Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Editorial: Endocrine modulators of neurological processes: potential treatment targets of pediatric neurological diseases.

Editorial on the Research Topic Endocrine Modulators of Neurological Processes: Potential Treatment Targets of Pediatric Neurological Diseases

Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy

Objective: Epileptogenesis after status epilepticus (SE) has a faster onset in rats treated to reduce brain levels of the anticonvulsant neurosteroid allopregnanolone with the 5α-reductase inhibitor finasteride; however, it still has to be evaluated whether treatments aimed at increasing allopregnanolone levels could result in the opposite effect of delaying epileptogenesis. This possibility could be tested using the peripherally active inhibitor of 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase trilostane, which has been shown repeatedly to increase allopregnanolone levels in the brain. Methods: Trilostane (50 mg/kg) was administered subcutaneously once daily for up to six consecutive days, starting 10 min after intraperitoneal administration of kainic acid (15 mg/kg). Seizures were evaluated by video-electrocorticographic recordings for 70 days maximum, and endogenous neurosteroid levels were assessed by liquid chromatography–electrospray tandem mass spectrometry. Immunohistochemical staining was performed to evaluate the presence of brain lesions. Results: Trilostane did not alter the latency of kainic acid-induced SE onset or its overall duration. When compared to the vehicle-treated group, rats receiving six daily trilostane injections presented a remarkable delay of the first spontaneous electrocorticographic seizure and subsequent tonic–clonic spontaneous recurrent seizures (SRSs). Conversely, rats treated with only the first trilostane injection during SE did not differ from vehicle-treated rats in developing the SRSs. Notably, trilostane did not modify neuronal cell densities or the overall damage in the hippocampus. In comparison to the vehicle group, repeated administration of trilostane significantly decreased the activated microglia morphology in the subiculum. As expected, allopregnanolone and other neurosteroid levels were remarkably increased in the hippocampus and neocortex of rats treated for 6 days with trilostane, but pregnanolone was barely detectable. Neurosteroids returned to basal levels after a week of trilostane washout.. Significance: Overall, these results suggest that trilostane led to a remarkable increase in allopregnanolone brain levels, which was associated with protracted effects on epileptogenesis

Organic dye for dye-sensitized solar cells

Organic dye for a dye-sensitized solar cell (DSSC) comprising at least one electron-acceptor unit and at least one π-conjugated unit. Said organic dye is particularly useful in a dye-sensitized photoelectric transformation element which, in its turn, can be used in a dye-sensitized solar cell (DSSC)

Modulation of morphology and glycan composition of mucins in farmed guinea fowl (Numida meleagris) intestine by the multi-strain probiotic slab51®

Probiotics have become highly recognized as supplements for poultry.Since gut health can be considered synonymous withanimal health, the effects of probiotic Slab51® on the morphology and the glycan composition of guineafowlintestine were examined. The probiotics were added in drinking water (2 × 1011 UFC/L) throughout the grow-out cycle.Birds were individually weighed andslaughtered after four months. Samples from the duodenum, ileum and caecum were collected and processed for morphological, morphometric, conventional and lectin glycohisto-chemical studies.The results were analyzed for statistical significance by Student’s t test. Compared with control samples, probiotic group revealed (1) significant increase in villus height (p < 0.001 in duodenum and ileum; p < 0.05 in caecum), crypt depth (p < 0.001 in duodenum and caecum;p < 0.05 in ileum) and goblet cells (GCs) per villus (p < 0.001) in all investigated tracts; (2) increase in galac-toseβl,3N-acetylgalacyosamine(Galβl,3GalNAc)terminating O-glycans and αl,2-fucosylated glycans secretory GCs in the duodenum; (3) increase in α2,6-sialoglycans and high-mannose N-linked glycans secretory GCs but reduction in GCs-secreting sulfoglycans in the ileum; (4) increase in Galβl,3GalNAc and high-mannose N-linked glycans secretory GCs and decrease in GCs-producing sulfomucins in the caecum; (5) increase in the numbers of crypt cells containing sulfate and non-sulfated acidic glycans. Overall, dietary Slab51® induces morphological and region-specific changes in glycoprotein composition of guinea fowl intestine, promoting gut health

Photovoltaic characterization of di-branched organic sensitizers for DSSCs.

In this work, the data on the effect of peripheral functionalization of a series of triphenylamine based di-branched dyes used as sensitizers in dye-sensitized solar cells are presented. The effect of different alkyl functionalities on the donor moiety upon the optical and photovoltaics parameters have been investigated in dye-sensitized solar cells (DSSCs) using a 10-μm TiO2 active layer. The absorption spectra, output efficiency, and incident photon to conversion efficiency of the DSSCs have been collected. The data can be exploited for properly designing efficient, stable, and industrially viable dyes for third generation solar devices

A hydroxypyrone-based inhibitor of metalloproteinase-12 displays neuroprotective properties in both status epilepticus and optic nerve crush animal models

Recently, we showed that matrix metalloproteinase-12 (MMP-12) is highly expressed in microglia and myeloid infiltrates, which are presumably involved in blood\u2013brain barrier (BBB) leakage and subsequent neuronal cell death that follows status epilepticus (SE). Here, we assessed the effects of a hydroxypyrone-based inhibitor selective for MMP-12 in the pilocarpine-induced SE rat model to determine hippocampal cell survival. In the hippocampus of rats treated with pilocarpine, intra-hippocampal injections of the MMP-12 inhibitor protected Cornu Ammonis 3 (CA3) and hilus of dentate gyrus neurons against cell death and limited the development of the ischemic-like lesion that typically develops in the CA3 stratum lacunosum-moleculare of the hippocampus. Furthermore, we showed that MMP-12 inhibition limited immunoglobulin G and albumin extravasation after SE, suggesting a reduction in BBB leakage. Finally, to rule out any possible involvement of seizure modulation in the neuroprotective effects of MMP-12 inhibition, neuroprotection was also observed in the retina of treated animals after optic nerve crush. Overall, these results support the hypothesis that MMP-12 inhibition can directly counteract neuronal cell death and that the specific hydroxypyrone-based inhibitor used in this study could be a potential therapeutic agent against neurological diseases/disorders characterized by an important inflammatory response and/or neuronal cell loss

Vitis vinifera subsp. sylvestris and sativa; so far, so close: a 20 SSR based comparison of the two taxa

In Vitis vinifera L., the hypothesis of secondary domestication center, located along the wild progenitor distribution areas, is suggestive and credible even if up to now close parentage relationships between domestic (Vitis vinifera L. subsp. sativa (DC.) Hegi) and wild (Vitis vinifera L. subsp. sylvestris (Gmel.) Hegi) grapevines have not been detected, possibly due to century long separation of the two subspecies. The aim of this work was to verify the possibility of tracing a flow between the two compartments basing on molecular data and thanks to the availability of a huge dataset comprising 645 wild and more than 1400 cultivated samples. Twenty SSR loci were used to describe and genotype both sylvestris and sativa compartments. The sylvestris samples were all collected in the frame of a three year census in Italy and are representative of the Italian distribution range from north to south. The cultivated sativa accessions mainly (1231 samples) belong to the Vassal (INRA-Montpellier) collection, while the remaining (200) were selected in the frame of the Italian grapevine germplasm. Results highlighted a high level of genetic diversity for both wild and cultivated groups. STRUCTURE analysis clearly evidenced the separation of the two compartments and no first or second degree relationships were evidenced between the two subspecies