Relaxation of hot electrons in a degenerate two-dimensional electron system: transition to one-dimensional scattering

The energy relaxation channels of hot electrons far from thermal equilibrium in a degenerate two-dimensional electron system are investigated in transport experiments in a mesoscopic three-terminal device. We observe a transition from two dimensions at zero magnetic field to quasi--one-dimensional scattering of the hot electrons in a strong magnetic field. In the two-dimensional case electron-electron scattering is the dominant relaxation mechanism, while the emission of optical phonons becomes more and more important as the magnetic field is increased. The observation of up to 11 optical phonons emitted per hot electron allows us to determine the onset energy of LO phonons in GaAs at cryogenic temperatures with a high precision, \eph=36.0\pm0.1\,meV. Numerical calculations of electron-electron scattering and the emission of optical phonons underline our interpretation in terms of a transition to one-dimensional dynamics.Comment: 15 pages, 9 figure

Mild Electrical Stimulation with Heat Shock Ameliorates Insulin Resistance via Enhanced Insulin Signaling

Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway

Rabies Management Implications Based on Raccoon Population Density Indexes

An estimate or index of target species density is important in determining oral rabies vaccination (ORV) bait densities to control and eliminate specific rabies variants. From 1997–2011, we indexed raccoon (Procyon lotor) densities 253 times based on cumulative captures on 163 sites from Maine to Alabama, USA, near ORV zones created to prevent raccoon rabies from spreading to new areas. We conducted indexing under a common cage trapping protocol near the time of annual ORV to aid in bait density decisions. Unique raccoons (n = 8,415) accounted for 68.0% of captures (n = 12,367). We recaptured raccoons 2,669 times. We applied Schnabel and Huggins mark‐recapture models on sites with ≥3 years of capture data and ≥25% recaptures as context for raccoon density indexes (RDIs). Simple linear relationships between RDIs and mark‐recapture estimates supported application of our 2 index. Raccoon density indexes ranged from 0.0–56.9 raccoons/km . For bait density decisions, we evaluated RDIs in the following 4 raccoon density groups, which were statistically different: (0.0–5.0 [n = 70], 5.1–15.0 [n = 129], 15.1–25.0 [n = 31], and \u3e25.0 raccoons/km2 [n = 23]). Mean RDI was positively associated with a higher percentage of developed land cover and a lower percentage of evergreen forest. Non‐target species composition (excluding recaptured raccoons) accounted for 32.0% of captures. Potential bait competitors accounted for 76.5% of non‐targets. The opossum (Didelphis virginiana) was the primary potential bait competitor from 27°N to 44°N latitude, north of which it was numerically replaced by the striped skunk (Mephitis mephitis). We selected the RDI approach over mark-recapture methods because of costs, geographic scope, staff availability, and the need for supplemental serologic samples. The 4 density groups provided adequate sensitivity to support bait density decisions for the current 2 bait density options. Future improvements to the method include providing random trapping locations to field personnel to prevent trap clustering and marking non‐targets to better characterize bait competitors

Sry delivery to the adrenal medulla increases blood pressure and adrenal medullary tyrosine hydroxylase of normotensive WKY rats

BACKGROUND: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes. METHODS: The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 μg of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection. RESULTS: In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2–3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage. CONCLUSION: These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity

Curcumin Prevents High Fat Diet Induced Insulin Resistance and Obesity via Attenuating Lipogenesis in Liver and Inflammatory Pathway in Adipocytes

Background: Mechanisms underlying the attenuation of body weight gain and insulin resistance in response to high fat diet (HFD) by the curry compound curcumin need to be further explored. Although the attenuation of the inflammatory pathway is an accepted mechanism, a recent study suggested that curcumin stimulates Wnt signaling pathway and hence suppresses adipogenic differentiation. This is in contrast with the known repressive effect of curcumin on Wnt signaling in other cell lineages. Methodology and Principal Findings: We conducted the examination on low fat diet, or HFD fed C57BL/6J mice with or without curcumin intervention for 28 weeks. Curcumin significantly attenuated the effect of HFD on glucose disposal, body weight/fat gain, as well as the development of insulin resistance. No stimulatory effect on Wnt activation was observed in the mature fat tissue. In addition, curcumin did not stimulate Wnt signaling in vitro in primary rat adipocytes. Furthermore, curcumin inhibited lipogenic gene expression in the liver and blocked the effects of HFD on macrophage infiltration and the inflammatory pathway in the adipose tissue. Conclusions and Significance: We conclude that the beneficial effect of curcumin during HFD consumption is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue, in the absence o

Gene regulatory network reveals oxidative stress as the underlying molecular mechanism of type 2 diabetes and hypertension

<p>Abstract</p> <p>Background</p> <p>The prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.</p> <p>Methods</p> <p>The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.</p> <p>Results</p> <p>By analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.</p> <p>Conclusion</p> <p>The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.</p

Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads to reduction in the height of preformed thrombi

Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation and inhibition. We hypothesised that Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton reversing platelet spreading, and therefore reduce the capability of thrombi to withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate, and a PKG-activating cGMP analogue reversed stress fibre formation and increased actin nodule formation in adherent platelets. This effect is sGC dependent and independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at ser188 in spread platelets. Interestingly NO and PGI2 synergise to reverse stress fibre formation at physiologically relevant concentrations. Analysis of high shear conditions indicated that platelets activated on fibrinogen, induced stress fibre formation, which was reversed by GSNO treatment. Furthermore, preformed thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus height in comparison to the control. This study demonstrates that NO can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling excessive thrombosis

Analytical expressions for stopping-power ratios relevant for accurate dosimetry in particle therapy

In particle therapy, knowledge of the stopping-power ratios (STPRs) of the ion beam for air and water is necessary for accurate ionization chamber dosimetry. Earlier work has investigated the STPRs for pristine carbon ion beams, but here we expand the calculations to a range of ions (1 <= z <= 18) as well as spread out Bragg peaks (SOBPs) and provide a theoretical in-depth study with a special focus on the parameter regime relevant for particle therapy. The Monte Carlo transport code SHIELD-HIT is used to calculate complete particle-fluence spectra which are required for determining STPRs according to the recommendations of the International Atomic Energy Agency (IAEA). We confirm that the STPR depends primarily on the current energy of the ions rather than on their charge z or absolute position in the medium. However, STPRs for different sets of stopping-power data for water and air recommended by the International Commission on Radiation Units & Measurements (ICRU) are compared, including also the recently revised data for water, yielding deviations up to 2% in the plateau region. In comparison, the influence of the secondary particle spectra on the STPR is about two orders of magnitude smaller in the whole region up till the practical range. The gained insights enable us to propose an analytic approximation for the STPR for both pristine and SOBPs as a function of penetration depth, which parametrically depend only on the initial energy and the residual range of the ion, respectively.Comment: 21 pages, 5 figures, fixed bug with figures in v

cGMP becomes a drug target

Cyclic guanosine 3′,5′-monophosphate (cGMP) serves as a second messenger molecule, which regulates pleiotropic cellular functions in health and disease. cGMP is generated by particulate or soluble guanylyl cyclases upon stimulation with natriuretic peptides or nitric oxide, respectively. Furthermore, the cGMP concentration is modulated by cGMP-degrading phosphodiesterases. Several targets of cGMP are utilized to effect its various cellular functions. These effector molecules comprise cGMP-dependent protein kinases, ion channels, and phosphodiesterases. During the last decade, it emerged that cGMP is a novel drug target for the treatment of pulmonary and cardiovascular disorders. In this respect, several drugs were developed, which are now in clinical phase studies for, e.g., pulmonary hypertension or cardiovascular diseases. These new drugs act NO-independently with/without heme on soluble guanylyl cyclases or induce subtypes of particular guanylyl cyclases and thereby lead to new therapeutic concepts and horizons. In this regard, the fifth cGMP meeting held in June 2011 in Halle, Germany, comprised the new therapeutic challenges with the novel functional and structural concepts of cGMP generating and effector molecules. This report summarizes the new data on molecular mechanisms, (patho)physiological relevance, and therapeutic potentials of the cGMP signaling system that were presented at this meeting