Structure and function of a membrane component SecDF that enhances protein export

Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF, which associates with SecYEG. The role of SecDF has remained unclear, although it is proposed to function in later stages of translocation as well as in membrane protein biogenesis. Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3?? resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4. Higher-resolution analysis of the periplasmic domains suggested that P1, which binds an unfolded protein, undergoes functionally important conformational changes. In vitro analyses identified an ATP-independent step of protein translocation that requires both SecDF and proton motive force. Electrophysiological analyses revealed that SecDF conducts protons in a manner dependent on pH and the presence of an unfolded protein, with conserved Asp and Arg residues at the transmembrane interface between SecD and SecF playing essential roles in the movements of protons and preproteins. Therefore, we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation.     

Macrobenthic communities in water bodies and streams of Svalbard,Norway

Diversity of macrobenthic communities was studied from water bodies and streams of Spitsbergen, Svalbard archipelago, Norway. In total 162 quantitative samples from different regions of Spitsbergen were analysed in relation to environmental variables. Macrobenthic communities were found on all kinds of substrates (except for the periglacial zone), representing a wide range of biological communities: solid-bottom, soft-bottom, macrophytes and small brook associated. However, taxonomical structure is very simplified, with particular dominance of the Chironomidae family. Chironomid larvae dominated highly in diversity, abundance and biomass. Overall macrobenthic communities were characteristic, with remarkable dominance of one species and general omnipresent taxonomical scarcity (average 2.8 species per sample). In total we found 30 taxa. We distinguished 16 types of macrobenthis communities, with characteristic dominance of different taxa: chironomids (11 types), oligochaete Enchytraeidae family (3), caddisfly Apatania zonella (1) and gammarid amphipod Gammarus setosus (1). Regarding environmental variables, temperature and pH had the most significant influence on the abundance of macrobenthic organisms. It is hypothesized that the structural convergence of different types of communities is their common response to extreme high Arctic living conditions. On the other hand, different chironomids may dominate in the same habitats and water bodies. This gives the effect of lower average similarity of communities and high β-diversity.     

Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway

Modulation of tumor suppressor activities may provide new opportunities for cancer therapy. Here we show that disruption of the gene Ppm1d encoding Wip1 phosphatase activated the p53 and p16 (also called Ink4a)-p19 (also called ARF) pathways through p38 MAPK signaling and suppressed in vitro transformation of mouse embryo fibroblasts (MEFs) by oncogenes. Disruption of the gene Cdkn2a (encoding p16 and p19), but not of Trp53 (encoding p53), reconstituted cell transformation in Ppm1d-null MEFs. In vivo, deletion of Ppm1d in mice bearing mouse mammary tumor virus (MMTV) promoter-driven oncogenes Erbb2 (also called c-neu) or Hras1 impaired mammary carcinogenesis, whereas reduced expression of p16 and p19 by methylation-induced silencing or inactivation of p38 MAPK correlated with tumor appearance. We conclude that inactivation or depletion of the Wip1 phosphatase with resultant p38 MAPK activation suppresses tumor appearance by modulating the Cdkn2a tumor-suppressor locus.     

Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR

Many biochemical processes proceed through the formation of functionally significant intermediates. Although the identification and characterization of such species can provide vital clues about the mechanisms of the reactions involved, it is challenging to obtain information of this type in cases where the intermediates are transient or present only at low population. One important example of such a situation involves the folding behaviour of small proteins that represents a model for the acquisition of functional structure in biology. Here we use relaxation dispersion nuclear magnetic resonance (NMR) spectroscopy to identify, for two mutational variants of one such protein, the SH3 domain from Fyn tyrosine kinase, a low-population folding intermediate in equilibrium with its unfolded and fully folded states. By performing the NMR experiments at different temperatures, this approach has enabled characterization of the kinetics and energetics of the folding process as well as providing structures of the intermediates. A general strategy emerges for an experimental determination of the energy landscape of a protein by applying this methodology to a series of mutants whose intermediates have differing degrees of native-like structure.     

Metal saturation in the upper mantle

The oxygen fugacity f(O2)of the Earth's mantle is one of the fundamental variables in mantle petrology. Through ferric-ferrous iron and carbon-hydrogen-oxygen equilibria, f(O2) influences the pressure-temperature positions of mantle solidi and compositions of small-degree mantle melts. Among other parameters, f(O2) affects the water storage capacity and rheology of the mantle. The uppermost mantle, as represented by samples and partial melts, is sufficiently oxidized to sustain volatiles, such as H2O and CO2, as well as carbonatitic melts, but it is not known whether the shallow mantle is representative of the entire upper mantle. Using high-pressure experiments, we show here that large parts of the asthenosphere are likely to be metal-saturated. We found that pyroxene and garnet synthesized at >7 GPa in equilibrium with metallic Fe can incorporate sufficient ferric iron that the mantle at >250 km depth is so reduced that an (Fe,Ni)-metal phase may be stable. Our results indicate that the oxidized nature of the upper mantle can no longer be regarded as being representative for the Earth's upper mantle as a whole and instead that oxidation is a shallow phenomenon restricted to an upper veneer only about 250 km in thickness.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.     

Ferrissia californica (Gastropoda: Planorbidae): the first record of a global invader in a cave habitat

Ferrissia californica (Rowell, 1863), an aquatic pulmonate [formerly widely known as Ferrisia fragilis (Tryon, 1863), is reported herein to have established a population in the Tskhal-Tsiteli, or Iazoni, Cave (Caucasus, Georgia), within the invasive range of this species. This is the first record of a sustained population of an invasive freshwater pulmonate in an underground environment. Possible consequences of this invasion are briefly discussed. It is possible that this alien snail may threaten the native snail species Motsametia borutzkii (Zhadin, 1932), which is endemic to Tskhal-Tsiteli Cave.     

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.     

Seismological evidence for mosaic structure of the surface of the Earth's inner core

The transition from the Earth's solid inner core to liquid outer core is the location where the inner core grows and from which compositional convection in the outer core originates. Most seismological models of the Earth describe the inner-core boundary as sharp and simple, although experimental data requiring the presence of a thin transition layer at the bottom of the outer core have been reported. The density jump at the inner-core boundary--an important parameter determining gravitational energy release and constraining the compositional difference between the inner and outer core-is also not well known. Estimates of this density jump obtained using free-oscillation eigenfrequencies give low values of 0.25-1.0 g cm(-3), whereas a method using the amplitude ratio of core-reflected phases yielded values of 0.6-1.8 g cm(-3) (refs 14, 15, 16-17). Here we analyse properties of waves precritically reflected from the Earth's inner core (PKiKP phases) that show significant variability in amplitude, consistent high-frequency content and stable travel times with respect to a standard Earth model. We infer that the data are best explained by a mosaic structure of the inner core's surface. Such a mosaic may be composed of patches in which the transition from solid inner to liquid outer core includes a thin partially liquid layer interspersed with patches containing a sharp transition.