bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effectiveness Study of Home-Based Interventions to Prevent CA-MRSA Infection Recurrence
Authors: Tobin Jonathan N. , Hower Suzanne , D’Orazio Brianna M. , de la Gándara María Pardos , Evering Teresa H. , Khalida Chamanara , Kost Rhonda G. , Vasquez Kimberly S. , de Lencastre Hermínia , Tomasz Alexander , Coller Barry S. , Vaughan Roger 
Published: July 2020

BACKGROUNDRecurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant (CA-MRSA) or Methicillin-SensitiveStaphylococcus aureus(CA-MSSA) present treatment challenges.OBJECTIVESCan an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) reduce SSTI recurrence, mitigate household contamination and transmission, and improve patient-reported outcomes?DESIGNRandomized trialSETTINGCommunity settingsPARTICIPANTSParticipants (n=186) with confirmed MRSA(+)/MSSA(+) SSTIs and household members.INTERVENTION Community Health Workers/Promotoras conducted home visits and provided participants with instructions, a five-day supply of mupirocin for nasal application, chlorhexidine for body cleansing, and disinfecting wipes for household cleaning (EXP) versus Usual Care (UC).MEASUREMENTSPrimary outcome was six-month SSTI recurrence recorded in electronic health records (EHR). Home visits (months 0/3) and telephone assessments (months 0/1/6) collected self-report data. Surveillance culture swabs (nares, axilla, groin) were obtained from index patients and participating household members. Secondary outcomes included household surface contamination, household member colonization and transmission, quality of life and satisfaction with care.RESULTSAmong patients with SSTIs (n=421), 44.2% were MRSA(+)/MSSA(+); an intent-to-treat analyses (n=186) demonstrated no significant differences in SSTI recurrence (OR: 1.4, 95% CI: 0.51-3.5). Among the enrolled cohort (n=119), there were no significant SSTI recurrence effects (OR=1.14, 95% CI=0.35-3.6). EXP participants showed reduced but non-significant colonization rates. There were no differential reductions in household member transmission or in reductions in proportions of households with ≥1 contaminated surface. Mupirocin resistance did not increase. No significant improvements for patient-reported outcomes were seen.LIMITATIONSA lower-than-predicted six-month recurrence rate may have limited the ability to detect effects.CONCLUSIONThis intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. No differences were observed for household members decolonization or household surfaces decontamination.
The architecture of the centriole cartwheel-containing region revealed by cryo-electron tomography
Authors: Klena Nikolai , Le Guennec Maeva , Tassin Anne-Marie , van den Hoek Hugo , Erdmann Philipp S. , Schaffer Miroslava , Geimer Stefan , Aeschlimann Gabriel , Kovacik Lubomir , Goldie Kenneth N. , Stahlberg Henning , Engel Benjamin D. , Hamel Virginie , Guichard Paul 
Published: July 2020

AbstractCentrioles are evolutionarily conserved barrels of microtubule triplets that form the core of the centrosome and the base of the cilium. In the proximal region of the centriole, nine microtubule triplets attach to each other via A-C linkers and encircle a central cartwheel structure, which directs the early events of centriole assembly. While the crucial role of the proximal region in centriole biogenesis has been well documented in many species, its native architecture and evolutionary conservation remain relatively unexplored. Here, using cryo-electron tomography of centrioles from four evolutionarily distant species, including humans, we report on the architectural diversity of the centriolar proximal cartwheel-bearing region. Our work reveals that the cartwheel central hub, previously reported to have an 8.5 nm periodicity inTrichonympha, is constructed from a stack of paired rings with an average periodicity of ∼4 nm. In all four examined species, cartwheel inner densities are found inside the hub’s ring-pairs. In bothParameciumandChlamydomonas, the repeating structural unit of the cartwheel has a periodicity of 25 nm and consists of three ring-pairs with 6 radial spokes emanating and merging into a single bundle that connects to the triplet microtubule via the pinhead. Finally, we identified that the cartwheel is indirectly connected to the A-C linker through a flexible triplet-base structure extending from the pinhead. Together, our work provides unprecedented evolutionary insights into the architecture of the centriole proximal region, which underlies centriole biogenesis.
A novel predicted ADP-ribosyltransferase family conserved in eukaryotic evolution
Authors: Wyżewski Zbigniew , Gradowski Marcin , Krysińska Marianna , Dudkiewicz Małgorzata , Pawłowski Krzysztof 
Published: July 2020

AbstractThe presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs)Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are involved in innate immune surveillance.The novel family appears as likely novel ADP-ribosylation “writers”, previously unnoticed new players in cell signaling by this emerging post-translational modification. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer signalling.
Sex-specific gut microbiota modulation of aversive conditioning and basolateral amygdala dendritic spine density
Authors: Geary Caroline Grace , Wilk Victoria Christina , Barton Katherine Louise , Jefferson Parvaneh Ottavia , Binder Tea , Bhutani Vasvi , Baker Claire , Fernando-Peiris Achal James , Lee Mousley Alexa , Rozental Stefano Freitas Andrade , Thompson Hannah Mae , Touchon Justin Charles , Esteban David Justin , Bergstrom Hadley Creighton 
Published: July 2020

ABSTRACTGut microbiota influence numerous aspects of host biology, including brain structure and function. Growing evidence implicates gut microbiota in aversive conditioning and anxiety-related behaviors, but research has focused almost exclusively on males. To investigate sex-specific effects of gut dysbiosis on aversive learning and memory, adult female and male C57BL/6N mice were orally administered a moderate dose of non-absorbable antimicrobial medications (ATMs; neomycin, bacitracin, pimaricin) or a control over 10 days. Changes in gut microbiome composition were analyzed by 16S rRNA sequencing. Open field behavior, cued aversive learning, context recall, and cued recall were assessed. Following behavioral testing, the morphology of basolateral amygdala (BLA) principal neuron dendrites and spines was characterized. Results revealed that ATMs induced distinct but overlapping patterns of gut dysbiosis across sex, with stronger effects in females. There were also sex-specific effects on behavior and neuroanatomy. Treated males but not females exhibited altered locomotor and anxiety-like behavior in the novel open field test. Treated females but not males showed impairments in aversive memory acquisition and cued recall. Context recall remained intact in both sexes, as did dendritic structure of BLA principal neurons. However, ATMs exerted sex-specific effects on spine density. A second experiment was conducted to isolate gut perturbation to cued recall. Results revealed no effect of ATMs on recall of a previously consolidated fear memory, suggesting that gut dysbiosis preferentially impacts aversive learning. These data shed new light on how gut microbiota interact with sex to influence aversive conditioning, anxiety-like behavior, and BLA dendritic spine architecture.SignificanceGut microbiota can influence brain function and behavior, including trauma and anxiety-related disorders. Although these disorders disproportionately affect women, preclinical research has focused almost exclusively on male rodent models. We investigated the impact of antimicrobial administration on gut microbiome structure, aversive conditioning, open field behavior, and basolateral amygdala principal neuron morphology in female and male mice. Results showed that treatment exerted wide-ranging effects, many of which were sex-specific. Our findings underscore the importance of studying sex differences and support a role for microbial modulation of aversive learning, anxiety-like behavior, and amygdala spine patterning.
DORGE: Discovery of Oncogenes and Tumor SuppressoR Genes Using Genetic and Epigenetic Features
Authors: Lyu Jie , Li Jingyi Jessica , Su Jianzhong , Peng Fanglue , Chen Yiling , Ge Xinzhou , Li Wei 
Published: July 2020

AbstractComprehensive data-driven discovery of cancer driver genes, including tumor suppressor genes (TSGs) and oncogenes (OGs), is imperative for cancer prevention, diagnosis, and treatment. Although epigenetic alterations are important contributors to tumor initiation and progression, most known driver genes were identified based on genetic alterations alone, and it remains unclear to what the extent epigenetic features would facilitate the identification and characterization of cancer driver genes. Here we developed a prediction algorithm DORGE (Discovery of Oncogenes and tumor suppressoR genes using Genetic and Epigenetic features), which integrates the most comprehensive collection of tumor genetic and epigenetic data to identify TSGs and OGs, particularly those with rare mutations. DORGE identified histone modifications as strong predictors for TSGs, and it found missense mutations, super enhancer percentages, and methylation differences between cancer and normal samples as strong predictors for OGs. We extensively validated novel cancer driver genes predicted by DORGE using independent functional genomics data. We also found that the dual-functional genes, which are both TSGs and OGs predicted by DORGE, are enriched at hubs in protein-protein interaction and drug-gene networks. Overall, our study has deepened the understanding of epigenetic mechanisms in tumorigenesis and revealed a previously undetected repertoire of cancer driver genes.
DreamAI: algorithm for the imputation of proteomics data
Authors: Ma Weiping , Kim Sunkyu , Chowdhury Shrabanti , Li Zhi , Yang Mi , Yoo Seungyeul , Petralia Francesca , Jacobsen Jeremy , Li Jingyi Jessica , Ge Xinzhou , Li Kexin , Yu Thomas , Calinawan Anna P. , Edwards Nathan , Payne Samuel H. , Boutros Paul C. , Rodriguez Henry , Stolovitzky Gustavo , Zhu Jun , Kang Jaewoo , Fenyo David , Saez-Rodriguez Julio , Wang Pei 
Published: July 2020

AbstractDeep proteomics profiling using labeled LC-MS/MS experiments has been proven to be powerful to study complex diseases. However, due to the dynamic nature of the discovery mass spectrometry, the generated data contain a substantial fraction of missing values. This poses great challenges for data analyses, as many tools, especially those for high dimensional data, cannot deal with missing values directly. To address this problem, the NCI-CPTAC Proteogenomics DREAM Challenge was carried out to develop effective imputation algorithms for labeled LC-MS/MS proteomics data through crowd learning. The final resulting algorithm, DreamAI, is based on an ensemble of six different imputation methods. The imputation accuracy of DreamAI, as measured by Pearson correlation, is about 15%-50% greater than existing tools among less abundant proteins, which are more vulnerable to be missed in proteomics data sets. This new tool notably enhances data analysis capabilities in proteomics research.
Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification
Authors: Galan Silvia , Serra François , Marti-Renom Marc A. 
Published: July 2020

ABSTRACTGenome-wide profiling of long-range interactions has revealed that the CCCTC-Binding factor (CTCF) often anchors chromatin loops and is enriched at boundaries of the so-called Topologically Associating Domains, which suggests that CTCF is essential in the 3D organization of chromatin. However, the systematic topological classification of pairwise CTCF-CTCF interactions has not been yet explored.Here, we developed a computational pipeline able to classify all CTCF-CTCF pairs according to their chromatin interactions from Hi-C experiments. The interaction profiles of all CTCF-CTCF pairs were further structurally clustered using self-organizing feature maps and their functionality characterized by their epigenetic states. The resulting clusters were then input to a convolutional neural network aiming at thede novodetecting chromatin loops from Hi-C interaction matrices.Our new method, called LOOPbit, is able to automatically detect significant interactions with a higher proportion of enhancer-promoter loops compared to any other callers. Our highly specific loop caller adds a new layer of detail to the link between chromatin structure and function.
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
Authors: Weisblum Yiska , Schmidt Fabian , Zhang Fengwen , DaSilva Justin , Poston Daniel , Lorenzi Julio C. C. , Muecksch Frauke , Rutkowska Magdalena , Hoffmann Hans-Heinrich , Michailidis Eleftherios , Gaebler Christian , Agudelo Marianna , Cho Alice , Wang Zijun , Gazumyan Anna , Cipolla Melissa , Luchsinger Larry , Hillyer Christopher D. , Caskey Marina , Robbiani Davide F. , Rice Charles M. , Nussenzweig Michel C. , Hatziioannou Theodora , Bieniasz Paul D. 
Published: July 2020

AbstractNeutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.
AscA (YecA) is a molecular chaperone involved in Sec-dependent protein translocation inEscherichia coli
Authors: Smith Tamar Cranford , Wynne Max , Carter Cailean , Jiang Chen , Jamshad Mohammed , Milner Mathew T. , Djouider Yousra , Hutchinson Emily , Lund Peter A. , Henderson Ian , Huber Damon 
Published: July 2020

ABSTRACTProteins that are translocated across the cytoplasmic membrane by Sec machinery must be in an unfolded conformation in order to pass through the protein-conducting channel during translocation. Molecular chaperones assist Sec-dependent protein translocation by holding substrate proteins in an unfolded conformation in the cytoplasm until they can be delivered to the membrane-embedded Sec machinery. For example, inEscherichia coli, SecB binds to a subset of unfolded Sec substrates and delivers them to the Sec machinery by interacting with the metal-binding domain (MBD) of SecA, an ATPase required for translocation in bacteria. Here, we describe a novel molecular chaperone involved Sec-dependent protein translocation, which we have named AscA (foraccessorySeccomponent). AscA contains a metal-binding domain (MBD) that is nearly identical to the MBD of SecA.In vitrobinding studies indicated that AscA binds to SecB and ribosomes in an MBD-dependent fashion.Saturated transposon mutagenesis and genetics studies suggested that AscA is involved in cell-envelope biogenesis and that its function overlaps with that of SecB. In support of this idea, AscA copurified with a range of proteins and prevented the aggregation of citrate synthasein vitro. Our results suggest that AscA is molecular chaperone and that it enhances Sec-dependent protein translocation by delivering its substrate proteins to SecB.IMPORTANCEThis research describes the discovery of a novel molecular chaperone, AscA (YecA). The function of AscA was previously unknown. However, it contains a small domain, known as the MBD, suggesting it could interact with the bacterial Sec machinery, which is responsible for transporting proteins across the cytoplasmic membrane. The work described this study indicates that the MBD allows AscA to bind to both the protein synthesis machinery and the Sec machinery. The previously function of the previously uncharacterised N-terminal domain is that of a molecular chaperone, which binds to unfolded substrate proteins. We propose that AscA binds to protein substrates as they are still be synthesised by ribosomes in order to channel them into the Sec pathway.
Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors
Authors: Zhang Yali , Wang Shaojuan , Wu Yangtao , Hou Wangheng , Yuan Lunzhi , Sheng Chenguang , Wang Juan , Ye Jianghui , Zheng Qingbing , Ma Jian , Xu Jingjing , Wei Min , Li Zonglin , Nian Sheng , Xiong Hualong , Zhang Liang , Shi Yang , Fu Baorong , Cao Jiali , Yang Chuanlai , Li Zhiyong , Yang Ting , Liu Lei , Yu Hai , Hu Jianda , Ge Shengxiang , Chen Yixin , Zhang Tianying , Zhang Jun , Cheng Tong , Yuan Quan , Xia Ningshao 
Published: July 2020

