Paleostress field reconstruction and revised tectonic history of the Donbas fold and thrust belt (Ukraine and Russia).

In the WNW-ESE Donbas fold belt (DF), inversion of 3500 microtectonic data collected at 135 sites, in Proterozoic, Devonian, Carboniferous, and Cretaceous competent rocks allowed reconstruction of 123 local stress states. Accordingly, four successive paleostress fields reveal the tectonic evolution of the DF. At the numerous sites that have been affected by polyphase tectonics, the chronology between local paleostress states (also paleostress fields) was established using classical criteria (crosscutting striae, pre- or post-folding stress states, stratigraphic control). The oldest event is an extensional stress field with NNE-SSW σ<inf>3</inf>. It corresponds to the rifting phases that generated the basin in Devonian times and its early Visean reactivation. Later, the DF was affected by a transtension, with NW-SE σ<inf>3</inf> characterizing Early Permian tectonism, including the development of the "Main Anticline" of the DF and the pronounced uplift of its southern margin and Ukrainian Shield. Two paleostress fields characterize the Cretaceous/Paleocene inversion of the DF, which was accompanied by folding and thrusting. Both are compressional in type but differ by the trend of σ<inf>1</inf>, which was first NW-SE and subsequently N-S. The discrete paleostress history of the DF allows a revised interpretation of its tectonic evolution with significant implications for understanding the geodynamic evolution of the southern margin of the East European Craton. Copyright 2003 by the American Geophysical Union

Distribution of sedimentary rock types through time in a back-arc basin: A case study from the Jurassic of the Greater Caucasus (Northern Neotethys)

Abstract The evolution of sedimentary basins can be explored by analyzing the changes in their lithologies and lithofacies (i.e. predominant lithologies). The Greater Caucasus Basin, which was located at the northern margin of the Neotethys Ocean, represents a complete Sinemurian-Tithonian succession. A quantitative analysis of compiled datasets suggests that principal lithologies and lithofacies are represented by siliciclastics, shale and carbonates. The relative abundance of siliciclastics and shale decreased throughout the Jurassic, whereas that of carbonates increased. Evaporites are known from the Upper Jurassic, while volcaniclastics and volcanics, as well as coals, are known only in the Lower to Middle Jurassic. Siliceous rocks are extremely rare. Lithology and lithofacies proportions change accordingly. The Sinemurian-Bathonian sedimentary complex is siliciclastic-and-shale-dominated, whereas the Callovian-Tithonian sedimentary complex is carbonate-dominated. A major change in the character of sedimentation occurred during the Aalenian-Callovian time interval. Regional transgressions and regressions were more important controls of changes in the sedimentary rock proportions than average basin depth. Landward shoreline shifts were especially favorable for carbonate accumulation, whereas siliciclastics and shale were deposited preferentially in regressive settings. An extended area of the marine basin, its lower average depth, and a sharp bathymetric gradient favored a higher diversity of sedimentation. An orogeny at the Triassic-Jurassic transition was responsible for a large proportion of siliciclastics and extensive conglomerate deposition. An arcarc collision in the Middle Jurassic also enhanced the siliciclastic deposition. Both phases of tectonic activity were linked with an increase in volcanics and volcaniclastics. Volcanism itself might have been an important control on sedimentation. A transition to carbonate-dominated sedimentation occurred in the Late Jurassic, reflecting a tectonically calm period

Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia

In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding the sodium channel Nav1.7 expressed in the peripheral nervous system plays a critical role in IEM. A gain-of-function mutation in this sodium channel leads to aberrant sensory neuronal activity and extreme pain, particularly in response to heat. Five patients with IEM were treated with a new potent and selective compound that blocked the Nav1.7 sodium channel resulting in a decrease in heat-induced pain in most of the patients. We derived induced pluripotent stem cell (iPSC) lines from four of five subjects and produced sensory neurons that emulated the clinical phenotype of hyperexcitability and aberrant responses to heat stimuli. When we compared the severity of the clinical phenotype with the hyperexcitability of the iPSC-derived sensory neurons, we saw a trend toward a correlation for individual mutations. The in vitro IEM phenotype was sensitive to Nav1.7 blockers, including the clinical test agent. Given the importance of peripherally expressed sodium channels in many pain conditions, our approach may have broader utility for a wide range of pain and sensory conditions

Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer

Aromatic amines, N-nitroso compounds and heterocyclic amines are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2 and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single-nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2 and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the polymerase chain reaction–restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33–3.72) and 2.54 (1.51–4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene, respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC

Is Evolution of Blind Mole Rats Determined by Climate Oscillations?

The concept of climate variability facilitating adaptive radiation supported by the ‘‘Court Jester’’ hypothesis is disputed by the ‘‘Red Queen’’ one, but the prevalence of one or the other might be scale-dependent. We report on a detailed, comprehensive phylo-geographic study on the ,4 kb mtDNA sequence in underground blind mole rats of the family Spalacidae (or subfamily Spalacinae) from the East Mediterranean steppes. Our study aimed at testing the presence of periodicities in branching patterns on a constructed phylogenetic tree and at searching for congruence between branching events, tectonic history and paleoclimates. In contrast to the strong support for the majority of the branching events on the tree, the absence of support in a few instances indicates that network-like evolution could exist in spalacids. In our tree, robust support was given, in concordance with paleontological data, for the separation of spalacids from muroid rodents during the first half of the Miocene when open, grass-dominated habitats were established. Marine barriers formed between Anatolia and the Balkans could have facilitated the separation of the lineage ‘‘Spalax’’ from the lineage ‘‘Nannospalax’’ and of the clade ‘‘leucodon’’ from the clade ‘‘xanthodon’’. The separation of the clade ‘‘ehrenbergi’’ occurred during the late stages of the tectonically induced uplift of the Anatolian high plateaus and mountains, whereas the separation of the clade ‘‘vasvarii’’ took place when the rapidly uplifting Taurus mountain range prevented the Mediterranean rainfalls from reaching the Central Anatolian Plateau. The separation of Spalax antiquus and S. graecus occurred when the southeastern Carpathians were uplifted. Despite the role played by tectonic events, branching events that show periodicity corresponding to 400-kyr and 100-kyr eccentricity bands illuminate the important role of orbital fluctuations on adaptive radiation in spalacids. At the given scale, our results supports the ‘‘Court Jester’’ hypothesis over the ‘‘Red Queen’’ one

Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?

Intellectual disability affects 2-3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between similar to 10,500 and similar to 400 years ago. We date the most recent common ancestor of all HBV lineages to between similar to 20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for similar to 4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.Molecular Technology and Informatics for Personalised Medicine and Healt

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic