Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium

One of the main outcomes of aerobic endurance exercise training is the improved maximal oxygen uptake, and this is pivotal to the improved work capacity that follows the exercise training. Improved maximal oxygen uptake in turn is at least partly achieved because exercise training increases the ability of the myocardium to produce a greater cardiac output. In healthy subjects, this has been demonstrated repeatedly over many decades. It has recently emerged that this scenario may also be true under conditions of an initial myocardial dysfunction. For instance, myocardial improvements may still be observed after exercise training in post-myocardial infarction heart failure. In both health and disease, it is the changes that occur in the individual cardiomyocytes with respect to their ability to contract that by and large drive the exercise training-induced adaptation to the heart. Here, we review the evidence and the mechanisms by which exercise training induces beneficial changes in the mammalian myocardium, as obtained by means of experimental and clinical studies, and argue that these changes ultimately alter the function of the whole heart and contribute to the changes in whole-body function

IPN localizations of Konus short gamma-ray bursts

Between the launch of the \textit{GGS Wind} spacecraft in 1994 November and the end of 2010, the Konus-\textit{Wind} experiment detected 296 short-duration gamma-ray bursts (including 23 bursts which can be classified as short bursts with extended emission). During this period, the IPN consisted of up to eleven spacecraft, and using triangulation, the localizations of 271 bursts were obtained. We present the most comprehensive IPN localization data on these events. The short burst detection rate, $\sim$18 per year, exceeds that of many individual experiments.Comment: Published versio

GRB 080407: An Ultra-long Burst Discovered by the IPN

We present observations of the extremely long GRB 080704 obtained with the instruments of the Interplanetary Network (IPN). The observations reveal two distinct emission episodes, separated by a approx.1500 s long period of quiescence. The total burst duration is about 2100 s. We compare the temporal and spectral characteristics of this burst with those obtained for other ultra-long GRBs and discuss these characteristics in the context of different models

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease

Inverse Compton X-ray Emission from Supernovae with Compact Progenitors: Application to SN2011fe

We present a generalized analytic formalism for the inverse Compton X-ray emission from hydrogen-poor supernovae and apply this framework to SN2011fe using Swift-XRT, UVOT and Chandra observations. We characterize the optical properties of SN2011fe in the Swift bands and find them to be broadly consistent with a "normal" SN Ia, however, no X-ray source is detected by either XRT or Chandra. We constrain the progenitor system mass loss rate to be lower than 2x10^-9 M_sun/yr (3sigma c.l.) for wind velocity v_w=100 km/s. Our result rules out symbiotic binary progenitors for SN2011fe and argues against Roche-lobe overflowing subgiants and main sequence secondary stars if >1% of the transferred mass is lost at the Lagrangian points. Regardless of the density profile, the X-ray non-detections are suggestive of a clean environment (particle density < 150 cm-3) for (2x10^15<R<5x10^16) cm around the progenitor site. This is either consistent with the bulk of material being confined within the binary system or with a significant delay between mass loss and supernova explosion. We furthermore combine X-ray and radio limits from Chomiuk et al. 2012 to constrain the post shock energy density in magnetic fields. Finally, we searched for the shock breakout pulse using gamma-ray observations from the Interplanetary Network and find no compelling evidence for a supernova-associated burst. Based on the compact radius of the progenitor star we estimate that the shock break out pulse was likely not detectable by current satellites.Comment: Submitted to Ap

Projected sensitivities of the LUX-ZEPLIN experiment to new physics via low-energy electron recoils

LUX-ZEPLIN is a dark matter detector expected to obtain world-leading sensitivity to weakly-interacting massive particles interacting via nuclear recoils with a ∼ 7 -tonne xenon target mass. This paper presents sensitivity projections to several low-energy signals of the complementary electron recoil signal type: 1) an effective neutrino magnetic moment, and 2) an effective neutrino millicharge, both for p p -chain solar neutrinos, 3) an axion flux generated by the Sun, 4) axionlike particles forming the Galactic dark matter, 5) hidden photons, 6) mirror dark matter, and 7) leptophilic dark matter. World-leading sensitivities are expected in each case, a result of the large 5.6 t 1000 d exposure and low expected rate of electron-recoil backgrounds in the < 100     keV energy regime. A consistent signal generation, background model and profile-likelihood analysis framework is used throughout