VDR TaqI is associated with obesity in the Greek population

The prevalence of obesity has increased dramatically during the last thirty years in western countries with severe complications for health and economy. Obesity is the outcome of the strong interplay between genetic and environmental factors and is therefore widely expected that the discovery of the many genetic factors underlying the heritable risk of obesity will contribute critically to our basic knowledge of the disease etiopathogenesis and the identification of new targets for therapeutic intervention. The aim of the present study was to assess the genetic contribution of known polymorphisms in two genes that are linked to the pathogenetic mechanism of obesity. Analysis of vitamin D receptor (VDR) TaqI (rs731236; T/C) and fat mass and obesity-associated (FTO) (rs9930506; A/T) polymorphisms in 82 obesity subjects and 102 controls showed significant association for VDR TaqI ‘T’ allele and obesity (OR: 2.07; 1.123–3.816; P = 0.019), contributing to an elevated BMI of 3 kg/m² per risk allele. No association was observed for the FTO polymorphism. These results further support a role for VDR as risk factor for obesity and suggest its further validation in larger independent populations as well as highlight a target for functional analysis towards therapeutic intervention in obese individuals.     

Three force fields' views of the 3(10) helix

Slowly but steadily bibliographic evidence is accumulating that the apparent convergence of the various biomolecular force fields as evidenced from simulations of proteins in the folded state does not hold true for folding simulations. Here we add one more example to the growing list of peptides and proteins for which different force fields show irreconcilable differences in their folding predictions, even at such a fundamental level as that of a peptide's secondary structure. We show that for an undecamer peptide that is known from two independent NMR structure determinations to have a mainly 3₁₀-helical structure in solution, three mainstream biomolecular force fields give completely disparate predictions: The CHARMM force field (with the CMAP correction) predicts an outstandingly stable α-helical structure, in disagreement not only with the experimental structures, but also with experimental evidence obtained from circular dichroism. OPLS-AA shows an almost totally disordered peptide with the most frequently observed folded conformation corresponding to a β-hairpin-like structure, again in disagreement with all available experimental evidence. Only the AMBER99SB force field appears to qualitatively agree with not only the general structural characteristics of the peptide (on the account of both NMR- and CD-based experiments), but to also correctly predict some of the experimentally observed interactions at the level of side chains. Possible interpretations of these findings are discussed.     

SUMOylation Is Required for Optimal TRAF3 Signaling Capacity

TNF receptor–associated factors (TRAFs) are multifunctional adaptor proteins involved in temporal and spatial coordination of signals necessary for normal immune function. Here, we report that TRAF3, a TRAF family member with a key role in Toll-like and TNF family receptor signaling and suppressor of lymphomagenesis, is post-translationally modified by the small ubiquitin-related modifier (SUMO). Through yeast two-hybrid and co-immunoprecipitation assays we have identified Ubc9, the SUMO conjugating enzyme, as a novel TRAF3-interacting protein. We show that Ubc9-dependent SUMOylation of TRAF3 modulates optimal association with the CD40 receptor, thereby influencing TRAF3 degradation and non-canonical NF-κB activation upon CD40 triggering. Collectively, our findings describe a novel post-translational modification of a TRAF family member and reveal a link between SUMOylation and TRAF-mediated signal transduction.     

Quantitative expression analysis of <Emphasis Type="BoldItalic">mleP</Emphasis> gene and two genes involved in the ABC transport system in <Emphasis Type="BoldItalic">Oenococcus oeni</Emphasis> during rehydration

Oenococcus oeni is recognized as the principal microorganism responsible for malolactic fermentation, and the control of its activity is of primary importance in winemaking. The aim of this study was to quantify the levels of expression of the malate transporter gene (mleP) and of two genes putatively involved in the ATP-binding cassette transport system (oeoe_1651, oeoe_0550) to better understand the physiological response of bacteria during rehydration. These genes coding for transporters were studied in different rehydration media. Initially, three different statistical algorithms were used to identify suitable reference genes to be used for the normalization of expression data in O. oeni during rehydration, and to this purpose, the best genes found were ddl and gyrB. The results showed that the genes for transporters of malate and sugar (mleP, oeoe_1651) were activated immediately after a few minutes of rehydration, when specific medium compositions were used.     

Understanding the role of chondrocytes in osteoarthritis: utilizing proteomics

Introduction: Proteomic analyses have been acknowledged to carry a significant prospective in elucidating the pathogenesis of several diseases, including osteoarthritis (OA). But it has not been an easy road: major technical issues, mainly derived from the complex and rigid nature of the cartilage tissue, had to be faced; an obstacle that led to the development of different approaches.

Areas covered: In this review, we categorized the proteomic studies undertaken (proteomic analyses of the cartilage, cartilage explants, cultured chondrocytes, and chondrocytes’ secretome) as part of the different strategies developed in order to overcome tissue and disease-specific challenges. Essentially these approaches aimed at identifying differences in the proteome of healthy vs diseased tissue. Our aim was to point out the novel players that have emerged from these analyses and highlight the associated mechanism(s) suggested to play a role in the pathogenesis of OA.

Expert commentary: The identified factors indicate the implication of age-associated mechanisms, such as metabolic deregulation, inflammation, and redox imbalance, in OA onset and/or progression. Taken together these results outline the causal network of the disease and place chondrocytes’ senescence at the center of the emerging aetiopathological atlas.     

A Phylogeny-Based Benchmarking Test for Orthology Inference Reveals the Limitations of Function-Based Validation

Accurate orthology prediction is crucial for many applications in the post-genomic era. The lack of broadly accepted benchmark tests precludes a comprehensive analysis of orthology inference. So far, functional annotation between orthologs serves as a performance proxy. However, this violates the fundamental principle of orthology as an evolutionary definition, while it is often not applicable due to limited experimental evidence for most species. Therefore, we constructed high quality "gold standard" orthologous groups that can serve as a benchmark set for orthology inference in bacterial species. Herein, we used this dataset to demonstrate 1) why a manually curated, phylogeny-based dataset is more appropriate for benchmarking orthology than other popular practices and 2) how it guides database design and parameterization through careful error quantification. More specifically, we illustrate how function-based tests often fail to identify false assignments, misjudging the true performance of orthology inference methods. We also examined how our dataset can instruct the selection of a “core” species repertoire to improve detection accuracy. We conclude that including more genomes at the proper evolutionary distances can influence the overall quality of orthology detection. The curated gene families, called Reference Orthologous Groups, are publicly available at http://eggnog.embl.de/orthobench2.     

An unusual case of Cat-Eye syndrome phenotype and extragonadal mature teratoma: review of the literature

BACKGROUND Cat-Eye syndrome (CES) with teratoma has not been previously reported. We present the clinical and molecular findings of a 9-month-old girl with features of CES and also a palpable midline neck mass proved to be an extragonadal mature teratoma, additionally characterized by array comparative genomic hybridization (aCGH). RESULTS High resolution oligonucleotide-based aCGH confirmed that the supernumerary marker chromosome (SMC) derived from chromosome 22, as was indicated by molecular cytogenetic analysis with fluorescence in situ hybridization (FISH). Additionally, aCGH clarified the size, breakpoints, and gene content of the duplication (dup 22q11.1q11.21; size:1.6 Mb; breakpoints: 15,438,946-17,041,773; hg18). The teratoma tissue was also tested with aCGH, in which the CES duplication was not found, but the analysis revealed three aberrations: del Xp22.3 (108,864-2788,689; 2.7 Mb hg18), dup Yp11.2 (6688,491-7340,982; 0.65 Mb, hg18), and dup Yq11.2q11.23 (12,570,853-27,177,133; 14.61 Mb, hg18). These results indicated 46 XY (male) karyotype of the teratoma tissue, making this the second report of mature extragonadal teratoma in a female neonate, probably deriving from an included dizygotic twin of opposite sex (fetus in fetu). CONCLUSIONS Our findings extend the phenotypic spectrum of CES syndrome, a disorder with clinical variability, pointing out specific dosage-sensitive genes that might contribute to specific phenotypic features.     

The changing spectrum of arrhythmogenic (right ventricular) cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a clinically and genetically heterogeneous heart muscle disorder associated with ventricular arrhythmias and risk of sudden death. The disease is heredo-familial, and mutations in desmosomal genes have been identified in about half of patients. Recent experimental models confirm this disease develops after birth due to progressive myocardial dystrophy. Genotype-phenotype correlations, including magnetic resonance and pathology studies on heart specimens, are currently demonstrating that the spectrum of the disease is wider than initially thought and usually referred to with the adjective "right ventricular", with the evidence of biventricular or even isolated left ventricular forms, so that it is increasingly identified simply as "arrhythmogenic cardiomyopathy". A revision of the diagnostic criteria encompassing familial, electrocardiographic, arrhythmic, morpho-functional and histopathologic findings, has been made to improve diagnostic sensitivity and specificity, in particular of the concealed forms and left-dominant subtypes of the disease. Experimental models are mandatory to gain an insight into the cascade of cellular and molecular events leading from gene defect to myocardial dystrophy in ARVC.