bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of four antibiotics on the diversity of the intestinal microbiota
Authors: Huang Ce , Feng Shengyu , Huo Fengjiao , Liu Hailiang 
Published: July 2021

ABSTRACTOral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, which increases the risk of colonization with intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and potentially pathogenic bacteria under conditions of gut microbiota dysbiosis. Additionally, it is controversial whether the effects of antibiotics on the gut microbiota are temporary or permanent. In this study, we used 16S rRNA gene sequencing to evaluate the short-term and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota by analyzing changes in the relative numbers of potentially beneficial and potentially pathogenic bacteria. We found that the changes in the intestinal microbiota reflected the antibiotics’ mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between the different bacterial communities. Thus, destruction of bacteria with beneficial potential increased the abundance of bacteria with pathogenic potential. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota and the relative proportions of bacteria with beneficial potential and bacteria with pathogenic potential, thereby increasing the risk of host disease.
Genotype of Human Papilloma virus in Male Genital Warts In Korean Men and Review of Literature
Authors: Moon Woochul , Jo Jungho , Yoon Jinhan ,   Korean Male HPV Study Group, Moon Jung Joo 
Published: July 2021

ABSTRACTPurposeGenital warts are one of the most common sexually transmitted infections and are known to develop due to human papillomavirus (HPV) infection, especially HPV types 6 and 11. However, their prevalence and subtypes in male genital warts remains poorly defined. HPV vaccine is administered to men in part to prevent anogenital warts and it is important to investigate their expected impact in male anogenital warts.Materials and MethodsWe have herein conducted a multicenter, prospective study to analyze HPV type distribution in genital warts of 1000 Korean men by using DNA microarray that can detect 40 types of genital HPV.Results1000 out of 1015 genital warts showed HPV DNA. Out of 1000 HPV-positive samples, 18.8% showed mixed infection and 81.2% showed single infection. Of 18 high-risk (16.2%) and 14 low-risk (94.3%) HPV types detected, the most common type of HPV types were HPV6 (59.5%), followed by HPV11 (24.3%), HPV16 (5.8%), HPV91 (5.3%), HPV40 (3.3%). 85.9% showed the 9 HPV types covered by the vaccine. Sixteen of the 200 HPV specimens submitted for sequencing showed discrepant results compared to the DNA sequencing.ConclusionsMale genital warts predominantly show low-risk type HPV (HPV 6 and 11). However, high-risk HPV is not uncommon and the role of high-risk HPV in genital warts may be considered. The Gardasil 9 HPV vaccine is expected to provide protection against about >80% of male genital warts. Further HPV typing studies in male genital warts are necessary in other races and geographical areas to define the role and management of high-risk type HPV in male genital warts.
Co-transcriptional RNA strand displacement circuits
Authors: Schaffter Samuel W. , Strychalski Elizabeth A. 
Published: July 2021

AbstractEngineered molecular circuits that process information in biological systems could address emerging human health and biomanufacturing needs. However, such circuits can be difficult to rationally design and scale. DNA-based strand displacement reactions have demonstrated the largest and most computationally powerful molecular circuits to date but are limited in biological systems due to the difficulty in genetically encoding components. Here, we develop scalable co-transcriptional RNA strand displacement (ctRSD) circuits that are rationally programmed via base pairing interactions. ctRSD addresses the limitations of DNA-based strand displacement circuits by isothermally producing circuit components via transcription. We demonstrate the programmability of ctRSD in vitro by implementing logic and amplification elements, and multi-layer signaling cascades. Further, we show ctRSD kinetics are accurately predicted by a simple model of coupled transcription and strand displacement, enabling model-driven design. We envision ctRSD will enable rational design of powerful molecular circuits that operate in biological systems, including living cells.
Mechanisms of translation inhibition and suppression of Stress Granule formation by cisplatin
Authors: Pietras Paulina , Aulas Anaïs , Fay Marta M. , Leśniczak Marta , Lyons Shawn M , Szaflarski Witold , Ivanov Pavel 
Published: July 2021

