On 2025-03-21 15:31:16, user Peter Diebold wrote:

Great work here! Looking through the metadata, I have a small suggestion. Could you include the full GTDB taxonomy in future versions?

Secondly, I'd suggest renaming the "dustbin" to something that doesn't imply trash. Seems like a large amount of the bacterial diversity is in the dustbin and the name could lead someone to incorrectly assume that they aren't important as was done in this paper https://doi.org/10.1093/bioinformatics/btae717 <br /> Lastly, I'd really love to see a few more basic statistics about what is in the database. Perhaps recreate some of the tables and figures that GTDB makes https://gtdb.ecogenomic.org/stats/r220 <br /> Thanks again for the great work!

EDIT:

I realized that you did not use GTDBtk to assign taxonomy but used Sylph. Then I guess you parsed the species name from the contigs? Unfortunately this will not provide the accurate taxonomy because GTDB does not correct the taxonomic names in each of the assemblies in the database. Very often the contig names and taxonomies do not match the taxonomy assigned by GTDB. This is a critical error in my opinion, but could be solved by simply building a table to associate the correct taxonomy for each contig. A better solution would be to run GTDB-tk on all the assemblies, but I understand this would take considerable time.

On 2025-03-21 13:57:33, user Rubayet Elahi wrote:

Now published in EMBO Reports https://www.embopress.org/doi/full/10.1038/s44319-025-00420-w

On 2025-03-20 14:53:04, user Ana wrote:

This preprint has been published. You can see it in the following link: https://doi.org/10.1186/s10194-025-01969-6

On 2025-03-19 20:10:32, user Lorenzo Calviello wrote:

Amazing work! Any chance to have the mapped crosslinks available (e.g. as bigwig files)?

On 2025-03-19 18:15:47, user Ana Nascimento wrote:

The peer-reviewed version of this pre-print can be found at: https://www.nature.com/articles/s41598-020-69944-6

On 2025-03-18 20:10:33, user Marie Moinet wrote:

I think the title should read P681H, not P680H

On 2025-03-18 19:59:26, user Brett Pike wrote:

Hello, thank you for sharing this mountain of data. In my preliminary evaluation I find that the orientation of the chromosomes is not standardized, i.e. about half need to be reverse complemented. I am writing to ask that you fix this, and I suggest using the orientation from cs10. ntSynt-viz with '--normalize' flag I find to be the simplest visualizer for this task. Thank you!

On 2025-03-18 13:47:33, user Andreas Bueckle, Ph.D. wrote:

Please note that this paper was published in Nature Methods on Thu, Mar 13, 2025: https://www.nature.com/articles/s41592-024-02563-5

On 2025-03-17 18:50:48, user Catherine Douds wrote:

Thank you so much for sharing this work, it’s a really great paper. My biggest criticism is that the methods section does not clearly define how the Ribo-seq and RNA-seq were aligned. Did you align with a different transcript or for each dataset? Or was there one transcript all data were aligned to? I’d love to see a more detailed methods section in the final version.

On 2025-03-17 14:47:54, user Simak Ali wrote:

Now published in Cancer Research. DOI: 10.1158/0008-5472.CAN-24-0013

On 2025-03-17 07:38:26, user YQ Hu wrote:

This preprint has been published in Nature entitled "Plasma proteomic associations with genetics and health in the UK Biobank (doi: 10.1038/s41586-023-06592-6)“ in 2023.

On 2025-03-16 17:51:31, user Paul Macklin wrote:

This is now published here:

https://doi.org/10.1007/s11538-024-01408-8

On 2025-03-15 05:20:17, user Stef wrote:

Interesting approach. It would be interesting to compare with sccomp. A count-based sum-contrained Beta-Binomial model https://doi.org/10.1073/pnas.2203828120

On 2025-03-15 04:05:42, user Min Zhu wrote:

The full version of this manuscript is online in Science Advances. https://www.science.org/doi/10.1126/sciadv.adt7274

On 2025-03-15 03:29:36, user Spencer Williams wrote:

The title is misleading. This paper is not about chaotropic agents. Remove this tangential information from title and abstract

On 2025-03-14 21:15:12, user Rajendra K C wrote:

We discussed this paper in our RNA journal club. We found the discovery of this novel splicing mechanism quite interesting, which seems like a last-resort strategy for cells to remove transposons that have already integrated into exons while still retaining some level of functional protein. The mutagenesis experiment to identify SOS splicing factors was particularly interesting. One question that came up in our discussion: What happens to the excised transposon post-SOS splicing? Is there any evidence that it gets degraded or reintegrated elsewhere in the genome?

On 2025-03-14 16:26:21, user staszek sdh wrote:

https://onlinelibrary.wiley.com/doi/full/10.1002/pro.5244

On 2025-03-14 11:51:35, user Jacob Hanimann wrote:

Love the approach of mixing morphology with molecular state in patient tissue for the identification of new biomarkers!

On 2025-03-14 06:51:45, user Thomas Bradley wrote:

This looks like great work, but I feel our prior work on this topic should have been cited ( https://www.nature.com/articles/s41467-023-39867-7 ) especially as we arrive at similar conclusions

On 2025-03-14 04:31:15, user makotokun wrote:

Introductin: "Though such mutations are rare, mammalian embryos and placentae face unique challenges during normal development that can impose GIN 1."<br /> 1. Why mammal is unique for the challenges of GIN? I can not find answer from Ref.1.<br /> 2. I believe the "placentae" should be "placenta".

On 2025-03-13 23:38:50, user Jesus Montoya wrote:

This seems to have been published last year in Communications Biology: https://www.nature.com/articles/s42003-024-07147-9

On 2025-03-13 13:24:44, user Justina Zvirblyte wrote:

Published: https://www.nature.com/articles/s42003-024-06478-x

On 2025-03-13 13:09:46, user marodon wrote:

Related to "Somewhat paradoxically, a recent pre-print study demonstrated a small but statistically significant decrease in basal heat sensitivity in both female and male mice conditionally depleted for Penk expression in systemic Tregs. Mechanical thresholds and other sensory modalities were however not examined ". This sentence is not accurate since the preprint had been significantly improved and was published in eLife as a Version of Record (VOR) in August 2024. Various mechanical tests were performed and are shown in a supplementary figure in the VOR. Moreover, mice depleted of Penk in Treg do not show a decrease in basal heat sensitivity but an increase (they are more sensitive @55° than the controls). These results are confirmed by Mendoza et al using the same mouse model. Best regards

On 2025-03-13 10:31:41, user Diethard Tautz wrote:

There are two key conclusions in this paper: 1) an ancestral origin of house mice from the Indo-Pakistan region and 2) incomplete lineage sorting for the observed alle sharing between contemporary populations.

Both conclusions are not sufficiently supported, given the current published evidence. I suggest that the authors carefully study this previous evidence and adjust their conclusions accordingly.

1. Origin of the house mouse radiation<br /> To trace the region of origin based on population genetic data, requires sufficient sampling of the relevant regions and comparable sample structures. The broadest samplings available to date that address the question of the origin are published in (Afzali, 2024; Hardouin et al., 2015). They show a high diversity of lineages in Iran and a complex history of populations across Asia. <br /> Lawal and Dumont include only one population from Iran, but do not capture the full diversity that is already known from there.<br /> Further, some of the population samples used by Lawal and Dumont represent sampling from local regions, while others are from broad regions (PAK and IND). Given the known deme structure in mice (Linnenbrink, Teschke, Montero, Vallier, & Tautz, 2018), the broad samplings of PAK and IND may cover different lineages that should not be lumped into a single one. This issue would need a deeper attention in the overall analysis.

