We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV. (2020) Michael Letko and Vincent Munster. bioRxiv doi: https://doi.org/10.1101/2020.01.22.915660 We will adhere to the Universal Principled (UP) Review guidelines proposed in: Universal Principled Review: A Community-Driven Method to Improve Peer Review. Krummel M,...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Maya A. Farha, Omar M. El-Halfawy; Robert T. Gale; Craig R. MacNair; Lindsey A. Carfrae; Xiong Zhang, Nicholas G. Jentsch; Jakob Magolan; Eric D. Brown. Uncovering the hidden antibiotic potential of Cannabis. BioRxiv 833392; doi: http://dx.doi.org/10.1101/833392 We will adhere to the Universal Principled (UP) Review guidelines proposed...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Maya A. Farha, Omar M. El-Halfawy; Robert T. Gale; Craig R. MacNair; Lindsey A. Carfrae; Xiong Zhang, Nicholas G. Jentsch; Jakob Magolan; Eric D. Brown. Uncovering the hidden antibiotic potential of Cannabis. BioRxiv 833392; doi: http://dx.doi.org/10.1101/833392 We will adhere to the Universal Principled (UP) Review guidelines proposed...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Keir M. Balla, Marlen C. Rice, James A. Gagnon, Nels C. Elde. Discovery of a prevalent picornavirus by visualizing zebrafish immune responses. BioRxiv 823989; doi: http://dx.doi.org/10.1101/823989 We will adhere to the Universal Principled (UP) Review guidelines proposed in: Universal Principled Review: A Community-Driven Method to Improve Peer...

In this preprint, Michael D. Schaller shares a cost-benefit analysis of shifting the balance of the research workforce to include more staff scientists. Proponents of this intervention (myself included) argue this would simultaneously address concerns about overproduction of trainees and also promote more durable institutional knowledge. However, the costs of employing staff scientists seem to present a serious barrier to implementation. As a consequence, an economic analysis of the type presented here is sorely needed....

In this preprint, Michael D. Schaller shares a cost-benefit analysis of shifting the balance of the research workforce to include more staff scientists. Proponents of this intervention (myself included) argue this would simultaneously address concerns about overproduction of trainees and also promote more durable institutional knowledge. However, the costs of employing staff scientists seem to present a serious barrier to implementation. As a consequence, an economic analysis of the type presented here is sorely needed....

Abstract This is a review of Białas et al. bioRxiv doi: https://doi.org/10.1101/2021.01.26.428286 posted on January 27, 2021. In this paper, the authors study the HMA domain from two NLR immune receptors. The authors identify a common ancestral version for these domains and highlight a convergent evolution that allows the interaction with a common effector. Summary HMA domains are integrated in some NLRs where they confer novel recognition specificities. The rice Pik-1 receptors, are such a...

Here, the authors seek to better understand the mechanism of Human Immunodeficiency Virus 1 (HIV-1) viral Integrase (IN). They hypothesize that four major sites on the C-terminal domain (CTD) are responsible for directing the viral integration site. They accomplish this by generating IN mutants at each of the four sites and generated different viruses carrying these mutations to assay for changes in viral transduction, proviral transcription, and viral integration sites. They found that viruses carrying...

Main Claim & Relevance: Extracellular vimentin might be critical to SARS-CoV-2 cell entry. These researchers demonstrated direct binding between vimentin and SARS-CoV-2 virus-like particles (VLPs) coated with SARS-CoV-2 spike protein. They also showed that antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection by up to 80% in ACE2 expressing cell lines. Are the findings strong, reliable, potentially informative, not informative, or misleading? Why?: The findings are potentially informative. Immunostaining of human...

By Yash S. Huilgol[1] UC Berkeley-UCSF Joint Medical Program, Berkeley, CA, USA[2] Editorial Office, Rapid Reviews: COVID-19 Main Claim & Relevance: In this preprint by Ramakrishnan et al [1], inhaled budesonide, a corticosteroid used for long-term COPD and asthma treatment, reducing the likelihood of urgent care, ED visit, or hospitalization among patients with early COVID-19 illness. This amounted to a relative risk reduction of 90%, or a difference in proportions of 13.1% between the budesonide...

In this manuscript, Ting et al. describe three gene clusters - named antagonism resistance clusters (arc1-3) - that are upregulated by the Gac/Rsm danger sensing system and proposed to work as an innate immunity system against antibacterial attacks. This work builds on their previous studies (LeRoux et al., 2015 eLife; LeRoux et al., 2015 J Mol Biol) in which the authors have identified a danger sensing mechanism that bacteria use to sense lysis of neighboring...

Prostate cancer can be assessed using clinicopathological information which takes into account factors such as patient age, PSA levels and also Gleason score. This enables clinicians to determine the severity and progress of the tumour, as well as to determine the most efficient therapeutic agents to treat the disease. Whilst most patients can be treated successfully to reduce tumour burden and to prevent tumour spread, some patients may progress to a more advanced disease state...

The major goal of this manuscript is to create a procedure to model the ensemble of conformations present in a cryoEM particle stack. This goal is accomplished by using a variational autoencoder with special attention paid to the ensemble nature of proteins and the low signal-to-noise in cryoEM images by drawing multiple samples from the posterior and summing their corresponding likelihoods in training. Using "simulated" data where the conformations are derived from MD simulation snapshots...