ABSTRACTPlatinum-based antineoplastic drugs, such as cisplatin, are commonly used to induce tumor cell death. Cisplatin is believed to induce apoptosis as a result of cisplatin-DNA adducts that inhibit DNA and RNA synthesis. Although idea that DNA damage underlines anti-proliferative effects of cisplatin is dominant in cancer research, there is a poor correlation between the degree of the cell sensitivity to cisplatin and the extent of DNA platination. Here, we propose a novel mechanism of cisplatin-mediated cytotoxicity. We show that cisplatin suppresses formation of Stress Granules (SGs), pro-survival RNA granules with multiple roles in cellular metabolism. Mechanistically, cisplatin inhibits cellular translation to promote disassembly of polysomes and aggregation of ribosomal subunits. As SGs are in equilibrium with polysomes, cisplatin-induced shift towards ribosomal aggregation suppresses SG formation and promotes cellular death. Our data also explain nephrotoxic, neurotoxic and ototoxic effects of cisplatin treatment.
Neural Collision Detection: an open source library to study the three-dimensional interactions of neurons and other tree-like structures
Authors: Har-Gil Hagai , Jacobson Yoav , Prönneke Alvar , Staiger Jochen F. , Tomer Omri , Halperin Dan , Blinder Pablo 
Published: July 2021

AbstractThe analysis of neuronal structure and its relation to function has become a fundamental pillar in neuroscience since its earliest days, with the underlying premise that morphological properties can modulate neuronal computations. It is often the case that the rich three-dimensional structure of neurons is quantified by tools developed in other fields, such as graph theory and computational geometry; nevertheless, some of the more advanced tools developed in these fields have not yet been made accessible to the neuroscience community. Here we present Neural Collision Detection, a library providing high-level interfaces to collision-detection routines and alpha shape calculations, as well as statistical analysis and visualizations for 3D objects, with the aim to lower the entry gap for neuroscientists into these worlds. Our work here also demonstrates a variety of use cases for the library and exemplary analysis and visualizations that were carried out with it on real neuronal and vascular data.
ChAdOx1 NiV vaccination protects against lethal Nipah Bangladesh virus infection in African green monkeys
Authors: van Doremalen Neeltje , Avanzato Victoria A. , Feldmann Friederike , Schulz Jonathan E. , Haddock Elaine , Okumura Atsushi , Lovaglio Jamie , Hanley Patrick W. , Cordova Kathleen , Saturday Greg , Lambe Teresa , Gilbert Sarah C. , Munster Vincent J. 
Published: July 2021

AbstractNipah virus (NiV) is a highly pathogenic and re-emerging virus which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkeys (AGMs) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5- and 7-days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in all but one swab and all tissues. Importantly, no to limited antibodies against fusion protein or nucleoprotein IgG could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication.One Sentence SummaryA single vaccination with ChAdOx1 NiV protects African green monkeys against lethal disease induced by Nipah virus inoculation.
Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription
Authors: Arragain Benoît , Trouilleton Quentin Durieux , Baudin Florence , Cusack Stephen , Schoehn Guy , Malet Hélène 
Published: July 2021

ABSTRACTSegmented negative-strand RNA bunyaviruses encode a multi-functional polymerase that performs genome replication and transcription. Here, we establish conditions for in vitro activity of La Crosse virus polymerase and visualize by cryo-electron microscopy its conformational dynamics, unveiling the precise molecular mechanics underlying its essential activities. Replication initiation is coupled to distal duplex promoter formation, endonuclease movement, prime-and-realign loop extension and closure of the polymerase core that direct the template towards the active site. Transcription initiation depends on C-terminal region closure and endonuclease movements that firstly prompt primer cleavage and secondly promote primer entry in the active site. Product realignment after priming, observed in replication and transcription, is triggered by the prime-and-realign loop. Switch to elongation results in polymerase reorganization and core region opening to facilitate template-product duplex formation in the active site cavity. The detailed uncovered mechanics will be crucial for future design of antivirals counteracting bunyaviral life-threatening pathogens.
An untargeted metabolomic approach to identify antiviral defense mechanisms in memory leukocytes secreting in vitro IgG anti-SARS-Cov-2
Authors: Federica Gevi , Giuseppina Fanelli , Veronica Lelli , Gianpaolo Zarletti , Massimo Tiberi , Veronica De Molfetta , Giuseppe Scapigliati , Maria Timperio Anna 
Published: July 2021

