bluuebunny/crossref_metadata_2025 huggingface dataset:
Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento
Authors: Stefanelli Paola , Bella Antonino , Fedele Giorgio , Fiore Stefano , Pancheri Serena , Benedetti Eleonora , Fabiani Concetta , Leone Pasqualina , Vacca Paola , Schiavoni Ilaria , Neri Arianna , Carannante Anna , Simmaco Maurizio , Santino Iolanda , Zuccali Maria Grazia , Bizzarri Giancarlo , Magnoni Rosa , Benetollo Pier Paolo , Brusaferro Silvio , Rezza Giovanni , Ferro Antonio
Published: November 2020

Background

There are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before.

Methods

All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID50) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA).

Findings

Overall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity.

Interpretation

A decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.
School-based screening and treatment may reduce P. falciparum transmission
Authors: Cohee Lauren M. , Valim Clarissa , Coalson Jenna E. , Nyambalo Andrew , Chilombe Moses , Ngwira Andrew , Bauleni Andy , Seydel Karl B. , Wilson Mark L. , Taylor Terrie E. , Mathanga Don P. , Laufer Miriam K.
Published: November 2020

In areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact of screening-and-treatment of asymptomatic schoolchildren (N=705) on gametocyte - the parasite stage responsible for human-to-mosquito transmission - carriage and use concomitant household-based surveys to predict the potential reduction in transmission in the surrounding community. Among 179 students with gametocyte-containing infections, 84% had positive malaria rapid diagnostic tests. While gametocyte burden remained constant in untreated children, treatment with artemether-lumefantrine reduced the gametocyte prevalence (p<0.0001) from 51.8% to 9.7% and geometric mean gametocyte density (p=0.008) from 0.52 to 0.05 gametocytes/microliter. Based on these estimates, the gametocyte burden in the community could be reduced by 25-55% depending on the season and the measure used to characterize gametocyte carriage. Thus, school-based interventions to treat asymptomatic infections may be a high-yield approach to not only improve the health and education of schoolchildren, but also decrease malaria transmission.
A computational analysis on Covid-19 transmission raises imuuno-epidemiology concerns
Authors: Kyriakopoulos Anthony M. , Zhao Shi
Published: November 2020

For Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) the investigation of the heterogeneity of individual infectiousness becomes important due to the cross reactive immunity of general population. Using a sample of infected population with SARS-COV-2 in close geographical proximity to the initial Severe Advanced Respiratory Syndrome-1 (SARS-1) outbreak, we explored the association between infector’s age and dispersion (or heterogeneity) of individual infectiousness (k) in order to investigate the relatedness with the age of an individual’s capability to disperse SARS-COV-2. Interestingly, we find a negative association between k and increase of infector’s age. Significantly this becomes more evident for the age group of 20-60 years comparing with the infectors with younger age. This raises important immuno-epidemiology concerns for effectiveness of public health measures to contain the disease.

One Sentence Summary

Dispersion of Coronavirus Disease-19 in China differed with age.
Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation
Authors: Ahmed Sheikh Rashel , Banik Anik , Anni Sadia Mahjabin , Chowdhury Mohammed Mehadi Hassan
Published: November 2020

The ZIKA virus has caused a heavy concern everywhere the globe because of its high infectivity and mortality rate. Still, there’s no specific drug or preventive medication to treat ZIKA infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant derived bioactive compounds against ZIKV by using both structure and ligand based virtual screening methods. A number of 35 plant metabolites were screened against ZIKA NS2B-NS3 protease (5LC0), Envelop protein (5JHM), Capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing molecular docking approach. Results showed that there have been four metabolites, i.e. Chicoric acid, Luteone, Reserpine and Rosmarinic acid provide highest binding affinity to targeted ZIKV proteins. Crucial binding sites and drug surface hotspots are unraveled for every targeted viral protein. The ADME study showed that neither of the candidate compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of top drug candidates. The RMSD values of ligand-macromolecule complexes were 2 Å apart from Envelop protein- Chicoric Acid, although the RMSF values showed normal atomic fluctuations within the molecular dynamics analysis, with the exception of Envelop protein- Chicoric Acid. The expected majority of the target class the highest drug candidates is enzyme classes (e.g. protease, hydrolase, phosphatase). In addition, the drug similarity prediction revealed several structural analogs from drugbank such as Isoformononetin (DB04202), Deserpidine (DB01089) and Rescinnamine (DB01180) etc. and these analogs could even be an option for the treatment of ZIKV infections. The study can pave the way for the creation of effective ZIKV medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings.
Pangenome-based genome inference
Authors: Ebler Jana , Clarke Wayne E. , Rausch Tobias , Audano Peter A. , Houwaart Torsten , Korbel Jan , Eichler Evan E. , Zody Michael C. , Dilthey Alexander T. , Marschall Tobias
Published: November 2020

