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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 212,235 papers from 844,985 authors.

Most tweeted biology preprints, last 24 hours

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282 results found. For more information, click each entry to expand.

1: Age-stratified infection fatality rate of COVID-19 in the non-elderly informed from pre-vaccination national seroprevalence studies
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Posted 13 Oct 2022

Age-stratified infection fatality rate of COVID-19 in the non-elderly informed from pre-vaccination national seroprevalence studies
94 tweets medRxiv epidemiology

Angelo Maria Pezzullo, Cathrine Axfors, Despina G. Contopoulos-Ioannidis, Alexandre Apostolatos, John Ioannidis

The infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection is important to estimate accurately, since 94% of the global population is younger than 70 years and 86% is younger than 60 years. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.035% (interquartile range (IQR) 0.013 - 0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036 - 0.125%,) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.003% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.129% at 50-59 years, and 0.501% at 60-69 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.

2: Vitamin D deficiency and SARS-CoV-2 infection: Big-data analysis from March 2020 to March 2021. D-COVID study
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Posted 28 Oct 2022

Vitamin D deficiency and SARS-CoV-2 infection: Big-data analysis from March 2020 to March 2021. D-COVID study
68 tweets bioRxiv pathology

Noemi Anguita

Methods: Using big-data analytics and artificial intelligence through the SAVANA Manager clinical platform, we analysed clinical data from patients with COVID-19 atended in a terciary university hospital from March 2020 to March 2021. Results: Of the 143.157 analysed patients, 36.261 subjects had COVID-19 infection (25.33%); during this period; of these 2588 had vitamin D deficiency (7.14%). Among subjects with COVID-19 and vitamin D deficiency, there was a higher proportion of women OR 1.45 [95% CI 1.33-1.57], adults older than 80 years OR 2.63 [95%CI 2.38-2.91], people living in nursing homes OR 2.88 [95%CI 2.95-3.45] and walking dependence OR 3.45 [95%CI 2.85-4.26]. Regarding clinical course, a higher number of subjects with COVID-19 and vitamin D deficiency required hospitalitation OR 2.41 [95%CI 2.22-2-61], intensive unit care (ICU) OR 2.22 [95% CI 1.64-3.02], had a longer mean hospital stay 3.94 (2.29) p=0.02 and higher mortality OR 1.82 [95%CI 1.66-2.01].) Conclusion: Low serum 25 (OH) Vitamin-D level was significantly associated with a worse clinical evolution and prognosis of COVID-19 infection. We found a higher proportion of institutionalised and dependent people over 80 years of age among patients with COVID-19 and vitamin D deficiency.

3: Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice
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Posted 22 Nov 2022

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice
53 tweets bioRxiv immunology

Valeria Fumagalli, Pietro Di Lucia, Micol Rava, Davide Marotta, Elisa Bono, Stefano Grassi, Lorena Donnici, Rolando Cannalire, Irina Stefanelli, Anastasia Ferraro, Francesca Esposito, Elena Pariani, Donato Inverso, Camilla Montesano, Serena Delbue, Enzo Tramontano, Raffaele De Francesco, Vincenzo Summa, Luca Guidotti, Matteo Iannacone

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir, an orally available inhibitor of the 3- chymotrypsin-like cysteine protease, has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

4: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2
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Posted 20 Oct 2022

Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2
35 tweets bioRxiv bioengineering

Valentin Bruttel, Alex Washburne, Antonius VanDongen

To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident. The genome of SARS-COV-2 contains a peculiar pattern of unique restriction endonuclease recognition sites allowing efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses. Here, we report the likelihood of observing such a pattern in coronaviruses with no history of bioengineering. We find that SARS-CoV-2 is an anomaly, more likely a product of synthetic genome assembly than natural evolution. The restriction map of SARS-CoV-2 is consistent with many previously reported synthetic coronavirus genomes, meets all the criteria required for an efficient reverse genetic system, differs from closest relatives by a significantly higher rate of synonymous mutations in these synthetic-looking recognitions sites, and has a synthetic fingerprint unlikely to have evolved from its close relatives. We report a high likelihood that SARS-CoV-2 may have originated as an infectious clone assembled in vitro.

5: A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections
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Posted 11 Jan 2022

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections
28 tweets bioRxiv bioinformatics

Tony Pan, Guoshuai Cao, Erting Tang, Yu zhao, Pablo Penaloza-MacMaster, Yun Fang, Jun Huang

SARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+ individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+ patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.

6: METTL17 is an Fe-S cluster checkpoint for mitochondrial translation
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Posted 24 Nov 2022

METTL17 is an Fe-S cluster checkpoint for mitochondrial translation
26 tweets bioRxiv cell biology

Tslil Ast, Yuzuru Itoh, Shayan Sadre, Jason G. McCoy, Gil Namkoong, Ivan Chicherin, Pallavi R. Joshi, Piotr Kamenski, Daniel L. M. Suess, Alexey Amunts, Vamsi K. Mootha

Friedreich's ataxia (FA) is the most common monogenic mitochondrial disease. FA is caused by a depletion of the mitochondrial protein frataxin (FXN), an iron-sulfur (Fe-S) cluster biogenesis factor. To better understand the cellular consequences of FA, we performed quantitative proteome profiling of human cells depleted for FXN. Nearly every known Fe-S cluster-containing protein was depleted in the absence of FXN, indicating that as a rule, cluster binding confers stability to Fe-S proteins. Proteomic and genetic interaction mapping identified impaired mitochondrial translation downstream of FXN loss, and specifically highlighted the methyltransferase-like protein METTL17 as a candidate effector. Using comparative sequence analysis, mutagenesis, biochemistry and cryogenic electron microscopy we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [Fe4S4]2+ cluster required for its stability on the mitoribosome. Notably, METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN null cells. Our data suggest that METTL17 serves as an Fe-S cluster checkpoint: promoting the translation and assembly of Fe-S cluster rich OXPHOS proteins only when Fe-S cluster levels are replete.

7: Ethylene-mediated phosphorylation of ORESARA1 induces sequential leaf death during flooding in Arabidopsis
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Posted 25 Nov 2022

Ethylene-mediated phosphorylation of ORESARA1 induces sequential leaf death during flooding in Arabidopsis
22 tweets bioRxiv plant biology

Tom Rankenberg, Hans van Veen, Mastoureh Sedaghatmehr, Che-Yang Liao, Muthanna Biddanda Devaiah, Salma Balazadeh, Rashmi Sasidharan

The volatile phytohormone ethylene is a major regulator of plant adaptive responses to flooding. In flooded plant tissues, it quickly increases to high concentrations due to its low solubility and diffusion rates in water. The passive, quick and consistent accumulation of ethylene in submerged plant tissues makes it a reliable cue for plants to trigger flood-acclimative responses. However, persistent ethylene accumulation can also have negative effects, notably accelerated leaf senescence. Ethylene is a well-established positive regulator of senescence which is a natural element of plant ageing. However stress-induced senescence hampers the photosynthetic capacity and stress recovery of plants. In submerged Arabidopsis shoots, senescence follows a strict age-dependent pattern starting with the older leaves. Although mechanisms underlying ethylene-mediated senescence have been uncovered, it is unclear how submerged plants avoid an indiscriminate breakdown of leaves despite high systemic accumulation of ethylene. Here we demonstrate in Arabidopsis plants that even though submergence triggers a leaf-age independent activation of ethylene signaling via EIN3, senescence was initiated only in the old leaves. This EIN3 stabilization also led to the overall transcript and protein accumulation of the senescence-promoting transcription factor ORESARA1 (ORE1). ORE1 protein accumulated in both old and young leaves during submergence. However, leaf age-dependent senescence could be explained by ORE1 activation via phosphorylation only in old leaves. Our results unravel a mechanism by which plants regulate the speed and pattern of senescence during environmental stresses like flooding. Such an age-dependent phosphorylation of ORE1 ensures that older expendable leaves are dismantled first, thus prolonging the life of younger leaves and meristematic tissues vital to whole plant survival.

8: Autolysosomal exocytosis of lipids protect neurons from ferroptosis
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Posted 24 Nov 2022

Autolysosomal exocytosis of lipids protect neurons from ferroptosis
21 tweets bioRxiv cell biology

Isha Ralhan, Jinlan Chang, Matthew J Moulton, Lindsey D. Goodman, Nathanael YJ Lee, Greg Plummer, Hilda Amalia Pasolli, Doreen Matthies, Hugo J. Bellen, Maria S. Ioannou

During oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role in several neurodegenerative diseases. Yet, the mechanisms of lipid release and its consequences on neuronal health are unclear. Here, we demonstrate that lipid-protein particle release by autolysosome exocytosis protects neurons from ferroptosis, a form of cell death driven by lipid peroxidation. We show that during oxidative stress, peroxidated lipids and iron are released from neurons by autolysosomal exocytosis which requires the exocytic machinery; VAMP7 and syntaxin 4. We observe membrane-bound lipid-protein particles by TEM and demonstrate that these particles are released from neurons using cryoEM. Failure to release these lipid-protein particles causes lipid hydroperoxide and iron accumulation and sensitizes neurons to ferroptosis. Our results reveal how neurons protect themselves from peroxidated lipids. Given the number of brain pathologies that involve ferroptosis, defects in this pathway likely play a key role in the pathophysiology of neurodegenerative disease.

9: Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
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Posted 19 Mar 2022

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
20 tweets bioRxiv immunology

Zhen Qin, Aurelie Bouteau, Christopher Herbst, Botond Igyarto

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune responses, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform's true impact on human health.

10: Plasticity in centromere organization: Holocentromeres can consist of merely a few megabase-sized satellite arrays
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Posted 25 Nov 2022

Plasticity in centromere organization: Holocentromeres can consist of merely a few megabase-sized satellite arrays
20 tweets bioRxiv plant biology

Yi-Tzu Kuo, Amanda Souza Camara, Veit Schubert, Pavel Neumann, Jiri Macas, Michael Melzer, Jianyong Chen, Joerg Fuchs, Simone Abel, Evelyn Klocke, Bruno Huettel, Axel Himmelbach, Dmitri Demidov, Frank Dunemann, Martin Mascher, Takayoshi Ishii, Andre Marques, Andreas Houben

The centromere is the chromosome region where the microtubules attach during cell division. In contrast to monocentric chromosomes with one centromere location, holocentric species usually distribute hundreds of centromere units along the entire chromatid. We assembled the chromosome-scale reference genome and analyzed the holocentromere and (epi)genome organization of the lilioid Chionographis japonica. Remarkably, each of its holocentric chromatids consists of only 7 to 11 evenly-spaced megabase-sized centromere-specific histone H3-positive units. These units contain satellite arrays of 23 and 28 bp-long monomers capable of forming palindromic structures. Like monocentric species, C. japonica forms distinctly clustered centromeres in chromocenters at interphase. Additionally, the large-scale eu- and heterochromatin arrangement differs between C. japonica and other known holocentric species. Using polymer simulations, we modeled the formation of prometaphase line-like holocentromeres from interphase centromere clusters. Our findings broaden the knowledge about the diversity of centromere organization, showing that holocentricity is not restricted to species with numerous and small centromere units.

11: Decoding COVID-19 mRNA Vaccine Immunometabolism in Central Nervous System: human brain normal glial and glioma cells by Raman imaging
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Posted 02 Mar 2022

Decoding COVID-19 mRNA Vaccine Immunometabolism in Central Nervous System: human brain normal glial and glioma cells by Raman imaging
19 tweets bioRxiv cell biology

Halina Abramczyk, Beata Brozek-Pluska, Karolina Beton

The paper presents the effect of COVID-19 mRNA (Pfizer/BioNT) vaccine on in vitro glial cells of the brain studied by means of Raman spectroscopy and imaging.. The results obtained for human brain normal and tumor glial cells of astrocytes, astrocytoma, glioblastoma incubated with the Covid-19 mRNA vaccine Pfizer/BioNT vaccine show alterations in the reduction-oxidation pathways associated with Cytochrome c. We found that the Pfizer/BioNT vaccine down regulate the concentration of cytochrome c in mitochondria upon incubation with normal and tumorous glial cells. Concentration of oxidized form of cytochrome c in brain cells has been shown to decrease upon incubation the mRNA vaccine. Lower concentration of oxidized cytochrome c results in lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis and lessened ATP production. Alteration of Amide I concentration, which may reflect the decrease of mRNA adenine nucleotide translocator. Moreover, mRNA vaccine leads to alterations in biochemical composition of lipids that suggest the increasing role of signaling. mRNA vaccine produce statistically significant changes in cell nucleus due to histone alterations. The results obtained for mitochondria, lipid droplets, cytoplasm may suggest that COVID-19 mRNA (Pfizer/BioNT) vaccine reprograms immune responses. The observed alterations in biochemical profiles upon incubation with COVID-19 mRNA in the specific organelles of the glial cells are similar to those we observe for brain cancer vs grade of aggressiveness.

