Regulation of neural circuit formation by protocadherins

The protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990s. Data implicating the Pcdhs, including ~60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ~10 non-clustered Pcdhs, in the regulation of neural development have continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination. We further discuss studies implicating mutation or epigenetic dysregulation of Pcdh genes in a variety of human neurodevelopmental and neurological disorders. With recent structural modeling of Pcdh proteins, the prospects for uncovering molecular mechanisms of Pcdh extracellular and intracellular interactions, and their role in normal and disrupted neural circuit formation, are bright.     

Dermal toxicity of DDT

Zusammenfassung Auf die Haut von Meerschweinchen appliziertes DDT bewirkt eine Verminderung im Amino-säuregehalt des Hautgewebes. Histopathologisch wurden Veränderungen im Bereich des Gewebes und der Zellen festgestellt.

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1,1,1-Trichloro-2, 2-bis(P-chlorophenyl ethane) (P-PDDT). P-P, isomer of 99.8% purity was generously supplied to us by J. R. Geigy & Co., Baslc, and their help is gratefully acknowledged by the authors.     

A 41, XYY mouse

Summary Cytogenetic analyses of bone marrow and meiotic cells in an apparently normal male mouse clearly revealed the presence of an extra Y chromosome leading to 2n=41, XYY. During meiosis the sex chromosomes formed all possible types of combinations (XYY, XY/Y, YY/X and X/Y/Y). Compared to 40, XY normal mice, the sperm count was significantly less, but the incidence of sperm head abnormality was at the normal level.Acknowledgment. The authors are grateful to Prof. G. K. Manna, Department of Zoology, Kalyani University, for his valuable comments and Prof. M. C. Dash, School of Life Sciences, Sambalpur University for providing necessary facilities. Thankful acknowledgment to CSIR, India for a SRF awarded to RNK.     

Epigenetic choreography of stem cells: the DNA demethylation episode of development

Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic information in eukaryotes. DNA demethylation plays a very significant role during embryonic development and stands out for its contribution in molecular reconfiguration during cellular differentiation for determining stem cell fate. DNA demethylation arbitrated extensive make-over of the genome via reprogramming in the early embryo results in stem cell plasticity followed by commitment to the principal cell lineages. This article attempts to highlight the sequential phases and hierarchical mode of DNA demethylation events during enactment of the molecular strategy for developmental transition. A comprehensive knowledge regarding the pattern of DNA demethylation during embryogenesis and organogenesis and study of the related lacunae will offer exciting avenues for future biomedical research and stem cell-based regenerative therapy.     

Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.