Genetic and environmental transactions underlying the associationbetween physical fitness/physical exercise and body composition

We examined mean effects and variance moderating effects of measures of physical activity and fitness on six measures of adiposity and their reciprocal effects in a subsample of the population-representative Danish Twin Registry. Consistent with prior studies, higher levels of physical activity suppressed variance in adiposity, but this study provided further insight. Variance suppression appeared to have both genetic and environmental pathways. Some mean effects appeared due to reciprocal influences of environmental circumstances differing among families but not between co-twins, suggesting these reciprocal effects are uniform. Some variance moderating effects also appeared due to biases in individual measures of adiposity, as well as to differences and inaccuracies in measures of physical activity. This suggests a need to avoid reliance on single measures of both physical activity and adiposity in attempting to understand the pathways involved in their linkages, and constraint in interpreting results if only single measures are available. Future research indications include identifying which physical activity-related environmental circumstances have relatively uniform effects on adiposity in everyone, and which should be individually tailored to maximize motivation to continue involvement.</p

OGLE-2013-SN-079: A LONELY SUPERNOVA CONSISTENT WITH A HELIUM SHELL DETONATION

We present observational data for a peculiar supernova discovered by the OGLE-IV survey and followed by the Public ESO Spectroscopic Survey for Transient Objects. The inferred redshift of z = 0.07 implies an absolute magnitude in the rest-frame I-band of MI ~ –17.6 mag. This places it in the luminosity range between normal Type Ia SNe and novae. Optical and near infrared spectroscopy reveal mostly Ti and Ca lines, and an unusually red color arising from strong depression of flux at rest wavelengths <5000 Å. To date, this is the only reported SN showing Ti-dominated spectra. The data are broadly consistent with existing models for the pure detonation of a helium shell around a low-mass CO white dwarf and "double-detonation" models that include a secondary detonation of a CO core following a primary detonation in an overlying helium shell

Mate-guarding constrains feeding activity but not energetic status of wild male long-tailed macaques (Macaca fascicularis).

Mate-guarding is an important determinant of male reproductive success in a number of species. Little is known however about the constraints of this behaviour, e.g. the associated energetic costs. We investigated these costs in long-tailed macaques where alpha males mate guard females to a lesser extent than predicted by the priority of access model. The study was carried out during two mating periods on three wild groups living in the Gunung Leuser National Park, Indonesia. We combined behavioural observations on males' locomotion and feeding activity, GPS records of distance travelled and non-invasive measurements of urinary C-peptide (UCP), a physiological indicator of male energetic status. Mate-guarding led to a decrease in feeding time and fruit consumption suggesting a reduced intake of energy. At the same time, vertical locomotion was reduced, which potentially saved energy. These findings, together with the fact that we did not find an effect of mate-guarding on UCP levels, suggest that energy intake and expenditure was balanced during mate-guarding in our study males. Mate-guarding thus seems to not be energetically costly under all circumstances. Given that in strictly seasonal rhesus macaques, high-ranking males lose physical condition over the mating period, we hypothesise that the energetic costs of mate-guarding vary inter-specifically depending on the degree of seasonality and that males of non-strictly seasonal species might be better adapted to maintain balanced energetic condition year-round. Finally, our results illustrate the importance of combining behavioural assessments of both energy intake and expenditure with physiological measures when investigating energetic costs of behavioural strategies

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

The Transcriptional Repressor TupA in Aspergillus niger Is Involved in Controlling Gene Expression Related to Cell Wall Biosynthesis, Development, and Nitrogen Source Availability.

The Tup1-Cyc8 (Ssn6) complex is a well characterized and conserved general transcriptional repressor complex in eukaryotic cells. Here, we report the identification of the Tup1 (TupA) homolog in the filamentous fungus Aspergillus niger in a genetic screen for mutants with a constitutive expression of the agsA gene. The agsA gene encodes a putative alpha-glucan synthase, which is induced in response to cell wall stress in A. niger. Apart from the constitutive expression of agsA, the selected mutant was also found to produce an unknown pigment at high temperatures. Complementation analysis with a genomic library showed that the tupA gene could complement the phenotypes of the mutant. Screening of a collection of 240 mutants with constitutive expression of agsA identified sixteen additional pigment-secreting mutants, which were all mutated in the tupA gene. The phenotypes of the tupA mutants were very similar to the phenotypes of a tupA deletion strain. Further analysis of the tupA-17 mutant and the DeltatupA mutant revealed that TupA is also required for normal growth and morphogenesis. The production of the pigment at 37 degrees C is nitrogen source-dependent and repressed by ammonium. Genome-wide expression analysis of the tupA mutant during exponential growth revealed derepression of a large group of diverse genes, including genes related to development and cell wall biosynthesis, and also protease-encoding genes that are normally repressed by ammonium. Comparison of the transcriptome of up-regulated genes in the tupA mutant showed limited overlap with the transcriptome of caspofungin-induced cell wall stress-related genes, suggesting that TupA is not a general suppressor of cell wall stress-induced genes. We propose that TupA is an important repressor of genes related to development and nitrogen metabolism

Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions. © 2009 Nature Publishing Group All rights reserved

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Conventionally assessed voluntary activation does not represent relative voluntary torque production

The ability to voluntarily activate a muscle is commonly assessed by some variant of the twitch interpolation technique (ITT), which assumes that the stimulated force increment decreases linearly as voluntary force increases. In the present study, subjects (n = 7) with exceptional ability for maximal voluntary activation (VA) of the knee extensors were used to study the relationship between superimposed and voluntary torque. This includes very high contraction intensities (90–100%VA), which are difficult to consistently obtain in regular healthy subjects (VA of ∼90%). Subjects were tested at 30, 60, and 90° knee angles on two experimental days. At each angle, isometric knee extensions were performed with supramaximal superimposed nerve stimulation (triplet: three pulses at 300 Hz). Surface EMG signals were obtained from rectus femoris, vastus lateralis, and medialis muscles. Maximal VA was similar and very high across knee angles: 97 ± 2.3% (mean ± SD). At high contraction intensities, the increase in voluntary torque was far greater than would be expected based on the decrement of superimposed torque. When voluntary torque increased from 79.6 ± 6.1 to 100%MVC, superimposed torque decreased from 8.5 ± 2.6 to 2.8 ± 2.3% of resting triplet. Therefore, an increase in VA of 5.7% (from 91.5 ± 2.6 to 97 ± 2.3%) coincided with a much larger increase in voluntary torque (20.4 ± 6.1%MVC) and EMG (33.9 ± 6.6%max). Moreover, a conventionally assessed VA of 91.5 ± 2.6% represented a voluntary torque of only 79.6 ± 6.1%MVC. In conclusion, when maximal VA is calculated to be ∼90% (as in regular healthy subjects), this probably represents a considerable overestimation of the subjects’ ability to maximally drive their quadriceps muscles