The molecular basis for the increased stability of the FUS-LC fibril at the anionic membrane- and air-water interfaces.

Self-organization of biomolecules can lead to the formation of liquid droplets, hydrogels, and irreversible aggregates that bear immense significance in biology and diseases. Despite the considerable number of studies conducted on biomolecular condensation in bulk solution, there is still a lack of understanding of how different surfaces regulate the condensation process. In this context, recent studies showed that, in contrast to zwitterionic lipid membranes, anionic membranes promoted the production of liquid droplets of FUsed in Sarcoma Low Complexity domain (FUS-LC) despite exhibiting no specific protein-lipid interactions.

Delineating the shape of COat Protein complex-II coated membrane bud.

Curvature-generating proteins that direct membrane trafficking assemble on the surface of lipid bilayers to bud transport intermediates, which move protein and lipid cargoes from one cellular compartment to another. However, it remains unclear what controls the overall shape of the membrane bud once curvature induction has begun. In vitro experiments showed that excessive concentrations of the COPII protein Sar1 promoted the formation of membrane tubules from synthetic vesicles, while COPII-coated transport intermediates in cells are generally more spherical or lobed in shape.

Early-warning of Cardiac Condition through Detection of Murmur in Heart Sound - A Case Study.

Cardiovascular disease, particularly Rheumatic Heart Disease (RHD), is one of the leading causes of death in many developing countries. RHD is manageable and treatable with early detection. However, multiple countries across the globe suffer from a scarcity of experienced physicians who can perform screening at large scales.

Interactions between the transcription factors FfmA and AtrR are required to properly regulate gene expression in the fungus Aspergillus fumigatus.

Transcriptional regulation of azole resistance in the filamentous fungus Aspergillus fumigatus is a key step in development of this problematic clinical phenotype. We and others have previously described a C2H2-containing transcription factor called FfmA that is required for normal levels of voriconazole susceptibility. Null alleles of ffmA exhibit a strongly compromised growth rate even in the absence of any external stress.

Correction: Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus.

[This corrects the article DOI: 10.1371/journal.pbio.

Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungus .

Transcriptional regulation of azole resistance in the filamentous fungus is a key step in development of this problematic clinical phenotype. We and others have previously described a C2H2-containing transcription factor called FfmA that is required for normal levels of voriconazole susceptibility and expression of an ATP-binding cassette transporter gene called . Null alleles of exhibit a strongly compromised growth rate even in the absence of any external stress.

Regulation of High-Affinity Iron Acquisition, Including Acquisition Mediated by the Iron Permease FtrA, Is Coordinated by AtrR, SrbA, and SreA in Aspergillus fumigatus.

Iron acquisition is crucial for virulence of the human pathogen Aspergillus fumigatus. Previous studies indicated that this mold regulates iron uptake via both siderophores and reductive iron assimilation by the GATA factor SreA and the SREBP regulator SrbA. Here, characterization of loss of function as well as hyperactive alleles revealed that transcriptional activation of iron uptake depends additionally on the ZnCys regulator AtrR, most likely via cooperation with SrbA.

Racial disparity in the co-occurrence of depression and type 2 diabetes mellitus. An electronic medical record study involving African American and White Caucasian adults from the US.

Introduction: Depression and diabetes commonly co-exist, however the temporal trends in the bidirectional association of both diseases in different sociodemographic setting has not been explored. We investigated the trends in prevalence and likelihood of having either depression or type 2 diabetes (T2DM) in African American (AA, or black) and White Caucasians (WC, or white).

Methods: In this nationwide population-based study, the US Centricity Electronic Medical Records was used to establish cohorts of >2.

Molecular mechanism of GTP binding- and dimerization-induced enhancement of Sar1-mediated membrane remodeling.

The Sar1 GTPase initiates coat protein II (COPII)-mediated protein transport by generating membrane curvature at subdomains on the endoplasmic reticulum, where it is activated by the guanine nucleotide exchange factor (GEF) Sec12. Crystal structures of GDP- and GTP-bound forms of Sar1 suggest that it undergoes a conformational switch in which GTP binding enhances the exposure of an amino-terminal amphipathic helix necessary for efficient membrane penetration. However, key residues in the amino terminus were not resolved in crystal structures, and experimental studies have suggested that the amino terminus of Sar1 is solvent-exposed in the absence of a membrane, even in the GDP-bound state.

Robustness of Multiple Imputation Methods for Missing Risk Factor Data from Electronic Medical Records for Observational Studies.

Unlabelled: Evaluating appropriate methodologies for imputation of missing outcome data from electronic medical records (EMRs) is crucial but lacking for observational studies. Using US EMR in people with type 2 diabetes treated over 12 and 24 months with dipeptidyl peptidase 4 inhibitors (DPP-4i,  = 38,483) and glucagon-like peptide 1 receptor agonists (GLP-1RA,  = 8,977), predictors of missingness of disease biomarker (HbA1c) were explored. Robustness of multiple imputation (MI) by chained equations, two-fold MI (MI-2F) and MI with Monte Carlo Markov Chain were compared to complete case analyses for drawing inferences.

Modeling the artificial intelligence-based imperatives of industry 5.0 towards resilient supply chains: A post-COVID-19 pandemic perspective.

The recent COVID-19 pandemic has significantly affected emerging economies' global supply chains (SCs) by disrupting their manufacturing activities. To ensure business survivability during the current and post-COVID-19 era, it is crucial to adopt artificial intelligence (AI) technologies to renovate traditional manufacturing activities. The fifth industrial revolution, Industry 5.

Biochemical Identification of a Nuclear Coactivator Protein Required for AtrR-Dependent Gene Regulation in Aspergillus fumigatus.

Azole drugs represent the primary means of treating infections associated with the filamentous fungal pathogen Aspergillus fumigatus. A central player in azole resistance is the ZnCys zinc cluster-containing transcription factor AtrR. This factor stimulates expression of both the gene, which encodes the azole drug target enzyme, as well as an ATP-binding cassette transporter-encoding gene called ().

Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study.

Background: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.

Methods: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA.

Adopting net-zero in emerging economies.

In recent years, rapid reduction in natural resources alongside climate change has prompted industries to adopt sustainable operational practices. Globalization is arguably a boon for people and societies worldwide but has also led to significant disruptions to our natural ecosystem. Consequently, it has caused environmental concerns and issues around public health.

Young Adult Depression, Antidepressant Prescriptions, and Therapy Intensification in People With Incident Depression in the United States.

To evaluate the temporal trend in young adult depression, prescription patterns of first- and second-line antidepressants, and factors influencing therapy intensification for depression stratified by sex. A retrospective cohort of people aged ≥ 18 years with incident depression between 2006 and 2017 was extracted from the Centricity Electronic Medical Records. Among 2,201,086 people with depression (82% on antidepressants), the mean age was 47 years, 29% were male, 40% had cardiometabolic multimorbidity, and 32% were diagnosed at age < 40 years (young adult depression).

Temporal trends in the prevalence and incidence of depression and the interplay of comorbidities in patients with young- and usual-onset type 2 diabetes from the USA and the UK.

Aims/hypothesis: We aimed to investigate the prevalence and incidence of depression, and the interplay of cardiometabolic comorbidities, in the differentiation of depression risk between young-onset diabetes (diagnosis at age <40 years) and usual-onset diabetes (diagnosis at age ≥40 years).

Methods: Using electronic medical records from the UK and USA, retrospective cohorts of adults with incident type 2 diabetes diagnosed between 2006 and 2017 were examined. Trends in the prevalence and incidence of depression, and risk of developing depression, in participants with young-onset type 2 diabetes compared with usual-onset type 2 diabetes were assessed separately by sex and comorbidity status.

A framework for the estimation of treatment costs of cardiovascular conditions in the presence of disease transition.

The current research aims to aid policymakers and healthcare service providers in estimating expected long-term costs of medical treatment, particularly for chronic conditions characterized by disease transition. The study comprised two phases (qualitative and quantitative), in which we developed linear optimization-based mathematical frameworks to ascertain the expected long-term treatment cost per patient considering the integration of various related dimensions such as the progression of the medical condition, the accuracy of medical treatment, treatment decisions at respective severity levels of the medical condition, and randomized/deterministic policies. At the qualitative research stage, we conducted the data collection and validation of various cogent hypotheses acting as inputs to the prescriptive modeling stage.

Bonactin and Feigrisolide C Inhibit Fungus and Control Wheat Blast Disease.

Wheat blast caused by the (MoT) pathotype is one of the most damaging fungal diseases of wheat. During the screening of novel bioactive secondary metabolites, we observed two marine secondary metabolites, bonactin and feigrisolide C, extracted from the marine bacteria spp. (Act 8970 and ACT 7619), remarkably inhibited the hyphal growth of an MoT isolate BTJP 4 (5) in vitro.

A novel methodology for perception-based portfolio management.

Selecting and investing in stock market with right proportions is one of the major challenges. Majority of the investors end up losing their invested equity capital due to uncertainty in the market. The present study provides a novel framework for novice investors to construct portfolio based on multicriteria decision making techniques under fuzzy environment.

Modeling a sustainable vaccine supply chain for a healthcare system.

This study develops a vaccine supply chain (VSC) to ensure sustainable distribution during a global crisis in a developing economy. In this study, a multi-objective mixed-integer programming (MIP) model is formulated to develop the VSC, ensuring the entire network's economic performance. This is achieved by minimizing the overall cost of vaccine distribution and ensuring environmental and social sustainability by minimizing greenhouse gas (GHG) emissions and maximizing job opportunities in the entire network.

Antidepressant prescriptions and therapy intensification in men and women newly diagnosed with depression in the UK.

Background: Evidence on therapeutic interventions and factors driving treatment intensification (TI) in people with incident depression in UK are scarce.

Aims: To explore antidepressant prescribing patterns and factors influencing TI.

Design: and setting: Retrospective cohort study of adults with incident depression diagnosed between 2006 and 2017 using UK primary care database.

Benchmarking sustainable E-commerce enterprises based on evolving customer expectations amidst COVID-19 pandemic.

The 2019 coronavirus disease (COVID-19) pandemic has seriously impacted the performance of all types of businesses. It has given a tremendous structural boost to e-commerce enterprises by forcing customers to online shopping over visiting physical stores. Moreover, customer expectations of the digital and operational capabilities of e-commerce firms are also increasing globally.