bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational entropy limits the transition from nucleation to elongation in amyloid aggregation
Authors: Phan Tien M. , Schmit Jeremy D. 
Published: June 2020

ABSTRACTThe formation ofβ-sheet rich amyloid fibrils in Alzheimer’s disease and other neurodegenerative disorders is limited by a slow nucleation event. To understand the initial formation ofβ-sheets from disordered peptides, we used all-atom simulations to parameterize a lattice model that treats each amino acid as a binary variable withβand non-βstates. We show that translational and conformational entropy give the nascentβ-sheet an anisotropic surface tension which can be used to describe the nucleus with two-dimensional Classical Nucleation Theory. Since translational entropy depends on concentration, the aspect ratio of the criticalβ-sheet changes with protein concentration. Our model explains the transition from the nucleation phase to elongation as the point where theβ-sheet core becomes large enough to overcome the conformational entropy cost to straighten the terminal molecule. At this point theβ-strands in the nucleus spontaneously elongate, which results in a larger binding surface to capture new molecules. These results suggest that nucleation is relatively insensitive to sequence differences in co-aggregation experiments because the nucleus only involves a small portion of the peptide.SIGNIFICANCEThe conversion of soluble proteins to amyloid aggregates is associated with many neurodegenerative diseases. Experiments have shown that this conversion occurs by a slow nucleation step followed by rapid growth. This work identifies the principle contributions to the free energy barrier that separates these two stages. It also shows how factors like protein concentration, sidechain interactions, and interactions with the environment can modify the barrier and affect nucleation times.
Notch Regulates Vascular Collagen IV Basement Membrane Through Modulation of Lysyl Hydroxylase 3 Trafficking
Authors: Gross Stephen J. , Webb Amelia M. , Peterlin Alek D. , Durrant Jessica R. , Judson Rachel , Kushner Erich J. 
Published: June 2020

SUMMARYDuring angiogenesis, endothelial cells secrete proteins that make up a planar protein network surrounding blood vessels termed basement membrane (BM). Collagen type IV (Col IV) is a BM protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. To date, little is known about how endothelial cells mediate intracellular transport and selective secretion of Col IV. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development. Knockdown of Rab10 reducedde novoCol IV secretionin vivoandin vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 resulted in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrated that Rab10 activation is downstream of Notch signaling, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Overall, our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune BM secretion during blood vessel development.
Lipid extraction from dried blood spots and dried milk spots for high throughput lipidomics
Authors: Furse Samuel , Koulman Albert 
Published: June 2020

AbstractDried blood spots (DBS) and dried milk spots (DMS) represent convenient matrices for collecting and storing human samples. However, the use of these sample types for researching lipid metabolism remains relatively poorly explored, and especially the efficiency of lipid extraction is unclear. A visual inspection of punched DBSs after standard extraction suggests that the samples remain largely intact. DMSs comprise a dense aggregate of milk fat globules on one side of the card, suggesting that the lipid fraction may be physically inaccessible. This led us to the hypotheses that decoagulating may facilitate lipid extraction from both DBSs and DMSs. We tested decoagulation using a mixture of strong chaeotropes (guanidine and thiourea) in both DBS and DMS in the context of high throughput lipidomics (96/384w plate). Extraction of lipids from DMSs was tested with established extractions and one novel solvent mixture in a high throughput format. We found that exposure of DBSs to chaeotropes facilitated collection of the lipid fraction but was ineffective for DMSs. The lipid fraction of DMSs was best isolated without water, using a mixture of xylene/methanol/isopropanol (1:2:4). We conclude that decoagulation is essential for efficient extraction of lipids from DBSs and that a non-aqueous procedure using a spectrum of solvents is the best procedure for extracting lipids from DMSs. These methods represent convenient steps that are compatible with the sample structure and type, and with high throughput lipidomics.HighlightsThe efficiency of lipid extractions on dried milk and dried blood spots was testedThe number of lipid variables and the total signal strength were used as objective measuresDecoagulation of dried blood spots improved extraction efficiencyA mixture of xylene, methanol and isopropanol isolates the lipid fraction best from DMSsAn aqueous extraction using dichloromethane was the most efficient method for isolating lipids from DBSs
Age-dependent glycomic response to the 2009 pandemic H1N1 influenza virus and its association with disease severity
Authors: Chen Shuhui , Kasper Brian , Zhang Bin , Lashua Lauren P. , Ross Ted M. , Ghedin Elodie , Mahal Lara K. 
Published: June 2020

ABSTRACTInfluenza A viruses cause a spectrum of responses, from mild cold-like symptoms to severe respiratory illness and death. Viral strains and intrinsic host factors, such as age, can influence the severity of the disease. Glycosylation plays a critical role in influenza pathogenesis, however the molecular drivers of influenza outcomes remain unknown. In this work, we characterized the glycomic response to the H1N1 2009 pandemic influenza A virus in age-dependent severity. Using a ferret model and a lectin microarray technology we have developed, we compared responses in newly weaned and aged animals, a model for young children and the elderly, respectively. Glycomic analysis revealed changes in glycosylation over the course of the infection, that were associated with severity in an age-dependent manner. These responses may help explain the differential susceptibility to influenza A virus infection of young children and the elderly.
miR156-mediated changes in leaf composition lead to altered photosynthetic traits during vegetative phase change
Authors: Lawrence Erica H. , Springer Clint J. , Helliker Brent R. , Poethig R. Scott 
Published: June 2020

SummaryPlant morphology and physiology change with growth and development. Some of these changes are due to change in plant size and some are the result of genetically programmed developmental transitions. In this study we investigate the role of the developmental transition, vegetative phase change (VPC), on morphological and photosynthetic changes.We used overexpression of miR156, the master regulator of VPC, to modulate the timing of VPC inPopulus tremula x alba, Zea maysandArabidopsis thalianato determine its role in trait variation independent of changes in size and overall age.Here we find that juvenile and adult leaves in all three species photosynthesize at different rates and that these differences are due to phase-dependent changes in specific leaf area (SLA) and leaf N but not photosynthetic biochemistry. Further, we found juvenile leaves with high SLA were associated with better photosynthetic performance at low light levels.This study establishes a role for VPC in leaf composition and photosynthetic performance across diverse species and environments. Variation in leaf traits due to VPC are likely to provide distinct benefits under specific environments and, as a result, selection on the timing of this transition could be a mechanism for environmental adaptation.
Retrospective Methodology to Estimate Daily Infections from Deaths (REMEDID) in COVID-19: the Spain case study
Authors: García-García David , Vigo María Isabel , Fonfría Eva S. , Herrador Zaida , Navarro Miriam , Bordehore Cesar 
Published: June 2020

AbstractThe number of new daily infections is one of the main parameters to understand the dynamics of an epidemic. During the COVID-19 pandemic in 2020, however, such information has been underestimated. Here, we propose a retrospective methodology to estimate daily infections from daily deaths, because those are usually more accurately documented. This methodology is applied to Spain and its 19 administrative regions. Our results showed that probable infections during the first wave were between 35 and 42 times more than those officially documented on 14 March, when the national government decreed a national lockdown and 9 times more than those documented by the updated version of the official data. The national lockdown had a strong effect on the growth rate of virus transmission, which began to decrease immediately. Finally, the first inferred infection in Spain is about 43 days before it was officially reported during the first wave. The current official data show delays of 15-30 days in the first infection relative to the inferred infections in 63% of the regions. In summary, we propose a methodology that allows reinterpretation of official daily infections, improving data accuracy in infection magnitude and dates because it assimilates valuable information from the National Seroprevalence Studies.
Clinical Characteristics in Children and Adolescents with SARS-CoV-2 Infection: Experience in a highly complex Public Hospital in the city of São Paulo
Authors: Vieira Rafael Santos Rodrigues , de Aguiar Erisson Linhares , de Araújo Evangelista Nara Michelle , Sarrubbo Sergio Antonio Bastos , Verlangieri Helmar Abreu Rocha , Otsuka Marcelo 
Published: June 2020

AbstractObjectiveFaced with the SARS-CoV-2 epidemic, the real impact of the disease on children and adolescents and the behavior of the disease in this population are questioned. This study aims to assess the clinical characteristics of children and adolescents with SARS-CoV-2 infection and the effectiveness of the measures adopted at the institution.MethodsThis is a prospective study carried out from 11/04/2020 to 19/06/2020. Investigated 346 patients between zero and eighteen years old, with analysis of patients diagnosed with COVID-19 confirmed by RT-PCR, obtained from a nasopharynx and oropharynx swab, attended at a highly complex public pediatric hospital in the city of São Paulo.Protocols for clinical management and treatment of cases of SARS-CoV-2 infection were adopted during the assistance and implementation of a preoperative screening protocol. They were evaluated according to sex, age, epidemiology, presence of comorbidities, clinical manifestations, therapy used, need for hospitalization in the ward and ICU, use of mechanical ventilation (MV) and evolution.Results66 confirmed patients with COVID 19 were identified. Median age was 7 years old, with the male gender predominant (2:1). 27 patients (40.9%) had contact with symptomatic respiratory individuals, comorbidity occurred in 50 cases (75.8%). Main clinical manifestations were: fever, 37 patients (56.1%); cough, 23 (34.8%); respiratory distress in 10 (15.2%) and gastrointestinal symptoms in 24 (36.4%). 38 patients (57.6%) received antibiotics and 13 (19.7%) received corticotherapy. 37 patients (56.1%) required hospitalization, eight (19.5%) in the ICU and six (75%) requiring MV. One death occurred and others with good evolution.ConclusionThis study corroborates the perception that the pediatric patient has a more benign manifestation, even in the presence of comorbidities, requiring the screening of surgical patients. The protocol adopted by the institution proved to be effective, with no contamination being observed among patients or between patients and collaborators.
Proteomic blood profiling in mild, severe and critical COVID-19 patients
Authors: Patel Hamel , Ashton Nicholas J , Dobson Richard J.B , Andersson Lars-Magnus , Yilmaz Aylin , Blennow Kaj , Gisslen Magnus , Zetterberg Henrik 
Published: June 2020

AbstractThe recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed athttps://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.
Maternal postnatal depression and offspring depression at age 24 years in a UK-birth cohort: the mediating role of maternal nurturing behaviours concerning feeding, crying and sleeping
Authors: Culpin Iryna , Hammerton Gemma , Bornstein Marc H , Heron Jon , Evans Jonathan , Cadman Tim , Sallis Hannah M , Tilling Kate , Stein Alan , Kwong Alex SF , Pearson Rebecca M 
Published: June 2020

AbstractImportanceFew longitudinal studies have examined the role of maternal nurturing parenting behaviours concerning feeding, crying and sleeping in the association between maternal postnatal depression (PND) and offspring depression in adulthood.ObjectiveTo examine the association between PND and offspring depression at age 24 years and the mediating role of maternal nurturing behaviours concerning feeding, crying and sleeping.DesignLongitudinal study of mothers and their offspring in the Avon Longitudinal Study of Parents and Children, followed up through age 24 years. Offspring ICD-10 depression diagnosis at age 24 years was established using the Clinical Interview Schedule-Revised. Symptoms of maternal depression were measured using the Edinburgh Postnatal Depression Scale at 8 months postnatally. Maternal nurturing behaviours concerning feeding, crying and sleeping were assessed using self-reported questionnaires administered from birth to age 3 years.ResultsThe sample with complete data on confounders for the mediation analyses was 5,881. In the fully adjusted model, there was evidence of an indirect effect from PND to offspring depression through the combination of all parenting factors (probit regression coefficient [B]=0.038, 95%CI 0.005, 0.071); however, there was no evidence of a direct effect from early maternal PND to adult offspring depression once the indirect effect via parenting factors was accounted for (B=0.009, 95%CI -0.075, 0.093). There was evidence for specific indirect effects through maternal worries about feeding (B=0.019, 95%CI 0.003, 0.035, p=0.010) and maternal perceptions and responses to crying (B=0.018, 95%CI 0.004, 0.032, p=0.012). Analyses in a larger sample using multiple imputation led to similar results.Conclusions and RelevanceThe adverse impact of PND on offspring depression in early adulthood was explained by maternal nurturing behaviours concerning feeding, crying and sleeping in early infancy. Residual confounding and measurement error are likely, limiting causal conclusions. If found to be causal, reducing worries around early maternal nurturing behaviours could be a target for interventions to reduce adverse outcomes in adult offspring of depressed mothers.
A Macroeconomic SIR Model for COVID-19
Authors: Bayraktar Erhan , Cohen Asaf , Nellis April 
Published: June 2020

AbstractThe current COVID-19 pandemic and subsequent lockdowns have highlighted the close and delicate relationship between a country’s public health and economic health. Macroeconomic models which use preexisting epidemic models to calculate the impacts of a disease outbreak are therefore extremely useful for policymakers seeking to evaluate the best course of action in such a crisis. We develop an SIR model of the COVID-19 pandemic which explicitly considers herd immunity, behavior-dependent transmission rates, remote workers, and indirect externalities of lockdown. This model is presented as an exit time control problem where the lockdown ends when the population achieves herd immunity, either naturally or via a vaccine. A social planner prescribes separate levels of lockdown for two separate sections of the adult population - those who are low-risk (ages 20-64) and those who are high-risk (ages 65 and over). These levels are determined via optimization of an objective function which assigns a macroeconomic cost to the level of lockdown and the number of deaths. We find that, by ending lockdowns once herd immunity is reached, high-risk individuals are able to leave lockdown significantly before the arrival of a vaccine without causing large increases in mortality. Additionally, if we incorporate a behavior-dependent transmission rate which represents increased personal caution in response to increased infection levels, both output loss and total mortality are lowered. Lockdown efficacy is further increased when there is less interaction between low- and high-risk individuals, and increased remote work decreases output losses. Overall, our model predicts that a lockdown which ends at the arrival of herd immunity, combined with individual actions to slow virus transmission, can reduce total mortality to one-third of the no-lockdown level, while allowing high-risk individuals to leave lockdown well before vaccine arrival.
Face mask wearing rate predicts COVID-19 death rates across countries
Authors: Miyazawa D , Kaneko G 
Published: June 2020

AbstractIdentifying biomedical and socioeconomic predictors of the number of deaths caused by COVID-19 can help the development of effective interventions. In this study, we used the hypothesis-driven regression approach to test the hypothesis that the mask wearing rate, along with age and obesity, can largely predict the cumulative number of deaths across countries. Our regression models explained 69% of the variation in the cumulative number of deaths per million (March to June 2020) among 22 countries, identifying the face mask wearing rate in March as an important predictor. The number of deaths per million predicted by our elastic net regression model showed high correlation (r = 0.86) with observed numbers. These findings emphasize the importance of face masks in preventing the ongoing pandemic of COVID-19.One Sentence SummaryFace mask wearing rate in March is a strong predictor of the cumulative number of deaths per million caused by COVID-19 among 22 countries.
Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19
Authors: Psichogiou Mina , Karabinis Andreas , Pavlopoulou Ioanna D. , Basoulis Dimitrios , Petsios Konstantinos , Roussos Sotirios , Patrikaki Maria , Jahaj Edison , Protopapas Konstantinos , Leontis Konstantinos , Rapti Vasiliki , Kotanidou Anastasia , Antoniadou Anastasia , Poulakou Garyphallia , Paraskevis Dimitrios , Sypsa Vana , Hatzakis Angelos 
Published: June 2020

AbstractGreece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95%CI 0.06%-0.26%). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in two hospitals and assess potential risk factors. Hospital-1 was involved in the care of COVID-19 patients while hospital-2 was not. A validated, rapid, IgM/IgG antibody point-of care test was used. 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.07% (95%CI 0.37-1.78) overall and 0.44% (95%CI 0.12-1.13) and 2.4% (95%CI 0.51-8.19) in hospital-1 and hospital-2, respectively. The overall, hospital-1, and hospital-2 seroprevalence was 9, 3 and 20 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals. These data have implications for the preparedness of a second wave of COVID-19 epidemic.
A primary care approach to the COVID-19 pandemic: clinical features and natural history of 2,073 suspected cases in the Corona São Caetano programme, São Paulo, Brazil
Authors: Leal Fabio E , Mendes-Correa Maria C , Buss Lewis F , Costa Silvia F , Bizario Joao CS , de Souza Sonia RP , Thomaz Osorio , Tozetto-Mendoza Tania R , Villas-Boas Lucy S , Silva Lea CO , Grespan Regina MZ , Capuani Ligia , Buccheri Renata , Domingues Helves , Alexander Neal DE , Mayaud Philippe , Sabino Ester C 
Published: June 2020

ABSTRACTBackgroundDespite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19.Methods and findingsThe Corona São Caetano program is a primary care initiative offering COVID-19 care to all residents of São Caetano do Sul, Brazil. After triage of potentially severe cases, consecutive patients presenting between 13th April and 13th May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days. RT-PCR-negative patients were offered SARS-CoV-2 serology. We describe the clinical features, virology and natural history of this prospective population-based cohort. Of 2,073 suspected COVID-19 cases, 1,583 (76·4%) were tested by RT-PCR, of whom 444 (28·0%, 95%CI: 25·9% - 30·3%) were positive; 604/1,136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8·6%) tested SARS-CoV-2 seropositive. The most common symptoms of COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever, anosmia, and ageusia were most associated with a positive COVID-19 diagnosis. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia, and around symptom onset. The rates of hospitalization and death among 444 RT-PCR-positive cases were 6·7% and 0·7%, respectively, with older age and obesity more frequent in the hospitalized group.ConclusionsCOVID-19 presents similarly to other mild respiratory disease in primary care. Some symptoms assist the differential diagnosis. Most patients can be managed at home.