bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative metagenomic analysis following treatment with vancomycin in C57BL/6 and BALB/c mice to elucidate host immunity and behavior
Authors: Ray Pratikshya , Das Debasmita , Pandey Uday , Aich Palok 
Published: May 2020

AbstractThe gut is the largest reservoir of the resident microbiota. The microbiota can affect the host behavior and immunity. While the consequence of treatment with antibiotics on the gut microbiota can be destructive but can be utilized as a tool to understand the host immunity and behavior. The magnitude of perturbation and time needed for the restoration of gut microbiota can depend on the immune bias of the host. In the current study, we therefore, observed the perturbation and restoration kinetics of gut microbiota following treatment with vancomycin and its effect on the host physiology in both Th1-(C57BL/6) and Th2-(BALB/c) biased mice. A comparative metagenomic analysis revealed that the treatment with vancomycin caused a significant decrease in the abundance of Firmicutes and Bacteroidetes phyla and an initial increase in Proteobacteria. Increase in Proteobacteria decreased with continued treatment with vancomycin to result into a significant rise in Verrucomicrobia phylum. We established the patterns of gut microbiota alteration and its effect on a) the behavior of mice, b) expression of key brain molecules and b) immunity related genes. We followed the gut microbiome restoration for a period of two months following withdrawal of treatment with vancomycin. Maximum restoration (>70%) of gut microbiota happened by the 15thday of withdrawal. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. The results, in general, revealed that along with the restoration of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal level.
Detection of SARS-CoV-2 RNA on public surfaces in a densely populated urban
area of Brazil
Authors: Abrahão Jônatas Santos , Sacchetto Lívia , Rezende Izabela Mauricio , Rodrigues Rodrigo , Crispim Ana Paula Correia , Moura César , Mendonça Diogo Correa , Reis Erik , Souza Fernanda , Oliveira Gabriela Fernanda Garcia , Domingos Iago José da Silva , Boratto Paulo , Silva Pedro Henrique Bastos e , Queiroz Victoria Fulgêncio , de Souza Silva Thaís Bárbara , Oliveira Graziele Pereira , de Souza Alves Viviane , Alves Pedro Augusto , Kroon Erna Geessien , de Souza Trindade Giliane , Drumond Betânia Paiva 
Published: May 2020

Abstract

Importance
The COVID-19 pandemic has resulted in more than 3.5 million cases and
245 thousand deaths worldwide as of May 6, 2020. Determining the extent of
the presence of the virus on public surfaces is critical for understanding
the potential risk of infection in these areas.

Objective
To evaluate the presence of SARS-CoV-2 RNA on public surfaces in a
densely populated urban area in Brazil.

Design and Setting
A total of 101 samples were collected from different surfaces in public
places in the region of Belo Horizonte with the highest number of COVID-19
cases. Samples were collected near the hospital and public transportation
areas using sterile swabs, and then submitted to nucleic acid extraction and
genomic detection and quantification by one-step qPCR.

Results
Seventeen of the 101 samples tested positive (16.8%) for SARS-CoV-2 RNA,
including samples from bus stations/terminals, public squares, and
sidewalks, including those near hospitals.

Conclusions and Relevance
Our data indicated the contamination of public surfaces by SARS-CoV-2,
especially near hospital areas, highlighting the risk of infection for the
population. Constant monitoring of the virus in urban areas is required as a
strategy to fight the pandemic and prevent further infections.

Key points

Question

Can SARS-CoV-2 be detected on surfaces in public areas used by a large
proportion of the population?

Findings
SARS-CoV-2 RNA was detected in different locations, including bus
stations/terminals, squares, and sidewalks, especially those near hospitals,
in a densely populated area of Belo Horizonte, Brazil.

Meaning
This study highlights the need for constant monitoring for the presence
of SARS-CoV-2 RNA in urban areas to support better strategies to fight the
COVID-19 pandemic and prevent further infections.
Defensin-driven viral evolution
Authors: Diaz Karina , Hu Ciara T. , Sul Youngmee , Bromme Beth A. , Myers Nicolle D. , Skorohodova Ksenia V. , Gounder Anshu P. , Smith Jason G. 
Published: May 2020

AbstractEnteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant to defensins and even appropriate them to enhance infection, despite neutralization of closely related microbes. We therefore hypothesized that defensins impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype of adenovirus in the presence of a human defensin, mutations in the major capsid protein hexon accumulated. In contrast, prior studies identified the vertex proteins as important determinants of defensin antiviral activity. Through infection and biochemical assays, we found that although all major capsid proteins serve a critical role in defensin-mediated neutralization, hexon is the sole determinant of enhancement. These results extensively revise our understanding of the interplay between defensins and non-enveloped viruses. Furthermore, they provide a feasible rationale for defensins shaping viral evolution, resulting in differences in infection phenotypes of closely related viruses.Author SummaryDefensins are potent antimicrobial peptides that are found on human mucosal surfaces and can directly neutralize viruses. They are abundant in the small intestine, which is constantly challenged by ingested viral pathogens. Interestingly, non-enveloped viruses, such as adenovirus, that infect the gastrointestinal system are unaffected by defensins or can even appropriate defensins to enhance their infection. In contrast, respiratory adenoviruses are neutralized by the same defensins. How enteric viruses overcome defensin neutralization is not well understood. Our studies are the first to show that defensins can drive the evolution of non-enveloped viruses. Furthermore, we identify important components within human adenovirus that dictate sensitivity to defensins. This refined understanding of defensin-virus interactions informs the development of defensin-based therapeutics.
Zika virus infection during pregnancy protects against secondary infection in the absence of CD8+ cells
Authors: Schouest Blake , Gilbert Margaret H. , Bohm Rudolf P , Schiro Faith , Aye Pyone P. , Panganiban Antonito T , Magnani Diogo M. , Maness Nicholas J 
Published: May 2020

AbstractWhile T cell immunity is an important component of the immune response to Zika virus (ZIKV) infection generally, the efficacy of these responses during pregnancy remains unknown. Here, we tested the capacity of CD8 lymphocytes to protect from secondary challenge in four macaques, two of which were depleted of CD8+ cells prior to rechallenge with a heterologous ZIKV isolate. The initial challenge during pregnancy produced transcriptional signatures suggesting complex patterns of immune modulation, but all animals efficiently controlled the rechallenge virus, implying that the primary infection conferred adequate protection. The secondary challenge promoted humoral responses and activation of innate and adaptive immune cells, suggesting a brief period of infection prior to clearance. These data confirm that ZIKV infection during pregnancy induces sufficient immunity to protect from a secondary challenge and suggest that this protection is not solely dependent on CD8 T cells but entails multiple arms of the immune system.
Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19
Authors: Ren Xiaohan , Wei Xiyi , Li Guangyao , Ren Shancheng , Chen Xinglin , Zhang Tongtong , Zhang Xu , Lu Zhongwen , You Zebing , Wang Shangqian , Qin Chao , Song Ninghong , Wang Zengjun 
Published: May 2020

AbstractBackgroundSince December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. From previously published evidence, ACE2 and TMPRSS2, are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Meanwhile, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome that is often observed in critically ill patients.MethodsWe investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially under specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2 specific signature.ResultsOur results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis, and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were remarkably concentrated in endothelial cells, macrophages, and spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging mechanisms via autoimmune attacks.ConclusionsThis study provided new insights into the pathogenicity mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.
Photorespiration pathways in a chemolithoautotroph
Authors: Claassens Nico J. , Scarinci Giovanni , Fischer Axel , Flamholz Avi I. , Newell William , Frielingsdorf Stefan , Lenz Oliver , Bar-Even Arren 
Published: May 2020

AbstractCarbon fixation via the Calvin cycle is constrained by the side activity of Rubisco with dioxygen, generating 2-phosphoglycolate. The metabolic recycling of 2-phosphoglycolate, an essential process termed photorespiration, was extensively studied in photoautotrophic organisms, including plants, algae, and cyanobacteria, but remains uncharacterized in chemolithoautotrophic bacteria. Here, we study photorespiration in the model chemolithoautotrophCupriavidus necator(Ralstonia eutropha) by characterizing the proxy-process of glycolate metabolism, performing comparative transcriptomics of autotrophic growth under low and high CO2concentrations, and testing autotrophic growth phenotypes of gene deletion strains at ambient CO2. We find that the canonical plant-like C2cycle does not operate in this bacterium and instead the bacterial-like glycerate pathway is the main photorespiratory pathway. Upon disruption of the glycerate pathway, we find that an oxidative pathway, which we term the malate cycle, supports photorespiration. In this cycle, glyoxylate is condensed with acetyl-CoA to give malate, which undergoes two oxidative decarboxylation steps to regenerate acetyl-CoA. When both pathways are disrupted, autotrophic growth is abolished at ambient CO2. We present bioinformatic data suggesting that the malate cycle may support photorespiration in diverse chemolithoautotrophic bacteria. This study thus demonstrates a so-far unknown photorespiration pathway, highlighting important diversity in microbial carbon fixation metabolism.
A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability
Authors: Chi Xiangyang , Yan Renhong , Zhang Jun , Zhang Guanying , Zhang Yuanyuan , Hao Meng , Zhang Zhe , Fan Pengfei , Dong Yunzhu , Yang Yilong , Chen Zhengshan , Guo Yingying , Zhang Jinlong , Li Yaning , Song Xiaohong , Chen Yi , Xia Lu , Fu Ling , Hou Lihua , Xu Junjie , Yu Changming , Li Jianmin , Zhou Qiang , Chen Wei 
Published: May 2020

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.
A conserved D/E-P motif in the nucleotide binding domain of plant ABCB/PGP-type ABC transporters defines their auxin transport capacity
Authors: Hao Pengchao , Xia Jian , Liu Jie , diDonato Martin , Pakula Konrad , Bailly Aurélien , Jasinski Michal , Geisler Markus 
Published: May 2020

AbstractAuxin transport activity of ABCB1 was suggested to be regulated by physical interaction with the FKBP42/Twisted Dwarf1 (TWD1), abona fidepeptidylprolylcis-transisomerase (PPIase), but all attempts to demonstrate such a PPIase activity on TWD1 have failed so far.By using a structure-based approach we have identified a series of surface-exposed proline residues in the C-terminal nucleotide binding fold and linker of Arabidopsis ABCB1 that do not alter ABCB1 protein stability or location but its catalytic transport activity. P1.008 was uncovered as part of a conserved signature D/E-P motif that seems to be specific forAuxin-TransportingABCBs, we now refer to as ATAs. Beside the proline, also mutation of the acidic moiety prior to the proline abolishes auxin transport activity by ABCB1. So far, all higher plant ABCBs for that auxin transport was safely proven carry this conserved motif underlining its diagnostic potential. Introduction of this D/E-P motif into malate importer, ABCB14, increases both its malate and its background auxin transport activity, suggesting that this motif has an impact on transport capacity. The D/E-P1.008 motif is also important for ABCB1-TWD1 interaction and activation of ABCB1-mediated auxin transport by TWD1, supporting a scenario in that TWD1 acts as an activator of ABCB1 transport activity by means of its PPIase.In summary, our data imply a dual function for TWD1 acting as an ABCB co-chaperone required for ABCB biogenesis and as a putative activator of ABCB-mediated auxin transport bycis-transisomerization of peptidyl-prolyl bonds.
ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity
Authors: Ali Fedaa , Elserafy Menattallah , Alkordi Mohamed H. , Amin Muhamed 
Published: May 2020

AbstractThe susceptibility of different populations to the SARS-CoV-2 infection is not yet understood. A deeper analysis of the genomes of individuals from different populations might explain their risk for infection. In this study, a combined analysis of ACE2 coding variants in different populations and computational chemistry calculations are conducted in order to probe the potential effects of ACE2 coding variants on SARS-CoV-2/ACE2 binding affinity. Our study reveals novel interaction data on the variants and SARS-CoV-2. We could show that ACE2-K26R; which is more frequent in the Ashkenazi Jewish population decrease the electrostatic attraction between SARS-CoV-2 and ACE2. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R were found to increase the electrostatic attraction and increase the binding to SARS-CoV-2; ordered by the strength of binding from weakest to strongest. I468V, R219C, K341R, D206G and G211R were more frequent in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. SARS-CoV-2/ACE2 interface in the WT protein and corresponding variants is showed to be a dominated by van der Waals (vdW) interactions. All the mutations except K341R induce an increase in the vdW attractions between the ACE2 and the SARS-CoV-2. The largest increase of is observed for the R219C mutant.
Proteomic Analysis Uncovers Measles Virus Protein C Interaction with p65/iASPP/p53 Protein Complex
Authors: Meignié Alice , Combredet Chantal , Santolini Marc , Kovács István A. , Douché Thibaut , Gianetto Quentin Giai , Eun Hyeju , Matondo Mariette , Jacob Yves , Grailhe Regis , Tangy Frédéric , Komarova Anastassia V. 
Published: May 2020

ABSTRACTViruses manipulate central machineries of host cells to their advantage. They prevent host cell antiviral responses to create a favorable environment for their survival and propagation. Measles virus (MV) encodes two non-structural proteins MV-V and MV-C known to counteract the host interferon response and to regulate cell death pathways. Several molecular mechanisms underlining MV-V regulation of innate immunity and cell death pathways have been proposed, whereas MV-C host protein partners are less studied. We suggest that some cellular factors that are controlled by MV-C protein during viral replication could be components of innate immunity and the cell death pathways. To determine which host factors are targeted by MV-C, we captured both direct and indirect host protein partners of MV-C protein. For this, we used a strategy based on recombinant viruses expressing tagged viral proteins followed by affinity purification and a bottom-up mass spectrometry analysis. From the list of host proteins specifically interacting with MV-C protein in different cell lines we selected the host targets that belong to immunity and cell death pathways for further validation. Direct protein partners of MV-C were determined by applying protein complementation assay (PCA) and the bioluminescence resonance energy transfer (BRET) approach. As a result, we found that MV-C protein specifically interacts with p65/iASPP/p53 protein complex that controls both cell death and innate immunity pathways.
Phytosphingosine induces systemic acquired resistance through activation of sphingosine kinase
Authors: Seo So Yeon , Kim Yu Jung , Nam Myung Hee , Park Ky Young 
Published: May 2020

AbstractPhytosphingosine (PHS) is a naturally occurring bioactive sphingolipid molecule. Intermediates such as sphingolipid long-chain bases (LCBs) in sphingolipid biosynthesis have been shown to have important roles as signaling molecules. In this study, exogenous addition of PHS caused rapid induction of transcripts responsible for transient synthesis of LCBs, reactive oxygen species, and ethylene. These events were followed by the induction of sphingolipid kinase (SphK), which metabolized PHS to phytosphingosine-1-phosphate in an biphasic manner. PHS alleviated not only pathogen-induced cell damage but also reduced the growth of virulent pathogens in the entire upper part of the PHS-treated plant stem during the necrotic stage after inoculation, suggesting the development of systemic acquired resistance (SAR) and plant immunity. Moreover, PHS treatment up-regulated the transcription and activity of SphK, accompanied by prominent increases in the transcription levels of serine palmitoyltransferase (LCB1andLCB2) forde novosynthesis of sphingolipids, as well as ROS-detoxifying enzymes and PR proteins at 48 h after virulent pathogen infection. The impairment of ROS production at this time is more beneficial for the activation of SphK and inhibition of pathogenicity during the necrotic stage of hemibiotrophic infection, indicating that necrotic cell death at the late stage is regulated by ROS-independent SphK. Phosphorylated LCBs significantly reduced pathogen-induced cell damage. These observations suggest that selective channeling of sphingolipids into phosphorylated forms in a time-dependent manner has a pro-survival effect by promoting SAR in plant immunity.4.One Sentence SummarySelective gene expression in sphingolipid biosynthesis and channeling into their phosphorylated forms are significant determinants of their roles as pro-survival signaling molecules.
A single-cell RNA expression map of human coronavirus entry factors
Authors: Singh Manvendra , Bansal Vikas , Feschotte Cédric 
Published: May 2020

SUMMARYTo predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell RNA-sequencing data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of the small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear most permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, central nervous system, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, to be highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early stages of embryonic and placental development show a moderate risk of infection. The nasal epithelium looks like another battleground, characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across human, chimpanzee and macaque organs examined. Our study establishes an important resource for investigations of coronavirus biology and pathology.
Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding
Authors: Gentles Lauren E. , Wan Hongquan , Eichelberger Maryna C. , Bloom Jesse D. 
Published: May 2020

AbstractInfluenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. But antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well-neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitivein vitrodetection of antibodies binding near the catalytic site of NA and enable selection of viral escape mutants.