👤 Chase J Boyer

To identify distinct profiles based on socioeconomic status (SES), marital status, home and neighborhood environments, and psychological symptoms, in a sample of primarily Mexican-origin mothers, and to examine how these profiles relate to maternal diurnal cortisol. Mexican-origin mothers (N = 143) were assessed for their objective (education, income-to-needs ratio) and subjective SES (perceived financial concern), marital status, home chaos, neighborhood environments (cohesion and quality), and maternal depressive symptoms when their child was approximately 6-months old. Maternal salivary cortisol levels were collected around the time of their wake-up and at their child's bedtime. Latent profile analysis (LPA) was used to identify distinct profiles of maternal risk and resilience. LPA revealed three distinct profiles with unique patterns of risk and resilience. The Higher-Risk profile (36%) was characterized by low SES, poor home and neighborhood environments, and heightened depressive symptoms. The Resilient profile (46%) displayed low objective SES but low financial concern, positive home and neighborhood environments, and fewer depressive symptoms. Lastly, the Lower-Risk profile (18%) showed relatively high SES, positive home and neighborhood environments, and fewer depressive symptoms. Mothers in the Higher-Risk profile exhibited less pronounced declines in cortisol from wake-up to bedtime compared to those in the Resilient and Lower-Risk profiles. The Resilient group showed a diurnal pattern similar to the Lower-Risk group. This study highlights that even in the context of objectively low SES, positively perceived SES, supportive home and neighborhood environments, and low depressive symptoms may serve as resilience factors, promoting healthier cortisol patterns among low-income Mexican-origin mothers. Show less

Transcription factor EB (TFEB) is a key transcription factor that orchestrates the cellular response to stress. Dysregulation of TFEB is associated with a range of human diseases, and understanding the regulatory mechanisms of TFEB is crucial for identifying potential drug targets. In this study, we used Show less

Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (H3/IDH-wt-pHGG) is a newly defined entity amongst brain tumours, primarily reported in children. It is a rare, ill-defined type of tumour and the only method to diagnose it is DNA methylation profiling. The case we report here carries new knowledge about this tumour which may, in fact, occur in elderly patients, be devoid of evocative genomic abnormalities reported in children and harbour a misleading mutation. Show less

RBPs (RNA-binding proteins) perform indispensable functions in the post-transcriptional regulation of gene expression. Numerous RBPs have been implicated in cardiac development or physiology based on gene knockout studies and the identification of pathogenic RBP gene mutations in monogenic heart disorders. The discovery and characterization of additional RBPs performing indispensable functions in the heart will advance basic and translational cardiovascular research. We performed a differential expression screen in zebrafish embryos to identify genes enriched in We identified 1848 genes enriched in the Our study identifies Show less

GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. Show less

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up. Show less

Striated muscle cells contain numerous architectural proteins that contribute to the function of muscle as generators of mechanical force. Among these proteins are crosslinkers belonging to the plakin family, namely plectin, microtubule-actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1 (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular plectin and Bpag1/dystonin, exist as several isoforms. The domain organization of these plakin variants dictates their subcellular location and the proteins with which they interact. Several studies suggest that plakins exert unique functions within various compartments of the muscle cell including the sarcolemma, the sarcomere, both neuromuscular and myotendinous junctions in skeletal muscle, and the intercalated discs in cardiac muscle. Plakins may also regulate the cellular placement and function of specific organelles, notably the nucleus, mitochondria, Golgi apparatus, and sarcoplasmic reticulum. Here we review and summarize our current knowledge of the function of plakins in striated muscle cells. Show less