P. Cinnamomi has been causing dieback in the ranges since at least 1950's in the Centennial Park, Cascades, and at Cornwallis. (Newhook 1974 and Atkinson) Cornwallis is an area of historic gum resin - so severe resinosis happened before? "The observation of a<br /> more widely dispersed and high genetic diversity species is suggestive that either P.<br /> agathidicida could be a native species or, alternatively, that there have been multiple<br /> introductions to New Zealand." (Black and Dickie Independent Kauri Dieback Review). Ohia tree dieback in hawaii thought to be catacalysmic attack by P. Cinnamomi was part of a multifactoral problem and successional resulting in dieback areas growing more and taller saplings.

On 2020-01-01 10:05:05, user Serguey Melnikov wrote:

Interesting paper! I wonder if you had a chance to look at our recent study on a similar topic where we showed that Lokiarchaeota have many segments in ribosomal proteins that are identical to nuclear localization signals in eukaryotic ribosomal proteins: https://www.biorxiv.org/con...

On 2019-12-31 18:11:21, user Paul Schanda wrote:

This is a very interesting work on the plasticity of the SurA chaperone in its apo state and binding outer-membrane proteins (OmpX, OmpF). The paper has a couple of nice experiments, and in particular the combination of techniques (smFRET, cross-linking mass spectrometry (XL-MS), mass-spec-detected hydrogen-deuterium exchange, a bit of MD simulations) is appealing.

Detecting and localizing chaperone-client protein contacts is a difficult endeavor and the authors primarily use mass-spec methods to this end. As I am not an expert with mass spectrometry I have questions, as some of the data are not entirely convincing to me.

1. the Lys-based XL-MS results are quite puzzling to me, and they even seem to be in contradiction to the "tag-transfer" XL-MS results. In particular, Figure 4 shows cross-linking of OmpX to almost all parts of SurA, including residues that are clearly turned outwards (in the structure shown, at least). In contrast, the experiment that uses MTS-diazirine and UV-cross linking shows a much more narrow cross-linking pattern. How should one interpret this?

Should one basically drop the results from the Lys-cross linking (with DSBU) altogether, as it seems to me that it may contain quite a number of false positives ?

1. the HDX-MS results are also a bit unclear to me. The mass uptake in D2O are fairly small, and the differences with/without client protein appear very small. For the shown peptide fragments (about 20 residues long) the differences in mass uptake with/without OMP are well below 1 Da (i.e. well below one hydrogen atom) over 100 minutes. In some cases, the difference is essentially zero in Figure S10 (e.g. first line second plot, or second line, plots 1 and 3, where there is even a cross-over, suggesting that the error bars are underestimated?).<br /> I do not have much experience with mass-spec detected HDX. How reliable are such data?

2. I was curious why the authors have not tried to detect FRET effects between the chaperone and the OMP, i.e. having one dye on each of these two proteins. Such an experiment may allow them to further localize the binding site.

Congratulations to this interesting paper.

On 2019-12-31 01:05:06, user Charles Warden wrote:

Hi,

Thank you for posting this pre-print.

There are 4 factors that I would guess would affect mutation calling:

1) Total number of reads<br /> 2) Pairing of reads (single-end versus paired-end)<br /> 3) Read length<br /> 4) Fragment length

Unless there was an advantage to having forward and reverse reads for the same position, I am assuming you would want a large enough fragment length to get different sequence from forward and reverse reads (and perhaps I shouldn't have thought of this when I first read "library size").

However, it looks like you mostly focus on the 1st criteria (total number of reads). Do you think this is a fair assessment of this paper?

For DNA-Seq, I would typically expect mutation calling to be performed with paired-end reads. At one point, I see you mentioning "45 CBF-AML RNA-Seq samples that were deeply sequenced with 100 base pair (bp) paired end (PE) reads". However, there is another point where "an independent AML cohort by using 136 50bp PE RNA-Seq samples" is mentioned.

I guess this means you would prefer to have paired-end reads (whereas single-end reads is more typically used for gene expression). However, do you mention anything about preference / effect of read length? I apologize if I overlooked this.

If you have reads that are twice as long, I would expect you might be OK with about half as many reads (and possibly also have some benefits with alignment). For example, is the recommendation of ~40M reads assuming that you have 100 bp PE reads (and perhaps would recommend ~80M reads if you had 50 bp PE reads, and perhaps recommend ~160M reads if you had 50 bp SE reads)?

That seems high for the SE reads, but I would probably only be looking at higher read fraction variants among higher expressed genes in that situation. I think I would also disagree with the total fragment count for gene expression in that situation (I think 20M 50 bp single-end reads is often OK for a polyA library, if you only do gene expression without variant calling). However, my impression is that you were describing higher sensitivity for variant calling in genes with FPKM < 1 with the paired-end reads (but please correct me if I am wrong). In that case, I think I agree with you (recommending at least 40M 100 bp paired-end reads).

Best Wishes,<br /> Charles

On 2019-12-31 00:29:29, user Charles Warden wrote:

Hi,

Thank you for posting this pre-print.

I looked into something somewhat similar in yeast, but this was predicted to occur more often in humans and flies.

One measure by which that would be true is with EvoFold predictions. While I think I have encountered some issues currently finding the source code, you can still see the predictions as a track for hg19:

https://genome.ucsc.edu/cgi...

It looks like you mostly use thermodynamic measures, but I think comparing overlap with conserved co-evolution of sites may also be interesting (which is what the EvoFold hg19 track may help accomplish).

There is some mention of human coding fRNAs in the original EvoFold paper (such as in the "New Coding fRNAs" section):

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

That paper also mentions some recovery of some specific examples (like A-to-I RNA editing), which I don't think I saw in this paper (and recovery of those types of annotations may provide some useful validation).

EvoFold was also able to identify a novel (non-coding) human gene (back in 2006):

https://www.nature.com/arti...

So, I think it may be worth looking into.

Best Wishes,<br /> Charles

On 2019-12-30 18:36:11, user Jonathan Weissman wrote:

We have critical concerns regarding this preprint by Dr. Reddy and co-workers. In particular we have previously communicated data that we feel directly refute the claims in this preprint to Dr. Reddy, yet they are ignored here. We therefore feel it is important to provide some context. A more complete description of our findings will be presented within 30 days following external review required by the terms by which we obtained some materials.

1. Although Dr. Reddy and co-workers suggest that the microtubule-destabilizing activity of rigosertib is mediated by a degradation product present in formulations obtained from commercial vendors, they are aware of our results demonstrating that pharmaceutical-grade rigosertib (>99.9% purity) and commercially obtained rigosertib elicit qualitatively indistinguishable phenotypes across multiple assays. The two compounds have indistinguishable chemical-genetic interactions with genes involved in modulating the microtubule network, both destabilize microtubules in cells and in vitro, and both show substantially reduced toxicity in cell lines expressing the L240F tubulin mutant, a rationally designed mutant in which the rigosertib binding site in tubulin is mutated. Our results demonstrate that pharmaceutical-grade rigosertib kills cancer cells by destabilizing microtubules, in agreement with our original findings and refuting the claims in this preprint.

2. Dr. Reddy and co-workers claim that the resistance conferred by our L240F tubulin mutant is non-specific without acknowledging that these claims are in direct conflict with a previously published report by an independent third party (Patterson et al. PMID: 31302152). In particular, Dr. Reddy and co-workers suggest a lack of specificity of the L240F tubulin mutant because in their hands expression appeared to confer mild resistance to the PLK1 inhibitor BI2536, but Patterson et al. conducted an essentially identical experiment and found that expression of the L240F tubulin mutant did not confer resistance to BI2536 (see Figure 7 in the manuscript by Patterson et al.). Their failure to cite or otherwise acknowledge Patterson et al. is all the more surprising, as we have previously brought this paper to their attention. Regardless, the combination of our previously published data and those presented by Patterson et al. firmly establish the specificity of the L240F tubulin mutant.

3. Dr. Reddy and co-workers claim that cells expressing the L240F tubulin mutant fail to proliferate in the presence of rigosertib, but we had demonstrated in our original manuscript that rigosertib-treated cells expressing the L240F tubulin mutant proliferated at the same rate as DMSO-treated cells over the course of multiple days (Fig. S6F in our original manuscript), and observe the same behavior with pharmaceutical-grade rigosertib. Thus, rigosertib-treated cells expressing L240F tubulin do not undergo senescence, as suggested by Reddy and co-workers, but actively proliferate.

Altogether, we conclude that there is no merit to the claims in this preprint and feel that any evaluation of the potential of Rigosertib as a clinical agent should be made in the context of these findings.

On 2019-12-30 18:12:36, user Fraser Lab wrote:

The major goal of this paper is to use diffuse scattering data to inform models of collective protein motions. This is a landmark paper that unites many disparate observations in the field and pushes the state of the art forward much more so than any paper since Wall et al, 1997 PNAS.

Through careful data collection, the authors are able to separate Bragg and diffuse scattering. The major experimental advance over previous work is that their fine-scale analysis enables them to integrate diffuse halos surrounding the Bragg peaks. This data yields the observations needed to model lattice dynamics. They find that lattice dynamics explain a significant fraction of the diffuse scattering data. Nonetheless, the authors noticed residual B-factors and turned to internal protein motions to explain the remaining disorder, which leaves signals both around the Bragg peaks and in hazy streaks and clouds between them.

To explain these residual features, they tested both normal modes analysis (NMA) and full molecular dynamics (MD). Furthermore, they were able to use Patterson analysis to choose between redundant NMA models, conquering an outstanding challenge in the field of macromolecular diffuse scattering. Surprisingly, the NM model that accounts for lattice motions and internal protein motions matches the data better than a crystalline MD model. What does this mean for MD that a reduced representation fits better?

Overall, the data collection and processing are extremely thorough. Opening up these analytical methods to the community is the next step - and publishing their code is the only essential revision we would request prior to publication.

Despite our enthusiastically positive interpretation, we do have a few minor questions and requests for clarification:

While examining the exponential decay in halos around the Bragg peaks, why are the 100 most intense peaks between 2 Å and 10 Å focused on? In Figure 2 it appears that there is a skew in the distribution of exponents toward a sharper decay (n > 2). How do the histograms look when more halos are sampled? Is it possible that this sharp decay could be explained by Bragg peaks that are leaking into adjacent voxels?

The authors are rigorous and explicit in their modeling efforts and make impressive strides forward. Still, we are left with questions about these models. For refinement of the lattice dynamics model, a small fraction of halos were chosen. Why did the authors not use all the halos? Why was the angular range of 2 Å to 2.5 Å chosen for refinement? Why does this resolution range differ from the analysis of halo decay ( 2 Å to 10 Å)?

As we commented above, we were surprised to see that a NMA model matched the diffuse intensities better than a crystalline MD model. We wonder whether incorporating the isotropic component of the diffuse scatter would alter this interpretation? Furthermore, since the authors scrupulously subtracted sources of isotropic background scatter, why was the remaining isotropic portion of diffuse scattering not used for refinement of the NMA and MD models?

Using diffuse scattering data to distinguish between competing models of motion has been a longstanding challenge in the field of macromolecular diffuse scattering, and we are impressed with the authors’ work in this regard. This is really a breakthrough! We were surprised to see how subtle the effects of restraining domain motions were upon the ΔPDF in Figure S17, can the authors comment on the statistical significance of this difference? What is the uncertainty in the Patterson map, and how does this play into the interpretation of the best model?

We have no major stylistic recommendations. The figures are elegant and clearly represent the main points of the paper. Similarly, the text is clear and concise, with thorough expansion in the supplemental material.

On a final note, this paper pushes the field forward, and we believe there is room for further speculation. A few areas to consider:<br /> How might crystallographers who encounter more mosaic Bragg peaks (these are some of the least mosaic crystals in existence!) separate the Bragg signal from the diffuse signal to analyze halos? <br /> In what ways can NMA models and MD be further improved to match diffuse scattering data? <br /> What complications might arise in crystals with more complex unit cells, and how can this be overcome? <br /> How do they reconcile the results of ref 18 with their analysis of the lattice dynamics (different systems obviously)?

The authors have done an excellent job of carefully collecting data, thoroughly analyzing it, and clearly explaining their work. We think that digging into the questions above may add to the already substantial impact of this paper, and look forward to their replies. Nonetheless, we think this important paper is worthy of publication as is (noting the caveat of code release).

We review non-anonymously, James Fraser and Alex Wolff (UCSF)

On 2019-12-30 14:59:49, user Lei Khiang Tswian wrote:

It would be great if Japanese and Siberian samples are included in the Admixture analysis. The purple source in Mongolic and Tungusic populations cannot be the same as that of Sino-Tibetans. It should be splitted into at least three sources including Northern Asian (Siberian), Eastern Asian (Japanese) and Sino-Tibetan (such as Yi/Naxi).

On 2019-12-30 06:58:01, user Koki Tsuyuzaki wrote:

I'm a developer of scTensor.<br /> Thanks for adding scTensor in your experiment,<br /> but there are many misleading or wrong parts as below,

so please consider the modification.

1. LRBase

In Figure 1C and the caption, you use "the database of scTensor", but please use "LRBase" (the name of our L-R database) instead.

Please note that the scTensor is the name of algorithm or the software package, and not L-R database.

Actually, scTensor can be used with any L-R database.<br /> https://rdrr.io/bioc/LRBase...

I think you should separately consider the effect of selection of L-R database and CCI detection algorithm based on the database.

2. Which is the largest LR database?

In the INTRODUCTION, you said

to the best of our knowledge, it is the largest database of this kind.

but in the Figure 1C, LRdb seems not so large.

3. Blank elements in Table 1

There are many blank elements in Table 1 scTensor column.

If you will add our method in your experiment, you should investigate it more.<br /> I still do not understand your intention of

complete pipeline<br /> the other items are as follow:

Accept preprocessed data Y

Export types<br /> tables Y<br /> circualar plots N<br /> graphML or equiv. N

Perhaps the complete pipeline means the built-in call type calling using t-SNE, k-means, or SIMLR but I don't think such name is appropriate, any tool can perform such task by combinined with the other tools.

Besides, if the user want to use other dimensional reduction, clustering, and cell type identification methods not included in your tool, your tool can be used with them?

4. UniProtKB/Swissprot

In the Comparison with other tools, you said

Swissprot annotations (secreted/membrane) automatically

but UniProt/Swissprot is based on the manual annotation.<br /> https://www.uniprot.org

We also used UniProt/TrEMBL and this database is based on the prediction by cellular localization algorithms.<br /> So please explain more accurately.

5. No registraction of LRdb in Bioconductor

In the AVAILABILITY, you said

the LRdb package is submitted to Bioconductor

but I couldn't confirm the submitted R/Bioconductor package,

although I could confirm that a TSV file is put on the GitHub.

https://github.com/Biocondu...<br /> https://www.bioconductor.or...<br /> https://github.com/SCA-IRCM...

Where was the package published?

6. Benchmark design

In the manuscript, you compared your method with other methods,

but the benchmark is not well designed; each method use different L-R databases and different algorithms, so even if your tool showed the good performance, the reader cannot understand why the tool was good.

Again, you should separately consider the effect of selection of L-R database and CCI detection algorithm based on the database.

7. Criticism against scTensor

As the criticism against scTensor, you said

We found 2 reliable LR pairs whereas scTensor returned 14 pairs, none in common<br /> or<br /> we found significant discrepancies with PyMINEr and scTensor

but there are no detail explanation or no quantitative evaluation,<br /> and these parts are just your impression.

Acutually, some L-R pairs detected by scTensor (Supplementary Table 3) are still curated and not "none in common".<br /> https://string-db.org/cgi/n...

Besides, as you said, LRBase includes many purative (not known) L-R pairs,<br /> you cannot simply say which L-R pair is correct or not.

On 2019-12-29 10:27:00, user Karel Riha wrote:

There are not so many studies trying to unravel the function of Ku at telomeres. Pity that some highly relevant are ignored here. https://www.ncbi.nlm.nih.go...

On 2019-12-29 09:33:00, user Kon Joo Lee wrote:

CFS / ME should be in a condition where cell or organ regulation is blocked. Adding only one drug to a cell culture activates or inactivates thousands of genes. CFS / ME may not be a matter of gene expression in individual cells but a body control system level problem.

On 2019-12-29 08:15:34, user Levi Yant wrote:

Correspondence should go to James Higgins or Levi Yant.

On 2019-12-29 07:57:55, user ankit agrawal wrote:

This article is published in Biophysical Journal under title "Nonequilibrium Biophysical Processes Influence the Large-Scale Architecture of the Cell Nucleus"<br /> https://www.sciencedirect.c...

On 2019-12-29 04:47:44, user Peter Rogan wrote:

Alternative splicing may also be the result of common polymorphisms: https://www.biorxiv.org/con...

On 2019-12-28 17:43:32, user Guilherme wrote:

Would be a better study if the natural frequency of the plant was investigated too. Is there any difference between the sound measured and the palant’s natural fequency? If so, how many octaves the measured sound differs from the plant natural frequency?

On 2019-12-21 10:52:34, user Alex Webb wrote:

Are these frequencies in the known hearing range of any animal? There is a lot of speculation in the discussion, it might be good to add some data from the literature about the overlap of the frequencies of the plant signal to that of the hearing range of animals.

On 2019-12-12 16:05:13, user Paul Goldsmith wrote:

How do the other plants "hear" them?

On 2019-12-12 13:56:01, user Rosemary Noblin wrote:

Altered phenotypes is the key term in this article. It’s as simple as understanding that every living thing carries its own vibration. It’s stands to reason based on that alone that altering a living state will change its forces. Has NOTHING to do with being a vegan or “tree hugger” for those that comment ignorantly.

On 2019-12-28 16:53:30, user MrPete wrote:

I'm a completely independent engineer and citizen scientist. This research was incredibly misleading.

They exposed rats to energy at 1.5 to 6.0 watts per kg of body mass.

Let’s take a worst-case human example…. a 14 year old girl. Average body weight about 60 kg. The exposure rate corresponds to a 75 to 300 watt light bulb being held close to your daughter’s body.

A real cell phone emits at MOST about 40 thousand times less energy. When idling (not in a call) it emits about 75 billion times less energy.

Ridiculous. (My calculations: http://bit.ly/2Q6zZQV

On 2019-12-27 16:39:11, user Ram Subramanian wrote:

Nice work. Substrate channeling is an interesting and looks like Aldehyde dehydrogenases are involved in many. Here is one from our lab - https://doi.org/10.1038/s41...

Think it might be useful to discuss the variations in ALDe metabolite channeling. IS there a common thread because most Aldehydes are toxic?

On 2019-12-26 16:49:15, user Vahe Demirjian wrote:

I would recommend the following revisions to this paper:

1. The reclassification of Piksi as a pterosaur (probably an ornithocheiroid) is based on Agnolin and Varricchio (2012). The authors note that the features that Varricchio (2002) used to place Piksi in Ornithothoraces are also present in advanced pterosaurs.

2. Santanadactylus araripensis is a nomen dubium following Pinheiro and Rodrigues (2017).

3. Considering that pteranodontids and nyctosaurids were recently described from the Maastrichtian of North Africa, it is possible that a number of problematic ornithocheiroids from the Aptian-Turonian interval could be referable to either family.

4. The recovery of Istiodactylus as paraphyletic relative to Gwawinapterus is flawed and doesn't make sense because Gwawinapterus had a tooth replacement pattern fundamentally different from all pterosaur taxa as noted by Vullo et al. (2012) and Gwawinapterus occurs way much later than confirmed istiodactylids, so Gwawinapterus had replacement teeth growing much faster than that of Nurhachius luei. And besides, toothed ornithocheiroids and toothless pterodactyloids like pteranodontids co-existed with each other in the Cenomanian, but all known post-Cenomanian pterosaurs are toothless, reflecting how latest Cretaceous pterosaurs developed toothless jaws to save weight, just like birds today. In any case, Gwawinapterus is clearly no pterosaur as Witton (2012) and Vullo et al. (2012) point out.

5. Lonchodectes is a nomen dubium as per Rodrigues and Kellner (2013), and thus the previous assignment of Serradraco to this family is untenable and the New Zealand pterosaur reported by Wiffen et al. (1988) and Navajodactylus occur far later than Lonchodectes, so might be either pteranodontids, nyctosaurids, or azhdarchids.

6. Under "Lonchodectid Ecology", you didn't mention that the postcrania that Averianov (2012) assigned to Ornithostoma don't overlap with the Lonchodectes compressirostris holotype and were assigned to Azhdarchoidea based on comparisons with azhdarchoid postcranial.

Agnolin, F.A., and Varricchio, D., (2012). Systematic reinterpretation of Piksi barbarulna Varricchio, 2002 from the Two Medicine Formation (Upper Cretaceous) of Western USA (Montana) as a pterosaur rather than a bird. Geodiversitas. 34 (4): 883–894. doi:10.5252/g2012n4a10.

Pinheiro FL, Rodrigues T. (2017) Anhanguera taxonomy revisited: is our understanding of Santana Group pterosaur diversity biased by poor biological and stratigraphic control? PeerJ 5:e3285 https://doi.org/10.7717/pee...

Rodrigues, T.; Kellner, A. (2013). Taxonomic review of the Ornithocheirus complex (Pterosauria) from the Cretaceous of England. ZooKeys 308: 1. doi:10.3897/zookeys.308.5559. edit

Witton MP (2012) New Insights into the Skull of Istiodactylus latidens (Ornithocheiroidea, Pterodactyloidea). PLoS ONE 7(3): e33170. https://doi.org/10.1371/jou...

On 2019-12-25 21:33:59, user HonSing wrote:

Hi Authors,

As the first person to image the ultrastructure of EVs with AFM (tapping mode, non-liquid), I am trying to understand the value of this preprint. I adore manuscripts/works that use AFM because in my opinion, there is just no other way to understand their volumetrics. But there are always major assumptions when using AFM for volumetrics.

Firstly, the cantilevers used (SNL-10 - or "A" in this preprint) have a forward angle of 15degrees and a back angle of 25degrees. This means that while you state it is impossible, multiple traces/scans must be performed if you want to measure the radius properly. As I understand it, the radius and height is critical for your analysis. From that you derive the contact angle, and then you will arrive at your stiffness (k) metric.

I did not see any incorporation of the forward/back angle into your calculations. If not, I will share with you why it is so critical. I remember that when I was a PhD student, I was informed by AFM experts that the angle of the tip will lead to an artefact when imaging and trying to ascertain what an object may topographcially look like. The tip is not perfectly shaped like a needle, it is a triangle shape and it is substantially larger than the object being scanned. Hence, vesicles/non-vesicles will become larger/wider than they really are.

I think that when you look at your different vesicle preps (which is a very cool experiment), you will find that due to your masks, some liposome preps are larger than others. Ie., the DOPC has smaller diameters, 40-60nm; whereas the DSPC has a median diameter of 120nm. This is a major difference when your team makes comparisons between liposome preps. When accounting for the geometry of the cantilever tip, this means that you are unfortunately comparing apples versus oranges. You need to control for size before calculating your stiffness (K). I think you will understand what I mean when you compare the LUT scales of the DOPC versus POPC, DPPC, and DSPC (40nm, 90nm, 140nm, 190nm). These are progressively larger and larger. This is why your Figure 4 (contact angle) exhibits a near linear relationship. The vesicles are simply just larger and hence, the contact angle is greater because the cantilever tip is not a perfect vertical tip, but a big-ass triangle.

The title states that it is a high-throughput screening method. But lets be very honest with each other, anyone that does AFM on EVs is already doing this "high-throughput" imaging by simply zooming out to a 5-10um FOV. In that instance, they will be able to image tens or hundreds of EVs in a single FOV. I'm quite sure this is not novel if this is something that all AFMers do when they simply are trying to look for the mica coverslip (when the cantilever engages the object of interest).

I also would like to see images of actual microparticles/microvesicles/ectosomes etcetcetc and what your contact angles as calculated are and what they look like. I think you will quickly see that they are no longer spherical but really highly heterogenerous objects with an irregular radial geometry and "rough" topography. That is because they will contain things like actin filaments and other structural components. That in itself would make a max/min XY radial measurement (that this work asserts) to arrive at a contact angle and stiffness (k) measurement an inaccurate one.