12: Automatic identification and annotation of MYB gene family members in plants
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Posted 16 Oct 2021

Automatic identification and annotation of MYB gene family members in plants
17 tweets bioRxiv plant biology

Boas Pucker

Background: MYBs are among the largest transcription factor families in plants. Consequently, members of this family are involved in a plethora of processes including development and specialized metabolism. The MYB families of many plant species were investigated in the last two decades since the first investigation looked at Arabidopsis thaliana. This body of knowledge and characterized sequences provide the basis for the identification, classification, and functional annotation of candidate sequences in new genome and transcriptome assemblies. Results: A pipeline for the automatic identification and functional annotation of MYBs in a given sequence data set was implemented in Python. MYB candidates are identified, screened for the presence of a MYB domain and other motifs, and finally placed in a phylogenetic context with well characterized sequences. In addition to technical benchmarking based on existing annotation, the transcriptome assembly of Croton tiglium and the annotated genome sequence of Castanea crenata were screened for MYBs. Results of both analyses are presented in this study to illustrate the potential of this application. The analysis of one species takes only a few minutes depending on the number of predicted sequences and the size of the MYB gene family. This pipeline, the required bait sequences, and reference sequences for a classification are freely available on github: https://github.com/bpucker/MYB_annotator. Conclusions: This automatic annotation of the MYB gene family in novel assemblies makes genome-wide investigations consistent and paves the way for comparative studies in the future. Candidate genes for in-depth analyses are presented based on their orthology to previously characterized sequences which allows the functional annotation of the newly identified MYBs with high confidence. The identification of orthologs can also be harnessed to detect duplication and deletion events.

13: Brain criticality predicts individual synchronization levels in humans
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Posted 24 Nov 2022

Brain criticality predicts individual synchronization levels in humans
16 tweets bioRxiv neuroscience

Marco Fusca, Felix Siebenhuhner, Sheng Hua Wang, Vladislav Myrov, Gabriele Arnulfo, Lino Nobili, J. Matias Palva, Satu Palva

Moderate levels of synchronization of neuronal oscillations are essential for healthy brain dynamics. Synchronization levels exhibit large inter-individual variability the origins of which are unknown. Neuronal systems have been postulated to operate near a critical transition point or in an extended regime between disorder (subcritical) and order (supercritical phase) characterized by moderate synchronization and emergent power-law long-range temporal correlations (LRTCs). We investigated whether inter-individual variability in synchronization levels is explained by the individual position along the critical regime by analyzing magnetoencephalography (MEG) and intra-cerebral stereo-electroencephalography (SEEG) human resting-state data. Here we show that variability in synchronization levels exhibits a positive linear and quadratic relationships with LRTCs in healthy participants and brain areas. In the epileptogenic zone this correlation was negative. These results show that variability in synchronization levels is regulated by the individual position along an extended critical-like regime, with healthy brain areas tending to operate in its subcritical and epileptogenic areas in its supercritical side.

14: Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States
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Posted 25 May 2022

Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States
15 tweets medRxiv infectious diseases

Seth Flaxman, Charles Whittaker, Elizaveta Semenova, Theo Rashid, Robbie Parks, Alexandra Blenkinsop, H Juliette T Unwin, Swapnil Mishra, Samir Bhatt, Deepti Gurdasani, Oliver Ratmann

Covid-19 has caused more than 1 million deaths in the US, including at least 1,204 deaths among children and young people (CYP) aged 0-19 years, with 796 occurring in the one year period April 1, 2021 - March 31, 2022. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from CDC WONDER on NCHS's 113 Selected Causes of Death, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 mortality is among the 10 leading causes of death in CYP aged 0-19 years in the US, ranking 8th among all causes of deaths, 5th in disease-related causes of deaths (excluding accidents, assault and suicide), and 1st in deaths caused by infectious or respiratory diseases. Covid-19 deaths constitute 2.3% of the 10 leading causes of death in this age group. Covid-19 caused substantially more deaths in CYP than major vaccine-preventable diseases did historically in the period before vaccines became available. Various factors including underreporting and Covid-19's role as a contributing cause of death from other diseases mean that our estimates may understate the true mortality burden of Covid-19. Our findings underscore the public health relevance of Covid-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, pharmaceutical and non-pharmaceutical interventions will continue to play an important role in limiting transmission of the virus in CYP and mitigating severe disease.

