bluuebunny/crossref_metadata_2025 huggingface dataset:
The quorum sensing system NprR-NprRB contributes to spreading and fitness in colony biofilms ofBacillus thuringiensis
Authors: Verdugo-Fuentes Abel , de la Torre Mayra , Rocha Jorge
Published: January 2021

Quorum sensing (QS) are intercellular communication mechanisms to coordinate bacterial gene expression in response to signaling molecules. InBacillus thuringiensisthe QS system NprR-NprRB (receptor protein-signaling peptide) regulates the expression of genes related to nutrient scavenging during necrotrophism and also modulates sporulation onset. However, the relevance of QS in free-living stages ofB. thuringiensisis less known. In this work, we depict the contribution of this QS system to spreading in colony biofilms. Through a spreading assay in spotted colonies ofB. thuringiensisBt8741 Wt and derived mutants, we find that the spreading phenotype depends on the NprR regulator and on the extracellular signaling NprRB peptide. We also show that this phenotype is associated to an increased fitness of the bacterium in these experimental conditions. Exogenous addition of a lipopeptide surfactant was sufficient to recover spreading in the ΔnprR-nprRBmutant, indicating that the phenotype could be mediated by the lipopeptide kurstakin. Finally, we suggest that the spreading is relevant in nature, since it occurs in the sole presence of soil nutrients, and it is conserved in several species ofBacilluscommonly found in soil. This novel function of NprR-NprRB highlights the relevance of this QS system on the evolution and on the free-lifestyle ecology ofB. thuringiensis.
Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data
Authors: De Salazar PM , Lu F , Hay JA , Gómez-Barroso D , Fernández-Navarro P , Martínez E , Astray-Mochales J , Amillategui R , García-Fulgueiras A , Chirlaque MD , Sánchez-Migallón A , Larrauri A , Sierra MJ , Lipsitch M , Simón F , Santillana M , Hernán MA
Published: January 2021

Designing public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus, an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020.

We address two data collection problems that affected the reliability of the available real-time epidemiological data, namely, the frequent missing information documenting when a patient first experienced symptoms, and the frequent retrospective revision of historical information (including right censoring). This is done by using a novel back-calculating procedure based on imputing patients’ dates of symptom onset from reported cases, according to a dynamically-estimated “backward” reporting delay conditional distribution, and adjusting for right censoring using an existing package, NobBS, to estimate in real time (nowcast) cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real-time.

At each step, we evaluate how different assumptions affect the recovered epidemiological events and compare the proposed approach to the alternative procedure of merely using curves of case counts, by report day, to characterize the time-evolution of the outbreak. Finally, we assess how these real-time estimates compare with subsequently documented epidemiological information that is considered more reliable and complete that became available later in time. Our approach may help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health surveillance systems in other locations.
Prevalence of Iron Deficiency, Iron Deficiency Anaemia and General Anaemia in Male Gambian Blood Donors Residing in Greater Banjul Region
Authors: Dibbasey Mustapha , Lawal Bolarinde , Umukoro Solomon , Mitchel Peter
Published: January 2021

Objective

The objective of this study is to determine the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) as well as general anaemia in male blood donors and their association with ageing process.

Methodology and Results

A total of two hundred and one (201) serum samples were analysed for ferritin in male Gambian blood donors. The ferritin measurement was achieved with COBAS® INTEGRA 400 plus. At the same time, haemoglobin values were retrospectively obtained from the archived haematological full blood count result in the GARIS database. IDA was defined as (Haemoglobin <13.0g/dL+ Ferritin<15ng/ml) whilst ID was defined as (Haemoglobin ≥13.0g/dL+ Ferritin<15ng/ml) and general anaemia was defined as haemoglobin <13.0g/dL in males. The prevalence of anaemia (20%, n=41), ID (22%, n=44) and IDA (10%, n=21), were recorded in male donors. The results show no relationship between ferritin and haemoglobin among the blood donors (collection coefficient (r) = 0.04). Besides, no linear association of having anaemia and ID with ageing was reported among the blood donor population.

Conclusion and potential application of findings

ID and IDA as well as general anaemia are highly prevalent among blood donors in the Gambia. Besides, no predisposition to ID and anaemia was observed in term of age, thus all blood donors from 18-60 should be considered for blood donation without any age preference.
Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study
Authors: Gabashvili Irene S.
Published: January 2021

Background

Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect on biochemical and biophysical activities both outside and within the human body. Breath analysis could provide non-invasive, cost-effective, real time early disease diagnosis and monitoring of therapeutic responses.

Objectives

The primary objective of this study was to assess the effectiveness of alveolar breath testing in diagnosing idiopathic systemic body and breath odors. Key secondary objectives were to assess if breath tests can reliably differentiate subtypes of idiopathic malodor in different environments and dietary regimens, and to map metabolites to biomedical functions and pathways.

Study Design

The basic design was to measure a cohort of idiopathic odor in order to identify potential molecular correlates with genotypic and phenotypic variables. Participants were subdivided in several different ways allowing for different cases and controls within the cohort, using prior and later test results and observations. Thus, this study was an observational retrospective case-cohort/nested case-control study.

Setting/Participants

Participants were recruited online via MEBO and TMAU support groups and on site, during the 3rd Annual MEBO Research conference held at Miami South Beach on June 23, 2012 and local meetups of support groups (Miami, Florida; New York, New York; Chicago, Illinois, US and Birmingham, England). Study population is individuals self-reporting systemic idiopathic malodor production. Inclusion criteria were good general health, desire and ability to travel to one of the participating sites and pay the lab fee. Exclusion Criteria were medical conditions that could prevent participation and age under 18.

Study Interventions and Measures

The main study procedure was the application of a rapid point-of-care breath testing system to collect and concentrate alveolar breath VOCs on a sorbent trap, using breath collection apparatus (BCA) 5.0. Samples were sent to central laboratory and analyzed with gas chromatography and mass spectroscopy. In addition, the participants filled out food frequency questionnaires and were offered to use Aurametrix, online software tool based on a participant-initiated ecological momentary assessment approach, allowing to recall the events at any time later. The tool analyzed dietary intakes, activities and environmental exposures for both individual and aggregate level data.

The primary endpoint was the composition of VOCs in breath samples, while diet and activity data, and results of alternative testing assessments were secondary endpoints. The main study outcome measure is the diagnostic accuracy of alveolar breath test in differentiating profiles of two main pre-defined sub-cohorts. Index of concordance with accuracy, sensitivity, specificity, positive predictive value and negative predictive value will be reported. A number of factors was assessed for confounding.
Contamination of air and surfaces in workplaces with SARS-CoV-2 virus: a systematic review
Authors: Cherrie JW , Cherrie MPC , Davis A , Holmes D , Semple S , Steinle S , MacDonald E , Moore G , Loh M
Published: January 2021

Objectives

This systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used to identify actions necessary to improve the quality of the data.

Methods

We searched Web of Science and Google Scholar until 24th December 2020 for relevant articles and extracted data on methodology and results.

Results

The vast majority of data come from healthcare settings, with typically around 6 % of samples having detectable concentrations of SARS-CoV-2 RNA and almost none of the samples collected had viable virus. There were a wide variety of methods used to measure airborne virus, although surface sampling was generally undertaken using nylon flocked swabs. Overall, the quality of the measurements was poor. Only a small number of studies reported the airborne concentration of SARS-CoV-2 virus RNA, mostly just reporting the detectable concentration values without reference to the detection limit. Imputing the geometric mean air concentration assuming the limit of detection was the lowest reported value, suggests typical concentrations in health care settings may be around 0.01 SARS-CoV-2 virus RNA copies/m3. Data on surface virus loading per unit area were mostly unavailable.

Conclusion

The reliability of the reported data is uncertain. The methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments should be standardised to facilitate more consistent interpretation of contamination and to help reliably estimate worker exposure.

Key messages

What is already known about this subject?

Low level contamination of air and surfaces in hospitals with SARS-CoV-2 RNA have been reported during the Covid-19 pandemic.

Limited data have published from non-healthcare settings.

What are the new findings?

Typically, around 6% of air and surface samples in hospitals were positive for SARS-COV-2 RNA, although there is very limited data for non-healthcare settings.

The quality of the available measurement studies is generally poor, with little consistency in the sampling and analytical methods used.

Few studies report the concentration of SARS-CoV-2 in air or as surface loading of virus RNA, and very few studies have reported culture of the virus.

The best estimate of typical air concentrations in health care settings is around 0.01 SARS-CoV-2 virus RNA copies/m3

How might this impact on policy or clinical practice in the foreseeable future?

There should be concerted efforts to standardise the methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments.
A cross-sectional survey of the workplace factors contributing to symptoms of anxiety and depression among nurses and physicians during the first wave of COVID-19 pandemic in two US healthcare systems
Authors: Burstyn Igor , Holt Karyn
Published: January 2021

Background

Anxiety and depression among physicians and nurses during COVID-19 pandemic in the USA is not well described and its modifiable causes poorly understood.

Methods

We conducted a cross-sectional survey of symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) among physicians and nurses in two US healthcare systems June-Sept 2020. We ascertained features of work as well as its perceptions and associated concerns in relation to risk of anxiety and depression, while controlling for health history via regression and path analyses.

Results

About a third of 684 nurses and 185 physicians surveyed showed symptoms of anxiety or depression, the excess was particularly prominent in nurses. Belief in having been infected was a dominant cause of anxiety and depression, more related to history of symptoms of pneumonia, then the contact with infected patients. Having confidence in competent use and access to personal protective equipment, maintaining usual working hours and being surrounded by colleagues who were both sufficient in numbers and not stressed, was protective. Having support of immediate family and religious communities lessened anxiety and depression after accounting for other factors. Involvement in aerosol-generating procedures with infected patients was linked with lower depression in nurses but higher among physicians. Likewise, the setting of recent patient encounters affected risk differently for physicians and nurses.

Conclusions

Our findings may help develop mitigation measures and underscore the need to help nurses and physicians bear the psychological burden of COVID-19 pandemic and similar events in the future.
Trends and clinical characteristics of COVID-19 vaccine recipients: a federated analysis of 57.9 million patients’ primary care records in situ using OpenSAFELY
Authors:   The OpenSAFELY Collaborative, Curtis Helen J , Inglesby Peter , Morton Caroline E , MacKenna Brian , Walker Alex J , Morley Jessica , Mehrkar Amir , Bacon Seb , Hickman George , Bates Chris , Croker Richard , Evans David , Ward Tom , Cockburn Jonathan , Davy Simon , Bhaskaran Krishnan , Schultze Anna , Rentsch Christopher T , Williamson Elizabeth , Hulme William , Green Amelia , Rowan Anna , Fisher Louis , McDonald Helen I , Tomlinson Laurie , Mathur Rohini , Drysdale Henry , Eggo Rosalind M , Wing Kevin , Wong Angel YS , Forbes Harriet , Parry John , Hester Frank , Harper Sam , O’Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Griffiths Paul , Fowles Aaron , Parkes Nasreen , Douglas Ian J , Evans Stephen JW , Smeeth Liam , Goldacre Ben
Published: January 2021

Background

On December 8th 2020, NHS England administered the first COVID-19 vaccination as part of an ambitious vaccination programme during a global health emergency.

Aims

To describe trends and variation in vaccine coverage by key clinical and demographic groups; to create a framework for near-real-time monitoring of vaccine coverage in key subgroups.

Methods

Working on behalf of NHS England we analysed 57.9 million patient records in situ and in near-real-time within the infrastructure of the Electronic Health Record (EHR) software vendors EMIS and TPP using OpenSAFELY. We describe vaccine coverage and time trends across a range of demographic and fine-grained clinical subgroups in eight Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts.

Results

20,852,692 patients (36%) received a COVID-19 vaccine between December 8th 2020 and March 17th 2021. Of patients aged ≥80 not in a care home (JCVI group 2) 94.7% received a vaccine, but with substantial variation by ethnicity (White 96.2% vaccinated, Black 68.3%) and deprivation (least deprived 96.6%, most deprived 90.7%). Overall, patients with pre-existing medical conditions were equally or more likely to be vaccinated with two exceptions: severe mental illness (89.5% vaccinated) and learning disability (91.4%). 275,205 vaccine recipients were identified as care home residents (priority group 1; 91.2% coverage). 1,257,914 (6.0%) recipients have had a second dose. Detailed characteristics of recipients in all cohorts are reported.

Conclusions

The NHS in England has rapidly delivered mass vaccination. We were able to deploy a data monitoring framework using publicly auditable methods and a secure, in-situ processing model, using linked but pseudonymised patient-level NHS data on 57.9 million patients with very short delays from vaccine administration to completed analysis. Targeted activity may be needed to address lower vaccination coverage observed among certain key groups: ethnic minorities, those living in deprived areas, and people with severe mental illness or learning disabilities.
Individual-level and neighborhood-level factors associated with longitudinal changes in cardiometabolic measures in participants of a care coordination program
Authors: Patil Sonal J , Golzy Mojgan , Johnson Angela , Wang Yan , Parker Jerry C , Haire-Joshu Debra , Mehr David R , Foraker Randi E , Kruse Robin L
Published: January 2021

Introduction

Identifying individual and neighborhood-level factors associated with less improvement or worsening cardiometabolic measures in participants of clinic-based interventions may help identify candidates for supplementary community-based interventions.

Methods

Study design: Secondary data analysis of data from care coordination program cohort, Leveraging Information Technology to Guide High Tech, High Touch Care (LIGHT2). Participants: Medicare, Medicaid, or dual-eligible adults from the University of Missouri Health System enrolled in LIGHT2. Intervention: Nurse-led care coordination in ten primary care clinics. Outcomes: Hemoglobin A1C, low-density-lipoprotein (LDL) cholesterol, and blood pressure. Multivariable generalized linear regression models assessed changes in outcomes after adjusting for clinical and sociodemographic factors, neighborhood-level factors, and driving time to primary care clinics.

Results

6378 participants had pre-and post-intervention cardiometabolic measures reported (61% women, 86.3% White, non-Hispanic ethnicity, mean age 62.7 [SD, 18.5] years). In adjusted models, pre-intervention measures and female gender were associated with worsening of all cardiometabolic measures. Women’s LDL-cholesterol worsened compared to men irrespective of pre-intervention levels (β 7.87, 95% CI 5.24 to 10.5, p<.001). Women with hemoglobin A1C> 6.8% had worsening hemoglobin A1C compared to men (main effect β −1.28, 95% CI −1.95 to −0.61, p<.001; interaction effect β 0.19, 95% CI 0.09 to 0.28, p<.001). Women with systolic blood pressure >121 mm of Hg had worsening diastolic blood pressure compared to men (main effect β −5.42, 95% CI −9.8 to 0.098, p = 0.016; interaction effect β 0.04, 95% CI 0.01 to 0.078, p = 0.009). Adding neighborhood-level factors or driving time to primary care clinics did not improve the overall fit of the models.

Conclusions

In a solely clinic-based care coordination program, increasing baseline cardiometabolic measures and female gender were associated with worsening cardiometabolic outcomes. Further research to understand the causes of these associations may help tailor clinic-community-linked interventions.
Geographic Variation in Influenza Vaccination among US Nursing Home Residents: A National Study
Authors: Silva Joe B. B. , Bosco Elliott , Riester Melissa R. , McConeghy Kevin W. , Moyo Patience , van Aalst Robertus , Bardenheier Barbara H. , Gravenstein Stefan , Baier Rosa , Loiacono Matthew M. , Chit Ayman , Zullo Andrew R.
Published: January 2021

Objective

Estimates of influenza vaccine use are not available at the county level for U.S. nursing home (NH) residents but are critically necessary to guide implementation of quality improvement programs aimed at increasing vaccination rates. Furthermore, estimates that account for differences in resident characteristics between counties are unavailable. We estimated risk-standardized vaccination rates among short- and long-stay NH residents by U.S. county and identified drivers of geographic variation.

Methods

We conducted a retrospective cohort study utilizing 100% of 2013-2015 fee-for-service Medicare claims, Minimum Data Set assessments, Certification and Survey Provider Enhanced Reports, and LTCFocUS. We separately evaluated short-stay (<100 days) and long-stay (≥100 days) residents aged ≥65 years old across the 2013-2014 and 2014-2015 influenza seasons. We estimated county-level risk-standardized vaccination rates (RSVRs) via hierarchical logistic regression adjusting for 32 resident-level covariates. We then used multivariable linear regression models to assess associations between county-level NHs predictors and RSVRs.

Results

The overall study cohort consisted of 2,817,217 residents in 14,658 NHs across 2,798 counties. Short-stay residents had lower RSVRs than long-stay residents (2013-2014: median [IQR], 69.6% [62.8-74.5] vs 84.0% [80.8-86.4]). Counties with the highest vaccination rates were concentrated in the Midwestern, Southern, and Northeast US. Several modifiable facility-level characteristics were associated with increased RSVRs, including higher registered nurse to total nurse ratio and higher total staffing for licensed practical nurses, speech language pathologists, and social workers. Characteristics associated with lower RSVRs included higher percentage of residents restrained, with a pressure ulcer, and NH-level hospitalizations per resident-year.

Conclusions

Substantial county-level variation in influenza vaccine use exists among short- and long-stay NH residents. Quality improvement interventions to improve vaccination rates can leverage these results to target NHs located in counties with lower risk-standardized vaccine use.
Computational structural genomics unravels common folds and predicted functions in the secretome of fungal phytopathogenMagnaporthe oryzae
Authors: Seong Kyungyong , Krasileva Ksenia V
Published: January 2021

Magnaporthe oryzaerelies on a diverse collection of secreted effector proteins to reprogram the host metabolic and immune responses for the pathogen’s benefit. Characterization of the effectors is thus critical for understanding the biology and host infection mechanisms of this phytopathogen. In rapid, divergent effector evolution, structural information has the potential to illuminate the unknown aspects of effectors that sequence analyses alone cannot reveal. It has recently become feasible to reliably predict the protein structures without depending on homologous templates. In this study, we tested structure modeling on 1854 secreted proteins fromM. oryzaeand evaluated success and obstacles involved in effector structure prediction. With sensitive homology search and structure-based clustering, we defined both distantly related homologous groups and structurally related analogous groups. With this dataset, we propose sequence-unrelated, structurally similar effectors are a common theme inM. oryzaeand possibly in other phytopathogens. We incorporated the predicted models for structure-based annotations, molecular docking and evolutionary analyses to demonstrate how the predicted structures can deepen our understanding of effector biology. We also provide new experimentally testable structure-derived hypotheses of effector functions. Collectively, we propose that computational structural genomic approaches can now be an integral part of studying effector biology and provide valuable resources that were inaccessible before the advent of reliable, machine learning-based structure prediction.
DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as Alk target in theDrosophilavisceral mesoderm
Authors: Mendoza-Garcia Patricia , Basu Swaraj , Sukumar Sanjay Kumar , Arefin Badrul , Wolfstetter Georg , Anthonydhason Vimala , Molander Linnea , Lindehell Henrik , Larsson Jan , Larsson Erik , Bemark Mats , Palmer Ruth H.
Published: January 2021

Development of the midgut visceral muscle ofDrosophilacrucially depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signalling, which is needed to specify founder cells (FCs) in the circular visceral mesoderm (VM). While activation of the Alk receptor by its ligand Jelly Belly (Jeb) is well characterized, only a small number of target molecules have been identified. Here, we assayed RNA polymerase II (Pol II) occupancy in VM cells by using the targeted DamID (TaDa) approach. To identify Alk targets we employed comparative analysis of embryos overexpressing Jebversusembryos with abrogated Alk activity, revealing differential expression of a number of genes, including the Snail/Scratch family transcription factorKahuli(Kah). Upon furtherin vivovalidation, we confirmed that Alk signalling regulatesKahmRNA expression in the VM. We show thatKahmutants display defects in the formation of midgut constrictions, similar to that ofpointed(pnt) mutants. Analysis of publicly available ChIP data defined a Kah target-binding site similar to that of Snail. In addition, we compared genes that were differentially expressed inKahmutants with publicly available Kah- and Pnt-ChIP datasets identifying a set of common target genes putatively regulated by Kah and Pnt in midgut constriction. Taken together, we (i) report a rich dataset of Alk responsive loci in the embryonic VM, (ii) provide the first functional characterization of the Kah transcription factor, identifying a role in embryonic midgut constriction, and (iii) suggest a model in which Kah and Pnt cooperate in embryonic midgut morphogenesis.
Comparison of endogenously expressed fluorescent protein fusions behaviour for protein quality control and cellular aging research
Authors: Schneider Kara L. , Wollman Adam , Nyström Thomas , Shashkova Sviatlana
Published: January 2021

The yeast Hsp104 protein disaggregase is often used as a reporter for misfolded or damaged protein aggregates and protein quality control and ageing research. Observing endogenously expressed Hsp104 fusions with fluorescent proteins is a popular approach to follow post stress protein aggregation, inclusion formation and disaggregation. Overall, such protein fusions used in molecular and microbiology research are often sparsely characterised. To address this issue, we performed a comparative assessment of Hsp104 fluorescent fusions function and behaviour. We provide experimental evidence that molecular behaviour may not only be altered by introducing a fluorescent protein tag but also varies depending on the fluorophore within the fusion. Although our findings are especially applicable to protein quality control and ageing research in yeast, similar effects and points may play a role in other eukaryotic systems.
Distance-based exclusion method for parentage analysis using microsatellites (SSR) markers
Authors: Francisco Gil-Muñoz , Sara Abrahamsson , Rosario García-Gil M
Published: January 2021

Genotyping mistakes represent a challenge in parental assignment where even small errors can lead to significant amounts of unassigned siblings. Different parental assignment algorithms have been designed to approach this problem. The Exclusion method is the most applied for its reliability and biological meaning. However, the resolving power of this method is the lowest for data containing genotyping errors. We introduce a new distance-based approach which we coin as Distance-Based Exclusion (DBE). The DBE method calculates the distance between the offspring haplotype and haplotype of each of the potential fathers. The father with the lowest distance is then assigned as candidate father according to a distance ratio (α). We have tested the Exclusion and DBE methods using a real dataset of 1230 offsprings subdivided into families of 25 individuals. Each family had six potential fathers and one known mother. Compared with the Exclusion method, the DBE method is able to solve 4.7% more individuals (64.4% Exclusion vs 69.1% DBE) using the most restrictive α tested without errors. DBE method can also be used together with the Exclusion method for error calculation and to further solve unassigned individuals. Using a two-step approach, we were able to assign 98.1% of the offsprings with a total predicted error of 4.7%. Considering the results obtained, we propose the use of the DBE method in combination with the Exclusion method for parental assignment.
BAG3 regulation of Rab35 mediates the Endosomal Sorting Complexes Required for Transport /endolysosome pathway and tau clearance
Authors: Lin Heng , Tang Maoping , Ji Changyi , Girardi Peter , Cvetojevic Gregor , Chen Yunpo , Koren Shon A. , Johnson Gail V. W.
Published: January 2021

Background

Declining proteostasis with aging contributes to increased susceptibility to neurodegenerative diseases, including Alzheimer’s disease (AD). Emerging studies implicate impairment of the endosome-lysosome pathway as a significant factor in the pathogenesis of these diseases. Our lab was the first to demonstrate that BAG3 regulates phosphorylated tau clearance. However, we did not fully define how BAG3 regulates endogenous tau proteostasis, especially in the early stages of disease progression.

Methods

Mass spectrometric analyses were performed to identify neuronal BAG3 interactors. Multiple biochemical assays were used to investigate the BAG3-HSP70-TBC1D10B-Rab35-Hrs regulatory networks. Live-cell imaging was used to study the dynamic of endosomal pathway. Immunohistochemistry and immunoblotting were performed in human AD brains and BAG3 overexpressed P301S tau transgenic mice.

Results

The primary group of neuronal BAG3 interactors identified are involved in the endocytic pathway. Among them were key regulators of small GTPases, such as the Rab35 GTPase activating protein, TBC1D10B. We demonstrated that a BAG3-HSP70-TBC1D10B complex attenuates the ability of TBC1D10B to inactivate Rab35. Thus, BAG3 interacts with TBC1D10B to support the activation of Rab35 and recruitment of Hrs, initiating ESCRT-mediated endosomal tau clearance. Further, TBC1D10B shows significantly less co-localization with BAG3 in AD brains than in age-matched controls. Overexpression of BAG3 in P301S tau transgenic mice increased the co-localization of phospho-tau with the ESCRT III protein CHMP2B and reduced the levels of the mutant human tau.

Conclusion

We identified a novel BAG3-TBC1D10B-Rab35 regulatory axis that modulates ESCRT-dependent protein degradation machinery and tau clearance. Dysregulation of BAG3 could contribute to the pathogenesis of AD.
Adherent and suspension baby hamster kidney cells have a different cytoskeleton and surface receptor repertoire
Authors: Dill Veronika , Pfaff Florian , Zimmer Aline , Beer Martin , Eschbaumer Michael
Published: January 2021

Animal cell culture, with single cells growing in suspension, ideally in a chemically defined environment, is a mainstay of biopharmaceutical production. The synthetic environment lacks exogenous growth factors and usually requires a time-consuming adaptation process to select cell clones that proliferate in suspension to high cell numbers. The molecular mechanisms that facilitate the adaptation and that take place inside the cell are largely unknown. Especially for cell lines that are used for virus antigen production such as baby hamster kidney (BHK) cells, the restriction of virus growth through the evolution of undesired cell characteristics is highly unwanted. The comparison between adherently growing BHK cells and suspension cells with different susceptibility to foot-and-mouth disease virus revealed differences in the expression of cellular receptors such as integrins and heparan sulfates, and in the organization of the actin cytoskeleton. Transcriptome analyses and growth kinetics demonstrated the diversity of BHK cell clones and confirmed the importance of well-characterized parental cell clones and mindful screening to make sure that essential cellular features do not get lost during adaptation.
Dendritic cell CX3CR1 and macrophages F4/80 play a central role in between gut micro biome and inflammation in Arsenic induced mice
Authors: Tikka Chiranjeevi , Manthari Ram Kumar , Niu Ruiyan , Sun Zilong , Wang Jundong
Published: January 2021

Microbiota plays a crucial role to protect the intestine contrary to the harmful foreign microorganisms and organize the immune system via numerous mechanisms, which include either direct or indirect environmental factors. The underlying mechanism arsenic (As) influenced immune system and regulates inflammation by altering gut microbiome in ileum remains unclear. However, chronic exposure to arsenic (at doses of 0.15 mg or 1.5 mg or 15 mg As2O3/ L in drinking water) significantly increased mRNA and protein levels of F4/80 and CX3CR1, concurrently, the increased levels of mRNA and protein IFNγ, TNFα, IL-18 and decreased levels of IL-10 were found in both 3 and 6 months exposure periods. High-throughput sequencing analysis revealed that gut microbiota at phylum; family and taxonomical levels were showed the abundance of gut microbiota. Evidentially, the ultra-structure of intestinal villi, microbes engulfed and immune cell migration were showed by the transmission electron microscopy. Chronic exposure to As influenced the inflammation by changing immune system and altered gut microbiota. In this study we conclude that chronic exposure to As breakdown the normal gut microbial community and increase the pathogenicity, the resultant risk pathogen direct contact with intestinal immune system and regulate the inflammation.
Generalizable prediction of stimulus-independent, task-unrelated thought from functional brain networks
Authors: Kucyi Aaron , Esterman Michael , Capella James , Green Allison , Uchida Mai , Biederman Joseph , Gabrieli John D.E. , Valera Eve M. , Whitfield-Gabrieli Susan
Published: January 2021

Neural substrates of “mind wandering” have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering—stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling—dominated by default-frontoparietal control subnetwork interactions—that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of attention-deficit/hyperactivity disorder (ADHD) adults. In three additional resting-state fMRI studies (totaln=1,115), including healthy and ADHD populations, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales, populations, and contexts.
Saccharide Analysis of Onion Outer Epidermal Walls
Authors: Wilson Liza A. , Deligey Fabien , Wang Tuo , Cosgrove Daniel J.
Published: January 2021

Background

Epidermal cell walls have special structural and biological roles in the life of the plant. Typically they are multi-ply structures encrusted with waxes and cutin which protect the plant from dehydration and pathogen attack. These characteristics may also reduce chemical and enzymatic deconstruction of the wall for sugar analysis and conversion to biofuels. We have assessed the saccharide composition of the outer epidermal wall of onion scales with different analytical methods. This wall is a particularly useful model for cell wall imaging and mechanics.

Results

Epidermal walls were depolymerized by acidic methanolysis combined with 2 M trifluoracetic acid hydrolysis and the resultant sugars were analyzed by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Total sugar yields based on wall dry weight were low (53%). Removal of waxes with chloroform increased the sugar yields to 73% and enzymatic digestion did not improve these yields. Analysis by gas chromatography/mass spectrometry (GC/MS) of per-O-trimethylsilyl (TMS) derivatives of the sugar methyl glycosides produced by acidic methanolysis gave a high yield for galacturonic acid (GalA) but glucose (Glc) was severely reduced. In a complementary fashion, GC/MS analysis of methyl alditols produced by permethylation gave substantial yields for glucose and other neutral sugars, but GalA was severely reduced. Analysis of the walls by13C solid-state NMR confirmed and extended these results and revealed 15% lipid content after chloroform extraction (potentially cutin and unextractable waxes).

Conclusions

Although exact values vary with the analytical method, our best estimate is that polysaccharide in the outer epidermal wall of onion scales is comprised of homogalacturonan (~50%), cellulose (~20%), galactan (~10%), xyloglucan (~10%) and smaller amounts of other polysaccharides. Low yields of specific monosaccharides by some methods may be exaggerated in epidermal walls impregnated with waxes and cutin and call for cautious interpretation of the results.
Nurse cell-derived small RNAs define paternal epigenetic inheritance inArabidopsis
Authors: Long Jincheng , Walker James , She Wenjing , Aldridge Billy , Gao Hongbo , Deans Samuel , Feng Xiaoqi
Published: January 2021

The plant male germline undergoes DNA methylation reprogramming, which methylates genesde novoand thereby alters gene expression and facilitates meiosis. Why reprogramming is limited to the germline and how specific genes are chosen is unknown. Here, we demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by germline-specific siRNAs transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) via activity of the tapetum-specific chromatin remodeler CLASSY3. Remarkably, tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Finally, we demonstrate that these nurse cell-derived siRNAs (niRNAs) silence germline transposons, thereby safeguarding genome integrity. Our results reveal that tapetal niRNAs are sufficient to reconstitute germline methylation patterns and drive extensive, functional methylation reprogramming analogous to piRNA-mediated reprogramming in animal germlines.
Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology
Authors: Terrey Markus , Adamson Scott I. , Chuang Jeffrey H. , Ackerman Susan L.
Published: January 2021

Translation-dependent quality control pathways such as no-go decay (NGD), non-stop decay (NSD) and nonsense-mediated decay (NMD) govern protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides derived from faulty and aberrant mRNAs. However, how translation is altered and thein vivodefects that arise in the absence of these pathways are poorly understood. Here, we show that the NGD/NSD factorsPeloandHbs1lare critical for cerebellar neurogenesis but expendable for survival of these neurons after development. Analysis of mutant embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, the translatome and cerebellar development were observed upon deletion of the NMD factorUpf2.These data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.
Benchmarking of lightweight-mapping based single-cell RNA-seq pre-processing
Authors: Booeshaghi A. Sina , Pachter Lior
Published: January 2021

We compare and benchmark the two lightweight-mapping tools that have been developed for pre-processing single-cell RNA-seq data, namely the kallisto-bustools and Salmon-Alevin-fry programs. We find that they output similar results, and to the extent that there are differences, they are irrelevant for downstream analysis. However, the Salmon-Alevin-fry program is significantly slower and requires much more memory to run, making it much more expensive to process large datasets limiting its use to larger servers.
Identification and analysis of novel variants in SARS-COV-2 genomes isolated from the Kingdom of Bahrain
Authors: bindayna Khalid M , Deifalla Abdel Halim , Mokbel Hicham Ezzat Mohammed
Published: January 2021

The challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccine’s availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SERS-CoV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SERS-CoV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrain’s SERS-CoV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-CoV2. Our research could have a high impact on vaccine development and distinguishes the source of SERS-CoV2 in the Kingdom of Bahrain.
COVID-19 Test Positivity Rate as a marker for hospital overload
Authors: Gaspari Mauro
Published: January 2021

The use of antigen tests for the diagnosis of COVID-19 in Italy has risen sharply in autumn 2020. Although, Italian regions like Alto Adige, Veneto, Toscana, Lazio, Piemonte and Marche did a large use of these tests for screening and surveillance purposes or for implementing diagnosis protocols, in addition to molecular tests, they were not reported in the statistics in the last months of 2020. As a consequence of this situation the test positivity rate (TPR) index, defined as the number of new positive cases divided by the number of tests, has lost in accuracy. Only in the recent days, starting from the 15th of January 2021, antigen tests have become part of the statistics for all the Italian regions. Despite the lack of data, we have noticed that TPR has a strong correlation with the number of patients admitted in hospitals, and that TPR peaks in general precede the peaks of hospitalized people which occur on average about 15 days later.

In this paper, we have deepened this intuition, analysing the TPR course and its relationship with the number of hospitalized people. To conduct the study we have defined a novel version of the TPR index which takes into account the number of tests done with respect to the population (considering both molecular and antigen tests), the number of infected individuals, and the number of patients healed. Successively, starting from a limited set of data which were made available in November 2020, we have reconstructed the antigen tests time series of four Italian regions, and we computed the TPR index for them.

The results show that TPR peaks precede peaks of hospitalized people in both the first and the second phases of the pandemic in Italy, provided that antigen tests are considered. Moreover, the TPR index trend, can be used to deduct important information on the course of the epidemic, and on the impact of COVID-19 in the health care system, which can be monitored in advance.
Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries
Authors: Landier Jordi , Paireau Juliette , Rebaudet Stanislas , Legendre Eva , Lehot Laurent , Fontanet Arnaud , Cauchemez Simon , Gaudart Jean
Published: January 2021

Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low.

During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1g/m3 was associated with a 0.15-unit increase of R0. Below 10°C, a temperature reduction of 1°C was associated with a 0.16-unit increase of R0.

Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer-to winter-like conditions likely contributed to the intensification of the second wave in north-west hemisphere countries. Adjustments of the levels of social mobility restrictions need to account for increased SARS-CoV-2 transmissibility in winter conditions.
High infection attack rates of SARS-CoV-2 in Dutch households revealed by dense sampling
Authors: Reukers Daphne F.M. , van Boven Michiel , Meijer Adam , Rots Nynke , Reusken Chantal , Roof Inge , van Gageldonk-Lafeber Arianne B. , van der Hoek Wim , van den Hof Susan
Published: January 2021

Background

Indoor environments are considered a main setting for transmission of SARS-CoV-2. Households in particular present a close-contact environment with high probability of transmission between persons of different ages and with different roles in society.

Methods

Complete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least three home visits were performed during 4-6 week of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, faeces and blood samples for molecular and serological analyses of all household members. Symptoms were recorded from two weeks before the first visit up to the last visit. Secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess transmission routes in the household.

Results

A total of 55 households with 187 household contacts were included. In 17 households no transmission took place, and in 11 households all persons were infected. Estimated SARs were high, ranging from 35% (95%CI: 24%-46%) in children to 51% (95%CI: 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared to adolescents and adults (0.67; 95%CI: 0.40-1.1).

Conclusion

Estimated SARs were higher than reported in earlier household studies, presumably owing to a dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated SAR in children was still high. Our results reinforce the role of households as main multiplier of SARS-CoV-2 infection in the population.

Key points

We analyze data from a SARS-CoV-2 household study and find higher secondary attack rates than reported earlier. We argue that this is due to a dense sampling strategy that includes sampling at multiple time points and of multiple anatomical sites.
Neutralization of UK-variant VUI-202012/01 with COVAXIN vaccinated human serum
Authors: Sapkal Gajanan N. , Yadav Pragya D. , Ella Raches , Deshpande Gururaj R. , Sahay Rima R. , Gupta Nivedita , Mohan V Krishna , Abraham Priya , Panda Samiran , Bhargava Balram
Published: January 2021

We performed the plaque reduction neutralization test (PRNT50) using sera collected from the recipients of BBV152/COVAXIN™ against hCoV-19/India/20203522 (UK-variant) and hCoV27 19/India/2020Q111 (heterologous strain). A comparable neutralization activity of the vaccinated individuals sera showed against UK-variant and the heterologous strain with similar efficiency, dispel the uncertainty of possible neutralization escape.