bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial profiles and their antimicrobial susceptibility pattern of Isolates from inanimate hospital environments at Tikur Anbessa Specialized Teaching Hospital, Addis Ababa, Ethiopia
Authors: Sebre Shemse , Erku Woldaregay , Seman Aminu , Awoke Tewachw , Desalegn Zelalem , Mihret Wude , Mihret Adane , Abebe Tamrat 
Published: September 2020

AbstractMicrobial contamination of hospital environment plays an important role in the spread of health care-associated infections (HCAIs). This study was conducted to determine bacterial contamination, bacterial profiles and antimicrobial susceptibility pattern of bacterial isolates from environmental surfaces and medical equipment. A cross-sectional study was conducted at Tikur Anbessa Specialized Hospital (TASH) from June to September, 2018. A total of 164 inanimate surfaces located at intensive care units (ICUs) and operation theaters (OTs) were swabbed. All isolates were identified by using routine bacterial culture, Gram staining and a panel of biochemical tests. For each identified bacteria, antibiogram profiles were determined by the Kirby Bauer disk diffusion method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Out of the 164 swabbed samples, 141 (86%) were positive for bacterial growth. The predominant bacteria identified from OTs and ICUs wereS. aureus(23% vs 11.5%),Acinetobacterspp (3.8% vs 17.5%) and Coagulase negativeStaphylococcus(CONS) (12.6% vs 2.7%) respectively. Linens were the most contaminated materials among items studied at the hospital (14.8%). The proportions of resistance among Gram-positive bacteria (GPB) were high for penicillin (92.8%), cefoxitin (83.5%) and erythromycin (54.1%). However, the most effective antibiotics were clindamycin with only 10.4% and 16.5% resistance rates, respectively. The antimicrobial susceptibility profiles of Gram-negative bacteria (GNB) revealed that the most effective antibiotics were amikacin, ciprofloxacin, and gentamicin with resistance rate of 25%, 37.5%, and 46.3%, respectively. However, the highest resistance was recorded against ampicillin (97.5%), ceftazidime (91.3%), ceftriaxone (91.3%) and aztreonam (90%). The inanimate surfaces near immediate patient environment and commonly touched medical equipment within OTs and ICUs are reservoirs of potential pathogenic bacteria that could predispose critically ill patients to acquire HCAIs. The proportions of antimicrobial resistance profile of the isolates are much higher from studied clean inanimate environments.
SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells
Authors: Hong Bixia , Lai Xinyuan , Chen Yangzhen , Luo Tianming , An Xiaoping , Song Lihua , Zhuang Hui , Fan Huahao , Li Tong , Xiang Kuanhui , Tong Yigang 
Published: September 2020

AbstractSince the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.
Microbial map of the world’s vineyards: Applying the concept of microbialterroiron a global scale
Authors: Gobbi A. , Acedo A. , Imam N. , Santini R.G. , Ortiz-Álvarez R. , Ellegaard-Jensen L. , Belda I. , Hansen L.H. 
Published: September 2020

AbstractThe specific microbial biodiversity linked to a particular vineyard location is reported to be a crucial aspect, in conjunction with edaphic, climatic and human factors, in the concept of wineterroir. These biogeographical patterns are known as microbialterroirs.This study applied an HTS amplicon library approach in order to conduct a global survey of vineyards’ soil microbial communities. In all, soil samples from 200 vineyards on four continents were analysed in an attempt to establish the basis for the development of a vineyard soil microbiome map to represent microbial wineterroirson a global scale.This study established links between vineyard locations and microbial biodiversity on different scales: between continents and countries, and between different wine regions within the same country. Geography had a strong effect on the composition of microbial communities on a global scale, which was also maintained on a country scale. Furthermore, a predictive model was developed, based on random forest analyses, to discriminate between microbial patterns in order to identify the geographical source of the samples with reasonable precision. Finally this study is the first to describe the microbial community of new and northern wine-producing regions, such as Denmark, that could be of great interest for viticulture adaptation in a context of climate change.
A high affinity human monoclonal antibody against Pfs230 binds multiple parasite stages and blocks oocyst formation in mosquitoes
Authors: Coelho Camila H. , Tang Wai Kwan , Burkhardt Martin , Galson Jacob D. , Muratova Olga , Salinas Nichole D. , Silva Thiago Luiz Alves e , Reiter Karine , MacDonald Nicholas J. , Nguyen Vu , Herrera Raul , Shimp Richard , Narum David L. , Byrne-Steele Miranda , Pan Wenjing , Hou Xiaohong , Brown Brittany , Eisenhower Mary , Han Jian , Jenkins Bethany J. , Doritchamou Justin Yai Alamou , Smelkinson Margery G. , Vega-Rodriguez Joel , Trück Johannes , Taylor Justin J. , Sagara Issaka , Renn Jonathan P. , Tolia Niraj H. , Duffy Patrick E. 
Published: September 2020

ABSTRACTMalaria elimination requires tools that interrupt parasite transmission. Here, we characterized B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230kDa gamete surface protein Pfs2301–3to neutralize sexual stageP. falciparumparasites and halt their further spread. We generated nine Pfs230 human monoclonal antibodies (mAbs). One mAb potently blocked transmission to mosquitoes in a complement-dependent manner and reacted strongly to gamete surface while eight mAbs showed only low or no blocking activity. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.
Meta-analysis of MERS, SARS and COVID-19in vitroInfection Datasets Reveals Common Patterns in Gene and Protein Expression
Authors: Martinelli Axel , Akhmedov Murodzhon , Kwee Ivo 
Published: September 2020

AbstractThree lethal lower respiratory tract coronavirus epidemics have occurred over the past 20 years. This coincided with major developments in genome-wide gene and protein expression analysis, resulting in a wealth of datasets in the public domain. Seven such invitrostudies were selected for comparative bioinformatic analysis through the VirOmics Playground, a visualisation and exploration platform we developed. Despite the heterogeneous nature of the data sets, several commonalities could be observed across studies and species. Differences, on the other hand, reflected not only variations between species, but also other experimental variables, such as cell lines used for the experiments, infection protocols and viral strains. The datasets analysed here are available online through our platform (https://public.bigomics.ch/app/omicsplayground_viromics).
A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters
Authors: Fagre Anna C. , Manhard John , Adams Rachel , Eckley Miles , Zhan Shijun , Lewis Juliette , Rocha Savannah M. , Woods Catherine , Kuo Karina , Liao Wuxiang , Li Lin , Corper Adam , Challa Dilip , Mount Emily , Tumanut Christine , Tjalkens Ronald B. , Aboelleil Tawfik , Fan Xiaomin , Schountz Tony 
Published: September 2020

AbstractThe emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virusin vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.
Adaptive and maladaptive expression plasticity underlying herbicide resistance in an agricultural weed
Authors: Josephs Emily B. , Van Etten Megan L. , Harkess Alex , Platts Adrian , Baucom Regina S. 
Published: September 2020

AbstractPlastic phenotypic responses to environmental change are common, yet we lack a clear understanding of the fitness consequences of these plastic responses. Here, we use the evolution of herbicide resistance in the common morning glory (Ipomoea purpurea) as a model for understanding the relative importance of adaptive and maladaptive gene expression responses to herbicide. Specifically, we compare leaf gene expression changes caused by herbicide to the expression changes that evolve in response to artificial selection for herbicide resistance. We identify a number of genes that show plastic and evolved responses to herbicide and find that for the majority of genes with both plastic and evolved responses, plastic responses appear to be adaptive. We also find that selection for herbicide response increases gene expression plasticity. Overall, these results show the importance of adaptive plasticity for herbicide resistance in a common weed and that expression changes in response to strong environmental change can be adaptive.Impact statementPredicting whether and how organisms will adapt to environmental change is a crucial goal. However, this goal can be complicated because environmental change can alter traits, in a process called plasticity. The extent and fitness consequences of plasticity will have important effects on the adaptive process. In this study, we use adaptation to herbicide in the agricultural weed, the common morning glory, as a model for understanding the extent and fitness consequences of plasticity in gene expression. We find evidence that gene expression plasticity is adaptive in the presence of herbicide, suggesting that understanding plasticity is crucial for understanding how organisms adapt to new environments.
The extracellular matrix protein agrin is essential for epicardial epithelial-to-mesenchymal transition during heart development
Authors: Sun Xin , Malandraki-Miller Sophia , Kennedy Tahnee , Bassat Elad , Klaourakis Konstantinos , Zhao Jia , Gamen Elisabetta , Vieira Joaquim Miguel , Tzahor Eldad , Riley Paul R. 
Published: September 2020

