ABSTRACT
Ketone bodies are the most energy‐efficient fuel and yield more ATP permole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ...ketones via high‐fat, low carbohydrate diets has been used for the treatment of drug‐refractory epilepsy and for neuro degenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a tread mill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palmoil (P < 0.05). Ketone‐fed rats completed an 8‐ arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts fromrats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using 31P‐ NMRspectroscopy. The novelketone diet, therefore, improved physical performance and cognitive function in rats, and its energy‐sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.—Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M.K., Atherton, H. J., Schroeder, M.A., Deacon, R.M. J., Kashiwaya, Y., King, M.T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance. FASEB J. 30, 4021–4032 (2016). www.fasebj.org
Results from a search for neutrinoless double-beta decay (0νββ) of ^{136}Xe are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by ...EXO-200, the energy resolution of the detector has been improved to σ/E=1.23%, the electric field in the drift region has been raised by 50%, and a system to suppress radon in the volume between the cryostat and lead shielding has been implemented. In addition, analysis techniques that improve topological discrimination between 0νββ and background events have been developed. Incorporating these hardware and analysis improvements, the median 90% confidence level 0νββ half-life sensitivity after combining with the full data set acquired before the upgrade has increased twofold to 3.7×10^{25} yr. No statistically significant evidence for 0νββ is observed, leading to a lower limit on the 0νββ half-life of 1.8×10^{25} yr at the 90% confidence level.
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD ...heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h
) for European-American females of 29% that is similar to h
for schizophrenia and is substantially higher than h
in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
The star formation rate (SFR) in the Central Molecular Zone (CMZ, i.e. the central 500 pc) of the Milky Way is lower by a factor of ≥10 than expected for the substantial amount of dense gas it ...contains, which challenges current star formation theories. In this paper, we quantify which physical mechanisms could be responsible. On scales larger than the disc scaleheight, the low SFR is found to be consistent with episodic star formation due to secular instabilities or possibly variations of the gas inflow along the Galactic bar. The CMZ is marginally Toomre-stable when including gas and stars, but highly Toomre-stable when only accounting for the gas, indicating a low condensation rate of self-gravitating clouds. On small scales, we find that the SFR in the CMZ may be caused by an elevated critical density for star formation due to the high turbulent pressure. The existence of a universal density threshold for star formation is ruled out. The H i–H2 phase transition of hydrogen, the tidal field, a possible underproduction of massive stars due to a bottom-heavy initial mass function, magnetic fields, and cosmic ray or radiation pressure feedback also cannot individually explain the low SFR. We propose a self-consistent cycle of star formation in the CMZ, in which the effects of several different processes combine to inhibit star formation. The rate-limiting factor is the slow evolution of the gas towards collapse – once star formation is initiated it proceeds at a normal rate. The ubiquity of star formation inhibitors suggests that a lowered central SFR should be a common phenomenon in other galaxies. We discuss the implications for galactic-scale star formation and supermassive black hole growth, and relate our results to the star formation conditions in other extreme environments.
Context. Small planets transiting bright nearby stars are essential to our understanding of the formation and evolution of exoplanetary systems. However, few constitute prime targets for atmospheric ...characterization, and even fewer are part of multiple star systems. Aims. This work aims to validate TOI-4336 A b, a sub-Neptune-sized exoplanet candidate identified by the TESS space-based transit survey around a nearby M dwarf. Methods. We validated the planetary nature of TOI-4336 A b through the global analysis of TESS and follow-up multi-band high-precision photometric data from ground-based telescopes, medium- and high-resolution spectroscopy of the host star, high-resolution speckle imaging, and archival images. Results. The newly discovered exoplanet TOI-4336 A b has a radius of 2.1 ± 0.1 R ⊕ . Its host star is an M3.5-dwarf star with a mass of 0.33 ± 0.01 M ⊙ and a radius of 0.33 ± 0.02 R ⊙ , and is a member of a hierarchical triple M-dwarf system 22 pc away from the Sun. The planet’s orbital period of 16.3 days places it at the inner edge of the habitable zone of its host star, which is the brightest of the inner binary pair. The parameters of the system make TOI-4336 A b an extremely promising target for the detailed atmospheric characterization of a temperate sub-Neptune by transit transmission spectroscopy with JWST.
Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we ...investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer's disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of β-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress.
Objective: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented ...elderly people. Methods: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing. Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex, age, education, treatment group, and test version when applicable. Results: We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed (p = 0.0075). In addition, we found that the progression in PVWMH volume paralleled the decline in mental processing speed (p = 0.024). In contrast, neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests. Conclusion: PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed.
How the solar wind influences the magnetospheres of the outer planets is a fundamentally important question, but is difficult to answer in the absence of consistent, simultaneous monitoring of the ...upstream solar wind and the large‐scale dynamics internal to the magnetosphere. To compensate for the relative lack of in‐situ solar wind data, propagation models are often used to estimate the ambient solar wind conditions at the outer planets for comparison to remote observations or in‐situ measurements. This introduces another complication: the propagation of near‐Earth solar wind measurements introduces difficult‐to‐assess uncertainties. Here, we present the Multi‐Model Ensemble System for the outer Heliosphere (MMESH) to begin to address these issues, along with the resultant multi‐model ensemble (MME) of the solar wind conditions near Jupiter. MMESH accepts as input any number of solar wind models together with contemporaneous in‐situ spacecraft data. From these, the system characterizes typical uncertainties in model timing, quantifies how these uncertainties vary under different conditions, attempts to correct for systematic biases in the input model timing, and composes a MME with uncertainties from the results. For the Juno‐era (04/07/2016–04/07/2023) MME hindcast for Jupiter presented here, three solar wind propagation models were compared to in‐situ measurements from the near‐Jupiter spacecraft Ulysses and Juno spanning diverse geometries and phases of the solar cycle across >14,000 hr of data covering 2.5 decades. The MME gives the most‐probable near‐Jupiter solar wind conditions for times within the tested epoch, outperforming the input models and returning quantified estimates of uncertainty.
Plain Language Summary
The sun interacts with all the planets in the solar system through the solar wind, a stream of charged particles which blow outwards from the sun in all directions, carrying the interplanetary magnetic field with them. Both the magnetic field and particles interact with planetary magnetic fields with dramatic effects, including the aurora–which shine not only on the Earth, but on gas giants of the outer solar system, like Jupiter, too. Characterizing the relationship between the solar wind and planetary magnetic fields is easiest with direct spacecraft measurements of both. Spacecraft between the Earth and Sun measure the solar wind, providing valuable context for understanding its interaction with the Earth. Unfortunately, there are no such permanent spacecraft near the other planets. Instead, models can be used to estimate the solar wind at these planets; however, these models can have significant, difficult‐to‐characterize uncertainties. Here we present the Multi‐Model Ensemble System for the outer Heliosphere (MMESH), a framework designed to measure these uncertainties and attempt to correct for them by comparing multiple solar wind models to spacecraft measurements over a long time span. The final result here is an improved solar wind model, with estimated uncertainties, for Jupiter.
Key Points
The performance of several existing solar wind propagation models at the orbit of Jupiter is measured for multiple spacecraft epochs
A flexible system is developed to generate an ensemble of multiple propagation models so as to best leverage each input model's strengths
Over the epoch tested, the multi‐model ensemble outperforms individual input models by 7%–110% in forecasting the solar wind flow speed
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