Identification of positions in human aldolase a that are neutral for apparent K.

According to evolutionary theory, many naturally-occurring amino acid substitutions are expected to be neutral or near-neutral, with little effect on protein structure or function. Accordingly, most changes observed in human exomes are also expected to be neutral. As such, accurate algorithms for identifying medically-relevant changes must discriminate rare, non-neutral substitutions against a background of neutral substitutions.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Objective: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel.

Design: Retrospective cohort study.

Methods: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques.

Conceptualizing Educational Comparability in Distributed Health Professions Education: A Scoping Review.

Purpose: This study aimed to create greater clarity about the current understanding and formulate a model of how educational comparability has been used in the literature to inform practice.

Method: The authors conducted a literature search of 9 online databases, seeking articles published on comparability in distributed settings in health professions education before August 2021, with an updated search conducted in May 2023. Using a structured scoping review approach, 2 reviewers independently screened articles for eligibility with inclusion criteria and extracted key data.

Saponin TQL1055 adjuvant-containing vaccine confers protection upon challenge in mice.

Tuberculosis (TB), caused by the intracellular pathogen (), affects the lungs of infected individuals (pulmonary TB) but can also affect other sites (extrapulmonary TB). The only licensed vaccine bacillus (BCG) protects infants and young children but exhibits variable efficacy in protecting against adult pulmonary TB. Poor compliance and prolonged treatment regimens associated with the use of chemotherapy has contributed to the development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) .

Divalent cations in human liver pyruvate kinase exemplify the combined effects of complex-equilibrium and allosteric regulation.

There is growing recognition that the functional outcome of binding of an allosteric regulator to a protein/enzyme is influenced by the presence of other ligands. Here, this complexity is exemplified in the allosteric regulation of human liver pyruvate kinase (hLPYK) that is influenced by the presence of a range of divalent cation types and concentrations. For this system, fructose-1,6-bisphosphate (activator) and alanine (inhibitor) both influence the protein's affinity for the substrate, phosphoenolpyruvate (PEP).

Emerging Trends in Machine Learning: A Polymer Perspective.

In the last five years, there has been tremendous growth in machine learning and artificial intelligence as applied to polymer science. Here, we highlight the unique challenges presented by polymers and how the field is addressing them. We focus on emerging trends with an emphasis on topics that have received less attention in the review literature.

Feasibility and acceptability of mobile methods to assess home and neighborhood environments related to adolescent sleep.

Objective: A growing evidence base suggests home and neighborhood environmental exposures may influence adolescent sleep, but few studies have assessed these relationships using methods that account for time-varying, location-specific exposures, or multiple neighborhood contexts. This study aimed to assess the feasibility and acceptability of using smartphone global positioning system (GPS) tracking and ecological momentary assessment (EMA) to assess time-varying home and neighborhood environmental exposures hypothesized to be associated with adolescent sleep.

Methods: Adolescents aged 15-17 years in Philadelphia completed 7 days of continuous smartphone GPS tracking, which was used to identify daily levels of exposure to geocoded neighborhood factors (eg, crime, green space).

Qualities of the dying experience of persons who access medical assistance in dying: A scoping review.

Defining a "good death" is complex and grounded in diverse cultural, social, and personal factors. Although there is a significant body of literature exploring the broad concepts of death and dying, there is a dearth in literature that has explored what constitutes a good death for persons undergoing assisted dying such as Medical Assistance in Dying (MAiD). In this scoping review of 19 articles, we explore dying experiences and what a good death entails for people accessing MAiD.

Odd one out? Functional tuning of Zymomonas mobilis pyruvate kinase is narrower than its allosteric, human counterpart.

Various protein properties are often illuminated using sequence comparisons of protein homologs. For example, in analyses of the pyruvate kinase multiple sequence alignment, the set of positions that changed during speciation ("phylogenetic" positions) were enriched for "rheostat" positions in human liver pyruvate kinase (hLPYK). (Rheostat positions are those which, when substituted with various amino acids, yield a range of functional outcomes).

Role of nanoparticle size and surface chemistry on ion transport and nanostructure of perfluorosulfonic acid ionomer nanocomposites.

Herein, we present a systematic investigation of the impact of silica nanoparticle (SiNP) size and surface chemistry on the nanoparticle dispersion state and the resulting morphology and vanadium ion permeability of the composite ionomer membranes. Specifically, Nafion containing a mass fraction of 5% silica particles, ranging in nominal diameters from 10 nm to >1 μm and with both sulfonic acid- and amine-functionalized surfaces, was fabricated. Most notably, an 80% reduction in vanadium ion permeability was observed for ionomer membranes containing amine-functionalized SiNPs at a nominal diameter of 200 nm.

