Segregation analysis of systolic and diastolic blood pressure in Middle Dalmatia Island population

A complex segregation analysis of systolic and diastolic blood pressure has been performed on pedigree data from rural populations inhabiting Middle Dalmatian islands of Brac, Hvar and Korcula and the Peljesac peninsula. The purpose of the performed analysis was to possibly elucidate a signal of a large-effect gene responsible for high prevalence of hypertension present in this population (the age-adjusted prevalence of developed hypertension being 31.82% in males and 28.23% in females). The analysis was performed on a sample of 389 two- and three-generation families consisting of 2 to 19 observed individuals (1126 examinees in total, 526 males and 600 females, aged 17 to 83). Since the examinees were randomly selected from census data encompassing 22.6% of the total population--the family relations having been established afterwards--the selected sample can be considered representative for the examined populations. By applying the usual transmission probability tests, the major gene model has been accepted for systolic as well as for diastolic blood pressure. The most parsimonious models showed that: (a) inheritance of blood pressure in the Middle Dalmatia population can be attributed to the effect of a major gene responsible for 34% (systolic) and 36% (diastolic) blood pressure variation; (b) alleles of that major gene act in co-dominant fashion; (c) allele frequency for high blood pressure (A2) is 18% (systolic) and 15% (diastolic blood pressure); and (d) the residual (non-major gene) familial correlation is negligible and can be constrained to zero. Since the results are also indicating heterogeneity within the sample in the genetic determination of the systolic blood pressure, the obtained results thus justify further search for the most promising subpopulation for incoming genetic epidemiological investigations of hypertension.     

Epithelial Cadherin Determines Resistance to Infectious Pancreatic Necrosis Virus in Atlantic Salmon

Infectious pancreatic necrosis virus (IPNV) is the cause of one of the most prevalent diseases in farmed Atlantic salmon (Salmo salar). A quantitative trait locus (QTL) has been found to be responsible for most of the genetic variation in resistance to the virus. Here we describe how a linkage disequilibrium-based test for deducing the QTL allele was developed, and how it was used to produce IPN-resistant salmon, leading to a 75% decrease in the number of IPN outbreaks in the salmon farming industry. Furthermore, we describe how whole-genome sequencing of individuals with deduced QTL genotypes was used to map the QTL down to a region containing an epithelial cadherin (cdh1) gene. In a coimmunoprecipitation assay, the Cdh1 protein was found to bind to IPNV virions, strongly indicating that the protein is part of the machinery used by the virus for internalization. Immunofluorescence revealed that the virus colocalizes with IPNV in the endosomes of homozygous susceptible individuals but not in the endosomes of homozygous resistant individuals. A putative causal single nucleotide polymorphism was found within the full-length cdh1 gene, in phase with the QTL in all observed haplotypes except one; the absence of a single, all-explaining DNA polymorphism indicates that an additional causative polymorphism may contribute to the observed QTL genotype patterns. Cdh1 has earlier been shown to be necessary for the internalization of certain bacteria and fungi, but this is the first time the protein is implicated in internalization of a virus.     

Parasite transmission and cannibalism in an amphipod (Crustacea)

In its freshwater amphipod host Gammarus duebeni celticus, the microsporidian parasite Pleistophora mulleri showed 23% transmission efficiency when uninfected individuals were fed infected tissue, but 0% transmission by water-borne and coprophagous routes. Cannibalism between unparasitised and parasitised individuals was significantly in favour of the former (37% compared to 0%). In addition, cannibalism between parasitised individuals was significantly higher than between unparasitised individuals (27% compared to 0%). Thus, parasitised individuals were more likely to be cannibalised by both unparasitised and parasitised individuals. We discuss the conflicting selective forces within this host/parasite relationship, the implications of parasite mediated cannibalism for host population structure and the impacts this may have on the wider aquatic community.     

Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors

Recent studies in Drosophila melanogaster retina indicate that absorption of light causes the translocation of signaling molecules and actin from the photoreceptor's signaling membrane to the cytosol, but the underlying mechanisms are not fully understood. As ezrin-radixin-moesin (ERM) proteins are known to regulate actin-membrane interactions in a signal-dependent manner, we analyzed the role of Dmoesin, the unique D. melanogaster ERM, in response to light. We report that the illumination of dark-raised flies triggers the dissociation of Dmoesin from the light-sensitive transient receptor potential (TRP) and TRP-like channels, followed by the migration of Dmoesin from the membrane to the cytoplasm. Furthermore, we show that light-activated migration of Dmoesin results from the dephosphorylation of a conserved threonine in Dmoesin. The expression of a Dmoesin mutant form that impairs this phosphorylation inhibits Dmoesin movement and leads to light-induced retinal degeneration. Thus, our data strongly suggest that the light- and phosphorylation-dependent dynamic association of Dmoesin to membrane channels is involved in maintenance of the photoreceptor cells.     

Gadd45 beta forms a homodimeric complex that binds tightly to MKK7

Gadd45α, β, and γ proteins, also known as growth arrest and DNA damage-inducible factors, have a number of cellular functions, including cell-cycle regulation and propagation of signals produced by a variety of cellular stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45β has been indicated as a major player in the endogenous NF-κB-mediated resistance to apoptosis in a variety of cell lines. In fibroblasts this mechanism involves the inactivation of MKK7, the upstream activator of JNK, by direct binding within the kinase ATP pocket. On the basis of a number of experimental data, the structures of Gadd45β and the Gadd45β-MKK7 complex have been predicted recently and data show that interactions are mediated by acidic loops 1 and 2, and helices 3 and 4 of Gadd45β. Here, we provide further evidence that Gadd45β is a prevailingly α-helical protein and that in solution it is able to form non covalent dimers but not higher-order oligomers, in contrast to what has been reported for the homologous Gadd45α. We show that the contact region between the two monomers is comprised of the predicted helix 1 (residues Q17-Q33) and helix 5 (residues K131-R146) of the protein, which appear to be antiparallel and to form a large dimerisation surface not involved in MKK7 recognition. The results suggest the occurrence of a large complex containing at least an MKK7-Gadd45β:Gadd45β-MKK7 tetrameric unit whose complexity could be further increased by the dimeric nature of the isolated MKK7.     

Genes involved in the regulation of vascular homeostasis determine renal survival rate in patients with chronic glomerulonephritis

Chronic glomerulonephritis (CGN) is one of the most severe kidney diseases. Genes of vascular reactivity are thought to play an important role in development and progression of CGN. In this study, we analyzed association of genes of vascular homeostasis with hypertension and renal survival of CGN patients. The study sample included 238 patients with CGN and 304 healthy subjects of population control. Ten polymorphisms of ten genes of vascular homeostasis were genotyped through polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis and TaqMan assays. Association of the genotypes with renal survival was analyzed by the Kaplan–Meier estimator. Genotypes 311SC and 311SS of the PON2 gene, (− 1166)AC and (− 1166)CC of the AGTR1 gene, (+ 46)AA of the ADRB2 gene, and 198KK and 198KN of the EDN1 gene were associated with decreased rate of renal survival of the patients. Polymorphisms S311C PON2, (− 1166)A/C AGTR1, (+ 46)G/A ADRB2, and K198N EDN1 were associated with the accelerated decline in kidney function in the CGN patients.     

Exocytosis in Astrocytes: Transmitter Release and Membrane Signal Regulation

Astrocytes, a type of glial cells in the brain, are eukaryotic cells, and a hallmark of these are subcellular organelles, such as secretory vesicles. In neurons vesicles play a key role in signaling. Upon a stimulus—an increase in cytosolic concentration of free Ca²⁺ ([Ca²⁺]_i)—the membrane of vesicle fuses with the presynaptic plasma membrane, allowing the exit of neurotransmitters into the extracellular space and their diffusion to the postsynaptic receptors. For decades it was thought that such vesicle-based mechanisms of gliotransmitter release were not present in astrocytes. However, in the last 30?years experimental evidence showed that astrocytes are endowed with mechanisms for vesicle- and non-vesicle-based gliotransmitter release mechanisms. The aim of this review is to focus on exocytosis, which may play a role in gliotransmission and also in other forms of cell-to-cell communication, such as the delivery of transporters, ion channels and antigen presenting molecules to the cell surface.