Effect of evaporite deposition on Early Cretaceous carbon and sulphur cycling

The global carbon and sulphur cycles are central to our understanding of the Earth's history, because changes in the partitioning between the reduced and oxidized reservoirs of these elements are the primary control on atmospheric oxygen concentrations. In modern marine sediments, the burial rates of reduced carbon and sulphur are positively coupled, but high-resolution isotope records indicate that these rates were inversely related during the Early Cretaceous period. This inverse relationship is difficult to reconcile with our understanding of the processes that control organic matter remineralization and pyrite burial. Here we show that the inverse correlation can be explained by the deposition of evaporites during the opening of the South Atlantic Ocean basin. Evaporite deposition can alter the chemical composition of sea water, which can in turn affect the ability of sulphate-reducing bacteria to remineralize organic matter and mediate pyrite burial. We use a reaction-transport model to quantify these effects, and the resulting changes in the burial rates of carbon and sulphur, during the Early Cretaceous period. Our results indicate that deposition of the South Atlantic evaporites removed enough sulphate from the ocean temporarily to reduce biologically mediated pyrite burial and organic matter remineralization by up to fifty per cent, thus explaining the inverse relationship between the burial rates of reduced carbon and sulphur during this interval. Furthermore, our findings suggest that the effect of changing seawater sulphate concentrations on the marine subsurface biosphere may be the key to understanding other large-scale perturbations of the global carbon and sulphur cycles.     

The signature of hot hydrogen in the atmosphere of the extrasolar planet HD 209458b

About ten per cent of the known extrasolar planets are gas giants that orbit very close to their parent stars. The atmospheres of these 'hot Jupiters' are heated by the immense stellar irradiation. In the case of the planet HD 209458b, this energy deposition results in a hydrodynamic state in the upper atmosphere, allowing for sizeable expansion and escape of neutral hydrogen gas. HD 209458b was the first extrasolar planet discovered that transits in front of its parent star. The size of the planet can be measured using the total optical obscuration of the stellar disk during an observed transit, and the structure and composition of the planetary atmosphere can be studied using additional planetary absorption signatures in the stellar spectrum. Here we report the detection of absorption by hot hydrogen in the atmosphere of HD 209458b. Previously, the lower atmosphere and the full extended upper atmosphere of HD 209458b have been observed, whereas here we probe a layer where the escaping gas forms in the upper atmosphere of HD 209458b.     

Ebola virus entry requires the cholesterol transporter Niemann-Pick C1

Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.     

Autophagy in immunity and inflammation

Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy - the 'autophagy proteins' - orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases.     

The role of site accessibility in microRNA target recognition

MicroRNAs are key regulators of gene expression, but the precise mechanisms underlying their interaction with their mRNA targets are still poorly understood. Here, we systematically investigate the role of target-site accessibility, as determined by base-pairing interactions within the mRNA, in microRNA target recognition. We experimentally show that mutations diminishing target accessibility substantially reduce microRNA-mediated translational repression, with effects comparable to those of mutations that disrupt sequence complementarity. We devise a parameter-free model for microRNA-target interaction that computes the difference between the free energy gained from the formation of the microRNA-target duplex and the energetic cost of unpairing the target to make it accessible to the microRNA. This model explains the variability in our experiments, predicts validated targets more accurately than existing algorithms, and shows that genomes accommodate site accessibility by preferentially positioning targets in highly accessible regions. Our study thus demonstrates that target accessibility is a critical factor in microRNA function.     

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ～10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.     

Note on occurrence of Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) in Montana: a new state record

The parasitic wasp Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) was collected at 4 sites within a canyon reach of the Kootenai River in Lincoln County, Montana. This minute species has only recently been described, but it appears to have a large distribution throughout the United States and to be associated with upland and riparian forests. La avispa parasitaria Mymaromella pala Huber y Gibson (Hymenoptera: Mymarommatidae) se recolectó en cuatro sitios a lo largo de un cañón del Río Kootenai en Lincoln Co., MT. Hace poco que se describió esta especie diminuta, pero parece tener una distribución extensa en los EE.UU. y estar asociada con bosques altos y ribereños.     

The stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression

Most preneoplastic lesions are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. Here we report that tissue-specific inactivation of the stress signaling kinase MKK7 in KRas(G12D)-driven lung carcinomas and NeuT-driven mammary tumors markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53, which is required for cell cycle arrest and suppression of epithelial cancers. These results show that MKK7 functions as a major tumor suppressor in lung and mammary cancer in mouse and identify MKK7 as a vital molecular sensor to set a cellular anti-cancer barrier.     

A bibliographical study of the introduction of Lavoisier's Traité élémentaire de chimie into Great Britain and America

As the most famous woman scientist of the twentieth century, there has been no shortage of books and articles on the life and career of Marie Curie (1867–1934). Her role as a director of a laboratory-based research school in the new scientific field of radioactivity, a field which embraced both chemistry and physics, however, has never been examined. In recent years, there has been a growing interest in the question of research schools, and Morrell, Ravetz, Geison, and Klosterman, amongst others, have written on this subject. Using, in part, the methodology of Morrell, this paper investigates the role of Marie Curie as a school director in the Paris Faculty in the years 1907–14, examining the work and characteristics of her school and assessing her effectiveness as a director.