The biarylitides: understanding the structure and biosynthesis of a fascinating class of Cytochrome P450 modified RiPP natural products.

The biarylitides are a recently discovered class of RiPP natural products that are fascinating both from the small size of the core peptides as well as the diversity of peptide crosslinking exhibited by the cytochrome P450 enzymes found in these systems. In this review, we address the discovery and biosynthetic diversity of these systems and discuss the methods and challenges of analysing the structures of these constrained cyclic peptides. We also discuss the structures of the P450 enzymes involved in these pathways and address the potential for alternate catalytic outcomes and activities as seen most recently with the inclusion of biarylitide related enzymes within rufomycin biosynthesis.

Loss of fluorine during crosslinking by the biarylitide P450 proceeds due to restricted peptide orientation.

The biarylitide crosslinking enzyme P450 can perform crosslinking between -F-Tyr-3 and His-5 residues within peptide substrates with concomitant and specific loss of fluorine. Our investigations suggest that a small intrinsic preference for coupling to fluorine is magnified by the binding of the peptide in a specific orientation that enforces the loss of fluorine during peptide crosslinking, likely a two-step reaction mechanism involving the non-enzyme catalysed reductive elimination of fluoride.

No Sex Differences in Perceptual Responses to High-Intensity Interval Training or Sprint Interval Training.

Coe, LN and Astorino, TA. No sex differences in perceptual responses to high-intensity interval training or sprint interval training. J Strength Cond Res 36(6): 1025-1032, 2024-High-intensity interval training (HIIT) elicits similar and, in some cases, superior benefits vs.

Reassignment of the Structure of a Tryptophan-Containing Cyclic Tripeptide Produced by the Biarylitide Crosslinking Cytochrome P450.

The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450 from Micromonospora sp. MW-13 has been reanalysed by a series of NMR, computational and isotope labelling experiments and shown to contain a C-N rather than a C-O bond. Additional in vivo experiments using such a modified peptide show there is a general tolerance of biarylitide crosslinking P450 enzymes for histidine to tryptophan mutations within their minimal peptide substrate sequences despite the lack of such residues noted in natural biarylitide gene clusters.

An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides.

Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450 enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown.

Examining Cultural Competency and Sexual Abuse Training Needs Among Service Providers Working with Black and Latino Sexual Minority Men.

Black and Latino sexual minority men (SMM) with a history of childhood sexual abuse (CSA) may be reluctant to disclose such experiences or may appraise them as consensual because of cultural norms. Anticipated stigma, medical mistrust, and concerns that providers lack training in sexuality may complicate their efforts to obtain treatment for long-term health consequences of CSA. It is important to examine the training needs of service providers working with SMM who may disclose sexual abuse.

gen. nov. sp. nov., a diatom symbiont isolated from the phycosphere of .

A diatom-associated bacterium, designated as strain F10, was isolated from a pure culture of the pennate diatom A3 and has since been used to characterize molecular mechanisms of symbiosis between phytoplankton and bacteria, including interactions using diatom-derived azelaic acid. Its origin from a hypersaline environment, combined with its capacity for quorum sensing, biofilm formation, and potential for dimethylsulfoniopropionate methylation/cleavage, suggest it is within the family . Initial phylogenetic analysis of the 16S rRNA gene sequence placed this isolate within the genus, but recent genomic and phylogenomic analyses show strain F10 is a separate lineage diverging from the genus .

Building a queer- and trans-inclusive microbiology conference.

Microbiology conferences can be powerful places to build collaborations and exchange ideas, but for queer and transgender (trans) scientists, they can also become sources of alienation and isolation. Many conference organizers would like to create welcoming and inclusive events but feel ill-equipped to make this vision a reality, and a historical lack of representation of queer and trans folks in microbiology means we rarely occupy these key leadership roles ourselves. Looking more broadly, queer and trans scientists are systematically marginalized across scientific fields, leading to disparities in career outcomes, professional networks, and opportunities, as well as the loss of unique scientific perspectives at all levels.

Sex differences in hemodynamic response to high-intensity interval exercise.

Sex differences in the cardiorespiratory and hemodynamic response to exercise exist due to differences in heart size, blood volume, and hemoglobin mass, eliciting higher maximal oxygen uptake (VO ) in men versus women. Data are equivocal whether sex differences in training responsiveness occur. This study investigated potential sex differences in the hemodynamic response (stroke volume (SV) and cardiac output (CO)) to high-intensity interval exercise (HIIE).

Aneurysm management in patients over 80 years old with good grade subarachnoid haemorrhage.

Background: An increasing proportion of aneurysmal subarachnoid haemorrhage (aSAH) occurs in older patients, in whom there is widespread variability in treatment rates due to a different balance of risks. Our aim was to compare outcomes of patients over 80 years old with good grade aSAH who underwent treatment of their aneurysm with those who did not.

Methods: Adult patients with good grade aSAH admitted to tertiary regional neurosciences centres contributing to the UK and Ireland Subarachnoid Haemorrhage Database (UKISAH) and a cohort of consecutive patients admitted from three regional cohorts were included for analysis.

Clinical Effectiveness of Calcium Oxalate Stone Treatments.

Introduction: Lowering kidney stone risk and urine calcium oxalate supersaturation is a primary clinical focus for kidney stone prevention and can be achieved with multiple strategies. Common strategies include advice to increase fluid intake, restrict dietary sodium, or prescribing a thiazide-type diuretic. We investigated how physicians make these decisions in real-world practice and evaluate their efficacy based on 24-h urine collections.

Recovery and Resilience in the Canal Community: Economic Impacts and Solutions During the COVID-19 Pandemic.

Background: Public health pandemics, such as COVID-19, not only impact the physical health and wellbeing of communities but also often have far-reaching effects on their social, psychological, environmental, and economic welfare. The coronavirus pandemic has highlighted the significant inequities experienced among those who are Black, Indigenous, and People of Color (BIPOC), especially in the areas of housing instability, unemployment, and debt accrual. This study investigates the socioeconomic impacts of COVID-19 on residents of the Canal neighborhood ("The Canal"), a low-income Latinx community in Marin County, California.

Service provider interpretations of childhood sexual experiences among sexual minority men.

In this study, we report findings from a directed content analysis of service provider (SP) interpretations of early sexual experiences depicted in vignettes created from retrospective interviews with Black sexual minority men. Specifically, we explore whether SP recognize circumstances of abuse in the vignette narrators' sexual histories. Data for this analysis come from in-person qualitative interviews conducted with 35 providers working in substance abuse treatment and allied health service settings (e.

Early Sexual Experiences, Mental Health, and Risk Behavior among Black Non-Hispanic and Hispanic / Latino Men Who Have Sex with Men (MSM).

Black and Latino men who have sex with men (MSM) are disproportionately affected by childhood sexual abuse (CSA). Investigating these histories is often confounded by underreporting and varied definitions of abuse. Unrecognized abuse may manifest in unhealthy ways, specifically psychological distress, substance use, and high-risk sexual behaviors.

An Integrated Approach to Falls Prevention: A Model for Linking Clinical and Community Interventions through the Massachusetts Prevention and Wellness Trust Fund.

Older adult falls continue to be a public health priority across the United States-Massachusetts (MA) being no exception. The MA Prevention and Wellness Trust Fund (PWTF) program within the MA Department of Public Health aims to reduce the physical and economic burdens of chronic health conditions by linking evidence-based clinical care with community intervention programs. The PWTF partnerships that focused on older adult falls prevention integrated the Centers for Disease Control and Prevention's toolkit into clinical settings.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 2. General Practices.

Work in a biosafety level 4 (BSL-4) containment laboratory requires time and great attention to detail. The same work that is done in a BSL-2 laboratory with non-high-consequence pathogens will take significantly longer in a BSL-4 setting. This increased time requirement is due to a multitude of factors that are aimed at protecting the researcher from laboratory-acquired infections, the work environment from potential contamination and the local community from possible release of high-consequence pathogens.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 1. Biosafety Level 4 Suit Laboratory Suite Entry and Exit Procedures.

Biosafety level 4 (BSL-4) suit laboratories are specifically designed to study high-consequence pathogens for which neither infection prophylaxes nor treatment options exist. The hallmarks of these laboratories are: custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure ("space") suits. The risk for laboratory specialists working with highly pathogenic agents is minimized through rigorous training and adherence to stringent safety protocols and standard operating procedures.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 4. Medical Imaging Procedures.

Medical imaging using animal models for human diseases has been utilized for decades; however, until recently, medical imaging of diseases induced by high-consequence pathogens has not been possible. In 2014, the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Integrated Research Facility at Fort Detrick opened an Animal Biosafety Level 4 (ABSL-4) facility to assess the clinical course and pathology of infectious diseases in experimentally infected animals. Multiple imaging modalities including computed tomography (CT), magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography are available to researchers for these evaluations.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 3. Aerobiology.

Aerosol or inhalational studies of high-consequence pathogens have recently been increasing in number due to the perceived threat of intentional aerosol releases or unexpected natural aerosol transmission. Specific laboratories designed to perform these experiments require tremendous engineering controls to provide a safe and secure working environment and constant systems maintenance to sustain functionality. Class III biosafety cabinets, also referred to as gloveboxes, are gas-tight enclosures with non-opening windows.

Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation.

Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Previous studies demonstrate that T1-diabetes decreases osteoblast activity and viability. Bisphosphonate therapy, commonly used to treat osteoporosis, is demonstrated to inhibit osteoclast activity as well as osteoblast apoptosis.