Project description:In this study, we recruited a patient with Hereditary spherocytosis (HS) detected to have a novel heterozygous variant in the SPTB in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism.
Project description:Many risk-eligible women refuse tamoxifen for primary prevention of breast cancer due to concerns about common side effects such as vasomotor symptoms. Tamoxifen may also induce or worsen insulin resistance and hypertriglyceridemia, especially in women with obesity. Bazedoxifene/conjugated estrogens (BZA/CE) reduces vasomotor symptoms and is currently undergoing evaluation for breast cancer risk reduction. However, the impact of BZA/CE on insulin resistance and metabolic health, particularly in those with excess adiposity, is understudied. Here, we examined the effects of obesity on response to BZA/CE in a rat model of breast cancer risk using older ovary-intact rats. Female Wistar rats received carcinogen to increase mammary cancer risk and were fed a high-fat diet to promote obesity. Lean and obese rats were selected based on adiposity, then randomized to BZA/CE or vehicle for 8 weeks. BZA/CE reduced adiposity, enriched small (insulin-sensitive) mammary adipocytes, increased the abundance of beneficial metabolic gut microbes (Faecalbaculum rodentium and Odoribacter laneus), and reversed obesity-associated changes in lipids and adipokines. BZA/CE also reversed obesity-induced mammary enrichment of cell proliferation pathways, consistent with risk-reducing effects. Together, these data support the use of BZA/CE to improve metabolic health and reduce breast cancer risk in individuals with obesity. RNA from mammary glands was analyzed by gene expression microarray.
Project description:In Sciara coprophila, paternally inherited X chromosomes are imprinted and selectively eliminated during early embryonic development. A controlling element (CE) located on the X chromosome is known to play a decisive role in this process, although the exact mechanism remains unknown. In this study, we test a proposed model in which the maternal cytoplasm regulates CE activity and thereby controls Xp elimination during embryogenesis. Using our de novo Sciara genome assembly, along with ChIP-Seq and MeDIP analyses, we identified a 1.2 Mb region within the CE locus that exhibits a repressive epigenetic signature on X chromosomes that are retained. These findings provide molecular support for the model. Remarkably, this signature also includes a unique enrichment of CpG methylation, suggesting a strong evolutionary conservation of imprinting mechanisms and identifying a promising candidate for the long-sought CE locus responsible for somatic Xp-chromosome elimination.
Project description:In this research, capillary electrophoresis was combined with liquid chromatography to sequence novel monoclonal antibodies. It was demonstrated CE can provide highly complemetary information to LC in the process of novel mAbs sequencing.
