Epigenetic Regulation of Associates With Myocardial Infarction and Platelet Function.

Background: DNA hypomethylation at the (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease.

Variation in the timing of enamel formation in modern human deciduous canines.

Objectives: Deciduous canines are now used increasingly in archaeological and forensic studies to establish the time of birth and as a retrospective source of trace elements incorporated into enamel before and after birth. However, data on the variability of deciduous enamel formation times are scarce. Our objectives were to use daily incremental markings to estimate daily secretion rates, the timing of prenatal, postnatal and total enamel formation and any changes in enamel coverage or prism and stria orientation that occur during enamel formation.

Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.

In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.

The Avon Longitudinal Study of Parents and Children (ALSPAC): an update on the enrolled sample of index children in 2019.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based study. Initial recruitment of pregnant women took place in 1990-1992 and the health and development of the index children from these pregnancies and their family members have been followed ever since. The eligible sampling frame was constructed retrospectively using linked recruitment and health service records.

The Effect of Pre-Analytical Conditions on Blood Metabolomics in Epidemiological Studies.

Serum and plasma are commonly used in metabolomic-epidemiology studies. Their metabolome is susceptible to differences in pre-analytical conditions and the impact of this is unclear. Participant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform ( = 151 traits).

Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort.

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years.

Maturation in Serum Thyroid Function Parameters Over Childhood and Puberty: Results of a Longitudinal Study.

Context: Serum thyroid hormone levels differ between children and adults, but have not been studied longitudinally through childhood.

Objective: To assess changes in thyroid-stimulating hormone (TSH) and thyroid hormone levels over childhood and their interrelationships.

Design: Cohort study.

Paradoxical Relationship Between Body Mass Index and Thyroid Hormone Levels: A Study Using Mendelian Randomization.

Context: Free T3 (FT3) has been positively associated with body mass index (BMI) in cross-sectional studies in healthy individuals. This is difficult to reconcile with clinical findings in pathological thyroid dysfunction.

Objective: We aimed to investigate whether childhood adiposity influences FT3 levels.

Migration and DNA methylation: a comparison of methylation patterns in type 2 diabetes susceptibility genes between indians and europeans.

Background: Type 2 diabetes is a global problem that is increasingly prevalent in low and middle income countries including India, and is partly attributed to increased urbanisation. Genotype clearly plays a role in type 2 diabetes susceptibility. However, the role of DNA methylation and its interaction with genotype and metabolic measures is poorly understood.

Birth weight and early socio-economic disadvantage as predictors of sex hormones and sex hormone binding globulin in men at age 49-51 years.

Objectives: A number of associations have been shown between early growth and later sex hormone levels in women, but less is known about this relationship in men. This study investigated life-course predictors of sex hormones in men in the Newcastle Thousand Families birth cohort.

Methods: The Newcastle Thousand Families Study is a prospective study initiated in 1947.

Modeling ATM mutant proteins from missense changes confirms retained kinase activity.

Ataxia-telangiectasia mutated (ATM) is the gene mutated in the cancer-predisposing disorder ataxia-telangiectasia (A-T). We modeled ATM sequence variants identified in UK A-T patients to determine the stability and kinase activity of the resulting proteins as well as the distribution of these mutations across the coding region. Of 20 missense changes modeled, 10 proteins showed ATM kinase activity and 10 showed none.

Variations in ATM protein expression during normal lymphoid differentiation and among B-cell-derived neoplasias.

The ataxia telangiectasia mutated (ATM) protein plays a central role in the cellular response to DNA double-strand breaks (DSBs). Developmentally programmed DSBs are restricted to cellular subsets within lymphoid tissues and we asked whether ATM expression is differentially regulated during lymphoid differentiation. We showed that immature B cells in bone marrow and immature T cells of the thymic cortex were negative or weakly ATM-positive.