Investigation of Structural Dynamics of Enzymes and Protonation States of Substrates Using Computational Tools.

This review discusses the use of molecular modeling tools, together with existing experimental findings, to provide a complete atomic-level description of enzyme dynamics and function. We focus on functionally relevant conformational dynamics of enzymes and the protonation states of substrates. The conformational fluctuations of enzymes usually play a crucial role in substrate recognition and catalysis. Protein dynamics can be altered by a tiny change in a molecular system such as different protonation states of various intermediates or by a significant perturbation such as a ligand association. Here we review recent advances in applying atomistic molecular dynamics (MD) simulations to investigate allosteric and network regulation of tryptophan synthase (TRPS) and protonation states of its intermediates and catalysis. In addition, we review studies using quantum mechanics/molecular mechanics (QM/MM) methods to investigate the protonation states of catalytic residues of β-Ketoacyl ACP synthase I (KasA). We also discuss modeling of large-scale protein motions for HIV-1 protease with coarse-grained Brownian dynamics (BD) simulations

Ophthalmology of clinically normal alpacas ( Vicugna pacos ) in the United Kingdom: a cross-sectional study

Background: Alpacas are being more frequently presented to veterinarians in the UK. It is important to validate whether published normal ocular parameters are consistent with the alpaca population in the UK. Methods: Ophthalmic examinations were performed on healthy alpacas (Vicugna pacos) from three farms in East Anglia, UK. Results: On direct ophthalmoscopy of 35 alpacas, there was a 50 per cent prevalence of opacities within the lens in alpacas older than two years old (n=8/16). There was a 36.8 per cent prevalence of persistent hyaloid arteries in alpacas under two years old (n=7/19). The mean Schirmer tear test-1 value was 20.0 ±6 mm/minute (n=40). The mean intraocular pressure measured by rebound tonometry was 17.2 ±5.5 mmHg (n=46), and applanation tonometry resulted in statistically similar values (P=0.30; n=25). There was a significant variation in intraocular pressure throughout a 24-hour period (n=8). Fluorescein dye was not detected at the nostrils of any of the alpacas which underwent a Jones test to assess nasolacrimal duct patency (n=8). Conclusion: The ophthalmic findings appear largely consistent with previously published values from North America and continental Europe. Variations include the large range of measurements obtained and evidence of diurnal variation in intraocular pressure

Chemical Exchange in Nuclear Magnetic Resonance

Nuclear magnetic resonance spectra of molecules undergoing chemical exchange have traditionally been quantified using a theory that combines a quantum-mechanical treatment of the spin dynamics with a kinetic model for the molecular exchange. This implicit factorization of spin and spatial degrees of freedom is without theoretical justification and yet it has been widely relied upon in chemical studies. In this thesis, a quantum-statistical theory of chemical exchange is presented for the calculation of lineshapes in dynamic nuclear magnetic resonance. In this treatment, the rates describing the exchange of spin coherence are shown to be complex valued due to the incomplete cancellation of the imaginary components of the spectral density of purely spatial perturbations. These imaginary components give rise to the previously unrecognized phenomena of exchange shifts, new contributions to the line positions which depend on spatial rates even in the fast-exchange limit. These shifts can be orders of magnitude greater than the experimental resolution. The same purely spatial fluctuations responsible for chemical exchange determine these shifts through a Hilbert-transform relationship. New measurements on the 13C NMR of methylcyclohexane show that, indeed, the traditional theory fails to relate spectra obtained in the regimes of fast and slow exchange. If interpreted using the traditional theory, the fast-exchange line positions in methylcyclohexane lead to an extracted equilibrium constant with an error of up to 30% and differing between isotopomers by up to 30%. With plausible assumptions on the temperature dependence of the chemical shifts and free energy, an overall fit of the fast­ and slow-exchange methylcyclohexane data is unsatisfactory, rigorously excluding the traditional theory. The exchange-shift theory indicates why additional information is needed to fit the fast-exchange line positions and allows a fit consistent with the observed experimental data on methylcyclohexane using a single conformer free energy difference linear in temperature over the entire experimental range.</p

