Cellular hypoxia: a key modulator of adipocyte function in obesity?

We have proposed that hypoxia develops in adipose tissue (white) as tissue mass expands in obesity, this leading to the inflammatory response which is considered to underpin the development of obesity-associated diseases. Direct evidence for hypoxia in adipose tissue in obesity has now been obtained in mice and in humans. Studies on adipocytes, both human and murine, in cell culture have shown that the expression and release of several inflammation-related adipokines, such as IL-6, leptin and VEGF are stimulated by low pO2. The production of adiponectin, which has anti-inflammatory and insulin-sensitising actions, is, however, inhibited. Glucose uptake and the release of lactate are increased in adipocytes by hypoxia, with a corresponding increase in the level of the GLUT1 and MCT1 transporters, consistent with a switch to glycolytic metabolism. In preadipocytes, which do not normally synthesize leptin, low pO2 leads to induction of the expression and secretion of this key hormone. Recent studies suggest that there are important interactions between hypoxia and specific long-chain fatty acids in the production of inflammation-related adipokines. It is suggested that hypoxia has a pervasive effect on adipocyte physiology and is central to the dysregulation of adipose tissue function that occurs in obesity.Adipobiology 2009; 1: 19-26

Roles of forest bioproductivity, transpiration and fire in a nine-year record of cave dripwater chemistry from southwest Australia

Forest biomass has the potential to significantly impact the chemistry and volume of diffuse recharge to cave dripwater via the processes of nutrient uptake, transpiration and forest fire. Yet to-date, this role has been under-appreciated in the interpretation of speleothem trace element records from forested catchments. In this study, the impact of vegetation is examined and quantified in a long-term monitoring program from Golgotha Cave, SW Australia. The contribution of salts from rain and dry-deposition of aerosols and dissolved elements from soil mineral and bedrock dissolution to dripwater chemistry are also examined. This study is an essential pre-requisite for the future interpretation of trace element data from SW Australian stalagmite records, whose record of past environmental change will include alterations in these biogeochemical fluxes. Solute concentrations in dripwater vary spatially, supporting the existence of distinct flow paths governed by varying amounts of transpiration as well as nutrient uptake by deeply-rooted biomass. Applying principal components analysis, we identify a common pattern of variation in dripwater Cl, Mg, K, Ca, Sr and Si, interpreted as reflecting increasing transpiration, due to forest growth. Mass-balance calculations show that increasing elemental sequestration into biomass has the largest impact on SO4, providing an explanation for the overall falling dripwater SO4 concentrations through time, in contrast to the transpiration-driven rising trend dominating other ions. The long-term rise in transpiration and nutrient uptake driven by increased forest bioproductivity and its impact on our dripwater chemistry is attributed to i. the post-fire recovery of the forest understorey after fire impacted the site in 2006 CE; ii. and/or increased water and nutrient demand as trees in the overlying forest mature. The impact of climate-driven changes on the water balance is also examined. Finally, the implications for interpreting SW Australian speleothem trace element records are discussed

Geoantineutrino Spectrum, 3He/4He-ratio Distribution in the Earth's Interior and Slow Nuclear Burning on the Boundary of the Liquid and Solid Phases of the Earth's Core

The description problem of geoantineutrino spectrum and reactor antineutrino experimental spectrum in KamLAND, which takes place for antineutrino energy \~2.8 MeV, and also the experimental results of the interaction of uranium dioxide and carbide with iron-nickel and silicaalumina melts at high pressure (5-10 GP?) and temperature (1600-2200C) have motivated us to consider the possible consequences of the assumption made by V.Anisichkin and coauthors that there is an actinid shell on boundary of liquid and solid phases of the Earth's core. We have shown that the activation of a natural nuclear reactor operating as the solitary waves of nuclear burning in 238U- and/or 232Th-medium (in particular, the neutron- fission progressive wave of Feoktistov and/or Teller-Ishikawa-Wood) can be such a physical consequence. The simplified model of the kinetics of accumulation and burnup in U-Pu fuel cycle of Feoktistov is developed. The results of the numerical simulation of neutron-fission wave in two-phase UO2/Fe medium on a surface of the Earth's solid core are presented. The georeactor model of 3He origin and the 3He/4He-ratio distribution in the Earth's interior is offered. It is shown that the 3He/4He ratio distribution can be the natural quantitative criterion of georeactor thermal power. On the basis of O'Nions-Evensen-Hamilton geochemical model of mantle differentiation and the crust growth supplied by actinid shell on the boundary of liquid and solid phases of the Earth's core as a nuclear energy source (georeactor with power of 30 TW), the tentative estimation of geoantineutrino intensity and geoantineutrino spectrum on the Earth surface are given.Comment: 28 pages, 12 figures. Added text, formulas, figures and references. Corrected equations. Changed content of some section

A national facility for biological cryo-electron microscopy

Three-dimensional electron microscopy is an enormously powerful tool for structural biologists. It is now able to provide an understanding of the molecular machinery of cells, disease processes and the actions of pathogenic organisms from atomic detail through to the cellular context. However, cutting-edge research in this field requires very substantial resources for equipment, infrastructure and expertise. Here, a brief overview is provided of the plans for a UK national three-dimensional electron-microscopy facility for integrated structural biology to enable internationally leading research on the machinery of life. State-of-the-art equipment operated with expert support will be provided, optimized for both atomic-level single-particle analysis of purified macromolecules and complexes and for tomography of cell sections. The access to and organization of the facility will be modelled on the highly successful macromolecular crystallography (MX) synchrotron beamlines, and will be embedded at the Diamond Light Source, facilitating the development of user-friendly workflows providing near-real-time experimental feedback

Monitoring quality of care in hepatocellular carcinoma: A modified delphi consensus

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE