223 research outputs found

    A Drosophila functional evaluation of candidates from human genome-wide association studies of type 2 diabetes and related metabolic traits identifies tissue-specific roles for dHHEX

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    BACKGROUND: Genome-wide association studies (GWAS) identify regions of the genome that are associated with particular traits, but do not typically identify specific causative genetic elements. For example, while a large number of single nucleotide polymorphisms associated with type 2 diabetes (T2D) and related traits have been identified by human GWAS, only a few genes have functional evidence to support or to rule out a role in cellular metabolism or dietary interactions. Here, we use a recently developed Drosophila model in which high-sucrose feeding induces phenotypes similar to T2D to assess orthologs of human GWAS-identified candidate genes for risk of T2D and related traits. RESULTS: Disrupting orthologs of certain T2D candidate genes (HHEX, THADA, PPARG, KCNJ11) led to sucrose-dependent toxicity. Tissue-specific knockdown of the HHEX ortholog dHHEX (CG7056) directed metabolic defects and enhanced lethality; for example, fat-body-specific loss of dHHEX led to increased hemolymph glucose and reduced insulin sensitivity. CONCLUSION: Candidate genes identified in human genetic studies of metabolic traits can be prioritized and functionally characterized using a simple Drosophila approach. To our knowledge, this is the first large-scale effort to study the functional interaction between GWAS-identified candidate genes and an environmental risk factor such as diet in a model organism system

    Electrochemistry at nanoscale electrodes : individual single-walled carbon nanotubes (SWNTs) and SWNT-templated metal nanowires

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    Individual nanowires (NWs) and native single-walled carbon nanotubes (SWNTs) can be readily used as well-defined nanoscale electrodes (NSEs) for voltammetric analysis. Here, the simple photolithography-free fabrication of submillimeter long Au, Pt, and Pd NWs, with sub-100 nm heights, by templated electrodeposition onto ultralong flow-aligned SWNTs is demonstrated. Both individual Au NWs and SWNTs are employed as NSEs for electron-transfer (ET) kinetic quantification, using cyclic voltammetry (CV), in conjunction with a microcapillary-based electrochemical method. A small capillary with internal diameter in the range 30–70 μm, filled with solution containing a redox-active mediator (FcTMA+ ((trimethylammonium)methylferrocene), Fe(CN)64–, or hydrazine) is positioned above the NSE, so that the solution meniscus completes an electrochemical cell. A 3D finite-element model, faithfully reproducing the experimental geometry, is used to both analyze the experimental CVs and derive the rate of heterogeneous ET, using Butler–Volmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k0, up to ca. 1 cm s–1 can be resolved. Using the same experimental configuration the electrochemistry of individual SWNTs can also be accessed. For FcTMA+/2+ electrolysis the simulated ET kinetic parameters yield very fast ET kinetics (k0 > 2 ± 1 cm s–1). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double-layer effects may influence ET at the nanoscale

    Using the nonlinear control of anaesthesia-induced hypersensitivity of EEG at burst suppression level to test the effects of radiofrequency radiation on brain function

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    Background In this study, investigating the effects of mobile phone radiation on test animals, eleven pigs were anaesthetised to the level where burst-suppression pattern appears in the electroencephalogram (EEG). At this level of anaesthesia both human subjects and animals show high sensitivity to external stimuli which produce EEG bursts during suppression. The burst-suppression phenomenon represents a nonlinear control system, where low-amplitude EEG abruptly switches to very high amplitude bursts. This switching can be triggered by very minor stimuli and the phenomenon has been described as hypersensitivity. To test if also radio frequency (RF) stimulation can trigger this nonlinear control, the animals were exposed to pulse modulated signal of a GSM mobile phone at 890 MHz. In the first phase of the experiment electromagnetic field (EMF) stimulation was randomly switched on and off and the relation between EEG bursts and EMF stimulation onsets and endpoints were studied. In the second phase a continuous RF stimulation at 31 W/kg was applied for 10 minutes. The ECG, the EEG, and the subcutaneous temperature were recorded. Results No correlation between the exposure and the EEG burst occurrences was observed in phase I measurements. No significant changes were observed in the EEG activity of the pigs during phase II measurements although several EEG signal analysis methods were applied. The temperature measured subcutaneously from the pigs' head increased by 1.6°C and the heart rate by 14.2 bpm on the average during the 10 min exposure periods. Conclusion The hypothesis that RF radiation would produce sensory stimulation of somatosensory, auditory or visual system or directly affect the brain so as to produce EEG bursts during suppression was not confirmed.BioMed Central Open acces

    Natural climate solutions for the United States

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    © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517

    Happiness around the world: A combined etic-emic approach across 63 countries

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    What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emicetic approach (Cheung, van de Vijver &amp; Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky &amp; Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto &amp; Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

    Development and recent progress on ammonia synthesis catalysts for Haber–Bosch process

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    Due to its essential use as a fertilizer, ammonia synthesis from nitrogen and hydrogen is considered to be one of the most important chemical processes of the last 100 years. Since then, an enormous amount of work has been undertaken to investigate and develop effective catalysts for this process. Although the catalytic synthesis of ammonia has been extensively studied in the last century, many new catalysts are still currently being developed to reduce the operating temperature and pressure of the process and to improve the conversion of reactants to ammonia. New catalysts for the Haber–Bosch process are the key to achieving green ammonia production in the foreseeable future. Herein, the history of ammonia synthesis catalyst development is briefly described as well as recent progress in catalyst development with the aim of building an overview of the current state of ammonia synthesis catalysts for the Haber–Bosch process. The new emerging ammonia synthesis catalysts, including electride, hydride, amide, perovskite oxide hydride/oxynitride hydride, nitride, and oxide promoted metals such as Fe, Co, and Ni, are promising alternatives to the conventional fused‐Fe and promoted‐Ru catalysts for existing ammonia synthesis plants and future distributed green ammonia synthesis based on the Haber–Bosch process
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