bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood Disadvantage and Active, Disabled and Total Life Expectancy Among Community-living Older Persons
Authors: Gill Thomas M. , Zang Emma X. , Murphy Terrence E. , Leo-Summers Linda , Gahbauer Evelyne A. , Festa Natalia , Falvey Jason R. , Han Ling
Published: February 2021

Background

Neighborhood disadvantage is a novel social determinant of health that could adversely affect the functional well-being and longevity of older persons. We evaluated whether estimates of active, disabled and total life expectancy differ on the basis of neighborhood disadvantage after accounting for individual-level socioeconomic characteristics and other prognostic factors.

Methods

We used data on 754 community-living older persons from South Central Connecticut, who completed monthly assessments of disability from 1998 to 2020. Scores on the area deprivation index were dichotomized at the 80thstate percentile to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80).

Results

Within 5-year age increments from 70 to 90, active and total life expectancy were consistently lower in participants from neighborhoods that were disadvantaged versus not disadvantaged, and these differences persisted and remained statistically significant after adjustment for individual-level race/ethnicity, education, income, and other prognostic factors. At age 70, adjusted estimates (95% CI) for active and total life expectancy (in years) were 12.3 (11.5-13.1) and 15.0 (13.8-16.1) in the disadvantaged group and 14.2 (13.5-14.7) and 16.7 (15.9-17.5) in the non-disadvantaged group. At each age, participants from disadvantaged neighborhoods spent a greater percentage of their projected remaining life disabled, relative to those from non-disadvantaged neighborhoods, with adjusted values (SE) ranging from 17.7 (0.8) vs. 15.3 (0.5) at age 70 to 55.0 (1.7) vs. 48.1 (1.3) at age 90.

Conclusions

Living in a disadvantaged neighborhood is associated with lower active and total life expectancy and a greater percentage of projected remaining life disabled.
Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic
Authors: Amaku Marcos , Covas Dimas Tadeu , Coutinho Francisco Antonio Bezerra , Azevedo Raymundo Soares , Massad Eduardo
Published: February 2021

OBJECTIVES

With declining numbers of COVID-19 cases in the State of São Paulo, Brazil, social distancing measures were gradually being lifted. The risk of an increase in the number of cases, however, cannot be overlooked. Even with the adoption of non-pharmaceutical interventions, such as restrictions on mass gatherings, wearing masks, and complete or partial closure of schools, other public health measures may help to control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing.

METHODS

We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the State of São Paulo.

RESULTS

For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact tracing strategy is performed.

CONCLUSION

Contact tracing of symptomatic individuals may be a potential alternative strategy when the number of diagnostic tests available is not sufficient for a massive testing strategy.
Ibrutinib as a Potential Therapeutic for Cocaine Use Disorder
Authors: Huggett Spencer B. , Hatfield Jeffrey S. , Walters Joshua D. , McGeary John E. , Welsh Justine W. , Mackay Trudy F. C. , Anholt Robert R. H. , Palmer Rohan H.C.
Published: February 2021

Cocaine use presents a worldwide public health problem with high socioeconomic cost. Current treatments for cocaine use disorder (CUD) are suboptimal and rely primarily on behavioral interventions. To explore pharmaceutical treatments for CUD, we analyzed genome-wide gene expression data from publically availble human brain tissues (midbrain, hippocampus and prefrontal cortex neurons) from 71 individuals (mean age = 39.9, 100% male, 36 with CUD and 35 matched controls). We leveraged the L1000 database to investigate molecular associations between neuronal mRNA profiles from 825 repurposable compounds (e.g., FDA approved) with human CUD gene expression in the brain. We identified 16 compounds that were negatively associated with CUD gene expression patterns across all brain regions (padj < 0.05), all of which outperformed current targets undergoing clinical trials for CUD (all padj > 0.05). We tested the effectiveness of these compounds using independent transcriptome-wide in vitro (neuronal cocaine exposure; n=18) and in vivo (mouse cocaine self-administration; prefrontal cortex, hippocampus and midbrain; n = 12-15) datasets. Among these medications, Ibrutinib demonstrated negative associations with both neuronal cocaine exposure and mouse cocaine self-administration. To obtain experimental confirmation of therapeutic effects of Ibrutinib on CUD, we used the Drosophila melanogaster model, which enables highthroughput quantification of behavioral responses in defined genetic backgrounds and controlled environmental conditions. Ibrutinib altered cocaine-induced changes in startle response and reduced the occurrence of cocaine-induced seizures (n = 61-142 per group; sex: 51%female). Our results identify Ibrutinib, an FDA approved medication, as a potential therapeutic for cocaine neurotoxicity.
Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease
Authors: Xiao Zhenxu , Wu Xue , Wu Wanqing , Yi Jingwei , Liang Xiaoniu , Ding Saineng , Zheng Li , Luo Jianfeng , Gu Hongchen , Zhao Qianhua , Xu Hong , Ding Ding
Published: February 2021

Background

Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the association with cognitive domains along the spectrum of cognitive performance deterioration have seldom been reported.

Methods

We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis of AD, amnestic mild cognitive impairment, and normal cognition (NC). Each participant was administered the neuropsychological tests assessing the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the Single molecule array platform.

Results

Along with plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, and NfL, p-tau181 significantly increased across the groups with the incremental CDR scores from NC (CDR = 0) to severe AD (CDR = 3). Compared with other biomarkers, p-tau181 had a stronger correlation with Global cognition (r= −0.494,P< 0.001), Memory (r= −0.417,P< 0.001), Attention (r= −0.388,P< 0.001), Visuospatial function (r= −0.328,P< 0.001), and Language (r= −0.123,P= 0.014). Among AD participants with CDR ≥ 1, higher p-tau181 was correlated with worse Global cognition (r= −0.295,P< 0.001), Memory (r= −0.172,P= 0.045), and Attention (r= −0.184,P= 0.031).

Conclusions

Plasma p-tau181 had a stronger correlation with cognitive domains than other biomarkers, especially in late-stage AD. It could reflect the AD pathology in vivo and may be a promising blood-based biomarker in clinical settings.
Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice
Authors: Liu Xingjian , Song Haozhi , Jiang Jianmin , Gao Xintao , Yi Yongzhu , Shang Yuting , Li Jialei , Li Dan , Zeng Zhen , Li Yinü , Zhang Zhifang
Published: February 2021

The spike (S), a homotrimer glycoprotein, is the most important antigen target in the research and development of SARS-CoV-2 vaccine. There is no doubt that fully simulating the advanced structure of this homotrimer in the subunit vaccine development strategy is the most likely way to improve the immune protective effect of the vaccine. In this study, the preparation strategies of S protein receptor-binding domain (RBD) trimer, S1 region trimer, and ectodomain (ECD) trimer nanoparticles were designed based on ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare these three nanoparticle vaccines with high expression levels in the silkworm. The immune results of mice show that the nanoparticle vaccine prepared by this strategy can not only induce an immune response by subcutaneous administration but also effective by oral administration. Given the stability of these ferritin-based nanoparticles vaccine, easy-to-use and low-cost oral immunization strategy can make up for the vaccination blind areas caused by the shortage of ultralow-temperature equipment and medical resources in underdeveloped areas. And the oral vaccine is also a very potential candidate to cut off the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.
Densified Collagen Tubular Grafts for Human Tissue Replacement and Disease Modelling Applications
Authors: Justin Alexander W , Cammarata Federico , Guy Andrew A , Estevez Silas R , Burgess Sebastian , Davaapil Hongorzul , Stavropoulou-Tatla Agavi , Ong John , Jacob Aishwarya G , Saeb-Parsy Kourosh , Sinha Sanjay , Markaki Athina E
Published: February 2021

There is a significant need across multiple indications for an off-the-shelf bioengineered tubular graft which fulfils the mechanical and biological requirements for implantation and function but does not necessarily require cells for manufacture or deployment. Herein, we present a tissue-like tubular construct using a cell-free, materials-based method of manufacture, utilizing densified collagen hydrogel. Our tubular grafts are seamless, mechanically strong, customizable in terms of lumen diameter and wall thickness, and display a uniform fibril density across the wall thickness and along the tube length. While the method enables acellular grafts to be generated rapidly, inexpensively, and to a wide range of specifications, the cell-compatible densification process also enables a high density of cells to be incorporated uniformly into the walls of the tubes, which we show can be maintained under perfusion culture. Additionally, the method enables tubes consisting of distinct cell domains with cellular configurations at the boundaries which may be useful for modelling aortic disease. Further, we demonstrate additional steps which allow for luminal surface patterning. These results highlight the universality of this approach and its potential for developing the next generation of bioengineered grafts.
Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection
Authors: Rao Youliang , Wang Ting-Yu , Qin Chao , Espinosa Bianca , Liu Qizhi , Ekanayake Arunika , Zhao Jun , Savas Ali Can , Zhang Shu , Zarinfar Mehrnaz , Liu Yongzhen , Zhu Wenjie , Graham Nicholas , Jiang Taijiao , Zhang Chao , Feng Pinghui
Published: February 2021

