Evidence of sex differences in ozone-induced oxysterol and cytokine levels in differentiated human nasal epithelial cells.

Acute exposure to ozone (O) causes upper and lower airway inflammation. We and others have previously demonstrated that O oxidizes lipids, particularly cholesterol, into electrophilic oxysterols, such as secosterol B (SecoB), which can adduct proteins, thus altering cellular signaling pathways. To investigate how O-derived oxysterols influence cytokine and chemokine release, nasal epithelial cells (HNECs) from healthy donors (N = 18 donors) were exposed to 0.

Neutral Lipid Storage Disease With Myopathy and Infiltrative Cardiomyopathy Initially Presenting as Right Arm Weakness.

Neutral lipid storage disease with myopathy is a rare genetic syndrome of abnormal intracellular lipolysis leading to lipid droplet accumulation in skeletal and cardiac muscle. Because of variability in clinical presentations, a multidisciplinary approach is essential for diagnosis and treatment.

Correction: Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.

Although in humans, the brain fails to heal after an injury, young zebrafish are able to restore tissue structural integrity in less than 24 h, thanks to the mechanical action of microglia.

Melatonin Vapes Contain Potential Contaminants and Alter the Human Bronchial Epithelial Transcriptome.

Melatonin vaping products, touted for their faster absorption than oral melatonin supplements, have been gaining popularity among adolescents as sleep aid. Here, we elucidated the response of human bronchial epithelial cells (hBECs) to high levels of melatonin from vaped aerosols, investigated the uptake of melatonin by hBECs , and characterized the chemical composition of three commercially available melatonin vapes. Melatonin vape exposure decreased the secretion of chemokines and produced an immunosuppressive gene expression signature.

Spatially heterogeneous lipid dysregulation in tuberculous meningitis.

Tuberculous (TB) meningitis is the deadliest form of extrapulmonary TB which disproportionately affects children and immunocompromised individuals. Studies in pulmonary TB have shown that Mycobacterium tuberculosis can alter host lipid metabolism to evade the immune system. Cholesterol lowering drugs (i.

Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.

Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investigated this process using in vivo observations of larval zebrafish brain injury. Our findings show that wound closure occurs within the first 24 h through global tissue contraction, as evidenced by live-imaging and drug inhibition studies.

"I need as much support as I can get": A qualitative study of young adult perspectives on family involvement in treatment for opioid use disorder.

Background: Opioid use disorder (OUD) among young adults (YAs) continues to persist as a national health crisis. Best practice recommendations for YA OUD treatment highlight the importance of medication for OUD (MOUD) and family involvement across the treatment services continuum for better treatment retention and outcomes. Yet, concerned significant others (CSOs) such as family members, romantic partners, and family-of-choice members are not routinely involved in OUD and MOUD treatment for YAs.

Heme-catalyzed degradation of linoleate 9-hydroperoxide (9-HPODE) forms two allylic epoxy-ketones via a proposed pseudo-symmetrical diepoxy radical intermediate.

Heme-initiated decomposition of unsaturated fatty acid hydroperoxides creates alkoxyl radicals that propagate a complex series of reactions to hydroxy, keto, epoxy and aldehydic products. Herein, among the products from the hematin-catalyzed degradation of 9-hydroperoxy-linoleic acid (9-HPODE), we observed a double peak on normal-phase HPLC that resolved on RP-HPLC into equal proportions of two epoxy-allylic ketones with identical UV spectra. Their proton NMR spectra were also indistinguishable and consistent with 9,10--epoxy-11-13-keto- and 9-keto-10-12,13--epoxy-octadecenoic acids.

A combinatorially complete epistatic fitness landscape in an enzyme active site.

Protein engineering often targets binding pockets or active sites which are enriched in epistasis-nonadditive interactions between amino acid substitutions-and where the combined effects of multiple single substitutions are difficult to predict. Few existing sequence-fitness datasets capture epistasis at large scale, especially for enzyme catalysis, limiting the development and assessment of model-guided enzyme engineering approaches. We present here a combinatorially complete, 160,000-variant fitness landscape across four residues in the active site of an enzyme.

Inhibition of post-lanosterol biosynthesis by fentanyl: potential implications for Fetal Fentanyl Syndrome (FFS).

A recent study discovered a novel, complex developmental disability syndrome, most likely caused by maternal fentanyl use disorder. This Fetal Fentanyl Syndrome (FFS) is biochemically characterized by elevated 7-dehydrocholesterol (7-DHC) levels in neonates, raising the question if fentanyl inhibition of the dehydrocholesterol reductase 7 (DHCR7) enzyme is causal for the emergence of the pathophysiology and phenotypic features of FFS. To test this hypothesis, we undertook a series of experiments on Neuro2a cells, primary mouse neuronal and astrocytic cultures, and human dermal fibroblasts (HDFs) with DHCR7 and DHCR7 genotype.

Standard Versus Family-Based Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Primary Care: Protocol for a Multisite Randomized Effectiveness Trial.

Background: Screening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning.

GAPDH inhibition mediated by thiol oxidation in human airway epithelial cells exposed to an environmental peroxide.

Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA.

The β-subunit of tryptophan synthase is a latent tyrosine synthase.

Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the β-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'.

Effects of saturated fatty acids with lysophospholipids on production and nutrient digestibility in lactating cows.

The objective of the experiment was to determine the effects of supplemental SFA sources, lysophospholipids (LPL), and their interaction on production and nutrient digestibility in lactating dairy cows. The experiment was conducted with 48 cows in a randomized complete block design. Cows were blocked (12 blocks total) by parity and days in milk and randomly assigned to 4 dietary treatments in each block (2 × 2 factorial arrangement), i.

Iron Heme Enzyme-Catalyzed Cyclopropanations with Diazirines as Carbene Precursors: Computational Explorations of Diazirine Activation and Cyclopropanation Mechanism.

The mechanism of cyclopropanations with diazirines as air-stable and user-friendly alternatives to commonly employed diazo compounds within iron heme enzyme-catalyzed carbene transfer reactions has been studied by means of density functional theory (DFT) calculations of model systems, quantum mechanics/molecular mechanics (QM/MM) calculations, and molecular dynamics (MD) simulations of the iron carbene and the cyclopropanation transition state in the enzyme active site. The reaction is initiated by a direct diazirine-diazo isomerization occurring in the active site of the enzyme. In contrast, an isomerization mechanism proceeding via the formation of a free carbene intermediate of a direct, one-step isomerization process was observed for model systems.

What is a Good Mother of Children with Autism? A Cross-Cultural Comparison Between the U.S. and Japan.

This study compared the characteristics of 'good mothers' of children with ASD (Autism Spectrum Disorder) as perceived by mothers of children with ASD in two countries-the U.S. and Japan.

CRL4b Inhibition Ameliorates Experimental Autoimmune Encephalomyelitis Progression.

Multiple sclerosis, and its murine model experimental autoimmune encephalomyelitis (EAE), is a neurodegenerative autoimmune disease of the CNS characterized by T cell influx and demyelination. Similar to other autoimmune diseases, therapies can alleviate symptoms but often come with side effects, necessitating the exploration of new treatments. We recently demonstrated that the Cullin-RING E3 ubiquitin ligase 4b (CRL4b) aided in maintaining genome stability in proliferating T cells.

Removal and detoxification of pentahalogenated phenols using a photocatalytically induced enzymatic process.

Poly-halogenated phenols generated from a range of industrial processes can find their way into rivers and ground water. Here we report on a potential treatment for reducing the toxicity of these aqueous pollutants using two highly toxic penta-halogenated phenols (pentachlorophenol (PCP) and pentabromophenol (PBP)) as surrogates. Solutions were passed through a glass column packed with a silica support fused with titanium dioxide (TiO) and horseradish peroxidase (HRP) immobilized on its TiO/glass surface (HRP-T).

c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8 T cell immunity.

During infection, virus-specific CD8 T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8 T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b).

Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism.

Background: Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers.

Methods: Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia.

Launching Relationship-Oriented Behavioral Services for Youth Opioid Use Disorder: Innovations in Medication Decision-Making and Adherence Planning.

This article presents behavioral interventions designed to enhance uptake and retention on medication for opioid use disorder (MOUD) among transition-age youth (16-25 years) enrolled in treatment services. The article describes three relationship-oriented interventions designed to address barriers to MOUD uptake, enhance MOUD adherence planning, and strengthen OUD recovery among youth: ; , and . These interventions are inter-connected can be delivered flexibly.