Understanding and controlling the dynamic process of aflatoxin B (AFB) accumulation by Aspergillus flavus (A. flavus) remains challenging. In this study, the A.
View Article and Find Full Text PDFThe stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate.
View Article and Find Full Text PDF-a mycotoxigenic fungus and food safety threat-coinhabits maize kernels with . This protective endophyte produces secondary metabolites of interest, pyrrocidines A and B, which inhibit the growth of and specifically block fumonisin biosynthesis. Previous transcriptomic analyses found (FVEG_00314), a gene adjacent to the fumonisin biosynthetic gene cluster, to be induced over 4,000-fold in response to pyrrocidine challenge.
View Article and Find Full Text PDFThe mycotoxigenic fungi, and , commonly co-colonize maize in the field, yet their direct interactions at the chemical communication level have not been well characterized. Here, we examined if and how the two most infamous mycotoxins produced by these species, aflatoxin and fumonisin, respectively, govern interspecies growth and mycotoxin production. We showed that fumonisin producing strains of suppressed the growth of while non-producers did not.
View Article and Find Full Text PDFUnlabelled: Policy Points A redirection of measurement in health care from a narrow focus on diseases and care processes towards assessing whole person health, as perceived by the person themself, may provide a galvanizing view of how health care can best meet the needs of people and help patients feel heard, seen, and understood by their care team. This review identifies key tensions to navigate as well as four overarching categories of whole person health for consideration in developing an instrument optimized for clinical practice. The categories (body and mind, relationships, living environment and finances, and engagement in daily life) include nine constituent domains.
View Article and Find Full Text PDFBackground: Fatigue is common in multiple sclerosis (MS); it significantly impairs quality of life, and treatment options are limited. A randomized controlled trial of Elevida, a self-guided, online German fatigue intervention, showed significant benefit. We tested an English version of Elevida with people with MS in Australia.
View Article and Find Full Text PDFObjective: Crafting high-quality value sets is time-consuming and requires a range of clinical, terminological, and informatics expertise. Despite widespread agreement on the importance of reusing value sets, value set repositories suffer from clutter and redundancy, greatly complicating efforts at reuse. When users encounter multiple value sets with the same name or ostensibly representing the same clinical condition, it can be difficult to choose amongst them or determine if any differences among them are due to error or intentional decision.
View Article and Find Full Text PDFBackground/objectives: Food insecurity (FI) is defined as the lack of consistent access to enough food for an active and healthy life. FI affects over 30 million Americans and is associated with poor clinical outcomes and impaired quality of life and drives significant health inequities. Despite the rising prevalence of FI and the federal focus on improving access to healthy food, there is a paucity of research on FI in patients with inflammatory bowel disease (IBD).
View Article and Find Full Text PDFRNAs are often studied in nonnative sequence contexts to facilitate structural studies. However, seemingly innocuous changes to an RNA sequence may perturb the native structure and generate inaccurate or ambiguous structural models. To facilitate the investigation of native RNA secondary structure by selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), we engineered an approach that couples minimal enzymatic steps to RNA chemical probing and mutational profiling (MaP) reverse transcription (RT) methods-a process we call template switching and mutational profiling (Switch-MaP).
View Article and Find Full Text PDFTerminology value sets are central to research studies using real-world patient data. We describe the considerable challenges that arise when researchers develop value sets for their studies or reuse those made by others. We present Value Set Hub (VS-Hub), software to overcome these challenges, describing its design, implementation, features, use in the field, lessons learned, and future directions.
View Article and Find Full Text PDFAs epigenetic therapies continue to gain ground as potential treatment strategies for cancer and other diseases, compounds that target histone lysine methylation and the enzyme complexes represent a major frontier for therapeutic development. Clinically viable therapies targeting the activities of histone lysine methyltransferases (HKMT) and demethylases (HKDMs) have only recently begun to emerge following FDA approval of the EZH2 inhibitor tazemetostat in 2020 and remain limited to compounds targeting the well-studied SET domain-containing HKMTs and their opposing HKDMs. These include the H3K27 methyltransferases EZH2/EZH1, the singular H3K79 methyltransferase DOT1L, and the H3K4 methyltransferase MLL1/COMPASS as well as H3K9 and H3K36 methyltransferases.
View Article and Find Full Text PDFBackground: Multiple Sclerosis (MS) is a chronic inflammatory neurodegenerative disease with diverse symptomatology, significantly impacting patients' quality of life (QoL). While pharmacological therapies focus primarily on reducing inflammation and relapse rates, non-pharmacological interventions, including digital health applications, have shown promise in improving QoL among persons with MS (PwMS). Pilot studies had shown the feasibility and acceptability of levidex, a digital health application based on cognitive behavioral therapy (CBT) principles, a broad set of behavior change techniques, and relevant lifestyle-change advice.
View Article and Find Full Text PDFFungal genetic systems ideally combine molecular tools for genome manipulation and a sexual reproduction system to create an informative assortment of combinations of genomic modifications. When employing the sexual cycle to generate multi-mutants, the background genotype variations in the parents may result in progeny phenotypic variation obscuring the effects of combined mutations. Here, to mitigate this variation in , we generated a strain that was near isogenic to the sequenced wild-type strain, FGSC7600.
View Article and Find Full Text PDFBackground: Right ventricular (RV) hemodynamic performance determines the prognosis of patients with RV pressure overload. Using ultrafast ultrasound, natural wave velocity (NWV) induced by cardiac valve closure was proposed as a new surrogate to quantify myocardial stiffness.
Objectives: This study aimed to assess RV NWV in rodent models and children with RV pressure overload vs control subjects and to correlate NWV with RV hemodynamic parameters.
Risk assessment is the cornerstone of working safely with biological agents. The World Health Organization (WHO) Laboratory Biosafety Manual Fourth Edition Monograph on Risk Assessment provides stepwise guidance for completing a risk assessment, from information gathering and identifying hazards to evaluating the risks, developing, and implementing controls and review.To support the development of a mature safety culture within laboratories, it is important that all staff who handle biological agents understand the fundamentals of risk assessment and receive training in identifying hazards created by their work activities (or tasks) and understand how to mitigate the risks arising from carrying out that work.
View Article and Find Full Text PDFSecondary and tertiary RNA structures play key roles in genome replication of single-stranded positive sense RNA viruses. Complex, functional structures are particularly abundant in the untranslated regions of picornaviruses, where they are involved in initiation of translation, priming of new strand synthesis and genome circularization. The 5' UTR of foot-and-mouth disease virus (FMDV) is predicted to include a c.
View Article and Find Full Text PDFMalnutrition is estimated to affect roughly 30%-80% of patients with inflammatory bowel disease (IBD). In those patients who cannot tolerate sufficient oral nutrition or there is no possibility for placing an enteral nutrition tube, parenteral nutrition offers a lifesaving alternative. However, this is not without risk.
View Article and Find Full Text PDFImportance: Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy.
Objective: To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy.