On 2017-10-12 13:14:59, user Anton Nekrutenko wrote:

This statement "Galaxy enables users to draw a tool chain in a web browser, and then automatically installs and executes this tools chain. However, it does not facilitate users to specify alternative tools for each step in a workflow; neither does it enumerate all possible combinations between the tools across steps. If a user wants to use Galaxy as a standalone application on a local machine, the full Galaxy system must be installed which is unnecessary and is wasting a lot of computing resources." makes me believe that authors actually do not understand what Galaxy is. I would recommend not making comparisons for the sake of comparisons, but instead provide a fair, fact-based evaluation. This is especially important today when fact-based discussion is becoming rare.

On 2020-06-02 16:05:36, user Esmeralda R. wrote:

This is a great article!<br /> It is a good news to know that everyone carries a highly neutralizing antibody. At least now, we know that the vaccine developed in the future may work very well. <br /> I hope Dr Nussensweig and team may be able to develp further a very efficient vaccine against SARS-Cov2. <br /> People from my company, Real Gramas are all excited about this vaccine to be lauched soon!

On 2025-01-28 09:50:55, user Richard McCulloch wrote:

This article is now published: Nucleic Acids Res. 2023 Nov 10;51(20):11123-11141. doi: 10.1093/nar/gkad836.

On 2024-04-12 14:54:46, user Rumiana Dimova wrote:

The manuscript was published: https://doi.org/10.1002/adv...<br /> A. Mangiarotti, M. Aleksanyan, M. Siri, T.-W. Sun, R. Lipowsky, R. Dimova, Photoswitchable Endocytosis of Biomolecular Condensates in Giant Vesicles. Adv. Sci. 2024, 2309864.

On 2020-07-05 05:13:04, user Ciro Leonardo Pierri wrote:

FYI: The ms linked here above has been accepted for publication in a more completr form on Cell Mol Life Sci: https://link.springer.com/a...

On 2020-09-19 03:03:44, user ??? wrote:

I think this is very important finding about how tumor can proliferate while other tissues of the body is wasting. Tumor may induce the wasting of other tissues, but they can escape from wasting and grow continuously.

On 2016-04-23 15:56:14, user Peter Carbonetto wrote:

Would you be willing to tell us how you created Fig. 1G? It is an interesting visualization of the pathway data.

On 2016-08-25 15:04:18, user elsherbini wrote:

I'm enjoying the paper, still a lot to digest. Minor point - I think in Oleson et. al. 2016 they used 100% OTUs fit all the OTUs to the model. The subset they report were OTUs that looked interesting given the model, they didn't limit it a priori. Also, they weren't really looking for interactions between OTUs, so it might not be appropriate to cite it in that context.

On 2019-04-08 12:20:56, user David Rosenkranz wrote:

This is a cool system to study PIWI/piRNA biology from the evolutionary point of view. Very interesting work! But don't these animals - like hamsters - have a piwil3 paralog? I thought piwil3 was lost somewhere on the lineage to muridae, which of course not rules out an independent loss in the squirrel clade.

On 2022-11-23 12:59:20, user David Roe wrote:

You state "There is no public sequencing data with annotated KIR information".<br /> This paper might be helpful. It describes how to obtain ground truth for any data set with PacBio HIFI data. It even gives an example from a 1KG/HPRC individual.<br /> 1. Roe D. Efficient Sequencing, Assembly, and Annotation of Human KIR Haplotypes. Frontiers in Immunology. 2020;11:11.

On 2020-08-18 19:12:57, user Rafael Feras UFCG odontologia wrote:

Great article. About Figure 1, I can't see the letter "D" in the figure!

On 2020-05-27 15:28:07, user Edward Marcotte wrote:

Is the xiFDR v2.0 software available? The Rappsilber lab link only seems to provide version 1.4.3.1: https://www.rappsilberlab.o...

On 2024-08-19 13:52:54, user Jonathan Rondeau-Leclaire wrote:

Dear authors, <br /> This study is promising, as you seem to have gathered quality data with a very interesting design that has great potential to generate insights into the impact of microbes on plant productivitiy. I must however venture in a technical comment, as I believe the statistical approach you have chosen is weak and prevents you from truly leveraging all the precious information you have generated with the sequencing experiments.

Using correlation to find associations between microbial abundance and environmental (or sample) characteristics using data derived from sequencing experiment is generally advised against, as the data is compositional, which means the values are set in a simplex, not a euclidean space. This means that the observed relative abundance values are not independent of each other, as there is an inherent correlation between all taxa: if any microbe increases its true abundance, the relative abundance of everyone else will decrease even if they did not change in true abundance.

To find bacterial genera associated with plant traits (or any other characteristic), you should use statistical methods developed specifically for handling microbial relative abundance data. You can look up ANCOM-BC, corncob, DESeq, Aldex, and many others that have been developed to work specifically with sequencing data. Some of these even estimate the changes in absolute abundances. There are other reasons to use these methods too, that have to do with special characteristics of sequencing data (which can hardly be ignored), such as sparseness, overdispersion, to name a few. I recommend the following reads:<br /> https://academic.oup.com/gigascience/article/doi/10.1093/gigascience/giz107/5572529 <br /> https://dx.plos.org/10.1371/journal.pcbi.1010467 <br /> https://www.nature.com/articles/s41522-020-00160-w

Moreover, I do not see any mention of multiple testing correction. As you test multiple genera, it is absolutely essential to correct your p-values for multiple testing, otherwise it is almost certain that some of the genera you identified as significantly correlated were only by pure chance, not for biological reasons. Most differential abundance tests mentioned above do this by default, as it is expected for credible results whenever conducting multiple statistical tests. More on this if you are not familiar with this correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099145/

I hope this helps, and good luck with your publication!

On 2020-06-05 14:06:17, user Renzo Huber wrote:

This manuscript was discussed in the MR-methods group headed by Benedikt Poser at MBIC, Maastricht in the group meeting on June 4th 2020. <br /> We would like to share a summary of our discussions below:

The manuscript entitled: “Arterial blood contrast (ABC) enabled by magnetization transfer (MT): a novel MRI technique for enhancing the measurement of brain activation changes” describes a new fMRI method to enhance the efficiency of conventional gradient echo BOLD fMRI by means of on-resonant magnetization transfer pulses.

We discussed the manuscript with great interest and enthusiasm.

The manuscript is the latest in a series of recent MT-prepared fMRI contrast papers. This one stands out compared to previous work since it allows a combination of the contrast with conventional BOLD. <br /> It has the potential of a) higher localization specificity, b) faster functional imaging with shorter TEs, c) reduced contribution of BOLD-driven physiological noise, d) higher CNR time-efficiency than other non-BOLD contrasts, e) smaller sensitivity to susceptibility (signal dropout) artifacts in challenging brain areas, f) improved CNR efficiency compared to GE-BOLD.

We believe the manuscript would benefit from a few clarifications listed below:

1.) The purpose of the new sequence was not entirely clear to us. In order to help everyone fully appreciate the usefulness of the proposed approach, it will be beneficial to explicitly mention what its application cases might be and what the particular motivation for its use is:<br /> 1a) Is it because of the higher localization specificity of arterial CBV as argued in the MT-prepared MOTIVE sequence descriptions from SG-Kim? (claim in abstract)<br /> Since the ABC-method is enhancing intra-vascular signals, it might be appropriate to discuss the potential of unwanted intravascular BOLD signals in large draining veins. In ABC, is this contrast component expected to have a larger relative functional contribution compared to the conventional GE-BOLD case? <br /> 1b) Is it due to the reduced BOLD-like physiological noise? (claim on page 9) <br /> If this is the case, the manuscript could benefit from empirical comparisons of variance explained e.g. in RETROICOR physiological noise modeling. For instance, this has been done with a sequence that is virtually identical to the ABC sequence, but with additional gradients https://doi.org/10.1016/j.n.... Since, the physiological noise is known to be dominated by cardiac-driven fluctuations, it was not clear to us why the claim was made (at the bottom of page 9). Cardiac-driven physiological noise is commonly not expected to be dependent on T2*-fluctuations, but it is thought to come from intravascular M0-fluctuations. Therefore, we would think that the ABC-method might actually be suffering from relative enhancements of physiological noise. Empirical data would help to solve our confusion. <br /> 1c) Is it because of an increased time efficiency by applying MT pulses compared to inversion pulses in VASO? (as claimed on page 10) <br /> Depending on the number of slices in the VASO protocol, approximately 85% of the sequence duration are commonly used for data acquisition https://youtu.be/KwX2rscnOx.... Only the remaining 15% are “dead-time” due to the inversion recovery delay.<br /> For the ABC sequence, however, the dead times are 6ms (MT)+3ms(spoiler) for three 9ms EPI readouts. This suggests that the time efficiency of the ABC is actually lower than VASO.<br /> Furthermore, if the user of a VASO sequence does not care about CBV-quantification in physical units of ml, a shorter VASO inversion delay is possible with duty cycles above 90%: https://doi.org/10.5281/zen.... Therefore, we feel that the efficiency comparison with VASO on page 10 could be rephrased. <br /> 1d) Is it because ABC is more sensitive than GE-BOLD? (claim in abstract)<br /> We were a bit confused by the corresponding data in Fig. 1B. To us, it seemed that the most plausible activation maps (incl. LGN) and the largest activated areas are from MT-off with TE28ms. Maybe this is an artifact of using differing ROIs across methods? But it looked to us like GE-BOLD is actually the method that provides the best data.

2.) We found the comparison across methods and TEs slightly confusing. <br /> We didn’t really understand if the purpose of the chosen multi-echo approach was <br /> a) to characterise the contrast underlying the ABC-sequence, or <br /> b) to investigate which of the methods compared is best for fMRI activation studies? <br /> If the authors are interested in understanding the underlying contrast mechanism, we would advise them to pool the functional signal from the same ROI across TEs and contrasts. Otherwise, it is confusing why the z-score is not increasing with TE for BOLD (Fig. 1b).<br /> If the authors are rather interested to see which method works best, they should take into account that each of the acquisition protocols might not be its optimized version for either contrasts. <br /> E.g. the Senior author of the manuscript rightfully has pointed out to us in the past, that high-resolution CBV-weighted contrast and GE-BOLD contrast should only be compared at their optimal TR. Since the ABC could theoretically be acquired with shorter TEs (and TRs), any comparison should contain a time-efficiency correction.

3.) We were a bit puzzled by the reporting of echo times. The values varied between 6.8 ms and 6.9 ms, and the time difference between consecutive echoes is non-homogeneous. Maybe this is due to rounding errors?

4.) We were wondering if the authors could comment on the individual contributions to the specific absorption rate (SAR). How much relative power did the MT pulses require, and there the experiment conducted at full SAR? This will play into the ability to use SMS acquisition which might ultimately be desired. As implied in the discussion, use of 3D readout is an option and will (partially) address any power constraints. <br /> 5.) Do the authors consider the ABC methods promising at UHF? This would be good to discuss but is currently not obvious from the paper. (likely power constraints, desire to use larger matriz size and consequences on TE vs T2* etc)

6.) We were uncertain about the claim on Page 9 that enhanced inflow effects can be ruled out due to the application of the body-transmit coil. We agree that the MT-module does not cause additional inflow effects. However, we believe that the suppressed extravascular signal and the relatively enhanced intravascular signal in ABC will result in a larger relative contribution of the 2D-excitation pulse driven inflow effects (that are also always present in 2D-BOLD).

7.) If the authors agree, they could acknowledge very similar previous work that used similar contrasts in humans https://doi.org/10.1002/mrm... https://doi.org/10.1002/mrm... or similar sequences https://doi.org/10.1016/j.n....

