bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial strategies for survival in the glass spongeVazella pourtalesii
Authors: Bayer Kristina , Busch Kathrin , Kenchington Ellen , Beazley Lindsay , Franzenburg Sören , Michels Jan , Hentschel Ute , Slaby Beate M. 
Published: May 2020

AbstractFew studies have thus far explored the microbiomes of glass sponges (Hexactinellida). The present study seeks to elucidate the composition of the microbiota associated with the glass spongeVazella pourtalesiiand the functional strategies of the main symbionts. We combined microscopic approaches with metagenome-guided microbial genome reconstruction and amplicon community profiling towards this goal. Microscopic imaging revealed that the host and microbial cells appeared within dense biomass patches that are presumably syncytial tissue aggregates. Based on abundances in amplicon libraries and metagenomic data, SAR324 bacteria, Crenarchaeota, Patescibacteria and Nanoarchaeota were identified as abundant members of theV. pourtalesiimicrobiome and their genomic potentials were thus analyzed in detail. A general pattern emerged in that theV. pourtalesiisymbionts had very small genome sizes in the range of 0.5-2.2 Mb and low GC contents, even below those of seawater relatives. Based on functional analyses of metagenome-assembled genomes (MAGs), we propose two major microbial strategies: the “givers”, namely Crenarchaeota and SAR324, heterotrophs and facultative anaerobes, produce and partly secrete all required amino acids and vitamins. The “takers”, Nanoarchaeota and Patescibacteria, are anaerobes with reduced genomes that tap into the microbial community for resources, e.g., lipids and DNA, likely using pili-like structures. We posit that the existence of microbial cells in sponge syncytia together with the low-oxygen conditions in the seawater environment are factors that shape the unique compositional and functional properties of the microbial community associated withV. pourtalesii.ImportanceWe investigated the microbial community ofV. pourtalesiithat forms globally unique, monospecific sponge grounds under low-oxygen conditions on the Scotian Shelf, where it plays a key role for its vulnerable ecosystem. The microbial community was found to be concentrated within biomass patches and is dominated by small cells (<1 μm). MAG analyses showed consistently small genome sizes and low GC contents, which is unusual in comparison to known sponge symbionts. These properties as well as the (facultatively) anaerobic metabolism and a high degree of interdependence between the dominant symbionts regarding amino acid and vitamin synthesis are likely adaptations to the unique conditions within the syncytial tissue of their hexactinellid host and the low-oxygen environment.
Oropouche virus glycoprotein topology and cellular requirements for virus assembly
Authors: Barbosa Natalia S. , Concha Juan O. , daSilva Luis L. P. , Crump Colin M. , Graham Stephen C. 
Published: May 2020

AbstractOropouche virus (OROV;Genus: Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. We used recombinant expression of the OROV M polyprotein, that encodes the surface glycoproteins Gn and Gc plus the non-structural protein NSm, to probe the cellular determinants for OROV assembly and budding. Gn and Gc self-assemble and are secreted independently of NSm. Mature OROV Gn has two predicted transmembrane domains that are crucial for glycoprotein translocation to the Golgi complex and glycoprotein secretion and, unlike related orthobunyaviruses, both transmembrane domains are retained during Gn maturation. Disruption of Golgi function using the drugs brefeldin A and monensin inhibit glycoprotein secretion. Infection studies have previously shown that the cellular Endosomal Sorting Complexes Required for Transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. A dominant negative form of the ESCRT-associated ATPase VPS4 significantly reduces recombinant OROV glycoprotein secretion and blocks virus release from infected cells, and VPS4 partly co-localizes with OROV glycoproteins and membranes co-stained with Golgi markers. Furthermore, immunoprecipitation and fluorescence microscopy experiments demonstrate that OROV glycoproteins interact with the ESCRT-III component CHMP6, with overexpression of a dominant negative form of CHMP6 significantly reducing OROV glycoprotein secretion. Taken together, our data highlights differences in M polyprotein processing across orthobunyaviruses, that Golgi and ESCRT function are required for glycoprotein secretion, and identifies CHMP6 as an ESCRT-III component that interacts with OROV glycoproteins.ImportanceOropouche virus causes Oropouche fever, a debilitating illness common in South America that is characterised by high fever, headache, myalgia and vomiting. The tripartite genome of this zoonotic virus is capable of reassortment and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We developed a recombinant protein expression system to investigate the cellular determinants of OROV glycoprotein maturation and secretion. We show that the proteolytic processing of the M polypeptide, which encodes the surface glycoproteins (Gn and Gc) plus a non-structural protein (NSm), differs between OROV and its close relative Bunyamwera virus. Furthermore, we demonstrate that OROV M glycoprotein secretion requires the cellular ESCRT membrane-remodelling machinery and identify that the OROV glycoproteins interact with the ESCRT protein CHMP6.
Pushing beyond specifications: Evaluation of linearity and clinical performance of a fully automated SARS-CoV-2 RT-PCR assay for reliable quantification in blood and other materials outside recommendations
Authors: Nörz Dominik , Frontzek André , Eigner Ulrich , Oestereich Lisa , Fischer Nicole , Aepfelbacher Martin , Pfefferle Susanne , Lütgehetmann Marc 
Published: May 2020

1AbstractBackgroundThe ongoing SARS-CoV-2 pandemic presents a unique challenge to diagnostic laboratories. There are preliminary studies correlating qRT-PCR results from different materials to clinical outcomes, yet, comparability is limited due to the plethora of different assays used for diagnostics. In this study we evaluate clinical performance and linear range for the SARS-CoV-2 IVD (cobas6800/8800 system, a fully automated sample-to-result platform) in different clinically relevant matrix materials outside official specifications.MethodsAssay performance was assessed in human plasma, BAL/BL and transport medium following chemical inactivation. For analytical evaluation, respective matrix materials were spiked with SARS-CoV-2 RNA in ten-fold dilution series. The efficacy of chemical inactivation by guanidine hydrochloride solution was confirmed in cell culture infectivity experiments. For correlation, a total of 235 predetermined clinical samples including respiratory swabs, plasma and BAL/BL were subjected to the SARS-CoV-2 IVD test and results were compared.ResultsThe SARS-CoV-2 IVD showed excellent linearity over five to seven log steps depending on matrix material. Chemical inactivation resulted in a reduction in plaque forming units of at least 3.5 log steps, while having no significant impact on assay performance. Inter-run consistency from three different testing sites demonstrated excellent comparability of RT-PCR results (maximum deviation was 1.53 CT). Clinical evaluation for respiratory swabs showed very good agreement with the comparator assay (Positive agreement 95.7%, negative agreement 98.9%).ConclusionThe SARS-CoV-2 IVD test for the cobas6800/8800 systems offers excellent linear range and inter-run consistency for quantification of SARS-CoV-2 RNA in different matrices outside official specifications.HighlightsEffective reduction of SARS-CoV-2 infectivity by chemical inactivation without affecting assay performance.SARS-CoV-2 IVD for the cobas 6800/8800 is linear over up to seven log steps in different materials including human plasma.Minimal variance of CT values between testing sites indicates high comparability of quantification results.
Investigating spatiotemporal patterns of the COVID-19 in São Paulo State, Brazil
Authors: Alcântara Enner , Mantovani José , Rotta Luiz , Park Edward , Rodrigues Thanan , Carvalho Fernando Campos , Filho Carlos Roberto Souza 
Published: May 2020

AbstractAs of May 16th, 2020, the number of confirmed cases and deaths in Brazil due to COVID-19 hit 233,142 and 15,633, respectively, making the country one of the most affected by the pandemic. The State of Sao Paulo (SSP) hosts the largest number of confirmed cases in Brazil, with over 60,000 cases to date. Here we investigate the spatial distribution and spreading patterns of COVID-19 in the SSP by mapping the spatial autocorrelation and the clustering patterns of the virus in relation to the population density and the number of hospital beds. Moran’s I and LISA clustering analysis indicated that Sao Paulo City is a significant hotspot for both the confirmed cases and deaths, whereas other cities across the State could be considered colder spots. Bivariate Moran’s I also showed that the population density is a key indicator for the number of deaths, whereas the number of hospital beds is less related, implying that the fatality depends substantially on the actual patient’s condition. Social isolation measures throughout the SSP have been gradually increasing since early March, an action that helped to slow down the emergence of the new confirmed cases, highlighting the importance of the safe-distancing measures in mitigating the local transmission within and between cities in the SSP.
Intensive COVID-19 testing associated with reduced mortality - an ecological analysis of 108 countries
Authors: Kenyon Chris 
Published: May 2020

AbstractBackgroundIntensive screening and testing for COVID-19 could facilitate early detection and isolation of infected persons and thereby control the size of the epidemic. It could also facilitate earlier and more targeted therapy. These factors could plausibly reduce attributable mortality which was the hypothesis tested in this study.MethodsLinear regression was used to assess the country-level association between COVID-19 attributable mortality per 100 000 inhabitants (mortality/capita) and COVID-19 tests/capita (number of tests/100 000 inhabitants) controlling for the cumulative number of COVID-19 infections/100 000 inhabitants (cases/capita), the age of the epidemic (number of days between first case reported and 8 April), national health expenditure per capita and WHO world region.ResultsThe COVID-19 mortality rate varied between 0.3 and 3110 deaths/100 000 inhabitants (median 30, IQR 8–105). The intensity of testing per 100 000 also varied considerably (median 21,970, IQR 2,735–89,095) as did the number of COVID-19 cases per 100 000 (median 1,600, IQR 340–4,760 cases/100 000). In the multivariate model, the COVID-19 mortality rate was negatively associated with tests/capita (Coef. –0.036, 95% CI –0.047- –0.025) and positively associated with cases/capita (Coef. 0.093, 95% CI 0.819- 1.034).ConclusionsThe results are compatible with the hypothesis that intensive testing and isolation could play a role in reducing COVID-10 mortality rates.
Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down Syndrome: a network science EEG study
Authors: Anagnostopoulou Alexandra , Styliadis Charis , Kartsidis Panagiotis , Romanopoulou Evangelia , Zilidou Vasiliki , Karali Chrysi , Karagianni Maria , Klados Manousos , Paraskevopoulos Evangelos , Bamidis Panagiotis D. 
Published: May 2020

AbstractUnderstanding the neuroplastic capacity of people with Down Syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a ten-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left to right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying DS processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov IdentifierNCT04390321.Author SummaryThe effects of cognitive and physical training on the neuroplasticity attributes of people with and without cognitive impairment have been well documented via neurophysiological evaluations and network science indices. However, there is still insufficient evidence for people with Down Syndrome (PwDS). We investigated the effects of a combinational training protocol on the brain network organization of 12 adult PwDS using EEG and network indices coupled with tests assessing their cognitive and physical capacity. We report evidence of adaptational neuroplastic effects, pointing to a transitional state towards a healthier organization with an increased ability to integrate and segregate information. Our findings underline the ability of the DS brain to respond to the cognitive demands of external stimuli, reflecting the possibility of developing independent-living skills.
Glaucoma home-monitoring using a tablet-based visual field test (Eyecatcher): An assessment of accuracy and adherence over six months
Authors: Jones Pete R. , Campbell Peter , Callaghan Tamsin , Jones Lee , Asfaw Daniel S. , Edgar David F. , Crabb David P. 
Published: May 2020

AbstractPurposeTo assess accuracy and adherence of visual field (VF) home-monitoring in a pilot sample of glaucoma patients.DesignProspective longitudinal observation.MethodsTwenty adults (median 71 years) with an established diagnosis of glaucoma were issued a tablet-perimeter (Eyecatcher), and were asked to perform one VF home-assessment per eye, per month, for 6 months (12 tests total). Before and after home-monitoring, two VF assessments were performed in-clinic using Standard Automated Perimetry (SAP; 4 tests total, per eye).ResultsAll 20 participants could perform monthly home-monitoring, though one participant stopped after 4 months (Adherence: 98%). There was good concordance between VFs measured at home and in the clinic (r = 0.94, P < 0.001). In 21 of 236 tests (9%) Mean Deviation deviated by more than ±3dB from the median. Many of these anomalous tests could be identified by applying machine learning techniques to recordings from the tablets’ front-facing camera (Area Under the ROC Curve = 0.78). Adding home-monitoring data to 2 SAP tests made 6 months apart reduced measurement error (between-test measurement variability) in 97% of eyes, with mean absolute error more than halving in 90% of eyes. Median test duration was 4.5mins (Quartiles: 3.9−5.2mins). Substantial variations in ambient illumination had no observable effect on VF measurements (r = 0.07, P = 0.320).ConclusionsHome-monitoring of VFs is viable for some patients, and may provide clinically useful data.
Sporadic Oncocytic Tumors with Features Intermediate between Oncocytoma and Chromophobe Renal Cell Carcinoma: Comprehensive Clinico-Pathological and Genomic Profiling
Authors: Liu Yajuan J , Ussakli Cigdem , Antic Tatjana , Liu Yuhua , Wu Yu , True Lawrence , Tretiakova Maria S 
Published: May 2020

ABSTRACTBackgroundMorphology, clinical behavior, and genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. However, there is a substantial group of sporadic oncocytic tumors with peculiar hybrid phenotypes as well as a perplexing degree of morphologic and immunohistochemical overlap between classic RO and ChRCC with eosinophilic cytoplasm. The aim of this study is to provide detailed characterization of these hybrid tumors.DesignThirty eight sporadic oncocytic neoplasms with ambiguous morphology from two institutions were reviewed by 4 pathologists. CKIT positivity was used as a selection criterion. We correlated CK7 and S100A1 immunostaining and detailed morphologic features with cytogenetic profiles. DNA from the FFPE tissues was extracted and analyzed using Cytogenomic Microarray Analysis (CMA) to evaluate copy number alterations and ploidy.ResultsCMA categorized cases into 3 groups: RO (N=21), RO variant (N=7) and ChRCC (N=10). Cytogenetic RO had either no CNA (48%) or loss of chromosome 1p, X or Y (52%). RO-variant had additional chromosomal losses [-9q, –14 (n=2), –13] and chromosomal gains [+1q (n=2), +4, +7 (n=2), +13, +19, +20, and +22]. ChRCC were either hypodiploid with numerous monosomies (40%) or hypotetraploid with multiple relative losses (60%). RO, RO-variant and ChRCC groups differed significantly in tumor architecture (p<0.01), stroma (p=0.013), presence of nuclear wrinkling, perinuclear halos and well-defined cell borders in >5% cells (p<0.01), focal cell clearing (p=0.048) and CK7 expression (p<0.02). Pathologic prediction of cytogenetic subtype using only two categories (benign RO or malignant ChRCC) would overcall or undercall up to 40% of tumors that were ChRCC based on cytogenetics. This finding provides the rationale for an intermediate diagnostic category of so-called hybrid tumors (HOCT). HOCT was a heterogeneous group enriched for cytogenetic RO-variant. Other HOCTs have a profile of either RO or ChRCC.ConclusionsGenomic profile allows classification of oncocytic tumors with ambiguous morphology into RO, RO-variant and ChRCC. Several architectural and cytologic features combined with CK7 expression are significantly associated with cytogenetic RO, RO-variant or ChRCC tumors. Doubled hypodiploidy by whole genome endoduplication is a common phenomenon in eosinophilic ChRCC.Parts of this study were presented in an abstract form at the 104th annual meeting of the United Stated and Canadian Academy of Pathology, Boston, March 21–27, 2015
QMRA of SARS-CoV-2 for workers in wastewater treatment plants
Authors: Zaneti Rafael Newton , Girardi Viviane , Spilki Fernando Rosado , Mena Kristina , Westphalen Ana Paula Campos , Colares Evandro Ricardo da Costa , Pozzebon Allan Guedes , Etchepare Ramiro Gonçalves 
Published: May 2020

AbstractFaecal-oral transmission of SARS-CoV-2 is a hot topic and additional research is needed to elucidate the risks of the novel coronavirus in sanitation systems. This is the first article that investigates the potential health risks of SARS-CoV-2 in sewage to wastewater treatment plants (WWTPs) workers. A quantitative microbial risk assessment (QMRA) is applied for three COVID-19 scenarios (moderate, aggressive and extreme) to study the effect of different stages of the pandemic, in terms of percentage of infected population, on the probability of infection. Results reveal that estimates of viral loads in sewage at the entrance of WWTPs ranged from 1.03×102 to 1.31×104 GC.mL−1 (0.1 to 13.06 PFU.mL−1, respectively) and that estimated risks for the aggressive and extreme scenarios (6.5×10−3 and 3.1×10−2, respectively) were likely to be above a WHO benchmark of tolerable risk used for virus infection of 10−3 and higher than the risk of infection of E. coli, used herein as common pathogen indicator for a relative comparison, thus reinforcing the concern of sewage systems as a transmission pathway of SARS-CoV-2. These findings are helpful as an early-warning tool and in prioritizing upcoming risk management strategies in the sanitation sector during COVID-19 pandemic.
Information theoretics for the machine learning detection of functionally conserved and coordinated protein motions
Authors: Babbitt Gregory A. 
Published: May 2020

AbstractTraditional information theoretic analysis of functionally conserved binding interactions described by multiple sequence alignments are unable to provide direct insights into the underlying strength, spatial distribution, and coordination of the biophysical motions that govern protein binding interactions during signaling and regulatory function. However, molecular dynamic (MD) simulations of proteins in bound vs. unbound conformational states can allow for the combined application of machine learning classification and information theory towards many problems posed by comparative protein dynamics. After both bound and unbound protein dynamic states are adequately sampled in MD software, they can be employed as a comparative training set for a binary classifier capable of discerning the complex dynamical consequences of protein binding interactions with DNA or other proteins. The statistical validation of the learner on MD simulations of homologs can be used to assess its ability to recognize functional protein motions that are conserved over evolutionary time scales. Regions of proteins with functionally conserved dynamics are identifiable by their ability to induce significant correlations in local learning performance across homologous MD simulations. Through case studies of Rbp subunit 4/7 interaction in RNA Pol II and DNA-protein interactions of TATA binding protein, we demonstrate this method of detecting functionally conserved protein dynamics. We also demonstrate how the concepts of relative entropy (i.e. information gain) and mutual information applied to the binary classification states of MD simulations can be used to compare the impacts of molecular variation on conserved dynamics and to identify coordinated motions involved in dynamic interactions across sites.