Captan Toxicity to Fathead Minnows (\u3ci\u3ePimephales promelas\u3c/i\u3e), Bluegills (\u3ci\u3eLepomis macrochirus\u3c/i\u3e), and Brook Trout (\u3ci\u3eSalvelinus fontinalis\u3c/i\u3e)

The toxic effects of capt an on survival, growth, and reproduction of fathead minnows (Pimephales promelas) and on survival of bluegiIIs (Lepomis macrochirus) and brook trout (Salvelinus fontinalis) were determined in a flow-through system. In a 45-week exposure of fathead minnows, survival and growth were adversely affected at 39.5 μLg/Iiter. Adverse effects on spawning were suspected but not statisticaIly demonstrated at 39.5 and 16.5 μLg/Iiter. The maximum acceptable toxicant concentration (MATC), based on survival and growth, lies between 39.5 and 16.5 μLg/liter. The lethal threshold concentration (LTC) derived from acute exposures was 64 μLg/liter, resulting in an application factor (MATC/LTC) between 0.26 and 0.62. LTC values for the bluegill and brook trout were 72 and 29 μLg/liter, respectively. The estimated MATC is between 44.6 and 18.7 μLg/liter for the bluegill and between 18.0 and 7.5 μLg/liter for the brook trout. The half-life of captan in Lake Superior water with a pH of 7.6 is about 7 hr at 12 C and about 1 hr at 25 C. Breakdown products from an initial 550 μLg/Iiter of captan were not lethal to 3-month-old fathead minnows

No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning

Pomeron and Reggeized Glueball/Sigma

It has long been believed that the Pomeron, which has been successful in phenomenological fits to high energy scattering data, is associated with gluonic exchange. By determining the Regge-nucleon vertex in terms of previously determined glueball-quark coupling we show that the Pomeron might be related to the Regge trajectory defined by a light scalar glueball/sigma system and a tensor glueball, which involves complicated nonperturbative QCD. We predict a tensor glueball at 2.8 GeV.Comment: tex file and two eps files with figure

Theoretical analysis of electronic processes occurring during ultrafast demagnetization of cobalt triggered by X-ray photons tuned to Co L3_3 resonance

Magnetization dynamics triggered with ultrashort laser pulses has been attracting significant attention, with strong focus on the dynamics excited by VIS/NIR pulses. Only recently, strong magnetic response in solid materials induced by intense X-ray pulses from free-electron lasers (FELs) has been observed. The exact mechanisms that trigger the X-ray induced demagnetization are not yet fully understood. They are subject of on-going experimental and theoretical investigations. Here, we present a theoretical analysis of electronic processes occurring during demagnetization of Co multilayer system irradiated by X-ray pulses tuned to L$_3$-absorption edge of cobalt. We show that, similarly as in the case of X-ray induced demagnetization at M-edge of Co, electronic processes play a predominant role in the demagnetization until the pulse fluence does not exceed the structural damage threshold. The impact of electronic processes can reasonably well explain the available experimental data, without a need to introduce the mechanism of stimulated elastic forward scattering.Comment: 10 pages, 4 figures (7 panels), 57 references; pdfRevTeX class; double column formatting; two appendices and 18 references added; author-created version submitted to and accepted in Physical Review B journal. arXiv admin note: text overlap with arXiv:2202.1384

A Fully Tunable Single-Walled Carbon Nanotube Diode

We demonstrate a fully tunable diode structure utilizing a fully suspended single-walled carbon nanotube (SWNT). The diode's turn-on voltage under forward bias can be continuously tuned up to 4.3 V by controlling gate voltages, which is ~6 times the nanotube bandgap energy. Furthermore, the same device design can be configured into a backward diode by tuning the band-to-band tunneling current with gate voltages. A nanotube backward diode is demonstrated for the first time with nonlinearity exceeding the ideal diode. These results suggest that a tunable nanotube diode can be a unique building block for developing next generation programmable nanoelectronic logic and integrated circuits.Comment: 14 pages, 4 figure