bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-viral parenchymal lung disease following COVID-19 and viral pneumonitis hospitalisation: A systematic review and meta-analysis
Authors: Fabbri Laura , Moss Samuel , Khan Fasihul , Chi Wenjie , Xia Jun , Robinson Karen A. , Smyth Alan , Jenkins Gisli , Stewart Iain
Published: March 2021

Background

Approximately half of COVID-19 survivors present persisting breathlessness, which may include development of pulmonary fibrosis.

Research Question

What is the prevalence of long-term radiological and functional pulmonary sequelae of parenchymal lung disease following hospitalisation with COVID-19 and other viral pneumonia?

Study design and methods

We performed systematic review and random effects meta-analysis of studies in adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV, or Influenza pneumonia and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, updated 29 July 2021. Primary outcomes were proportion of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) impaired gas transfer. Heterogeneity was explored in meta-regression.

Results

Ninety-five studies were included for qualitative synthesis, of which 70 were suitable for meta-analysis, including 60 studies of SARS-CoV-2 with a median follow up of 3 months. In SARS-CoV-2 the overall estimated proportion of inflammatory changes during follow up was 0.50 (95%CI 0.41 to 0.58, I2=94.6%), whilst fibrotic changes were estimated at 0.29 (95%CI 0.22 to 0.37, I2=94.1%). Inflammatory changes reduced compared with CTs performed during hospitalisation (−0.47; 95%CI -0.56 to -0.37), whereas no significant resolution was observed in fibrotic changes (−0.09; 95%CI -0.25 to 0.07). Impaired gas transfer was estimated at 0.38 (95%CI 0.32 to 0.44, I2=92.1%), which was greater than estimated restrictive impairment (0.17; 95%CI 0.13 to 0.23, I2=92.5%). High heterogeneity means that estimates should be interpreted with caution. Confidence in the estimates was deemed low due to the heterogeneity and because studies were largely observational without controls.

Interpretation

A substantial proportion of radiological and functional sequelae consistent with parenchymal lung disease are observed following COVID-19 and other viral pneumonitis. Estimates of prevalence are limited by differences in case mix and initial severity. This highlights the importance of extended radiological and functional follow-up post hospitalisation.

PROSPERO registration

CRD42020183139 (April 2020)
Quantitative Comparison of SARS-CoV-2 Nucleic Acid Amplification Test and Antigen Testing Algorithms: A Decision Analysis Simulation Model
Authors: Salvatore Phillip P. , Shah Melisa M. , Ford Laura , Delaney Augustina , Hsu Christopher H. , Tate Jacqueline E. , Kirking Hannah L.
Published: March 2021

Background

Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations continue to recommend different strategies for utilizing NAATs and antigen tests in various settings. There has not yet been a quantitative comparison of the expected performance of these strategies.

Methods

We utilized a decision analysis approach to simulate the expected outcomes of six algorithms for implementing NAAT and antigen testing, analogous to testing strategies recommended by public health organizations. Each algorithm was simulated 50,000 times for four SARS-CoV-2 infection prevalence levels ranging from 5% to 20% in a population of 100000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.

Results

Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Substituting repeat antigen testing in lieu of NAAT confirmation of all initial negative antigen tests resulted in 2,280 missed cases (95% UR: 1,507-3,067) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case at 10% prevalence compared to exclusive use of antigen tests.

Conclusions

No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities; each presents a trade-off between prioritized outcomes and resource constraints. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and constraints.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.
A Longitudinal Analysis of COVID-19 Lockdown Stringency on Sleep and Resting Heart Rate Measures across 20 Countries
Authors: Ong Ju Lynn , Lau TeYang , Karsikas Mari , Kinnunen Hannu , Chee Michael WL
Published: March 2021

Lockdowns imposed to stem the spread of COVID-19 massively disrupted the daily routines of many worldwide, but studies to date are mostly confined to observations within a limited number of countries, based on subjective reports and survey from specific time periods during the pandemic. We investigated associations between lockdown stringency and objective sleep and resting-heart rate measures in 113,000 users of a consumer sleep tracker across 20 countries from Jan-Jul 2020. With stricter lockdown measures, midsleep times were universally delayed, particularly on weekdays, while midsleep variability and resting heart rate declined. These shifts (midsleep: +0.09 to +0.58 hours; midsleep variability: –0.12 to –0.26 hours; resting heart rate: –0.35 to –2.08 bpm) correlated with the severity of lockdown across different countries and highlight the graded influence of mobility restriction and social isolation on human physiology.
A map of binary SARS-CoV-2 protein interactions implicates host immune regulation and ubiquitination
Authors: Kim Dae-Kyum , Weller Benjamin , Lin Chung-Wen , Sheykhkarimli Dayag , Knapp Jennifer J. , Kishore Nishka , Sauer Mayra , Rayhan Ashyad , Young Veronika , Marin-de la Rosa Nora , Pogoutse Oxana , Spirohn Kerstin , Strobel Alexandra , Laval Florent , Schwehn Patrick , Li Roujia , Rothballer Simin , Altmann Melina , Cassonnet Patricia , Dugied Guillaume , Cote Atina G. , Vergara Lena Elorduy , Hazelwood Isaiah , Liu Bingruo B. , Nguyen Maria , Pandiarajan Ramakrishnan , Rodriguez Coloma Patricia A. , Willems Luc , Twizere Jean-Claude , Demeret Caroline , Jacob Yves , Hao Tong , Hill Dave E. , Falter Claudia , Vidal Marc , Calderwood Michael A. , Roth Frederick P. , Falter-Braun Pascal
Published: March 2021

Key steps in viral propagation, immune suppression, and pathology are mediated by direct, binary, physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary interactions between viral and host proteins, complementing previous co-complex association maps by conveying more direct mechanistic understanding and potentially enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, and confirming high quality of these interactions via a calibrated orthogonal assay. Host proteins interacting with SARS-CoV-2 proteins are enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The binary virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.
A simple coloring method to distinguish colonies of the yeastsLachancea thermotoleransandSaccharomyces cerevisiaeon agar media
Authors: Melkonian Chrats , Haver Auke , Wagner Marijke , Kalmoua Zakaria , Hellmuth Anna-Sophia , Mendoza Sebastián N. , Molenaar Douwe
Published: March 2021

The yeastLachancea thermotoleransconverts consumed sugar partly to lactic acid instead of ethanol and is therefore used together withSaccharomyces cerevisiaeto produce wines with a lower alcohol content. Being able to distinguish these yeasts is important for quality control and quantitative assessment of the contributions of both yeasts to wine fermentations. Commonly used methods to routinely distinguish these organisms are indirect or rely on commercial products of undisclosed composition. Here we describe that adding bromocresol purple to agar media inducesLachanceacolonies to develop a brown color, whereasSaccharomycescolonies remain white.
Histone H3 clipping is a novel signature of human neutrophil extracellular traps
Authors: Tilley Dorothea O , Abuabed Ulrike , Arndt Ursula Zimny , Schmid Monika , Florian Stefan , Jungblut Peter R. , Brinkmann Volker , Herzig Alf , Zychlinsky Arturo
Published: March 2021

Neutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis. However, NETosis, and the subsequent degradation of NETs, can become dysregulated. NETs are proposed to play a role in infectious as well as many non-infection related diseases including cancer, thrombosis, autoimmunity and neurological disease. Consequently, there is a need to develop specific tools for the study of these structures in disease contexts. In this study, we identified a NET-specific histone H3 cleavage event and harnessed this to develop a cleavage site-specific antibody for the detection of human NETs. By microscopy, this antibody distinguishes NETs from chromatin in purified and mixed cell samples. It also detects NETs in tissue sections. We propose this antibody as a new tool to detect and quantify NETs.
The phosphoproteome of rice leaves responds to water and nitrogen supply
Authors: Hamzelou Sara , Melino Vanessa J. , Plett Darren C. , Kamath Karthik Shantharam , Nawrocki Arkadiusz , Larsen Martin R. , Atwell Brian J. , Haynes Paul A.
Published: March 2021

The scarcity of freshwater is an increasing concern in flood-irrigated rice, whilst excessive use of nitrogen fertilizers is both costly and contributes to environmental pollution. To co-ordinate growth adaptation under prolonged exposure to limited water or excess nitrogen supply, plants have processes for signalling and regulation of metabolic processes. There is limited information on the involvement of one of the most important post-translational modifications (PTMs), protein phosphorylation, on plant adaptation to long-term changes in resource supply.Oryza sativacv. Nipponbare was grown under two regimes of nitrogen from the time of germination to final harvest. Twenty-five days after germination, water was withheld from half the pots in each nitrogen treatment and low water supply continued for an additional 26 days, while the remaining pots were well watered. Leaves from all four groups of plants were harvested after 51 days in order to test whether phosphorylation of leaf proteins responded to prior abiotic events. The dominant impact of these resources is exerted in leaves, where PTMs have been predicted to occur. Proteins were extracted and phosphopeptides were analysed by nanoLC-MS/MS analysis, coupled with label-free quantitation. Water and nitrogen regimes triggered extensive changes in phosphorylation of proteins involved in membrane transport, such as the aquaporin OsPIP2-6, a water channel protein. Our study reveals phosphorylation of several peptides belonging to proteins involved in RNA-processing and carbohydrate metabolism, suggesting that phosphorylation events regulate the signalling cascades that are required to optimize plant response to resource supply.
A signature of Neanderthal introgression on molecular mechanisms of environmental responses
Authors: Findley Anthony S , Zhang Xinjun , Boye Carly , Lin Yen Lung , Kalita Cynthia A , Barreiro Luis , Lohmueller Kirk E , Pique-Regi Roger , Luca Francesca
Published: March 2021

Ancient human migrations led to the settlement of population groups in varied environmental contexts worldwide. The extent to which adaptation to local environments has shaped human genetic diversity is a longstanding question in human evolution. Recent studies have suggested that introgression of archaic alleles in the genome of modern humans may have contributed to adaptation to environmental pressures such as pathogen exposure. Functional genomic studies have demonstrated that variation in gene expression across individuals and in response to environmental perturbations is a main mechanism underlying complex trait variation. We considered gene expression response toin vitrotreatments as a molecular phenotype to identify genes and regulatory variants that may have played an important role in adaptations to local environments. We investigated if Neanderthal introgression in the human genome may contribute to the transcriptional response to environmental perturbations. To this end we used eQTLs for genes differentially expressed in a panel of 52 cellular environments, resulting from 5 cell types and 26 treatments, including hormones, vitamins, drugs, and environmental contaminants. We found that SNPs with introgressed Neanderthal alleles (N-SNPs) disrupt binding of transcription factors important for environmental responses, including ionizing radiation and hypoxia, and for glucose metabolism. We identified an enrichment for N-SNPs among eQTLs for genes differentially expressed in response to 8 treatments, including glucocorticoids, caffeine, and vitamin D. Using Massively Parallel Reporter Assays (MPRA) data, we validated the regulatory function of 21 introgressed Neanderthal variants in the human genome, corresponding to 8 eQTLs regulating 15 genes that respond to environmental perturbations. These findings expand the set of environments where archaic introgression may have contributed to adaptations to local environments in modern humans and provide experimental validation for the regulatory function of introgressed variants.
Borreliainfection in rodent host has dramatic effects on the microbiome of ticks
Authors: Hamilton Phineas T. , Maluenda Elodie , Sarr Anouk , Belli Alessandro , Hurry Georgia , Duron Olivier , Plantard Olivier , Voordouw Maarten J.
Published: March 2021

Background

Vector-borne diseases remain major causes of human morbidity and mortality. It is increasingly recognized that the community of microbes inhabiting arthropods can strongly affect their vector competence, but the role of the tick microbiome inBorreliatransmission – the cause of Lyme disease – remains unclear.

Results

Here, we use a large-scale experiment to clarify the reciprocal interactions betweenBorrelia afzeliiand the microbiome ofIxodes ricinus, its primary vector. In contrast to other reports, we find that depletion of the bacterial microbiome in larval ticks has no effect on their subsequent acquisition ofB. afzeliiduring blood feeding on infected mice. Rather, exposure toB. afzelii-infected hosts drives pervasive changes to the tick microbiome, decreasing overall bacterial abundance, shifting bacterial community composition, and increasing bacterial diversity. These effects appear to be independent of the acquisition ofB. afzeliiby ticks, suggesting they are mediated by physiological or immunological aspects ofB. afzeliiinfection in the rodent host.

Conclusions

Manipulation of the microbiome ofI. ricinuslarvae had no effect on their ability to acquireB. afzelii. In contrast,B. afzeliiinfection in the mouse had dramatic effects on the composition of the gut microbiome inI. ricinusnymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector.
Sub-second multi-channel magnetic control of select neural circuits in behaving flies
Authors: Sebesta Charles , Torres Daniel , Wang Boshuo , Asfouri Joseph , Li Zhongxi , Duret Guillaume , Jiang Kaiyi , Xiao Zhen , Zhang Linlin , Zhang Qingbo , Colvin Vicki , Goetz Stefan M , Peterchev Angel V , Dierick Herman , Bao Gang , Robinson Jacob T.
Published: March 2021

Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, thein vivoresponse time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we produce sub-second behavioral responses inDrosophila melanogasterby combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve sub-second, multichannel stimulation, analogous to multi-color optogenetic stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.
Precartilage condensation during limb skeletogenesis occurs by tissue phase separation controlled by a bistable cell-state switch with suppressed oscillatory dynamics
Authors: Glimm T. , Kaźmierczak B. , Cui C. , Newman S.A. , Bhat R.
Published: March 2021

The tetrapod limb skeleton is initiated in unpatterned limb bud mesenchyme by the formation of precartilage condensations. Here, based on time-lapse videographic analysis of a forming condensation in a high-density culture of chicken limb bud mesenchyme, we observe a phase transition to a more fluidized state for cells within spatial compacted foci (protocondensations that will progress to condensations), as reflected in their spatial confinement, cell-substratum interaction and speed of motion. Previous work showed that galectin-8 and galectin-1A, two proteins of the galactoside-binding galectin family, are the earliest determinants of this process in the chicken limb bud, and that their interactions in forming skeletogenic patterns of condensations can be interpreted mathematically through a reaction-diffusion-adhesion framework. Based on this framework, we use an ordinary differential equation-based approach to analyze the core switching modality of the galectin reaction network and characterize the states of the network independent of the diffusive and adhesive arms of the patterning mechanism. We identify two steady states where the concentrations of both galectins are respectively, negligible, and very high. An explicit Lyapunov function shows that there are no periodic solutions. For sigmoidal galectin production terms, the model exhibits a bistable switch that arises from a monostable state via saddle-node bifurcation. Our model therefore predicts that the galectin network exists in low and high expression states separated in space or time without any intermediate states. This provides a causal basis for the observed outside vs. inside transition observed in the in vitro video data. We performed a quantitative analysis of the distribution of galectin-1A in cultures of condensing chick limb mesenchymal cells and found that the interior of the protocondensations had concentrations of this protein (compared to the immediate exterior) over and above that expected from its higher cell density, consistent with the model’s predictions. The galectin-based patterning network is thus suggested, on theoretical grounds, to incorporate a core switch independent of any spatial or temporal dynamics, that drives the chondrogenic cell state transition in limb skeletogenesis.
Simple morphometrics for predicting lordosis-induced deviations of body-shape in reared Gilthead seabream (Sparus aurataL.)
Authors: Fragkoulis Stefanos , Koumoundouros George
Published: March 2021

Haemal lordosis, V-shape bending of the haemal vertebrae, is a frequent abnormality of reared fish. Lordosis severity ranges from light deformations of vertebral axis, with insignificant effects on external morphology, to severe axis deformations with significant impact on body-shape. In the present study, we developed a simple morphometric index (PrAn) that links lordosis severity at the juvenile stage with fish body-shape at harvesting, without requiring to radiograph or sacrifice the samples. Examined seabream specimens were part of our previous study (Fragkoulis et al. 2019, Sci. Rep. 9, 9832), which monitored the effects of lordosis on the external morphology of pit-tagged seabream juveniles during their growth, up to harvest size. At both juvenile and adult stages, PrAn was effective in discriminating the normal fish from ca the 70% of lordotic fish. Our results suggest the PrAn as a valuable scale of quality, which quantifies the lordosis effects on fish external morphology, both at the juvenile stage and at harvest. Depending on the lordosis rates, and the hatchery strategy on the maximum allowed abnormality rates, this scale can cull out different rates of lordotic fish, without affecting the fish with normal phenotype or the lordotic fish with high recovery potential.
Structure, Mechanism and Crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase
Authors: Newman Joseph A , Douangamath Alice , Yazdani Setayesh , Yosaatmadja Yuliana , Aimon Anthony , Brandão-Neto José , Dunnett Louise , Gorrie-stone Tyler , Skyner Rachel , Fearon Daren , Schapira Matthieu , von Delft Frank , Gileadi Opher
Published: March 2021

The global COVID-19 pandemic is caused by the SARS-CoV-2 virus and has infected over 100 million and caused over 2 million fatalities worldwide at the point of writing. There is currently a lack of effective drugs to treat people infected with SARS-CoV-2. The SARS-CoV-2 Non-structural protein 13 (NSP13) is a superfamily1B helicase that has been identified as a possible target for anti-viral drugs due to its high sequence conservation and essential role in viral replication. In this study we present crystal structures of SARS-CoV-2 NSP13 solved in the APO form and in the presence of both phosphate and the non-hydrolysable ATP analogue (AMP-PNP). Comparisons of these structures reveal details of global and local conformational changes that are induced by nucleotide binding and hydrolysis and provide insights into the helicase mechanism and possible modes of inhibition. Structural analysis reveals two pockets on NSP13 that are classified as “druggable” and include one of the most conserved sites in the entire SARS-CoV-2 proteome. To identify possible starting points for anti-viral drug development we have performed a crystallographic fragment screen against SARS-CoV-2 NSP13 helicase. The fragment screen reveals 65 fragment hits across 52 datasets, with hot spots in pockets predicted to be of functional importance, including the druggable nucleotide and nucleic acid binding sites, opening the way to structure guided development of novel antiviral agents.
Cytotoxic efficiency of human CD8+T cell memory subtypes
Authors: Knörck Arne , Schwär Gertrud , Alansary Dalia , Thurner Lorenz , Hoth Markus , Schwarz Eva C.
Published: March 2021

Immunological memory is an important concept to protect humans against recurring diseases. Memory CD8+T cells are required for quick expansion into effector cells but also provide immediate cytotoxicity against their targets. Whereas many functions of the two main cytotoxic subtypes, effector memory CD8+T cells (TEM) and central memory CD8+T cells (TCM), are relatively well defined, single TEMand TCMcell cytotoxicity has not been quantified. Here, we analyze human CD8+subtype distribution following SEA stimulation and quantify the expression of death mediators, including perforin, granzyme B, FasL and TRAIL. We find higher perforin, granzyme B and FasL expression in TEMand compared to TCM. To quantify single TEMand TCMcytotoxicity, we develop a FRET-based fluorescent assay with NALM6 target cells stably transfected with a GFP-RFP FRET construct based on a caspase-cleavage sequence (apoptosis sensor Casper-GR). Applying this assay, TEMor TCMinduced target cell apoptosis or necrosis can be quantified. We find that single TEMare much more effective than TCMin killing their targets mainly by apoptosis and secondary necrosis. The reason for this is the higher perforin expression and on a more efficient lytic immunological synapse during TEM-target contact compared to TCM-target contact. Defining and quantifying single TEMand TCMcytotoxicity and the respective mechanism should be helpful to optimize future subset-based immune therapies.
SPIRO – the automated Petri plate imaging platform designed by biologists, for biologists
Authors: Ohlsson Jonas A , Leong Jia Xuan , Elander Pernilla H , Ballhaus Florentine , Holla Sanjana , Dauphinee Adrian N , Johansson Johan , Lommel Mark , Hofmann Gero , Betnér Staffan , Sandgren Mats , Schumacher Karin , Bozhkov Peter V , Minina Elena A
Published: March 2021

Phenotyping of model organisms grown on Petri plates is often carried out manually, despite the procedures being time-consuming and laborious. The main reason for this is the limited availability of automated phenotyping facilities, whereas constructing a custom automated solution can be a daunting task for biologists.

Here, we describe SPIRO, the Smart Plate Imaging Robot, an automated platform that acquires time-lapse photos of up to four vertically oriented Petri plates in a single experiment, corresponding to 192 seedlings for a typical root growth assay and up to 2500 seeds for a germination assay. SPIRO is catered specifically to biologists’ needs, requiring no engineering or programming expertise for assembly and operation. Its small footprint is optimized for standard incubators, the inbuilt green LED enables imaging under dark conditions, and remote control provides access to the data without interfering with sample growth. SPIRO’s excellent image quality is suitable for automated image processing, which we demonstrate on the example of seed germination and root growth assays. Furthermore, the robot can be easily customized for specific uses, as all information about SPIRO is released under open-source licenses.

Importantly, uninterrupted imaging allows considerably more precise assessment of seed germination parameters and root growth rates compared to manual assays. Moreover, SPIRO enables previously technically challenging assays such as phenotyping in the dark. We illustrate the benefits of SPIRO in proof-of-concept experiments which yielded a novel insight on the interplay between autophagy, nitrogen sensing and photoblastic response.
Genome assembly of the maize inbred line A188 provides a new reference genome for functional genomics
Authors: Ge Fei , Qu Jingtao , Liu Peng , Pan Lang , Zou Chaoying , Yuan Guangsheng , Yang Cong , Gao Shibin , Pan Guangtang , Huang Jianwei , Ma Langlang , Shen Yaou
Published: March 2021

Heretofore, little is known about the mechanism underlying the genotype-dependence of embryonic callus (EC) induction, which has severely inhibited the development of maize genetic engineering. Here, we report the genome sequence and annotation of a maize inbred line with high EC induction ratio, A188, which is assembled from single-molecule sequencing and optical genome mapping. We assembled a 2,210 Mb genome with a scaffold N50 size of 11.61 million bases (Mb), compared to those of 9.73 Mb for B73 and 10.2 Mb for Mo17. Comparative analysis revealed that ∼30% of the predicted A188 genes had large structural variations to B73, Mo17 and W22 genomes, which caused considerable protein divergence and might lead to phenotypic variations between the four inbred lines. Combining our new A188 genome, previously reported QTLs and RNA sequencing data, we reveal 8 large structural variation genes and 4 differentially expressed genes playing potential roles in EC induction.

Highlight

Our manuscript presents a high-quality reference genome of the inbred line A188, and provides new insights into candidate genes underlying maize embryonic callus induction and other maize agronomic traits.
oCEM: Automatic detection and analysis of overlapping co-expressed gene modules
Authors: Nguyen Quang-Huy , Le Duc-Hau
Published: March 2021

Background

When it comes to the co-expressed gene module detection, its typical challenges consist of overlap between identified modules and local co-expression in a subset of biological samples. The nature of module detection is the use of unsupervised clustering approaches and algorithms. Those methods are advanced undoubtedly, but the selection of a certain clustering method for sample- and gene-clustering tasks is separate, in which the latter task is often more complicated.

Results

This study presented an R-package, Overlapping CoExpressed gene Module (oCEM), armed with the decomposition methods to solve the challenges above. We also developed a novel auxiliary statistical approach to select the optimal number of principal components using a permutation procedure. We showed that oCEM outperformed state-of-the-art techniques in the ability to detect biologically relevant modules additionally.

Conclusions

oCEM helped non-technical users easily perform complicated statistical analyses and then gain robust results. oCEM and its applications, along with example data, were freely provided athttps://github.com/huynguyen250896/oCEM.
tbg - a new file format for genomic data
Authors: Schönnenbeck Philipp , Schell Tilman , Gerber Susanne , Pfenninger Markus
Published: March 2021

Motivation

The question of determining whether a Single-Nucleotide Polymorphism (SNP) or a variant in general leads to a change in the amino acid sequence of a protein coding gene is often a laborious and time-consuming challenge. Here, we introduce the tbg file format for storing genomic data and tbg-tools, a user-friendly toolbox for the faster analysis of SNPs. The file format stores information for each nucleotide in each gene, allowing to predict which change in the amino acid sequence will be caused by a variant in the nucleotide sequence. Our new tool therefore has the potential to make biological sense of the unprecedented amount of genome-wide genetic variation that researchers currently face.

Results

The new tab-separated file for storing the nucleotide data can be easily analyzed and used for a wide variety of biological research. It is also possible to automate some of these analyses using the additional analysis tools fromtbg-tools

Availability

tbg-toolsis written in Python and allows the installation from the command line. It can be found onhttps://github.com/Croxa/tbg-tools.

Contact

pschoenn@students.uni-mainz.de
Causal inference on microbiome-metabolome relations viain silico in vivoassociation pattern analyses
Authors: Hertel Johannes , Heinken Almut , Thiele Ines
Published: March 2021

The effects of the microbiome on the host’s metabolism are core to understanding the role of the microbiome in health and disease. Herein, we develop the paradigm ofin silico in vivoassociation pattern analyses, entailing a methodology to combine microbiome metabolome association studies within silicoconstraint-based microbial community modelling. By dissecting confounding and causal paths, we show thatin silico in vivoassociation pattern analyses allows for causal inference on microbiome-metabolome relations in observational data. Then, we demonstrate the feasibility and validity of our approach on a published multi-omics dataset (n=346), demonstrating causal microbiome-metabolite relations for 43 out of 53 metabolites from faeces. Finally, we utilise the identifiedin silico in vivoassociation pattern to estimate the microbial component of the faecal metabolome, revealing that the retrieved metabolite prediction scores correlate with the measured metabolite concentrations, and they also reflect the multivariate structure of the faecal metabolome. Concluding, we integrate with hypothesis free screening association studies and knowledge-basedin silicomodelling two major paradigms of systems biology, generating a promising new paradigm for causal inference in metabolic host-microbe interactions.
Using machine learning and big data to explore the drug resistance landscape in HIV
Authors: Blassel Luc , Tostevin Anna , Villabona-Arenas Christian Julian , Peeters Martine , Hué Stéphane , Gascuel Olivier
Published: March 2021

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number 435621. Therefore, the author does not wish this work to be cited as reference for the project. Please cite and refer to the preprint 435621 (DOI:https://doi.org/10.1101/2021.03.16.435621). If you have any questions, please contact the corresponding authors.
Genome-wide association study of gastric cancer- and duodenal ulcer-derivedHelicobacter pyloristrains reveals discriminatory amino acid differences and novel oncoprotein candidates
Authors: Tuan Vo Phuoc , Yahara Koji , Quy Dung Ho Dang , Binh Tran Thanh , Tung Pham Huu , Tri Tran Dinh , Minh Thuan Ngo Phuong , Khien Vu Van , Huyen Trang Tran Thi , Phuc Bui Hoang , Tshibangu-Kabamba Evariste , Matsumoto Takashi , Akada Junko , Suzuki Rumiko , Okimoto Tadayoshi , Kodama Masaaki , Murakami Kazunari , Yano Hirokazu , Fukuyo Masaki , Takahashi Noriko , Kato Mototsugu , Nishiumi Shin , Azuma Takeshi , Ogura Yoshitoshi , Hayashi Tetsuya , Toyoda Atsushi , Kobayashi Ichizo , Yamaoka Yoshio
Published: March 2021

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such asHelicobacter pylori, which causes gastric cancer (GC). We conducted a GWAS followed by regression-based prediction of GC and duodenal ulcerH. pyloristrains. We identified 14 single nucleotide polymorphisms (11 amino acid changes) that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into GC pathogenesis and a basis for identifying a set of biomarkers for application in clinical settings.
Morphometry of newborn piglets and its relevance at weaning
Authors: Silva Lucas M. , Fidelis Pedro H. S. , Gomes Lígia V. L. , Santos Gleyson A. , Oliveira Amanda M. A. , Medeiros Elias S. , Araújo Marcelle S. , Moreira Rennan H. R.
Published: March 2021

This study aimed to evaluate the development of suckling piglets using morphometric parameters. Different models were created to predict the probability to occur any of the three weight classes (light, medium, and heavy) based on the piglets’ weaning weight. The variables in this research were birth weight (PWB), lactation length (Lac), and morphometric parameters– body length (BL), heart girth (HG), body mass index (BMI), ponderal index (PI), surface-mass ratio (SM), and birth order (BO). An adjustment of the ordinal regression was proposed to predict the weight classifications. The model with a significant effect of the Lac variables was selected. The light and heavy piglets, regardless of their morphometry, have a high chance of staying in the same weight class at weaning. However, this does not occur in medium piglets with diverse morphometry.

