Multiple Topology Replica Exchange of Expanded Ensembles for Multidimensional Alchemical Calculations.

Relative free energy (RFE) calculations are now widely used in academia and the industry, but their accuracy is often limited by poor sampling of the complexes' conformational ensemble. To help address conformational sampling problems when simulating many relative binding free energies, we developed a novel method termed multiple topology replica exchange of expanded ensembles (MT-REXEE). This method enables parallel expanded ensemble calculations, facilitating iterative RFE computations while allowing conformational exchange between parallel transformations.

Replica Exchange of Expanded Ensembles: A Generalized Ensemble Approach with Enhanced Flexibility and Parallelizability.

Generalized ensemble methods such as Hamiltonian replica exchange (HREX) and expanded ensemble (EE) have been shown effective in free energy calculations for various contexts, given their ability to circumvent free energy barriers via nonphysical pathways defined by states with different modified Hamiltonians. However, both HREX and EE methods come with drawbacks, such as limited flexibility in parameter specification or the lack of parallelizability for more complicated applications. To address this challenge, we present the method of replica exchange of expanded ensembles (REXEE), which integrates the principles of HREX and EE methods by periodically exchanging coordinates of EE replicas sampling different yet overlapping sets of alchemical states.

Genomic Analysis of Lymphoma Risk in Bullmastiff Dogs.

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases.

Identification of Genomic Signatures in Bullmastiff Dogs Using Composite Selection Signals Analysis of 23 Purebred Clades.

Dog breeds represent canine sub-populations with distinctive phenotypic features and limited genetic diversity. We have established a resource to study breed-specific genetic diversity. Utilising genetic resources within our laboratory biobank, public domain genotype data and the phylogenetic framework of 23 breed clades, the primary objective for this study was to identify genomic regions that differentiate the Bullmastiff breed.

Alchemical Metadynamics: Adding Alchemical Variables to Metadynamics to Enhance Sampling in Free Energy Calculations.

Performing alchemical transformations, in which one molecular system is nonphysically changed to another system, is a popular approach adopted in performing free energy calculations associated with various biophysical processes, such as protein-ligand binding or the transfer of a molecule between environments. While the sampling of alchemical intermediate states in either parallel (e.g.

Analysis of dog breed diversity using a composite selection index.

During breed development, domestic dogs have undergone genetic bottlenecks and sustained selective pressures, as a result distinctive genomic diversity occurs to varying degrees within and between breed groups. This diversity can be identified using standard methods or combinations of these methods. This study explored the application of a combined selection index, composite selection signals (CSS), derived from multiple methods to an existing genotype dataset from three breed groups developed in distinct regions of Asia: Qinghai-Tibet plateau dogs (adapted to living at altitude), Xi dogs (with superior running ability) and Mountain hounds (used for hunting ability).

physical_validation: A Python package to assess the physical validity of molecular simulation results.

Molecular simulations such as molecular dynamics (MD) and Monte Carlo (MC) simulations are powerful tools allowing the prediction of experimental observables in the study of systems such as proteins, membranes, and polymeric materials. The quality of predictions based on molecular simulations depend on the validity of the underlying physical assumptions. physical_validation allows users of molecular simulation programs to perform simple yet powerful tests of physical validity on their systems and setups.

Quality of Life Among Geriatric Community Members Following the Kaohsiung Gas Explosion: A 5-Year Cross-Sectional Study.

Objective: The aim was to conduct a follow-up study of the quality of life (QoL) and to measure lifestyle factors among the aging survivors of a petrochemical gas explosion in Taiwan 5 years after the event.

Methods: A community-based survey with cross-sectional assessments was conducted with residents of a community who experienced a petrochemical gas explosion 5 years after the disaster. Short Form 12v2 (SF-12v2) was used to survey a representative sample of participants.

Identifying signatures of proteolytic stability and monomeric propensity in O-glycosylated insulin using molecular simulation.

Insulin has been commonly adopted as a peptide drug to treat diabetes as it facilitates the uptake of glucose from the blood. The development of oral insulin remains elusive over decades owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked glycosylation patterns could enhance insulin's proteolytic stability and reduce its dimerization propensity, but understanding such phenomena at the molecular level is still difficult.

A Community Survey of Quality of Life and Psychiatric Disorders among Residents Following the Kaohsiung Gas Explosion: a 5-Year Cross-Sectional Follow-Up Study.

To investigate factors associated with quality of life (QoL) and disaster-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and major depressive episode (MDE), in the survivors of a gas explosion in Taiwan 5 years after the event. A community-based cross-sectional study of residents from an area that experienced a gas explosion was conducted 5 years after the event. The Short Form 12v2 (SF-12v2) was used to screen 2511 participants.

Evaluation of genetic diversity and management of disease in Border Collie dogs.

Maintaining genetic diversity in dog breeds is an important consideration for the management of inherited diseases. We evaluated genetic diversity in Border Collies using molecular and genealogical methods, and examined changes to genetic diversity when carriers for Trapped Neutrophil Syndrome (TNS) and Neuronal Ceroid Lipofuscinosis (NCL) are removed from the genotyped population. Genotype data for 255 Border Collies and a pedigree database of 83,996 Border Collies were used for analysis.

Bilateral pedal edema associated with lurasidone: a case report.

Lurasidone, an atypical antipsychotic, is currently approved for treatment of schizophrenia and bipolar depression. Little is known about whether lurasidone might also cause pedal edema. A 55-year-old female patient had been diagnosed with bipolar I disorder from the age of 26.

Exploring the influence of brilliant blue G on amyloid fibril formation of lysozyme.

Evidence suggests that amyloid fibril mitigation/inhibition is considered a promising approach toward treating amyloid diseases. In this work, we first examined how amyloid fibrillogenesis of lysozyme was affected by BBG, a safe triphenylmethane compound with nice blood-brain-barrier-permeability, and found that shorter fibrillar species were formed in the lysozyme samples treated with BBG. Next, alterations in the features including the secondary as well as tertiary structure, extent of aggregation, and molecular distribution of lysozyme triggered by the addition of BBG were examined by various spectroscopic techniques, right-angle light scattering, dynamic light scattering, and SDS-PAGE.

Alteration of mesenchymal stem cells polarity by laminar shear stimulation promoting β-catenin nuclear localization.

Mesenchymal stem cell (MSC) is mechanosensitive and the respond to mechanical force is pattern specific. We previously reported that oscillatory shear stress at 0.5 ± 4 dyne/cm guided MSCs polarity vertical to net flow direction before apolaric stage at 30 min resulting in phosphorylation of β-catenin and inhibition of Wnt signaling.

Lysozyme amyloid fibrillization in presence of tacrine/acridone-coumarin heterodimers.

Amyloid aggregates of proteins are one of the most abundant and important naturally occurring self-associated assemblies. Formation of poly/peptide amyloid aggregates is also associated with the widely spread diseases, so called amyloidosis, which include Alzheimer's disease, diabetes mellitus and lysozyme amyloidosis. These disorders are still incurable and novel therapeutical approaches are focused on using small molecules for inhibition of amyloid aggregation.

Comparative Studies on Ultraviolet-Light-Derived Photoresponse Properties of ZnO, AZO, and GZO Transparent Semiconductor Thin Films.

ZnO, Al-doped ZnO (AZO), and Ga-doped ZnO (GZO) semiconductor thin films were deposited on glass substrates via a sol-gel spin-coating process for application in a photoconductive ultraviolet (UV) detector. The doping concentrations of Al and Ga were 1.0 at % in the precursor solutions.

Brilliant blue R dye is capable of suppressing amyloid fibril formation of lysozyme.

Amyloid fibril formation is associated with an array of degenerative diseases. While no real cure is currently available, evidence suggests that suppression of amyloid fibrillogenesis is an effective strategy toward combating these diseases. Brilliant blue R (BBR), a disulfonated triphenylmethane compound, has been shown to interact with fibril-forming proteins but exert different effects on amyloid fibrillogenesis.

Investigating the effects of erythrosine B on amyloid fibril formation derived from lysozyme.

Formation of amyloid fibrils has been associated with at least 30 different protein aggregation diseases. The 129-residue polypeptide hen lysozyme, which is structurally homologous to human lysozyme, has been demonstrated to exhibit amyloid fibril-forming propensity in vitro. This study is aimed at exploring the influence of erythrosine B on the in vitro amyloid fibril formation of hen lysozyme at pH 2.

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway.

The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion.

Regulation of metastatic ability and drug resistance in pulmonary adenocarcinoma by matrix rigidity via activating c-Met and EGFR.

Lung fibrosis is a poor prognostic factor for pulmonary adenocarcinoma, and the effect of a rigid microenvironment on cancer behavior is unclear. We cultured A549 cells on matrices of 0.2, 2, and 25 kPa to mimic the rigidities of normal lung parenchyma, progressive fibrotic change, and lung fibrosis, respectively.

Oscillatory shear stress mediates directional reorganization of actin cytoskeleton and alters differentiation propensity of mesenchymal stem cells.

Shear stress stimuli differentially regulate cellular functions based on the pattern, magnitude as well as duration of the flow. Shear stress can modify intracellular kinase activities and cytoskeleton reorganization to result in changes of cell behavior. Mesenchymal stem cells (MSCs) are mechano-sensitive cells, but little is known about the effects of oscillatory shear stress (OS).

The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p.

Introduction: Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion.

Methods: LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours.

Evaluation of dazomet as fumigant for the control of brown root rot disease.

Background: Brown root rot disease caused by Phellinus noxius is widespread in approximately 216 tree and plant species in tropical and subtropical countries. No direct means of protection against P. noxius infection have thus far been developed.