Subclinical immune reactions to viral infections may correlate with child and adolescent diagnosis of attention-deficit/hyperactivity disorder: A preliminary study from Turkey

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neuro-developmental disorders of childhood and  adolescence. Studies focusing on the relationship of infectious agents and ADHD are scarce. It is also known that cerebellar injury may lead to  hyperactive behavior. This study aimed to evaluate the relationship  between viral agents of cerebellitis and the diagnosis of ADHD.Methods: The study group was formed of 60 consecutive ADHD patients and 30 healthy children. IgG levels for VZV; HSV-1, CMV, Measles, Mumps, Rubella and EBV were evaluated.Results: Males were significantly higher among patients with ADHD (65% vs. 40%, p=0.025). Patients with ADHD displayed significantly higher positivity for measles IgG (80% vs. 60%, p=0.044). When patients with ADHD were classified according to their pubertal status, adolescents with ADHD displayed higher positivity for mumps (100% vs. 74.4%, p=0.043). Most of the patients were diagnosed with ADHD-Combined or  Hyperactive/Impulsive Subtypes (56.6%) while 43.3% were diagnosed with ADHD-predominantly inattentive type. When patients with subtypes of ADHD were compared in terms of seropositivity, it was found that patients with ADHD-Combined/ Hyperactive-Impulsive subtypes had significantly elevated reactions for Rubella (100% vs. 88.5%, p=0.044).Conclusion: Although limited to a single center and may be prone to sampling biases, our results may support the notion that immune reactions may be related with ADHD among children and adolescents. Further,  prospective studies from multiple centers are needed to support our  findings and establish causality.Key words: ADHD, infection, immunology, measles, rubella, mumps, Ig

Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth

The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK

The 2013 European Seismic Hazard Model: key components and results

The 2013 European Seismic Hazard Model (ESHM13) results from a community-based probabilistic seismic hazard assessment supported by the EU-FP7 project “Seismic Hazard Harmonization in Europe” (SHARE, 2009–2013). The ESHM13 is a consistent seismic hazard model for Europe and Turkey which overcomes the limitation of national borders and includes a through quantification of the uncertainties. It is the first completed regional effort contributing to the “Global Earthquake Model” initiative. It might serve as a reference model for various applications, from earthquake preparedness to earthquake risk mitigation strategies, including the update of the European seismic regulations for building design (Eurocode 8), and thus it is useful for future safety assessment and improvement of private and public buildings. Although its results constitute a reference for Europe, they do not replace the existing national design regulations that are in place for seismic design and construction of buildings. The ESHM13 represents a significant improvement compared to previous efforts as it is based on (1) the compilation of updated and harmonised versions of the databases required for probabilistic seismic hazard assessment, (2) the adoption of standard procedures and robust methods, especially for expert elicitation and consensus building among hundreds of European experts, (3) the multi-disciplinary input from all branches of earthquake science and engineering, (4) the direct involvement of the CEN/TC250/SC8 committee in defining output specifications relevant for Eurocode 8 and (5) the accounting for epistemic uncertainties of model components and hazard results. Furthermore, enormous effort was devoted to transparently document and ensure open availability of all data, results and methods through the European Facility for Earthquake Hazard and Risk (www.​efehr.​org)

Two-dimensional Schr\"odinger Hamiltonians with Effective Mass in SUSY Approach

The general solution of SUSY intertwining relations of first order for two-dimensional Schr\"odinger operators with position-dependent (effective) mass is built in terms of four arbitrary functions. The procedure of separation of variables for the constructed potentials is demonstrated in general form. The generalization for intertwining of second order is also considered. The general solution for a particular form of intertwining operator is found, its properties - symmetry, irreducibility, separation of variables - are investigated.Comment: 16 page

Genomic basis for RNA alterations in cancer

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed ‘bridged’ fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

Human TorsinA can function in the yeast cytosol as a molecular chaperone

TorsinA (TorA) is an AAA+ ATPAse linked to dystonia type 1 (DYT1), a neurological disorder that leads to uncontrollable muscular movements. Although DYT1 is linked to a 3bp deletion in the C terminus of TorA, the biological function of TorA remains to be established. Here we use the yeast Saccharomyces cerevisiae as a tractable in vivo model to explore TorA function. We demonstrate that TorA can protect yeast cells against different forms of environmental stress and show that in the absence of the molecular disaggregase Hsp104, TorA can refold heat-denatured luciferase in vivo in an ATP-dependent manner. However, this activity requires TorA to be translocated to the cytoplasm from the ER in order to access and process cytoplasmic protein aggregates. Furthermore, mutational or chemical inactivation of the ATPase activity of TorA blocks this activity. We also find that TorA can inhibit the propagation of certain conformational variants of [ PSI +], the aggregated prion form of the endogenous Sup35 protein. Finally, we show that while cellular localisation remains unchanged in the dystonia-linked TorA mutant ?E302-303, the ability of this mutant form of TorA to protect against cellular stress and to facilitate protein refolding, is impaired, consistent with it being a loss of function mutation