The XVth World Congress of Psychiatric Genetics, October 7–11, 2007: Rapporteur summaries of oral presentations

The World Congress of Psychiatric Genetics (WCPG) has become an annual event since the early 1990's sponsored by the International Society of Psychiatric Genetics (ISPG). Each year the latest published and unpublished findings are aired for discussion by representatives of the majority of research programs on this topic world-wide. The 2007 congress was held in New York City and attracted over 1000 researchers. The topics emphasized included results from whole genome association studies, the significance of copy number variation and the important contributions of epigenetic events to psychiatric disorders. There were over 20 oral sessions devoted to these and other topics of interest. Young investigator recipients of travel awards served as rapporteurs to summarize sessions and these summaries follow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58040/1/30711_ftp.pd

On the quest for selective constraints shaping the expressivity of the genes casting retropseudogenes in human

<p>Abstract</p> <p>Background</p> <p>Pseudogenes, the nonfunctional homologues of functional genes are now coming to light as important resources regarding the study of human protein evolution. Processed pseudogenes arising by reverse transcription and reinsertion can provide molecular record on the dynamics and evolution of genomes. Researches on the progenitors of human processed pseudogenes delved out their highly expressed and evolutionarily conserved characters. They are reported to be short and GC-poor indicating their high efficiency for retrotransposition. In this article we focused on their high expressivity and explored the factors contributing for that and their relevance in the milieu of protein sequence evolution.</p> <p>Results</p> <p>We here, analyzed the high expressivity of these genes configuring processed or retropseudogenes by their immense connectivity in protein-protein interaction network, an inclination towards alternative splicing mechanism, a lower rate of mRNA disintegration and a slower evolutionary rate. While the unusual trend of the upraised disorder in contrast with the high expressivity of the proteins encoded by processed pseudogene ancestors is accredited by a predominance of hub-protein encoding genes, a high propensity of repeat sequence containing genes, elevated protein stability and the functional constraint to perform the transcription regulatory jobs. Linear regression analysis demonstrates mRNA decay rate and protein intrinsic disorder as the influential factors controlling the expressivity of these retropseudogene ancestors while the latter one is found to have the most significant regulatory power.</p> <p>Conclusions</p> <p>Our findings imply that, the affluence of disordered regions elevating the network attachment to be involved in important cellular assignments and the stability in transcriptional level are acting as the prevailing forces behind the high expressivity of the human genes configuring processed pseudogenes.</p

Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism

Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling

Atmospheric electrification in dusty, reactive gases in the solar system and beyond

Detailed observations of the solar system planets reveal a wide variety of local atmospheric conditions. Astronomical observations have revealed a variety of extrasolar planets none of which resembles any of the solar system planets in full. Instead, the most massive amongst the extrasolar planets, the gas giants, appear very similar to the class of (young) Brown Dwarfs which are amongst the oldest objects in the universe. Despite of this diversity, solar system planets, extrasolar planets and Brown Dwarfs have broadly similar global temperatures between 300K and 2500K. In consequence, clouds of different chemical species form in their atmospheres. While the details of these clouds differ, the fundamental physical processes are the same. Further to this, all these objects were observed to produce radio and X-ray emission. While both kinds of radiation are well studied on Earth and to a lesser extent on the solar system planets, the occurrence of emission that potentially originate from accelerated electrons on Brown Dwarfs, extrasolar planets and protoplanetary disks is not well understood yet. This paper offers an interdisciplinary view on electrification processes and their feedback on their hosting environment in meteorology, volcanology, planetology and research on extrasolar planets and planet formation

Regulation of GSK-3 Activity as A Shared Mechanism in Psychiatric Disorders

Serin/Treonin kinaz ailesinin üyelerinden bir kinaz olarak ilk kez glikojen sentaz’ı inhibe ettiği keşfedilen glikojen sentaz kinaz-3 (GSK-3), günümüzde bilinen 50’den fazla substratı ile birçok hücre içi düzenleyici mekanizmada görev alan geniş etki spektrumlu bir enzim olarak kabul edilmektedir. GSK-3’ün memelilerde GSK-3α ve GSK-3β olmak üzere yapısal olarak yüksek homoloji gösteren iki izoformu bulunmaktadır. Her iki izoform birçok dokuda yaygın dağılım göstermekle beraber, en yüksek oranda beyinde bulunmakta ve genellikle benzer fonksiyonlar göstermektedirler. Diğer protein kinazların aksine GSK-3 uyarılmamış hücrede yapısal olarak aktif yani defosforile halde bulur. Protein kinaz A (PKA), protein kinaz B (PKB;AKT) ve protein kinaz C (PKC) gibi diğer protein kinazlarla fosforilasyona uğrayarak olarak inaktive edilir. Günümüzde artmış GSK-3 aktivitesinin major depresyon, bipolar bozukluk, hiperaktivite bozuklukları gibi hastalıklar ve şizofreni oluşumunda rol oynayabileceğine ilişkin önemli bulgular mevcuttur. Bu nedenle söz konusu psikiyatrik hastalıklarda arttığı gösterilen GSK-3 aktivitesinin azaltılmasının tedavide umut verici bir yaklaşım olabileceği kabul edilebilir. Bu gözden geçirme çalışmasında yukarıda sözü edilen psikiyatrik hastalıkların oluşmasında görev alan GSK-3 aracılı mekanizmalara kısaca değinilerek GSK-3’ün aktivitesinin düzenlenmesinde rol oynadığı gösterilen klinikte kullanılan ilaçlara yer verilmiştir. Anahtar sözcükler: GSK-3, depresyon, bipolar bozukluk, şizofren

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research