2. Incomplete lineage sorting instead of introgression<br /> This issue has been addressed in a large number of papers. All of these authors have carefully evaluated the two alternatives. The analysis presented by Lawal and Dumont is too superficial to make a strong claim that runs contrary to all of these previous data and analysis. <br /> Probably the strongest argument against incomplete lineage sorting is the existence of large introgressed haplotypes that segregate in the different subspecies and species and that were found to be subject to adaptive introgression (Song et al., 2011; Staubach et al., 2012). Several of such regions have subsequently been studied in detail and the long haplotype structures were confirmed, e.g. in (Banker, Bonhomme, & Nachman, 2022; Hasenkamp, Solomon, & Tautz, 2015; Linnenbrink, Ullrich, McConnell, & Tautz, 2020). <br /> Neither incomplete lineage sorting, nor long-term balancing selection can explain the existence of such long introgressed haplotypes, since they would be broken up by recombination over time. Note that although the mouse lineage divergence times seem "shallow" with being shorter than 0.5 Million years, the number of generations is actually high, given the short generation times. To suggest that incomplete lineage sorting is a possible explanation for the shared alleles would require to show with appropriate simulations that long haplotypes could be retained over hundreds of thousands of generations without breaking them up.<br /> Such simulations have been extensively used for the comparisons between Neandertals and humans, where introgression at specific loci is distinguished from ILS by comparing expected haplotype lengths.

Afzali, Y. (2024). Asian Mus musculus: subspecies divergence, genetic diversity, and historical biogeography. JOURNAL OF MAMMALOGY, 105(6), 1378-1391. doi:10.1093/jmammal/gyae075<br /> Banker, S., Bonhomme, F., & Nachman, M. (2022). Bidirectional Introgression between Mus musculus domesticus and Mus spretus. GENOME BIOLOGY AND EVOLUTION, 14(1). doi:10.1093/gbe/evab288<br /> Hardouin, E. A., Orth, A., Teschke, M., Darvish, J., Tautz, D., & Bonhomme, F. (2015). Eurasian house mouse (Mus musculus L.) differentiation at microsatellite loci identifies the Iranian plateau as a phylogeographic hotspot. Bmc Evolutionary Biology, 15. doi:10.1186/s12862-015-0306-4<br /> Hasenkamp, N., Solomon, T., & Tautz, D. (2015). Selective sweeps versus introgression - population genetic dynamics of the murine leukemia virus receptor Xpr1 in wild populations of the house mouse (Mus musculus). Bmc Evolutionary Biology, 15. doi:10.1186/s12862-015-0528-5<br /> Linnenbrink, M., Teschke, M., Montero, I., Vallier, M., & Tautz, D. (2018). Meta-populational demes constitute a reservoir for large MHC allele diversity in wild house mice (Mus musculus). Frontiers in Zoology, 15. doi:10.1186/s12983-018-0266-9<br /> Linnenbrink, M., Ullrich, K. K., McConnell, E., & Tautz, D. (2020). The amylase gene cluster in house mice (Mus musculus) was subject to repeated introgression including the rescue of a pseudogene. Bmc Evolutionary Biology, 20(1). doi:10.1186/s12862-020-01624-5<br /> Song, Y., Endepols, S., Klemann, N., Richter, D., Matuschka, F. R., Shih, C. H., . . . Kohn, M. H. (2011). Adaptive Introgression of Anticoagulant Rodent Poison Resistance by Hybridization between Old World Mice. Current Biology, 21(15), 1296-1301. doi:10.1016/j.cub.2011.06.043<br /> Staubach, F., Lorenc, A., Messer, P. W., Tang, K., Petrov, D. A., & Tautz, D. (2012). Genome Patterns of Selection and Introgression of Haplotypes in Natural Populations of the House Mouse (Mus musculus). Plos Genetics, 8(8). doi:10.1371/journal.pgen.1002891

On 2025-03-12 17:30:11, user xyz wrote:

I read your paper the study is nice but I have certain questions regarding your paper<br /> 1. In figure 5 why the percentage of macrophage with phagocytosis and trogocytosis in case of suspended cells same.<br /> 2. In figure 6 can you please confirm what was the effect on macrophage trogocytosis on increasing the cell adhesion<br /> 3. Also what was the cell nature adherent or suspended when you din different integrin knockout<br /> Hope to hear from you back

On 2025-03-12 09:54:00, user achilleas_frangakis wrote:

It appears that the molecular architecture of the kidney slit diaphragm is evolutionarily conserved from Drosophila to mice!

On 2025-03-12 03:33:39, user Researcher_872 wrote:

RNA sequencing and proteomics data indicate that midnolin is expressed ubiquitously across a wide range of cell lines and tissues (DepMap and Proteinatlas). Therefore, it is unclear why the authors suggest in the abstract that midnolin is predominantly expressed in lymphocytes.

A previous BioRxiv paper reports the structure of midnolin bound to the proteasome (PMID: 40027645), which was not acknowledged or cited in this paper. The authors cannot state the mechanism is "unknown" when there is a 2023 Science paper describing the mechanism (PMID: 37616343). Furthermore, there is a 2016 Dev Cell paper (PMID: 27326929) that is the first to explore the role of midnolin in vivo and its interaction with the proteasome, which was also not cited in this preprint or the authors' previous paper (PMID: 38625151).

Overall, the authors should be more mindful of the literature and accurately cite seminal papers that preceded their work.

On 2025-03-11 16:46:46, user Nikhil Thomas wrote:

This manuscript has been published in PLoS Genetics at the following link:<br /> https://doi.org/10.1371/journal.pgen.1011370

On 2025-03-11 05:53:34, user John Golz wrote:

This manuscript has now been published and a link to the publication could now be included.

https://doi.org/10.1186/s12896-024-00864-3

Thanks

On 2025-03-10 19:52:40, user Sr. Galán wrote:

A peer reviewed version of this article is now published in Ecosistemas, link here:<br /> https://www.revistaecosistemas.net/index.php/ecosistemas/article/view/2847

On 2025-03-10 04:21:18, user Young Cho wrote:

Dear Authors,<br /> Thank you for sharing your insightful work, "In Silico Engineering of Stable siRNA Lipid Nanoparticles: Exploring the Impact of Ionizable Lipid Concentrations for Enhanced Formulation Stability." Your study makes an important contribution to the field of lipid nanoparticle (LNP) research by highlighting the role of ionizable lipid concentrations in siRNA encapsulation and stability. The use of coarse-grained molecular dynamics (MD) simulations and steered molecular dynamics (SMD) provides a detailed molecular-level understanding of LNP formation, which is particularly valuable for optimizing RNA-based drug delivery systems.<br /> Summary<br /> This study examines how neutral and positive ionizable lipids influence LNP stability and siRNA encapsulation efficiency. The findings indicate that LNPs with positive ionizable lipids encapsulate siRNA more effectively than those with neutral lipids, likely due to their integration with phospholipids and the prevention of siRNA escape. Interestingly, low and medium concentrations of both neutral and positive DLKC2 showed better compartment formation and encapsulation efficiency compared to high concentrations. Additionally, neutral lipids exhibited greater aggregation, which could impact LNP stability.<br /> Introduction<br /> Your introduction effectively establishes the relevance of this study by situating it within the broader context of LNP research. The discussion of existing challenges in siRNA delivery and the role of lipid composition is well-articulated. However, further elaboration on how your study builds upon previous experimental findings could help connect computational insights with practical applications.<br /> Results<br /> The figures and data presentation generally support your conclusions. Figure 4, which illustrates LNP compartment formation at different lipid concentrations, is particularly valuable in showing how high concentrations lead to instability. We do think that some quantitative metrics such as bilayer thickness, lipid density, or compartment size would enhance the strength of these findings. Additionally, since water is omitted from the visualizations for clarity, we think it would be beneficial to include a figure that shows water so we can visualize the hydration effects and lipid-water interactions.<br /> Discussion<br /> Your discussion effectively compares findings with prior studies, reinforcing that positive ionizable lipids enhance siRNA encapsulation and that lipid aggregation in neutral systems may reduce stability. While you mention previous molecular dynamics studies (e.g., Paloncýová et al. and Trollmann & Böckmann), we feel a more direct comparison of numerical data and trends from these works would further contextualize your results. Additionally, discussing potential experimental validation techniques (e.g., cryogenic electron microscopy or encapsulation efficiency assays) could provide future directions for integrating simulations with laboratory-based studies. However, that is just our opinion as we do understand that this study takes on a more computational approach and is still very impactful.<br /> Suggestions for Improvement<br /> 1. Expand quantitative analysis in Figure 4 by including measurements of bilayer thickness, lipid density, and compartment size to provide a more rigorous validation of LNP stability.<br /> 2. Clarify the role of hydration in lipid-water interactions since water was omitted in visualizations.<br /> 3. Strengthen comparisons with previous molecular dynamics and experimental studies by integrating direct numerical contrasts.<br /> 4. Discuss potential experimental validation approaches that could complement your computational findings and enhance their real-world applicability.<br /> Final Thoughts<br /> Overall, this paper presents a well-structured and valuable contribution to siRNA delivery research. With minor refinements in quantitative analysis, literature comparisons, and discussion of experimental validation, the study could be even more impactful. Thank you for your efforts in advancing the field of LNP-based RNA therapeutics!<br /> Best regards,<br /> UHM MBBE 602 Graduate Students

