bluuebunny/crossref_metadata_2025 huggingface dataset:
The Polls—Trends
Authors: Holman Mirya R , Kalmoe Nathan P
Published: July 2021

Attitudes about sexual harassment in the United States are multifaceted and have shifted over time. This article examines a quarter century of public opinion trends from several major national surveys. The polls reveal the complexity and dynamism of these views amidst broader societal changes involving gender and views of discrimination. While perceptions of sexual harassment as a problem have dramatically shifted, some questions suggest that public interest ebbs and flows with national political events. This article also documents small gaps between women and men on these views and large gaps between Democrats and Republicans. While recent national attention has increased the survey record on sexual harassment attitudes, inconsistent question wording and temporal gaps between relevant surveys have led to uneven metrics over time.
Moral Geographies of Care across Borders: The Experience of Migrant Grandparents in Australia
Authors: Hamilton Myra , Hill Elizabeth , Kintominas Angela
Published: July 2021

Literature on transnational grandparenting rarely focuses on how migrant grandparents contribute to the work/care reconciliation of their adult children, how they provide and receive care in contexts of mobility and precariousness, and the ways in which this is shaped by migration and social policy regimes. Drawing on the concept of moral geographies of care, this study reveals how idealized norms of care interact with Australian migration and work/care regimes in complex and contradictory ways to produce configurations of care in migrant families. We conclude that migration and work/care regimes are poorly aligned, compromising migrant families’ well-being and economic security.
BlitzkriegAgainst Democracy: Gender Equality and the Rise of the Populist Radical Right in Spain
Authors: Alonso Alba , Espinosa-Fajardo Julia
Published: July 2021

Populist radical right parties (PRRPs) are generally considered detrimental to democracy. Research on their damaging potential tends to focus on their influence in triggering policy backsliding but leaves the promotion of gender equality out of the equation. This study explores the case of Vox in Andalusia, a southern region of Spain, to show how PRRPs also contribute to de-democratization through their capacity to erode the equality framework. We demonstrate how they can effectively dismantle and reframe crucial policies, even when not in office. This opens new analytical pathways for studying the role of PRRPs in undermining democratic systems.
Prevalence of Strongyloides stercoralis in the immunocompetent and immunocompromised individuals in Iran: a systematic review and meta-analysis
Authors: Eslahi Aida Vafae , Olfatifar Meysam , Houshmand Elham , Johkool Morteza Ghanbari , Zibaei Mohammad , Foroutan Masoud , Hosseini Hamid , Badri Milad
Published: July 2021

Strongyloidiasis is a neglected tropical disease mostly distributed in tropical and subtropical regions. The current study evaluated the prevalence of Strongyloides stercoralis in immunocompetent and immunodeficient patients in Iran. The available online literature published from June 1994 to October 2020 was obtained from multiple English databases (PubMed, Science Direct, Scopus, Web of Science and Google Scholar) and four Persian databases (Magiran, Iran Medex, Iran Doc and SID). All statistical analyses were performed using R software (version 3.6) meta-package and p-values <0.05 were considered significant. From 1051 articles, 74 studies (248 656 individuals) met the inclusion criteria. The pooled prevalence of S. stercoralis was 2% (95% confidence interval [CI] 1 to 3) and 4% (95% CI 1 to 8) in immunocompetent and immunodeficient patients, respectively. In immunodeficient cases, the pooled prevalence of studies utilizing serology, culture and microscopic methods was 10% (95% CI 2 to 23), 1% (95% CI 0 to 6) and 1% (95% CI 0 to 1), respectively. In immunocompetent cases, the pooled prevalence of studies utilizing microscopic, culture and molecular methods was 2% (95% CI 1 to 3), 2% (95% CI 1 to 4) and 2% (95% CI 0 to 6), respectively. We propose an appropriate screening and control program along with comprehensive research regarding the frequency of strongyloidiasis in the country.
The interaction of the severe acute respiratory syndrome coronavirus 2 spike protein with drug-inhibited angiotensin converting enzyme 2 studied by molecular dynamics simulation
Authors: Nami Babak , Ghanaeian Avrin , Ghanaeian Kasra , Houri Rozhin , Nami Negin , Ghasemi-Dizgah Armin , Caluseriu Oana
Published: July 2021

Background:

Hypertension has been identified as the most common comorbidity in coronavirus disease 2019 (COVID-19) patients, and has been suggested as a risk factor for COVID-19 disease outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host human cells via binding to host cell angiotensin-converting enzyme 2 (ACE2) receptors. Inhibition of ACE2 has been proposed as a potential therapeutic approach to block SARS-CoV-2 contagion. However, some experts suggest that ACE2 inhibition could worsen the infection. Here, we aimed to study the effect of ACE2 inhibition on the SARS-CoV-2 spike protein binding to ACE2.

