Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory.

Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates its genome in a membrane-associated replication complex. Nonstructural protein 4B (NS4B) induces the specific membrane alteration, designated as membranous web (MW), that harbours this complex. HCV NS4B is an integral membrane protein predicted to comprise four transmembrane segments in its central part. The N-terminal part comprises two amphipathic alpha-helices of which the second has the potential to traverse the membrane bilayer, likely upon oligomerisation. The C-terminal part comprises a predicted highly conserved alpha-helix, a membrane-associated amphipathic alpha-helix and two reported palmitoylation sites. NS4B interacts with other viral nonstructural proteins and has been reported to bind viral RNA. In addition, it was found to harbour an NTPase activity. Finally, NS4B has recently been found to have a role in viral assembly. Much work needs to be done with respect to further dissecting these multiple functions as well as providing a refined membrane topology and complete structure of NS4B. Progress in this direction should yield important insights into the functional architecture of the HCV replication complex and may reveal new opportunities for antiviral intervention against a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide.

The hypogene iron oxide copper-gold mineralization in the Mantoverde District, Northern Chile

The Mantoverde iron oxide copper-gold (IOCC) district, northern Chile, is known for its Cu production from supergene ores. Recently, exploration outlined an additional hypogene ore resource of 440 Mt with 0.56 percent Cu, and 0.12 g/t An. The hypogene sulfide mineralization occurs mainly as chalcopyrite and pyrite, typically in specularite or magnetite-cemented breccias and associated stockworks. The host rocks underwent variably intense K feldspar alteration, chloritization, sericitization, silicification, and/or carbonatization. A district scale Na(-Ca) alteration is absent. The IOCC mineralization in the district shows a strong tectonic control by northwest- to north-northwest-trending brittle structures. Large Cu sulfide-rich veins or Cu sulfide-cemented breccias are absent. Therefore, head grades of 4 percent Cu are an exception. There is a positive correlation between Cu and An grades. Gold is probably contained mostly in chalcopyrite and pyrite. Elevated concentrations of light rare-earth elements (LREE) occur locally but are attributed to redistribution of LREE within the deposits rather than to derivation from external sources. The Cu-Au ores in the Mantoverde district are low in and have relatively low contents in heavy metals that are potentially hazardous to the environment, such as As (avg 14 ppm), Hg (<5 ppm), or Cd (<0.2 ppm). The sulfur isotope ratios of chalcopyrite from the IOCC deposits lie between -5.6 and 8.9 per mil delta(34)S(VCDT). They show systematic variations within the district, which are interpreted to reflect relative distance to inferred fluid conduits and the level of deposition within the hydrothermal system. Most initial (87)Sr/(86)Sr values of altered volcanic rocks and hydrothermal calcite from the Mantoverde district are between 0.7031 and 0.7060 and are similar to those of the igneous rocks of the region. Lead isotope ratios of chalcopyrite are consistent with Pb (and by inference Cu) derived from Early Cretaceous magmatism. The sulfur, strontium, and lead isotope data of chalcopyrite, calcite gangue, or altered host rocks, respectively, are compatible with a genetic model that involves cooling of metal and sulfur-bearing magmatic-hydrothermal fluids that mix with meteoric waters or seawater at relatively shallow crustal levels. An additional exotic sulfur input is likely, though not required, for the copper mineralization. Apart from the IOCC. deposits, there are a number of smaller magnetite(-apatite) bodies in the district. These are geologically similar to the Cu-Au-bearing magnetite bodies, but are related to splays of the north-south-trending Atacama fault zone and differ in alteration and texture.

