Disruption of the Hippocampal and Hypothalamic Blood-Brain Barrier in a Diet-Induced Obese Model of Type II Diabetes: Prevention and Treatment by the Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. Methods: BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. Results: High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Conclusions: Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial carbonic anhydrase inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model

Recent and future trends in synthetic greenhouse gas radiative forcing

Atmospheric measurements show that emissions of hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons are now the primary drivers of the positive growth in synthetic greenhouse gas (SGHG) radiative forcing. We infer recent SGHG emissions and examine the impact of future emissions scenarios, with a particular focus on proposals to reduce HFC use under the Montreal Protocol. If these proposals are implemented, overall SGHG radiative forcing could peak at around 355 mW m[superscript −2] in 2020, before declining by approximately 26% by 2050, despite continued growth of fully fluorinated greenhouse gas emissions. Compared to “no HFC policy” projections, this amounts to a reduction in radiative forcing of between 50 and 240 mW m[superscript −2] by 2050 or a cumulative emissions saving equivalent to 0.5 to 2.8 years of CO2 emissions at current levels. However, more complete reporting of global HFC emissions is required, as less than half of global emissions are currently accounted for.Natural Environment Research Council (Great Britain) (Advanced Research Fellowship NE/I021365/1)United States. National Aeronautics and Space Administration (Upper Atmospheric Research Program Grant NNX11AF17G)United States. National Oceanic and Atmospheric Administratio

Revisiting the anatomy of the cephalic vein, its origin, course and possible clinical correlations in relation to the anatomical snuffbox among Jordanian

Background: The cephalic vein is one of the most distinguished superficial veins of the upper limb. Its clinical value lies in venous access. There is little known about the variation of its formation in relation to the anatomical snuffbox. Hence, anatomical variants in the origin of the cephalic vein are important in clinical practice. Subsequently, this study was designed to examine the variation of the cephalic vein formation in relation to the anatomical snuffbox. Materials and methods: A cross-sectional study of 438 subjects (722 hands), was prepared to study the cephalic vein among Jordanian students and staff of one of the major governmental Medical College in Jordan, by using infrared illumination system. The obtained data was analysed according to; gender, sidedness, and handedness. Results: Four sites for the formation of the cephalic vein in relation to the anatomical snuffbox were found. There was a significant relation between gender and sidedness, and the sites of formation of the cephalic vein (p < 0.0001 and p = 0.048, respectively). Conclusions: For the first time this study identified different sites for the formation of the cephalic vein in relation to the anatomical snuffbox. However, regardless of its sites of formation, the cephalic vein was running in 98% of the examined hands in the anatomical snuffbox

The variability of methane, nitrous oxide and sulfur hexafluoride in Northeast India

High-frequency atmospheric measurements of methane (CH[subscript 4]), nitrous oxide (N[subscript 2]O) and sulfur hexafluoride (SF[subscript 6]) from Darjeeling, India are presented from December 2011 (CH[subscript 4])/March 2012 (N[subscript 2]O and SF[subscript 6]) through February 2013. These measurements were made on a gas chromatograph equipped with a flame ionization detector and electron capture detector, and were calibrated on the Tohoku University, the Scripps Institution of Oceanography (SIO)-98 and SIO-2005 scales for CH[subscript 4], N[subscript 2]O and SF[subscript 6], respectively. The observations show large variability and frequent pollution events in CH[subscript 4] and N[subscript 2]O mole fractions, suggesting significant sources in the regions sampled by Darjeeling throughout the year. By contrast, SF[subscript 6] mole fractions show little variability and only occasional pollution episodes, likely due to weak sources in the region. Simulations using the Numerical Atmospheric dispersion Modelling Environment (NAME) particle dispersion model suggest that many of the enhancements in the three gases result from the transport of pollutants from the densely populated Indo-Gangetic Plains of India to Darjeeling. The meteorology of the region varies considerably throughout the year from Himalayan flows in the winter to the strong south Asian summer monsoon. The model is consistent in simulating a diurnal cycle in CH[subscript 4] and N[subscript 2]O mole fractions that is present during the winter but absent in the summer and suggests that the signals measured at Darjeeling are dominated by large-scale (~100 km) flows rather than local (<10 km) flows.Massachusetts Institute of Technology. Center for Global Change Science (Director's Fund)Massachusetts Institute of Technology. Joint Program on the Science & Policy of Global ChangeMartin Family Society of Fellows for SustainabilityMIT Energy InitiativeMIT International Science and Technology InitiativeUnited States. National Aeronautics and Space Administration (Grant NNX11AF17G)United States. National Oceanic and Atmospheric Administration (Contract RA133R09CN0062

