bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between HIV PrEP Indications and Use in a National Sexual Network Study of Men Who Have Sex with Men
Authors: Weiss Kevin M. , Prasad Pragati , Sanchez Travis , Goodreau Steven M. , Jenness Samuel M. 
Published: March 2021

ABSTRACTBackgroundHIV preexposure prophylaxis (PrEP) is effective in preventing HIV transmission. US Public Health Service (USPHS) clinical practice guidelines define biobehavioral indications for initiation. To assess guideline implementation, it is critical to quantify PrEP non-users who are indicated and PrEP users who are not indicated.MethodsUsing data from a national web-based study of men who have sex with men (MSM) between 2017 and 2019, we estimated the association between PrEP use and PrEP indications. Log-binomial regression was used to estimate the relationship between PrEP indications and PrEP use, adjusted for geography and demographics.ResultsOf 3508 sexually active, HIV-negative MSM, 34% met indications for PrEP. The proportion with current PrEP use was 32% among those meeting indications and 11% among those without indications. Nearly 40% of those currently using PrEP did not meet indications for PrEP, and 68% of MSM with indications for PrEP were not currently using PrEP. After adjusting for geography and demographics, MSM with PrEP indications were about 3 times as likely to be currently using PrEP. This association varied slightly by geography and demography.ConclusionsIndications for PrEP strongly predicted current PrEP use among MSM. However, we identified substantial misalignment between indications and use in both directions (indicated MSM who were not benefitting from PrEP, and MSM taking PrEP while not presently being indicated). This calls for further implementation efforts to improve PrEP delivery to those most in need during periods of elevated sexual risk.
Kinetics of SARS-CoV-2 anti-s IgG after BNT162b2 vaccination
Authors: Grupel Daniel , Gazit Sivan , Schreiber Licita , Nadler Varda , Wolf Tamar , Lazar Rachel , Supino-Rosin Lia , Perez Galit , Peretz Asaf , Tov Amir Ben , Mizrahi-Reuveni Miri , Chodick Gabriel , Patalon Tal 
Published: March 2021

AbstractDeployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020.This is a retrospective analysis of serological data, describing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli healthcare workers administrated the BNT162b2 vaccine.Seroconversion occurred by day 14 in all individuals, with IgG levels peaking approximately 30 days post inoculation.This study demonstrated the kinetics of the antibody response post vaccination with BNT162b2. The robustness of seroconversion was observed, alongside a statistically significant difference in IgG levels between employees over and younger 50 years of afge. Further research is required in order to examine the antibody kinetics overtime, as well as whether the age-dependent difference persists.
Physiologic flow-conditioning limits vascular dysfunction in engineered human capillaries
Authors: Haase Kristina , Piatti Filippo , Marcano Minerva , Shin Yoojin , Visone Roberta , Redaelli Alberto , Rasponi Marco , Kamm Roger D. 
Published: March 2021

AbstractHemodynamics play a central role in the health and disease of the coronary and peripheral vascular systems. Vessel-lining endothelial cells are known mechanosensors, responding to disturbances in flow – with mechanosensitivity hypothesized to change in response to metabolic demands. The health of our smallest microvessels have been lauded as a prognostic marker for cardiovascular health. Yet, despite numerous animal models, studying these small vessels has proved difficult. Microfluidic technologies have allowed a number of 3D vascular models to be developed and used to investigate human vessels. Here, two such systems are employed for examining 1) interstitial flow effects on neo-vessel formation, and 2) the effects of flow-conditioning on vascular remodelling following sustained static culture. Interstitial flow is shown to enhance early vessel formation via significant remodeling of vessels and interconnected tight junctions of the endothelium. In formed vessels, continuous flow maintains a stable vascular diameter and causes significant remodeling, contrasting the continued anti-angiogenic decline of statically cultured vessels. This study is the first to couple complex 3D computational flow distributions and microvessel remodeling from microvessels grown on-chip (exposed to flow or no-flow conditions). Flow-conditioned vessels (WSS < 1Pa for 30 micron vessels) increase endothelial barrier function, result in significant changes in gene expression and reduce reactive oxygen species and anti-angiogenic cytokines. Taken together, these results demonstrate microvessel mechanosensitivity to flow-conditioning, which limits deleterious vessel regressionin vitro, and could have implications for future modeling of reperfusion/no-flow conditions.
Conserving evolutionary history to safeguard our future: incorporating the Tree of Life into biodiversity policy
Authors: Gumbs Rikki , Chaudhary Abhishek , Daru Barnabas H. , Faith Daniel P. , Forest Félix , Gray Claudia L. , Kowalska Aida , Lee Who-Seung , Pellens Roseli , Pipins Sebastian , Pollock Laura J. , Rosindell James , Scherson Rosa A. , Owen Nisha R. 
Published: March 2021

AbstractFollowing our failure to fully achieve any of the 20 Aichi biodiversity targets, the future of biodiversity rests in the balance. The Convention on Biological Diversity’s Post-2020 Global Biodiversity Framework (GBF) presents us with the opportunity to preserve Nature’s Contributions to People (NCPs) for current and future generations through conserving biodiversity and averting extinction across the Tree of Life. Here we call attention to our need to conserve the Tree of Life to maintain its benefits into the future as a key mechanism for achieving intergenerational equity. We highlight two indicators available for adoption in the post-2020 GBF to monitor our progress towards safeguarding the Tree of Life. The Phylogenetic Diversity indicator, adopted by IPBES, can be used to monitor biodiversity’s capacity to maintain NCPs for future generations. The EDGE (Evolutionarily Distinct and Globally Endangered) Index monitors how well we are performing at averting the greatest losses across the Tree of Life by conserving the most distinctive species. By committing to safeguarding the Tree of Life post-2020, we can reduce biodiversity loss to preserve nature’s contributions to humanity now and into the future.
A low sugar diet enhancesDrosophilabody size in males and females via sex-specific mechanisms
Authors: Millington Jason W. , Wat Lianna W. , Sun Ziwei , Basner-Collins Paige J. , Brownrigg George P. , Rideout Elizabeth J. 
Published: March 2021

ABSTRACTInDrosophila, changes to dietary protein elicit different body size responses between the sexes. Whether this sex difference in nutrient-dependent body size regulation extends to other nutrients, such as dietary sugar, remains unclear. Here, we show that reducing dietary sugar enhanced body size inDrosophilamale and female larvae. Indeed, the largest body size was found in larvae reared in a diet without added sugar. Despite the equivalent body size effects of a low sugar diet between males and females, we detected sex-specific changes to the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways. Further, we show that the metabolic changes observed in larvae reared on a low sugar diet differ between the sexes. Thus, despite identical phenotypic responses to dietary sugar in males and females, distinct changes to cell signaling pathways and whole-body metabolism were associated with the increased body size in each sex. This highlights the importance of including both sexes in all mechanistic studies on larval growth, as males and females may use different molecular and metabolic mechanisms to achieve similar phenotypic outcomes.
Toxigenic Profile ofClostridium perfringensStrains Isolated from Natural Ingredient Laboratory Animal Diets
Authors: Johnston Michael D. , Whiteside Tanya E. , Williamson Michelle E. , Kurtz David M. 
Published: March 2021

AbstractClostridium perfringensis an anaerobic, gram-positive, spore-forming bacterium that ubiquitously inhabits a wide variety of natural environments including the gastrointestinal tract of humans and animals.C. perfringensis an opportunistic enteropathogen capable of producing at least 20 different toxins in various combinations. Strains ofC. perfringensare currently categorized into seven toxinotypes (A, B, C, D, E, F & G) based on the presence/absence of four major toxins (alpha, beta, epsilon & iota) and two minor toxins (enterotoxin & netB). Each toxinotype is associated with specific histotoxic and enteric diseases. The Quality Assurance Laboratory (QAL) at the National Institute of Environmental Health Sciences (NIEHS) screens incoming animal feeds for aerobic, enteric pathogens, such asSalmonellaspp. andE. coli. Recently, QAL has incorporated anaerobic screening of incoming animal feeds. To date, the lab has isolated numerousClostridium species, includingC. perfringens, from 23 lots of natural-ingredient laboratory animal diets.ImportancePublished reports ofClostridium perfringensisolation from laboratory animal feeds could not be found in the literature. Therefore, we performed a toxin profile screening of our isolated strains ofC. perfringensto determine which toxinotypes were present in our laboratory animal diets. As studies progress with immunocompromised strains, gnotobiotic models, and animals with perturbed gut flora, the presence ofC. perfringenscould potentially lead to infection, disease and mortality which would substantiate the need to properly eliminate the bacterium and its spores from diets given to high risk animal populations.
Scaling dictates the decoder structure
Authors: Shen Jingxiang , Liu Feng , Tang Chao 
Published: March 2021

