SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Huntingtons disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies

Low Gain Avalanche Detectors (LGAD) for particle physics and synchrotron applications

A new avalanche silicon detector concept is introduced with a low gain in the region of ten, known as a Low Gain Avalanche Detector, LGAD. The detector's characteristics are simulated via a full process simulation to obtain the required doping profiles which demonstrate the desired operational characteristics of high breakdown voltage (500 V) and a gain of 10 at 200 V reverse bias for X-ray detection. The first low gain avalanche detectors fabricated by Micron Semiconductor Ltd are presented. The doping profiles of the multiplication junctions were measured with SIMS and reproduced by simulating the full fabrication process which enabled further development of the manufacturing process. The detectors are 300 μm thick p-type silicon with a resistivity of 8.5 kΩcm, which fully depletes at 116 V. The current characteristics are presented and demonstrate breakdown voltages in excess of 500 V and a current density of 40 to 100 nAcm−2 before breakdown measured at 20oC. The gain of the LGAD has been measured with a red laser (660 nm) and shown to be between 9 and 12 for an external bias voltage range from 150 V to 300 V

A search for rotating radio transients and fast radio bursts in the Parkes high-latitude pulsar survey

Discoveries of rotating radio transients and fast radio bursts (FRBs) in pulsar surveys suggest that more of such transient sources await discovery in archival data sets. Here we report on a single-pulse search for dispersed radio bursts over a wide range of Galactic latitudes (|b| < $60^{\circ}$) in data previously searched for periodic sources by Burgay et al. We re-detected 20 of the 42 pulsars reported by Burgay et al. and one rotating radio transient reported by Burke-Spolaor. No FRBs were discovered in this survey. Taking into account this result, and other recent surveys at Parkes, we corrected for detection sensitivities based on the search software used in the analyses and the different backends used in these surveys and find that the all-sky FRB event rate for sources with a fluence above 4.0 Jy ms at 1.4 GHz to be ${\cal R} = 4.4^{+5.2}_{-3.1} \times 10^3$ FRBs day$^{-1}$ sky$^{-1}$, where the uncertainties represent a $99\%$ confidence interval. While this rate is lower than inferred from previous studies, as we demonstrate, this combined event rate is consistent with the results of all systematic FRB searches at Parkes to date and does not require the need to postulate a dearth of FRBs at intermediate latitudes.Comment: Accepted, 10 pages, 6 figure

Case-control study of arsenic in drinking water and lung cancer in California and Nevada.

Millions of people are exposed to arsenic in drinking water, which at high concentrations is known to cause lung cancer in humans. At lower concentrations, the risks are unknown. We enrolled 196 lung cancer cases and 359 controls matched on age and gender from western Nevada and Kings County, California in 2002-2005. After adjusting for age, sex, education, smoking and occupational exposures, odds ratios for arsenic concentrations ≥85 µg/L (median = 110 µg/L, mean = 173 µg/L, maximum = 1,460 µg/L) more than 40 years before enrollment were 1.39 (95% CI = 0.55-3.53) in all subjects and 1.61 (95% CI = 0.59-4.38) in smokers. Although odds ratios were greater than 1.0, these increases may have been due to chance given the small number of subjects exposed more than 40 years before enrollment. This study, designed before research in Chile suggested arsenic-related cancer latencies of 40 years or more, illustrates the enormous sample sizes needed to identify arsenic-related health effects in low-exposure countries with mobile populations like the U.S. Nonetheless, our findings suggest that concentrations near 100 µg/L are not associated with markedly high relative risks

Tall Fescue and Orchardgrass Productivity and Persistence Under Grazing Systems in Tennessee

The primary forage species used by cow-calf producers in grazing systems in Tennessee is tall-fescue. Tall fescue is considered an excellent cool-season perennial forage crop due to its high quality, production, and extended growing season. However, most of these tall fescue grazing systems are composed of tall fescue cv. Kentucky 31, which is known for containing a fungus endophyte that can be toxic to animals. Alternatively, orchardgrass is also a vastly used and important perennial cool-season forage in the United States. It can be used as a pasture, hay, and is a high-quality forage that is desirable for most livestock producers, especially dairy, beef and equine industries. The goal of this project was to compare four different cool-season forage species under grazing pressure while increasing productivity and persistence of the paddocks. The project assessed herbage mass, botanical composition, morphological composition, along with persistence of four different cool season grasses. While no statistical difference was seen among treatments within a single year for herbage mass, year did influence herbage mass. Additionally, botanical composition was noted as being significant on the year by treatment interaction

Strong Shift Equivalence of C∗C^*-correspondences

We define a notion of strong shift equivalence for $C^*$-correspondences and show that strong shift equivalent $C^*$-correspondences have strongly Morita equivalent Cuntz-Pimsner algebras. Our analysis extends the fact that strong shift equivalent square matrices with non-negative integer entries give stably isomorphic Cuntz-Krieger algebras.Comment: 26 pages. Final version to appear in Israel Journal of Mathematic

Biomass Fuel Use and Cardiac Function in Nepali Women.

BackgroundExposure to household air pollution (HAP) from cooking with biomass fuel affects billions of people. We hypothesized that HAP from woodsmoke, compared to other household fuels, was associated with adverse cardiovascular outcomes, of which there have been few studies.MethodsA cross-sectional study was completed in 299 females aged 40-70 years in Kaski District, Nepal, during 2017-18. All participants underwent a standard 12-lead ECG, ankle and brachial systolic blood pressure measurement, and 2D color and Doppler echocardiography. Current stove type was confirmed by inspection. Blood pressure, height, and weight were measured using a standardized protocol. Hypertension was defined as ≥140/90 mmHg or prior diagnosis. Hemoglobin A1c (HbA1c) was obtained, with diabetes mellitus defined as a prior diagnosis or HbA1C ≥ 6.5%. We used adjusted linear and logistic multivariable regressions to examine the relationship of stove type with cardiac structure and function.ResultsThe majority of women primarily used liquified petroleum gas (LPG) stoves (65%), while 12% used biogas, and 23% used wood-burning cook-stoves. Prevalence of major cardiovascular risk factors was 35% with hypertension, 19% with diabetes mellitus, and 15% current smokers. After adjustment, compared to LPG, wood stove use was associated with increased indexed left atrial volume (β = 3.15, 95% CI 1.22 to 5.09) and increased indexed left ventricular end diastolic volume (β = 7.97, 95% CI 3.11 to 12.83). There was no association between stove type and systemic hypertension, left ventricular mass, systolic dysfunction, diastolic dysfunction, pulmonary hypertension, abnormal ankle-brachial index, or clinically significant ECG abnormalities.ConclusionBiomass fuel use was associated with increased indexed left atrial volume and increased indexed left ventricular diastolic volume in Nepali women, suggesting subclinical adverse cardiac remodeling from HAP in this cross-sectional study. We did not find evidence of an association with hypertension or typical cardiac sequelae of hypertension. Future studies to confirm these results are needed