Isidella elongata (Cnidaria: Alcyonacea) facies in the western Mediterranean Sea: Visual surveys and descriptions of its ecological role

Isidella elongata is a candelabrum-shaped alcyonacean forming important facies on the bathyal muddy bottoms of the Mediterranean Sea, currently considered a sensitive habitat and heavily impacted by deep-sea fisheries. Until a few decades ago, this facies was a widespread habitat of the deep Mediterranean seabed and I. elongata was a common species in the trawling fishery's bycatch. Despite its current persistence in dense aggregations being very scarce, a dense facies of I. elongata was revealed during several ROV (Remotely Operated Vehicle) surveys carried out from 2010 to 2014 on the muddy bottoms between two seamounts east of Ibiza (Balearic Sea). The facies developed in an area between 480 and 615 m in depth where trawling is forbidden, with an extraordinary density of about 2300–2683 colonies/ha, representing one of the biggest facies of I. elongata currently known for the Mediterranean Sea considering the surface covered and the colonies' density. The associated community was surveyed, with 50 taxa identified. Moreover, a canyon southwest of Formentera characterised by the presence of I. elongata together with a high trawling impact was investigated. The density of the colonies was 53–62 colonies/ha and only 19 taxa of associated fauna were observed. The results of the two areas are compared and discussed in the framework of the protection of such an important habitat

Rhodolith beds heterogeneity along the apulian continental shelf (Mediterranean sea)

Rhodolith beds represent a key habitat worldwide, from tropical to polar ecosystems. Despite this habitat is considered a hotspot of biodiversity, providing a suite of ecosystem goods and services, still scarce quantitative information is available thus far about rhodolith beds occurrence and ecological role, especially in the Mediterranean Sea. This study reports the composition and patterns of distribution of rhodolith assemblages found in four study areas along ca. 860 km of coast in the Central Mediterranean Sea. These rhodolith beds were studied for the first time and significant differences at all spatial scales have been highlighted, documenting the high variability of this habitat. Rhodolith species composition, morphology and distribution have been discussed considering the potential role of environmental factors in driving these patterns. The need for improving their protection is discussed to complement present conservation and management initiatives, particularly in the frame of the EU Marine Strategy Framework Directive

New deep-water cnidarian sites in the southern Adriatic Sea

Recent ROV (Remotely Operated Vehicle) exploration and bottom sampling in the southern Adriatic Sea (Apulian and Montenegrin margins) resulted in the discovery of cnidarian-rich deep-sea habitats in the depth range of ca. 400-700 m. In particular, ROV inspection of Montenegrin canyons reveals the existence of megabenthic communities dominated by a variety of cnidarians, including scleractinians (Madrepora oculata, Lophelia pertusa, Dendrophyllia cornigera),antipatharians (Leiopathes glaberrima) and gorgonians (Callogorgia verticillata) as major habitat forming taxa, often in association with sponges and, subordinately, serpulids. All such cnidarians are new records for the south-eastern side of the Adriatic Sea. Our investigation indicates that an almost continuous belt of patchy cold water coral sites occurs along the entire south-western margin (Apulian),basically connecting the Adriatic populations with those inhabiting the Ionian margin (Santa Maria di Leuca coral province)

SLC30A3 Responds to Glucose- and Zinc Variations in ß-Cells and Is Critical for Insulin Production and In Vivo Glucose-Metabolism During ß-Cell Stress

BACKGROUND:Ion transporters of the Slc30A- (ZnT-) family regulate zinc fluxes into sub-cellular compartments. beta-cells depend on zinc for both insulin crystallization and regulation of cell mass. METHODOLOGY/PRINCIPAL FINDINGS:This study examined: the effect of glucose and zinc chelation on ZnT gene and protein levels and apoptosis in beta-cells and pancreatic islets, the effects of ZnT-3 knock-down on insulin secretion in a beta-cell line and ZnT-3 knock-out on glucose metabolism in mice during streptozotocin-induced beta-cell stress. In INS-1E cells 2 mM glucose down-regulated ZnT-3 and up-regulated ZnT-5 expression relative to 5 mM. 16 mM glucose increased ZnT-3 and decreased ZnT-8 expression. Zinc chelation by DEDTC lowered INS-1E insulin content and insulin expression. Furthermore, zinc depletion increased ZnT-3- and decreased ZnT-8 gene expression whereas the amount of ZnT-3 protein in the cells was decreased. Zinc depletion and high glucose induced apoptosis and necrosis in INS-1E cells. The most responsive zinc transporter, ZnT-3, was investigated further; by immunohistochemistry and western blotting ZnT-3 was demonstrated in INS-1E cells. 44% knock-down of ZnT-3 by siRNA transfection in INS-1E cells decreased insulin expression and secretion. Streptozotocin-treated mice had higher glucose levels after ZnT-3 knock-out, particularly in overt diabetic animals. CONCLUSION/SIGNIFICANCE:Zinc transporting proteins in beta-cells respond to variations in glucose and zinc levels. ZnT-3, which is pivotal in the development of cellular changes as also seen in type 2 diabetes (e.g. amyloidosis in Alzheimer's disease) but not previously described in beta-cells, is present in this cell type, up-regulated by glucose in a concentration dependent manner and up-regulated by zinc depletion which by contrast decreased ZnT-3 protein levels. Knock-down of the ZnT-3 gene lowers insulin secretion in vitro and affects in vivo glucose metabolism after streptozotocin treatment

Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value

Recently, several Genome Wide Association (GWA) studies in populations of European descent have identified and validated novel single nucleotide polymorphisms (SNPs), highly associated with type 2 diabetes (T2D). Our aims were to validate these markers in other European and non-European populations, then to assess their combined effect in a large French study comparing T2D and normal glucose tolerant (NGT) individuals. rs7903146 SNP, were combined (8.68-fold for the 14% of French individuals carrying 18 to 30 risk alleles with an allelic OR of 1.24). With an area under the ROC curve of 0.86, only 15 novel loci were necessary to discriminate French individuals susceptible to develop T2D. strongly associate with T2D in French individuals, and mostly in populations of Central European descent but not in Moroccan subjects. Genes expressed in the pancreas interact together and their combined effect dramatically increases the risk for T2D, opening avenues for the development of genetic prediction tests

Down-Regulation of ZnT8 Expression in INS-1 Rat Pancreatic Beta Cells Reduces Insulin Content and Glucose-Inducible Insulin Secretion

The SLC30A8 gene codes for a pancreatic beta-cell-expressed zinc transporter, ZnT8. A polymorphism in the SLC30A8 gene is associated with susceptibility to type 2 diabetes, although the molecular mechanism through which this phenotype is manifest is incompletely understood. Such polymorphisms may exert their effect via impacting expression level of the gene product. We used an shRNA-mediated approach to reproducibly downregulate ZnT8 mRNA expression by >90% in the INS-1 pancreatic beta cell line. The ZnT8-downregulated cells exhibited diminished uptake of exogenous zinc, as determined using the zinc-sensitive reporter dye, zinquin. ZnT8-downregulated cells showed reduced insulin content and decreased insulin secretion (expressed as percent of total insulin content) in response to hyperglycemic stimulus, as determined by insulin immunoassay. ZnT8-depleted cells also showed fewer dense-core vesicles via electron microscopy. These data indicate that reduced ZnT8 expression in cultured pancreatic beta cells gives rise to a reduced insulin response to hyperglycemia. In addition, although we provide no direct evidence, these data suggest that an SLC30A8 expression-level polymorphism could affect insulin secretion and the glycemic response in vivo

Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants

International audienceObjective. Zinc ions are essential for the formation of hexameric insulin and hormone crystallisation. Correspondingly, a non-synonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. Here, we describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. Research Design and Methods. Slc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection, or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles, were undertaken using standard protocols. Results. ZnT8(-/-) mice displayed age, sex and diet-dependent abnormalities in glucose tolerance, insulin secretion and body weight. Islets isolated from null mice had reduced granule zinc content, and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion and insulin crystal dissolution, as assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8(-/-) islets. Insulin processing was normal. Molecular modelling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn(2+) transport activity than W325 ZnT8 by fluorescence-based assay. Discussion and conclusions. ZnT8 is required for normal insulin crystallisation and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risk

THE ELDERLY PROGNOSTIC INDEX (EPI) PREDICTS EARLY MORTALITY IN OLDER PATIENTS WITH DLBCL. A SUBSTUDY OF THE ELDERLY PROJECT BY THE FONDAZIONE ITALIANA LINFOMI (FIL)

n/