NESTOR: A neutrino particle astrophysics underwater laboratory for the Mediterranean

Abstract An underwater neutrino astrophysics laboratory, to be located in the international waters off the Southwest of Greece, near the town of Pylos is now under construction. In the last two years a group of physicists from Greece and Russia have carried out two demonstration experiments in 4km deep water, counting muons and verifying the adequacy of the deep sea site. Plans are presented for a 100, 000 m 2 high energy neutrino detector composed of a hexagon of hexagonal towers, with 1176 optical detector units. A progress report is given and the physics potential of a siggle tower with 168 phototubes (currently under construction) is described

Drosophila muscleblind Codes for Proteins with One and Two Tandem Zinc Finger Motifs

Muscleblind-like proteins, Muscleblind (Mbl) in Drosophila and MBNL1-3 in vertebrates, are regulators of alternative splicing. Human MBNL1 is a key factor in the etiology of myotonic dystrophy (DM), a muscle wasting disease caused by the occurrence of toxic RNA molecules containing CUG/CCUG repeats. MBNL1 binds to these RNAs and is sequestered in nuclear foci preventing it from exerting its normal function, which ultimately leads to mis-spliced mRNAs, a major cause of the disease. Muscleblind-proteins bind to RNAs via N-terminal zinc fingers of the Cys3-His type. These zinc fingers are arranged in one (invertebrates) or two (vertebrates) tandem zinc finger (TZF) motifs with both fingers targeting GC steps in the RNA molecule. Here I show that mbl genes in Drosophila and in other insects also encode proteins with two TZF motifs, highly similar to vertebrate MBNL proteins. In Drosophila the different protein isoforms have overlapping but possibly divergent functions in vivo, evident by their unequal capacities to rescue the splicing defects observed in mbl mutant embryos. In addition, using whole transcriptome analysis, I identified several new splicing targets for Mbl in Drosophila embryos. Two of these novel targets, kkv (krotzkopf-verkehrt, coding for Chitin Synthase 1) and cora (coracle, coding for the Drosophila homolog of Protein 4.1), are not muscle-specific but expressed mainly in epidermal cells, indicating a function for mbl not only in muscles and the nervous system

Water transparency measurements in the deep Ionian Sea

A long optical base line spectrophotometer designed to measure light transmission in deep sea waters is described. The variable optical path length allows measurements without the need for absolute or external calibration. The spectrophotometer uses eight groups of uncollimated light sources emitting in the range 370–530 nm and was deployed at various depths at two locations in the Ionian Sea that are candidate sites for a future underwater neutrino telescope. Light transmission spectra at the two locations are presented and compared

Hyaluronan Binding Motifs of USP17 and SDS3 Exhibit Anti-Tumor Activity

BACKGROUND: We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells. Furthermore, USP17 and SDS3 mutually interact with each other to block cell proliferation in HeLa cells but the mechanism for this inhibition in cell proliferation is not known. We wished to investigate whether the HABMs of USP17 were responsible for tumor suppression activity. METHODOLOGY/PRINCIPAL FINDINGS: Similarly to USP17, we have identified that SDS3 also has three consecutive HABMs and shows direct binding with hyaluronan (HA) using cetylpyridinium chloride (CPC) assay. Additionally, HA oligosaccharides (6-18 sugar units) competitively block binding of endogenous HA polymer to HA binding proteins. Thus, administration of HA oligosaccharides antagonizes the interaction between HA and USP17 or SDS3. Interestingly, HABMs deleted USP17 showed lesser interaction with SDS3 but retain its deubiquitinating activity towards SDS3. The deletion of HABMs of USP17 could not alter its functional regulation on SDS3-associated HDAC activity. Furthermore, to explore whether HABMs in USP17 and SDS3 are responsible for the inhibition of cell proliferation, we investigated the effect of USP17 and SDS3-lacking HABMs on cell proliferation by soft agar, apoptosis, cell migration and cell proliferation assays. CONCLUSIONS: Our results have demonstrated that these HABMs in USP17 and its substrate SDS3 are mainly involved in the inhibition of anchorage-independent tumor growth

The role of epigenetics in renal ageing

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

An update to 21-hydroxylase deficient congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH) is distinguished in classical (C-CAH) and non-classical form (NC-CAH), and it is also one of the most common autosomal recessive inherited disorders in humans. The prevalence of C-CAH is between 1:10,000 and 1:15,000 among the live neonates of North America and Europe while the NC-CAH occurs in approximately 0.2 of the general white population. The highest incidence of CAH (1:282 and 1:2141, respectively) has been evaluated in Yupik Eskimos in Alaska and in the populations of the island La Reunion (France), while the lower was detected in New Zealand newborns (0.3). Nowadays, it has been established that except for the adrenal cortex in CAH cases, the adrenal medulla was also affected. In human 21-OH deficient adrenal gland it has been discovered that not only the chromaffin cells formed extensive neurites, expanding between adrenocortical cells, but also that the adrenal androgens promote outgrowth, whereas glucocorticoids preserve neuroendocrine cells. It seems that normal cortisol secretion by the adrenal cortex is necessary for adrenomedullary organogenesis. The synthesis of 21-OH is controlled by the active CYP21A2 gene located at a distance of 30kb from a highly homologous pseudogene designated CYP21A1P. © 2010 Informa UK Ltd