Abstract

Typical analysis workflows map reads to a reference genome in order to detect genetic variants. Generating such alignments introduces references biases, in particular against insertion alleles absent in the reference and comes with substantial computational burden. In contrast, recent k-mer-based genotyping methods are fast, but struggle in repetitive or duplicated regions of the genome. We propose a novel algorithm, called PanGenie, that leverages a pangenome reference built from haplotype-resolved genome assemblies in conjunction with k-mer count information from raw, short-read sequencing data to genotype a wide spectrum of genetic variation. The given haplotypes enable our method to take advantage of linkage information to aid genotyping in regions poorly covered by unique k-mers and provides access to regions otherwise inaccessible by short reads. Compared to classic mapping-based approaches, our approach is more than 4× faster at 30× coverage and at the same time, reached significantly better genotype concordances for almost all variant types and coverages tested. Improvements are especially pronounced for large insertions (> 50bp), where we are able to genotype > 99.9% of all tested variants with over 90% accuracy at 30× short-read coverage, where the best competing tools either typed less than 60% of variants or reached accuracies below 70%. PanGenie now enables the inclusion of this commonly neglected variant type in downstream analyses.
A model of egocentric to allocentric understanding in mammalian brains
Authors: Uria Benigno , Ibarz Borja , Banino Andrea , Zambaldi Vinicius , Kumaran Dharshan , Hassabis Demis , Barry Caswell , Blundell Charles
Published: November 2020

In the mammalian brain, allocentric representations support efficient self-location and flexible navigation. A number of distinct populations of these spatial responses have been identified but no unified function has been shown to account for their emergence. Here we developed a network, trained with a simple predictive objective, that was capable of mapping egocentric information into an allocentric spatial reference frame. The prediction of visual inputs was sufficient to drive the appearance of spatial representations resembling those observed in rodents: head direction, boundary vector, and place cells, along with the recently discovered egocentric boundary cells, suggesting predictive coding as a principle for their emergence in animals. Strikingly, the network learned a solution for head direction tracking and stabilisation convergent with known biological connectivity. Moreover, like mammalian representations, responses were robust to environmental manipulations, including exposure to novel settings. In contrast to existing reinforcement learning approaches, agents equipped with this network were able to flexibly reuse learnt behaviours —adapting rapidly to unfamiliar environments. Thus, our results indicate that these representations, derived from a simple egocentric predictive framework, form an efficient basis-set for cognitive mapping.
TIGA: Target illumination GWAS analytics
Authors: Yang Jeremy J , Grissa Dhouha , Lambert Christophe G , Bologa Cristian G , Mathias Stephen L , Waller Anna , Wild David J , Jensen Lars Juhl , Oprea Tudor I
Published: November 2020

Genome wide association studies (GWAS) can reveal important genotype–phenotype associations, however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. Here, we describe rational ranking, filtering and interpretation of inferred gene–trait associations and data aggregation across studies by leveraging existing curation and harmonization efforts. Each gene–trait association is evaluated for confidence, with scores derived solely from aggregated statistics, linking a protein-coding gene and phenotype. We propose a method for assessing confidence in gene–trait associations from evidence aggregated across studies, including a bibliometric assessment of scientific consensus based on the iCite Relative Citation Ratio, and meanRank scores, to aggregate multivariate evidence. This method, intended for drug target hypothesis generation, scoring and ranking, has been implemented as an analytical pipeline, available as open source, with public datasets of results, and a web application designed for usability by drug discovery scientists, athttps://unmtid-shinyapps.net/tiga/.
Detection and Purification of Lewy Pathology from Formalin Fixed Primary Human Tissue Using Biotinylation by Antigen Recognition
Authors: Killinger BA , Marshall L , Chatterjee D , Chu Y , Kordower JH
Published: November 2020

