Development of a framework to structure decision-making in environmental and occupational health: A systematic review and Delphi study.

Background: Environmental and occupational health (EOH) assessments increasingly utilize systematic review methods and structured frameworks for evaluating evidence about the human health effects of exposures. However, there is no prevailing approach for how to integrate this evidence into decisions or recommendations. Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision (EtD) frameworks provide a structure to support standardized and transparent consideration of relevant criteria to inform health decisions.

The Albany Conversations Are Now the Next Generation Conversations: Albany @ Ruston.

This commentary is a report on the 1st Next Gen. Conversation: Albany @ Ruston 2024 held on the campus of Louisiana Tech University June 11-15, 2024. The 2nd Next Gen.

Navigating the complexity of p53-DNA binding: implications for cancer therapy.

Abstract: The tumor suppressor protein p53, a transcription factor playing a key role in cancer prevention, interacts with DNA as its primary means of determining cell fate in the event of DNA damage. When it becomes mutated, it opens damaged cells to the possibility of reproducing unchecked, which can lead to formation of cancerous tumors. Despite its critical role, therapies at the molecular level to restore p53 native function remain elusive, due to its complex nature.

Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders.

The accumulation of senescent cells induces several aging phenotypes, and the p53 tumor suppressor protein regulates one of the two known cellular senescence pathways. p53's regulation of senescence is however not clear. For example, p53 deficiency in some mice has been shown to rescue premature aging while others display significant aging phenotype when p53-deficient.

Projecting the Potential Clinical and Economic Impact of HIV Prevention Resource Reallocation in Tennessee.

Background: In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST).

Methods: We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation, funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST).

GNN Codon Adjacency Tunes Protein Translation.

The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons.

Reconnaissance of Allostery via the Restoration of Native p53 DNA-Binding Domain Dynamics in Y220C Mutant p53 Tumor Suppressor Protein.

Allosteric regulation of protein dynamics infers a long-range deliberate propagation of information via micro- and macroscale interactions. The Y220C structural mutant is one of the most frequent cancerous p53 mutants. The mutation is distally located from the DNA-binding site of the p53 DNA-binding domain yet causes changes in DNA recognition.

Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard.

Background: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS.

Objectives: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest.

Molecular dynamics of mismatch detection-How MutS uses indirect readout to find errors in DNA.

The mismatch repair protein MutS safeguards genomic integrity by finding and initiating repair of basepairing errors in DNA. Single-molecule studies show MutS diffusing on DNA, presumably scanning for mispaired/unpaired bases, and crystal structures show a characteristic "mismatch-recognition" complex with DNA enclosed within MutS and kinked at the site of error. But how MutS goes from scanning thousands of Watson-Crick basepairs to recognizing rare mismatches remains unanswered, largely because atomic-resolution data on the search process are lacking.

Network Analysis of Molecular Dynamics Sectors in the p53 Protein.

Design of allosteric regulators is an emergent field in the area of drug discovery holding promise for currently untreated diseases. Allosteric regulators bind to a protein in one location and affect a distant site. The ubiquitous presence of allosteric effectors in biology and the success of serendipitously identified allosteric compounds point to the potential they hold.

Allosteric Signaling in PDZ Energetic Networks: Embedding Error Analysis.

Allosteric signaling in proteins has been known for some half a century, yet how the signal traverses the protein remains an active area of research. Recently, the importance of electrostatics to achieve long-range signaling has become increasingly appreciated. Our laboratory has been working on developing network approaches to capture such interactions.

Variable Regions of p53 Isoforms Allosterically Hard Code DNA Interaction.

Allosteric regulation of protein activity pervades biology as the "second secret of life." We have been examining the allosteric regulation and mutant reactivation of the tumor suppressor protein p53. We have found that generalizing the definition of allosteric effector to include entire proteins and expanding the meaning of binding site to include the interface of a transcription factor with its DNA to be useful in understanding the modulation of protein activity.

Case studies to explore the optimal use of randomized and nonrandomized studies in evidence syntheses that use GRADE.

Objectives: Randomized controlled trials (RCTs) are the preferred source of evidence for the relative effect of healthcare interventions summarized in knowledge syntheses. Nonrandomized studies of interventions (NRSI) may provide replacement, sequential, or complementary evidence to RCTs. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach can provide different options for properly using RCTs and NRSI integrated in health syntheses.