AbstractDuring embryonic heart development, epicardial cells residing within the outer layer of the heart undergo epithelial-mesenchymal transition (EMT) and migrate into the myocardium to support and stimulate organ growth and morphogenesis. Disruption of epicardial EMT results in aberrant heart formation and embryonic lethality. Despite being an essential process during development, the regulation of epicardial EMT is poorly understood. Here we report EMT on the epicardial surface of the embryonic heart at subcellular resolution using scanning electron microscopy (SEM). We identified high- and low-EMT regions within the mesothelial layer of the epicardium and an association with key components of the extracellular matrix (ECM). The ECM basement membrane-associated proteoglycan agrin was found to localize in the epicardium in regions actively undergoing EMT. Deletion of agrin resulted in impaired EMT and compromised development of the epicardium, accompanied by down-regulation of the epicardial EMT regulator WT1. Agrin enhanced EMT in human embryonic stem cell-derived epicardial-like cells by decreasing β-catenin and promoting pFAK localization at focal adhesions. In addition, agrin promoted the aggregation of its receptor dystroglycan to the Golgi apparatus in murine epicardial cells and loss of agrin resulted in dispersal of dystroglycan throughout the epicardial cells in embryos, disrupting basement membrane integrity and impairing EMT. Our results provide new insights into the role of the ECM in heart development, and implicate agrin as a critical regulator of EMT, functioning to ensure dystroglycan connects signals between the ECM and activated epicardial cells.Summary statementThe basement membrane-associated proteoglycan agrin regulates epicardial epithelia-to-mesenchyme transition (EMT) through dystroglycan localizing on the Golgi apparatus. This ensures ECM and cytoskeletal connectivity and mechanical integrity of the transitioning epicardium and has important implications for the role of the extracellular matrix (ECM) in heart development.
Exponential-family embedding with application to cell developmental trajectories for single-cell RNA-seq data
Authors: Lin Kevin Z. , Lei Jing , Roeder Kathryn 
Published: September 2020

AbstractScientists often embed cells into a lower-dimensional space when studying single-cell RNA-seq data for improved downstream analyses such as developmental trajectory analyses, but the statistical properties of such non-linear embedding methods are often not well understood. In this article, we develop theeSVD(exponential-family SVD), a non-linear embedding method for both cells and genes jointly with respect to a random dot product model using exponential-family distributions. Our estimator uses alternating minimization, which enables us to have a computationally-efficient method, prove the identifiability conditions and consistency of our method, and provide statistically-principled procedures to tune our method. All these qualities help advance the single-cell embedding literature, and we provide extensive simulations to demonstrate that the eSVD is competitive compared to other embedding methods.We apply the eSVD via Gaussian distributions where the standard deviations are proportional to the means to analyze a single-cell dataset of oligodendrocytes in mouse brains (Marques et al., 2016). Using the eSVD estimated embedding, we then investigate the cell developmental trajectories of the oligodendrocytes. While previous results are not able to distinguish the trajectories among the mature oligodendrocyte cell types, our diagnostics and results demonstrate there are two major developmental trajectories that diverge at mature oligodendrocytes.
Insights into the mechanism of bovine spermiogenesis based on comparative transcriptomic studies
Authors: Li Xin , Duan Chenying , Li Ruyi , Wang Dong 
Published: September 2020

AbstractTo reduce the reproductive loss caused by semen quality and provide theoretical guidance for the eradication of human male infertility, differential analysis of the bovine transcriptome among round spermatids, elongated spermatids, and epididymal sperm was carried out with the reference of the mouse transcriptome, and the homology trends of gene expression to the mouse were also analysed. First, to explore the physiological mechanism of spermiogenesis that profoundly affects semen quality, homological trends of differential genes were compared during spermiogenesis in dairy cattle and mice. Next, the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network (PPI network), and bioinformatics analysis uncovered the regulation network of acrosome formation during the transition from round to elongated spermatids. In addition, processes that regulate gene expression during spermiogenesis from elongated spermatid to epididymal sperm, such as ubiquitination, acetylation, deacetylation, glycosylation, and the functional gene ART3 may play an important role during spermiogenesis. Therefore, its localisation in the seminiferous tubule was investigated by immunofluorescent analysis, and its structure and function were also predicted. This study provides important data for revealing the mystery of life during spermiogenesis resulting from acrosome formation, histone replacement, and the fine regulation of gene expression.
Origin of diverse phosphorylation patterns in the ERBB system
Authors: Okada T. , Miyagi H. , Sako Y. , Hiroshima M. , Mochizuki A. 
Published: September 2020

AbstractIntercellular signals induce various cellular responses, including growth, proliferation, and differentiation, via the dynamic processes of signal transduction pathways. For cell-fate decisions, ligand-binding induces the phosphorylation of ERBB receptors, which in turn activate downstream molecules. The ERBB family includes four subtypes, which diverged through two gene duplications from a common ancestor, of different kinetic properties. Differences in the expression patterns of the subtypes have been reported between different organs in the human body. However, how these different kinetic and expression properties influence the diverse phosphorylation dynamics of ERBB proteins is not well understood. Here we study the phosphorylation dynamics by experimental and mathematical analyses. The experimental measurements clarified that the phosphorylation dynamics heavily depend on the ERBB expression profiles. We developed a mathematical model consisting of the four subtypes as monomers, homodimers and heterodimers and estimated the rate constants governing the phosphorylation dynamics from the experimental data. To understand the origin of the diversity of the phosphorylation responses of the ERBB system, we analyzed the expression profiles and reaction rates of the ERBB subtypes. The difference in phosphorylation rates between ERBB subtypes showed a much larger contribution to the diversity of the phosphorylation responses than did the dimerization rates. This result implies that divergent evolution in phosphorylation reactions rather than in dimerization reactions after whole genome duplications was essential for increasing the diversity of the phosphorylation responses.Statement of SignificanceIt is known that the expression patterns of a protein family are different between different organs in the human body. This difference is considered essential for the functional diversity between organs. However, the dynamical processes that translate expression patterns into function are not well understood. Here we study the origin of the diversity in ERBB phosphorylation patterns by combining experimental and mathematical methods. We confirmed experimentally that phosphorylation patterns depend on the ERBB expression profiles. Our mathematical model found that differences in phosphorylation rates made the largest contribution to the diversity of phosphorylation patterns between ERBB subtypes.
Single-molecule light-sheet microscopy with local nanopipette delivery
Authors: Li B. , Ponjavic A. , Chen W. H. , Hopkins L. , Hughes C. , Ye Y. , Bryant C. , Klenerman D. 
Published: September 2020

AbstractDetection of single molecules in biological systems has rapidly increased in resolution over the past decade. However, delivery of single molecules has remained a challenge. Currently there is no effective method that can both introduce a precise amount of molecules onto or into a single cell at a defined position, and then image the cellular response. Here we have combined light sheet microscopy with local delivery, using a nanopipette, to accurately deliver individual proteins to a defined position. We call this method local delivery selective plane illumination microscopy (ldSPIM). ldSPIM uses a nanopipette and the ionic feedback current at the nanopipette tip to control the position from which molecules are delivered. The number of proteins delivered can be controlled by varying the voltage applied. For single-molecule detection, we implemented single-objective SPIM using a reflective atomic force microscopy cantilever to create a 2µm thin sheet. Using this setup, we demonstrate that ldSPIM can deliver single fluorescently-labeled proteins onto the plasma membrane of HK293 cells or into the cytoplasm. Next, we deposited aggregates of amyloid-β, which causes proteotoxicity relevant to Alzheimer’s disease, onto a single macrophage stably expressing a MyDD88-eGFP fusion construct. Whole-cell imaging in 3D mode enables live detection of MyDD88 accumulation and formation of MyDDosome signaling complexes, as a result of aggregate-induced triggering of toll-like receptor 4. Overall, we demonstrate a novel multifunctional imaging system capable of precise delivery of single proteins to a specific location on the cell surface or inside the cytoplasm and high-speed 3D detection at single-molecule resolution within live cells.Statement of SignificanceThis paper describes and validates a new method to study biological processes based on the controlled local delivery of molecules onto or into the cell, combined with single molecule imaging using light sheet microscopy. we not only demonstrate the instrument’s capability of delivering controlled numbers of molecules to a defined position, down to the level of single molecules, but also its potential in study of the triggering of the innate immune response by protein aggregates, a key process in the development of neurodegenerative diseases such as Alzheimer’s disease. The same approach could be applied to a wide range of other important biological processes allowing them to be followed in live cells in real-time, hence it will be of great interest to the biophysical community.