Free-Energy Landscape and Rate Estimation of the Aromatic Ring Flips in Basic Pancreatic Trypsin Inhibitors Using Metadynamics.

Aromatic side chains (phenylalanine and tyrosine) of a protein flip by 180° around the - axis (χ dihedral of the side chain), producing two symmetry-equivalent states. The study of ring flip dynamics with nuclear magnetic resonance (NMR) experiments helps to understand local conformational fluctuations. Ring flips are categorized as slow (milliseconds and onward) or fast (nanoseconds to near milliseconds) based on timescales accessible to NMR experiments.

Comparative analysis of RNA secondary structure accuracy on predicted RNA 3D models.

RNA structure is conformationally dynamic, and accurate all-atom tertiary (3D) structure modeling of RNA remains challenging with the prevailing tools. Secondary structure (2D) information is the standard prerequisite for most RNA 3D modeling. Despite several 2D and 3D structure prediction tools proposed in recent years, one of the challenges is to choose the best combination for accurate RNA 3D structure prediction.

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022.

Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics).

Epitaxial growth of 1D GaN-based heterostructures on various substrates for photonic and energy applications.

GaN is an important III-V semiconductor for a variety of applications owing to its large direct band gap. GaN nanowires (NWs) have demonstrated significant potential as critical building blocks for nanoelectronics and nanophotonic devices, as well as integrated nanosystems. We present a comprehensive analysis of the vapor-liquid-solid (VLS) as a general synthesis technique for NWs on a variety of substrates, the morphological and structural characterization, and applications of GaN NWs in piezoelectric nanogenerators, light-emitting diodes, and solar-driven water splitting.

High Performance, Stable, and Flexible Piezoelectric Nanogenerator Based on GaN:Mg Nanowires Directly Grown on Tungsten Foil.

Rapid development of micro-electromechanical systems increases the need for flexible and durable piezoelectric nanogenerators (f-PNG) with high output power density. In this study, a high-performance, flexible, and highly stable f-PNG is prepared by directly growing the Mg-doped semi-insulating GaN nanowires (NWs) on a 30-µm-thick tungsten foil using vapor-liquid-solid growth mechanism. The direct growth of NWs on metal foil extends the overall lifetime of the f-PNG.

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Second International Conference on 3Rs Research and Progress, Hyderabad, 2021.

The fact that animal models fail to replicate human disease faithfully is now being widely accepted by researchers across the globe. As a result, they are exploring the use of alternatives to animal models. The time has come to refine our experimental practices, reduce the numbers and eventually replace the animals used in research with human-derived and human-relevant 3-D disease models.

Accurate prediction of B-form/A-form DNA conformation propensity from primary sequence: A machine learning and free energy handshake.

DNA carries the genetic code of life, with different conformations associated with different biological functions. Predicting the conformation of DNA from its primary sequence, although desirable, is a challenging problem owing to the polymorphic nature of DNA. We have deployed a host of machine learning algorithms, including the popular state-of-the-art LightGBM (a gradient boosting model), for building prediction models.

Interleaflet Decoupling in a Lipid Bilayer at Excess Cholesterol Probed by Spectroscopic Ellipsometry and Simulations.

Artificial lipid membranes are often investigated as a replica of the cell membrane in the form of supported lipid bilayers (SLBs). In SLBs, the phase state of a lipid bilayer strongly depends on the presence of molecules such as cholesterol, ceramide, and physical parameters such as temperature. Cholesterol is a key molecule of biological membranes and it exerts condensing effect on lipid bilayers.

The Effects of Furosemide on Oxygenation in Mechanically Ventilated Children with Bronchiolitis.

Fluid balance management, including diuretic administration, may influence outcomes among mechanically ventilated children. We retrospectively compared oxygenation saturation index (OSI) before and after the initial furosemide bolus among 65 mechanically ventilated children. Furosemide was not associated with a significant change in median OSI (6.

Spectroscopic Ellipsometry of fluid and gel phase lipid bilayers in hydrated conditions.

The biological membranes play a crucial role in the various biological processes due to their characteristic physical properties. The parameters such as membrane composition, thickness undulations, and the influence of external stimuli play a crucial role in the phase state behavior of biological membranes. The supported lipid bilayer (SLBs) systems closely represent cell membranes and are often studied to understand their behavior.

Insilico direct folding of thrombin-binding aptamer G-quadruplex at all-atom level.

The reversible folding of the thrombin-binding DNA aptamer G-quadruplexes (GQs) (TBA-15) starting from fully unfolded states was demonstrated using a prolonged time scale (10-12 μs) parallel tempering metadynamics (PTMetaD) simulation method in conjunction with a modified version of the AMBER bsc1 force field. For unbiased descriptions of the folding free energy landscape of TBA-15, this force field was minimally modified. From this direct folding simulation using the modified bsc1 force field, reasonably converged free energy landscapes were obtained in K+-rich aqueous solution (150 mM), providing detailed atomistic pictures of GQ folding mechanisms for TBA-15.

Understanding B-DNA to A-DNA transition in the right-handed DNA helix: Perspective from a local to global transition.

The right-handed DNA helix exhibits two major conformations, A-DNA and B-DNA, depending on the environmental conditions. The B-DNA to A-DNA (B→A) transition is sequence specific, cooperative, and reversible. The reduced water activity due to the addition of solvents like ethanol or the presence of protein or drug molecules causes B→A transition.

Water modulates the ultraslow dynamics of hydrated ionic liquids near CG rich DNA: consequences for DNA stability.

Ionic liquids are known to stabilize DNA for much longer than water can. While the source of this stability has commonly been attributed to thermodynamic aspects, we probe the dynamical aspects of the ionic liquids near DNA to further our understanding of this stability. Using molecular dynamics simulation, we calculated the mean residence time (MRT) of the cations of five different ionic liquids (ILs) in the grooves and around phosphate groups of AT and CG rich DNA segments.

Ionic liquid induced G-quadruplex formation and stabilization: spectroscopic and simulation studies.

Among different polymorphs of DNA, G-quadruplex (GQ) formation in guanine rich sequences has received special attention due to its direct relevance to cellular aging and abnormal cell growths. To date, smaller ions like Na, K, Li, and NH are the best possible selective GQ stabilizing materials. Herein, we report that an ionic liquid (IL), i.

Computational Approach to Explore the B/A Junction Free Energy in DNA.

Protein-DNA interactions induce conformational changes in DNA such as B- to A-form transitions at a local level. Such transitions are associated with a junction free energy cost at the boundary of two different conformations in a DNA molecule. In this study, we performed umbrella sampling simulations to find the free energy values of the B-A transition at the dinucleotide and trinucleotide level of DNA.

Avian scavengers and the threat from veterinary pharmaceuticals.

Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a 'vulture-safe' alternative.

Depth inpainting by tensor voting.

Depth maps captured by range scanning devices or by using optical cameras often suffer from missing regions due to occlusions, reflectivity, limited scanning area, sensor imperfections, etc. In this paper, we propose a fast and reliable algorithm for depth map inpainting using the tensor voting (TV) framework. For less complex missing regions, local edge and depth information is utilized for synthesizing missing values.

Sequence dependent free energy profiles of localized B- to A-form transition of DNA in water.

DNA carries an inherent polymorphism, which surfaces under various external conditions. While B-form remains predominant under normal physiological conditions for most of the DNA sequences, low humidity and increased ion concentration cause B- to A-form transition. Certain proteins and molecules also sometimes cause local deformation of the DNA to the specific A-form.

Rapid detection of carbapenemase activity through monitoring ertapenem hydrolysis in Enterobacteriaceae with LC-MS/MS.

Background: Bacteria are increasingly resistant to antibiotics used to treat life-threatening infections in critically ill patients. The carbapenems represent the last line of defense against Gram-negative rods that are increasingly resistant to all other classes of β-lactam antibiotics used to treat life-threatening infections in critically ill patients. Carbapenem resistance in Gram-negative rods is most commonly caused by expression of carbapenemases, enzymes that hydrolyze the β-lactam ring of carbapenem antibiotics rendering them inactive.

Molecular sexing of threatened Gyps vultures: an important strategy for conservation breeding and ecological studies.

During the last two decades populations of three resident species of Gyps vulture have declined dramatically and are now threatened with extinction in South Asia. Sex identification of vultures is of key importance for the purpose of conservation breeding as it is desirable to have an equal sex ratio in these monogamous species which are housed together in large colony aviaries. Because vultures are monomorphic, with no differences in external morphology or plumage colour between the sexes, other methods are required for sex identification.

The population decline of Gyps vultures in India and Nepal has slowed since veterinary use of diclofenac was banned.

Populations of oriental white-backed vulture (Gyps bengalensis), long-billed vulture (Gyps indicus) and slender-billed vulture (Gyps tenuirostris) crashed during the mid-1990s throughout the Indian subcontinent. Surveys in India, initially conducted in 1991-1993 and repeated in 2000, 2002, 2003 and 2007, revealed that the population of Gyps bengalensis had fallen by 2007 to 0.1% of its numbers in the early 1990s, with the population of Gyps indicus and G.

N-Myc is a downstream target of RET signaling and is required for transcriptional regulation of p18(Ink4c) by the transforming mutant RET(C634R).

Inherited activating mutations in RET predispose humans to Multiple Endocrine Neoplasia type-2 (MEN2). The MEN2A-specific mutation RET(C634R), RET2A, has been shown to simultaneously downregulate the CDKIs p18 and p27, and upregulate cyclin D1. Importantly, the loss of p18 is necessary and sufficient for RET2A-mediated hyperproliferation.

Two independent histidines, one in human prolactin and one in its receptor, are critical for pH-dependent receptor recognition and activation.

Human prolactin (hPRL), a member of the family of hematopoietic cytokines, functions as both an endocrine hormone and autocrine/paracrine growth factor. We have previously demonstrated that recognition of the hPRL·receptor depends strongly on solution acidity over the physiologic range from pH 6 to pH 8. The hPRL·receptor binding interface contains four histidines whose protonation is hypothesized to regulate pH-dependent receptor recognition.