Benchmarking Alzheimer's disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies.

Background: The success of selecting high risk or early-stage Alzheimer's disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer's disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.

Effect of Severe Fever With Thrombocytopenia Syndrome Virus Genotype on Disease Severity, Viral Load, and Cytokines in South Korea.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by (SFTS virus [SFTSV]). Recently, at least 6 different genotypes of SFTSV have been identified, with genotypes A, D, and F dominant in China and B dominant in Japan and Korea. This study investigated the effect of SFTSV genotypes circulating in South Korea on disease severity, viral load, and cytokine profile.

Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

Background: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC.

Methods: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023.

CRISPR-aided genome engineering for secondary metabolite biosynthesis in Streptomyces.

Unlabelled: The demand for discovering novel microbial secondary metabolites is growing to address the limitations in bioactivities such as antibacterial, antifungal, anticancer, anthelmintic, and immunosuppressive functions. Among microbes, the genus Streptomyces holds particular significance for secondary metabolite discovery. Each Streptomyces species typically encodes approximately 30 secondary metabolite biosynthetic gene clusters (smBGCs) within its genome, which are mostly uncharacterized in terms of their products and bioactivities.

An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.

The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized.

A robust and adaptive framework for interaction testing in quantitative traits between multiple genetic loci and exposure variables.

The identification and understanding of gene-environment interactions can provide insights into the pathways and mechanisms underlying complex diseases. However, testing for gene-environment interaction remains a challenge since a.) statistical power is often limited and b.

A Pitx3-deficient developmental mouse model for fine motor, olfactory, and gastrointestinal symptoms of Parkinson's disease.

Parkinson's disease (PD) is characterized by the selective death of substantia nigra pars compacta (SNpc) dopaminergic neurons and includes both motor and non-motor symptoms. While numerous models exist for the study of typical PD motor deficits, fewer exist for non-motor symptoms. Previous studies have shown that a Pitx3 mouse model (aphakia or ak mouse) has specific developmental failure of the dopaminergic neuron population in the SNpc and that it can be used for the study of PD-related gross motor dysfunction as well as cognitive functional deficits.

System-Level Analysis of Transcriptional and Translational Regulatory Elements in .

Bacteria belonging to have the ability to produce a wide range of secondary metabolites through a shift from primary to secondary metabolism regulated by complex networks activated after vegetative growth terminates. Despite considerable effort to understand the regulatory elements governing gene expression related to primary and secondary metabolism in , system-level information remains limited. In this study, we integrated four multi-omics datasets from NBRC 13350: RNA-seq, ribosome profiling, dRNA-seq, and Term-Seq, to analyze the regulatory elements of transcription and translation of differentially expressed genes during cell growth.

Genome-scale analysis of genetic regulatory elements in Streptomyces avermitilis MA-4680 using transcript boundary information.

Background: The gram-positive bacterium, Streptomyces avermitilis, holds industrial importance as the producer of avermectin, a widely used anthelmintic agent, and a heterologous expression host of secondary metabolite-biosynthetic gene clusters. Despite its industrial importance, S. avermitilis' genome organization and regulation of gene expression remain poorly understood.

Genetics and functional genomics of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease with genetic predisposition. Over the last decade, genome-wide association studies with increasing sample size led to the discovery of robustly associated genetic variants at an exponential rate. More than 200 genetic loci have been associated with MS susceptibility and almost half of its heritability can be accounted for.

as Microbial Chassis for Heterologous Protein Expression.

Heterologous production of recombinant proteins is gaining increasing interest in biotechnology with respect to productivity, scalability, and wide applicability. The members of genus have been proposed as remarkable hosts for heterologous production due to their versatile nature of expressing various secondary metabolite biosynthetic gene clusters and secretory enzymes. However, there are several issues that limit their use, including low yield, difficulty in genetic manipulation, and their complex cellular features.

Interaction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function.

Importance: The risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures of lung function.

Objective: To assess the interaction of cigarette smoking and polygenic risk score in association with reduced lung function.

Design, Setting, And Participants: This UK Biobank cohort study included UK citizens of European ancestry aged 40 to 69 years with genetic and spirometry data passing quality control metrics.

Re-classification of strains and mining secondary metabolite biosynthetic gene clusters.

species have attracted considerable interest as a reservoir of medically important secondary metabolites, which are even diverse and different between strains. Here, we reassess ten strains by presenting the highly resolved classification, using 16S rRNA sequencing, MALDI-TOF MS protein profiling, and whole-genome sequencing. The results revealed that seven of the ten strains were misclassified as .

A higher burden of multiple sclerosis genetic risk confers an earlier onset.

Background: Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration.

Objectives: Determine the influence of MS genetic predisposition on age of onset.

Methods: We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex.

Elucidating the Regulatory Elements for Transcription Termination and Posttranscriptional Processing in the Streptomyces clavuligerus Genome.

Identification of transcriptional regulatory elements in the GC-rich genome is essential for the production of novel biochemicals from secondary metabolite biosynthetic gene clusters (smBGCs). Despite many efforts to understand the regulation of transcription initiation in smBGCs, information on the regulation of transcription termination and posttranscriptional processing remains scarce. In this study, we identified the transcriptional regulatory elements in β-lactam antibiotic-producing ATCC 27064 by determining a total of 1,427 transcript 3'-end positions (TEPs) using the term-seq method.

Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture.

Actinomycetes are a rich source of bioactive natural products important for novel drug leads. Recent genome mining approaches have revealed an enormous number of secondary metabolite biosynthetic gene clusters (smBGCs) in actinomycetes. However, under standard laboratory culture conditions, many smBGCs are silent or cryptic.

Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1.

Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity.

Systems and synthetic biology to elucidate secondary metabolite biosynthetic gene clusters encoded in genomes.

Covering: 2010 to 2020 Over the last few decades, Streptomyces have been extensively investigated for their ability to produce diverse bioactive secondary metabolites. Recent advances in Streptomyces research have been largely supported by improvements in high-throughput technology 'omics'. From genomics, numerous secondary metabolite biosynthetic gene clusters were predicted, increasing their genomic potential for novel bioactive compound discovery.

Genome-scale determination of 5´ and 3´ boundaries of RNA transcripts in Streptomyces genomes.

Streptomyces species are gram-positive bacteria with GC-rich linear genomes and they serve as dominant reservoirs for producing clinically and industrially important secondary metabolites. Genome mining of Streptomyces revealed that each Streptomyces species typically encodes 20-50 secondary metabolite biosynthetic gene clusters (smBGCs), emphasizing their potential for novel compound discovery. Unfortunately, most of smBGCs are uncharacterized in terms of their products and regulation since they are silent under laboratory culture conditions.

Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.

Risk of chronic obstructive pulmonary disease (COPD) is determined by both cigarette smoking and genetic susceptibility, but little is known about gene-by-smoking interactions. We performed a genome-wide association analysis of 179,689 controls and 21,077 COPD cases from UK Biobank subjects of European ancestry recruited from 2006 to 2010, considering genetic main effects and gene-by-smoking interaction effects simultaneously (2-degrees-of-freedom (df) test) as well as interaction effects alone (1-df interaction test). We sought to replicate significant results in COPDGene (United States, 2008-2010) and SpiroMeta Consortium (multiple countries, 1947-2015) data.

Toward a Unified Framework for Cognitive Maps.

In this study, we integrated neural encoding and decoding into a unified framework for spatial information processing in the brain. Specifically, the neural representations of self-location in the hippocampus (HPC) and entorhinal cortex (EC) play crucial roles in spatial navigation. Intriguingly, these neural representations in these neighboring brain areas show stark differences.

System-level understanding of gene expression and regulation for engineering secondary metabolite production in Streptomyces.

The gram-positive bacterium, Streptomyces, is noticed for its ability to produce a wide array of pharmaceutically active compounds through secondary metabolism. To discover novel bioactive secondary metabolites and increase the production, Streptomyces species have been extensively studied for the past decades. Among the cellular components, RNA molecules play important roles as the messengers for gene expression and diverse regulations taking place at the RNA level.