The intracellular misfolding and accumulation of alpha-synuclein into structures collectively called Lewy pathology is a central phenomenon for the pathogenesis of Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy. Understanding the molecular architecture of Lewy pathology is crucial for understanding disease origins and progression. Here we developed a method to label, extract, and purify molecules from Lewy pathology of formalin fixed PD and DLB brain for blotting and mass spectrometry analysis. Using the biotinylation antibody recognition (BAR) technique, we labeled phosphoserine 129 alpha-synuclein positive pathology and associated molecules with biotin. Formalin crosslinks were then reversed, protein extracted, and pathology associated molecules isolated with streptavidin beads. Results showed superior immunohistochemical staining of Lewy pathology following the BAR protocol when compared to standard avidin biotin complex (ABC) based detection. The enhanced staining was particularly apparent for fibers of the medial forebrain bundle and punctate pathology within the striatum and cortex, which otherwise were weakly labeled or not detected. Subsequent immunoblotting BAR-labeled Lewy pathology extracts revealed the presence of high molecular weight alpha-synuclein, ubiquitin protein conjugates, and phosphoserine 129 alpha-synuclein. Mass spectrometry analysis of BAR-labeled Lewy pathology extracts from PD and DLB patients identified 815 proteins with significant enrichment for many pathways. Notably the most significant KEGG pathway was Parkinson’s disease (FDR = 2.48 × 10−26) and GO Cellular compartment was extracellular exosomes (GO Cellular Compartment; FDR = 2.66× 10−34). We used enrichment data to create a functional map of Lewy Pathology from primary disease tissues, which implicated Vesicle Trafficking as the primary disease associated pathway in DLB and PD. In summary, this protocol can be used to enrich for Lewy pathology from formalin fixed human primary tissues, which allows the determination of molecular signatures of Lewy pathology. This technique has broad potential to help understand the phenomenon of Lewy pathology in primary human tissue and animal models.
VGLUT modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration
Authors: Buck Silas A. , Steinkellner Thomas , Aslanoglou Despoina , Villeneuve Michael , Bhatte Sai H. , Childers Victoria C. , Rubin Sophie A. , De Miranda Briana R. , O’Leary Emma I. , Neureiter Elizabeth G. , Fogle Keri J. , Palladino Michael J. , Logan Ryan W. , Glausier Jill R. , Fish Kenneth N. , Lewis David A. , Greenamyre J. Timothy , Bonci Antonello , McCabe Brian D. , Cheetham Claire E. J. , Hnasko Thomas S. , Freyberg Zachary
Published: November 2020

Age is the greatest risk factor for Parkinson’s disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. We found that vesicular glutamate transporter (VGLUT) expression mediates vulnerability to age-related DA neurodegeneration in a sex-dependent manner, providing a new mechanism for sex differences in selective DA neuron vulnerability. These findings lay the groundwork for novel therapeutic strategies to boost neuronal resilience throughout aging.
Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach
Authors: An Hyunsu , Park Jihwan
Published: November 2020

Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available athttps://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
Identification of a Putative Sensor Protein Involved in Regulation of Vesicle Production by a Hypervesiculating Bacterium,Shewanella vesiculosaHM13
Authors: Yokoyama Fumiaki , Imai Tomoya , Aoki Wataru , Ueda Mitsuyoshi , Kawamoto Jun , Kurihara Tatsuo
Published: November 2020

Bacteria secrete and utilize nanoparticles, called extracellular membrane vesicles (EMVs), for survival in their growing environments. Therefore, the amount and components of EMVs should be tuned in response to the environment. However, how bacteria regulate vesiculation in response to the extracellular environment remains largely unknown. In this study, we identified a putative sensor protein, HM1275, involved in the induction of vesicle production in a hypervesiculating Gram-negative bacterium,Shewanella vesiculosaHM13. This protein was predicted to possess typical sensing and signaling domains of sensor proteins, such as methyl-accepting chemotaxis proteins. Comparison of vesicle production between thehm1275-disrupted mutant and the parent strain revealed that HM1275 is involved in lysine-induced hypervesiculation. Moreover, HM1275 has sequence similarity to a biofilm dispersion protein, BdlA, ofPseudomonas aeruginosaPAO1, andhm1275disruption increased the amount of biofilm. Thus, this study showed that the induction of vesicle production and suppression of biofilm formation in response to lysine concentration are under the control of the same putative sensor protein.
Shapes and Genescapes: Mapping Multivariate Phenotype-Biological Process Associations for Craniofacial Shape
Authors: Aponte J. David , Katz David C. , Roth Daniela M. , Garcia Marta Vidal , Liu Wei , Andrade Fernando , Roseman Charles C. , Murray Stephen A. , Cheverud James , Graf Daniel , Marcucio Ralph S. , Hallgrímsson Benedikt
Published: November 2020

Realistic mappings of genes to morphology are inherently multivariate on both sides of the equation. The importance of coordinated gene effects on morphological phenotypes is clear from the intertwining of gene actions in signaling pathways, gene regulatory networks, and developmental processes underlying the development of shape and size. Yet, current approaches tend to focus on identifying and localizing the effects of individual genes and rarely leverage the information content of high dimensional phenotypes. Here, we explicitly model the joint effects of biologically coherent collections of genes on a multivariate trait—craniofacial shape — in a sample ofn= 1,145 mice from the Diversity Outbred (DO) experimental line. We use biological process gene ontology (GO) annotations to select skeletal and facial development gene sets and solve for the axis of shape variation that maximally covaries with gene set marker variation. We use our process-centered, multivariate genotype-phenotype (MGP) approach to determine the overall contributions to craniofacial variation of genes involved in relevant processes and how variation in different processes corresponds to multivariate axes of shape variation. Further, we compare the directions of effect in phenotype space of mutations to the primary axis of shape variation associated with broader pathways within which they are thought to function. Finally, we leverage the relationship between mutational and pathway-level effects to predict phenotypic effects beyond craniofacial shape in specific mutants. We also introduce an online application which provides users the means to customize their own process-centered craniofacial shape analyses in the DO. The process-centered approach is generally applicable to any continuously varying phenotype and thus has wide-reaching implications for complex-trait genetics.
Neuraminidase inhibitors rewire neutrophil functionin vivoin murine sepsis andex vivoin COVID-19
Authors: de Oliveira Formiga Rodrigo , Amaral Flávia C. , Souza Camila F. , Mendes Daniel A. G. B. , Wanderley Carlos W. S. , Lorenzini Cristina B. , Santos Adara A. , Antônia Juliana , Faria Lucas F. , Natale Caio C. , Paula Nicholas M. , Silva Priscila C. S. , Fonseca Fernanda R. , Aires Luan , Heck Nicoli , Starick Márick R. , Queiroz-Junior Celso M. , Santos Felipe R. S. , de Souza Filipe R. O. , Costa Vivian V. , Barroso Shana P. C. , Morrot Alexandre , Van Weyenbergh Johan , Sordi Regina , Alisson-Silva Frederico , Cunha Fernando Q. , Rocha Edroaldo L. , Chollet-Martin Sylvie , Hurtado-Nedelec Maria Margarita , Martin Clémence , Burgel Pierre-Régis , Mansur Daniel S. , Maurici Rosemeri , Macauley Matthew S. , Báfica André , Witko-Sarsat Véronique , Spiller Fernando
Published: November 2020

Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils.In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections.

At a Glance

In a severe systemic inflammatory response, such as sepsis and COVID-19, neutrophils play a central role in organ damage. Thus, finding new ways to inhibit the exacerbated response of these cells is greatly needed. Here, we demonstrate thatin vitrotreatment of whole blood with the viral neuraminidase inhibitors Oseltamivir or Zanamivir, inhibits the activity of human neuraminidases as well as the exacerbated response of neutrophils. In experimental models of severe sepsis, oseltamivir decreased neutrophil activation and increased the survival rate of mice. Moreover, Oseltamivir or Zanamivirex vivotreatment of whole blood cells from severe COVID-19 patients rewire neutrophil function.
Conformational dynamics regulate SHANK3 actin and Rap1 binding
Authors: Salomaa Siiri I , Miihkinen Mitro , Kremneva Elena , Paatero Ilkka , Lilja Johanna , Jacquemet Guillaume , Vuorio Joni , Antenucci Lina , Hassani-Nia Fatemeh , Hollos Patrik , Isomursu Aleksi , Vattulainen Ilpo , Coffey Eleanor T. , Kreienkamp Hans-Jürgen , Lappalainen Pekka , Ivaska Johanna
Published: November 2020

Actin-rich cellular protrusions direct versatile biological processes from cancer cell invasion to dendritic spine development. The stability, morphology and specific biological function of these protrusions are regulated by crosstalk between three main signaling axes: integrins, actin regulators and small GTPases. SHANK3 is a multifunctional scaffold protein, interacting with several actin-binding proteins, and a well-established autism risk gene. Recently, SHANK3 was demonstrated to sequester integrin-activating small GTPases Rap1 and R-Ras to inhibit integrin activity via its N-terminal SPN domain. Here, we demonstrate that SHANK3 interacts directly with actin using its SPN domain. Actin binding can be inhibited by an intramolecular closed conformation of SHANK3, where the adjacent ARR domain covers the actin-binding interface of the SPN domain. Actin and Rap1 compete with each other for binding to SHANK3 and loss of SHANK3-actin binding augments inhibition of Rap1-mediated integrin activity. This dynamic crosstalk has functional implications for filopodia formation in cancer cells, dendritic spine morphology in neurons and autism-linked phenotypesin vivo.
Pipefish locally adapted to low salinity in the Baltic Sea retain phenotypic plasticity to cope with ancestral salinity levels
Authors: Goehlich Henry , Sartoris Linda , Wagner Kim Sara , Wendling Carolin C. , Roth Olivia
Published: November 2020

Genetic adaptation and phenotypic plasticity facilitate the invasion of new habitats and enable organisms to cope with a rapidly changing environment. In contrast to genetic adaptation that spans multiple generations as an evolutionary process, phenotypic plasticity allows acclimation within the life-time of an organism. Genetic adaptation and phenotypic plasticity are usually studied in isolation, however, only by including their interactive impact, we can understand acclimation and adaptation in nature. We aimed to explore the contribution of adaptation and plasticity in coping with an abiotic (salinity) and a biotic (Vibrio bacteria) stressor using six different populations of the broad-nosed pipefish Syngnathus typhle that originated from either high or low saline environments. We hypothesized that wild S. typhle populations are locally adapted to the salinity and prevailing pathogens of their native environment, and that short-term acclimation of parents to a novel salinity may aid in buffering offspring phenotypes in a matching environment. To test these hypotheses, we exposed all wild caught animals, to either high or low salinity, representing native and novel salinity conditions and allowed animals to mate. After male pregnancy, offspring was split and each half was exposed to one of the two salinities and infected with Vibrio alginolyticus bacteria that were evolved at either of the two salinities in a fully reciprocal design. We investigated life history traits of fathers (offspring survival, offspring size) and expression of 47 target genes in mothers and offspring.

Pregnant males originating from high salinity exposed to low salinity were highly susceptible to opportunistic fungi infections resulting in decreased offspring size and number. In contrast, no signs of fungal infection were identified in fathers originating from low saline conditions suggesting that genetic adaptation has the potential to overcome the challenging conditions of low salinity. Genetic adaptation increased survival rates of juveniles from parents in lower salinity (in contrast to those from high salinity). Juvenile gene expression indicated patterns of local adaptation, trans-generational plasticity and developmental plasticity. The results of our study suggest that pipefish locally adapted to low salinity retain phenotypic plasticity, which allows them to also cope with ancestral salinity levels and prevailing pathogens.
Mental Health Status of Adolescents During the COVID-19 Pandemic: A Cross-sectional Survey among the Bangladeshi Graduate Students at Dhaka City
Authors: Husain Taha , Uddin Mohammad Main , Chowdhury Saber Ahmed , Kalimullah Nazmul Ahsan
Published: November 2020

Objectives

To identify the level of Mental Health Status of Adolescents During the COVID-19 Pandemic among the Bangladeshi Graduate Student at Dhaka

Method

A cross-sectional survey was conducted with 330 students from different public and Private Universities in Dhaka, Bangladesh between April 01, 2020 and July 31, 2020 amid the COVID-19 lockdown period in Bangladesh. A standard, self-administered online questionnaire consisting of questions on socio-demographic variables, mental health status, as well as stress management sent to the respondents through social networking platforms. Data were analyzed using descriptive statistics, t-test, one-way ANOVA and correlation tests.

Results

The mean score of mental health status was 2.08 based on four points scale. They felt problem in decision making (3.04), in doing the things well (2.92), in enjoying normal day to day life (2.88), in playing a useful part in life (2.85), in doing their task (2.75), living in perfectly well and in good health (2.70). The respondents also developed a suicidal tendency (2.55), felt nervous in strung-up (2.24), took longer time to do things (2.14), felt tightness and pressure in head (2.12), and found themselves pressurized by various stuff (2.05). This study also found a significant positive relationship between mental health status and age, living with parents, and parents’ attitude. Finally, this study revealed that the respondents managed their stress by chatting with their friends, parents and siblings, and by sleeping.

Conclusion

Mental health status of adolescents was found moderate in this study. This study suggests further large-scale study including different socio-economic settings in order to figure out the real scenario of adolescents’ mental health status of the country during the pandemic.
Oxygen-dependent changes in HIF binding partners and post-translational modifications regulate stability and transcriptional activity
Authors: Daly Leonard , Brownridge Philip J. , Sée Violaine , Eyers Claire E.
Published: November 2020

Adaption of cells to low oxygen environments is an essential process mediated in part by the Hypoxia Inducible Factors (HIFs). Like other transcription factors, the stability and transcriptional activity of HIFs, and consequently the hypoxic response, are regulated by post-translational modification (PTM) and changes in biomolecular interactions. However, our current understanding of PTM-mediated regulation of HIFs is primarily based on in vitro protein fragment-based studies, with validation typically having been conducted by in cellulo fragment expression and hypoxia mimicking drugs. Consequently, we still lack an understanding of true oxygen deprivation signaling via HIFα. Using an immunoprecipitation-based, mass spectrometry approach, we characterize the regulation of in cellulo expressed full-length HIF-1α and HIF-2α, in terms of both PTM and binding partners, in response to normoxia (21% oxygen) and hypoxia (1% oxygen). These studies revealed that a change in oxygen tension significantly alters the complexity and composition of HIF-α protein interaction networks, with HIF-2α in particular having an extended hypoxia-induced interactome, most notably with mitochondrial-associated proteins. Both HIFα isoforms are heavily covalently modified: we define ~40 different sites of PTM on each of HIF-1α and HIF-2α, comprising 13 different PTM types, including multiple cysteine modifications and a highly unusual phosphocysteine. Over 80% of the PTMs identified are novel, and approximately half exhibit oxygen-dependency under these conditions. Combined with domain and evolutionary analysis of >225 vertebrate species, we validate Ser31 phosphorylation on HIF-1α as a regulator of transcription, and propose functional roles for Thr406, Thr528 and Ser581 on HIF-2α.
Identifying and prioritizing potential human-infecting viruses from their genome sequences
Authors: Mollentze Nardus , Babayan Simon A. , Streicker Daniel G.
Published: November 2020

Determining which animal viruses may be capable of infecting humans is currently intractable at the time of their discovery, precluding prioritization of high-risk viruses for early investigation and outbreak preparedness. Given the increasing use of genomics in virus discovery and the otherwise sparse knowledge of the biology of newly-discovered viruses, we developed machine learning models that identify candidate zoonoses solely using signatures of host range encoded in viral genomes. Within a dataset of 861 viral species with known zoonotic status, our approach outperformed models based on the phylogenetic relatedness of viruses to known human-infecting viruses (AUC = 0.773), distinguishing high-risk viruses within families that contain a minority of human-infecting species and identifying putatively undetected or so far unrealized zoonoses. Analyses of the underpinnings of model predictions suggested the existence of generalisable features of viral genomes that are independent of virus taxonomic relationships and that may preadapt viruses to infect humans. Our model reduced a second set of 645 animal-associated viruses that were excluded from training to 272 high and 41 very high-risk candidate zoonoses and showed significantly elevated predicted zoonotic risk in viruses from non-human primates, but not other mammalian or avian host groups. A second application showed that our models could have identified SARS-CoV-2 as a relatively high-risk coronavirus strain and that this prediction required no prior knowledge of zoonotic SARS-related coronaviruses. Genome-based zoonotic risk assessment provides a rapid, low-cost approach to enable evidence-driven virus surveillance and increases the feasibility of downstream biological and ecological characterisation of viruses.
96-Well Oxygen Control Using a 3D-Printed Device
Authors: Szmelter Adam , Jacob Jason , Eddington David
Published: November 2020

Oxygen concentration varies tremendously within the body and has proven to be a critical variable in cell differentiation, proliferation, and drug metabolism among many other physiological processes. Currently, researchers study the gas’s role in biology using low-throughput gas-control incubators or hypoxia chambers in which all cells in a vessel are exposed to a single oxygen concentration. Here, we introduce a device which can simultaneously deliver 12 unique oxygen concentrations to cells in a 96-well plate and seamlessly integrate into biomedical research workflows. The device inserts into 96-well plates and delivers gas to the headspace thus avoiding undesirable contact with media. This simple approach isolates each well using gas-tight pressure resistant gaskets effectively creating 96 “mini-incubators”. Each of the twelve columns of the plate is supplied by a distinct oxygen concentration from a gas-mixing gradient generator supplied by two feed gases. The wells within each column are then supplied by an equal flow-splitting distribution network. Using equal feed flow rates, concentrations ranging from 0.6% to 20.5% were generated within a single plate. A549 lung carcinoma cells were then used to show that O2levels below 9% caused a stepwise increase in cell death for cells treated with the hypoxia-activated anti-cancer drug Tirapirizamine (TPZ). Additionally, the 96-well plate was further leveraged to simultaneously test multiple TPZ concentrations over an oxygen gradient and generate a 3D dose response landscape. The results presented here show how microfluidic technologies can be integrated into, rather than replace, ubiquitous biomedical labware allowing for increased throughput oxygen studies.
New Insights and Enhanced Human Norovirus Cultivation in Human Intestinal Enteroids
Authors: Ettayebi Khalil , Tenge Victoria R , Cortes-Penfield Nicolas W. , Crawford Sue E. , Neill Frederick H. , Zeng Xi-Lei , Yu Xiaomin , Ayyar B. Vijayalakshmi , Burrin Douglas , Ramani Sasirekha , Atmar Robert L. , Estes Mary K.
Published: November 2020