Method:

Crystallographic structures of the SARS-CoV-2 spike protein, the spike receptor-binding domain, native ACE2, and the ACE2 complexed with MLN-4760 were used as the study model structures. The spike proteins were docked to the ACE2 structures and the dynamics of the complexes, ligand–protein, and protein–protein interactions were studied by molecular dynamics simulation for 100 ns.

Results:

Our result showed that inhibition of ACE2 by MLN-4760 increased the affinity of the SARS-CoV-2 spike protein binding to ACE2. Results also revealed that spike protein binding to the ACE2 inhibited by MLN-4760 restored the enzymatic active conformation of the ACE2 from closed/inactive to open/active conformation by removing MLN-4760 binding from the ligand-binding pocket of ACE2.

Conclusion:

We conclude that using ACE2 inhibitors can increase the risk of SARS-CoV-2 infection and worsen COVID-19 disease outcome. We also found that the SARS-CoV-2 can abrogate the function of ACE2 inhibitors and rescue the enzymatic activity of ACE2. Therefore, ACE2 inhibition is not a useful treatment against COVID-19 infection.
Streptomyces acididurans sp. nov., isolated from peat swamp forest soil
Authors: Chantavorakit Tanatorn , Klaysubun Chollachai , Duangmal Kannika
Published: July 2021

A novel actinomycete, designated strain KK5PA1T, was isolated from a soil sample collected from Kuan Kreng peat swamp forest, Nakhon Si Thammarat Province, Thailand. The morphological, chemotaxonomic and phylogenetic characteristics were consistent with its classification in the genus

Streptomyces

. Strain KK5PA1T was most closely related to

Streptomyces bryophytorum

NEAU-HZ10T (98.0 %) and

Streptomyces guanduensis

701T (97.6 %). The G+C content of the genomic DNA was 72.3 mol%. Digital DNA–DNA hybridization and average nucleotide identity values between the genome sequence of strain KK5PA1T and those of

S. bryophytorum

DSM 42138T(25.1 and 79.1 %) and

S. guanduensis

DSM 41944T(25.1 and 79.7%) were below the thresholds of 70 and 96 % for prokaryotic conspecific assignation. Chemotaxonomic data revealed that strain KK5PA1T possessed MK-9(H6) and MK-9(H8) as the predominant menaquinones. It contained ll
-diaminopimelic acid as the diagnostic diamino acid and galactose, glucose, mannose and ribose as whole-cell sugars. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, two unidentified aminolipids, five unidentified phospholipids and an unidentified lipid. The predominant cellular fatty acids were iso-C16 : 0, anteiso-C15 : 0 and C16 : 0. On the basis of these genotypic and phenotypic data, it is proposed that strain KK5PA1T represents a novel species of the genus

Streptomyces

, for which the name Streptomyces acididurans sp. nov. is proposed. The type strain is strain KK5PA1T (=TBRC 13094T=NBRC 114802T).
Inopinatum lactosum gen. & comb. nov., the first yeast-like fungus in Leotiomycetes
Authors: Haelewaters Danny , Peterson Robyn A. , Nevalainen Helena , Aime M. Catherine
Published: July 2021

Sporobolomyces lactosus is a pink yeast-like fungus that is not congeneric with other members of Sporobolomyces (Basidiomycota, Microbotryomycetes, Sporidiobolales). During our ongoing studies of pink yeasts we determined that S. lactosus was most closely related to Pseudeurotium zonatum (Ascomycota, Leotiomycetes, Thelebolales). A molecular phylogenetic analysis using sequences of the ITS region and the small and large subunit (SSU, LSU) rRNA genes, indicated that four isolates of S. lactosus, including three ex-type isolates, were placed in Thelebolales with maximum support. A new genus is proposed to accommodate S. lactosus, Inopinatum. This is the first pink yeast reported in Leotiomycetes.
Mangrovivirga cuniculi gen. nov., sp. nov., a moderately halophilic bacterium isolated from bioturbated Red Sea mangrove sediment, and proposal of the novel family Mangrovivirgaceae fam. nov.
Authors: Sefrji Fatmah O. , Michoud Grégoire , Marasco Ramona , Merlino Giuseppe , Daffonchio Daniele
Published: July 2021

A strictly aerobic, Gram-stain-negative, non-motile, rod-shaped bacterium, designated strain R1DC9T, was isolated from sediments of a mangrove stand on the Red Sea coast of Saudi Arabia via diffusion chamber cultivation. Strain R1DC9T grew at 20–40 °C (optimum, 37 °C), pH 6–10 (optimum, pH 8) and 3–11 % NaCl (optimum, 7–9 %) in the cultivation medium. The genome of R1DC9T was 4 661 901 bp long and featured a G+C content of 63.1 mol%. Phylogenetic analyses based on the 16S rRNA gene sequence and whole-genome multilocus sequence analysis using 120 concatenated single-copy genes revealed that R1DC9T represents a distinct lineage in the order

