History or ecology? Substrate type as a major driver of patial genetic structure in Alpine plants

Climatic history and ecology are considered the most important factors moulding the spatial pattern of genetic diversity. With the advent of molecular markers, species' historical fates have been widely explored. However, it has remained speculative what role ecological factors have played in shaping spatial genetic structures within species. With an unprecedented, dense large-scale sampling and genome-screening, we tested how ecological factors have influenced the spatial genetic structures in Alpine plants. Here, we show that species growing on similar substrate types, largely determined by the nature of bedrock, displayed highly congruent spatial genetic structures. As the heterogeneous and disjunctive distribution of bedrock types in the Alps, decisive for refugial survival during the ice ages, is temporally stable, concerted post-glacial migration routes emerged. Our multispecies study demonstrates the relevance of particular ecological factors in shaping genetic patterns, which should be considered when modelling species projective distributions under climate change scenarios.     

Syndapin Promotes Formation of a Postsynaptic Membrane System in Drosophila

Syndapins belong to the F-BAR domain protein family whose predicted functions in membrane tubulation remain poorly studied in vivo. At Drosophila neuromuscular junctions, syndapin is associated predominantly with a tubulolamellar postsynaptic membrane system known as the subsynaptic reticulum (SSR). We show that syndapin overexpression greatly expands this postsynaptic membrane system. Syndapin can expand the SSR in the absence of dPAK and Dlg, two known regulators of SSR development. Syndapin's N-terminal F-BAR domain, required for membrane tubulation in cultured cells, is required for SSR expansion. Consistent with a model in which syndapin acts directly on postsynaptic membrane, SSR expansion requires conserved residues essential for membrane binding in vitro. However, syndapin's Src homology (SH) 3 domain, which negatively regulates membrane tubulation in cultured cells, is required for synaptic targeting and strong SSR induction. Our observations advance knowledge of syndapin protein function by 1) demonstrating the in vivo relevance of membrane remodeling mechanisms suggested by previous in vitro and structural analyses, 2) showing that SH3 domains are necessary for membrane expansion observed in vivo, and 3) confirming that F-BAR proteins control complex membrane structures.     

High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism

Autism is a behaviorally defined disorder of unknown etiology that is thought to be influenced by genetic and environmental factors. High levels of homocysteine and oxidative stress are generally associated with neuropsychiatric disorders. The purpose of this study was to compare the level of homocysteine and other biomarkers in children with autism to corresponding values in age-matched healthy children. We measured total homocysteine (tHcy), vitamin B(12), paraoxonase and arylesterase activities of human paraoxonase 1 (PON1) in plasma and glutathione peroxidase (GPx) activity in erythrocytes from 21 children: 12 with autism (age: 8.29 +/- 2.76 years) and 9 controls (age: 8.33 +/- 1.82 years). We found statistically significant differences in tHcy levels and in arylesterase activity of PON1 in children with autism compared to the control group: 9.83 +/- 2.75 vs. 7.51 +/- 0.93 micromol/L (P < or =0.01) and 72.57 +/- 11.73 vs. 81.83 +/- 7.39 kU/L (P < or =0.005). In the autistic group there was a strong negative correlation between tHcy and GPx activity and the vitamin B(12) level was low or suboptimal. In conclusion, our study shows that in children with autism there are higher levels of tHcy, which is negatively correlated with GPx activity, low PON1 arylesterase activity and suboptimal levels of vitamin B(12).     

Production of Deuterated Lutein by Chlorella protothecoides and its Detection by Mass Spectrometric Methods

Chlorella protothecoides, a lutein-producing microalga, was grown aerobically in a mineral medium prepared with 70% (v/v) deuterated water. HPLC/atmospheric pressure chemical ionization-mass spectrometry (HPLC/APCI-MS) analysis revealed 58% replacement of hydrogen by deuterium atoms as indicated by the molecular mass cluster at around m/z 599. The rapidly growing microalga had much higher levels (58%) of deuterium substitution relative to previously reported (9–15%) natural sources of lutein.     

Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm

Somitogenesis requires bilateral rhythmic segmentation of paraxial mesoderm along the antero-posterior axis. The location of somite segmentation depends on opposing signalling gradients of retinoic acid (generated by retinaldehyde dehydrogenase-2; Raldh2) anteriorly and fibroblast growth factor (FGF; generated by Fgf8) posteriorly. Retinoic-acid-deficient embryos exhibit somite left-right asymmetry, but it remains unclear how retinoic acid mediates left-right patterning. Here, we demonstrate that retinoic-acid signalling is uniform across the left-right axis and occurs in node ectoderm but not node mesoderm. In Raldh2(-/-) mouse embryos, ectodermal Fgf8 expression encroaches anteriorly into node ectoderm and neural plate, but its expression in presomitic mesoderm is initially unchanged. The late stages of somitogenesis were rescued in Raldh2(-/-) mouse embryos when the maternal diet was supplemented with retinoic acid until only the 6-somite stage, demonstrating that retinoic acid is only needed during node stages. A retinoic-acid-reporter transgene marking the action of maternal retinoic acid in rescued Raldh2(-/-) embryos revealed that the targets of retinoic-acid signalling during somitogenesis are the node ectoderm and the posterior neural plate, not the presomitic mesoderm. Our findings suggest that antagonism of Fgf8 expression by retinoic acid occurs in the ectoderm and that failure of this mechanism generates excessive FGF8 signalling to adjacent mesoderm, resulting initially in smaller somites and then left-right asymmetry.     

Application of multiplex FISH, CGH and MSSCP techniques for cytogenetic and molecular analysis of transitional cell carcinoma (TCC) cells in voided urine specimens

Multiplex FISH (UroVysion), Comparative Genomic Hybridization (CGH), and Multitemperature Single-Strand Conformation Polymorphism (MSSCP) were applied for non-invasive diagnosis and prognosis of bladder cancer. The UroVysion test was positive in 80% of patients with pT1 and in 100% of patients with either pT2 or pT3 tumours. Tumours with pT3T4 stages were characterized by high numbers of chromosomal imbalances, detected by CGH. The mutation of the p53 gene was detected in 16% of patients, but only in those with pT2 or pT3 tumours.     

Thyroid hormones and the cardiomyocytes

The authors present the current knowledge on the intracellular mechanisms of thyroid hormone action in the cardiomyocytes. Many of the clinical manifestations of thyroid diseases are due to the ability of thyroid hormone to alter cardiovascular hemodynamics. Triiodothyronine affects the hemodynamic state mainly by its influence on the expression of cardiomyocyte genes. These genes encode both structural and regulatory proteins in the heart (myosin heavy chains, sarcoplasmic reticulum calcium-activated ATP-ase, phospholamban). The impaired myocardium contractile activity in hypothyreosis reminds findings in heart failure and may warrant further exploration of therapeutic approaches using thyroid hormone to improve cardiac function in heart failure.