Human noroviruses (HuNoVs) are the leading cause of epidemic and sporadic acute gastroenteritis worldwide. We previously demonstrated human intestinal stem cell-derived enteroids (HIEs) support cultivation of several HuNoV strains. However, HIEs did not support virus replication from every HuNoV-positive stool sample, which led us to test and optimize new media conditions, identify characteristics of stool samples that allow replication, and evaluate consistency of replication over time. Optimization of our HIE-HuNoV culture system has shown that: 1) A new HIE culture media made with conditioned medium from a single cell line and commercial media promote robust replication of HuNoV strains that replicated poorly in HIEs grown in our original culture media made with conditioned media from 3 separate cell lines; 2) GI.1, eleven GII genotypes (GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.8, GII.12, GII.13, GII.14 and GII.17) and six GII.4 variants, can be cultivated in HIEs; 3) successful replication is more likely with virus in stools with higher virus titers; 4) GII.4_Sydney_2012 virus replication was reproducible over three years; and 5) HuNoV infection is restricted to the small intestine, based on replication in duodenal and ileal HIEs but not colonoids from the same donors. These results improve the HIE culture system for HuNoV replication. Use of HIEs by several laboratories worldwide to study the molecular mechanisms that regulate HuNoV replication confirms the usefulness of this culture system and our optimized methods for virus replication will advance the development of effective therapies and methods for virus control.

Importance

Human noroviruses (HuNoVs) are highly contagious and cause acute and sporadic diarrheal illness in all age groups. In addition, chronic infections occur in immunocompromised cancer and transplant patients. These viruses are antigenically and genetically diverse and there are strain-specific differences in binding to cellular attachment factors. In addition, new discoveries are being made on strain-specific differences in virus entry and replication and the epithelial cell response to infection in human intestinal enteroids. Human intestinal enteroids are a biologically-relevant model to study HuNoVs; however, not all strains can be cultivated at this time. A complete understanding of HuNoV biology thus requires cultivation conditions that will allow the replication of multiple strains. We report optimization of HuNoV cultivation in human intestinal enteroid cultures to increase the numbers of cultivatable strains and the magnitude of replication, which is critical for testing antivirals, neutralizing antibodies and methods of virus inactivation.
Non-transmissibility of Pepper whitefly borne vein yellows virus (PeWBVYV) by the Mediterranean species ofBemisia tabaciand identification of a candidate insect receptor protein for poleroviruses
Authors: Ghosh Saptarshi , Bello Vinicius Henrique , Ghanim Murad
Published: November 2020

Recent reports of transmission of poleroviruses by whiteflies is indicative of evolution of new virus-vector relationships. Pepper whitefly-borne vein yellows virus (PeWBVYV), was the first report of a polerovirus infecting pepper in Israel which was transmitted by whiteflies (MEAM1) and not aphids. This study reports the inability of the Mediterranean species (MED, Q biotype) ofB. tabacito transmit PeWBVYV. However we show that non-transmission of PeWBVYV by MED is not due to the lack of interaction with the GroEL protein of theHamiltonellasymbiont. Although not transmitted by MED, PeWBVYV was detected in its hemolymph, indicating its translocation across the MED midgut barrier. The aphid transmittedPepper vein yellows virus 2(PeVYV-2) was also detected in the hemolymph of MEAM1 whiteflies but PeWBVYV could not be detected in the aphid hemolymph. Interestingly, relative amounts of PeWBVYV in the hemolymph of the, MED was much lower than in hemolymph of MEAM1 whiteflies. We also identified a candidate receptor protein, complement component 1Q sub-complement binding protein (C1QBP) which interacts with the capsid proteins of PeWBVYV and PeVYV-2 but not with the whitefly transmittedTomato yellow leaf curl virusby a yeast two-hybrid approach using the minor capsid protein (RTD) as bait to screen for interacting proteins against the whitefly cDNA library. C1QBP, is a known receptor of bacterial and viral pathogens but this is the first report of its interaction with a plant virus.
Nucleotide-resolution bacterial pan-genomics with reference graphs
Authors: Colquhoun Rachel M , Hall Michael B , Lima Leandro , Roberts Leah W , Malone Kerri M , Hunt Martin , Letcher Brice , Hawkey Jane , George Sophie , Pankhurst Louise , Iqbal Zamin
Published: November 2020

Background

Bacterial genomes follow a U-shaped frequency distribution whereby most genomic loci are either rare (accessory) or common (core); the union of these is the pan-genome. The alignable fraction of two genomes from a single species can be low (e.g. 50-70%), such that no single reference genome can access all single nucleotide polymorphisms (SNPs). The pragmatic solution is to choose a close reference, and analyse SNPs only in the core genome. Given much bacterial adaptability hinges on the accessory genome, this is an unsatisfactory limitation.

Results

We present a novel pan-genome graph structure and algorithms implemented in the softwarepandora, which approximates a sequenced genome as a recombinant of reference genomes, detects novel variation and then pan-genotypes multiple samples. The method takes fastq as input and outputs a multi-sample VCF with respect to an inferred data-dependent reference genome, and is available athttps://github.com/rmcolq/pandora.

Constructing a reference graph from 578E. coligenomes, we analyse a diverse set of 20E. coliisolates. We showpandorarecovers at least 13k more rare SNPs than single-reference based tools, achieves equal or better error rates with Nanopore as with Illumina data, 6-24x lower Nanopore error rates than other tools, and provides a stable framework for analysing diverse samples without reference bias. We also show that our inferred recombinant VCF reference genome is significantly better than simply picking the closest RefSeq reference.

Conclusions

This is a step towards comprehensive cohort analysis of bacterial pan-genomic variation, with potential impacts on genotype/phenotype and epidemiological studies.
Long-read RNA sequencing reveals widespread sex-specific alternative splicing in threespine stickleback fish
Authors: Naftaly Alice S. , Pau Shana , White Michael A.
Published: November 2020

Alternate isoforms contribute immensely to phenotypic diversity across eukaryotes. While short read RNA-sequencing has increased our understanding of isoform diversity, it is challenging to accurately detect full-length transcripts, preventing the identification of many alternate isoforms. Long-read sequencing technologies have made it possible to sequence full length alternative transcripts, accurately characterizing alternative splicing events, alternate transcription start and end sites, and differences in UTR regions. Here, we utilize PacBio long read RNA-sequencing (Iso-Seq) to examine the transcriptomes of five tissues in threespine stickleback fish (Gasterosteus aculeatus), a widely used genetic model species. The threespine stickleback fish has a refined genome assembly with gene annotations that are based on short-read RNA sequencing and predictions from coding sequence of other species. This suggests some of the existing annotations may be inaccurate or alternative transcripts may not be fully characterized. Using Iso-Seq we detected thousands of novel isoforms, indicating many isoforms are absent in the current Ensembl gene annotations. In addition, we refined many of the existing annotations within the genome. We noted many improperly positioned transcription start sites that were refined with long-read sequencing. The Iso-Seq predicted transcription start sites were more accurate, verified through ATAC-seq. We were also able to detect many alternative splicing events between sexes and across tissues. We found a substantial number of genes in both somatic and gonad tissue that had sex-specific isoforms. Our study highlights the power of long-read sequencing to study the complexity of transcriptomes, greatly improving genomic resources for the threespine stickleback fish.
Tracking the Movement of Electronic Cigarette Flavor Chemicals and Nicotine from Refill Fluids to Aerosol, Lungs and Exhale
Authors: Khachatoorian Careen , McWhirter Kevin J. , Luo Wentai , Pankow James F. , Talbot Prue
Published: November 2020

Electronic cigarettes (ECs) have been linked to lung diseases, including COVID-19, with little understanding of exposure, retention, and exhalation of EC aerosol chemicals. Here, flavor chemicals and nicotine were quantified in two refill fluids, their transfer efficiency to EC aerosols was determined, exhalation by human participants was measured, and chemical retention was modeled. Nicotine transferred well to aerosols irrespective of topography; however, transfer efficiencies of flavor chemicals depended on the chemical, puff volume, puff duration, pump head, and EC power. Participants could be classified as “mouth inhalers” or “lung inhalers” based on their retention and exhale of flavor chemicals and nicotine. Only mouth inhalers exhaled sufficient concentrations of flavor chemicals and nicotine to contribute to chemical deposition on environmental surfaces. These data help distinguish two types of EC users, add to our knowledge of chemical exposure during vaping, and provide information useful in treating EC-related diseases and regulating EC use.
Flexible loans and access to agricultural credit for smallholder farmers in Kenya
Authors: Odhiambo Fredrick Onyango , Upadhyaya Radha
Published: November 2020

Purpose

The purpose of this paper is to determine the level of flexibility in loan products offered to smallholder farmers in Siaya County in Kenya and to examine the effect of flexibility on access to credit.

Design/methodology/approach

The paper uses primary survey data from a sample of smallholder farmers in Siaya County in Kenya who had borrowed from various lending institutions within the study area. The paper develops an index variable of loan flexibility using multiple correspondence analysis (MCA) technique. The model is estimated using both OLS and truncated regression analyses. Access to credit is measured as the amount of loan borrowed by each farmer.

Findings

The authors find that the level of flexibility of loans offered to farmers is low. Furthermore, the authors find that the level of flexibility is not significantly correlated to access to credit. Further analysis using individual components of flexible loans show that refinancing and lines of credit are more likely to improve access to credit when farmers are more educated and wealthier, respectively. The age of a farmer, the type of lender, the type of loan, education and household wealth are the main determinants of access to credit.

Originality/value

The paper adds to the debate on access to credit by showing that theoretically, while loan flexibility should lead to higher credit access, this is not a key determinant of access to credit in this context.