15: Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine
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Posted 25 Nov 2022

Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine
15 tweets bioRxiv bioinformatics

Sinan Ugur Umu, Havard Trondsen, Vanessa M. Paynter, Tilo Buschmann, Trine B. Rounge, Kevin J Peterson, Bastian Fromm

Understanding the evolution of organismic complexity and the genomic basis of gene-regulation is one of the main challenges in the postgenomic era. While thousands of new genomes are available today, no accurate methods exist to reliably mine those for microRNAs, an important class of post-transcriptional regulators. Currently, their prediction and annotation depend on the availability of transcriptomics data sets and hands-on expert knowledge leading to the large discrepancy between novel genomes made available and the availability of high-quality microRNA complements. Using the more than 16,000 microRNA entries from the manually curated microRNA gene database MirGeneDB, we generated and trained covariance models for each conserved microRNA family. These models are available in MirMachine, our new pipeline for automated annotation of conserved microRNAs. We show that MirMachine can be used to accurately and precisely predict conserved microRNA complements from genome assemblies, correctly identifying the number of paralogues, and by establishing the novel microRNA score, the completeness of assemblies. Built and trained on representative metazoan microRNA complements, we used MirMachine on a wide range of animal species, including those with very large genomes or additional genome duplications and extinct species such as mammoths, where deep small RNA sequencing data will be hard to produce. With accurate predictions of conserved microRNAs, the MirMachine workflow closes a long-persisting gap in the microRNA field that will not only facilitate automated genome annotation pipelines and can serve as a solid foundation for manual curation efforts, but deeper studies on the evolution of genome regulation, even in extinct organisms. MirMachine is freely available (https://github.com/sinanugur/MirMachine) and also implemented as a web application (www.mirmachine.org).

16: Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron
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Posted 11 Jan 2022

Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron
15 tweets medRxiv infectious diseases

Olha Puhach, Kenneth Adea, Nicolas Hulo, Pascale Sattonnet-Roche, Camille Genecand, Anne Iten, Frederique Jacquerioz Bausch, Laurent Kaiser, Pauline Vetter, Isabella Eckerle, Benjamin Meyer

Abstract Background Viral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine-breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance. Methods We assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed IVTs during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18). Findings Correlation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. Vaccinated Delta infected individuals had significantly lower RNA genome copies and IVTs compared to unvaccinated subjects and cleared virus faster. In addition, vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections. Interpretation Quantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine-breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron. Funding This work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privee des Hopitaux Universitaires de Geneve.

17: Post-COVID syndrome prevalence and risk factors in children and adolescents: A population-based serological study
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Posted 24 Aug 2022

Post-COVID syndrome prevalence and risk factors in children and adolescents: A population-based serological study
13 tweets medRxiv epidemiology

Roxane Dumont, Viviane Richard, Elsa Lorthe, Andrea Loizeau, HELENE H BAYSSON, Francesco Pennacchio, Maria Eugenia Zaballa, Mayssam Nehme, Anne Perrin, Arnaud H L'Huillier, Laurent Kaiser, Remy Barbe, Klara Posfay Barbe, Silvia Stringhini, Idris Guessous

Objectives Post-COVID syndrome remain poorly studied in children and adolescents. In this study, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Study design We used data from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), which included children (aged 6 months to 17 years) selected from random samples drawn from state registries or who had a household member participating in a COVID-19 seroprevalence study conducted by our group. Children were tested for anti-SARS-CoV-2 N antibodies. Parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID syndrome. Results From December 1st, 2021 to February 16th, 2022, 1034 children were included, among whom 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference ({Delta}aPrev) of 4.1% (95%CI: 1.1;7.3). After stratification by age group, the prevalence was higher among adolescents aged 12-17 years ({Delta}aPrev=8.3%, 95%CI: 3.5;13.5) than among younger children (0.0%, 95%CI: -5.2;5.2 among 6-11 years old and 4.2%; 95%CI: -4.4;13.3 among 0-5 years old). The most frequently declared persistent symptoms among seropositives were smell loss, trouble concentrating and abdominal pain. Older age, having a chronic condition and lower socioeconomic conditions were identified as risk factors. Conclusion A significant proportion of seropositive children, particularly adolescents, experienced persistent symptoms. While there is a need for further investigation, growing evidence of pediatric post-COVID syndrome urges early screening and primary care management.

18: Mechanism of RanGTP priming the release of H2A-H2B from Kap114 and Importin-9
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Posted 22 Nov 2022

Mechanism of RanGTP priming the release of H2A-H2B from Kap114 and Importin-9
13 tweets bioRxiv biochemistry

Jenny Jiou, Joy M Shaffer, Natalia E Bernardes, Kiran Tripathi, Ho Yee Joyce Fung, Oladimeji S . Olaluwoye, Juliana Kikumoto Dias, Yuh Min Chook, Sheena D'Arcy

Previously we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus (Padavannil et al. 2019). However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9*H2A-H2B complex and formation of RanGTP*Importin-9*H2A-H2B facilitates H2A-H2B release to the assembling nucleosome (Padavannil et al. 2019). Here we show cryo-EM structures of Importin-9*RanGTP and of its yeast homolog Kap114, including Kap114*RanGTP, Kap114*H2A-H2B, and RanGTP*Kap114*H2A-H2B. In combination with hydrogen-deuterium exchange analysis of Importin-9 complexes and nucleosome assembly assays, we explain how the conserved Kap114/Importin-9 importins bind H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. We show that RanGTP binds to the N-terminal repeats of Kap114/Importin-9 as in Kap114/Importin-9*RanGTP, and H2A-H2B binds via its acidic patch to the Kap114/Importin-9 C-terminal repeats as in Kap114/Importin-9*H2A-H2B. RanGTP-binding in RanGTP*Kap114*H2A-H2B changes Kap114/Importin-9 conformation such that it no longer contacts the surface of H2A-H2B proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome. The reduced affinity of RanGTP for Kap114/Importin-9 when H2A-H2B is bound may ensure release of H2A-H2B only at chromatin.

19: Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body
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Posted 05 Feb 2019

Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body
12 tweets bioRxiv cancer biology

Chenchen Pan, Oliver Schoppe, Arnaldo Parra-Damas, Ruiyao Cai, Mihail Ivilinov Todorov, Gabor Gondi, Bettina von Neubeck, Alireza Ghasemi, Madita Alice Reimer, Javier Coronel, Boyan K. Garvalov, Bjoern Menze, Reinhard Zeidler, Ali Ertürk

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of tumor cells more than 100-fold by applying the vDISCO method to image single cancer cells in intact transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantifications in a model of spontaneous metastasis using human breast cancer cells allowed us to systematically analyze clinically relevant features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in whole mice. DeepMACT can thus considerably improve the discovery of effective therapeutic strategies for metastatic cancer.

20: Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine
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Posted 17 Nov 2022

Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine
12 tweets bioRxiv microbiology

Jing Zou, Chaitanya Kurhade, Sohil Patel, Nicholas Kitchin, Kristin Tompkins, Mark Cutler, David Cooper, Qi Yang, Hui Cai, Alexander Muik, Ying Zhang, Dung-Yang Lee, Ugur Sahin, Annaliesa S. Anderson, William C. Gruber, Xuping Xie, Kena A. Swanson, Pei-Yong Shi

The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4th dose of monovalent BNT162b2 vaccine induced a 3.0, 2.9, 2.3, 2.1, 1.8, and 1.5 geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8, 13.0, 11.1, 6.7, 8.7, and 4.8 GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4, 3.0, 2.5, 2.0, 1.5, and 1.3 GMFRs, respectively; the bivalent vaccine induced 9.9, 26.4, 22.2, 8.4, 12.6, and 4.7 GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.

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