Cytophagales

and the phylum

Bacteroidetes

separated from the

Roseivirgaceae

and

Marivirgaceae

families. R1DC9T displayed 90 and 89 % 16S rRNA gene sequence identities with

Marivirga sericea

DSM 4125T and

Roseivirga ehrenbergii

KMM 6017T, respectively. The predominant quinone was MK7. The polar lipids were phosphatidylethanolamine, two unknown phospholipids and two unknown lipids. The predominant cellular fatty acids were the saturated branch chain fatty acids iso-C15 : 0, iso-C17 : 0 3-OH and iso-C17 : 0, along with a low percentage of the monounsaturated fatty acid C16 : 1
 ω5c. Based on differences in phenotypic, physiological and biochemical characteristics from known relatives, and the results of phylogenetic analyses, R1DC9T (=KCTC 72349T=JCM 33609T=NCCB 100698T) is proposed to represent a novel species in a new genus, and the name Mangrovivirga cuniculi gen. nov., sp. nov. is proposed. The distinct phylogenetic lineage among the families in the order

Cytophagales

indicates that R1DC9T represents a new family for which the name Mangrovivirgaceae fam. nov. is proposed.
COVID-19 Flow-Maps: An open geographic information system on COVID-19 and human mobility for Spain
Authors: Ponce-de-Leon Miguel , del Valle Javier , Fernandez José María , Bernardo Marc , Cirillo Davide , Sanchez-Valle Jon , Smith Matthew , Capella-Gutierrez Salvador , Gullón Tania , Valencia Alfonso
Published: July 2021

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has spread all over the world leading to a global pandemic. The fast progression of COVID-19 has been mainly related to the high contagion rate of the virus and the worldwide mobility of humans. In the absence of pharmacological therapies, governments from different countries have introduced several non-pharmaceutical interventions to reduce human mobility and social contact. Several studies based on Anonymised Mobile Phone Data have been published analysing the relationship between human mobility and the spread of coronavirus. However, to our knowledge, none of these data-sets integrates cross-referenced geo-localised data on human mobility and COVID-19 cases into one all-inclusive open resource. Herein we present COVID-19 Flow-Maps, a cross-referenced Geographic Information System that integrates regularly updated time-series accounting for population mobility and daily reports of COVID-19 cases in Spain at different scales of time spatial resolution. This integrated and up-to-date data-set can be used to analyse the human dynamics to guide and support the design of more effective non-pharmaceutical interventions.
Use of recently vaccinated individuals to detect bias in test-negative case-control studies of COVID-19 vaccine effectiveness
Authors: Hitchings Matt D.T. , Lewnard Joseph A. , Dean Natalie E. , Ko Albert I. , Ranzani Otavio T. , Andrews Jason R. , Cummings Derek A.T.
Published: July 2021

Post-authorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. While bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper we introduce a theoretical framework to describe the interpretation of such a bias-indicator in test-negative studies, and outline assumptions that would allow the use of recently vaccinated individuals to correct bias due to unmeasured confounding.
Thyroid function and risk of anemia: a multivariable-adjusted and Mendelian Randomization analysis in the UK Biobank
Authors: van Vliet Nicolien A. , Kamphuis Annelies E.P. , den Elzen Wendy P.J. , Blauw Gerard J. , Gussekloo Jacobijn , Noordam Raymond , van Heemst Diana
Published: July 2021

Context

Thyroid dysfunction is associated with higher anemia prevalence, though causality remains unclear.

Objective

To investigate a potential causal relationship between thyroid function and anemia.

Design

Cross-sectional and Mendelian Randomization study

Setting

Europeans from UK Biobank

Participants

445,482 participants, mean age 56.77 years (SD 8.0) and 54.2% were women. Self-reported clinical diagnosis of hypothyroidism was stated by 21,860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3,431 (0.8%).

Main Outcome Measure

Anemia, defined as hemoglobin level of <13 g/dL in men and <12 g/dL in women, was present in 18,717 (4.2%) participants.

Results

In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12, 95%CI 1.05-1.19 and OR 1.09, 95%CI 0.91-1.30), though with wide confidence intervals for hyperthyroidism. Although we considered a possible non-linear relationship, we did not observe an association of higher or lower genetically-influenced thyrotropin (TSH) with anemia (versus middle tertile: OR lowest tertile 0.98, 95% CI 0.95-1.02; highest tertile 1.02, 95% CI 0.98-1.06), nor of genetically-influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05, 95% CI 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes.

Conclusions

While self-reported clinical diagnosis of hypothyroidism was associated with a higher prevalence of anemia, we did not found evidence supporting this association was causal. However, intracellular regulation of thyroid hormones might play a role in developing anemia.
Face mask use and associated factors among students in rural Eastern Uganda amidst the COVID-19 pandemic
Authors: Mwesige Denis , Nalugya Aisha , Bulafu Douglas , Tigaiza Arnold , Nagawa Bridget Tamale , Balinda Emmanuel , Walekhwa Abel Wilson
Published: July 2021

Background

The Corona Virus Disease of 2019 (COVID-19) has gravely affected several aspects of national and global society, including education. Given the risk it poses, the Government of Uganda (GOU) adopted and recommended face mask use as one of the preventive measures to limit its transmission in communities. However, there is limited data on the levels of face mask usage and associated factors among students in schools in Uganda. This study aimed at assessing the face mask usage and associated factors among students in schools in rural Eastern Uganda amidst the COVID-19 pandemic.

Methods

A cross sectional quantitative descriptive study was conducted among 423 students in schools in rural Eastern Uganda. Multi-stage sampling method was employed in the selection of study participants. The data was collected by trained data collectors using structured questionnaires pre-installed on ODK enabled smart phones. The data entered was cleaned using Excel 2016 and exported to Stata14.0 statistical software (Statacorp, College station, Texas, USA) for analysis. Bivariate and multivariable logistic regression analyses were employed using 95% CI (confidence interval). Variables with p-value < 0.20 and those with literature backup evidence were included in the multivariable model. Variables with p-value < 0.05 were considered to be statistically significant. This study revealed that less than three quarters (62.3%) wore face masks correctly.

Results

Almost all, 98.9% of the participants mentioned that they wore face masks due to fear of missing classes and 49.0% disagreed that they were vulnerable to COVID-19. Students in boarding schools (AOR = 1.61, 95%CI: 1.05-2.47), those who believed that they were vulnerable to COVID-19 (AOR = 1.70, 95%CI: 1.11-2.10), and those who disagreed that masks are uncomfortable (AOR = 1.62, 95%CI: 1.06-2.46) were more likely to wear facemasks correctly.

Conclusion

This study revealed that more than a third of the students did not wear face masks correctly. Correct wearing of face masks was associated with being in a boarding school, belief that they were susceptible to COVID-19, and disagreeing that masks were uncomfortable. This therefore highlights the need for sensitization programmes in academic institutions in order to improve students’ perceptions toward COVID-19 and face masks, and consequently increase correct face mask usage in schools.
An immune-protein signature combining TRAIL, IP-10 and CRP for accurate prediction of severe COVID-19 outcome
Authors: Mastboim Niv Samuel , Angel Alon , Shaham Oded , Ber Tahel Ilan , Navon Roy , Simon Einav , Rosenberg Michal , Israeli Yael , Hainrichson Mary , Avni Noa , Reiner Eran , Feigin Paul , Oved Kfir , Tadmor Boaz , Singer Pierre , Kagan Ilya , Lev Shaul , Diker Dror , Jarjou’i Amir , Kurd Ramzi , Ben-Chetrit Eli , Danziger Guy , Papan Cihan , Motov Sergey , Shapira Ma’anit , Stein Michal , Klein Adi , Gottlieb Tanya M , Eden Eran
Published: July 2021

BACKGROUND

Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Tools integrating host-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity.

METHODS

Adults with COVID-19 were recruited at medical centers in Israel, Germany, and the United States. Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) and interferon gamma inducible protein-10 (IP-10; also known as CXCL10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes. A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Patients were assigned to 4 score bins.

RESULTS

Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. The signature’s area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001).

CONCLUSION

The derived immune-protein signature combined with a rapid measurement platform is an accurate predictive tool for early detection of COVID-19 patients at-risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation.

FUNDING

MeMed funded the study
Exploration of alcohol use disorder-associated brain miRNA-mRNA regulatory networks
Authors: Lim Yolpanhchana , Beane-Ebel Jennifer E. , Tanaka Yoshiaki , Ning Boting , Husted Christopher R. , Henderson David C. , Xiang Yangfei , Park In-Hyun , Farrer Lindsay A. , Zhang Huiping
Published: July 2021

Alcohol use disorder (AUD) is due to gene expression changes in specific brain regions, but the underlying mechanism is not fully understood. We investigated AUD-associated miRNA-mRNA regulatory networks in multiple brain regions by analyzing transcriptomic changes in two sets of postmortem brain tissue samples and ethanol-exposed human embryonic stem cell (hESC)-derived cortical interneurons. miRNA and mRNA transcriptomes were profiled in 192 postmortem tissue samples (Set 1) from eight brain regions (amygdala, caudate nucleus, cerebellum, hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of 12 AUD and 12 control Caucasians. Nineteen differentially expressed miRNAs (fold-change>2.0 &P<0.05) and 97 differentially expressed mRNAs (fold-change>2.0 &P<0.001) were identified in one or multiple brain regions of AUD subjects. AUD-associated miRNA-mRNA regulatory networks in each brain region were constructed using differentially expressed and negatively correlated miRNA-mRNA pairs. AUD-relevant pathways (includingCREB Signaling, IL-8 Signaling, andAxonal Guidance Signaling) were potentially regulated by AUD-associated brain miRNA-mRNA pairs. Moreover, miRNA and mRNA transcriptomes were mapped in additional 96 postmortem tissue samples (Set 2) from six of the above eight brain regions of eight AUD and eight control Caucasians, and some of the AUD-associated miRNA-mRNA regulatory networks were confirmed. Additionally, miRNA and mRNA transcriptomes were analyzed in hESC-derived cortical interneurons with and without ethanol exposure, and ethanol-influenced miRNA-mRNA regulatory networks were constructed. This study provided evidence that alcohol could induce concerted miRNA and mRNA expression changes in reward-related or alcohol-responsive brain regions. We concluded that altered brain miRNA-mRNA regulatory networks might contribute to AUD development.
CFTR-mediated monocyte-macrophage dysfunction revealed by cystic fibrosis proband- parent comparisons
Authors: Zhang Xi , Moore Camille , Harmacek Laura , Domenico Joanne , Rangaraj Vittobai , Ideozu Justin E. , Knapp Jennifer R. , Woods Kate A. , Jump Stephanie , Jia Shuang , Prokop Jeremy W. , Bowler Russel , Hessner Martin J. , Gelfand Erwin W. , Levy Hara
Published: July 2021