AbstractDespite fluctuations in embryo size within a species, the spatial gene expression pattern and hence the embryonic structure developin proportionwith embryo size, known as the scaling phenomenon. For morphogen induced patterning of gene expression, the positional information encoded in the morphogen profile is decoded by the downstream genetic network (the decoder). In this paper, we show that the requirement of scaling sets severe constraints on the geometric structure of the decoder, which in turn enables deduction of mutants’ behavior and extraction of regulation information without going into any molecular details. We demonstrate that theDrosophilagap gene system achieves scaling in the way consistent with our theory – the decoder geometry required by scaling correctly accounts for the observed gap gene expression pattern in nearly all maternal morphogen mutants. Furthermore, the regulation logic and the coding/decoding strategy of the gap gene system can also be revealed from the decoder geometry. Our work provides a general theoretical framework on a large class of problems where scaling output is induced by non-scaling input, as well as a unified understanding of scaling, mutants’ behavior and gene regulation for theDrosophilagap gene system.
A novel conformational state for SARS-CoV-2 main protease
Authors: Fornasier Emanuele , Macchia Maria Ludovica , Giachin Gabriele , Sosic Alice , Pavan Matteo , Sturlese Mattia , Salata Cristiano , Moro Stefano , Gatto Barbara , Bellanda Massimo , Battistutta Roberto 
Published: March 2021

AbstractThe SARS-CoV-2 main protease (Mpro) has a pivotal role in mediating viral genome replication and transcription of coronavirus, making it a promising target for drugs against Covid-19 pandemic. Here we present a crystal structure of Mprodisclosing new structural features of key regions of the enzyme. We show that the oxyanion loop, involved in substrate recognition and enzymatic activity, can adopt a new conformation, which is stable and significantly different from the known ones. In this new state the S1 subsite of the substrate binding region is completely reshaped and a new cavity near the S2’ subsite is created. This new structural information expands the knowledge of the conformational space available to Mpro, paving the way for the design of novel classes of inhibitors specifically designed to target this unprecedented binding site conformation, thus enlarging the chemical space for urgent antiviral drugs against Covid-19 pandemic.
The parathyroid hormone-dependent activation of osteoblasts enhances hematopoietic stem cell migration and reduces their engraftment abilities
Authors: Even Yasmine , Yi Lin , Chang Chih-Kai , Rossi Fabio M.V. 
Published: March 2021

AbstractHematopoietic stem cells (HSCs) in the bone marrow (BM) reside in HSC niches ensuring their maintenance. The HSC niche is made up of perivascular and trabecular cells including osteoblasts whose role on HSCs remains to be clearly defined. Increased numbers of osteoblasts have been observed in the CL2 transgenic mouse expressing a constitutively activated form of the parathyroid hormone (PTH)/PTH-related peptide receptor. This mouse model mimicking PTH anabolic effect has also been described to exhibit increased numbers of the BM stem/progenitor population. Furthermore, PTH is known to induce BM stem/progenitor cell migration into blood circulation. However PTH role on long-term repopulating HSCs (LT-HSCs) is incompletely known. Here we show that CL2 BM contains a regular proportion of LT-HSCs, suggesting that osteoblasts may not be a determinant of LT-HSC numbers but act mainly on more mature progenitors. We further show increased LT-HSC migration in CL2 mice correlated with higher granulocyte colony-stimulating factor (G-CSF) serum levels, supporting the idea that PTH can enhance the migration of LT-HSCs. Finally, we found a defect in the ability of CL2 BM HSCs to reconstitute irradiated BM suggesting that PTH activation of osteoblasts negatively influences abilities of HSC population to engraft and reconstitute irradiated BM. In summary, our study highlights new insights into the role of the PTH-dependent activation of osteoblasts on LT-HSC migration and their BM repopulation abilities. Our findings will be useful to improve treatments on hematological disorders, especially therapies involving HSC harvest and transplantation.
Killing of Gram-negative and Gram-positive bacteria by a bifunctional cell wall-targeting T6SS effector
Authors: Le Nguyen-Hung , Pinedo Victor , Lopez Juvenal , Cava Felipe , Feldman Mario 
Published: March 2021

AbstractThe type VI secretion system (T6SS) is a powerful tool deployed by Gram-negative bacteria to antagonize neighboring organisms. Here, we report thatAcinetobacter baumanniiATCC 17978 (Ab17978) secretes D-lysine (D-Lys), increasing the extracellular pH and enhancing the peptidoglycanase activity of the T6SS effector Tse4. This synergistic effect of D-Lys on Tse4 activity enables Ab17978 to outcompete Gram-negative bacterial competitors, demonstrating that bacteria can modify their microenvironment to increase their fitness during bacterial warfare. Remarkably, this lethal combination also results in T6SS-mediated killing of Gram-positive bacteria. Further characterization revealed that Tse4 is a bifunctional enzyme consisting of both lytic transglycosylase and endopeptidase activities, thus representing a novel family of modularly organized T6SS PG degrading effectors with an unprecedented impact in antagonistic bacterial interactions.One sentence summaryBy modulating local environmental pH through D-Lys secretion,Acinetobacter baumanniienhances the activity of a bifunctional cell wall-targeting T6SS effector, increasing its killing activity against Gram-negative and -positive competitors.
Mutation Profiles, Glycosylation Site Distribution and Codon Usage Bias of HPV16
Authors: Liu Wei , Li Junhua , Du Hongli , Ou Zhihua 
Published: March 2021

AbstractHuman papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1,597 full genomes of HPV16, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias of the eight open reading frames (ORFs) of HPV16 genomes from different lineages and sublineages. Multiple lineage- or sublineage-specific mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of unique potential glycosylation site in both L1 and L2 capsid protein, which might lead to their antigenic distances from other HPV16 lineages. Nucleotide composition of HPV16 showed that the overall AT content was higher than GC content at the 3rdcodon position. Relatively high ENC values suggested that the HPV16 ORFs didn’t have strong codon usage bias. Most of the HPV16 ORFs were mainly governed by natural selection pressure such as translational pressure, except for L2. HPV16 only shared some of the preferred codons with human, which might help reduce competition in translational resources. These findings may help increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells, which might facilitate HPV classification and improve vaccine development and application.
Molecular mechanism regulating transcriptional control of the hig toxin-antitoxin locus of antibiotic-resistance plasmid Rts1 from Proteus vulgaris
Authors: Pavelich Ian , Schureck Marc A. , Wang Dongxue , Hoffer Eric D. , Boamah Michelle , Onuoha Nina , Miles Stacey J. , Okafor C. Denise , Dunham Christine M. 
Published: March 2021

ABSTRACTRegulation of ubiquitous bacterial type II toxin-antitoxin (TA) gene pairs occurs via a negative feedback loop whereby their expression is typically responsive to changing levels of toxins at the transcriptional level similar to a molecular rheostat. While this mechanism can explain how certain TA complexes are regulated, accumulating evidence suggests diversity in this regulation. One system for which the negative feedback loop is not well defined is the plasmid-encoded HigBHigA TA pair originally identified in a post-operative infection with antibiotic resistant Proteus vulgaris. In contrast to other type II TA modules, each hig operator functions independently and excess toxin does not contribute to increased transcription in vivo. Structures of two different oligomeric complexes of HigBHigA bound to its operator DNA reveal similar interactions are maintained suggesting plasticity in how hig is repressed. Consistent with this result, molecular dynamic simulations reveal both oligomeric states exhibit similar dynamics. Further, engineering a dedicated trimeric HigBHigA complex does not regulate transcriptional repression. We propose that HigBHigA functions via a simple on/off transcriptional switch regulated by antitoxin proteolysis rather than a molecular rheostat. The present studies thus expand the known diversity of how these abundant bacterial protein pairs are regulated.IMPORTANCEBacteria respond to various stimuli by rapidly regulating gene expression to control growth. The diversity in how bacteria inhibit growth is exemplified by the abundance and diversity of toxin-antitoxin (TA) gene pairs. To tightly regulate their own expression, antitoxin proteins function as transcriptional autorepressors with additional regulation imparted by responsiveness of the system to toxin concentrations, similar to a molecular rheostat. However, some TAs do not appear to be responsive to changing levels of toxin. To expand our understanding of diverse TAs, we studied the regulation of a structurally distinct TA called host inhibition of growth (HigBA) originally discovered on the antibiotic resistance Rts1 plasmid associated with Proteus vulgaris. We find that the hig operon is regulated via a simple on/off transcriptional switch that is incalcitrant to changing toxin levels. These results expand the known mechanistic diversity of how TA pairs regulate their expression.
Insights from the first genome assembly of Onion (Allium cepa)
Authors: Finkers Richard , van Kaauwen Martijn , Ament Kai , Burger-Meijer Karin , Egging Raymond , Huits Henk , Kodde Linda , Kroon Laurens , Shigyo Masayoshi , Sato Shusei , Vosman Ben , van Workum Wilbert , Scholten Olga 
Published: March 2021