Based on our enthusiasm for the paper, Maastricht’s MR-Methods group decided to follow the authors suggestion from their discussion section and combine this novel contrast with 3D-EPI and spiral readouts.<br /> -> Specifically we are planning to use the MT-prepared 3D-EPI version for distortion matched anatomical reference data in layer-fMRI at 7T as described for instance here https://layerfmri.page.link... and here: https://ww4.aievolution.com...<br /> -> We plan to combined the proposed MT-preparation with our (multi-band) spiral sequence for very short TE imaging at 7T; with the goal to investigate the spatial specificity (insensitivity to draining veins) and CNR time-efficiency compared to inversion-less MAGEC-VASO. <br /> We enthusiastically anticipate the publication of the paper in a prestigious journal.

Renzo Huber, Dimo Ivanov and Benedikt Poser.

On 2020-10-10 15:55:23, user Gustavo Stolovitzky wrote:

Please note there is a discrepancy in the accuracy of the synergy prediction algorithm reported in this preprint (AUC=0.84) and the accuracy reported in the now published paper (AUC=0.77)(https://elifesciences.org/a... ). The correct accuracy is AUC=0.77 as reported in the published version.

On 2022-11-27 12:46:31, user Kresten Lindorff-Larsen wrote:

Review of “Optimizing the Martini 3 force field reveals the effects of the intricate balance between protein-water interaction strength and salt concentration on biomolecular condensate formation” by Gül H. Zerze<br /> Reviewed by F. Emil Thomasen and Kresten Lindorff-Larsen

Comments:The preprinted manuscript by Zerze reports on molecular dynamics simulations of the intrinsically disordered low complexity domain (LCD) of FUS using a beta version of the coarse-grained force field Martini 3. The author performed simulations to study the formation of FUS LCD condensates under varying protein-water interaction strengths (in the Martini force field) and at different NaCl concentrations, and concludes that strengthening protein-water interactions by a factor of 1.03 improves the agreement with experimental transfer free energies between the dilute and dense phases. Additionally, the author concludes that the NaCl concentration affects condensate morphology and protein-protein interactions in the condensate, and that the effect of NaCl concentration on protein-protein interactions in the condensate is sensitive to rescaling of the protein-water interactions. The preprint provides an interesting and novel benchmark of the (beta) Martini 3 model in predicting phase separation of IDPs, and reveals potential short-comings of the model in predicting protein concentrations in (or volumes of) the condensed and dilute phases. This benchmark will be useful for readers who wish to simulate liquid-liquid phase separation of IDPs with Martini 3, and the work will be interesting to a wider audience interested in the biophysics of IDPs and their condensates.

Below we outline some questions and comments that the author might take into account when revising the manuscript. Our main comment regards a clearer assessment of the convergence of the simulations and correspondingly the lack of error estimates for observables calculated from the simulations. We also suggest a clearer presentation of the experimental data used to validate the simulations. While some of these changes are mostly textual, in other cases we suggest additional simulations. We realize that some of these simulations require substantial resources; if these are beyond what is available, we suggest at least to clarify caveats as per the points below.

We have the following suggestions for revisions to the manuscript:

1)<br /> Fig. 1 and 2: The finding of non-spherical droplets is interesting and intriguing. To examine whether the formation of these shapes in the simulations with higher salt and ?-values represent stable states or perhaps trapped metastable states of the system, we suggest that:

1a) The author runs simulations with the parameters that give rise to non-spherical morphologies (e.g. ?=1.025 and 50 mM NaCl) starting from the structure of the spherical droplet (for example formed with ?=1.0 and no salt) and observe whether the non-spherical morphology is recovered or the droplet remains stable. If the droplet remains stable, then the effect of salt concentration on the inter-chain contacts (Fig. 6) could be assessed without potentially confounding factors from different dense phase morphologies.

1b) The author shows time-series or distributions of an observable that reports on the dynamics of the proteins in the non-spherical droplet (e.g. Rg, mean square displacement, residue-residue contacts) and/or of an observable that reports on the dynamics of the droplet shape (e.g. the x-, y-, and z-components of the gyration tensor).

1c) Additionally, independent replicas of droplet formation for each condition and parameter set would be ideal, but we realize that this would be expensive in computational resources and may be infeasible.

2)<br /> “As ? increases, the volume of the dense phase increases (and condensed phase concentration decreases accordingly) until the system is not capable of forming a dense phase (? >1.03)”: From Fig. 1 it seems that the rate of cluster formation decreases as ? increases. Is it not then possible that droplet formation at ?>1.03 is stable at equilibrium, but occurs on time-scales greater than those tested in the simulations? To support the statement that no droplets are stable at ?>1.03, we suggest that the author runs simulations with a higher value of ? starting from the structure of the spherical droplet (formed with ?=1.0 and no salt) to observe whether the droplet is dissolved or remains stable.

3)<br /> Figure 3: The use of the radial distribution does not seem ideal for the droplets that have a non-spherical morphology, as certain distances will report on an average over the dense and dilute phases. This should at a minimum be discussed.

4)<br /> Table 1: It seems that the discrepancy between the sigmoidal fit approach and the surface reconstruction approach increases with ?, possibly due to sensitivity to the shape of the droplets, illustrating that there might be significant uncertainty associated with the reported dense phase volumes. We think it would be useful to have an error estimate for the reported dense phase volumes (e.g. an error over volume calculation approaches and/or over different probe sizes).

5)<br /> Table 2 and Fig. 4: We suggest that the author more explicitly states which experimental data was used for comparison with the simulations in Fig. 4. We also suggest a more direct comparison with experimental data points where possible (e.g. by showing the experimental values of csat as a function of NaCl concentration).

6)<br /> “We used the “tiny” bead type (TQ1) both for Na+ and Cl- ions”: The author should clarify the reason for and possible effects of choosing the TQ1 bead type, as TQ5 is, we think, the standard bead type for Na+ and Cl- ions in Martini 3.

7)<br /> We suggest that the author, where possible, reports error estimates for the various observables, for example from block error analysis and/or repeated simulations.

8)<br /> It would be useful to include a discussion of the effects of simulation convergence and simulation starting configurations on the reported results.

9)<br /> A discussion of the potential differences in the effect of non-bonded cut-offs in the dilute and dense phase would also be useful.

10)<br /> It would be very useful if the inputs/settings (including starting configurations) used for simulation and code for analysis were available.

We also have the following suggestions for minor changes to the manuscript:

1)<br /> “We kept the protein-protein interactions unmodified (and no additional elastic backbone constraints were applied)”: The author should clarify whether this includes assignment of secondary structure and/or side chain angle and dihedral restraints (ss and scfix in Martinize).

2)<br /> “All simulations were performed using GROMACS MD engine (version 2016.3).”: Error in references.

3)<br /> In the Cluster Formation Analysis section: We suggest that the author cites the specific package used (e.g. SciPy).

4)<br /> Fig. 2: There are small red dots on the droplets, which should either be explained in the figure text or removed.

5)<br /> Fig. 3: It would be useful for the reader if the NaCl concentration was labelled at the top of each column. Additionally, the radial distribution of the ion concentration is shown as two separate rows, which we assume corresponds to Na+ and Cl- ions. This should be clearly labelled.

6)<br /> “We found the largest water fraction For the ionic species…”: Typo?

7)<br /> Fig. 4: Depending on how the plot is updated with more details on the experiments, perhaps the range shown on the y-axis could be made smaller.

8)<br /> Fig. 5: May be clearer with a colourmap with three colours, as in figure 6.

On 2018-11-30 09:56:43, user Matthias Meurer wrote:

It will take another couple of weeks until the pMaCTag plasmids will appear on Addgene. Until then please feel free to contact the corresponding author Michael Knop for any plasmid request. The web page for primer design is already up and running: http://www.pcr-tagging.com/

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 2020-07-30 13:39:22, user Jane wrote:

The authors eliminated OX-neurons at P20-P25 when both OX-neurons amount and blood pressure were significantly higher in SHR than that in WKY. Why do not eliminate OX-neurons at P7-9 in SHR prior its blood pressure goes up?

How blood pressure will be changed if eliminating OX-neurons in WKY?

Blood pressure in SHR reaches at a hypertensive plateau at 8 weeks old. However, the authors determined blood pressure changes at P40 days around 6 week post OX-neurons elimination.

How orexin A levels changes by age in cardiovascular brain regions innervated by OX-neurons? Does it change chronologically with OX-neurons in SHR?

Do the authors eliminate OX-neurons in one side of brain or both sides? If in one side, orexin A level in cardiovascular brain regions is decreased? OX-neurons have cross-projections and innervation and compensation effects may occur if only one side of OX-neurons are eliminated, for example increased expression of OX receptors.

The authors quantified oreixn A neurons. How about orexin B neurons in SHR compared with WKY? Orexin A neurons and Orexin B neruons are the same neurons or different group of neurons? Orexin B also plays a role in blood pressure regulation.

Orexins involve in food intake and appetite. How about body weight changes in SHR after OX-neurons elimination?

On 2017-02-03 14:18:09, user John Common wrote:

Dear Omer, thanks for the insightful comments! In reply.. 1. PacBio reads are a useful technology for highly repetitive genes and are indeed useful for FLG but currently this was still too expensive (at least in Singapore) for a larger scale solution to sample stratification in our cohorts of interest. Hence we didn't pursue this for this manuscript. It would definitely improve the CNV genotyping and clarify which LoF mutations are carried on which alleles. 2. Thank you for your clarification on the evolution of the gene and congratulations on your important paper in this field.

On 2020-02-04 10:53:08, user David Escors wrote:

The published peer-reviewed version of this paper can be found in: https://www.mdpi.com/2072-6...<br /> https://doi.org/10.3390/can... (registering DOI)

On 2019-05-20 08:22:53, user Jiri Hulcr wrote:

Hello Kirk et al.<br /> I am glad to see that you all are still interested in ambrosia beetles. With respect to the hypothesis about cycloheximide tolerance in some Ophiostomatales as related to their symbiosis with ambrosia beetles, I think it is important to consider that the tolerance is widespread in that fungal family, pre-dating their engagement with the beetles. I don't know the literature that well, but I would guess that cycloheximide tolerance is probably present in many Ophios that are not relevant to the beetles, or even compete with them. <br /> Have you measured whether the compound occurs in the galleries in quantities comparable to those in your media? That might get us close to a test whether it is related to higher fitness of the fungus, which would support your hypothesis. <br /> Thank you!<br /> Jiri Hulcr

On 2017-03-31 11:11:51, user Adrian Biddle wrote:

Thanks for the invitation to comment!

I think you present a really nice overview of current considerations in the field. I think the discussion of MET-dependent versus MET-independent metastatic pathways, possibly reflecting differing levels of genomic instability or different cells of origin, is a particularly well-made point.

One thing possibly missing is a discussion of the role of EpCAM (ESA) as an epithelial marker that may be retained in the partial EMT state and enable discrimination of a partial from a full EMT in studies assessing ‘stemness’. To my knowledge, this method was first used by John Stingl to sort EpCAM+ multipotent breast stem cells from lineage-restricted EpCAM- myoepithelial cells (Stingl et al., 1998). In the seminal Al-Hajj paper, they noted that only those CD44+CD24- cells that also retained EpCAM expression were able to seed tumours (Al-Hajj et al., 2003). This suggested that retention of epithelial markers in the CD44+CD24- EMT sub-population was essential for tumour-initiating ability. Finally, our own work (Biddle et al., 2011) demonstrated that the ability to undergo MET was only exhibited by those cells in the EMT sub-population that retained EpCAM expression. In combination with the other studies you’ve cited demonstrating that ability to undergo MET is essential for carcinoma metastasis (Ocana et al., 2012; Tsai et al., 2012), these findings indicate that retention of the epithelial marker EpCAM (indicative of a partial EMT) is essential to the ability to seed metastases through an MET-dependent pathway.

Adrian Biddle

@DrABiddle

Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., and Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100, 3983-3988.

Biddle, A., Liang, X., Gammon, L., Fazil, B., Harper, L. J., Emich, H., Costea, D. E., and Mackenzie, I. C. (2011). Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res 71, 5317-5326.

Ocana, O. H., Corcoles, R., Fabra, A., Moreno-Bueno, G., Acloque, H., Vega, S., Barrallo-Gimeno, A., Cano, A., and Nieto, M. A. (2012). Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 709-724.

Stingl, J., Eaves, C. J., Kuusk, U., and Emerman, J. T. (1998). Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast. Differentiation 63, 201-213.

Tsai, J. H., Donaher, J. L., Murphy, D. A., Chau, S., and Yang, J. (2012). Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 22, 725-736.

On 2020-08-05 10:33:59, user Small Cat wrote:

Interesting article! I do wonder about the "completeness" of the 3 PW databases mentioned; if I'm correct, PW databases do not cover more then 60% of the total amount of proteins. You compare the gene sets between database; it would also be interesting to know which area's are missing within these 2 databases, to put your results in (more) perspective.

On 2018-01-18 18:12:56, user Christina Cuomo wrote:

Updated post-review version of our paper comparing genomes of systemic dimorphic fungi to related rare and non-pathogenic species. 104 days (and counting) of early access on #bioRxiv

On 2017-09-26 13:18:08, user Marco Pietrosanto wrote:

Nice method and good choice of result visualization! I wonder if you considered comparing against other new tools like SMARTIV or BEAM Motif finder

On 2016-03-22 15:35:49, user James Wilson, M.D. wrote:

Dear colleagues, this preprint is truly a draft and actually a placeholder for ongoing evaluation of the Zika importation data for the United States. It remains unclear at this point whether we will pursue formal submission.

We submitted this to the WHO Bulletin and received a concerning answer from the Editor:

"Thank you for submitting your paper to the Bulletin of the World Health Organization.

All manuscripts are screened for originality, timeliness, public health relevance and suitability for the Bulletin's general readership. Unfortunately, this initial assessment has resulted in your paper not being considered for publication.

We regret this negative decision and would like to wish you the best with publication elsewhere on this occasion."

My reply:

"This is unfortunate given the results of this simple assessment that begins to challenge claims of this event representing a "pandemic"... and indeed, why Zika was declared a PHEIC whereas Chikungunya was not."

The Editor's reply:

"We'd be happy to reconsider if you'd like to submit a paper in which your objective is stated explicitly and a full description of the actual model is provided such that others may replicate. Just to clarify WHO's position, the congenital malformations and neurological complications associated with Zika are what distinguishes this otherwise mild illness from Chikungunya and warrant the PHEIC declaration."

My reply:

"The model was explicitly documented and explained in the paper. The mathematics were simple, and indeed considered by myself to be perhaps too simple for a full manuscript.

I am aware of WHO's concerns that people are submitting subpar manuscripts. We did not intend to submit a full manuscript either given the level of effort involved versus the lack of formal peer review. Further, the rejection wilthout explanation sent a message that The Bulletin is a) either not serious in its objectives with Zika Open or b) there is political interference.

Chikungunya, if you confer with Pasteur, was most certainly not a "mild" disease from the perspective of the Reunion experience. As the individual who played a central role in providing warning to WHO regarding H1N1's emergence in Mexico as well as discovery of the UN Mirebalais base as the source of the Haiti cholera disaster, I will suggest that WHO's intelligence process in this matter has been flawed. WHO has indeed determined causality pointing to Zika, however the full array of causality (including the potential role of Chikungunya) has not been established.

Expect that the observation that risk of Zika emergence in the temperate zones of the world is not as great as previously suggested will be expanded upon and well documented as we proceed."

Bottom line: it remains our observation that <br /> 1. The etiology of birth defects, as reported in Brazil and elsewhere, has not been fully investigated.<br /> 2. The opportunity to expand consideration for Chikungunya-related birth defects has been lost, as the initial wave of "virgin soil" Chikungunya transmission has largely passed in Central / South America.<br /> 3. There is a disturbing lack of apparent acknowledgement of Pasteur's findings in Reunion.<br /> 4. There is a lack of balance in the global threat assessment of Zika emergence and overuse of a highly politicized term, "pandemic" and public comparisons made to Ebola that we do not believe are supported by the data.

On 2016-12-17 15:36:54, user Daniel Lam wrote:

"enabling long-range and target-specific activity of promiscuous enhancers." Don't target-specific and promiscuous mean the exact opposite?

On 2018-04-14 05:21:15, user bennedose wrote:

The period 690 to 1300 CE is within the historic period. Migrations from Iran to India are well documented. Recall that Emperor Darius was a Zoroastrian and his Behistun inscription dates to 500 BC - so the migrations documented in this study have nothing to do with original migrations in the 1000 BC period and earlier. Zoroastrianism was already at its peak in 500 BC

On 2017-05-29 14:11:14, user Christopher Ehrhardt wrote:

This manuscript has been accepted/published:

Analysis of cellular autofluorescence in touch samples by flow cytometry: implications for front end separation of trace mixture evidence. Journal Analytical and Bioanalytical Chemistry. DOI: 10.1007/s00216-017-0364-0.

On 2025-07-17 19:35:01, user Biswapriya Biswavas Misra wrote:

Dear Authors,

The text says, " Finalized .msp files for both ionization modes are provided in the Supplementary Material" but I can not find any .msp files that are downloadable as supplementary material. Just a word file with other tables. Kindly upload/ share.

Thanks again,<br /> Biswa

On 2021-09-20 16:07:37, user Rath R. Weird wrote:

Not sure that entries like that would be sufficient to offset the advertisement machine unleashed in support of the AlphaFold, but I do welcome a systematic attempt to evaluate AlphaFold performance in realistic applications. There is lots of anecdotes out there, when people turned to AlphaFold for structural info, and got gobs of disordered strings in return. Personally I compared some of the 2-3 year old models built by I-TASSER to AlphaFold output and found no discernible difference - typical homology modeling performance, none have much in looking-ahead capabilities, but at least the guys behind I-TASSER don't claim to have it. Here we have a more deliberate evaluation of the heuristic AlphaFold imbalance between physical realism and template alignment. Template alignment wins, to the detriment of physical realism.

On 2024-09-30 15:40:53, user Christopher Dunn wrote:

I left a comment earlier, but it doesn't appear, so I am trying again.

This is an interesting paper, but I am not sure how wide an interest it will achieve. That aside, I need to re-read this and provide more detailed comments.

That said, I would note that the official state flower of Connecticut is not the marvel of Peru (Mirabilis jalapa). That species is the State's "Children's flower."

The official state flower of Connecticut is Kalmia latifolia (mountain-laurel). This is the species that should be used in the analysis.

On 2024-11-04 12:05:23, user S. Krishnaswamy wrote:

Sleep in bacteria and archae is usually associated with a state of dormancy or persistency. But that is different from the circadian cycle of sleep. It is therefore surprising to see orthologs of human sleep genes in the deep sea vent dweller like this archae. Unless they had a different function there. It would be interesting to mutate some of the identified genes and see the effect in the cultures grown in the lab of Hiroyuki Imachi

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

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

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

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

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

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

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

On 2022-11-19 13:38:52, user Mahad AZAM wrote:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Some critiques I have with the paper include:

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

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

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

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

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

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

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

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

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

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

Dear authors,

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

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

Kind regards,<br /> Sebastian Van Blerk

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

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

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

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

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

We have already issued a detailed response refuting these claims.

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

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

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

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

This is a comment about version 5 of the manuscript.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

We welcome comments. Enjoy.

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

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

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

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

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

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

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

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

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

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

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

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

Congratulations on the great paper! Very impressive work.

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

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

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

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

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

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

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

Good study! I'm wondering is it published?

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

Great work, looking forward to the future applications!

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

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

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

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

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

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

Some thoughts and questions:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References

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

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

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

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

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

Published in PLOS Computational Biology, April 27, 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hi all,

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

All the best,<br /> Noah Dolev

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

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

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

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

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

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

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

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

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

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

My apologies,

Kind regards,<br /> Lien

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

So are you planning to sell these?

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

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

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

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

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

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

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

I have similar ideas and the theory would be investigated soon

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hello,

Nice data and work.

The Proteomics and Transcriptomics data are archived.

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

Thanks,<br /> Biswa

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

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

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

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

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

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

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

Cellular pH rules insulin secretion. Important finding!

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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