Endocytic tethers modulate unconventional GAPDH secretion.

Yeast cell walls contain both classically-secreted and unconventionally-secreted proteins. The latter class lacks the signal sequence for translocation into the ER, therefore these proteins are transported to the wall by uncharacterized mechanisms. One such protein is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which is abundant in the cytosol, but also found in the yeast cell wall where it is enzymatically active.

Proton Transfer Equilibrium in Pseudoprotic Ionic Liquids: Inferences on Ionic Populations.

Nonstoichiometric pseudoprotic ionic liquids (NPPILs) are an emerging class of ionic liquids with interesting physical properties and intriguing prospects for technological applications. However, fundamental questions remain about the proton transfer equilibria that underlie their ionic character. We use a combination of nuclear magnetic resonance spectroscopy, infrared spectroscopy, and small-angle X-ray scattering to characterize the equilibria of trihexylamine/butyric acid and water/butyric acid mixtures.

Developing Guidelines for Conducting Stigma Research With Transgender and Nonbinary Individuals: Protocol for Creation of a Trauma-Informed Approach to Research.

Background: Transgender and nonbinary individuals have received increasing attention within HIV research, with studies documenting the pervasive role stigma plays in creating and sustaining health inequities. However, the proliferation of HIV stigma research with this population has also raised concerns about research practices that may unintentionally stigmatize or retraumatize the very communities they are designed to benefit. Conducting stigma research is critical for generating accurate information about HIV epidemiology, risk and protective factors, and intervention strategies for transgender and nonbinary individuals.

Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.

Molecular docking methods are widely used in drug discovery efforts. RAS proteins are important cancer drug targets, and are useful systems for evaluating docking methods, including accounting for solvation effects and covalent small molecule binding. Water often plays a key role in small molecule binding to RAS proteins, and many inhibitors─including FDA-approved drugs─covalently bind to oncogenic RAS proteins.

Numerical dosimetry of specific absorption rate of insects exposed to far-field radiofrequency electromagnetic fields.

Purpose: This paper reports a study of electromagnetic field (EMF) exposure of several adult insects: a ladybug, a honey bee worker, a wasp, and a mantis at frequencies ranging from 2.5 to 100 GHz. The purpose was to estimate the specific absorption rate (SAR) in insect tissues, including the brain, in order to predict the possible biological effects caused by EMF energy absorption.

Single-Walled Carbon Nanotubes as Optical Transducers for Nanobiosensors In Vivo.

Semiconducting single-walled carbon nanotubes (SWCNTs) may serve as signal transducers for nanobiosensors. Recent studies have developed innovative methods of engineering molecularly specific sensors, while others have devised methods of deploying such sensors within live animals and plants. These advances may potentiate the use of implantable, noninvasive biosensors for continuous drug, disease, and contaminant monitoring based on the optical properties of single-walled carbon nanotubes (SWCNTs).

Nonlinear Elasticity of Amorphous Silicon and Silica from Density Functional Theory.

Density functional theory calculations and a finite deformation method are used to calculate second- and, most notably, third-order elastic constants of amorphous silicon and amorphous silicon dioxide, as represented by model structures generated via melt-quench force-field molecular dynamics simulations. Linear and nonlinear elastic constants are used to deduce macroscopic elastic moduli, such as the bulk and shear moduli, their pressure derivatives, and the elastic Grüneisen parameter. Our calculations show that the elastic properties of amorphous silicon reach the isotropic elastic limit within the nanometer length scale, attaining characteristics, both linear and nonlinear, comparable to those of crystalline silicon.

Nuclear quantum effects on glassy water under pressure: Vitrification and pressure-induced transformations.

We perform classical molecular dynamics (MD) and path-integral MD (PIMD) simulations of H2O and D2O using the q-TIP4P/F model over a wide range of temperatures and pressures to study the nuclear quantum effects (NQEs) on (i) the vitrification of liquid water upon isobaric cooling at different pressures and (ii) pressure-induced transformations at constant temperature between low-density amorphous and high-density amorphous ice (LDA and HDA) and hexagonal ice Ih and HDA. Upon isobaric cooling, classical and quantum H2O and D2O vitrify into a continuum of intermediate amorphous ices (IA), with densities in-between those of LDA and HDA (depending on pressure). Importantly, the density of the IA varies considerably if NQEs are included (similar conclusions hold for ice Ih at all pressures studied).

Peer social support moderates the impact of ethnoracial discrimination on mental health among young sexual minority men of color.

Few studies have examined developmentally relevant sources of resilience, such as peer social support, among young sexual minority men (SMM) of color experiencing discrimination and mental health distress. To address this gap in the literature, we examined the role of peer social support in the association between discrimination and mental health distress in a sample of young SMM of color. Ninety-four cisgender young SMM of color (aged 16-29) were recruited through community-based organizations in the New York City metropolitan area as part of an effectiveness trial of a tailored Motivational Interviewing intervention.

Ohm's law lost and regained: observation and impact of transmission and velocity zeros.

The quantum conductance and its classical wave analogue, the transmittance, are given by the sum of the eigenvalues of the transmission matrix. However, neither measurements nor theoretical analysis of the transmission eigenchannels have been carried out to explain the dips in conductance found in simulations as new channels are introduced. Here, we measure the microwave transmission matrices of random waveguides and find the spectra of all transmission eigenvalues, even at dips in the lowest transmission eigenchannel that are orders of magnitude below the noise in the transmission matrix.

Supercritical density fluctuations and structural heterogeneity in supercooled water-glycerol microdroplets.

Recent experiments and theoretical studies strongly indicate that water exhibits a liquid-liquid phase transition (LLPT) in the supercooled domain. An open question is how the LLPT of water can affect the properties of aqueous solutions. Here, we study the structural and thermodynamic properties of supercooled glycerol-water microdroplets at dilute conditions (χ = 3.

Potential energy landscape formalism for quantum molecular liquids.

The potential energy landscape (PEL) formalism is a powerful tool within statistical mechanics to study the thermodynamic properties of classical low-temperature liquids and glasses. Recently, the PEL formalism has been extended to liquids/glasses that obey quantum mechanics, but applications have been limited to atomistic model liquids. In this work, we extend the PEL formalism to liquid/glassy water using path-integral molecular dynamics (PIMD) simulations, where nuclear quantum effects (NQE) are included.

Truly the best of both worlds: Merging lineage-specific and universal probe kits to maximize phylogenomic inference.

Premise: Hybridization capture kits are now commonly used for reduced representation approaches in genomic sequencing, with both universal and clade-specific kits available. Here, we present a probe kit targeting 799 low-copy genes for the plant family Annonaceae.

Methods: This new version of the kit combines the original 469 genes from the previous Annonaceae kit with 334 genes from the universal Angiosperms353 kit.

Effect of a SARS-CoV-2 Protein Fragment on the Amyloidogenic Propensity of Human Islet Amyloid Polypeptide.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the onset of COVID-19 have been linked to an increased risk of developing type 2 diabetes. While a variety of mechanisms may ultimately be responsible for the onset of type 2 diabetes under these circumstances, one mechanism that has been postulated involves the increased aggregation of human islet amyloid polypeptide (hIAPP) through direct interaction with SARS-CoV-2 viral proteins. Previous computational studies investigating this possibility revealed that a nine-residue peptide fragment known as SK9 (SFYVYSRVK) from the SARS-CoV-2 envelope protein can stabilize the native conformation of hIAPP by interacting with the N-terminal region of amylin.

Fentanyl exposure alters rat CB1 receptor expression in the insula, nucleus accumbens and substantia nigra.

Prolonged periods of opioid use have been shown to cause neuroadaptations in the brain's reward circuitry, contributing to addictive behaviors and drug dependence. Recently, considerable focus has been placed on the role of the endocannabinoid system (ECS) and its CB receptors in opioid-driven behaviors. However, opioid-induced neuroadaptations to the ECS remain understudied.

Risk of infection due to airborne virus in classroom environments lacking mechanical ventilation.

The COVID-19 pandemic highlighted the role of indoor environments on disease transmission. However, our understanding of how transmission occurred evolved as the pandemic progressed. Enclosed spaces where pathogen-laden aerosols accumulate were strongly linked to increased transmission events.

Unveiling Nucleosome Dynamics: A Comparative Study Using All-Atom and Coarse-Grained Simulations Enhanced by Principal Component Analysis.

This study investigates nucleosome dynamics using both all-atom and coarse-grained (CG) molecular dynamics simulations, focusing on the SIRAH force field. Simulations are performed for two nucleosomal DNA sequences-ASP and Widom-601-over six microseconds at physiological salt concentrations. Comparative analysis of structural parameters, such as groove widths and base pair geometries, reveals good agreement between atomistic and CG models, though CG simulations exhibit broader conformational sampling and greater breathing motion of DNA ends.

The effect of cancer and cancer treatment on attention control: evidence from anti-saccade performance.

Purpose: Cancer and cancer treatment have been associated with cognitive changes in survivorship, with forgetfulness and distractibility reported years post-treatment. Deficits in attention control may explain these difficulties. We assessed breast cancer survivors using a primary measure of attention control, the saccade/antisaccade task, to assess the effects of diagnosis and treatment.

Engaging sexual minority adolescents in nationwide at-home HIV prevention research in the U.S.

Objectives: This study examined research-related privacy and confidentiality concerns among adolescent sexual minority males (ASMM) and provides lessons learned to inform recruitment and enrollment strategies for this population.

Methods: Participants were a 2017-2018 internet-based U.S.

Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Strategy for the Synthesis of α-Methoxytropones.

α-Methoxytropone is a structural motif found in various natural products and other compounds of interest to the scientific community but remains a synthetic challenge. The present Note describes the synthesis of variously substituted α-methoxytropones and related compounds through an intermolecular 3-hydroxy-4-pyrone-based oxidopyrylium (5 + 2) cycloaddition followed by a samarium iodide-mediated reductive ring-opening. The strategy is highlighted in the synthesis of a novel AC-ring analogue of colchicine to compare it to existing methods.

Neuroprotective effect of neuron-specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis.

Ceramide C16 is a sphingolipid detected at high levels in several neurodegenerative disorders, including multiple sclerosis (MS). It can be generated de novo or from the hydrolysis of other sphingolipids, such as sphingomyelin or through the recycling of sphingosine, in what is known as the salvage pathway. While the myelin damage occurring in MS suggests the importance of the hydrolytic and salvage pathways, the growing interest on the importance of diet in demyelinating disorders, prompted us to investigate the involvement of de novo ceramide C16 synthesis on disease severity.

Binding Selectivity Analysis from Alchemical Receptor Hopping and Swapping Free Energy Calculations.

We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol, where a ligand is alchemically transferred from one receptor to another in one simulation, directly yields the ligand's binding selectivity free energy (BSFE) for the two receptors, which is the difference between the two individual binding free energies. In the receptor swapping protocol, the first ligand of a pair is transferred from one receptor to another while the second ligand is simultaneously transferred in the opposite direction.

Elucidating structure and metabolism of insect biomaterials by solid-state NMR.

Among the many natural biomaterials for which information on atomic-level structure and reorientational motion can offer essential clues to function, insoluble multi-component composites with limited degrees of order are among the most challenging to study. Despite its limited sensitivity, solid-state NMR (ssNMR) is often the technique of choice to ferret out these details in carbon- and nitrogen-rich materials: this spectroscopic approach can probe many biomaterials in their native or near-native states, either with or without the introduction of stable NMR-active isotopes, or with the assistance of dynamic nuclear polarization technology. During a span of close to four decades, such research targets and ssNMR approaches have been exemplified by insects, a diverse and evolutionarily agile group of organisms with global impacts that include ecology, agriculture, and human disease.