On 2025-03-10 04:17:10, user Young Cho wrote:

Summary:<br /> This study provides a comprehensive analysis of miRNA profiles in Culex tarsalis, identifying 86 known miRNAs and 20 novel miRNAs, is a significant contribution to the field of insect molecular biology and vector research. This works sets the foundation for future studies on gene regulation and host-pathogen interactions in Cx. tarsalis, a major vector of West Nile Virus (WNV). While the methodology is robust and the findings are compelling, the paper would benefit from some minor revisions to strengthen data presentation, clarify experimental choices, and align its conclusions more closely with the results. <br /> Introduction: <br /> The introduction frames the importance of miRNA research in Cx. tarsalis well, particularly in the context of understanding its role as a vector for WNV. However, the title of the paper may be misleading since the findings do not directly link the identified miRNAs to WNV vectoring. Reframing the title and introduction to focus on the broader importance of miRNA characterization in Cx. tarsal without overemphasizing the WNV connection would improve clarity and prevent misalignment between the study’s scope and its claims. <br /> Results: <br /> The results section presents a comprehensive dataset of miRNAs identified through computational comparison with other mosquito species and validated using RT-qPCR. The discovery of novel miRNAs and the observed isomiR variations are particularly noteworthy, with the predominance of 3’ end insertions being a finding of potential significance in gene regulation. That said, clearer justification for the selection of the 10 miRNAs validated by qPCR would strengthen the interpretability of the results. <br /> Discussion: <br /> The discussion effectively places the study’s findings within the broader context of existing research on mosquito miRNAs and draws meaningful comparisons with other species like Aedes albopictus and Cx. quinquefasciatus. The evolutionary conservation of miR-184 and the identification of unique miRNAs in Cx. tarsalis offer valuable insights. However, the paper would benefit from further discussion on the functional implications of these miRNAs, particularly their potential roles in development, immunity, and host-pathogen interactions. Additionally, the observed differences in miRNA expression between cell lines and whole organisms raise important questions that warrant more exploration. <br /> Suggestions: <br /> 1. Revise the title to better reflect the study’s current findings and avoid overemphasizing WNV. <br /> 2. Clarify the rationale behind the selection of the 10 miRNAs for qPCR validation. <br /> 3. Expand the discussion on the functional roles of the identified miRNAs and their potential involvement in host-pathogen interactions. <br /> 4. Address the limitations more explicitly, such as the reliance on a single genome assembly, the lack of data from different mosquito life stages and tissues, and the absence of additional validation methods like Northern blot. <br /> 5. Consider including a statistical analysis to highlight differences in miRNA expression between cell lines and whole organisms. <br /> 6. Discuss the potential influence of feeding behavior on gene expression and its relevance to vector competence.

On 2025-03-09 11:44:16, user Jake Ivan P. Baquiran wrote:

Now published in Environmental Microbiology doi: 10.1111/1462-2920.70041

On 2025-03-07 18:39:57, user Randall Eck wrote:

Exciting article! Given the role of 3' UTR alternative polyadenylation (APA) in RNA localization and stability (PMC9261900) and the role of TDP-43 in regulating 3' UTR APA (PMC10849503), is there a relationship between TDP-43 regulation of RNA localization and 3' UTR APA in your data?

On 2025-03-07 12:28:58, user Marc RobinsonRechavi wrote:

Under Data Accessibility, the authors write:

Data and R code sufficient to replicate all analyses will be made publicly available upon acceptance of this manuscript for publication.

This is a publication, i.e. it is made public as part of the scientific record and is citable, thus I strongly invite the authors to make the corresponding data and code available without delay.

On 2025-03-07 07:27:12, user Marc RobinsonRechavi wrote:

Under Code Sharing Plan, the authors write:

All the code used for the generation of datasets and subsequent analysis will be made publicly available in<br /> a GitHub repository upon publication

This is a publication, i.e. it is made public as part of the scientific record and is citable, thus I strongly invite the authors to make the corresponding code available without delay.

On 2025-03-06 09:47:18, user Alexei Korennykh wrote:

As a corresponding author, Alexei Korennykh hereby documents the timeline of our discovery of Nocturnin NADP(H) phosphatase activity.

[2018, December 17]<br /> Our Manuscript "The Metabolites NADP+ and NADPH are the Targets of Circadian Protein Nocturnin (Curled)" was submitted to a high-quality journal (per BioRxiv policy journal name cannot be mentioned here) (under id ....2018-12-17736A)

[2018, December 19]<br /> The editor sends the work to referees.

[2018, December 21]<br /> We submit our Nocturnin-NADP co-crystal structure to the PDB database and obtain PDB ID 6NF0.

https://www.rcsb.org/structure/6NF0 has the following permanent record:

Deposited: 2018-12-18 <br /> Released: 2019-05-01 <br /> Deposition Author(s): Estrella, M.A., Du, J., Korennykh, A.

[2019, January 15]<br /> Journal rejects the manuscript, based substantially on negative remarks of Ref#3, who is “an expert on Nocturnin”:

Referee expertise:

1: crystal structure

2: NADPH/NADP metabolism

3: nocturnin biology and function

Although we responded that all concerns can be addressed directly and without experiments, the journal is not willing to re-consider our work.

[2019, January 30]<br /> We posted our manuscript here, to BioRxiv and it became available to the public.

[2019, March 28] <br /> We submitted the paper to the final publishing journal (see top of the page, "Now published in ") and the paper was received and sent for review.

[2019, April 18] <br /> The paper was accepted (see top of the page, "Now published in ").

[2019, May 30] <br /> The paper was published (see top of the page, "Now published in ").

[2019, June 5] <br /> Alexei Korennykh wrote to change Uniprot annotation of Nocturnin

Wed Jun 05 05:20:37 2019, akorenny@princeton.edu wrote:

Major changes in NOCT (CCRN4L) gene function and description. <br /> Source:<br /> https://www.nature.com/articles/s41467-019-10125-z <br /> Suggested revisions:

"Circadian deadenylase"<br /> changes to<br /> "Circadian NADP(H) phosphatase"

"Catalytic activity: Exonucleolytic cleavage of poly(A) to 5'-AMP. EC:3.1.13.4"<br /> changes to:<br /> "Catalytic activity: 2'-Phosphate removal from NADP+ and NADPH. EC:to be created"

[2019, June 7] <br /> UniProt Begins re-annotation<br /> Dear Alexei,

Thank you for having submitted a request for the update of a UniProtKB entry.

Your request has already been sent to an annotator and will be handled with<br /> high priority.

We will send you an e-mail when the update is completed.

Best regards

SP

[2019, July 1] <br /> UniProt changes Deadenylase to Phosphatase for Nocturnin:

Dear Alexei,

Thank you for passing on the details of your recent paper. The nocturnin <br /> entry has been updated and will be available as part of UniProt release <br /> 2019_08 on 18th September. In the meantime, I have included the entry <br /> below in text format. Please feel free to get back in touch if you have <br /> any comments about the content.

Kind regards,<br /> MM

ID NOCT_HUMAN Reviewed; 431 AA.<br /> AC Q9UK39; D3DNY5; Q14D51; Q9HD93; Q9HD94; Q9HD95;<br /> DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.<br /> DT 04-NOV-2008, sequence version 2.<br /> DT 31-JUL-2019, entry version 148.<br /> ……<br /> CC NAD(+) and of NADPH to NADH (PubMed:31147539). Shows a small<br /> CC preference for NADPH over NADP(+) (PubMed:31147539). Represses<br /> CC translation and promotes degradation of target mRNA molecules<br /> CC (PubMed:29860338

…

[2019, July 1]

Up to this date (i.e. 5 months since our BioArxive paper became publically available) no work by others, which described Nocturnin as NADP(H) phosphatase was published or submitted to any journal, to the best of our knowledge.