AbstractOnion is an important vegetable crop with an estimated genome size of 16Gb. We describe the de novo assembly and ab initio annotation of the genome of a doubled haploid onion line DHCU066619, which resulted in a final assembly of 14.9 Gb with a N50 of 461 Kb. Of this, 2.2 Gb was ordered into 8 pseudomolecules using five genetic linkage maps. The remainder of the genome is available in 89.8 K scaffolds. Only 72.4% of the genome could be identified as repetitive sequences and consist, to a large extent, of (retro) transposons. In addition, an estimated 20% of the putative (retro) transposons had accumulated a large number of mutations, hampering their identification, but facilitating their assembly. These elements are probably already quite old. The ab initio gene prediction indicated 540,925 putative gene models, which is far more than expected, possibly due to the presence of pseudogenes. Of these models, 86,073 showed similarity to published proteins (UNIPROT). No gene rich regions were found, genes are uniformly distributed over the genome. Analysis of synteny with A. sativum (garlic) showed collinearity but also major rearrangements between both species. This assembly is the first high-quality genome sequence available for the study of onion and will be a valuable resource for further research.
Political connection, political promotion and corporate environmental information disclosure in China
Authors: Li Yuxuan , Wong Christina W.Y. , Miao Xin 
Published: March 2021

Purpose
This study aims to examine how the political career concerns of top executives affect corporate environmental practices.

Design/methodology/approach
Based on rent-seeking theory, this work uses empirical analysis to investigate the impact of top executives’ political connection and political promotion on corporate environmental information disclosure (EID). Data were collected from Chinese listed firms in heavily polluting industries in the Shanghai Stock Market in 2014–2016.

Findings
The results reveal that the highly politically connected top executives are more likely to be promoted in their political positions than their counterparts. However, the firms under the management of these highly politically connected executives show low level of EID. The results suggest that the political motivations of top executives with political connection hinders corporate EID.

Originality/value
This paper extends literature system about the impact of executives' rent-seeking on corporate EID by examining the informal mechanisms in terms of political connection and political promotion. It provides insights for studies of corporate environmental strategies and governmental environmental responsibility.
Do females in audit firm governance affect firm performance? Findings from Turkey
Authors: Ocak Murat 
Published: March 2021

PurposeThis study aims to contribute to the literature by offering a different sector and emphasising the importance of females in audit firm (AF) governance on audit firm performance (AFP).Design/methodology/approachOrdinary least squares (OLS) and instrument variables regression (IVREG) with two-stage least squares are used to test the paper’s hypotheses.FindingsBoth OLS and IVREG estimation results show that both the proportion of females and gender diversity at board and owner levels and the total number of shares of female owners seem to enhance the performance of AFs.Practical implicationsThese results may be important for policymakers and regulators to set a quota for women’s representation on AF governance or decide arrangements for women in AFs as in the regulations for the high hierarchical levels of other corporate firms.Originality/valueThis paper extends the current literature in the context of AFs in Turkey, positing that females in AF governance might enhance performance to a great extent.