AbstractThe ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.
Electric field mediated fibronectin-hydroxyapatite interaction: A molecular insight
Authors: Basu Subhadip , Gorai Biswajit , Basu Bikramjit , Maiti Prabal K. 
Published: July 2020

AbstractIn experimental research driven biomaterials science, the influence of different material properties (elastic stiffness, surface energy, etc.), and to a relatively lesser extent, the biophysical stimulation (electric/magnetic) on the cell-material interaction has been extensively investigated. Considering the central importance of the protein adsorption on cell-material interaction, the role of physiochemical factors on the protein adsorption is also probed. Despite its significance, the quantitative analysis of many such aspects remains largely unexplored in biomaterials science. In recent studies, the critical role of electric field stimulation towards modulation of cell functionality on implantable biomaterials has been experimentally demonstrated. Given this background, we investigated the influence of external electric field stimulation (upto 1.00 V/nm) on fibronectin (FN) adsorption on hydroxyapatite, HA (100) surface at 300K using all-atom MD simulation method. Fibronectin adsorption was found to be governed by the attractive electrostatic interaction, which changed with the electric field strength. Non-monotonous changes in structural integrity of fibronectin were recorded with the change in field strength and direction. This can be attributed to the spatial rearrangement of local charges and global structural changes of the protein. The dipole moment vectors of fibronectin, water and HA quantitatively exhibited similar pattern of orienting themselves parallel to the field direction, with field strength dependent increase in their magnitudes. No significant change has been recorded for radial distribution function of water surrounding fibronectin. Field dependent variation in the salt bridge nets and number of hydrogen bonds between fibronectin and hydroxyapatite were also examined. One of the important results in the context of the cell-material interaction is that the RGD sequence of FN was exposed to solvent side, when the field was applied along a direction outward perpendicular to HA (001) surface. Summarizing, the present study provides quantitative insights into the influence of electric field stimulation on biomolecular interactions involved in fibronectin adsorption on hydroxyapatite surface.
Inadequate level of knowledge, mixed outlook and poor adherence to COVID-19 prevention guideline among Ethiopians
Authors: Negera Edessa , Demissie Tesfaye Moti , Tafess Ketema 
Published: July 2020

AbstractCOVID-19 has a potential to cause chaos in Ethiopia due to the country’s already daunting economic and social challenges. Living and working conditions are highly conducive for transmission, as people live in crowded inter-generational households that often lack running water and other basic sanitary facilities. Thus, the aim of this study was to investigate the knowledge, attitudes and practices (KAP) of Ethiopians toward COVID-19 following the introduction of state of emergency by the Ethiopian government to curb the spread of the disease. A cross-sectional study design was conducted in nine reginal states and two chartered cities. Data for demographic, Knowledge, attitude and practice toward COVID-19 were collected through telephone interview from 1570 participants. Descriptive and bivariate analyses using chi-square test, t-test or analysis of variance were performed as appropriate. Binary and multiple logistic regression analysis were used to measure the relationship between the categorical dependent variables and one or more socio-demographic independent variables with two-tailed at α=0.05 significance level and 95% of confidence interval. The level of good knowledge, favourable attitude and good practice among the respondents were 42%, 53.8% and 24.3% respectively. Being rural resident, older than 50 years, having at least primary education, being resident of Amhara and Oromia regions were independent predictors of knowledge level. While being rural resident, married, employed, having at least basic education, being residents of Afar, Amhara, Gambela, Oromia and Somali regions were found to be the best predictors of the attitude, being rural resident, government employee, having at least basic education, and living outside of the capital were the independent predictors of practice level of the respondents. The finding revealed that Ethiopians have inadequate level of knowledge and are generally have a mixed outlook on overcoming the pandemic with poor adherence to COVID-19 prevention practice. reinforcing preventive measures and intensifying sensitization campaigns to fill the knowledge gap and persuading people to follow the preventive measures set by the government with concurrent evaluation of the impacts of these measures on knowledge and practice is highly recommended to mitigate the disease.