I think what would be valuable is a calculation that accounts for the forward/back angle of a cantilever and its limits of imaging a quasi-3D object, such as an EV. I think that is the most important issue that faces AFMers - the fact that the tip itself produces an imaging artefact and that I have seen very little in terms of how we account for how big this error is when we image dome-shaped things smaller than 500nm. I did enjoy reading about this work and I hope that with more work, it will be something that I and many other AFMs can cite and refer to in the future. Good luck!

Cheers,<br /> Hon S. Leong

On 2019-12-25 06:35:28, user chetan arya wrote:

Our little contribution to understand how nature designs and evolves novel systems to counteract man-made mess of environment. Evolution of new robust enzymes which can perform very basic but essential chemical reactions under extreme conditions is the theme of this study. Breaking a stable ubiquitous amide bond such as DMF is well studied in chemistry field but is an unknown phenomenon in biochemistry field. Being a recalcitrant and well used organic solvent, there is nothing organic in DMF when it comes to pollution. We found a microbial system which can denitrify DMF for their food source. Most important enzyme of DMF metabolic pathway, which is a hydrolase is proven novel at every levels. Complete different spectrum of sequence, structure, catalytic activity and mechanism. So please find more about this interesting enzyme through this paper.

On 2019-12-19 20:48:48, user Swagatha Ghosh wrote:

Mystery solved! An interesting article from my former lab describing the structural and molecular basis of degradation of DMF, a human-made industrial solvent, by a naturally existing enzyme. This study will open up many new opportunities for evolution and design of enzymes and micro-organisms useful for bioremediation. Cheers to Chetan et. al. ! #cryoem #proteinfold #bioremediation

On 2019-12-25 01:02:02, user Janarth wrote:

This article has been peer reviewed and published in BBREP:

https://www.sciencedirect.c...

On 2019-12-24 10:43:00, user Dilawar Singh wrote:

This is published: https://doi.org/10.1016/j.b...

On 2019-12-23 13:58:29, user Christophe Leterrier wrote:

This work has been published in Nature Communications on Dec. 20, 2019: https://www.nature.com/arti...

On 2019-12-23 04:38:47, user GaelicSoxFan wrote:

Who is the funder?

On 2019-12-22 16:17:01, user Erlembaldo wrote:

Good evening authors,

I can't find the Supplementary Tables and Information... are they available?

On 2019-12-19 02:04:15, user Richard Rocca wrote:

Please add Supplementary information referenced in the pre-print.

On 2019-12-21 05:49:22, user Prateek Bhatia wrote:

Seamlessly use AI to get hold of good variants from an Ion Torrent run Data...high intelligence quotient!!

On 2019-12-20 20:07:10, user Concerned reader wrote:

It is important to give correct credit where credit is due in citations of prior work: The authors talk about PCR-based random access yet completely ignore the original work that proposed this scheme, published in 2015 (Tabatabaei Yazdi et al, Nature SR). Citing follow-up papers and not the original contribution is not appropriate.

On 2019-12-20 13:48:54, user bankspin wrote:

The authors employed an interesting strategy to increase the drug delivery of a thyromimetic, a proposed therapy for X-ALD, in the CNS of Abcd1 KO mice. They did so by using Sob-AM2, a CNS-selective prodrug of sobetirome. Consistently, Sob-AM2 administration caused a similar decrease in C26 in the CNS compared to sobetirome but had reduced effects in serum and adrenal glands, the peripheral tissues in which FAAH has lower activity. This study shows some promise for the use of this kind of pharmacological approach to increase drug delivery into the CNS for X-ALD patients.<br /> After reading the manuscript, I have some comments that I think could be taken into account to improve this scientific work:

• The title of this manuscript does not describe well the scientific worked that has been performed here. Since there is not any proof of clinical or even preclinical improvement of the disease, I would suggest to change the title, which induces confusion to the readership.