On 2025-03-06 02:33:06, user Charles Warden wrote:

Thank you very much for posting this preprint!

The "Code availability" section indicates "We provide supplementary files containing an R script with functions to run our CRF-based correction procedure as well as a tutorial notebook illustrating how to run it.".

However, I think I see anything uploaded as supplemental files. Am I overlooking anything, or does the supplemental code need to be added in a revision?

Thank you very much!

Sincerely,<br /> Charles

On 2025-03-06 00:00:06, user Laura Lackner wrote:

An updated version of this preprint has been published in MBoC - https://doi.org/10.1091/mbc.E23-05-0168 . The revised and accepted version has a slight modification to the title.

On 2025-03-05 19:55:42, user Enrico Radaelli wrote:

In this viral video on YouTube<br /> https://www.youtube.com/watch?v=WNuzopVDFQs <br /> The company claims that "There were no unintended consequences except adorability".<br /> However, the mice are clearly pruritic and they exhibit crusty/flaky skin in glabrous areas (especially paws and eyelids).<br /> I wonder if this is part of the phenotype or if the mice contracted infections that might have caused these lesions (mites, C. bovis, etc.).

On 2025-03-04 21:05:38, user Simone Picelli wrote:

Hi, I think there is a mistake in the name of the company used to make the modified TSO. It's not Biosyn Corporation ( http://biosyncorp.com ), as you wrote, but rather Bio-Synthesis ( http://biosyn.com ). <br /> Moreover, in the TSO sequence: "/5Biosg/" is the acronym used by IDT for a 5' biotin. The "g" has nothing to do with deoxyguanosine (G), but you write in the paper "5BiosG/" and this can be confusing. The standard 10x TSO sequence is, in fact: 5’-AAGCAGTGGTATCAACGCAGAGTACATrGrGrG-3’<br /> so no G at the 5' (like there was never a G at the 5' of the SMART-seq oligo, from which 10x took their sequence).<br /> The code for biotin at Biosyn is [Btn] (standard C6 spacer, which I assume is the one you mean here).

On 2025-03-04 02:45:42, user Andrei Drabovich wrote:

Interesting technology, but Table 2 "Total Ion Usage Rate" calculations for timsTOF vs SLIM-QTOF are not clear.<br /> Seems like all major advantages in numbers are due to "TOF transmission efficiency" but not to ion mobility.

On 2025-03-04 02:21:17, user Nelly Olova wrote:

This work has now been published in the Methods in Molecular Biology book series, volume 2866 (Springer Nature)

On 2025-03-03 17:25:34, user Johannes Daniel Scharwies wrote:

This is the author's version of the work. It is posted here by AAAS for personal use, not for redistribution. The definitive version was published in Science on 6 Feb 2025, DOI: 10.1126/science.ads5999.

On 2025-03-03 16:11:50, user hansdb wrote:

One Corded Ware (CGG107476) and two Bell Beaker individuals (CGG106805 and CGG106737) from your interesting study belong to Y-DNA haplogroup I2-L38 (aka I2a1b2a).<br /> As decribed in my citizen scientist paper ( https://www.academia.edu/115363574/RECONSTRUCTING_THE_JOURNEY_OF_Y_DNA_HAPLOGROUP_I2_S2555_TO_I2_L38_Tracing_Genetic_Footprints_Across_Time_and_Space ) this haplogroup was also related to:<br /> * an EBA Unetice sample from Germany (I0114)<br /> * an EBA Unetice sample from Bohemia (I7959)<br /> * an IA Hallstatt sample from Germany (MBG008)<br /> * an IA La Tène sample from Bohemia (I17327)<br /> * an IA La Tène sample from France: GLN32

Most interestly this haplogroup also occured among the Urnfield epoch Lichtenstein clan from Osterode-am-Harz. Since it is mentioned (paragrapghs 194 to 196) that very few genomes from the Urnfield Culture exist (as a result of the cremation practice) it would be interesting if the well-preserved samples of the Lichtenstein cave could be integrated in your study.

On 2025-03-03 14:46:23, user Elisa Rosati wrote:

A couple of questions:<br /> 1) How can you be sure that the MAIT cells you observed are not bystander activated during the T cell stimulation and thus not really Myelin-specific? I would perhaps perform the experiments with two additional setups:<br /> a) MHC-blockage (If MAIT cells are really specific they should appear here) <br /> b) MR1-blockage (if MAIT cells are specific and activated via TCR they should not appear here)

2) Have you tried to perform the analyses separately for HLA-DRB1*15:01 positive and negative individuals separately? It was shown by a study from Adaptive Biotechnology that a limited number of TCR clusters enriched in MS exist and that these clusters are mostly CD4 and very different in DRB1*15:01 positive and negative individuals.

On 2025-03-03 06:36:55, user Siddhartha Saha wrote:

Very insightful article. there was another outbreak of avian influenza among tigers in a nearby area around same time, so wondering whether any relation to that outbreak has been ruled out. Even in that outbreak, specimens were sent to NIHSAD ( https://www.thehindu.com/sci-tech/energy-and-environment/leopard-three-tigers-die-of-avian-flu-in-maharashtras-gorewada-rescue-centre/article69064307.ece )

On 2025-03-02 15:54:05, user Ambrose, Zandrea wrote:

This study has been peer reviewed and published: https://journals.asm.org/doi/10.1128/mbio.00169-25

On 2025-03-01 00:59:54, user Tim wrote:

While groundbreaking, I wish this paper expanded up author N.R.B.’s de novo inclusion of huel in the fine tuning of the RFDiffusion network compared to the characterization of fermented yeast to acetaldehyde formation chain on massive (1 million samples or more) scales.

On 2025-02-28 12:53:50, user Prof. T. K. Wood wrote:

l 339: Paris is a toxin/antitoxin system and TAs are the most-prevalent phage inhibition system; this should be noted.

l 365: The seminal identification of of TAs and phage inhibition (1996) should cited:<br /> doi: 10.1128/jb.178.7.2044-2050.1996

On 2025-02-28 10:05:42, user Giampaolo Minetti wrote:

This preprint has now been published as a peer reviewed, open access article in Cell Death Discovery:<br /> Minetti G, Dorn I, Köfeler H, Perotti C, Kaestner L. Insights from lipidomics into the terminal maturation of circulating human reticulocytes. Cell Death Discov. 11, 79 (2025). doi: /10.1038/s41420-025-02318-x<br /> Stable, shortened URL:<br /> https://rdcu.be/ebvgH

On 2025-02-28 08:34:44, user Bjarke Jensen wrote:

Dear authors,

Congratulations with this interesting study.

In my view it would be helpful if you further develop the descriptions of the state of trabeculation. For example, did you make measurements (counting, thicknesses, proportions) of the trabecular and compact layer, what were the values and how do they relate to diagnostic criteria associated with trabeculation? It would also be helpful if you support this part of your Results with clinical imaging (echocardiography and CMR) onto which is shown the measurements (or overt phenotype) that led to the interpretation of 'hypertrabeculation'. I for one would not mind a full text figure dedicated to this part. <br /> Part of the reason for giving these suggestions is of course that your title states 'hypertrabeculation' while the associated phenotyping is proportionally very small and accordingly a bit unclear.

Best wishes and good luck with the publication.

Bjarke

On 2025-02-27 23:06:56, user Yuliana Pullas wrote:

Hi,<br /> 1. In your text you have "Consistent with proteins accounting for 13–23% of EPS (Fig. 3A)" I think it is Fig. 2A.