Examining the Macrosystem Level of Influence on Community Health Worker Effectiveness in the State of Nebraska: A Qualitative Approach.

Community health workers (CHWs) serve as the linkage between community and providers and are stakeholders for bridging services to the public. However, integration of CHWs into health care organizations is often lacking. This study explored macrosystem level barriers faced by CHWs and their ability to do their jobs effectively.

Substitutions at a rheostat position in human aldolase A cause a shift in the conformational population.

Some protein positions play special roles in determining the magnitude of protein function: at such "rheostat" positions, varied amino acid substitutions give rise to a continuum of functional outcomes, from wild type (or enhanced), to intermediate, to loss of function. This observed range raises interesting questions about the biophysical bases by which changes at single positions have such varied outcomes. Here, we assessed variants at position 98 in human aldolase A ("I98X").

Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation.

When amino acids vary during evolution, the outcome can be functionally neutral or biologically-important. We previously found that substituting a subset of nonconserved positions, "rheostat" positions, can have surprising effects on protein function. Since changes at rheostat positions can facilitate functional evolution or cause disease, more examples are needed to understand their unique biophysical characteristics.

Nurtured in Nature: a Pilot Randomized Controlled Trial to Increase Time in Greenspace among Urban-Dwelling Postpartum Women.

Spending time in nature is associated with numerous mental health benefits, including reduced depression and improved well-being. However, few studies examine the most effective ways to nudge people to spend more time outside. Furthermore, the impact of spending time in nature has not been previously studied as a postpartum depression (PPD) prevention strategy.

Addressing the challenges of modeling the scattering from bottlebrush polymers in solution.

Small-angle scattering measurements of complex macromolecules in solution are used to establish relationships between chemical structure and conformational properties. Interpretation of the scattering data requires an inverse approach where a model is chosen and the simulated scattering intensity from that model is iterated to match the experimental scattering intensity. This raises challenges in the case where the model is an imperfect approximation of the underlying structure, or where there are significant correlations between model parameters.

Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression.

Expression of the Human Endogenous Retrovirus Type K (HERV-K), the youngest and most active HERV, has been associated with various cancers and neurodegenerative diseases. As in all retroviruses, a fraction of HERV-K transcripts is exported from the nucleus in unspliced or incompletely spliced forms to serve as templates for translation of viral proteins. In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA appears to be mediated by a cis-acting signal on the mRNA, the RcRE, and the protein Rec-these are analogous to the RRE-Rev system in HIV-1.

Radiology Workload Changes During the COVID-19 Pandemic: Implications for Staff Redeployment.

Rationale And Objectives: Quantify changes in total and by-subspecialty radiology workload due to deferring nonurgent services during the initial COVID-19 pandemic, and describe operational strategies implemented due to shifts in priority.

Materials And Methods: This retrospective, Institutional Review Board-exempt, study was performed between February 3, 2020 and April 19, 2020 at a large academic medical center. During March 9-15 (intervention period), nonurgent outpatient service deferments began.

Effect of Carbohydrate Mouth Rinse on Resistance Exercise Performance.

Green, MS, Kimmel, CS, Martin, TD, Mouser, JG, and Brune, MP. Effect of carbohydrate mouth rinse on resistance exercise performance. J Strength Cond Res 36(7): 1916-1921, 2022-A carbohydrate mouth rinse (CMR) has been shown to enhance short duration endurance performance and raises the possibility that a similar strategy could improve performance during resistance exercise.

H/D Exchange Characterization of Silent Coupling: Entropy-Enthalpy Compensation in Allostery.

The allosteric coupling constant in K-type allosteric systems is defined as a ratio of the binding of substrate in the absence of effector to the binding of the substrate in the presence of a saturating concentration of effector. As a result, the coupling constant is itself an equilibrium value comprised of a ΔH and a TΔS component. In the scenario in which TΔS completely compensates ΔH, no allosteric influence of effector binding on substrate affinity is observed.

Identification of biochemically neutral positions in liver pyruvate kinase.

Understanding how each residue position contributes to protein function has been a long-standing goal in protein science. Substitution studies have historically focused on conserved protein positions. However, substitutions of nonconserved positions can also modify function.

Bottlebrush polymers in the melt and polyelectrolytes in solution share common structural features.

Uncharged bottlebrush polymer melts and highly charged polyelectrolytes in solution exhibit correlation peaks in scattering measurements and simulations. Given the striking superficial similarities of these scattering features, there may be a deeper structural interrelationship in these chemically different classes of materials. Correspondingly, we constructed a library of isotopically labeled bottlebrush molecules and measured the bottlebrush correlation peak position [Formula: see text] by neutron scattering and in simulations.