The role of SLC19A2 variants in the wide spectrum of non-autoimmune abnormalities of glucose homeostasis.

Aims/hypothesis: Biallelic pathogenic variants in SLC19A2 (the solute carrier family 19 member 2, which encodes thiamine transporter 1, responsible for thiamine intake) cause a recessive syndromic diabetes of infancy or early childhood in the context of thiamine-responsive megaloblastic anaemia, characterised by sensorineural deafness. Indeed, it has been reported, although only once, that even a heterozygous missense loss-of-function variant of SLC19A2 causes dominantly inherited non-syndromic diabetes. Finally, it is unknown whether rare SLC19A2 pathogenic variants modulate the risk of type 2 diabetes at the population level.

Autoimmune hyperglycemia: beyond type 1 diabetes.

Background: Autoimmune polyglandular syndrome type 1 (APS1) is characterized by chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal insufficiency and sporadically by other autoimmune conditions including thyroiditis and diabetes mellitus. APS1 is usually caused by recessive mutations in the AIRE gene, though rare dominant mutations can result in mild, late-onset clinical manifestations. Whether and to what extent autoimmune diabetes is present in these latter forms has been poorly addressed.

Transcriptomic effects of alginate hydrogel applied to the production of bovine embryos.

-produced blastocysts are exposed to different stimuli when compared with ones. This includes the culture of embryos in a sturdy petri-dish, while embryos develop in a soft and dynamic structure. Here we hypothesized that a softer environment could differently modulate the produced embryos To that aim, presumptive zygotes were produced by fertilization and divided into three groups: 1) Cultured in a regular Petri dish - Control (CON); 2) Cultured on top of an alginate hydrogel surface (TOP); 3) Encapsulated inside an alginate hydrogel sphere (ENC) and cultured.

Small extracellular vesicles derived from the crosstalk between early embryos and the endometrium potentially mediate corpus luteum function†.

The first interactions among the embryo, endometrium, and corpus luteum are essential for pregnancy success. Small extracellular vesicles (sEVs) are part of these interactions. We previously demonstrated that small extracellular vesicles from in vivo- or in vitro-produced bovine embryos contain different miRNA cargos.

Labeled extracellular vesicles can be found in the blood plasma shortly after intrauterine infusion in bovine.

This study explored the migration of follicular fluid (FF)-derived extracellular vesicles (EVs) of the uterine environment to the bloodstream and their interaction with neutrophils and . For the experiment, six Nellore heifers () received an intrauterine infusion seven days after ovulation with 1X PBS only (sham group; n=1), 1X PBS stained with lipophilic dye PKH26 (control group; n=2), or FF-derived EVs stained with PKH26 (treated group; n=3). Plasma was collected at 0, 10, 30, 60-, 180-, 360-, 720-, and 1440-min post-infusion to obtained EVs for analysis by nano flow cytometry.

Rare forms of monogenic diabetes in non-European individuals. First reports of CEL and RFX6 mutations from the Indian subcontinent.

Aims: Monogenic diabetes is one of the few examples in metabolic diseases in which a real precision medicine approach can be implemented in daily clinical work. Unfortunately, most of what is known today comes from studies in Whites, thus leaving much uncertainty about the genetics and the clinical presentation of monogenic diabetes in non-Europeans. To fill this gap, we report here two pedigrees from Bangladesh with CEL- and RFX6- diabetes, two rare types of monogenic diabetes which have never been described so far in individuals of the Indian subcontinent.

Extracellular vesicles derived from bovine adipose-derived mesenchymal stromal cells enhance in vitro embryo production from lesioned ovaries.

Background And Aims: Ovum pick-up (OPU) is an intrinsic step of in vitro fertilization procedures. Nevertheless, it can cause ovarian lesions and compromise female fertility in bovines. Recently, we have shown that intraovarian injection of adipose-derived mesenchymal stromal cells (AD-MSCs) effectively preserves ovarian function in bovines.

A longer period of epididymal sperm interaction with extender components during cryopreservation improves sperm quality, decreases the size of sperm distal cytoplasmic droplets, and changes the number of nanoparticles in the extender.

While cryopreservation of cauda epididymal sperm (SpCau) allows the preservation of post-mortem bulls' gametes, the process triggers sperm damage. Although improving post-thaw sperm quality, using egg yolk extenders (EY) raises biosafety concerns which forces the use of EY-free extenders (EYFE). Since EYFE are less efficient in preserving post-thaw sperm quality, a strategy for ejaculated sperm (SpEj) frozen with EYFE is to add an Equilibrium Time (ET) step period to the cryopreservation process.

GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes.

Aims: Aim of this study was to investigate in type 2 diabetes whether expression level of GALNT2, a positive modulator of insulin sensitivity, is associated with a metabolic signature.

Methods: Five different metabolite families, including acylcarnitines, aminoacids, biogenic amines, phospholipids and sphingolipids were investigated in fasting serum of 70 patients with type 2 diabetes, by targeted metabolomics. GALNT2 expression levels were measured in peripheral white blood cells by RT-PCR.

Infection with different Neospora caninum strains causes differences in the glycosylation pattern in the uteri and placentae of Neospora caninum-infected heifers.

Neospora caninum is an obligate intracellular parasite that causes abortion in ruminants. Different strains produce differences in the severity of disease outcomes. These differences may cause physiological or pathological changes in cells, modifying the intercellular interactions and intracellular transport pathways that could be evidenced by identifying the terminal sugars.

Cytoplasmic granules in bovine oocytes do not affect embryonic or fetal development.

Oocyte cytoplasmic evaluation is based on homogeneity and granular appearance. Our study investigated if a granular cytoplasm, highly heterogeneous, would affect oocyte competence in bovine. In two experiments, bovine cumulus-oocyte complexes (COCs) with homogeneous cytoplasm (control, CC) and granulated cytoplasm (granular, GC) were selected from a regular pool of COCs.

Enhanced fluorescence detection of miRNA by means of Bloch surface wave-based biochips.

We report on the use of biochips based on one-dimensional photonic crystals sustaining Bloch surface waves to specifically detect target miRNA that is characteristic of hemorrhagic stroke (miR-16-5p) at low concentration in a buffer solution. The biochips were functionalized with streptavidin and ssDNA oligonucleotides to enable miRNA detection. To discriminate the target miRNA from a non-specific control (miR-101a-3p), we made use of an optical platform developed to work both in label-free and fluorescence detection modes.

Outstanding Gir oocyte donors: How does individual factor affect in vitro embryo production efficiency?

The oocyte donor plays a pivotal role in bovine in vitro embryo production (IVP) success. The individual factor affects blastocyst/oocyte ratio and determine the existence of outstanding performing animals. The aim of this study was to assess the extent of individual factor effect to IVP efficiency, in a population of Gir oocyte donors.

Luteinizing hormone secretion, ovulatory capacity, and oocyte quality in peripubertal Gir heifers.

Induction of puberty in cattle breeds that attain puberty in later stages, such as Gir, allows the earlier beginning of reproductive life and it might increase oocyte quality. Here, the ovulatory capacity of prepuberal Gir heifers was studied and its relationship to follicular growth, luteinizing hormone (LH) secretion and oocyte quality was evaluated. Peripubertal Gir heifers were treated with a progesterone-based protocol and according to ovulatory response were separated into groups: not-ovulated (N-OV) and ovulated (OV).

Bovine in vitro oocyte maturation and embryo culture in liquid marbles 3D culture system.

Despite the advances in in vitro embryo production (IVP) over the years, the technique still has limitations that need to be overcome. In cell cultures, it is already well established that three-dimensional culture techniques are more physiological and similar to the in vivo development. Liquid marble (LM) is a three-dimensional system based on the use of a hydrophobic substance to create in vitro microbioreactors.

Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia.

Several studies have shown that downregulation of GALNT2 (Polypeptide N-Acetylgalactosaminyltransferase 2), encoding polypeptide N-acetylgalactosaminyltransferase 2, decreases high-density lipoprotein cholesterol (HDL-C) and increases triglycerides levels by glycosylating key enzymes of lipid metabolism, such as angiopoietin like 3, apolipoprotein C-III, and phospholipid transfer protein. GALNT2 is also a positive modulator of insulin signaling and action, associated with in vivo insulin sensitivity and during adipogenesis strongly upregulates adiponectin. Thus, the hypothesis that GALNT2 affects HDL-C and triglycerides levels also through insulin sensitivity and/or circulating adiponectin, is tested.

MicroRNA Profiling Using a PCR-Based Method.

MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional regulation of specific mRNA targets, thus possibly controlling many biological processes. The miRNA profiling analysis can contribute to understanding several signaling pathways, as biomarkers for molecular diagnostic, as well as potential to be used as therapeutic targets. The miRNAs expression can be analyzed by quantitative reverse transcription PCR (RT-qPCR), microarrays, and RNA sequencing.

Early-Onset Diabetes in an Infant with a Novel Frameshift Mutation in LRBA.

We describe early-onset diabetes in a 6-month-old patient carrying an LRBA gene mutation. Mutations in this gene cause primary immunodeficiency with autoimmune disorders in infancy. At admission, he was in diabetic ketoacidosis, and treatment with fluid infusion rehydration and then i.

Cognitive, neuropsychological and emotional-behavioural functioning in a sample of children with myotonic dystrophy type 1.

Aim: An observational longitudinal study to evaluate the feasibility of assessing cognitive, neuropsychological and emotional-behavioural functioning in children with myotonic dystrophy type 1 (DM1), and to estimate prospectively changes in functioning over time.

Method: Ten DM1 patients, aged 1.5-16 years (mean 9.