No abstract

HBV may have another virion form in which the nucleic acid is composed of RNA, not DNA. The level of HBV RNA virion in serum may be associated with risk of HBV viral rebound after withdrawal of treatment, and therefore, a potential predictive biomarker to monitor the safe discontinuation of nucleot(s)ide analogues-therapy.

Alzheimer's disease-associated ␤-amyloid peptides (A␤) are generated by the sequential proteolytic processing of amyloid precursor protein (APP) by ␤-and ␥-secretases. There is growing evidence that cholesterol-and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP. BACE1, the major ␤-secretase in neurons is a palmitoylated transmembrane protein that resides in lipid rafts. A subset of APP is subject to amyloidogenic processing by BACE1 in lipid rafts, and this process depends on the integrity of lipid rafts. Here we describe the association of all four components of the ␥-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. In PS1 ؊/؊ /PS2 ؊/؊ and NCT ؊/؊ fibroblasts, ␥-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires ␥-secretase complex assembly. Biochemical evidence shows that subunits of the ␥-secretase complex and three TGN/endosomeresident SNAREs cofractionate in sucrose density gradients, and show similar solubility or insolubility characteristics in distinct non-ionic and zwitterionic detergents, indicative of their co-residence in membrane microdomains with similar protein-lipid composition. This notion is confirmed using magnetic immunoisolation of PS1-or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation. These findings are consistent with the localization of ␥-secretase in lipid raft microdomains of postGolgi and endosomes, organelles previously implicated in amyloidogenic processing of APP.Alzheimer's disease, a neurodegenerative dementing disorder, is pathologically characterized by the cerebral deposition of 39 -42 amino acid peptides termed ␤-amyloid (A␤) 1 peptides.

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.