• What are the levels of C26 and C26/C22 and C26-LPC in the wild-type control animals? That would allow the authors to compare the treated animals with the WT animals, and also to see the increase of VLCFA in the batch of Abcd1 KO animals used in this study.

• Thyromimetics are claimed to act by the upregulation of ABCD2. Is there any change in ABCD2 levels in the different tissues of Abcd1 KO mice after the administration of the drug? I think this is an important point to understand the action of this drug.

• How much increase of C26 is present in Abcd1 KO tissues at 3 weeks of age when the treatment starts? I would suggest for future studies to test the efficacy of the drug on middle-age animals as well, at 12 months of age, which would replicate better the situation of AMN adult patients that need treatment.

• It is puzzling that the Abcd1 KO mice are not developing the behavioral phenotype that has already been described. It has to be taken into account that the phenotype of aged Abcd1 KO mice is kind of mild, and drug testing has been performed elsewhere in double Abcd1/Abcd2 KO animals, which have an earlier-onset and more severe phenotype. Open-field test may not be the best test to visualize the axonopathy present in Abcd1 KO mice. Bar-cross and/or treadmill in aged Abcd1 KO may be better alternatives. Another question that came to my mind is the degree of increase of C26 that was present in that Abcd1 KO set of animals at 15 months of age. Is it similar to what has been described before?

• Given the mechanism of action of sobetirome of induced oligodendrogenesis, authors could consider studying how does myelin look in the axons of Abcd1 KO mice untreated and treated with the drug. This has been well described in the literature and could provide more insights into the action of this drug.

On 2019-12-20 07:16:18, user Mick Watson wrote:

You might enjoy our paper where we show complete bacterial genome assemblies from nanopore sequencing of a complex metagenome

https://www.nature.com/arti...

On 2019-12-19 20:09:09, user Justin wrote:

Could you please take a look at the genotype quality of low frequency variants, particularly rs117913124 (MAF=0.03) which has the largest effect size?

On 2019-12-19 14:19:11, user Arjun Khakhar wrote:

Great work! We put out a paper a while back that might be of interest if y'all wanna further rewire post-translational ERK signaling: https://elifesciences.org/a...

On 2019-12-19 11:00:58, user Xiaoran Lai wrote:

A. Köhn-Luque would like to acknowledge that the research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement number 609020 - Scientia Fellows, and M. E. Rognes would like to acknowledge the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under grant agreement 714892 for its support. We also would like to acknowledge the help received from the Department for Research Computing at USIT, the University of Oslo IT-department

On 2019-12-19 10:54:00, user R Casero wrote:

Good work. You may be interested in looking at "Transformation diffusion reconstruction of three-dimensional histology volumes from two-dimensional image stacks" (2017)(https://doi.org/10.1016/j.m..., which is later work to the Burton et al [21] you cite, where we reconstructed a whole mouse heart from serial histology (we also had damaged tissue, but we didn't tackle that issue in that paper). Although you have your own histology reconstruction approach, I think our discussion about external references for reconstruction, reconstruction drift, and the possibility to replace slow registrations by much faster operations in transformation space could be of interest.

On 2019-12-19 06:10:46, user Vikash Kumar wrote:

Nice work explaining role XTHs in secondary wall development.

On 2019-12-18 02:21:46, user 王锦 wrote:

Why not supplemental tables? How can I get the supplemental tables?

On 2019-12-17 20:26:18, user R. Rocca wrote:

Given the expansion of ancient samples to 70, please republish the XLS table. Thanks!

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 2019-12-17 00:31:43, user Chahat Upreti wrote:

Hi! I wanted to ask if you recommend the use of Stringtie2 over Stringtie1 for short reads (50-75 bp). The paper does mention that Stringtie2 is better in terms of memory usage and speed, but for accuracy purposes, would you recommend switching to Stringtie2?

On 2019-12-16 23:12:26, user Felix Wu wrote:

Supplementary Data will be uploaded once the paper has gone through review. If you would like access before, please email us (flw2113@cumc.columbia.edu).

On 2019-12-16 21:36:52, user Ross Jones wrote:

Updated reference for DiAndreth et al: related work from our lab developing a library of endoRNases, of which CasE is one: https://www.biorxiv.org/con...