The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promotede novoCTP synthesis while shutting down IFN induction.De novosynthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.
ORFhunteR: an accurate approach for the automatic identification and annotation of open reading frames in human mRNA molecules
Authors: Grinev Vasily V. , Yatskou Mikalai M. , Skakun Victor V. , Chepeleva Maryna K. , Nazarov Petr V.
Published: February 2021

Motivation

Modern methods of whole transcriptome sequencing accurately recover nucleotide sequences of RNA molecules present in cells and allow for determining their quantitative abundances. The coding potential of such molecules can be estimated using open reading frames (ORF) finding algorithms, implemented in a number of software packages. However, these algorithms show somewhat limited accuracy, are intended for single-molecule analysis and do not allow selecting proper ORFs in the case of long mRNAs containing multiple ORF candidates.

Results

We developed a computational approach, corresponding machine learning model and a package, dedicated to automatic identification of the ORFs in large sets of human mRNA molecules. It is based on vectorization of nucleotide sequences into features, followed by classification using a random forest. The predictive model was validated on sets of human mRNA molecules from the NCBI RefSeq and Ensembl databases and demonstrated almost 95% accuracy in detecting true ORFs. The developed methods and pre-trained classification model were implemented in a powerful ORFhunteR computational tool that performs an automatic identification of true ORFs among large set of human mRNA molecules.

Availability and implementation

The developed open-source R package ORFhunteR is available for the community at GitHub repository (https://github.com/rfctbio-bsu/ORFhunteR), from Bioconductor (https://bioconductor.org/packages/devel/bioc/html/ORFhunteR.html) and as a web application (http://orfhunter.bsu.by).
Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize
Authors: Zhao Mingxia , Peng Zhao , Qin Yang , Zhang Ling , Tian Bin , Chen Yueying , Liu Yan , Lin Guifang , Zheng Huakun , He Cheng , Lv Kaiwen , Trick Harold N. , Liu Yunjun , Cho Myeong-Je , Park Sunghun , Wei Hairong , Zheng Jun , White Frank F. , Liu Sanzhen
Published: February 2021

Cellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the γ-proteobacterium genusXanthomonasand secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen,Xanthomonas vasicolapv.vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize geneglossy3(gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146gl3downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68gl3downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from thegl3downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.
Loss of ClpP Function inClostridioides difficile630 Significantly Impacts Sporulation Systems
Authors: Bishop Catherine E. , Shadid Tyler , Lavey Nathan P. , Kempher Megan L. , Ahsan Nagib , Ballard Jimmy D. , Duerfeldt Adam S.
Published: February 2021

The Gram-positive bacteriumClostridioides difficileis a primary cause of hospital-acquired diarrhea, threatening both immunocompromised and healthy individuals. An important aspect of elucidating mechanisms that driveC. difficilepersistence and virulence relies on developing a more complete understanding of sporulation.C. difficilesporulation is the single determinant of transmission and complicates treatment and prevention due to the chemical and physical resilience of spores. Hence, the identification of potentially druggable targets that significantly attenuate sporulation is important. In this report, we describe the impact of the loss of caseinolytic protease P (ClpP) isoforms inC. difficilestrain 630 on sporulation phenotypes. Using CRISPR-Cas9 nickase mediated genome editing, stop codons were inserted early in the coding sequence forclpP1andclpP2to generateC. difficilemutants that no longer produced ClpP1 or ClpP2. The data show that these genetic modifications lead to altered sporulation phenotypes, germination efficiencies, and cytotoxicity. Comparative proteome profiling ofC. difficile630 WT andclpPmutants reveals potential proteolytic targets of ClpP that are involved in sporulation. These analyses further reveal the potential for preferred co-chaperone interactions for each ClpP isoform. Taken together, our results demonstrate that ClpP, a promising target in other Gram-positive pathogens, holds promise as an anti-sporulation target inC. difficile.
Mendelian Randomization Analysis Using Multiple Biomarkers of an Underlying Common Exposure
Authors: Jin Jin , Qi Guanghao , Yu Zhi , Chatterjee Nilanjan
Published: February 2021

Summary

Mendelian Randomization (MR) analysis is increasingly popular for testing the causal effect of exposures on disease outcomes using data from genome-wide association studies. In some settings, the underlying exposure, such as systematic inflammation, may not be directly observable, but measurements can be available on multiple biomarkers or other types of traits that are coregulated by the exposure. We propose a method for MR analysis on latent exposures (MRLE), which tests the significance for, and the direction of, the effect of a latent exposure by leveraging information from multiple related traits. The method is developed by constructing a set of estimating functions based on the second-order moments of GWAS summary association statistics for the observable traits, under a structural equation model where genetic variants are assumed to have indirect effects through the latent exposure and potentially direct effects on the traits. Simulation studies show that MRLE has well-controlled type I error rates and enhanced power compared to single-trait MR tests under various types of pleiotropy. Applications of MRLE using genetic association statistics across five inflammatory biomarkers (CRP, IL-6, IL-8, TNF-α, and MCP-1) provide evidence for potential causal effects of inflammation on increasing the risk of coronary artery disease, colorectal cancer, and rheumatoid arthritis, while standard MR analysis for individual biomarkers fails to detect consistent evidence for such effects.
Multi-omic characterization of the thermal stress phenome in the stony coralMontipora capitata
Authors: Pathmanathan Jananan S. , Williams Amanda , Stephens Timothy G. , Su Xiaoyang , Chiles Eric N. , Conetta Dennis , Putnam Hollie M. , Bhattacharya Debashish
Published: February 2021

We used network methods to analyze transcriptomic and polar metabolomic data generated from the stress resistant stony coralMontipora capitata. Corals were exposed to ambient or thermal stress conditions over a five-week period that coincided with a mass spawning event of this species. Gene co-expression networks showed that the early thermal stress response involves downregulation of growth and DNA replication, whereas signaling and the immune response are strongly upregulated. Later stages are dominated by suppression of metabolite transport and biomineralization and enhanced expression of transcriptional regulators. Integration of gene-metabolite data demonstrates that the major outcome of the thermal treatment is activation of animal redox stress pathways with detoxification of reactive oxygen species being dominant. Differential regulation of the highly conserved cytochrome P450 gene family was of particular interest with downregulation of CYP1A1, involved in progesterone metabolism, potentially explaining the attenuated mass spawning observed during the sampling period.
Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies
Authors: Tada Takuya , Dcosta Belinda M. , Samanovic-Golden Marie , Herati Ramin S. , Cornelius Amber , Mulligan Mark J. , Landau Nathaniel R.
Published: February 2021

The increasing prevalence of SARS-CoV-2 variants with mutations in the spike protein has raised concerns that recovered individuals may not be protected from reinfection and that current vaccines will become less effective. The B.1.1.7 isolate identified in the United Kingdom and B.1.351 isolate identified in the Republic of South Africa encode spike proteins with multiple mutations in the S1 and S2 subunits. In addition, variants have been identified in Columbus, Ohio (COH.20G/677H), Europe (20A.EU2) and in domesticated minks. Analysis by antibody neutralization of pseudotyped viruses showed that convalescent sera from patients infected prior to the emergence of the variant viruses neutralized viruses with the B.1.1.7, B.1.351, COH.20G/677H Columbus Ohio, 20A.EU2 Europe and mink cluster 5 spike proteins with only a minor decrease in titer compared to that of the earlier D614G spike protein. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus and neutralized virus with the B.1.351 spike with, on average, a 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). The reduction in titer was attributable to the E484K mutation in the RBD. The B.1.1.7 and B.1.351 viruses were not more infectious than D614G on ACE2.293T cellsin vitrobut N501Y, an ACE2 contacting residue present in the B.1.1.7, B.1.351 and COH.20G/677H spike proteins caused higher affinity binding to ACE2, likely contributing to their increased transmissibility. These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K.
Innovations to expand drone data collection and analysis for rangeland monitoring
Authors: Gillan Jeffrey K. , Ponce-Campos Guillermo E. , Swetnam Tyson L. , Gorlier Alessandra , Heilman Philip , McClaran Mitchel P.
Published: February 2021

In adaptive management of rangelands, monitoring is the vital link that connects management actions with on-the-ground changes. Traditional field monitoring methods can provide detailed information for assessing the health of rangelands, but cost often limits monitoring locations to a few key areas or random plots. Remotely sensed imagery, and drone-based imagery in particular, can observe larger areas than field methods while retaining high enough spatial resolution to estimate many rangeland indicators of interest. However, the geographic extent of drone imagery products is often limited to a few hectares (for resolution ≤ 1 cm) due to image collection and processing constraints. Overcoming these limitations would allow for more extensive observations and more frequent monitoring. We developed a workflow to increase the extent and speed of acquiring, processing, and analyzing drone imagery for repeated monitoring of two common indicators of interest to rangeland managers: vegetation cover and vegetation heights. By incorporating a suite of existing technologies in drones (real-time kinematic GPS), data processing (automation with Python scripts, high performance computing), and cloud-based analysis (Google Earth Engine), we greatly increased the efficiency of collecting, analyzing, and interpreting high volumes of drone imagery for rangeland monitoring. End-to-end, our workflow took 30 days, while a workflow without these innovations was estimated to require 141 days to complete. The technology around drones and image analysis is rapidly advancing which is making high volume workflows easier to implement. Larger quantities of monitoring data will significantly improve our understanding of the impact management actions have on land processes and ecosystem traits.
Tissue-type specific accumulation of the plastoglobular proteome, transcriptional networks and plastoglobular functions
Authors: Michel Elena J.S. , Ponnala Lalit , Wijk Klaas J. van
Published: February 2021

Plastoglobules (PGs) are dynamic protein-lipid micro-compartments in plastids enriched for isoprenoid-derived metabolites. Chloroplast PGs support formation, remodeling and controlled dismantling of thylakoids during developmental transitions and environmental responses. However, the specific molecular functions of most PG proteins are still poorly understood. This study harnesses recent co-mRNA expression from ATTED-II using combined microarray and RNAseq information on an updated inventory of 34 PG proteins, as well as proteomics data across 30 Arabidopsis tissue types from ATHENA. Hierarchical clustering based on relative abundance for the PG proteins across non-photosynthetic and photosynthetic tissue types showed their coordinated protein accumulation across Arabidopsis parts, tissue types, development and senescence. We generated multiple mRNA-based networks by applying different coefficient thresholds; functional enrichment was determined for each network and PG gene. Combined analysis of these stringency networks identified a central hub and four peripheral modules. Enrichment of specific nuclear transcription factors (e.g. Golden2-like) and support for cross-talk between PGs and the plastid gene expression was observed, and specific ABC1 kinases seem part of a light signaling network. Examples of other specific findings are that FBN7b is involved with upstream steps of tetrapyrrole biosynthesis and that ABC1K9 is involved in starch metabolism.

Highlight

The plastoglobular proteome shows coherent tissue-specific accumulation, whereas combined analysis of transcriptional co-expression networks, at different stringencies and following in-depth functional annotation, associate selected plastoglobular proteins to specific metabolic functions.
The ability ofPseudomonas aeruginosato adopt a Small Colony Variant (SCV) phenotype is conserved, and not restricted to clinical isolates
Authors: Besse Alison , Trottier Mylène , Groleau Marie-Christine , Déziel Eric
Published: February 2021

A subpopulation of Small Colony Variants (SCVs) is a frequently observed feature ofPseudomonas aeruginosaisolated from cystic fibrosis (CF) lungs biofilms. SCVs have almost exclusively been reported from infected hosts, essentially CF individuals or, by extension, from laboratory cultivation of strains originated from infected hosts. We previously reported the identification ofP. aeruginosaSCVs emerging from a non-clinical strain and displaying features shared with clinical SCVs. In the present work, we investigated the ability of 22P. aeruginosaisolates from various environmental origins to, under laboratory culture conditions, spontaneously adopt a SCV-like smaller alternative morphotype distinguishable from the ancestral parent strain. Unexpectedly, we found that all theP. aeruginosastrains tested have the ability to adopt a SCV morphotype, regardless of their origin. Based on the phenotypes already described for SCVs, the SCV-like morphotypes obtained were clustered in two groups displaying various phenotypic profiles, including one characteristic of already described SCVs. We conclude that the ability to switch to a SCV phenotype is a conserved feature inPseudomonas aeruginosa.

IMPORTANCE

P. aeruginosais an opportunistic pathogen that thrives in many environments. It is significant public health concern, notably because it is the most prevalent pathogen found in the lungs of people with cystic fibrosis (CF). In infected hosts, its persistence is believed to be related to the emergence of an alternative small colony variant (SCV) phenotype. By reporting the distribution ofP. aeruginosaSCVs in various non-clinical environments, this work contributes to understanding a conserved adaptation mechanism used byP. aeruginosato rapidly adapt in all environments. Counteraction of this strategy could preventP. aeruginosapersistent infection in the future.
Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
Authors: Washington Nicole L. , Gangavarapu Karthik , Zeller Mark , Bolze Alexandre , Cirulli Elizabeth T. , Barrett Kelly M. Schiabor , Larsen Brendan B. , Anderson Catelyn , White Simon , Cassens Tyler , Jacobs Sharoni , Levan Geraint , Nguyen Jason , Ramirez Jimmy M. , Rivera-Garcia Charlotte , Sandoval Efren , Wang Xueqing , Wong David , Spencer Emily , Robles-Sikisaka Refugio , Kurzban Ezra , Hughes Laura D. , Deng Xianding , Wang Candace , Servellita Venice , Valentine Holly , De Hoff Peter , Seaver Phoebe , Sathe Shashank , Gietzen Kimberly , Sickler Brad , Antico Jay , Hoon Kelly , Liu Jingtao , Harding Aaron , Bakhtar Omid , Basler Tracy , Austin Brett , Isaksson Magnus , Febbo Phillip G. , Becker David , Laurent Marc , McDonald Eric , Yeo Gene W. , Knight Rob , Laurent Louise C. , de Feo Eileen , Worobey Michael , Chiu Charles , Suchard Marc A. , Lu James T. , Lee William , Andersen Kristian G.
Published: February 2021

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.
Antibody Tests: They Are More Important Than We Thought
Authors: Guimarães Luís
Published: February 2021

Antibody testing is a non-pharmaceutical intervention – not recognized so far in the literature – to prevent COVID-19 contagion. I show this in a simple economic model of an epidemic in which agents choose social activity under health state uncertainty. In the model, susceptible and asymptomatic agents are more socially active when theythinkthey might be immune. And this increased activity escalates infections, deaths, and welfare losses. Antibody testing, however, prevents this escalation by revealing that those agents are not immune. Through this mechanism, I find that antibody testing prevents about 12% of COVID-19 related deaths within 12 months.
Automated Detection of COVID-19 through Convolutional Neural Network using Chest x-ray images
Authors: Sarki Rubina , Ahmed Khandakar , Wang Hua , Zhang Yanchun , Wang Kate
Published: February 2021

The COVID-19 epidemic appears to have a catastrophic impact on global well-being and public health. More than 10 million confirmed cases have been reported worldwide until now. Due to the growing number of confirmed cases, timely and accurate classification of healthy and infected patients is essential to control and treat COVID-19. To this end, in this paper, we aim to develop a deep learning-based system for the persuasive classification and reliable detection of COVID-19 using chest radiography. Firstly, we evaluate the performance of various state-of-the-art convolutional neural networks (CNNs) proposed over recent years for medical image classification. Secondly, we develop and train CNN from scratch. In both cases, we use a recently published public X-Ray dataset for training and validation purposes. For transfer learning, we obtain 100% accuracy for binary classification (i.e., Normal/COVID-19) and 87.50% accuracy for tertiary classification (Normal/COVID-19/Pneumonia). With the CNN trained from scratch, we achieve 93.75% accuracy for tertiary classification. We observe, in the case of transfer learning, the classification accuracy drops with an increased number of classes. Our comprehensive ROC and confusion metric analysis with 10-fold cross-validation strongly underpin our findings.
Comparative reproductive biology of deep-sea ophiuroids inhabiting polymetallic-nodule fields in the Clarion-Clipperton Fracture Zone
Authors: Laming Sven R , Christodoulou Magdalini , Arbizu Pedro Martinez , Hilário Ana
Published: February 2021

Deep-sea mining in the Pacific Clarion-Clipperton Fracture Zone (CCZ), a low-energy sedimentary habitat with polymetallic nodules, is expected to have considerable and long-lasting environmental impact. The CCZ hosts extraordinarily high species diversity across representatives from all Domains of Life. Data on species biology and ecology remain scarce, however. The current study describes the reproductive biology ofOphiosphalma glabrum(Lütken & Mortensen, 1899) (Ophiosphalmidae) andOphiacantha cosmica(Lyman, 1878) (Ophiacanthidae), two ophiuroids frequently found in the CCZ. Specimens collected in Spring 2015 and 2019 in four contract areas were examined morphologically and histologically. Size-class frequencies (disc diameter and oocytes feret diameters), sex ratios, gametogenic status, putative reproductive mode and a simple proxy for fecundity are presented. Habitat use differs in each. WhileOphiosphalma glabrumis epibenthic, occurring as single individuals,Ophiacantha cosmicaoften form size-stratified groups living on stalked sponges, suggesting gregarious settlement or retention of offspring (though no brooding individuals were found). Further molecular analyses are needed to establish whetherO. cosmicagroups are familial. InOphiosphalma glabrum, for which sample sizes were larger, sex ratios approximated a 1:1 ratio with no size-structuring. In both species, individuals were at various stages of gametogenic maturity but no ripe females were identified. Based on this,O. glabrumis most probably gonochoric. Reproductive mode remains inconclusive forOphiacantha cosmica. Both species are presumptively lecithotrophic, with vitellogenic-oocyte feret diameters exceeding 250 µm. Oocyte feret diameters at times exceeded 400 µm inOphiosphalma glabrum, indicating substantial yolk reserves. Estimates of instantaneous fecundity (vitellogenic specimens ofO. glabrumonly) were confounded by interindividual variability in gonad characteristics. The well-furnished lecithotrophic larvae ofO. glabrumwould be capable of dispersing even under food-impoverished conditions. The current study examines ophiuroid reproductive biology over multiple localities in the CCZ concurrently for the first time, at sites characterised by differing productivity regimes. The reproductive biology of each species is thus discussed with reference to past evolutionary (habitat stability), contemporary (food supply) and future environmental drivers (potential impacts of deep-sea mining).
Speciation across the Earth driven by global cooling in terrestrial Orchids
Authors: Thompson Jamie B. , Davis Katie E. , Dodd Harry O. , Wills Matthew A. , Priest Nicholas K.
Published: February 2021

Though climate change has been implicated as a major catalyst of diversification, its effects are thought to be inconsistent and much less pervasive than localised climate or the accumulation of species with time. But, we need focused analyses of highly specious clades to disentangle the consequences of climate change, geography and time. Here, we show that global cooling shapes the biodiversity of terrestrial orchids. Employing a phylogenetic framework of 1,450 species of Orchidoideae, the largest terrestrial orchid subfamily, we find that speciation rate is causally linked with historic global cooling, not time, habitation in the tropics, altitude, variation in chromosome number, or other types of historic climate change. Relative to the gradual accumulation of species with time, models specifying speciation driven by historic global cooling are 328 times more likely. Evidence ratios estimated for 212 other plant and animal groups reveal that the orchidoids represent one of the best-supported cases of temperature-spurred speciation yet reported. Employing >1.4 M georeferenced records, we find that global cooling drove contemporaneous diversification in each of the seven major orchid bioregions of the earth. With current emphasis on understanding and predicting the immediate impacts of global warming, our study provides a clear case study of the longterm impacts of global climate change on biodiversity.

Significance statement

The staggering biodiversity of angiosperms has been difficult to reconcile with the gradual Darwinian process thought to create it. Changes in climate through the Earth’s history could have instigated this diversification, but perceived variability across clades and geography has restrained generalisation. In this paper, we reconstruct the evolutionary history of a rich terrestrial orchid subfamily favoured by Darwin (Orchidoideae, ~5,000 species), and use >1.4 million georeferenced records to test how and where those orchid species arose. We find that global cooling between the Oligocene and present day spurred an avalanche of speciation in orchidoid assemblages across the Earth. This work resolves the orchidoid phylogeny and provides a clear example of how historic climate change drives global patterns of biodiversity.
A clonal fresh water plants acquires transgenerational stress resistance under recurring copper excess
Authors: Huber Meret , Gablenz Saskia , Höfer Martin
Published: February 2021

Although non-genetic inheritance is thought to play an important role in plant ecology and evolution, evidence for adaptive transgenerational plasticity is scarce. Here, we investigated the consequences of copper excess on offspring defences and fitness in the giant duckweed (Spirodela polyrhiza) across multiple asexual generations. We found that exposing large monoclonal populations (>10,000 individuals) for 30 generations to copper excess decreased plant fitness during the first few generations but increased their fitness in consecutive generations under recurring stress when plants were grown for 5 generations under control conditions prior recurring conditions. Similarly, propagating individual plants as single descendants for 5 or 10 generations under copper excess decreased plant fitness when 5 generations and improved plant fitness when 10 generations passed between initial and recurring stress; thus, transgenerational stress responses likely contributed to the observed variations in offspring fitness of long-term copper exposed populations. Fitness benefits under recurring stress were partially associated with avoidance of excessive copper accumulation, which in turn correlated with transgenerationally modified flavonoid concentrations. Taken together, these data demonstrate time-dependent adaptive transgenerational responses under recurring stress, which highlights the importance of non-genetic inheritance for plant ecology and evolution.
Social selection is density dependent but makes little contribution to total selection in New Zealand giraffe weevils
Authors: Fisher David N , LeGrice Rebecca J , Painting Christina J
Published: February 2021

Social selection occurs when traits of interaction partners influence an individual’s fitness and can fundamentally alter total selection strength. Unlike for direct selection, however, we have little idea of what factors influence the strength of social selection. Further, social selection only contributes to overall selection when there is phenotypic assortment, but simultaneous estimates of social selection and phenotypic assortment are rare. Here we estimated social selection on body size in a wild population of New Zealand giraffe weevils (Lasiorhynchus barbicornis). We did this in a range of contexts and measured phenotypic assortment for both sexes. Social selection was mostly absent and not affected by sex ratio or the body size of the focal individual. However, at high densities selection was negative for both sexes, consistent with competitive interactions based on size for access to mates. Phenotypic assortment was also density dependent, flipping from positive at low densities to negative at high densities. However, it was always close to zero, indicating negative social selection at high densities will not greatly impede the evolution of larger body sizes. Despite its predicted importance, social selection may only influence evolutionary change in specific contexts, leaving direct selection as the dominant driver of evolutionary change.
The role of claw colouration in fiddler crabs’ mate choice: Private communication channel or handicap?
Authors: Silva Diogo Jackson Aquino , Erickson Marilia Fernandes , Guidi Raiane dos Santos , Pessoa Daniel Marques Almeida
Published: February 2021

Colour cues play an important role in sexual selection and conspecific recognition. Literature shows that conspecifics might enjoy their everyday chat, without ever worrying about occasional eavesdroppers (e.g., predators), when information interchange evolves into a private communication channel. Yet, when signalling is converted into foraging cues by predators, their prey must pay the due cost for sustaining conversation. For that matter, fiddler crabs draw attention for having flashy enlarged claws that could potentially attract the attention of many predators. Surprisingly, the costs associated with claw colouration in fiddler crabs are still poorly understood and have never been studied in American species. Here, we initially examine whether hypertrophied claws of American thin-fingered fiddler crabs (Leptuca leptodactyla) reflect UV-light and how conspecific females react to these cues. Then we test two alternative hypotheses concerning the role of claw colouration in fiddler crabs’ mate choice: a) that claw colouration evolved into a private communication channel, which could have significantly lowered signalling costs for males; b) that claw colouration is conspicuous to potential reproductive partners, as well as to predators, making colour signalling by males very costly (i.e., a handicap). Thereafter, we measured the reflectance spectra from several enlarged claws and modelled their chromatic contrast against the background spectrum, considering the visual systems of conspecific fiddler crabs and two kinds of predators (terns and plovers). We also tested female conspecifics’ preference towards enlarged claws that reflected UV-light or other colour cues, by artificially altering claw colouration. Our results show a clear female preference for UV reflecting males. We also found that natural enlarged claws should be highly detectable by avian predators, refuting the private communication channel hypothesis. Furthermore, since female fiddler crabs select the most flamboyant claws from the sandy background, claw colouration in fiddler crabs can be understood as an honest signal.

HIGHLIGHTS

The hypertrophied claws of maleLeptuca leptodactylareflect UV light.

Female fiddler crabs display a natural preference for UV light cues.

Conspicuous claws function as handicaps and may honestly signal individual quality.

Male enlarged claws are more conspicuous to birds than to crabs.

Our data refute the presence of a private communication channel inL. leptodactyla.
Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study
Authors: Batty G. David , Deary Ian J. , Gale Catharine R.
Published: February 2021

Background

Poorer performance on standard tests of cognitive function is related to an elevated risk of death from lower respiratory tract infections. Whether pre-pandemic measures of cognition are related to COVID-19 mortality is untested.

Methods

UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when a reaction time test was administered to the full sample, and verbal-numeric reasoning assessed in a subgroup. Death from COVID-19 was ascertained from participant linkage to a UK-wide national registry.

Results

Between April 1st and September 23rd 2020, there were 388 deaths (138 women) ascribed to COVID-19 in the 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the 180,198 (97,794 women) for whom there were data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation (118.2 msec) slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28). A one standard deviation disadvantage (2.16 point) on the verbal-numeric reasoning test was also associated with an elevated risk of death (1.32; 1.09, 1.59). Attenuation after adjustment for additional covariates followed a similar pattern for both measures of cognition. For verbal-numeric reasoning, for instance, the hazard ratios were 1.22 (0.98, 1.51) after control for socioeconomic status, 1.16 (0.96, 1.41) after lifestyle factors, 1.25 (1.04, 1.52) after co-morbidity, and 1.29 (1.01, 1.64) after physiological indices.

Conclusions

In the present study, poorer performance on two pre-pandemic indicators of cognitive function, including reaction time, a knowledge-reduced measure, was related to death ascribed to COVID-19.