Modelling changes in stable isotope compositions of minerals during net transfer reactions in a contact aureole: Wollastonite growth at the northern Hunter Mountain Batholith (Death Valley National Park, USA)

One of the world's largest wollastonite deposits was formed at the contact of the northern Hunter Mountain Batholith (California, USA) in Paleozoic sediments. Wollastonite occurs as zones of variable thickness surrounding layers or nodules of quartzite in limestones. A minimum formation temperature of 650 degrees C is estimated from isolated periclase-bearing lenses in that area. Contact metamorphism of siliceous carbonates has produced mineral assemblages that are consistent with heterogeneous, and partly limited infiltration of water-rich fluids, compatible with O-18/O-16 and C-13/C-12 isotopic patterns recorded in carbonates. Oxygen isotope compositions of wollastonites in the study area may also not require infiltration of large quantities of externally-derived fluids that were out of equilibrium with the rocks. 8180 values of wollastonite are high (14.8 parts per thousand to 25.0 parts per thousand; median: 19.7 parts per thousand) and close to those of the host limestone (19.7 parts per thousand to 28 parts per thousand; median: 24.9 parts per thousand) and quartz (18.0 parts per thousand. to 29.1 parts per thousand; median: 22.6 parts per thousand). Isotopic disequilibrium exists at quartz/wollastonite and wollastonite/calcite boundaries. Therefore, classical batch/Rayleigh fractionation models based on reactant and product equilibrium are not applicable to the wollastonite rims. An approach that relies on local instantaneous mass balance for the reactants, based on the wollastonite-forming reaction is suggested as an alternative way to model wollastonite reaction rims. This model reproduces many of the measured delta O-18 values of wollastonite reaction rims of the current study to within +/- 1 parts per thousand, even though the wollastonite compositions vary by almost 10 parts per thousand. (C) 2011 Elsevier B.V. All rights reserved.

Structural and metamorphic evolution of the northern Himachal Himalaya, NW India - (Spiti-eastern Lahul-Parvati valley traverse)

The Himalayan orogen is the result of the collision between the Indian and Asian continents that began 55-50 Ma ago, causing intracontinental thrusting and nappe formation. Detailed mapping as well as structural and microfabric analyses on a traverse from the Tethyan Himalaya southwestward through the High Himalayan Crystalline and the Main Central Thrust zone (MCT zone) to the Lesser Himalayan Sequence in the Spiti-eastern Lahul-Parvati valley area reveal eight main phases of deformation, a series of late stage phases and five stages of metamorphic crystallization. This sequence of events is integrated into a reconstruction of the tectonometamorphic evolution of the Himalayan orogen in northern Himachal Pradesh. The oldest phase D-1 is preserved as relies in the High Himalayan Crystalline. Its deformational conditions are poorly known, but the metamorphic evolution is well documented by a prograde metamorphism reaching peak conditions within the upper amphibolite facies. This indicates that D-1 was an important tectonometamorphic event including considerable crustal thickening. The structural, metamorphic and sedimentary record suggest that D-1 most probably represents an early stage of continental collision. The first event clearly attributed to the collision between India and Asia is documented by two converging nappe systems, the NE-verging Shikar Beh Nappe and the SW-verging north Himalayan nappes. The D-2 Shikar Beh Nappe is characterized by isoclinal folding and top-to-the NE shearing, representing the main deformation in the High Himalayan Crystalline. D-2 also caused the main metamorphism in the High Himalayan Crystalline that was of a Barrovian-type, reaching upper amphibolite facies peak conditions. The Shikar Beh Nappe is interpreted to have formed within the Indian crust SW of the subduction zone. Simultaneously with NE-directed nappe formation, incipient subduction of India below Asia caused stacking of the SW-verging north Himalayan Nappes, that were thrust from the northern edge of the subducted continent toward the front of the Shikar Beh Nappe. As a result, the SW-verging folds of the D-3 Main Fold Zone formed in the Tethyan Himalaya below the front of the north Himalayan nappes. D-3 represents the main deformation in the Tethyan Himalaya, associated with a greenschist facies metamorphism. Folding within the Main Fold Zone subsequently propagated toward SW into the High Himalayan Crystalline, where it overprinted the preexisting D-2 structures. After subduction at the base of the north Himalayan nappes, the subduction zone stepped to the base of the High Himalayan Crystalline, where D-3 folds were crosscut by SW-directed D-4 thrusting. During D-4, the Crystalline Nappe, comprising the Main Fold Zone and relies of the Shikar Beh Nappe was thrust toward SW over the Lesser Himalayan Sequence along the 4 to 5 kms thick Main Central Thrust zone. Thrusting was related to a retrograde greenschist facies overprint at the base of the Crystalline Nappe and to pro-grade greenschist facies conditions in the Lesser Himalayan Sequence. Simultaneously with thrusting at the base of the Crystalline Nappe, higher crustal levels were affected by NE-directed D-5 normal extensional shearing and by dextral strike-slip motion, indicating that the high-grade metamorphic Crystalline Nappe was extruded between the low-grade metamorphic Lesser Himalayan Sequence at the base and the north Himalayan nappes at the top. The upper boundary of the Crystalline Nappe is not clearly delimited and passes gradually into the low-grade rocks at the front of the north Himalayan nappes. Extrusion of the Crystalline Nappe was followed by the phase D-6, characterized by large-scale, upright to steeply inclined, NE-verging folds and by another series of normal and extensional structures D-7+D-8 that may be related to ongoing extrusion of the Crystalline Nappe. The late stage evolution is represented by the phases D-A and D-B that indicate shortening parallel to the axis of the mountain chain and by D-C that is interpreted to account for the formation of large-scale domes with NNW-SSE-trending axes, an example of which is exposed in the Larji-Kullu-Rampur tectonic window.

