Local context review by single institutional review boards: Results from a modified Delphi process.

Introduction: Local context is the most common concern regarding use of a single institutional review board (sIRB). Yet what "local context" constitutes remains underspecified. Developing a shared understanding of the goals of local context review, the categories of information that should be considered, as well as the types of studies for which sIRB review may be inappropriate, are critical for ensuring that sIRB review provides adequate protections for human subjects.

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Perceptions of Molecular HIV Surveillance Among Men Who Have Sex with Men in the United States.

Expanding HIV cluster detection using molecular HIV surveillance (MHS) raises ethical and social concerns, which may impede HIV outbreak detection and response as well as deter people living with HIV from seeking care. This underscores the need for effective communication strategies. We examined two methods for explaining MHS among men who have sex with men (MSM) living with HIV and at-risk without HIV in the United States.

Blurring Boundaries: A Proposed Research Agenda for Ethical, Legal, Social, and Historical Studies at the Intersection of Infectious and Genetic Disease.

Contemporary understanding of the mechanisms of disease increasingly points to examples of "genetic diseases" with an infectious component and of "infectious diseases" with a genetic component. Such blurred boundaries generate ethical, legal, and social issues and highlight historical contexts that must be examined when incorporating host genomic information into the prevention, outbreak control, and treatment of infectious diseases.

EMhub: a web platform for data management and on-the-fly processing in scientific facilities.

Most scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports and invoices presents additional challenges. To address these challenges, EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility, has been introduced.

Dynamic metal coordination controls chemoselectivity in radical halogenases.

The activation of inert C( )-H bonds by non-heme Fe enzymes plays a key role in metabolism, epigenetics, and signaling, while providing a powerful biocatalytic platform for the chemical synthesis of molecules with increased complexity. In this context, Fe /α-ketoglutarate-dependent radical halogenases represent a broadly interesting system, as they are uniquely capable of carrying out transfer of a diverse array of bound anions following C-H activation. Here, we provide the first experimental evidence that bifurcation of H-atom abstraction and radical rebound is driven both by the ability of a dynamic metal coordination sphere to reorganize as well as by a second-sphere hydrogen-bond network where only two residues (Asn224 and Ile151) are necessary and sufficient.

From Care to Corrections: A Scoping Review of Pathways from Child Protection to Adult Criminal Justice Systems.

Individuals who have experienced child protection system involvement are over-represented in criminal justice systems. This group faces greater risks of serious offending and justice system entrenchment relative to their peers without child protection system contact. Understanding the pathways from child protection to adult criminal justice system contact is critical for informing crime prevention policy and practice, yet most research on the maltreatment-offending relationship solely focuses on children's pathways from child protection to youth justice systems.

User experience with HIV molecular epidemiology in research, surveillance, and cluster detection and response: a needs assessment.

Objective: HIV molecular epidemiology (HIV ME) is a tool that aims to improve HIV research, surveillance, and cluster detection and response. HIV ME is a core pillar of the U.S.

Some remarks on "Efficient removal of total arsenic (As) from contaminated water by novel strategies mediated iron and plant extract activated waste flowers of marigold".

We explain here that the authors of the article cited in the title have misrepresented the species of As(III) and As(V) in solutions and, in particular, have neglected their speciation as a function of pH. Their discussion of (ad)sorption mechanisms is therefore unsatisfactory, especially since organic matter (flower waste) and the presence of iron oxyhydroxides should be taken into account. Furthermore, the modeling of (ad)sorption kinetics and isotherms was based on linearized equations, whereas the corresponding nonlinear equations should have been used.

Probing Ferryl Reactivity in a Nonheme Iron Oxygenase Using an Expanded Genetic Code.

The ability to introduce noncanonical amino acids as axial ligands in heme enzymes has provided a powerful experimental tool for studying the structure and reactivity of their Fe=O ("ferryl") intermediates. Here, we show that a similar approach can be used to perturb the conserved Fe coordination environment of 2-oxoglutarate (2OG) dependent oxygenases, a versatile class of enzymes that employ highly-reactive ferryl intermediates to mediate challenging C-H functionalizations. Replacement of one of the cis-disposed histidine ligands in the oxygenase VioC with a less electron donating -methyl-histidine (MeHis) preserves both catalytic function and reaction selectivity.

Single IRB Review and Local Context Considerations: A Scoping Review.

A leading concern about single IRB (sIRB) review for multisite studies, as is now required by federal policies, is whether and how sIRBs consider local context in their review. While several types of local context considerations have been proposed, there is no shared agreement among those charged with the ethics oversight of human subjects research as to the goals and content of local context review, nor the types of research studies for which sIRB review might be inappropriate. Through a scoping review of published scholarship, public comments, and federal guidance documents, we identified five assumed goals for local context review: protecting the rights and welfare of local participants; ensuring compliance with applicable laws and policies; assessing feasibility; promoting the quality of research; and promoting procedural justice.

Adolescent high fat diet alters the transcriptional response of microglia in the prefrontal cortex in response to stressors in both male and female mice.

Both obesity and high fat diets (HFD) have been associated with an increase in inflammatory gene expression within the brain. Microglia play an important role in early cortical development and may be responsive to HFD, particularly during sensitive windows, such as adolescence. We hypothesized that HFD during adolescence would increase proinflammatory gene expression in microglia at baseline and potentiate the microglial stress response.

An Unusual Ferryl Intermediate and Its Implications for the Mechanism of Oxacyclization by the Loline-Producing Iron(II)- and 2-Oxoglutarate-Dependent Oxygenase, LolO.

-Acetylnorloline synthase (LolO) is one of several iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenases that catalyze sequential reactions of different types in the biosynthesis of valuable natural products. LolO hydroxylates C2 of 1--acetamidopyrrolizidine before coupling the C2-bonded oxygen to C7 to form the tricyclic loline core. Each reaction requires cleavage of a C-H bond by an oxoiron(IV) (ferryl) intermediate; however, different carbons are targeted, and the carbon radicals have different fates.

Prioritization of ethical concerns regarding HIV molecular epidemiology by public health practitioners and researchers.

Background: HIV molecular epidemiology (HIV ME) can support the early detection of emerging clusters of new HIV infections by combining HIV sequence data routinely obtained during the clinical treatment of people living with HIV with behavioral, geographic, and sociodemographic information. While information about emerging clusters promises to facilitate HIV prevention and treatment efforts, the use of this data also raises several ethical concerns. We sought to assess how those working on the frontlines of HIV ME, specifically public health practitioners (PHPs) and researchers, prioritized these issues.

Stress-induced dysfunction of neurovascular astrocytes contributes to sex-specific behavioral deficits.

Astrocytes form an integral component of the neurovascular unit, ensheathing brain blood vessels with projections high in aquaporin-4 (AQP4) expression. These AQP4-rich projections facilitate interaction between the vascular endothelium, astrocytes, and neurons, and help stabilize vascular morphology. Studies using preclinical models of psychological stress and post-mortem tissue from patients with major depressive disorder (MDD) have reported reductions in AQP4, loss of astrocytic structures, and vascular impairment in the prefrontal cortex (PFC).

New Sorption Isotherms Derived from a Gamma Distribution of Binding Constants.

New sorption isotherms for heterogeneous sorbents are derived by combining a Gamma distribution of binding constants with a local isotherm defined by a Langmuir or Hill equation. The new "Gamma isotherms" are expressed as Stieltjes transforms of the distribution and involve generalized exponential integrals. The related energy distributions are asymmetric and present a peak corresponding to the mean binding constant.

Comparison of cerebrospinal fluid, plasma and neuroimaging biomarker utility in Alzheimer's disease.

Alzheimer's disease biomarkers are crucial to understanding disease pathophysiology, aiding accurate diagnosis and identifying target treatments. Although the number of biomarkers continues to grow, the relative utility and uniqueness of each is poorly understood as prior work has typically calculated serial pairwise relationships on only a handful of markers at a time. The present study assessed the cross-sectional relationships among 27 Alzheimer's disease biomarkers simultaneously and determined their ability to predict meaningful clinical outcomes using machine learning.

Rooting out faulty adsorption models. Comment on "Magnetic Prussian blue nanoshells are controllable (sic) anchored on the surface of molybdenum disulfide nanosheets for efficient separation of radioactive cesium from water".

This correspondence critically examines and rectifies modeling deficiencies identified in a recent article published in this journal. Our analysis covers a range of models and issues, including the Temkin isotherm, the Flory-Huggins isotherm, the pseudo-first-order kinetic model, the pseudo-second-order kinetic model, the intraparticle diffusion model, the Elovich kinetic model, and the computation of thermodynamic parameters. The elucidation and correction of these modeling issues contribute to a more accurate and reliable understanding of the studied phenomena, thereby enhancing the scientific rigor of the subject paper.

Stakeholder perspectives on data sharing from pragmatic clinical trials: Unanticipated challenges for meeting emerging requirements.

Introduction: Numerous arguments have been advanced for broadly sharing de-identified, participant-level clinical trial data. However, data sharing in pragmatic clinical trials (PCTs) presents ethical challenges. While prior scholarship has described aspects of PCTs that raise distinct considerations for data sharing, there have been no reports of the experiences of those at the leading edge of data-sharing efforts for PCTs, including how these particular challenges have been navigated.

Steric Perturbation of the Grob-like Final Step of Ethylene-Forming Enzyme Enables 3-Hydroxypropionate and Propylene Production.

Ethylene-forming enzyme (EFE) is an iron(II)-dependent dioxygenase that fragments 2-oxoglutarate (2OG) to ethylene (from C3 and C4) and 3 equivs of carbon dioxide (from C1, C2, and C5). This major ethylene-forming pathway requires l-arginine as the effector and competes with a minor pathway that merely decarboxylates 2OG to succinate as it oxidatively fragments l-arginine. We previously proposed that ethylene forms in a polar-concerted (Grob-like) fragmentation of a (2-carboxyethyl)carbonatoiron(II) intermediate, formed by the coupling of a C3-C5-derived propion-3-yl radical to a C1-derived carbonate coordinated to the Fe(III) cofactor.

Repeated Activation of Pyramidal Neurons in the Prefrontal Cortex Alters Microglial Phenotype in Male Mice.

Aberrant neuronal activity in the cortex alters microglia phenotype and function in several contexts, including chronic psychologic stress and neurodegenerative disease. Recent findings even suggest that heightened levels of neuronal activity spur microglia to phagocytose synapses, with potential impacts on cognition and behavior. Thus, the present studies were designed to determine if activation of neurons alone-independent of disease or dysfunction-is sufficient to alter microglial phenotype in the medial prefrontal cortex (mPFC), a brain region critical in emotion regulation and cognition.