PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis. METHODS: We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31–46 and PKD2 . RESULTS: Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2. CONCLUSION: In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course

Electrochemical evaluation of iron-binding ligands along the Australian GEOTRACES southwestern Pacific section (GP13)

In this work, we performed electrochemical investigations of Fe-binding ligands in water samples collected in autumn 2011 along the Australian GEOTRACES southwestern Pacific section (GP13, between 153 degrees E and 170 degrees W longitude along the 30 degrees S line East of Australia, 0-1000 m depth). We determined the capacity of the bulk organic ligands to complex Fe using competitive ligand exchange-adsorptive cathodic stripping voltammetry (CLEAdCSV) with salicylaldoxime as the competing ligand. Two categories of organic ligands, humic substances (HS-like) and catalytically active polymers (Cat. P) were electrochemically quantified in order to better define the bulk of Fe-binding ligands. Finally, Fe speciation results have been linked to oceanographic data, phytoplankton biomass, and two groups of cyanobacteria (Prochlorococcus and Synechococcus) which are prominent members of the phototrophic community in the study region. Across the section, higher total ligand concentrations over dissolved Fe concentrations were observed, as well as the predominance of "weak" Fe-binding ligands (log K'(Fe'L) < 12). Highest "excess ligands" were mostly concentrated in the upper layer of the water column, suggesting a direct link with biological activity. None of the two groups of organic ligands measured (HS-like and Cat. P) accounted for the bulk of the total Fe-binding ligands concentration, hindering a better characterization of the nature of in-situ Fe-binding ligands. Cat. P concentrations showed statistically significant positive correlations with all biomarker pigments and the abundance of Prochlorococcus, suggesting that this material, resembling polysaccharides, could be a good parameter to probe organic compounds from specific biological origin. Amongst the biological parameters, only Prochlorococcus was related to Fe' concentrations

Abstracts

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Glycogen Synthase Kinase-3 Is Required for Efficient Dictyostelium Chemotaxis

We present a new role for glycogen synthase kinase (GSK) in the regulation of aggregation and chemotaxis in Dictyostelium. GSK regulates two chemotactic pathways, PIP3 and TORC2; hence, a loss of function of GSK leads to poor chemotaxis, an observation not previously seen when only one chemotactic pathway was targeted

Dictyostelium as a model to assess site-specific ADP-ribosylation events

The amoeba Dictyostelium discoideum is a single-cell organism that can undergo a simple developmental program, making it an excellent model to study the molecular mechanisms of cell motility, signal transduction, and cell-type differentiation. A variety of human genes that are absent or show limited conservation in other invertebrate models have been identified in this organism. This includes ADP-ribosyltransferases, also known as poly-ADP-ribose polymerases (PARPs), a family of proteins that catalyze the addition of single or poly-ADP-ribose moieties onto target proteins. The genetic tractability of Dictyostelium and its relatively simple genome structure makes it possible to disrupt PARP gene combinations, in addition to specific ADP-ribosylation sites at endogenous loci. Together, this makes Dictyostelium an attractive model to assess how ADP-ribosylation regulates a variety of cellular processes including DNA repair, transcription, and cell-type specification. Here we describe a range of techniques to study ADP-ribosylation in Dictyostelium, including analysis of ADP-ribosylation events in vitro and in vivo, in addition to approaches to assess the functional roles of this modification in vivo