Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.
View Article and Find Full Text PDFMicrobiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbial pathways using data generated by shotgun metagenomic sequencing (n = 683).
View Article and Find Full Text PDFPrevious research has demonstrated that hearing impairment is associated with heightened subjective experiences of listening effort, fatigue, and stress, impacting daily functioning. This study aimed to evaluate whether hearing impairment alters physiological stress systems and whether different aspects of hearing impairment could vary in predicting dysregulation in these systems. Hallmark measures of parasympathetic and sympathetic nervous system activity were derived from electrocardiography, impedance cardiography, and electrodermal activity recordings taken from 133 individuals, aged 37 to 73, over two 24-hr periods, including sleep.
View Article and Find Full Text PDFIntroduction: Alzheimer's disease (AD) is a highly heritable disease (60%-80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.
View Article and Find Full Text PDFObjective: Type D (Distressed) personality combines negative affectivity (NA) and social inhibition (SI) and is associated with an increased risk of cardiometabolic diseases. Here, we examined the association of Type D traits with 230 (predominantly) lipid metabolites and metabolite ratios.
Methods: Four Dutch cohorts were included, comprising 10,834 individuals.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by a high metastatic potential with an overall survival rate of ~5%. The transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed by >50% of tumors, including SCLC, but its role in SCLC development and metastasis is unclear. Here, we show that, while STAT3 deletion restricts primary tumor growth, it paradoxically enhances metastatic spread by promoting immune evasion.
View Article and Find Full Text PDFUsing heart rate (HR) measurements to detect mental stress in naturalistic settings is hampered by the physiological impact of hemodynamic and metabolic demands. Correcting HR for these demands can help isolate fluctuations in HR associated with psychosocial stress responses, a concept termed additional heart rate (aHR). This study examined whether adding predictors for posture, activity type, and lagged movement intensity for the prolonged impact of physical activity (PA) improved aHR estimation across various manipulations of mental stress, posture, and PA in a controlled laboratory environment (n = 197).
View Article and Find Full Text PDFBackground: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma.
Methods: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families.
Background: Obesity may affect an individual's immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection.
View Article and Find Full Text PDFBackground: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants.
View Article and Find Full Text PDFInterferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors.
View Article and Find Full Text PDFCigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.
View Article and Find Full Text PDFObjectives: Listening effort involves the mental effort required to perceive an auditory stimulus, for example in noisy environments. Prolonged increased listening effort, for example due to impaired hearing ability, may increase risk of health complications. It is therefore important to identify valid and sensitive measures of listening effort.
View Article and Find Full Text PDFThis Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV.
View Article and Find Full Text PDFDuring infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides.
View Article and Find Full Text PDFIn recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37-72 years, pure-tone average hearing thresholds at the best ear between -5.
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