AbstractAvailable knowledge shows that individuals infected by SARS-CoV-2 undergo an altered metabolic state in multiple organs. Metabolic activities are directly involved in modulating the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism relates with inflammatory responses. To better elucidate the underlying biochemistry of leukocytes response, we focused our analysis on the possible relationships between SARS-CoV-2 post-infection stages and distinct metabolic pathways. Indeed, in cultures of peripheral blood mononuclear cells (PBMC, n=48) obtained 60-90 days after infection and showing in vitro IgG antibody memory for spike-S1 antigen (n=19), we observed a significant altered metabolism of tryptophan and urea cycle pathways. This work for the first time identifies metabolic routes in cell metabolism possibly related to later stages of immune defense against SARS-Cov-2 infection, namely when circulating antibodies may be absent, but an antibody memory is present. The results suggest a reprogramming of leukocyte metabolism after viral pathogenesis through activation of specific amino acid pathways possibly related to protective immunity against SARS-CoV-2.
Immunodominant surface epitopes power immune evasion in the African trypanosome
Authors: Gkeka Anastasia , Aresta-Branco Francisco , Triller Gianna , Vlachou Evi P. , Lilic Mirjana , Olinares Paul Dominic B. , Perez Kathryn , Chait Brian T. , Blatnik Renata , Ruppert Thomas , Stebbins C. Erec , Papavasiliou F. Nina 
Published: July 2021

AbstractThe African trypanosome survives the immune response of its mammalian host by antigenic variation of its major surface antigen (the Variable Surface Glycoprotein, or VSG). Here we describe the antibody repertoires elicited by different VSGs. We show that the repertoires are highly restricted, and are directed predominantly to distinct epitopes on the surface of the VSGs. They are also highly discriminatory: minor alterations within these exposed epitopes confer antigenically-distinct properties to these VSGs and elicit different repertoires. We propose that the patterned and repetitive nature of the VSG coat focuses host immunity to a restricted set of immunodominant epitopes per VSG, eliciting a highly stereotyped response, minimizing cross reactivity between different VSGs and facilitating prolonged immune evasion through epitope variation.
Transcription factor regulation of eQTL activity across individuals and tissues
Authors: Flynn Elise D. , Tsu Athena L. , Kasela Silva , Kim-Hellmuth Sarah , Aguet Francois , Ardlie Kristin G. , Bussemaker Harmen J. , Mohammadi Pejman , Lappalainen Tuuli 
Published: July 2021

AbstractTens of thousands of genetic variants associated with gene expression (cis-eQTLs) have been discovered in the human population. These eQTLs are active in various tissues and contexts, but the molecular mechanisms of eQTL variability are poorly understood, hindering our understanding of genetic regulation across biological contexts. Since many eQTLs are believed to act by altering transcription factor (TF) binding affinity, we hypothesized that analyzing eQTL effect size as a function of TF level may allow discovery of mechanisms of eQTL variability. Using GTEx Consortium eQTL data from 49 tissues, we analyzed the interaction between eQTL effect size and TF level across tissues and across individuals within specific tissues and generated a list of 6,262 TF-eQTL interactions across 1,598 genes that are supported by at least two lines of evidence. These TF-eQTLs were enriched for various TF binding measures, supporting with orthogonal evidence that these eQTLs are regulated by the implicated TFs. We also found that our TF-eQTLs tend to overlap genes with gene-by-environment regulatory effects and to colocalize with GWAS loci, implying that our approach can help to elucidate mechanisms of context-specificity and trait associations. Finally, we highlight an interesting example of IKZF1 TF regulation of an APBB1IP gene eQTL that colocalizes with a GWAS signal for blood cell traits. Together, our findings provide candidate TF mechanisms for a large number of eQTLs and offer a generalizable approach for researchers to discover TF regulators of genetic variant effects in additional QTL datasets.Author SummaryGene expression is regulated by local genomic sequence and can be affected by genetic variants. In the human population, tens of thousands of cis-regulatory variants have been discovered that are associated with altered gene expression across tissues, cell types, or environmental conditions. Understanding the molecular mechanisms of how these small changes in the genome sequence affect genome function would offer insight to the genetic regulatory code and how gene expression is controlled across tissues and environments. Current research efforts suggest that many regulatory variants’ effects on gene expression are mediated by them altering the binding of transcription factors, which are proteins that bind to DNA to regulate gene expression. Here, we exploit the natural variation of TF activity among 49 tissues and between 838 individuals to elucidate which TFs regulate which regulatory variants. We find 6,262 TF-eQTL interactions across 1,598 genes that are supported by at least two lines of evidence. We validate these interactions using functional genomic and experimental approaches, and we find indication that they may pinpoint mechanisms of environment-specific genetic regulatory effects and genetic variants associated to diseases and traits.
SARS-CoV-2 Restructures the Host Chromatin Architecture
Authors: Wang Ruoyu , Lee Joo-Hyung , Xiong Feng , Kim Jieun , Hasani Lana Al , Yuan Xiaoyi , Shivshankar Pooja , Krakowiak Joanna , Qi Chuangye , Wang Yanyu , Eltzschig Holger K. , Li Wenbo 
Published: July 2021

ABSTRACTSARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin1, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model2 highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.
PRE-CLINICAL IMMUNE RESPONSE AND SAFETY EVALUATION OF THE PROTEIN SUBUNIT VACCINE NANOCOVAX FOR COVID-19
Authors: Mai Tran Thi Nhu , May Bruce , Thuan Ung Trong , Khoi Nguyen Mai , Trang Nguyen Thi Thuy , Van Long Dinh , Chung Doan Chinh , Vinh Tran The , Hiep Khong , Truc Nguyen Thi Thanh , Huy Hua Hoang Quoc , Anh Nguyen Viet , Phat Ha Tan , Luu Phan Dang , An Nguyen Truong , Ngoc Bui Thi , My Tu Tieu , Theo Nguyen Thi , Hang Le Thi Thuy , Lan Dong Thi , Hieu Huynh Trong , Huong Ho Phien , Thao Le Nguyen Thanh , Thao Truong Cong , Phi Pham Hoang , Luong Cong Y , Lim Nie , Ngoc Cao Minh , Khanh Nguyen Duy , Hung Trinh Thanh , Si Do Minh 
Published: July 2021

AbstractThe Coronavirus disease-2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has become a dire global health concern. The development of vaccines with high immunogenicity and safety is crucial for control of the global COVID-19 pandemic and prevention of further illness and fatalities. Here, we report development of SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the S protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG, as well neutralizing antibody in three animal models including Balb/C mice, Syrian hamsters, and non-human primate (Macaca leonina). In addition, the viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. No adverse effects were induced by Nanocovax in swiss mice (Musmusculus var. Albino), Rats (Rattus norvegicus), and New Zealand rabbits. These pre-clinical results indicated that Nanocovax is safe and effective.
Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil
Authors: Pogodalla Nicole , Kranenburg Holger , Rey Simone , Rodrigues Silke , Cardona Albert , Klämbt Christian 
Published: July 2021

AbstractIn the central nervous system (CNS), functional tasks are often allocated to distinct compartments. This is also evident in the insect CNS where synapses and dendrites are clustered in distinct neuropil regions. The neuropil is separated from neuronal cell bodies by ensheathing glia, which as we show using dye injection experiments forms an internal diffusion barrier. We find that ensheathing glial cells are polarized with a basolateral plasma membrane rich in phosphatidylinositol-(3,4,5)-triphosphate (PIP3) and the Na+/K+-ATPase Nervana2 (Nrv2) that abuts an extracellular matrix formed at neuropil-cortex interface. The apical plasma membrane is facing the neuropil and is rich in phosphatidylinositol-(4,5)-bisphosphate (PIP2) that is supported by a sub-membranous ßHeavy-Spectrin cytoskeleton. ßHeavy-spectrin mutant larvae affect ensheathing glial cell polarity with delocalized PIP2 and Nrv2 and exhibit an abnormal locomotion which is similarly shown by ensheathing glia ablated larvae. Thus, polarized glia compartmentalizes the brain and is essential for proper nervous system function.
Regular graph-based free route flight planning approach
Authors: Samolej Sławomir , Dec Grzegorz , Rzonca Dariusz , Majka Andrzej , Rogalski Tomasz 
Published: July 2021

Purpose
The purpose of this study is to provide an alternative graph-based airspace model for more effective free-route flight planning.

Design/methodology/approach
Based on graph theory and available data sets describing airspace, as well as weather phenomena, a new FRA model is proposed. The model is applied for near to optimal flight route finding. The software tool developed during the study and complexity analysis proved the applicability and timed effectivity of the flight planning approach.

Findings
The sparse bidirectional graph with edges connecting only (geographically) closest neighbours can naturally model local airspace and weather phenomena. It can be naturally applied to effective near to optimal flight route planning.

Research limitations/implications
Practical results were acquired for one country airspace model.

Practical implications
More efficient and applicable flight planning methodology was introduced.

Social implications
Aircraft following the new routes will fly shorter trajectories, which positively influence on the natural environment, flight time and fuel consumption.

Originality/value
The airspace model proposed is based on standard mathematical backgrounds. However, it includes the original airspace and weather mapping idea, as well as it enables to shorten flight planning computations.