On 2025-02-27 20:34:24, user Michael Roswell wrote:

This paper was published in January, 2025 https://onlinelibrary.wiley.com/doi/10.1111/ddi.13969

On 2025-02-27 17:50:50, user Maxwell Neal wrote:

A peer-reviewed version of this article has been published by Nucleic Acids Research: Genomics and Bioinformatics<br /> https://doi.org/10.1093/nargab/lqaf008

On 2025-02-27 16:02:16, user Pär Jonsson wrote:

Article: https://doi.org/10.1021/acs.jcim.4c01799 <br /> Code & Data: https://github.com/edvinforsgren/OPLS-HDA

On 2025-02-27 04:18:23, user Manoj Menon wrote:

Published now in Molecular & Cellular Biology https://doi.org/10.1080/10985549.2025.2454421

On 2025-02-27 02:16:06, user Le Zhen wrote:

Now this manuscript has been accepted for publication in the journal Biomaterials, with a new title: Synthetic Vascular Graft That Heals and Regenerates (doi: https://doi.org/10.1016/j.biomaterials.2025.123206) .

On 2025-02-26 17:21:48, user Leonardo Di Bari wrote:

Thanks for the analysis, the study is promising. I am, Leonardo Di Bari, a PhD student in the SPQB ( https://sites.google.com/view/spqb ) group of Martin Weigt and Francesco Zamponi: we have utilized the entropy that you present in the following three articles.<br /> https://arxiv.org/pdf/2412.01969 <br /> https://www.pnas.org/doi/abs/10.1073/pnas.2406807121 <br /> https://www.nature.com/articles/s41467-022-31643-3 <br /> I think it would be interesting to maybe compare the two formulations. <br /> Best regards,<br /> Leonardo Di Bari

On 2025-02-26 10:03:48, user Young Cho wrote:

This is a comment from a Journal Club of MBBE 602 in Univ of Hawaii.

Summary<br /> This paper explores the capabilities of twin prime editing (twinPE) for large DNA sequence modifications, including deletions, replacements, integrations, and inversions. The authors demonstrate the efficiency of twinPE in human cells (HEK293T & Huh7) and its potential for therapeutic applications when combined with the Bxb1 integrase. Key findings include precise and flexible editing with fewer indels, high knock-in efficiency, and the ability to bypass certain DNA repair pathways. However, the study lacks long-term data on genomic stability and scalability for human applications, and some experimental details and comparisons with other gene-editing techniques are insufficiently explored.

Introduction<br /> The introduction provides a solid foundation for the study but could benefit from more background information on the therapeutic applications explored, as well as the mechanism that resulted in limitations relating to the pegRNA pairs, or the low Bxb1 efficiency.

Results<br /> Figure 2:<br /> The figure demonstrates twinPE’s efficiency in large DNA sequence insertion and replacement. However, the formatting is poor, the figure legend is separate from the figure and labels are a bit confusing. The authors should revise the figure to improve readability.<br /> The large error bar in Fig. 2F (deletion size 589) suggests variability in the editing strategy. The authors should address this in the text, discussing potential outliers or variability in the system.

Figure 3:<br /> This figure effectively shows the mechanism and efficiency of twinPE combined with Bxb1 integrase. However, the authors should clarify why certain pegRNA pairs performed better than others and why some loci (e.g., CCR5, AAVS1) were more successful.<br /> The discussion should also address the limitations of single transfection compared to sequential transfection to allow researchers to build off of this work.

Figure 4:<br /> The figure explores therapeutic applications of twinPE, particularly in correcting inversions at recombination hotspots. The authors should expand on the implications of these findings for gene therapy and discuss potential challenges in scaling up for human applications.

Discussion<br /> The discussion is well-written but could be strengthened by addressing the following:<br /> Limitations of twinPE: The authors should discuss why lower frequencies occurred in single transfection compared to sequential transfection and why some pegRNA pairs performed better than others. Additionally, they should explore the potential limitations of using Bxb1 integrase and whether other integrases could be more effective.<br /> Comparison with other gene-editing techniques: The authors briefly mention the advantages of twinPE over CRISPR but do not provide a direct comparison. Including experimental data or a discussion comparing twinPE to CRISPR or other editing methods would strengthen the paper.<br /> Long-term implications: The study lacks long-term data on genomic stability after large DNA modifications. The authors should discuss potential risks, such as off-target effects or genomic instability, and suggest future studies to address these concerns.

Suggestions<br /> Improve Figure Quality: Revise figures to ensure they are clear, readable, and properly formatted. Include detailed legends and consider adding summary panels to highlight key findings.<br /> Expand on Limitations: Discuss the limitations of twinPE in more detail, including variability in editing efficiency, challenges in scaling up for human applications, and potential long-term effects on genomic stability.<br /> Compare with Other Techniques: Include a direct comparison of twinPE with CRISPR or other gene-editing methods to highlight its advantages and disadvantages.<br /> Explore Additional Integrases: Investigate the use of other integrases in combination with twinPE to determine if they offer improved efficiency or precision.<br /> Provide Long-Term Data: Conduct follow-up studies to assess the long-term effects of large DNA modifications on genomic stability and cell viability.<br /> Enhance the Introduction: Add more background information on the limitations of existing gene-editing technologies and how twinPE addresses these challenges.<br /> Address Variability in Results: Discuss potential outliers or variability in the data, particularly in Fig. 2F, and suggest ways to improve consistency in future experiments.

Editorial Decision<br /> The paper presents significant advancements in gene-editing technology and demonstrates the potential of twinPE for precise and efficient large DNA sequence modifications. However, the study would benefit from addressing the limitations and expanding on the comparisons with other gene-editing techniques. This publication could be strengthened with revisions to improve figure quality, clarify data interpretation, and exploring long-term stability the genetic edits. Overall, the paper was dense with information so the limitations are understandable, as only so much can be presented in one publication.

On 2025-02-26 09:56:55, user Jonathan Rondeau-Leclaire wrote:

was looking forward to that preprint (saw your talk at cshl microbiome!)

quick suggestion for figure 5: use a horizontal jitter so we can distinguish points that fully overlap (e.g. both VAMB in panel b. seem to be perfectly overlapping, but we can't be sure)

best of lucks for publication!

On 2025-02-25 21:24:18, user Xiaotong Yao wrote:

The measurements for the "realistic"-ness of the simulated genomes seems inadequate. For examples, what are the VAFs of mutations in the LOH or homozygously deleted or amplified regions?

On 2025-02-25 21:16:36, user Xiaotong Yao wrote:

No. You simply cannot "simulate" structural variants as if they are just rows in a BEDPE file.

Doing it in the way of this paper won't even guarantee your CNV boundaries are matched correctly with the junction breakends! Let alone consistent junction copy numbers or realistic complex SV events. This approach of treating each "variant" as an individual event only works for short variants, and CNVs to some extent.

To truly forward simulate a cancer genome that is accumulating structural variants/CNVs requires virtual cell cycles and keeping tabs on the junction balance constraints and linear/circular DNA structures, e.g., losing a telomere, di-centric chromsomes. We tried this before, but it is very very hard as the genomes coming out of the simulations are not anything remotely survivable for a cell and nothing like the real cancer genomes. So this is a fascinating and challenging open question.

On 2025-02-25 20:42:31, user Victor Gonzalez Perdomo wrote:

This study seems biased, there is very little data from the Paleolithic, you have data mostly around Neolithic. Also it seems that you have very little ancient data around the southeast Europe. You neither aproach the fact most light pigmentation features appeared close to the atlantic coast then seems to spred to the interior.

On 2025-02-25 05:38:33, user Roberto Nava wrote:

The reporter system is genius! Any chance the authors would be willing to share the supplemental tables? They don't appear in the PDF.

On 2025-02-25 01:58:05, user Maria Rebolleda Gomez wrote:

Really interesting paper showing that variation across strains in the relationship between growth rate and antibiotic-induced lysis as well as interactions can shape the outcomes of community re-structuring after antibiotic treatment. The authors are able to use data from individual E. coli strains to predict the overall enrichment in the community after antibiotics. However, the last step of the derivation in the methods was not clear to me why is it G_m,i + C - It is not clear what that constant is. Also in the main body of the paper it states that this is an approximation, but in the derivation is stated as an identity relationship.

On 2025-02-25 00:16:29, user Meet Zandawala wrote:

This study investigates the dynamics of neuropeptide release and activity following blood feeding in female Aedes aegypti mosquitoes. Sajadi et al. provide valuable insights into the temporal signaling dynamics of diuretic and anti-diuretic hormones, significantly enhancing our understanding of excretory physiology in mosquitoes. The authors employ heterologous expression of receptors to quantify circulating peptide levels, a robust methodological approach that strengthens receptor-ligand interaction validation and hormone quantification. Notably, the study demonstrates a synergistic interaction between DH31 and kinin-like peptides on Malpighian tubules, contributing novel findings to the existing literature on neuropeptide-mediated excretory regulation in mosquitoes. Overall, the study presents an innovative and well-executed investigation with high methodological rigor.

The authors have presented their findings in a clear and well-structured manner. We only have a few questions and comments/suggestions that could help improve the clarity of the manuscript:<br /> 1.     Can the authors clarify the exact number of female mosquitoes used in each condition (blood-fed vs. non-blood-fed) at each time point, specifically in methodology section 3.2 for the haemolymph collection?<br /> 2.     Were there any biological replicates across different mosquito cohorts? Did the authors observe variability between different mosquito batches? Sample sizes have been provided in the figure captions but what does n signify? <br /> 3.     The study utilizes specific time points for haemolymph collection post-blood feeding. Can the authors provide justification for selecting these intervals? Were preliminary studies conducted to determine these as the most informative time-points, or were they based on prior literature?<br /> 4.     The authors acknowledge the roles of serotonin (5HT) and DH44 in regulating fluid secretion but focus their experimental analysis on DH31, kinin, and CAPA peptides. Could they clarify why 5HT and DH44 were not included in their haemolymph quantification assays? Were there methodological limitations, or were these hormones not expected to show significant post-bloodmeal changes, or is this something they plan to address in the future?<br /> 5.     The study quantifies neuropeptide levels over time but does not discuss the mechanisms responsible for their clearance from haemolymph. Can the authors speculate on whether DH31, kinin, and CAPA peptides are degraded enzymatically, removed through receptor-mediated internalization, or cleared by the Malpighian tubules? Can they use in silico approaches to predict the half-life of these peptides based on their sequence composition? Alternatively, can they extract hemolymph when the peptide has peak activity and test this extract after different times to see how much bioactivity they retain over time? Addressing this would enhance our understanding of neuropeptide turnover and regulation.<br /> 6.     Including the individual data points in the bar graphs can provide more information on the spread of the data.

Comments prepared by Bilal Amir (on behalf of Zandawala lab)

On 2025-02-24 11:41:36, user Peer wrote:

Hello,<br /> I know it's not 100% necessary to mention this in your paper, but through what kind of screen did you identify ISIC1/2 and STIR1/2? <br /> Thx:)

On 2025-02-24 03:43:01, user ryhisner wrote:

I am unable to copy and paste anything into the reference window in the variability tab. It only allows me to type, not copy and paste. This means I would have to type in the entire nucleotide sequence by hand, which I'd rather not do.

On 2025-02-24 01:16:55, user Alex Monell wrote:

Hi bioRxiv staff,

The published version of this manuscript is out at https://www.nature.com/articles/s41586-024-08466-x

Thanks!

On 2025-02-23 17:35:21, user Sean Rands wrote:

This work was published last year in Open Biology -- see https://doi.org/10.1098/rsob.230430

On 2025-02-23 17:33:44, user Sean Rands wrote:

This work was published last year in Royal Society Open Science - see https://doi.org/10.1098/rsos.231882

On 2025-02-23 10:16:14, user Christian Wunder wrote:

Available on NCB:

https://doi.org/10.1038/s41556-025-01616-x

https://rdcu.be/eaLM9

On 2025-02-23 02:33:22, user Cecil Saunders wrote:

I believe there is a typo in the abstract citation; Charles, 2019 should be Darwin, 2019.

On 2025-02-21 20:37:42, user Krzysztof Kozak wrote:

Multiple technological choices resulted in fatal flaws that make the conclusions of this manuscript unjustifiable:<br /> 1. Inadequate chain of custody of the samples, likely leading to massive contamination.<br /> 2. Application of insufficient sequencing methods and inappropriate data processing tools, potentially resulting in various technical artefacts.<br /> 3. Lack of replication, further exacerbated by deliberate mixing of the isolates.<br /> 4. A simplistic and biased interpretation of the observed patterns of change in the molecular sequences.

I posted a full review of the paper on ResearchHub: https://www.researchhub.com/paper/9161412/discovery-of-single-stranded-dna-in-meteorite-derived-cultures-evidence-of-novel-genetic-elements/reviews

On 2025-02-21 15:30:18, user Yuan Fu wrote:

The paper was published in JIPB on February 21, 2025. The DOI link is: https://doi.org/10.1111/jipb.13867 . Please cite it.

On 2025-02-21 14:20:17, user JJ wrote:

In figure 2, part D, the figure legend says - "The median UMI/gene count is shown as a number above a dataset and as a bold line". Does the numbers say UMI/gene or is it just the Median Number of Genes for each dataset?

On 2025-02-21 11:30:52, user mcsu wrote:

Hi, <br /> Care must be taken when using old data tables for example in table S1 the uniprot_IDs given for the following U. maydis proteins no longer map:-<br /> PRA1_USTMA <br /> PRA2_USTMD <br /> UM03423

but are <br /> P31302<br /> P31303<br /> A0A0D1E0T5

In addition, given these errors how confident are you that the Literature-sourced GPCRs are classified correctly?<br /> Many of the Pfam domains claimed to be "consistent with their associated GPCR class (Table 1)" are not found in the exemplar sequences of each class in table S1.<br /> For example, the Git3 Pfam PF11710 suggested as associated with CPCR class 3 is only found in GPR1_YEAST and not the other 4 proteins suggested as Class 3 GPCRs in table S1; see A0A1U8QVN2_EMENI, A0A1U8QIJ6_EMENI, A0A1U8QJM4_EMENI or Q7SAB9_NEUCR

https://uploads.disquscdn.c...

On 2025-02-21 09:14:43, user Wenjun wrote:

Great work! In addition to enhancing light collection efficiency, the proposed method also effectively reduces the number of optical components in the remote imaging system.

On 2025-02-21 09:00:55, user Froy wrote:

A pity this citation is missing: https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00444-2

On 2025-02-21 01:11:53, user Charles Warden wrote:

Thank you very much for posting this preprint for the Giotto Suite!

You have a couple different citations for STalign.

I believe this is the correct citation (Reference 34):

34.↵Clifton, K. et al. Alignment of spatial transcriptomics data using diffeomorphic metric mapping. BioRxiv Prepr. Serv. Biol. 2023.04.11.534630 (2023) doi:10.1101/2023.04.11.534630.Abstract/FREE Full TextGoogle Scholar

However, I think the following reference (to Hildebrandt et al. 2021) may not be correct?

"Image registration was performed using STalign [Reference 2]"

Best Wishes,<br /> Charles

On 2025-02-21 00:46:47, user Hurrian Fan wrote:

Congratulations to the team on some amazing work! The steppe component visible in East_steppe_Sets in Chalcolithic and Bronze Age western Anatolia is modeled with Yamnaya, CWC, and Bell Beaker, which are chronologically and geographically somewhat improbable for the early samples. <br /> Have the authors considered checking potentially more proximal sources of potential steppe ancestry, such as the Kartal A & B clusters from Penske et al 2023?

The subclades of y-hg I-L699 found in the Kulluoba and Kalehoyuk samples are not only shared with Serednii Stih individuals, but also Cernavoda (KTL001 & KTL006) and Thracian EBA individuals (Bul4 & I2165), which might lend some plausibility to this source.