This review is the result of a virtual, live-streamed preprint journal club organized and hosted by PREreview and OHSU's BioData Club. The discussion was joined by 9 people, including OHSU researchers and the event organizing team. Wylezinski et al. investigated the impact of clinical and social determinants of health (SDOH) risk factors on the COVID-19 case growth in Tennessee. To that aim, they used a variety of publicly available data to train machine learning (ML)...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations. Shane Miersch, Zhijie Li, Reza Saberianfar, Mart Ustav, James Brett Case, Levi Blazer, Chao Chen, Wei Ye, Alevtina Pavlenco, Maryna Gorelik, Julia Garcia Perez, Suryasree Subramania, Serena Singh, Lynda Ploder, Safder Ganaie, Rita E. Chen,...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Horizontal and vertical transmission of transgenerational memories via the Cer1 transposon. Rebecca S. Moore, Rachel Kaletsky, Chen Lesnik, Vanessa Cota, Edith Blackman, Lance R. Parsons, Zemer Gitai, Coleen T. Murphy. bioRxiv 2020.12.28.424563; doi: https://doi.org/10.1101/2020.12.28.424563 We will adhere to the Universal Principled (UP) Review guidelines proposed in: Universal...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Poly(rC)-binding protein 1 limits hepatitis C virus assembly and egress. Sophie E. Cousineau, Selena M. Sagan. bioRxiv 2021.02.28.433252; doi: https://doi.org/10.1101/2021.02.28.433252 We will adhere to the Universal Principled (UP) Review guidelines proposed in: Universal Principled Review: A Community-Driven Method to Improve Peer Review. Krummel M, Blish C,...

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint: Rachel Eguia, Katharine H. D. Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L. Greninger, Janet A. Englund, Michael J. Boeckh, Jesse D. Bloom. A human coronavirus evolves antigenically to escape antibody immunity. bioRxiv 2020.12.17.423313; doi:https://doi.org/10.1101/2020.12.17.423313 We will adhere to the Universal Principled (UP) Review guidelines proposed in: Universal...

Summary Pettman et al. present a commendable approach to a pressing enigma in T cell immunology: how does a T cell receptor (TCR) differentiate between its target and off-targets? The authors developed an SPR method to measure TCR affinity for off-target peptide-MHC complexes that interact with lower affinity than was previously detectable by existing SPR-based approaches . They paired SPR measurements with substantial in vitro work to correlate biophysical affinity with human T cell agonism....

GENERAL COMMENTS ON PREPRINT BY Frost, Rocha and Ciulli In this preprint, Frost, Rocha and Ciulli report results of how cells respond to compounds previously described as inhibitors of von Hippel–Lindau (VHL) protein as measured by quantitative mass spectrometry (MS)-based proteomics. VHL is a well-studied protein that serves as a substrate recruiting/recognition subunit of Cullin RING E3 ligase CRL2VHL. The best characterized substrate of VHL is HIF1a, a hypoxia-inducible transcription factor that is under strict...

COMMENTS ON THE PREPRINT BY Dölle, Adhikari et al. Targeted protein degradation is a very active field at the moment. Many efforts in this area are focusing on transforming known ligands (binders, inhibitors) of proteins with a clear disease relevance into bifunctional (PROTAC-based) degrader molecules. Unlike the traditional antagonist/inhibitor based compounds in preclinical and clinical use that diminish (inhibit) activity of the target, these degrader molecules induce selective degradation of the target. Thus, they remove...

Dear authors, thank you for sharing this preprint with everyone. I recently decided to support research in chemical biology by providing feedback and thoughts on preprints in this field. Your preprint caught my eye, and I hope you will find the comments below useful (I hesitate to call this peer review, but if you would like to share what I wrote with a journal please feel free). Kind regards, Milka Comments to authors: In this...

This study addresses an essential question of the contribution of different cell types and rejuvenation strategies to the process of aging. Since many of the models used in this field are based on bulk tissue input or purified cell populations, the contribution of specific cell types is difficult to discern. The authors use single-cell transcriptomic data to define 'aging clocks' to predict chronological and biological age using the subventricular zone (SVZ) neurogenic region of young...

Background Studies dating back to 1980 anticipated that the adult mammalian heart contains several cell populations other than cardiomyocytes, including macrophages [1]. However, thanks to the development of state-of-the-art tools (e.g. genetic fate mapping, advanced flow cytometry, single-cell RNA-sequencing), we are now becoming conscious of the abundance, functional heterogeneity, and diverse ontogeny of cardiac macrophages. A line of research of the Lavine lab is devoted to describe the diversity, ontogeny and function of cardiac resident...

Dalia Murra and colleagues characterized CORT level and behavioral changes in susceptible and resilient animals after social stress, this is a very simple but fundamental study in social defeat field. The authors first studies whether pre-stress social ratio predict/align with the post-stress and no correlation found in pre-post SI ratio or CORT level. Then they showed two very interesting findings: first, different coping behavior on the first day actually can predict resiliency, the mice that...