Most tweeted biology preprints, last 24 hours
*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.
112 results found. For more information, click each entry to expand.
3 tweets bioRxiv neuroscience
Memories are thought to be encoded in populations of neurons called memory trace or engram cells. However, little is known about the dynamics of these cells because of the difficulty in real-time monitoring of them over long periods of time in vivo. To overcome this limitation, we present a genetically-encoded RNA indicator (GERI) mouse for intravital chronic imaging of endogenous Arc mRNA - a popular marker for memory trace cells. We used our GERI to identify Arc-positive neurons in real time without the delay associated with reporter protein expression in conventional approaches. We found that the Arc-positive neuronal populations rapidly turned over within two days in the hippocampal CA1 region, whereas ~4% of neurons in the retrosplenial cortex (RSC) consistently expressed Arc following contextual fear conditioning and repeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 of mice navigating a virtual reality environment revealed that only the population of neurons expressing Arc during both encoding and retrieval exhibited relatively high calcium activity in a context-specific manner. This in vivo RNA imaging approach opens the possibility of unraveling the dynamics of the neuronal population underlying various learning and memory processes.
3 tweets medRxiv infectious diseases
Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Peter Halfmann, Anna Kocharian, Kelsey R Florek, Ryan Westergaard, Allen Bateman, Gunnar E Jeppson, Yoshihiro Kawaoka, David H O'Connor, Thomas C Friedrich, Katarina M Grande
The SARS-CoV-2 Delta variant is highly transmissible and contains mutations that confer partial immune escape. We compared RT-PCR cycle threshold (Ct) data from 699 test-positive anterior nasal swab specimens from fully vaccinated (n = 310) or unvaccinated (n=389) individuals. We observed low Ct values (<25) in 212 of 310 fully vaccinated (68%) and 246 of 389 (63%) unvaccinated individuals. Testing a subset of these low-Ct samples revealed infectious SARS-CoV-2 in 15 of 17 specimens (88%) from unvaccinated individuals and 37 of 39 (95%) from vaccinated people. To determine whether infectious virus titers differed in vaccinated and unvaccinated persons, we performed plaque assays on an additional set of 48 samples with Ct <25, finding no difference in infectious virus titer between groups.
3 tweets medRxiv public and global health
Arjun Puranik, Patrick Lenehan, Eli Silvert, Michiel JM Niesen, Juan Corchado-Garcia, John C O'Horo, Abinash Virk, Melanie D Swift, John Halamka, Andrew D Badley, AJ Venkatakrishnan, Venky Soundararajan
Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). However, in July, the effectiveness against infection was considerably lower for mRNA-1273 (76%, 95% CI: 58-87%) with an even more pronounced reduction in effectiveness for BNT162b2 (42%, 95% CI: 13-62%). Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.
2 tweets bioRxiv immunology
Rafael Ramiro de Assis, Aarti Jain, Rie Nakajima, Algis Jasinskas, Saahir Khan, Anton Palma, Daniel M. Parker, Anthony Chau, Amanda Leung, Christina Grabar, Fjolla Muqolli, Ghali Khalil, Jessica Colin Escobar, Jenny Ventura, Huw Davies, Bruce Albala, Bernadette Boden-Albala, Sebastian Schubl, Philip L Felgner
We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.
2 tweets bioRxiv genomics
To gain genetic insights into the early-flowering phenotype of ornamental cherry, also known as sakura, we determined the genome sequences of two early-flowering cherry (Cerasus x kanzakura) varieties, 'Kawazu-zakura' and 'Atami-zakura'. Since the two varieties are interspecific hybrids, likely derived from crosses between Cerasus campanulata (early-flowering species) and Cerasus speciosa, we employed the haplotype-resolved sequence assembly strategy. Genome sequence reads obtained from each variety by single molecule real-time sequencing (SMRT) were split into two subsets, based on the genome sequence information of the two probable ancestors, and assembled to obtain haplotype-phased genome sequences. The resultant genome assembly of 'Kawazu-zakura' spanned 519.8 Mb with 1,544 contigs and an N50 value of 1,220.5 kb, while that of 'Atami-zakura' totaled 509.6 Mb with 2,180 contigs and an N50 value of 709.1 kb. A total of 72,702 and 72,528 potential protein-coding genes were predicted in the genome assemblies of 'Kawazu-zakura' and 'Atami-zakura', respectively. Gene clustering analysis identified 2,634 clusters uniquely presented in the C. campanulata haplotype sequences, which might contribute to its early-flowering phenotype. Genome sequences determined in this study provide fundamental information for elucidating the molecular and genetic mechanisms underlying the early-flowering phenotype of ornamental cherry tree varieties and their relatives.