Disaster Risk, Livelihoods and Natural Barriers, Strengthening Decision-Making Tools for Disaster Risk Reduction: A case study from northern Pakistan

The goal of this interdisciplinary study is to better understand the land use factors that increase vulnerability of mountain areas in northern Pakistan. The study will identify and analyse the damages and losses caused by the October 2005 earthquake in two areas of the same valley: one "low-risk" watershed with sound natural resources management, the other, "high-risk" in an ecologically degraded watershed. Secondly, the study will examine natural and man-made causes of secondary hazards in the study area, especially landslides; and third it will evaluate the cost of the earthquake damage in the study areas on the livelihoods of local communities and the sub-regional economy. There are few interdisciplinary studies to have correlated community land use practices, resources management, and disaster risk reduction in high-risk mountain areas. By better understanding these linkages, development- humanitarian- and donor agencies focused on disaster reduction can improve their risk reduction programs for mountainous regions.

Fluid flow through the sedimentary cover in northern Switzerland recorded by calcite-celestite veins (Oftringen borehole, Olten)

Abundant veins filled by calcite, celestite and pyrite were found in the core of a 719 m deep borehole drilled in Oftringen near Olten, located in the north-western Molasse basin, close to the thrust of the Folded Jura. Host rocks are calcareous marl, argillaceous limestone and limestone of the Dogger and Malm. The delta O-18 values of vein calcite are lower than in host rock carbonate and, together with microthermometric data from fluid inclusions in vein calcite, indicate precipitation from a seawater-dominated fluid at average temperatures of 56-68A degrees C. Such temperatures were reached at the time of maximum burial of the sedimentary pile in the late Miocene. The depth profile of delta C-13 and Sr-87/Sr-86 values and Sr content of both whole-rock carbonate and vein calcite show marked trends towards negative delta C-13, high Sr-87/Sr-86, and low Sr content in the uppermost 50-150 m of the Jurassic profile (upper Oxfordian). The Sr-87/Sr-86 of vein minerals is generally higher than that of host rock carbonate, up to very high values corresponding to Burdigalian seawater (Upper Marine Molasse, Miocene), which represents the last marine incursion in the region. No evidence for internally derived radiogenic Sr (clay minerals) has been found and so an external source is required. S and O isotope composition of vein celestite and pyrite can be explained by bacterial reduction of Miocene seawater sulphate. The available data set suggests the vein mineralization precipitated from descending Burdigalian seawater and not from a fluid originating in the underlying Triassic evaporites.

Global alcohol exposure estimates by country, territory and region for 2005--a contribution to the Comparative Risk Assessment for the 2010 Global Burden of Disease Study.

AIMS: This study aimed to estimate the prevalence of life-time abstainers, former drinkers and current drinkers, adult per-capita consumption of alcohol and pattern of drinking scores, by country and Global Burden of Disease region for 2005, and to forecast these indicators for 2010. DESIGN: Statistical modelling based on survey data and routine statistics. SETTING AND PARTICIPANTS: A total of 241 countries and territories. MEASUREMENTS: Per-capita consumption data were obtained with the help of the World Health Organization's Global Information System on Alcohol and Health. Drinking status data were obtained from Gender, Alcohol and Culture: An International Study, the STEPwise approach to Surveillance study, the World Health Survey/Multi-Country Study and other surveys. Consumption and drinking status data were triangulated to estimate alcohol consumption across multiple categories. FINDINGS: In 2005 adult per-capita annual consumption of alcohol was 6.1 litres, with 1.7 litres stemming from unrecorded consumption; 17.1 litres of alcohol were consumed per drinker, 45.8% of all adults were life-time abstainers, 13.6% were former drinkers and 40.6% were current drinkers. Life-time abstention was most prevalent in North Africa/Middle East and South Asia. Eastern Europe and Southern sub-Saharan Africa had the most detrimental pattern of drinking scores, while drinkers in Europe (Eastern and Central) and sub-Saharan Africa (Southern and West) consumed the most alcohol. CONCLUSIONS: Just over 40% of the world's adult population consumes alcohol and the average consumption per drinker is 17.1 litres per year. However, the prevalence of abstention, level of alcohol consumption and patterns of drinking vary widely across regions of the world.

The Carboniferous Baralacha La basaltic dykes (Upper Lahul, Ladakh): remnants of an early rifting event along the Indian northern plate

The Lower Carboniferous Baralacha La basaltic dykes were emplaced along transtensional faults. The basalts exhibit tholeiitic and alkaline affinities. The tholeiites are TiO2-poor, moderately enriched in light rare earth (LREE), and display Nb and Ta negative and Th positive anomalies. The alkali basalts, compared to the tholeiites, have higher TiO2, rare earth and highly incompatible trace element contents and greater LREE enrichments. The Nd and Pb isotope compositions of the Baralacha La basalts suggest that they derive from the partial melting of an enriched OIB mantle source. characterized by a HIMU component, and contaminated by the lower continental crust. The Baralacha La dyke swarm represent the remnants of an early rifting event on the northern Indian passive margin.

The role of territory choice mate choice and arrival date on breeding success in the Savi's warbler (Locustella luscinioides)

We investigated how territory quality, settlement date and morphometry affected several components of yearly breeding success of a Swiss population of Savi's Warblers Locustella luscinioides. Territories occupied by males differed from unoccupied sites of similar size and location by having higher and denser reeds, a more extensive straw litter, and a thicker cover of dead sedge leaves. Territories with these characteristics were the ones first chosen by males upon spring arrival. These males, however, did not differ in morphometry from those that arrived later. Availability of suitable nesting sites; rather than food availability, appears to be an important choice criterion for territories. Early arriving males had higher breeding success than late males because of a higher mating success and more successful clutches. The positive correlation between male breeding success and territory quality was thus mediated through their common dependence on occupancy date. Female breeding success decreased with the date of first-clutch laying, mainly because late-nesting females fledged fewer broods. Breeding success in either sex did not correlate with morphometry. Our results provide clear support for territory choice by males, but not for mate or territory choice by females, and show the crucial role played by individual settlement date on many aspects of the breeding cycle of both sexes. We propose a lottery model of mate choice. arriving females obtain the best available territories even without choosing mates or territories; since males occupy territories sequentially and in order of decreasing quality, the few unpaired males available at any moment also occupy the best available territories.

Discovery of Dogger in the internal limestone dorsale to the S of Tetouan (Northern Rif, Morocco) - Paleogeographic consequences

The Dogger (Bajocian-Lower Bathonian) has been dated for the first time in the internal Limestone Dorsale of the Rif by means of ammonites and radiolarians. It shows radiolarian and nodular limestone facies. It is concluded, then, that radiolarian sedimentation began during the Dogger in this realm, and that a drowning of the `'Ghomaride margin'' occurred at that time.