Cystic fibrosis (CF) is an inherited disorder caused by biallelic mutations of the cystic fibrosis transmembrane conductance regulator gene (CFTR). Converging lines of evidence suggest that CF carriers with only one defective CFTR copy are at increased risk for CF-related conditions and pulmonary infections, but the molecular mechanisms underpinning this effect remain unknown. Here, we performed transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) of CF child-parent trios (proband, father, and mother) and healthy control PBMCs or THP-1 cells incubated with the plasma of these subjects. Transcriptomic analyses revealed suppression of cytokine-enriched immune-related genes (IL-1β, CXCL8, CREM) implicating lipopolysaccharide tolerance in innate immune cells (monocytes) of CF probands and their parents and in the control innate immune cells incubated with proband or parent plasma. These data suggest that not only a homozygous but also a heterozygous CFTR mutation can modulate the immune/inflammatory system. This conclusion is further supported by the findings of lower numbers of circulating monocytes in CF probands and their parents compared to healthy controls, the abundance of mononuclear phagocyte subsets (macrophages, monocytes, and activated dendritic cells) which correlated with Pseudomonas aeruginosa infection, lung disease severity, and CF progression in the probands. This study provides insight into demonstrated CFTR-related innate immune dysfunction in individuals with CF and carriers of a CFTR mutation that may serve as a target for personalized therapy.
Partners in space: Discordant population structure between legume hosts and rhizobium symbionts in their native range
Authors: Riley Alex B. , Grillo Michael A. , Epstein Brendan , Tiffin Peter , Heath Katy D.
Published: July 2021

Coevolution is predicted to depend on how the genetic diversity of interacting species is geographically structured. Plant-microbe symbioses such as the legume-rhizobium mutualism are ecologically and economically important, but distinct life history and dispersal mechanisms for these host and microbial partners, plus dynamic genome composition in bacteria, present challenges for understanding spatial genetic processes in these systems. Here we study the model rhizobium Ensifer meliloti using a hierarchically-structured sample of 191 strains from 21 sites in the native range and compare its population structure to that of its host plant Medicago truncatula. We find high local genomic variation and minimal isolation by distance across the rhizobium genome, particularly at the two symbiosis elements pSymA and pSymB, which have evolutionary histories and population structures that are similar to each other but distinct from both the chromosome and the host. While the chromosome displays weak isolation by distance, it is uncorrelated with hosts. Patterns of discordant population structure among elements with the bacterial genome has implications for bacterial adaptation to life in the soil versus symbiosis, while discordant population genetic structure of hosts and microbes might restrict local adaptation of species to each other and give rise to phenotypic mismatches in coevolutionary traits.
Isolation and characterization of novel phages targeting pathogenic Klebsiella pneumoniae
Authors: Li Na , Zeng Yigang , Bao Rong , Zhu Tongyu , Tan Demeng , Hu Bijie
Published: July 2021

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming prevalent, the use of bacteriophages to treat pathogenic bacterial infections is becoming revitalized. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapies. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these K. pneumoniae isolates, three phages were isolated and characterized to evaluate the application of lytic phages against these 22 ST11 K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant mutants. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.
Inconsistent patterns of microbial diversity and composition between highly similar sequencing protocols: a case study with reef-building corals
Authors: Epstein Hannah E. , Hernandez-Agreda Alejandra , Starko Samuel , Baum Julia K. , Thurber Rebecca Vega
Published: July 2021

16S rRNA gene profiling (amplicon sequencing) is a popular technique for understanding host-associated and environmental microbial communities. Most protocols for sequencing amplicon libraries follow a standardized pipeline that can differ slightly depending on laboratory facility and user. Given that the same variable region of the 16S gene is targeted, it is generally accepted that sequencing output from differing protocols are comparable and this assumption underlies our ability to identify universal patterns in microbial dynamics through meta-analyses. However, discrepant results from a combined 16S rRNA dataset prepared by two labs whose protocols differed only in DNA polymerase and sequencing platform led us to scrutinize the outputs and challenge the idea of confidently combining them for standard microbiome analysis. Using technical replicates of reef-building coral samples from two species, Montipora aequituberculata and Porites lobata, we evaluated the consistency of alpha and beta diversity metrics between data resulting from these highly similar protocols. While we found minimal variation in alpha diversity between platform, significant differences were revealed with most beta diversity metrics, dependent on host species. These inconsistencies persisted following removal of low abundance taxa and when comparing across higher taxonomic levels, suggesting that bacterial community differences associated with sequencing protocol are likely to be context dependent and difficult to correct without extensive validation work. The results of this study encourage caution in the statistical comparison and interpretation of studies that combine rRNA sequence data from distinct protocols and point to a need for further work identifying mechanistic causes of these observed differences.

Importance

Amplicon sequencing remains a popular technique for characterizing organism and environmental microbiomes. The publication of sequence data from microbiome studies on open-access repositories provides an opportunity to identify universal patterns in microbial dynamics. To this end, it has been widely accepted that sequencing output from differing protocols are comparable and can be combined for analysis, so long as the same gene region is targeted. While most protocols for amplicon sequencing follow standardized pipelines, they can differ slightly between laboratory facility and user. In this study, we compared technical replicates of coral samples to evaluate the efficacy of combining organism-associated microbial datasets derived from two differing protocols. We found inconsistencies in the differences between bacterial communities, which persisted following data manipulations intended to increase comparability. These results suggest caution must be taken in the statistical comparison and interpretation of studies that combine data derived from distinct protocols.
Activation of Adipocyte mTORC1 Increases Milk Lipids in a Mouse Model of Lactation
Authors: Habbal Noura El , Meyer Allison C. , Hafner Hannah , Redd JeAnna R. , Carlson Zach , Mulcahy Molly C. , Gregg Brigid , Bridges Dave
Published: July 2021

Human milk is the recommended nutrient source for newborns. The mammary gland comprises multiple cell types including epithelial cells and adipocytes. The contributions of mammary adipocytes to breast milk composition and the intersections between mammary nutrient sensing and milk lipids are not fully understood. A major nutrient sensor in most tissues is the mechanistic target of rapamycin 1 (mTORC1). To assess the role of excess nutrient sensing on mammary gland structure, function, milk composition, and offspring weights, we used an Adiponectin-Cre driven Tsc1 knockout model of adipocyte mTORC1 hyperactivation. Our results show that the knockout dams have higher milk fat contributing to higher milk caloric density and heavier offspring weight during lactation. Additionally, milk of knockout dams displayed a lower percentage of saturated fatty acids, higher percentage of monounsaturated fatty acids, and a lower milk ω6: ω3 ratio driven by increases in docosahexaenoic acid (DHA). Mammary gland gene expression analyses identified changes in eicosanoid metabolism, adaptive immune function, and contractile gene expression. Together, these results suggest a novel role of adipocyte mTORC1 in mammary gland function and morphology, milk composition, and offspring growth.
Drosophila larval models of invasive tumourigenesis for in vivo studies on tumour/peripheral host tissue interactions during cancer cachexia
Authors: Hodgson Joseph A. , Parvy Jean-Philippe , Yu Yachuan , Vidal Marcos , Cordero Julia B.
Published: July 2021

Cancer cachexia is a common deleterious paraneoplastic syndrome that represents an area of unmet clinical need, partly due to its poorly understood aetiology and complex multifactorial nature. We have interrogated multiple genetically defined larval Drosophila models of tumourigenesis against key features of human cancer cachexia. Our results indicate that cachectic tissue wasting is dependent on the genetic characteristics of the tumour and demonstrate that host malnutrition or tumour burden are not sufficient to drive wasting. We show that JAK/STAT and TNF-α/Egr signalling are elevated in cachectic muscle and promote tissue wasting. Furthermore, we introduce a dual driver system that allows independent genetic manipulation of tumour and host skeletal muscle. Overall, we present a novel Drosophila larval paradigm to study tumour/host tissue crosstalk in vivo, which may contribute to future research in cancer cachexia and impact the design of therapeutic approaches for this pathology.
Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern
Authors: Jongeneelen Mandy , Kaszas Krisztian , Veldman Daniel , Huizingh Jeroen , van der Vlugt Remko , Schouten Theo , Zuijdgeest David , Uil Taco , van Roey Griet , Guimera Nuria , Navis Marjon , Bos Rinke , le Gars Mathieu , Sadoff Jerald , Muchene Leacky , Juraszek Jarek , Langedijk Johannes PM , Vogels Ronald , Custers Jerome , Schuitemaker Hanneke , Brandenburg Boerries
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and recently emerging variants with substitutions in the Spike protein have led to growing concerns over increased transmissibility and decreased vaccine coverage due to immune evasion. Here, sera from recipients of a single dose of our Ad26.COV2.S COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants of concern. All tested variants demonstrated susceptibility to Ad26.COV2.S-induced serum neutralization albeit mainly reduced as compared to the B.1 strain. Most pronounced reduction was observed for the B.1.351 (Beta; 3.6-fold) and P.1 (Gamma; 3.4-fold) variants that contain similar mutations in the receptor-binding domain (RBD) while only a 1.6-fold reduction was observed for the widely spreading B.1.617.2 (Delta) variant.
Effects of High-Volume versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations
Authors: Vann Christopher G. , Sexton Casey L. , Osburn Shelby C. , Smith Morgan A. , Haun Cody T. , Rumbley Melissa N. , Mumford Petey W. , Ferguson Brian K. , Montgomery Nathan T. , Fox Carlton D. , Ruple Bradley A. , McKendry James , Mcleod Jonathan , Bashir Adil , Beyers Ronald J. , Brook Matthew S. , Smith Kenneth , Atherton Philip J , Beck Darren T. , McDonald James R. , Young Kaelin C. , Phillips Stuart M. , Roberts Michael D.
Published: July 2021

