The Association of AMPK with ULK1 Regulates Autophagy

Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex

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

Effects of resistance training, detraining, and retraining on strength and functional capacity in elderly

Background: The interruption of training (detraining) results in loss of the gains acquired. Partial retention could occur after detraining, and variation in training stimuli may optimize retraining adaptations. Aim: To evaluate the effect of a resistance-retraining program on strength and functional capacity performance after a detraining period. Methods: Ten elderly men and women (63–68 years) completed 12 weeks of training, 16 weeks of detraining, and 8 weeks of retraining. One-repetition maximum (1-RM) at 45° leg press, maximum isometric knee extension torque, rate of torque development (RTD), 30-s sit-to-stand, timed up and go, and stair ascent and descent tests were assessed. Results: The 1-RM increased after training (p 0.05). For RTD and 30-s sit-to-stand, there was an increase after retraining when compared to pre-training values (p < 0.05). For timed up and go and stair ascent and descent, reductions were observed between pre-training and post-training periods (p < 0.05), only timed up and go increased after the detraining period (p < 0.01). Discussion: After 16 weeks of detraining, the maximum strength did not return to baseline levels, and a retraining with explosive strength exercise sessions can recover maximum strength gains, RTD, and functional capacity at the same level obtained after a detraining period. Conclusions: The inclusion of an explosive strength session in retraining period improves RTD and 30-s sit-to-stand performance and can accelerate the recovery of strength after a detraining period.</p