Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model

10.1038/s41419-020-02983-zCell Death and Disease11980

Low-latency gravitational-wave alerts for multimessenger astronomy during the second Advanced LIGO and Virgo observing run

Advanced LIGO's second observing run (O2), conducted from 2016 November 30 to 2017 August 25, combined with Advanced Virgo's first observations in 2017 August, witnessed the birth of gravitational-wave multimessenger astronomy. The first ever gravitational-wave detection from the coalescence of two neutron stars, GW170817, and its gamma-ray counterpart, GRB 170817A, led to an electromagnetic follow-up of the event at an unprecedented scale. Several teams from across the world searched for EM/neutrino counterparts to GW170817, paving the way for the discovery of optical, X-ray, and radio counterparts. In this article, we describe the online identification of gravitational-wave transients and the distribution of gravitational-wave alerts by the LIGO and Virgo collaborations during O2. We also describe the gravitational-wave observables that were sent in the alerts to enable searches for their counterparts. Finally, we give an overview of the online candidate alerts shared with observing partners during O2. Alerts were issued for 14 candidates, 6 of which have been confirmed as gravitational-wave events associated with the merger of black holes or neutron stars. Of the 14 alerts, 8 were issued less than an hour after data acquisition

A guide to LIGO–Virgo detector noise and extraction of transient gravitational-wave signals

The LIGO Scientific Collaboration and the Virgo Collaboration have cataloged eleven confidently detected gravitational-wave events during the first two observing runs of the advanced detector era. All eleven events were consistent with being from well-modeled mergers between compact stellar-mass objects: black holes or neutron stars. The data around the time of each of these events have been made publicly available through the gravitational-wave open science center. The entirety of the gravitational-wave strain data from the first and second observing runs have also now been made publicly available. There is considerable interest among the broad scientific community in understanding the data and methods used in the analyses. In this paper, we provide an overview of the detector noise properties and the data analysis techniques used to detect gravitational-wave signals and infer the source properties. We describe some of the checks that are performed to validate the analyses and results from the observations of gravitational-wave events. We also address concerns that have been raised about various properties of LIGO–Virgo detector noise and the correctness of our analyses as applied to the resulting data

Enhanced performance in fusion plasmas through turbulence suppression by megaelectronvolt ions

© 2022, The Author(s), under exclusive licence to Springer Nature Limited.Alpha particles with energies on the order of megaelectronvolts will be the main source of plasma heating in future magnetic confinement fusion reactors. Instead of heating fuel ions, most of the energy of alpha particles is transferred to electrons in the plasma. Furthermore, alpha particles can also excite Alfvénic instabilities, which were previously considered to be detrimental to the performance of the fusion device. Here we report improved thermal ion confinement in the presence of megaelectronvolts ions and strong fast ion-driven Alfvénic instabilities in recent experiments on the Joint European Torus. Detailed transport analysis of these experiments reveals turbulence suppression through a complex multi-scale mechanism that generates large-scale zonal flows. This holds promise for more economical operation of fusion reactors with dominant alpha particle heating and ultimately cheaper fusion electricity.N

Disruption prediction with artificial intelligence techniques in tokamak plasmas

In nuclear fusion reactors, plasmas are heated to very high temperatures of more than 100 million kelvin and, in so-called tokamaks, they are confined by magnetic fields in the shape of a torus. Light nuclei, such as deuterium and tritium, undergo a fusion reaction that releases energy, making fusion a promising option for a sustainable and clean energy source. Tokamak plasmas, however, are prone to disruptions as a result of a sudden collapse of the system terminating the fusion reactions. As disruptions lead to an abrupt loss of confinement, they can cause irreversible damage to present-day fusion devices and are expected to have a more devastating effect in future devices. Disruptions expected in the next-generation tokamak, ITER, for example, could cause electromagnetic forces larger than the weight of an Airbus A380. Furthermore, the thermal loads in such an event could exceed the melting threshold of the most resistant state-of-the-art materials by more than an order of magnitude. To prevent disruptions or at least mitigate their detrimental effects, empirical models obtained with artificial intelligence methods, of which an overview is given here, are commonly employed to predict their occurrence—and ideally give enough time to introduce counteracting measures

Search for multimessenger sources of gravitational waves and high-energy neutrinos with Advanced LIGO during its first observing run, ANTARES, and IceCube

Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes