Identification of disease-specific extracellular vesicle-associated plasma protein biomarkers for Duchenne Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy.

Objective: Reliable, circulating biomarkers for Duchenne, Becker and facioscapulohumeral muscular dystrophies (DBMD and FSHD) remain unvalidated. Here, we investigated the plasma extracellular vesicle (EV) proteome to identify disease-specific biomarkers that could accelerate therapy approvals.

Methods: We extracted EVs from the plasma of DBMD and FSHD patients and healthy controls using size-exclusion chromatography, conducted mass spectrometry on the extracted EV proteins, and performed comparative analysis to identify disease-specific biomarkers.

tRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.

Aims/hypothesis: tRNAs play a central role in protein synthesis. Besides this canonical function, they were recently found to generate non-coding RNA fragments (tRFs) regulating different cellular activities. The aim of this study was to assess the involvement of tRFs in the crosstalk between immune cells and beta cells and to investigate their contribution to the development of type 1 diabetes.

Small RNAs derived from tRNA fragmentation regulate the functional maturation of neonatal β cells.

tRNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs with distinct cellular functions. Here, we studied the contribution of tRFs to the regulation of postnatal β cell maturation, a critical process that may lead to diabetes susceptibility in adulthood. We identified three tRFs abundant in neonatal rat islets originating from 5' halves (tiRNA-5s) of histidine and glutamate tRNAs.

Emerging Classes of Small Non-Coding RNAs With Potential Implications in Diabetes and Associated Metabolic Disorders.

Most of the sequences in the human genome do not code for proteins but generate thousands of non-coding RNAs (ncRNAs) with regulatory functions. High-throughput sequencing technologies and bioinformatic tools significantly expanded our knowledge about ncRNAs, highlighting their key role in gene regulatory networks, through their capacity to interact with coding and non-coding RNAs, DNAs and proteins. NcRNAs comprise diverse RNA species, including amongst others PIWI-interacting RNAs (piRNAs), involved in transposon silencing, and small nucleolar RNAs (snoRNAs), which participate in the modification of other RNAs such as ribosomal RNAs and transfer RNAs.

A circular RNA generated from an intron of the insulin gene controls insulin secretion.

Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling.

Roles of Noncoding RNAs in Islet Biology.

The discovery that most mammalian genome sequences are transcribed to ribonucleic acids (RNA) has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs), PIWI-associated RNAs, small nucleolar RNAs, tRNA-derived fragments, long non-coding RNAs, and circular RNAs. While the involvement of miRNAs in islet function and in the etiology of diabetes is now well documented, there is emerging evidence indicating that other classes of ncRNAs are also participating in different aspects of islet physiology.

Proteomic Characterization of the Venom of Five Bombus (Thoracobombus) Species.

Venomous animals use venom, a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees ( sp.

Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation.

Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells.

Inhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan.

A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1).