Aim

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular markers.

Methods

Trained men (n=15, age: 23±3 y; training experience: 7±3 y) performed unilateral lower body training for 6 weeks (3x weekly), where single legs were assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within subjects repeated measures ANOVAs were performed on all dependent variables except tracer data, which was compared using dependent samples t-tests.

Results

A significant (p<0.05) interaction existed for unilateral leg extension 1RM (HV<HL at POST and POSTPR). Six-week integrated sarcoplasmic protein synthesis (iSarcoPS) rates were higher in the HV versus HL leg, while no difference between legs existed for integrated myofibrillar protein synthesis rates. Main time effects existed for unilateral leg press strength (PRE<POST and POSTPR), knee extensor peak torque (PRE and POST<POSTPR), dual-energy x-ray absorptiometry (DXA)-derived upper leg lean mass (PRE<POST and POSTPR), ultrasound-derived VL thickness (PRE and POSTPR<POST), sarcoplasmic protein concentrations (POST and POSTPR<PRE), and tropomyosin and troponin protein abundances (POST and POSTPR<PRE).

Conclusions

With the exception of differences in leg extensor strength and iSarcoPS between legs, our data suggest that short-term (6 weeks) HV and HL training elicit similar hypertrophic, strength, and molecular-level adaptations.
Spectro-temporal neural dynamics during sentence completion
Authors: Coolen Tim , Dumitrescu Alexandru Mihai , Wens Vincent , Bourguignon Mathieu , Gómez Gustavo Lucena , Rovai Antonin , Sadeghi Niloufar , Urbain Charline , Goldman Serge , De Tiège Xavier
Published: July 2021

This magnetoencephalography (MEG) study aimed at characterizing the spectro-temporal dynamics of brain oscillatory activity elicited by sentence completion (SC). For that purpose, we adapted a version of the SC experimental paradigm typically used in functional magnetic resonance imaging to MEG investigation constraints. Twenty right-handed healthy young adults underwent MEG recordings while they were sequentially presented with short sentences divided in three parts: the first two giving context and the last requiring completion. MEG data were then analysed using a prior-free, non-parametric statistical approach with stringent control of the family-wise error rate. We identified three successive significant neural response patterns associated with distinct spatial and spectro-temporal characteristics: (i) an early (<300 ms) bioccipital 4-10-Hz event-related synchronization (ERS); (ii) an intermediate (at about 400 ms) 8-30-Hz event-related desynchronization (ERD) in an extended semantic network involving the ventral language stream as well as bilateral posterior nodes of the default mode network (DMN) in both hemispheres; (iii) a late (>800 ms) 8-30 Hz ERD involving the left dorsal language stream. Furthermore, the left component of the ventral language stream displayed prolonged ERD after 800 ms compared to the right which showed signs of inhibition in the form of ERS. Overall, this study elucidates the dynamics of the recruitment of the language network that accompany SC and the spectro-temporal signature of an extended semantic network. This MEG adaptation of an SC paradigm also paves the way for novel approaches in presurgical language mapping and may help to understand the neural underpinnings of the alterations of sentence completion in various neurologic disorders affecting language.
Modeling site-specific nucleotide biases affecting Himar1 transposon insertion frequencies in TnSeq datasets
Authors: Choudhery Sanjeevani , Brown A. Jacob , Akusobi Chidiebere , Rubin Eric J. , Sassetti Christopher M. , Ioerger Thomas R.
Published: July 2021

