Mutations in dynamin 2 cause dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.     

Plasma catecholamines in conscious rats: Influence of sodium,stress and heredity

Summary Plasma catecholamines are increased in sodium-loaded rats under both resting and stress conditions. Under stress, Na⁺ resistant rats have lower plasma catecholamines than salt-sensitive ones.Supported in part by grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS) and Délégation Générale à la Recherche Scientifique et Technique (DGRST).     

Determination of plasma catecholamines in conscious normotensive and hypertensive (sodium and desoxycorticosterone) rats]

Plasma noradrenaline and adrenaline were measured in conscious Rats on 50 microliter samples by a radiometric technique. In normotensive Rats a moderate haemorrhage increased catecholamine levels. In Rats rendered hypertensive by salt loading and by desoxycorticosterone treatment noradrenaline levels were increased.     

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways. Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r(+/-) mice live on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r(+/-) mice live 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r(+/-) mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.     

The ever-growing complexity of the mitochondrial fission machinery

The mitochondrial network constantly changes and remodels its shape to face the cellular energy demand. In human cells, mitochondrial fusion is regulated by the large, evolutionarily conserved GTPases Mfn1 and Mfn2, which are embedded in the mitochondrial outer membrane, and by OPA1, embedded in the mitochondrial inner membrane. In contrast, the soluble dynamin-related GTPase Drp1 is recruited from the cytosol to mitochondria and is key to mitochondrial fission. A number of new players have been recently involved in Drp1-dependent mitochondrial fission, ranging from large cellular structures such as the ER and the cytoskeleton to the surprising involvement of the endocytic dynamin 2 in the terminal abscission step. Here we review the recent findings that have expanded the mechanistic model for the mitochondrial fission process in human cells and highlight open questions.     

An overview of RNAs with regulatory functions in gram-positive bacteria

During the last decade, RNA molecules with regulatory functions on gene expression have benefited from a renewed interest. In bacteria, recent high throughput computational and experimental approaches have led to the discovery that 10–20% of all genes code for RNAs with critical regulatory roles in metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many of these RNAs act through binding to their target mRNAs while others modulate protein activity or target DNA. The cis-acting RNAs include regulatory regions of mRNAs that can respond to various signals. These RNAs often provide the missing link between sensing changing conditions in the environment and fine-tuning the subsequent biological responses. Information on their various functions and modes of action has been well documented for gram-negative bacteria. Here, we summarize the current knowledge of regulatory RNAs in gram-positive bacteria.     

Irregular tropical glacier retreat over the Holocene epoch driven by progressive warming

The causes and timing of tropical glacier fluctuations during the Holocene epoch (10,000 years ago to present) are poorly understood. Yet constraining their sensitivity to changes in climate is important, as these glaciers are both sensitive indicators of climate change and serve as water reservoirs for highland regions. Studies have so far documented extra-tropical glacier fluctuations, but in the tropics, glacier-climate relationships are insufficiently understood. Here we present a (10)Be chronology for the past 11,000?years (11?kyr), using 57 moraines from the Bolivian Telata glacier (in the Cordillera Real mountain range). This chronology indicates that Telata glacier retreated irregularly. A rapid and strong melting from the maximum extent occurred from 10.8?±?0.9 to 8.5?±?0.4?kyr ago, followed by a slower retreat until the Little Ice Age, about 200 years ago. A dramatic increase in the rate of retreat occurred over the twentieth century. A glacier-climate model indicates that, relative to modern climate, annual mean temperature for the Telata glacier region was -3.3?±?0.8 °C cooler at 11?kyr ago and remained -2.1?±?0.8 °C cooler until the end of the Little Ice Age. We suggest that long-term warming of the eastern tropical Pacific and increased atmospheric temperature in response to enhanced austral summer insolation were the main drivers for the long-term Holocene retreat of glaciers in the southern tropics.