2 tweets medRxiv infectious diseases
Po Ying Chia, Sean Ong, Calvin J Chiew, Li Wei Ang, Jean-marc Gilbert Chavatte, Tze Minn Mak, Lin Cui, Shirin Kalimuddin, Wan Ni Chia, Chee Wah Tan, Louis Yi Ann Chai, Seow Yen Tan, Shuwei Zheng, Raymong Tzer Pin Lin, Linfa Wang, Yee-Sin Leo, Vernon J. Lee, David Chien Lye, Barnaby Edward Young
Objectives Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. Methods We conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. Results Of 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. Conclusion The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.
2 tweets medRxiv infectious diseases
Sheila F Lumley, Denise O’Donnell, Nicole E Stoesser, Philippa C Matthews, Alison Howarth, Stephanie B Hatch, Brian D Marsden, Stuart Cox, Tim James, Fiona Warren, Liam J Peck, Thomas G Ritter, Zoe de Toledo, Laura Warren, David Axten, Richard J Cornall, E Yvonne Jones, David I. Stuart, Gavin R. Screaton, Daniel Ebner, Sarah Hoosdally, Meera Chand, Oxford University Hospitals Staff Testing Group, Derrick W Crook, Anne-Marie O’Donnell, Christopher P Conlon, Koen B Pouwels, A Sarah Walker, Tim EA Peto, Susan Hopkins, Timothy M Walker, Katie Jeffery, David W Eyre
BackgroundIt is critical to understand whether infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) protects from subsequent reinfection. MethodsWe investigated the incidence of SARS-CoV-2 PCR-positive results in seropositive and seronegative healthcare workers (HCWs) attending asymptomatic and symptomatic staff testing at Oxford University Hospitals, UK. Baseline antibody status was determined using anti-spike and/or anti-nucleocapsid IgG assays and staff followed for up to 30 weeks. We used Poisson regression to estimate the relative incidence of PCR-positive results and new symptomatic infection by antibody status, accounting for age, gender and changes in incidence over time. ResultsA total of 12219 HCWs participated and had anti-spike IgG measured, 11052 were followed up after negative and 1246 after positive antibody results including 79 who seroconverted during follow up. 89 PCR-confirmed symptomatic infections occurred in seronegative individuals (0.46 cases per 10,000 days at risk) and no symptomatic infections in those with anti-spike antibodies. Additionally, 76 (0.40/10,000 days at risk) anti-spike IgG seronegative individuals had PCR-positive tests in asymptomatic screening, compared to 3 (0.21/10,000 days at risk) seropositive individuals. Overall, positive baseline anti-spike antibodies were associated with lower rates of PCR-positivity (with or without symptoms) (adjusted rate ratio 0.24 [95%CI 0.08-0.76, p=0.015]). Rate ratios were similar using anti-nucleocapsid IgG alone or combined with anti-spike IgG to determine baseline status. ConclusionsPrior SARS-CoV-2 infection that generated antibody responses offered protection from reinfection for most people in the six months following infection. Further work is required to determine the long-term duration and correlates of post-infection immunity.
2 tweets medRxiv infectious diseases
The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. MethodsWe included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. ResultsWhere specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I 29%, low-certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person (OR 0.93, 95% CI 0.68 to 1.28, I 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DiscussionBased on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.
2 tweets bioRxiv biophysics
Here, positronium imaging is presented to determine cardiac myxoma (CM) extracted from patients undergoing urgent cardiac surgery due to unexpected atrial masses. Positronium is an atom build from an electron and a positron, produced copiously in intra-molecular voids during the PET imaging. CM, the most common cardiac tumor in adults, accounts for 50-75% of benign cardiac tumors. We aimed to assess if positronium serves as a biomarker for diagnosing CM. Perioperative examinations and histopathology staining in six patients confirmed the primary diagnosis of CM. We observed significant differences in the mean positronium lifetime between tumor and normal tissues, with an average value of 1.92(02) ns and 2.72(05) ns for CM and the adipose tissue, respectively. Our findings, combined with positronium lifetime imaging, reveals the novel emerging positronium biomarker for cardiovascular imaging.
2 tweets medRxiv neurology
Jennifer A. Frontera, Allal Boutajangout, Arjun Masurkar, Rebecca A Betensky, Yulin Ge, Alok Vedvyas, Ludovic Debure, Andre Moreira, Ariane Lewis, Joshua Huang, Sujata Thawani, Laura Balcer, Steven Galetta, Thomas Wisniewski
INTRODUCTION: Older adults hospitalized with COVID-19 are susceptible to neurological complications, particularly encephalopathy, which may reflect age-related neurodegenerative processes. METHODS: Serum total tau, ptau-181, GFAP, NFL, UCHL1, and amyloid-beta(AB-40,42) were measured in hospitalized COVID-19 patients without a history of dementia, and compared among patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions using multivariable Cox proportional hazards regression analyses. RESULTS: Among 251 patients, admission serum ptau-181 and UCHL1 were significantly elevated in patients with encephalopathy (both P<0.05) and total tau, GFAP, and NFL were significantly lower in those discharged home(all P<0.05). These markers correlated significantly with severity of COVID illness. NFL, GFAP and UCH-L1 were significantly higher in hospitalized COVID patients than in non-COVID controls with mild cognitive impairment or Alzheimer's disease(AD). DISCUSSION: Age-related neurodegenerative biomarkers were elevated to levels observed in AD and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
2 tweets bioRxiv genomics
Most eukaryotic genes comprise exons and introns thus requiring the precise removal of introns from pre-mRNAs to enable protein biosynthesis. U2 and U12 spliceosomes catalyze this step by recognizing motifs on the transcript in order to remove the introns. A process which is dependent on precise definition of exon-intron borders by splice sites, which are consequently highly conserved across species. Only very few combinations of terminal dinucleotides are frequently observed at intron ends, dominated by the canonical GT-AG splice sites on the DNA level. Here we investigate the occurrence of diverse combinations of dinucleotides at predicted splice sites. Analyzing 121 plant genome sequences based on their annotation revealed strong splice site conservation across species, annotation errors, and true biological divergence from canonical splice sites. The frequency of non-canonical splice sites clearly correlates with their divergence from canonical ones indicating either an accumulation of probably neutral mutations, or evolution towards canonical splice sites. Strong conservation across multiple species and non-random accumulation of substitutions in splice sites indicate a functional relevance of non-canonical splice sites. The average composition of splice sites across all investigated species is 98.7% for GT-AG, 1.2% for GC-AG, 0.06% for AT-AC, and 0.09% for minor non-canonical splice sites. RNA-Seq data sets of 35 species were incorporated to validate non-canonical splice site predictions through gaps in sequencing reads alignments and to demonstrate the expression of affected genes. We conclude that bona fide non-canonical splice sites are present and appear to be functionally relevant in most plant genomes, if at low abundance.
2 tweets bioRxiv plant biology
Max Coulter, Juan Carlos Entizne, Wenbin Guo, Micha Bayer, Ronja Wonneberger, Linda Milne, Miriam Schreiber, Allison Haaning, Gary Muehlbauer, Nicola McCallum, John Fuller, Craig Simpson, Nils Stein, John WS Brown, Robbie Waugh, Runxuan Zhang
Accurate characterization of splice junctions as well as transcription start and end sites in reference transcriptomes allows precise quantification of transcripts from RNA-seq data and enable detailed investigations of transcriptional and post-transcriptional regulation. Using novel computational methods and a combination of PacBio Iso-seq and Illumina short read sequences from 20 diverse tissues and conditions, we generated a comprehensive and highly resolved barley reference transcript dataset (RTD) from the European 2-row spring barley cultivar Barke (BaRTv2.18). Stringent and thorough filtering was carried out to maintain the quality and accuracy of the splice junctions and transcript start and end sites. BaRTv2.18 shows increased transcript diversity and completeness compared to an earlier version, BaRTv1.0. The accuracy of transcript level quantification, splice junctions and transcript start and end sites has been validated extensively using parallel technologies and analysis, including high resolution RT PCR and 5 prime RACE. BaRTv2.18 contains 39,434 genes and 148,260 transcripts, representing the most comprehensive and resolved reference transcriptome in barley to date. It provides an important and high-quality resource for advanced transcriptomic analyses, including both transcriptional and post-transcriptional regulation, with exceptional resolution and precision.
2 tweets medRxiv epidemiology
Background: COVID-19 pandemic mitigation requires evidence-based strategies. Because COVID-19 can spread via respired droplets, most US states mandated mask use in public settings. Randomized control trials have not clearly demonstrated mask efficacy against respiratory viruses, and observational studies conflict on whether mask use predicts lower infection rates. We hypothesized that statewide mask mandates and mask use were associated with lower COVID-19 case growth rates in the United States. Methods: We calculated total COVID-19 case growth and mask use for the continental United States with data from the Centers for Disease Control and Prevention and Institute for Health Metrics and Evaluation. We estimated post-mask mandate case growth in non-mandate states using median issuance dates of neighboring states with mandates. Results: Earlier mask mandates were not associated with lower total cases or lower maximum growth rates. Earlier mandates were weakly associated with lower minimum COVID-19 growth rates. Mask use predicted lower minimum but not lower maximum growth rates. Growth rates and total growth were comparable between US states in the first and last mask use quintiles during the Fall-Winter wave. These observations persisted for both natural logarithmic and fold growth models and when adjusting for differences in US state population density. Conclusions: We did not observe association between mask mandates or use and reduced COVID-19 spread in US states. COVID-19 mitigation requires further research and use of existing efficacious strategies, most notably vaccination.
2 tweets bioRxiv genomics
Background: Along with specialized functions, cells of multicellular organisms also perform essential functions common to most if not all cells. Whether diverse cells do this by using the same set of genes, interacting in a fixed coordinated fashion to execute essential functions, remains a central question in biology. Single-cell RNA-sequencing (scRNA-seq) measures gene expression of individual cells, enabling researchers to discover gene expression patterns that contribute to the diversity of cell functions. Current analyses focus primarily on identifying differentially expressed genes across cells. However, patterns of co-expression between genes are probably more indicative of biological processes than are the expression of individual genes. Using single cell transcriptome data from the fly brain, here we focus on gene co-expression to search for a core cellular network. Results: In this study, we constructed cell type-specific gene co-expression networks using single cell transcriptome data of brains from the fruit fly, Drosophila melanogaster. We detected a set of highly coordinated genes preserved across cell types in fly brains and defined this set as the core cellular network. This core is very small compared with cell type-specific gene co-expression networks and shows dense connectivity. Modules within this core are enriched for basic cellular functions, such as translation and ATP metabolic processes, and gene members of these modules have distinct evolutionary signatures. Conclusions: Overall, we demonstrated that a core cellular network exists in diverse cell types of fly brains and this core exhibits unique topological, structural, functional and evolutionary properties.
2 tweets bioRxiv microbiology
Yafei Liu, Noriko Arase, Jun-ichi Kishikawa, Mika Hirose, Songling Li, Asa Tada, Sumiko Matsuoka, Akemi Arakawa, Kanako Akamatsu, Chikako Ono, Hui Jin, Kazuki Kishida, Wataru Nakai, Masako Kohyama, Atsushi Nakagawa, Yoshiaki Yamagishi, Hironori Nakagami, Atsushi Kumanogoh, Yoshiharu Matsuura, Daron M Standley, Takayuki Kato, Masato Okada, Manabu Fujimoto, Hisashi Arase
mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.
1 tweet bioRxiv genomics
Damien Richard, Liam P. Shaw, Robert Lanfear, Russell Corbett-Detig, Yatish Turakhia, Angie S. Hinrichs, Jakob McBroome, Mislav Acman, Christopher Owen, Cedric C.S. Tan, Lucy van Dorp, Francois Balloux
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally to cause the COVID-19 pandemic. Despite the constant accumulation of genetic variation in the SARS-CoV-2 population, there was little evidence for the emergence of significantly more transmissible lineages in the first half of 2020. Starting around November 2020, several more contagious and possibly more virulent Variants of Concern (VoCs) were reported in various regions of the world. These VoCs share some mutations and deletions that haven arisen recurrently in distinct genetic backgrounds. Here, we build on our previous work modelling the association of mutations to SARS-CoV-2 transmissibility and characterise the contribution of individual recurrent mutations and deletions to estimated viral transmissibility. We then assess how patterns of estimated transmissibility in all SARS-CoV-2 clades have varied over the course of the COVID-19 pandemic by summing transmissibility estimates for all individual mutations carried by any sequenced genome analysed. Such an approach recovers the Delta variant (21A) as the most transmissible clade currently in circulation, followed by the Alpha variant (20I). By assessing transmissibility over the time of sampling, we observe a tendency for estimated transmissibility within clades to slightly decrease over time in most clades. Although subtle, this pattern is consistent with the expectation of a decay in transmissibility in mainly non-recombining lineages caused by the accumulation of weakly deleterious mutations. SARS-CoV-2 remains a highly transmissible pathogen, though such a trend could conceivably play a role in the turnover of different global viral clades observed over the pandemic so far.
1 tweet bioRxiv neuroscience
During deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats. At first, we determined the fMRI signatures of burst-suppression in human EEG-fMRI data. Applying this method to animal fMRI datasets, we found distinct burst-suppression signatures in all species. The burst-suppression maps revealed a marked inter-species difference: in rats the entire neocortex engaged in burst-suppression, while in primates most sensory areas were excluded--predominantly the primary visual cortex. We anticipate that the identified species-specific fMRI signatures and whole-brain maps will guide future targeted studies investigating the cellular and molecular mechanisms of burst-suppression in unconscious states.
1 tweet medRxiv allergy and immunology
George Ronald Nahass, Rachel E. Salomon-Shulman, Grace Blacker, Kazim Haider, Rich Brotherton, Kristine Teague, Ying Ying Yiu, Rachel E. Brewer, Sarah Danielle Galloway, Paige Hansen, Gabriel Marquez-Arreguin, Salma Sheikh-Mohamed, Gary Y.C. Chao, Baweleta Isho, Evan Do, Iris Chang, Theo Snow, Alexandra S Lee, STANFORD COVID-19 BIOBANK, Monali Manohar, Samuel Yang, Andra L. Blomkalns, Angela J. Rogers, Allison McGeer, Anne-Claude Gingras, Sharon Straus, Phillip Grant, Kari C. Nadeau, Catherine A. Blish, Jennifer L. Gommerman, Erin C. Sanders, Irving L. Weissman, Michal Caspi Tal
Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2.
1 tweet bioRxiv microbiology
Iron is a critical nutrient for most microbial pathogens, and the innate immune system exploits this requirement by sequestering iron and other metals through a process termed nutritional immunity. The opportunistic pathogen Pseudomonas aeruginosa provides a model system for understanding the microbial response to host iron depletion, as this organism exhibits a high requirement for iron as well as an exquisite ability to overcome iron deprivation during infection. Hallmarks of P. aeruginosa’s iron starvation response include the induction of multiple high affinity iron acquisition systems and an “iron sparing response” that is post-transcriptionally mediated by the PrrF small regulatory RNAs (sRNAs). Here, we used liquid chromatography-tandem mass spectrometry to conduct label-free proteomics of the P. aeruginosa iron starvation response, revealing several iron-regulated processes that have not been previously described. Iron starvation induced multiple proteins involved in branched chain and aromatic amino acid catabolism, providing the capacity for iron-independent entry of carbons into the TCA cycle. Proteins involved in sulfur assimilation and cysteine biosynthesis were reduced upon iron starvation, while proteins involved in iron-sulfur cluster biogenesis were paradoxically increased, highlighting the central role of iron in P. aeruginosa metabolism. Iron starvation also resulted in changes in the expression of several zinc-responsive proteins, as well as the first experimental evidence for increased levels of twitching motility proteins upon iron starvation. Subsequent proteomics analyses demonstrated that the PrrF sRNAs were required for iron regulation of many of these newly-identified proteins, and we identified PrrF complementarity with mRNAs encoding key iron-regulated proteins involved in amino acid metabolism, iron-sulfur biogenesis, and zinc homeostasis. Combined, these results provide the most comprehensive view of the P. aeruginosa iron starvation response to date and outline novel roles for the PrrF sRNAs in the P. aeruginosa iron sparing response and pathogenesis.
1 tweet bioRxiv genomics
Arabidopsis thaliana is one of the best studied plant model organisms. Besides cultivation in greenhouses, cells of this plant can also be propagated in suspension cell culture. At7 is one such cell line that has been established about 25 years ago. Here we report the sequencing and the analysis of the At7 genome. Large scale duplications and deletions compared to the Col-0 reference sequence were detected. The number of deletions exceeds the number of insertions thus indicating that a haploid genome size reduction is ongoing. Patterns of small sequence variants differ from the ones observed between A. thaliana accessions e.g. the number of single nucleotide variants matches the number of insertions/deletions. RNA-Seq analysis reveals that disrupted alleles are less frequent in the transcriptome than the native ones.
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