In bacterial TnSeq experiments, a library of transposons insertion mutants is generated, selected under various growth conditions, and sequenced to determine the profile of insertions at different sites in the genome, from which the fitness of mutant strains can be inferred. The widely used Himar1 transposon is known to be restricted to insertions at TA dinucleotides, but otherwise, few site-specific biases have been identified. As a result, most analytical approaches assume that insertion counts are expected a priori to be randomly distributed among TA sites in non-essential regions. However, recent analyses of independent Himar1 Tn libraries in M. tuberculosis have identified a local sequence pattern that is non-permissive for Himar1 insertion. This suggests there are site-specific biases that affect the frequency of insertions of the Himar1 transposon at different TA sites. In this paper, we use statistical and machine learning models to characterize patterns in the nucleotides surrounding TA sites associated with high and low insertion counts. We not only affirm that the previously discovered non-permissive pattern (CG)GnTAnC(CG) suppresses insertions, but conversely show that an A in the -3 position or T in the +3 position from the TA site encourages them. We demonstrate that these insertion preferences exist in Himar1 TnSeq datasets other than M. tuberculosis, including mycobacterial and non-mycobacterial species. We build predictive models of Himar1 insertion preferences as a function of surrounding nucleotides. The final predictive model explains about half of the variance in insertion counts, presuming the rest comes from stochastic variability between libraries or due to sampling differences during sequencing. Based on this model, we present a new method, called the TTN-Fitness method, to improve the identification of conditionally essential genes or genetic interactions, i.e., to better distinguish true biological fitness effects by comparing the observed counts to expected counts using a site-specific model of insertion preferences. Compared to previous methods like Hidden Markov Models, the TTN-Fitness method can make finer distinctions among genes whose disruption causes a fitness defect (or advantage), separating them out from the large pool of non-essentials, and is able to classify the essentiality of many smaller genes (with few TA sites) that were previously characterized as uncertain.
Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E
Authors: Zhu Yue , Scholle Frank , Kisthardt Samantha C. , Xie De-Yu
Published: July 2021

Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus, however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (Mpro) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an appropriate candidate to screen potential medicinal compounds. Flavonols and dihydroflavonols are two groups of plant flavonoids. In this study, we report docking simulation with two Mpro enzymes and five flavonols and three dihydroflavonols, in vitro inhibition of the SARS-CoV-2 Mpro, and in vitro inhibition of the HCoV 229E replication. The docking simulation results predicted that (+)-dihydrokaempferol, (+)-dihydroquercetin, (+)-dihydromyricetin, kaempferol, quercetin, myricentin, isoquercetin, and rutin could bind to at least two subsites (S1, S1’, S2, and S4) in the binding pocket and inhibit the activity of SARS-CoV-2 Mpro. Their affinity scores ranged from −8.8 to −7.4. Likewise, these compounds were predicted to bind and inhibit the HCoV-229E Mpro activity with affinity scores ranging from −7.1 to −7.8. In vitro inhibition assays showed that seven available compounds effectively inhibited the SARS-CoV-2 Mpro activity and their IC50 values ranged from 0.125 to 12.9 µM. Five compounds inhibited the replication of HCoV-229E in Huh-7 cells. These findings indicate that these antioxidative flavonols and dihydroflavonols are promising candidates for curbing the two viruses.
What drives microfinance institution lending behavior? Empirical evidence from Sub-Saharan Africa
Authors: Tehulu Tilahun Aemiro
Published: July 2021

Purpose

While poverty alleviation is the first core goal of Sustainable Development Goals (SDGs), and microfinance institutions (MFIs) are considered important instruments for poverty alleviation in developing countries as they provide credit access to the poor, there is surprisingly little evidence of the drivers of the lending behavior of microfinance institutions. Hence, the purpose of this study is to identify the factors that influence the credit growth of MFIs in Sub-Saharan Africa (SSA).

Design/methodology/approach

The study relies on unbalanced panel dataset of 130 MFIs operating across 31 countries in SSA during the period 2004–2014 constituting 546 useable observations. The study uses the Arellano-Bover/Blundell-Bond two-step generalized method of moments (GMM) Windmeijer bias-corrected standard errors to estimate the models.

Findings

The results confirm that while capitalization, liquidity and size are positively associated with credit growth, profitability negatively impacts credit growth; whereas, other MFI specific factors namely portfolio quality, deposit growth and nondeposit borrowing growth have little direct effects on MFI credit growth. The results also show that MFI credit growth is pro-cyclical but negatively related to GDP per capita consistent with the theory of convergence. On the other hand, inflation and employment are not important covariates in the credit growth of MFIs.

Practical implications

The findings suggest that if MFIs improve their liquidity and size by attracting more deposits and nondeposit borrowings, among others, they can increase credit access to the poor. Moreover, since the lending behavior of MFIs is not resilient to GDP shocks, different measures are needed to increase the financial stability of the microfinance industry. In this respect, since MFI capitalization is positively associated with credit growth and MFI credit growth is pro-cyclical, the findings provide useful insights to central banks/regulatory authorities and the Basel Committee as to the need for a counter-cyclical capital buffer requirement in the microfinance industry.

Originality/value

The study is the first comprehensive study to examine the drivers of MFI lending behavior as an extension to lending behavior models from the banking industry.