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

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Overview of NMR in drug design

NMR spectroscopy is an extremely valuable tool in the pharmaceutical sciences. This chapter gives an overview of the use of this tool in drug design. It sets the scene for the specialist chapters that are included in this Handbook of Modern Magnetic Resonance

Interrogating Regulatory Mechanisms in Signaling Proteins by Allosteric Inhibitors and Activators: A Dynamic View Through the Lens of Residue Interaction Networks

Computational studies of allosteric interactions have witnessed a recent renaissance fueled by the growing interest in modeling of the complex molecular assemblies and biological networks. Allosteric interactions in protein structures allow for molecular communication in signal transduction networks. In this chapter, we discuss recent developments in understanding of allosteric mechanisms and interactions of protein systems, particularly in the context of structural, functional, and computational studies of allosteric inhibitors and activators. Computational and experimental approaches and advances in understanding allosteric regulatory mechanisms are reviewed to provide a systematic and critical view of the current progress in the development of allosteric modulators and highlight most challenging questions in the field. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Structural and computational studies of protein kinases have generated in recent decade significant insights that allowed leveraging knowledge about conformational diversity and allosteric regulation of protein kinases in the design and discovery of novel kinase drugs. We discuss recent developments in understanding multilayered allosteric regulatory machinery of protein kinases and provide a systematic view of the current state in understanding molecular basis of allostery mediated by kinase inhibitors and activators. In conclusion, we highlight the current status and future prospects of computational biology approaches in bridging the basic science of protein kinases with the discovery of anticancer therapies.https://digitalcommons.chapman.edu/scs_books/1049/thumbnail.jp