Widening the Road to Health Professions Education: Expanding Access for Diverse and Underserved Populations.

The Spring 2023 Webinar Audio Seminar (WAS) of the International Association of Medical Science Educators (IAMSE), titled "Widening the Road to Health Professions Education: Expanding Access for Diverse and Underserved Populations," was designed to help health science educators explore innovative practices in recruiting and enrolling students from underserved populations into health sciences programs. From March 2, 2023, to March 30, 2023, this five-part webinar series was broadcast live to institutions and educators worldwide. This series helped participants learn about creating pathways for students to meet the unique needs of their communities.

Degradation of polypropylene by fungi Coniochaeta hoffmannii and Pleurostoma richardsiae.

The urgent need for better disposal and recycling of plastics has motivated a search for microbes with the ability to degrade synthetic polymers. While microbes capable of metabolizing polyurethane and polyethylene terephthalate have been discovered and even leveraged in enzymatic recycling approaches, microbial degradation of additive-free polypropylene (PP) remains elusive. Here we report the isolation and characterization of two fungal strains with the potential to degrade pure PP. Twenty-seven fungal strains, many isolated from hydrocarbon contaminated sites, were screened for degradation of commercially used textile plastic. Of the candidate strains, two identified as Coniochaeta hoffmannii and Pleurostoma richardsiae were found to colonize the plastic fibers using scanning electron microscopy (SEM). Further experiments probing degradation of pure PP films were performed using C. hoffmannii and P. richardsiae and analyzed using SEM, Raman spectroscopy and Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). The results showed that the selected fungi were active against pure PP, with distinct differences in the bonds targeted and the degree to which each was altered. Whole genome and transcriptome sequencing was conducted for both strains and the abundance of carbohydrate active enzymes, GC content, and codon usage bias were analyzed in predicted proteomes for each. Enzymatic assays were conducted to assess each strain's ability to degrade naturally occurring compounds as well as synthetic polymers. These investigations revealed potential adaptations to hydrocarbon-rich environments and provide a foundation for further investigation of PP degrading activity in C. hoffmannii and P. richardsiae.

Fatty Acid Synthesis Knockdown Promotes Biofilm Wrinkling and Inhibits Sporulation in Bacillus subtilis.

Many bacterial species typically live in complex three-dimensional biofilms, yet much remains unknown about differences in essential processes between nonbiofilm and biofilm lifestyles. Here, we created a CRISPR interference (CRISPRi) library of knockdown strains covering all known essential genes in the biofilm-forming Bacillus subtilis strain NCIB 3610 and investigated growth, biofilm colony wrinkling, and sporulation phenotypes of the knockdown library. First, we showed that gene essentiality is largely conserved between liquid and surface growth and between two media. Second, we quantified biofilm colony wrinkling using a custom image analysis algorithm and found that fatty acid synthesis and DNA gyrase knockdown strains exhibited increased wrinkling independent of biofilm matrix gene expression. Third, we designed a high-throughput screen to quantify sporulation efficiency after essential gene knockdown; we found that partial knockdowns of essential genes remained competent for sporulation in a sporulation-inducing medium, but knockdown of essential genes involved in fatty acid synthesis exhibited reduced sporulation efficiency in LB, a medium with generally lower levels of sporulation. We conclude that a subset of essential genes are particularly important for biofilm structure and sporulation/germination and suggest a previously unappreciated and multifaceted role for fatty acid synthesis in bacterial lifestyles and developmental processes. IMPORTANCE For many bacteria, life typically involves growth in dense, three-dimensional communities called biofilms that contain cells with differentiated roles held together by extracellular matrix. To examine how essential gene function varies between vegetative growth and the developmental states of biofilm formation and sporulation, we created and screened a comprehensive library of strains using CRISPRi to knockdown expression of each essential gene in the biofilm-capable Bacillus subtilis strain 3610. High-throughput assays and computational algorithms identified a subset of essential genes involved in biofilm wrinkling and sporulation and indicated that fatty acid synthesis plays important and multifaceted roles in bacterial development.

Addressing the Opioid Crisis: A Dynamic Case-Based Module Set for Interprofessional Educators, Learners, and Clinicians.

Introduction: In 2017, the opioid crisis was declared a public health emergency in the United States. The CDC has called for a multifaceted, collaborative approach to address the opioid epidemic. Though many resources have been made available for provider education, much of what has been published to date has focused narrowly on specific contexts and/or has become outdated. Methods: To address the need for more up-to-date and broad-based training, we designed a dynamic, module-based curriculum aligned with the 2016 CDC Opioid Prescribing Guideline. The three-part module set addresses safe opioid prescribing, recognizing and treating opioid use disorders, and opioids and pain management. Each module contains interactive content and assessments and culminates in case-based applications. The modules provide an anchor point for supplemental activities that can be utilized in various contexts. Results: As of May 2021, we recorded 3,529 module completions (≥80% performance on module assessments). A 6-month follow-up survey revealed that the majority of respondents had used the strategies they had learned to improve their prescribing practice and believed they had improved outcomes for patients. Discussion: The modules and supplementary resources can be used by clinicians and educators to combat the opioid epidemic with best practices in patient care and by meeting many state licensure requirements. Included supplemental resources are ideal for learners, providing a comprehensive understanding of the opioid crisis as well as tools for medication-assisted treatment that create capacity to immediately address these issues once learners become fully licensed.

Circadian Clock Control of Translation Initiation Factor eIF2α Activity Requires eIF2γ-Dependent Recruitment of Rhythmic PPP-1 Phosphatase in Neurospora crassa.

The circadian clock controls the phosphorylation and activity of eukaryotic translation initiation factor 2α (eIF2α). In Neurospora crassa, the clock drives a daytime peak in the activity of the eIF2α kinase CPC-3, the homolog of yeast and mammalian GCN2 kinase. This leads to increased levels of phosphorylated eIF2α (P-eIF2α) and reduced mRNA translation initiation during the day. We hypothesized that rhythmic eIF2α activity also requires dephosphorylation of P-eIF2α at night by phosphatases. In support of this hypothesis, we show that mutation of N. crassa PPP-1, a homolog of the yeast eIF2α phosphatase GLC7, leads to high and arrhythmic P-eIF2α levels, while maintaining core circadian oscillator function. PPP-1 levels are clock-controlled, peaking in the early evening, and rhythmic PPP-1 levels are necessary for rhythmic P-eIF2α accumulation. Deletion of the N terminus of N. crassa eIF2γ, the region necessary for eIF2γ interaction with GLC7 in yeast, led to high and arrhythmic P-eIF2α levels. These data supported that N. crassa eIF2γ functions to recruit PPP-1 to dephosphorylate eIF2α at night. Thus, in addition to the activity of CPC-3 kinase, circadian clock regulation of eIF2α activity requires dephosphorylation by PPP-1 phosphatase at night. These data show how the circadian clock controls the activity a central regulator of translation, critical for cellular metabolism and growth control, through the temporal coordination of phosphorylation and dephosphorylation events.IMPORTANCE Circadian clock control of mRNA translation contributes to the daily cycling of a significant proportion of the cellular protein synthesis, but how this is accomplished is not understood. We discovered that the clock in the model fungus Neurospora crassa regulates rhythms in protein synthesis by controlling the phosphorylation and dephosphorylation of a conserved translation initiation factor eIF2α. During the day, N. crassa eIF2α is phosphorylated and inactivated by CPC-3 kinase. At night, a clock-controlled phosphatase, PPP-1, dephosphorylates and activates eIF2α, leading to increased nighttime protein synthesis. Translation requires significant cellular energy; thus, partitioning translation to the night by the clock provides a mechanism to coordinate energy metabolism with protein synthesis and cellular growth.

Feasibility of Implementing a Tai Chi Program in an Assisted Living Facility: Reducing Fall Risks and Improving Quality of Life.

One in four American older adults fall every year, resulting in injuries, death, and significant financial burden. Although fall etiology is multifactorial, the medical problems and aging factors that lead to unsteady gait and imbalance represent one of the major fall risks among older adults. A growing number of research studies support the health benefits of regular Tai Chi (TC) practice including improved physical, cognitive, and psychological function. The purpose of this quality improvement project was to assess the feasibility of establishing a 12-week (45 min per session) Tai Chi (TC) program (Sun Style Tai Chi) in a 75 bed assisted living facility as well as to evaluate the potential of the TC program to improve the fear of falling and functional mobility (as proxy for fall risk) and quality of life (QoL). A nurse who was a certified TC instructor taught the program. Twenty-three participants, 96% female and 96% white, mean (SD) age 83 (±7) years, attended one or more TC classes. Class attendance, self-reported questionnaires (e.g., fear of falling, QoL), and objective measure Timed Up and Go (TUG) were used to collect data. Nine participants (39%) completed 9 out of 12 sessions. Eleven participants (48%) completed both pre- and post-intervention measurements and twelve (52%) provided feedback on a post-intervention satisfaction survey. Participants showed 20% improvement in fear of falling (mean relative change) and 21% decrease (mean relative change) in TUG test (p = 0.001) with no clinically important changes in QoL. This quality improvement project suggested that TC is a feasible exercise that might have the potential to reduce risk of falls in older adults, and the program was well accepted with no serious or other adverse events reported. Further research studies are needed to examine the potential effects of TC programs with an appropriately powered RCT and longer intervention period.

Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.

The aplyronines are a family of highly cytotoxic marine natural products with potential application in targeted cancer chemotherapy. To address the severe supply issue, function-oriented molecular editing of their macrolactone scaffold led to the design of a series of simplified aplyronine analogues. Enabled by a highly convergent aldol-based route, the total synthesis of four analogues was achieved, with a significant improvement in step economy versus previous compounds, and their cancer cell growth inhibition in the HeLa cell line was determined. The modular strategy presented offers a means for significantly shortening their chemical synthesis to facilitate the continued development of this promising class of anticancer agent.

Economic and technical assessment of rooftop solar photovoltaic potential in Brownsville, Texas, U.S.A.

Localized assessment of solar energy economic feasibility will benefit the structuring of residential solar energy deployment globally. In the U.S. growing interest in rooftop residential solar among city managers has spurred the development of photovoltaic (PV) feasibility maps of the technical and economic solar potential within cities. The City of Brownsville, Texas was interested in evaluating solar feasibility for their city but lacked information to make informed policy decisions on PV development. This paper presents novel and systems approaches for determining the technical and economic feasibility of solar development for homes in the Brownsville using LiDAR and local information. Residential technical and economic potential was assessed by optimizing the internal rate of return (IRR) and an average residential building demand profile to determine ideal size and placement of solar arrays. Results showed that residential structures in Brownsville have the technical potential to generate approximately 11% of the total energy provided by the local utility; however, average IRR was only 2.9% with a payback period of over 15 years. Five neighborhoods in the City of Brownsville were identified with spatially clustered homes that had relatively higher IRRs compared with other areas in the city. Despite the high technical potential, modeled results indicate that perspective home owners interested in solar development may require additional incentives to improve the economic feasibility of PV in Brownsville. This study provides a demonstration of an interdisciplinary systems approach and methodology that can be adopted internationally to evaluate the feasibility of solar development in other areas.

2'-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA.

Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2'-alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron-electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information.

Mechanisms for the formation of organic acids in the gas-phase ozonolysis of 3-carene.

This paper describes experimental studies aimed at elucidating mechanisms for the formation of low-volatility organic acids in the gas-phase ozonolysis of 3-carene. Experiments were carried out in a static chamber under 'OH-free' conditions. A range of multifunctional acids-which are analogous to those observed from alpha-pinene ozonolysis-were identified in the condensed phase using gas chromatography coupled to mass spectrometry after derivation. Product yields were determined as a function of different OH radical scavengers and relative humidities to give mechanistic information about their routes of formation. Furthermore, an enone and an enal derived from 3-carene were ozonised in order to probe the early mechanistic steps in the reaction and, in particular, which of the two initially formed Criegee intermediates gives rise to which products. Branching ratios for the formation of the two Criegee Intermediates are determined. Similarities and differences in product formation from 3-carene and alpha-pinene ozonolysis are discussed and possible mechanisms-supported by experimental evidence-are developed for all acids investigated.

Organic acid formation in the gas-phase ozonolysis of alpha-pinene.

The mechanism of formation of pinonic and norpinonic acids from alpha-pinene ozonolysis has been investigated by studying the products of the ozonolysis of an enone derived from alpha-pinene using gas chromatography coupled to mass spectrometry.

A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14.

The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.