Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals' EBV immune response and perceived fatigue in a community dwelling cohort (n = 864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response - with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI).
View Article and Find Full Text PDFBackground: Intracerebral hemorrhage (ICH) stands out as the most fatal subtype of stroke, currently devoid of effective therapy. Recent research underscores the significance of Axl and its ligand growth arrest-specific 6 (Gas6) in normal brain function and a spectrum of neurological disorders, including ICH. This study is designed to delve into the role of Gas6/Axl signaling in facilitating hematoma clearance and neuroinflammation resolution following ICH.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is a global public-health problem. Astrocytes, and their mitochondria, are important factors in the pathogenesis of TBI-induced secondary injury. Mitochondria extracted from healthy tissues and then transplanted have shown promise in models of a variety of diseases.
View Article and Find Full Text PDFEvolutionary changes in the hepatitis B virus (HBV) genome could reflect its adaptation to host-induced selective pressure. Leveraging paired human exome and ultra-deep HBV genome-sequencing data from 567 affected individuals with chronic hepatitis B, we comprehensively searched for the signatures of this evolutionary process by conducting "genome-to-genome" association tests between all human genetic variants and viral mutations. We identified significant associations between an East Asian-specific missense variant in the gene encoding the HBV entry receptor NTCP (rs2296651, NTCP S267F) and mutations within the receptor-binding region of HBV preS1.
View Article and Find Full Text PDFThe Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aimed to assess if bacterial genetics governs MTBC pathogenesis or if local co-adaptation translates into differential susceptibility of human macrophages to infection by different MTBC genotypes.
View Article and Find Full Text PDFChondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear.
View Article and Find Full Text PDFBackground: Predicting the outcome of oral squamous cell carcinoma (OSCC) is challenging due to its diverse nature and intricate causes. This research explores how lysosome-associated genes (LRGs) might forecast overall survival (OS) and correlate with immune infiltration in OSCC patients.
Methods: We analyzed OSCC patients' LRGs' mRNA expression data and clinical details from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
Summary: Joint analyses of paired host and pathogen genome sequences have the potential to enhance our understanding of host-pathogen interactions. A systematic approach to conduct such a joint analysis is through a "genome-to-genome" (G2G) association study, which involves testing for associations between all host and pathogen genetic variants. Significant associations reveal host genetic factors that might drive pathogen variation, highlighting biological mechanisms likely to be involved in host control and pathogen escape.
View Article and Find Full Text PDFIn settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data.
View Article and Find Full Text PDFCoronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD.
View Article and Find Full Text PDFStudies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased.
View Article and Find Full Text PDFGenome-wide association studies (GWASs) have demonstrated that most common diseases have a strong genetic component from many genetic variants each with a small effect size. GWAS summary statistics have allowed the construction of polygenic scores (PGSs) estimating part of the individual risk for common diseases. Here, we propose to improve PGS-based risk estimation by incorporating genetic ancestry derived from genome-wide genotyping data.
View Article and Find Full Text PDFGenome-wide association studies rely on the statistical inference of untyped variants, called imputation, to increase the coverage of genotyping arrays. However, the results are often suboptimal in populations underrepresented in existing reference panels and array designs, since the selected single nucleotide polymorphisms (SNPs) may fail to capture population-specific haplotype structures, hence the full extent of common genetic variation. Here, we propose to sequence the full genomes of a small subset of an underrepresented study cohort to inform the selection of population-specific add-on tag SNPs and to generate an internal population-specific imputation reference panel, such that the remaining array-genotyped cohort could be more accurately imputed.
View Article and Find Full Text PDFMendelian randomization is the use of genetic variants to assess the effect of intervening on a risk factor using observational data. We consider the scenario in which there is a pharmacomimetic (i.e.
View Article and Find Full Text PDFTransient receptor potential vanilloid 1 (TRPV1) is expressed widely in the central nervous system and is activated by various stimuli. Inhibiting TRPV1 has neuroprotective effects in cerebral ischemia. The role of inhibiting TRPV1 to maintain blood-brain barrier (BBB) integrity after traumatic brain injury (TBI) remains unclear, however.
View Article and Find Full Text PDFBackground: Gliomas are usually located in the supratentorial region and are extremely rare at the cerebellopontine angle (CPA). Consequently, gliomas in the CPA are easy to misdiagnose preoperatively.
Case Description: This paper presents a 55-year-old man with an extraaxial CPA glioblastoma arising from the proximal portion of cranial nerve (CN) VIII.
Adjudin, a small molecular compound that is used as a male contraceptive, has been reported to play a neuroprotective role in an ischemic stroke injury model. However, its effect on traumatic brain injury (TBI) has not been assessed. Hence, we investigated the effects of adjudin on cerebral edema using a mouse model of TBI and explored the underlying mechanisms.
View Article and Find Full Text PDFWe directly visualize the topology-mediated interactions between an unwinding site on a supercoiled DNA plasmid and a specific probe molecule designed to bind to this site, as a function of DNA supercoiling and temperature. The visualization relies on containing the DNA molecules within an enclosed array of glass nanopits using the Convex Lens-induced Confinement (CLiC) imaging method. This method traps molecules within the focal plane while excluding signal from out-of-focus probes.
View Article and Find Full Text PDFSesamin, a major lignan of sesame oil, was reported to have neuroprotective effects in several brain injury models. However, its protective action in maintaining blood-brain barrier (BBB) integrity has not been studied. In this study we investigated the effects of sesamin on the BBB in a mouse model of traumatic brain injury (TBI) and explored the underlying mechanisms.
View Article and Find Full Text PDFGlibenclamide is a hypoglycemic drug that is widely used for the treatment of diabetes mellitus type 2 (DM II), but it also plays a protective role following injury to the central nervous system (CNS). However, the precise mechanisms underlying its neuroprotective actions remain to be elucidated. Therefore, the present study evaluated the effects of glibenclamide on the blood-brain barrier (BBB) in a mouse model of traumatic brain injury (TBI).
View Article and Find Full Text PDFSirtuin 2 (SIRT2) is a member of the sirtuin family of NAD(+) -dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI).
View Article and Find Full Text PDFAim: This study aimed to investigate the microsurgical anatomy of perforating arteries in the hypothalamic area, which are associated with diabetes insipidus.
Material And Methods: A total of 20 adult cadaver heads soaked in formalin were infused with red latex through the carotid artery and vertebral artery, and supplementary perfusion was performed after 1 day.
Results: The perforating arteries in the hypothalamic area could be divided into three groups according to their origins, namely, the former, below and outside groups.
Influence maximization in social networks has been widely studied motivated by applications like spread of ideas or innovations in a network and viral marketing of products. Current studies focus almost exclusively on unsigned social networks containing only positive relationships (e.g.
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