Summary statement

This manuscript demonstrates how morphometry can influence the development of animals, even with similar weights.
phastSim: efficient simulation of sequence evolution for pandemic-scale datasets
Authors: De Maio Nicola , Boulton William , Weilguny Lukas , Walker Conor R. , Turakhia Yatish , Corbett-Detig Russell , Goldman Nick
Published: March 2021

Sequence simulators are fundamental tools in bioinformatics, as they allow us to test data processing and inference tools, as well as being part of some inference methods. The ongoing surge in available sequence data is however testing the limits of our bioinformatics software. One example is the large number of SARS-CoV-2 genomes available, which are beyond the processing power of many methods, and simulating such large datasets is also proving difficult. Here we present a new algorithm and software for efficiently simulating sequence evolution along extremely large trees (e.g. < 100, 000 tips) when the branches of the tree are short, as is typical in genomic epidemiology. Our algorithm is based on the Gillespie approach, and implements an efficient multi-layered search tree structure that provides high computational efficiency by taking advantage of the fact that only a small proportion of the genome is likely to mutate at each branch of the considered phylogeny. Our open source software is available fromhttps://github.com/NicolaDM/phastSimand allows easy integration with other Python packages as well as a variety of evolutionary models, including indel models and new hypermutatability models that we developed to more realistically represent SARS-CoV-2 genome evolution.

Author summary

One of the most influential responses to the SARS-CoV-2 pandemic has been the widespread adoption of genome sequencing to keep track of viral spread and evolution. This has resulted in vast availability of genomic sequence data, that, while extremely useful and promising, is also increasingly hard to store and process efficiently. An important task in the processing of this genetic data is simulation, that is, recreating potential histories of past and future virus evolution, to benchmark data analysis methods and make statistical inference. Here, we address the problem of efficiently simulating large numbers of closely related genomes, similar to those sequenced during SARS-CoV-2 pandemic, or indeed to most scenarios in genomic epidemiology. We develop a new algorithm to perform this task, that provides not only computational efficiency, but also extreme flexibility in terms of possible evolutionary models, allowing variation in mutation rates, non-stationary evolution, and indels; all phenomena that play an important role in SARS-CoV-2 evolution, as well as many other real-life epidemiological scenarios.
A NEW CASE OF DIPLOIDY WITHIN A HAPLOID GENUS OF ENTOMOPATHOGENIC FUNGI
Authors: Nielsen Knud Nor , Salgado João Felipe Moreira , Natsopoulou Myrsini Eirini , Stajich Jason E , De Fine Licht Henrik H.
Published: March 2021

Fungi in the genusMetarhiziumare soil-borne plant-root endophytes and rhizosphere colonisers, but also potent insect pathogens with highly variable host ranges. These ascomycete fungi are predominantly asexually reproducing and ancestrally haploid, but two independent origins of persistent diploidy within the Coleoptera-infectingM. majusspecies complex are known and has been attributed to incomplete chromosomal segregation following meiosis during the sexual cycle. There is also evidence for infrequent sexual cycles in the locust-specific pathogenic fungusMetarhizium acridum(Hypocreales: Clavicipitaceae), which is an important entomopathogenic biocontrol agent used for the control of grasshoppers in agricultural systems as an alternative to chemical control. Here, we show that the genome of theM. acridumisolate ARSEF 324, which is formulated and commercially utilised under the name ‘Green Guard’, is functionally diploid. We used single-molecule real-time (SMRT) sequencing technology to complete a high-quality assembly of ARSEF 324. Kmer frequencies, intragenomic collinearity between contigs and single nucleotide variant read depths across the genome revealed the first incidence of diploidy described within the speciesM. acridum. The haploid assembly of 44.7 Mb consisting of 20.8% repetitive elements, which is the highest proportion described of anyMetarhiziumspecies. The genome assembly and the inferred diploid state, can shed light on past research on this strain and could fuel future investigation into the fitness landscape of aberrant ploidy levels, not least in the contest of biocontrol agents.
Deletion of Rap-Phr systems inBacillus subtilisinfluencesin vitrobiofilm formation and plant root colonization
Authors: Christensen Mathilde Nordgaard , Mortensen Rasmus Møller Rosenbek , Kirk Nikolaj Kaae , Gallegos-Monterrosa Ramses , Kovács Ákos T.
Published: March 2021

Natural isolates of the soil-dwelling bacteriumBacillus subtilisform robust biofilms under laboratory conditions and colonize plant roots.B. subtilisbiofilm gene expression displays phenotypic heterogeneity that is influenced by a family of Rap-Phr regulatory systems. Most Rap-Phr systems inB. subtilishave been studied independently, in different genetic backgrounds and under distinct conditions, hampering true comparison of the Rap-Phr systems’ impact on bacterial differentiation. Here, we investigated each of the 12 Rap-Phr systems ofB. subtilisNCIB 3610 for their effect on biofilm formation. By studying single Δrap-phrmutants, we show that despite redundancy between the cell-cell communication systems, deletion of each of the 12 Rap-Phr systems influences matrix gene expression, which could possibly enable fine-tuning of the timing and level of matrix production in response to specific conditions. Furthermore, some of the Δrap-phrmutants demonstrated altered biofilm formationin vitroand colonization ofArabidopsis thalianaroots, but not necessarily similarly in both processes, indicating that the pathways regulating matrix gene expression and other factors important for biofilm formation may be differently regulated under these distinct conditions.

Significance Statement

Natural isolates ofBacillus subtilisform robust biofilmsin vitroand on plant roots. The formation of these heterogeneous populations is regulated by diverse Rap-Phr systems. However, most Rap-Phr systems inB. subtilishave been studied independently and in different genetic backgrounds. Here, we report that all 12 Rap-Phr systems affect matrix gene expression, while some of them affect development ofin vitrobiofilms and plant root colonization. Our study highlights the importance of the Rap-Phr systems in environmental adaptation ofB. subtilis, specifically during biofilm formation in the rhizosphere.
Twenty years of change in benthic communities across the Belizean Barrier Reef
Authors: Alves Catherine , Aronson Richard B. , Bood Nadia , Castillo Karl D. , Cox Courtney , Fieseler Clare , Locklear Zachary , McField Melanie , Mudge Laura , Umbanhowar James , Valdivia Abel , Bruno John F.
Published: March 2021

Disease, ocean warming, and pollution have caused catastrophic declines in the cover of living coral on reefs across the Caribbean. Subsequently, reef-building corals have been replaced by invertebrates and macroalgae, leading to changes in ecological functioning. We describe changes in benthic community composition and cover at 15 sites across the Belizean Barrier Reef (BBR) following numerous major disturbances—bleaching, storms, and disease outbreaks—over the 20-year period 1997–2016. We tested the role of potential drivers of change on coral reefs, including local human impacts and ocean temperature. From 1997 to 2016, mean coral cover significantly declined from 26.3% to 10.7%, while macroalgal cover significantly increased from 12.9% to 39.7%. We documented a significant decline over time of the reef-building coralsOrbicellaspp. and described a major shift in benthic composition between early sampling years (1997–2005) and later years (2009–2016). The covers of hard-coral taxa, includingAcroporaspp.,M. cavernosa, Orbicellaspp., andPoritesspp., were negatively related to marine heatwave frequency. Only gorgonian cover was related, negatively, to our metric of the magnitude of local impacts (the Human Influence Index). Changes in benthic composition and cover were not associated with local protection or fishing. This result is concordant with studies throughout the Caribbean that have documented living coral decline and shifts in reef-community composition following disturbances, regardless of local fisheries restrictions. Our results suggest that benthic communities along the BBR have experienced disturbances that are beyond the capacity of the current management structure to mitigate. We recommend that managers devote greater resources and capacity to enforce and expand existing marine protected areas and that government, industry, and the public act to reduce global carbon emissions.
A biomechanical comparison of the jerk, back jerk, vertical jump and jump squat
Authors: Liu Jiatian
Published: March 2021

Although weightlifting exercises and their pulling and catching derivatives have been well studied, less is known about the group of weightlifting overhead pressing derivatives (WOPDs). There were two purposes of the present study. Above all, it was to compare WOPDs (i.e. jerk and back jerk) with jump squat in enhancing sport performance such as vertical jump in the perspective of biomechanics. Furthermore, it was to gain a better understanding of the biomechanical difference between jerk and back jerk. The study compared the kinetics, kinematics, and muscle activation of the jerk, back jerk, vertical jump and jump squat. Ground reaction forces, joint angle data and electromyography were collected from 20 track and field athletes while they performed the four movements. The joint coordination pattern and EMG characters of the jump squat were more similar to those of the vertical jump. WOPDs, especially jerk, exhibited less similarity with vertical jump in joint coordination, as well as the subsequent peak activation. The electromyography data demonstrated significant differences in rectus femoris and gluteus maximus in the relative timing of peak activations and the maximum activation. Jump squat was greater in peak force (2211N) than jerk (P < .005), greater peak power (4749W) than jerk and back jerk (P < .001) and no significant difference with WOPDs in rate of force development. Back jerk produced a greater peak force (2223 N), peak power (3767W) and eccentric RFD (15965 N·s−1) than jerk (2061N)(P < .001) (3364W)(P < .05) (12280 N·s−1)(P < .01)and the opposite in concentric RFD that jerk (7702 N·s−1) was greater than back jerk (5972 N·s−1)(P < .05). We can conclude that for runner and jumpers, jump squat was better for improving vertical jump than WOPDs and back jerk is better than jerk in power training.