Combined QM/MM Study of Thyroid and Steroid Hormone Analogue Interactions with αvβ3 Integrin

Recent biochemical studies have identified a cell surface receptor for thyroid and steroid hormones that bind near the arginine-glycine-aspartate (RGD) recognition site on the heterodimeric αvβ3 integrin. To further characterize the intermolecular interactions for a series of hormone analogues, combined quantum mechanical and molecular mechanical (QM/MM) methods were used to calculate their interaction energies. All calculations were performed in the presence of either calcium (Ca2+) or magnesium (Mg2+) ions. These data reveal that 3,5′-triiodothyronine (T3) and 3,5,3′,5′-tetraiodothyroacetic acid (T4ac) bound in two different modes, occupying two alternate sites, one of which is along the Arg side chain of the RGD cyclic peptide site. These orientations differ from those of the other ligands whose alternate binding modes placed the ligands deeper within the RGD binding pocket. These observations are consistent with biological data that indicate the presence of two discrete binding sites that control distinct downstream signal transduction pathways for T3

Performance metrics and auditing framework using application kernels for high‐performance computer systems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97468/1/cpe2871.pd

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Physiological, biochemical, and ultrastructural characterization of selenium toxicity in cowpea plants

Selenium (Se) is considered a beneficial element for plants; however, in high concentrations, it causes negative effects on plant physiology and development. This study reports the first physiological, nutritional, and ultrastructural description of Se toxicity in cowpea growing under field conditions. Selenium was supplied as a foliar application of sodium selenite at varying concentrations (0, 50, 100, 200, 400, 800, 1200, and 1600 g ha−1). An increased yield was observed with the application of 50 g ha−1 Se. Application of concentrations higher than 50 g ha−1 caused leaf toxicity. Increased lipid peroxidation and hydrogen peroxide concentration and reduced total sugars, sucrose, and carotenoid concentration were observed at highest doses tested (1200 and 1600 g ha−1). Applications of more than 50 g ha−1 Se reduced the phloem diameter, caused chlorosis of the leaf blade with a coalescence of lesions, and caused pink salt deposits to appear. Lesions were observed mainly near the trichomes on the adaxial surface of the leaf blade. An analysis of the element distribution with microprobe X-ray fluorescence spectrometry (μ-XRF) revealed accumulation of Se, calcium (Ca), potassium (K), copper (Cu), and manganese (Mn) near the primary vein and in the necrotic brown areas of the leaf lesions. In contrast, Na was homogeneously distributed in the leaf tissue