Greenhouse gas measurements from a UK network of tall towers: technical description and first results

A network of three tall tower measurement stations was set up in 2012 across the United Kingdom to expand measurements made at the long-term background northern hemispheric site, Mace Head, Ireland. Reliable and precise in situ greenhouse gas (GHG) analysis systems were developed and deployed at three sites in the UK with automated instrumentation measuring a suite of GHGs. The UK Deriving Emissions linked to Climate Change (UK DECC) network uses tall (165–230 m) open-lattice telecommunications towers, which provide a convenient platform for boundary layer trace gas sampling. In this paper we describe the automated measurement system and first results from the UK DECC network for CO2, CH4, N2O, SF6, CO and H2. CO2 and CH4 are measured at all of the UK DECC sites by cavity ring-down spectroscopy (CRDS) with multiple inlet heights at two of the three tall tower sites to assess for boundary layer stratification. The short-term precisions (1σ on 1 min means) of CRDS measurements at background mole fractions for January 2012 to September 2015 is < 0.05 µmol mol−1 for CO2 and < 0.3 nmol mol−1 for CH4. Repeatability of standard injections (1σ) is < 0.03 µmol mol−1 for CO2 and < 0.3 nmol mol−1 for CH4 for the same time period. N2O and SF6 are measured at three of the sites, and CO and H2 measurements are made at two of the sites, from a single inlet height using gas chromatography (GC) with an electron capture detector (ECD), flame ionisation detector (FID) or reduction gas analyser (RGA). Repeatability of individual injections (1σ) on GC and RGA instruments between January 2012 and September 2015 for CH4, N2O, SF6, CO and H2 measurements were < 2.8 nmol mol−1, < 0.4 nmol mol−1, < 0.07 pmol mol−1, < 2 nmol mol−1 and < 3 nmol mol−1, respectively. Instrumentation in the network is fully automated and includes sensors for measuring a variety of instrumental parameters such as flow, pressures, and sampling temperatures. Automated alerts are generated and emailed to site operators when instrumental parameters are not within defined set ranges. Automated instrument shutdowns occur for critical errors such as carrier gas flow rate deviations. Results from the network give good spatial and temporal coverage of atmospheric mixing ratios within the UK since early 2012. Results also show that all measured GHGs are increasing in mole fraction over the selected reporting period and, except for SF6, exhibit a seasonal trend. CO2 and CH4 also show strong diurnal cycles, with night-time maxima and daytime minima in mole fractions

Search for Relativistic Magnetic Monopoles with IceCube

We present the first results in the search for relativistic magnetic monopoles with the IceCube detector, a subsurface neutrino telescope located in the South Polar ice cap containing a volume of 1 km$^{3}$. This analysis searches data taken on the partially completed detector during 2007 when roughly 0.2 km$^{3}$ of ice was instrumented. The lack of candidate events leads to an upper limit on the flux of relativistic magnetic monopoles of \Phi_{\mathrm{90%C.L.}}\sim 3\e{-18}\fluxunits for $\beta\geq0.8$. This is a factor of 4 improvement over the previous best experimental flux limits up to a Lorentz boost $\gamma$ below $10^{7}$. This result is then interpreted for a wide range of mass and kinetic energy values.Comment: 11 pages, 11 figures. v2 is minor text edits, no changes to resul