On 2025-02-20 20:30:48, user Jesse Conklin wrote:

This should be linked to the final publication:

Conklin, J. R., Verkuil, Y. I., Lefebvre, M. J. M., Battley, P. F., Bom, R. A., Gill, R. E. Jr, Hassell, C. J., ten Horn, J., Ruthrauff, D. R., Tibbitts, T. L., Tomkovich, P. S., Warnock, N., Piersma, T., & Fontaine, M. C. (2024). High dispersal ability versus migratory traditions: Fine-scale population structure and post-glacial colonisation in bar-tailed godwits. Molecular Ecology, 33, e17452. https://doi.org/10.1111/mec.17452

On 2025-02-20 19:02:49, user Raoul wrote:

There is a previous report that has targeted a disease resistance gene to generate plants with enhance resistance. Similar to what is said in this pre-print ("SNC1 is an attractive target for proof-of-principle modulation of disease resistance by epigenome engineering").<br /> Reference: CRISPRa-mediated transcriptional activation of the SlPR-1 gene in edited tomato plants<br /> Plant Sci, 329 (2023), Article 111617, 10.1016/j.plantsci.2023.111617<br /> Recently a review article has mentioned that: "One notable example of enhancing disease resistance in crops involved the CRISPR activation (CRISPRa) system to activate the defense gene PATHOGENESIS-RELATED GENE 1 gene (SlPR-1) conferring enhanced resistance to Clavibacter michiganensis subsp. michiganensis infection in tomatoes" (taken from: https://doi.org/10.1016/j.pbi.2024.102669 ).<br /> Consequently, the concept has shown to be scientifically and technically feasible, as shown previously in 10.1016/j.plantsci.2023.111617.<br /> Thus, what is stated in this preprint is not really new, for plants: "The results demonstrate that epigenome-engineering of a single defense gene, SNC1, is sufficient to generate plants with improved disease resistance phenotypes."

On 2025-02-20 14:08:04, user Prashant Kaushik wrote:

Could the author kindly comment on how human plasma was processed post collection? Were there sequential centrifugation steps involved and were they consistent among different MS based tech? <br /> Thank you for sharing your fantastic Work

On 2025-02-20 13:55:28, user andy wrote:

Dont forget Bdellovibrio has deacetylases - comment on statement in manuscript about lack of these in Gram negatives

On 2025-02-20 12:15:37, user kei wrote:

Thank you for your interesting paper.

I am curious about the behavior when only the non-natural amino acids in cyclic peptides are not tokenized at the atomic level, and all cyclic peptides are represented using SMILES. I am thinking of investigating this.

That said, I have one question:<br /> What is the input format when inferring complexes of cyclic peptides containing non-natural amino acids and proteins?<br /> (In other words, how are non-natural amino acids formatted in the input?)

If possible, I would appreciate it if you could share an example of the YAML file or other input data used for Boltz1.

Thank you in advance.

On 2025-02-19 13:17:06, user Ali Ryan wrote:

MdaB is not a membrane associated quinone reductase as suggested in figure 5a, it is homodimeric and cytosolic as far as anyone has characterised.

On 2025-02-19 03:28:56, user Yue Jia-Xing wrote:

Author comment:<br /> This work has been formally published in Genome Research recently under a different title:<br /> "Interactive visualization and interpretation of pangenome graphs by linear reference–based coordinate projection and annotation integration".<br /> Advanced online on 2025.01.13, formal publication in 2025.02.<br /> DOI: 10.1101/gr.279461.124 <br /> Link: https://genome.cshlp.org/content/35/2/296.full

On 2025-02-18 17:40:04, user Dongyao Li wrote:

Great work, thank you! I have one comment regarding comparison of cell segmentation. The paper states:

Overall, the CosMx 6K segmentation tool produced cells with larger sizes, higher solidity, and better circularity, indicative of more regular and convex cell shapes compared to other platforms

I would argue "larger", "more circular", and "convex" do not necessarily mean better segmentation. For example, "more circular" and "convex" could be the bias of the particular segmentation model. If more circular is better, then "nucleus segmentation + large expansion" (basically the first version of Xenium segmentation prior to multi modal cell segmentation stain) is the better segmentation since it's large, circular, and convex.

The paper later states:

Among the ST platforms, Xenium 5K showed better separation of marker gene pairs after segmentation

We further visualized marker gene expression across the annotated cell types. Xenium 5K exhibited the most distinct expression patterns (Supplementary Fig. 8d), facilitating more accurate cell type annotations.

and concludes:

Despite exhibiting more irregular segmentation shapes, Xenium 5K effectively distinguished different cell types and minimized transcript mixing between adjacent cells

"Better separation of marker gene pairs", "distinguish different cell types" and "minimize transcript mixing" are indeed the more principled and biologically meaningful metrics to evaluate cell segmentation. The word "despite" in the conclusion suggests circularity means better segmentation, which I don't necessarily agree.

On 2025-02-18 15:37:48, user Andrew Kennard wrote:

This preprint has since been peer-reviewed, revised, and published in a journal:

Kennard AS et al. (2025). Tubulin sequence divergence is associated with the use of distinct microtubule regulators. Current Biology 35(2): p233-248.e8. doi: https://doi.org/10.1016/j.cub.2024.11.022

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

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

On 2025-02-17 18:48:35, user Michael Young wrote:

We just discussed this paper in our lab - nice work! One minor comment and one general one. Figure 2f - use same x-axis for both plots. More importantly, the paper is trying to do a lot. Not sure whether we would suggest splitting into two papers, relegating some elements to supplementary materials, or keeping as is with details relegated to supplementary.

On 2025-02-17 08:16:49, user Jeziel Dener Damasceno wrote:

Please, could this preprint be linked to the final publication, please: https://www.nature.com/articles/s41467-025-56785-y

On 2025-02-16 01:30:11, user Nikolai Slavov wrote:

Code and data for reproducing the analysis are available at: <br /> https://github.com/SlavovLab/Protein-Clearance

On 2025-02-15 17:23:55, user Maxwell Neal wrote:

A peer-reviewed version of this manuscript has been published at https://doi.org/10.1093/bioinformatics/btae442

On 2025-02-15 03:06:45, user Jayson Zhao wrote:

how about the nearest neighbor search algorithm behind that strongly affect the loss function of non-linear dimension reduction and dataset dimension, in which we will have hubs. See some discussion here: https://academic.oup.com/nargab/article/6/4/lqae172/7928174

On 2025-02-15 02:39:09, user sa pa wrote:

I read this paper with great interest.

Is there a name given to the single-cell RNA-seq using the “Solution-phase indexing by kinetic confinement” technique that you are proposing?

It would be easier to cite it as a single-cell RNA-seq method if it had a name like “xxx-seq”, but what should we call it officially?

In the text, it says “Single cell RNAseq using Kinetic Confinement”, is this correct?

On 2025-02-14 04:28:23, user Felix wrote:

I have only skimmed the paper, but I wonder if the link given for the fungal catalogue ( https://entrepot.recherche.data.gouv.fr/dataset.xhtml?persistentId=doi:10.15454/WQ4UTV ) is the correct one. It redirects to human oral microbiota gene and species catalogue rather than fungal-specific catalogue.

On a somewhat related topic, have the authors considered expanding the fungal catalogue with the recent cultivated human gut fungi resource ( https://doi.org/10.1016/j.cell.2024.04.043 )?

On 2025-02-13 22:20:55, user Amer Alam wrote:

The peer reviewed version of this manuscript has been published in the EMBO journal:

Structural insights into binding-site access and ligand recognition by human ABCB1

PMID: 39806099 DOI: 10.1038/s44318-025-00361-z

On 2025-02-13 19:40:38, user Pick Up Litter wrote:

This paper will help move science away from studying "cute" species and to be objective. Perhaps the most severe example is the housecat-- still portrayed as cute in media, but in the feral form a worldwide destroyer of birds. One critique concerning the Ivory-billed Woodpecker-- the number quoted by Troy et al, 20 million dollars spent for studies, is misleading. Most of the efforts are university and private, not governmental, and if the bird is proven to be extant, will have conservation benefits since it is a wide-ranging and keystone species. I help with research for the Ivory-billed Woodpecker. The growing body of evidence that this species exists is more rational than the critique-- see other BioRxiv papers and the work of Mike Collins for example. John D Williams

On 2025-02-13 17:59:30, user Mikaela Gray wrote:

This preprint has now been published in ACS Omega. Here is the link: https://pubs.acs.org/doi/10.1021/acsomega.4c07666

On 2025-02-13 15:16:40, user XUAN ZHANG wrote:

Now published in Cell: https://www.cell.com/cell/fulltext/S0092-8674(24)01273-X

On 2025-02-12 14:36:44, user Sergio Angel wrote:

Very interesting. Our anti-TgATM antibody also labeled the cytosol, with phleomycin in cytosol and some foci in nucleus.

On 2025-02-12 10:42:04, user Claudio Vasapollo wrote:

This manuscript has been published with a different title wanted by the journal. You can find the published version on the PeerJ website at the link:<br /> https://peerj.com/articles/18765/

Thank you.<br /> Claudio Vasapollo

On 2025-02-12 06:12:29, user Prof. Sergio Manni Vanzini wrote:

The paper presents a novel perspective on the application of oxygen-ozone therapy in spine disorders, introducing the concept of adaptive chaos as a key mechanism in biological resilience and healing. A significant strength lies in its interdisciplinary approach, integrating mathematical modeling, bioinformatics, and clinical insights to establish a framework for understanding the therapeutic effects of ozone therapy. The use of Lyapunov exponents, Shannon entropy, and fractal dimensions to quantify biological complexity is particularly innovative, providing a structured means of evaluating systemic responses to treatment. Additionally, the study’s emphasis on precision dosing—highlighting the differential effects of low versus high ozone concentrations—adds valuable insight into the hormetic nature of the therapy, reinforcing the need for controlled perturbations in medical interventions. The thorough review of existing literature, including randomized controlled trials, strengthens the credibility of the findings and underscores the translational potential of the proposed model.<br /> However, certain limitations must be acknowledged. The reliance on mathematical simulations, while insightful, may not fully capture the variability of real-world biological responses, as complex physiological interactions are difficult to model with absolute accuracy. Additionally, while the study references clinical data, it does not provide direct experimental validation, making it difficult to assess the immediate applicability of the findings in clinical practice. The concept of adaptive chaos, though compelling, remains somewhat abstract, and further empirical studies are needed to establish its clinical relevance definitively. Lastly, some of the statistical approaches, particularly the unusually high values of Lyapunov exponents, may require re-evaluation to ensure their biological plausibility and proper contextualization within established dynamical system theory. Despite these challenges, the study provides a groundbreaking theoretical framework with promising implications for regenerative medicine and personalized therapy.

On 2025-02-10 12:29:07, user Alberto Farleschi wrote:

I came through these data, which represents a novelty for me, endeavoured in the field of bioinformatics. The study by Chirumbolo et al. presents a compelling and innovative perspective on adaptive chaos and its role in modulating oxygen-ozone therapy for spine disorders. By integrating mathematical modeling, bioinformatics, and clinical insights, the authors provide a rigorous framework to understand how mild chaotic perturbations can enhance systemic complexity and biological resilience.<br /> A particular strength of this work lies in its multidimensional approach, incorporating Shannon entropy, Lyapunov exponents, and fractal dimensions to quantify the therapeutic impact of oxygen-ozone therapy. Therefire, in my opinion, the authors successfully demonstrate that low-dose ozone (20–40 µg/ml O3) fosters adaptive chaos, leading to reduced inflammation, enhanced repair, and improved systemic stability. In contrast, higher doses (>60 µg/ml O3) appear to push the system into pathological chaos, emphasizing the importance of precision dosing in regenerative medicine. Really interesting outcomes!<br /> The translational significance of this study cannot be overstated. It not only advances our understanding of chaos-driven medical interventions but also sets a precedent for personalized medicine strategies that leverage nonlinear dynamics to optimize therapeutic outcomes. Future research could expand on these findings by incorporating real-world clinical datasets and patient-specific modeling, further solidifying the role of adaptive chaos in medical practice.<br /> I trust this study is a landmark contribution to the fields of biophysics, complexity science, and regenerative medicine, offering novel insights into the interplay between biological chaos and therapeutic control.<br /> Great results!!

On 2025-02-12 01:34:43, user Ddeadpanscience wrote:

I think normally rfdiffusion will require that you test at least 48 or 96 designs. The success rate is not that high

On 2025-02-11 09:45:35, user Jianhua Xing wrote:

Some movies do not show up. Before I upload a revised version, one can download them here<br /> https://drive.google.com/file/d/1tgdOd6X_d5oRtmamBrLf-TOA8T52xft1/view?usp=sharing

On 2025-02-10 16:30:17, user Pierre L wrote:

last references are not present in the article.

On 2025-02-10 16:19:15, user David Lähnemann wrote:

At the time of writing, the GitHub repository simply gives a 404 This is not the web page you are looking for at:<br /> https://github.com/wbvguo/BSReadSim.git <br /> Did you forget to make the repo public? Or is there a typo in there somewhere?

On 2025-02-10 12:31:19, user Caroline Fernandes Dos Santos wrote:

Published version: https://doi.org/10.1590/0001-3765202520240363

On 2025-02-10 11:32:39, user malandrin wrote:

The prepint is now published in Ticks and Tick Borne Diseases DOI10.1016/j.ttbdis.2024.102434.

On 2025-02-10 11:10:36, user Siobhán McClean wrote:

This article is now published in Microbiology Open. The citation is as follows:

Dennehy, R., Duggan, N., Dignam, S., McCormack, S., Dillon, E., Molony, J., ... & McClean, S. (2022). Protein with negative surface charge distribution, Bnr1, shows characteristics of a DNA‐mimic protein and may be involved in the adaptation of Burkholderia cenocepacia. MicrobiologyOpen, 11(1), e1264.

On 2025-02-09 11:10:57, user Zheng Gong wrote:

The authors should note that in line 549, the promoter that drives gRNA expression is the U6 snoRNA promoter and not a "Ubiquitin 6" promoter. Otherwise, a very interesting read!

Thank you!

On 2025-02-07 23:35:18, user Prof. T. K. Wood wrote:

1. Line 231: as the author knows full well, the first report of MqsR was https://doi.org/10.1371/journal.ppat.1000706 in 2009 in which MqsR was characterized via its X-ray structure. It is inappropriate to not cite this seminal work and instead cite a lesser work by the author that added little to MqsR characterization.
2. Line 50: the first link of TA systems in biofilms was https://doi.org/10.1128/jb.01465-08 in 2009, not the current refs by Laub which have nothing to do with biofilms.
3. Line 234: MqsRAC has been solidly linked to persistence and phage inhibition and should be cited (10.1128/spectrum.03388-23).

On 2025-02-07 21:55:49, user Patricia Legler wrote:

We made FRET substrates for CHIKV PMID: 30742841. They are in the Suppl. Info.

On 2025-02-06 17:30:29, user John LaCava wrote:

This is now published at Mobile DNA: https://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-024-00339-4

On 2025-02-06 16:55:23, user Max wrote:

It would be really interesting to see a network of sample relatedness plotted geographically. Maybe this would reveal some interesting trends that are masked by only analyzing spatial distance.

On 2025-02-06 12:27:20, user Prof. T. K. Wood wrote:

page 51: CRISPR-Cas type IE is NOT inactive as found by at least two groups. It has been shown to control the cryptic prophages ( https://www.mdpi.com/1422-0067/23/24/16195 ).

On 2025-02-06 06:08:45, user Jubin Rodriguez wrote:

Why use words such as "we" and "our" when there is only study author?

On 2025-02-06 02:55:28, user Tom Liang wrote:

Excellent contribution to understanding the microscopic mechanisms of anion transport across Band 3! I would like to draw the author’s attention to a highly relevant recent publication in Langmuir: https://doi.org/10.1021/acs.langmuir.4c00216

On 2025-02-05 23:24:58, user Emry Gutierrez wrote:

Great paper! I was curious on the procedures regarding preparing the 48 well plates, as we've been trying to implement these methods into our experiments. Who can I reach out to for more information?

On 2025-02-05 17:50:10, user Emry Gutierrez wrote:

Great paper! Would any of the authors be able to share their procedures for preparing the 48 well plates? We've been trying to implement this methodology and this has been causing us some difficulties!

On 2025-02-05 21:55:34, user Evan Saitta wrote:

This preprint has been formally published:<br /> https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0298957

On 2025-02-05 21:52:46, user Evan Saitta wrote:

This preprint has now been formally published:<br /> https://www.sciencedirect.com/science/article/pii/S0016703723005781

On 2025-02-05 21:51:35, user Evan Saitta wrote:

This preprint has now been formally published: https://elifesciences.org/articles/46205

On 2025-02-05 17:26:07, user Star pupil wrote:

There are other cysteineless interns reported to be equally fast if not faster https://www.lens.org/lens/patent/129-790-217-267-302