Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells

An interdisciplinary approach to characterize peanut-allergic patients - first data from the FOOD@ consortium

BACKGROUND: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. METHODS: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. RESULTS: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. CONCLUSION: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies

The Electrochemical Performance and Applications of Several Popular Lithium-ion Batteries for Electric Vehicles - A Review

The Lithium-ion battery is one of the most common batteries used in Electric Vehicles (EVs) due to the specific features of high energy density, power density, long life span and environment friendly. With the development of lithium-ion battery technology, different materials have been adopted in the design of the cathodes and anodes in order to gain a better performance. $LiMn_{2}O_{4}$ , $LiNiMnCoO_{2}$ , $LiNiCoAlO_{2}$ , $LiFePO_{4}$ and $Li_{4}Ti_{5}O_{12}$ are five common lithium-ion batteries adopted in commercial EVs nowadays. The characteristics of these five lithium-ion batteries are reviewed and compared in the aspects of electrochemical performance and their practical applications

Keratan sulphate in the tumour environment

Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes

Взаємозв'язок здоров'я людини і мобільного телефону

Research of scientists and medical observations indicate that The tools of quick communication that are familiar to us are not entirely innocent, especially The newest models offering more and more functions, thus forcing We spend more time with the device turned on. But mobile The phone will not harm if you follow the basic security rules Its use.Исследования ученых и наблюдения медиков свидетельствуют о том, что привычные нам инструменты быстрой связи не совсем невинны, особенно новейшие модели, предлагающие все больше функций, таким образом, заставляя нас проводить больше времени у включенного аппарата. Но мобильный телефон не причинит вреда, если следовать элементарным правилам безопасности его использования.Дослідження вчених і спостереження медиків свідчать про те, що звичні нам інструменти швидкого зв'язку не зовсім невинні, особливо новітні моделі, що пропонують все більше функцій, таким чином, змушуючи нас проводити більше часу у включеного апарату. але мобільний телефон не заподіє шкоди, якщо слідувати елементарним правилам безпеки його використання