Structural determination and characterisation of the CYP105Q4 cytochrome P450 enzyme from Mycobacterium marinum.

The cytochrome P450 family of heme metalloenzymes (CYPs) catalyse important biological monooxygenation reactions. Mycobacterium marinum contains a gene encoding a CYP105Q4 enzyme of unknown function. Other members of the CYP105 CYP family have key roles in bacterial metabolism including the synthesis of secondary metabolites.

A single polymorphic residue in humans underlies species-specific restriction of HSV-1 by the antiviral protein MxB.

Herpesviruses present a major global disease burden. Understanding the host cell mechanisms that block viral infections, as well as how viruses can evolve to counteract these host defenses, is critically important for understanding viral disease pathogenesis. This study reveals that the major human variant of the antiviral protein myxovirus resistance protein B (MxB) inhibits the human pathogen herpes simplex virus (HSV-1), whereas a minor human variant and orthologous MxB genes from even closely related primates do not.

In vivo acoustic patterning of endothelial cells for tissue vascularization.

Strategies to fabricate microvascular networks that structurally and functionally mimic native microvessels are needed to address a host of clinical conditions associated with tissue ischemia. The objective of this work was to advance a novel ultrasound technology to fabricate complex, functional microvascular networks directly in vivo. Acoustic patterning utilizes forces within an ultrasound standing wave field (USWF) to organize cells or microparticles volumetrically into defined geometric assemblies.

Methamphetamine and emerging drugs of concern: A training needs analysis of Australian alcohol and other drug helplines.

Introduction: Fielding greater than 100,000 calls annually, telephone helplines are an important point of entry to alcohol and other drug (AOD) support and services in Australia. Methamphetamine and emerging drugs can present a particular challenge for this workforce. We sought to identify training needs for these services, so that appropriate targeted resources can be developed.

A single polymorphic residue in humans underlies species-specific restriction of HSV-1 by the antiviral protein MxB.

Unlabelled: Myxovirus resistance proteins (MxA and MxB) are interferon-induced proteins that exert antiviral activity against a diverse range of RNA and DNA viruses. In primates, MxA has been shown to inhibit myxoviruses, bunyaviruses, and hepatitis B virus, whereas MxB restricts retroviruses and herpesviruses. As a result of their conflicts with viruses, both genes have been undergoing diversifying selection during primate evolution.

Selective carbon-hydrogen bond hydroxylation using an engineered cytochrome P450 peroxygenase.

The cytochrome P450 enzyme CYP102A1 (P450BM3) is a versatile monooxygenase enzyme which has been adapted and engineered for multiple applications in chemical synthesis. Mutation of threonine 268 to glutamate (Thr268Glu) converted the heme domain of this enzyme into a HO utilizing peroxygenase. This variant displayed significantly increased peroxide driven hydroxylation activity towards the saturated linear fatty acids tested (undecanoic through to hexadecenoic acid) when compared to the wild-type heme domain.

Antagonism of Protein Kinase R by Large DNA Viruses.

Decades of research on vaccinia virus (VACV) have provided a wealth of insights and tools that have proven to be invaluable in a broad range of studies of molecular virology and pathogenesis. Among the challenges that viruses face are intrinsic host cellular defenses, such as the protein kinase R pathway, which shuts off protein synthesis in response to the dsRNA that accumulates during replication of many viruses. Activation of PKR results in phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), inhibition of protein synthesis, and limited viral replication.

A comparison of the bacterial CYP51 cytochrome P450 enzymes from Mycobacterium marinum and Mycobacterium tuberculosis.

Members of the CYP51 family of cytochrome P450 enzymes are classified as sterol demethylases involved in the metabolic formation of cholesterol and related derivatives. The CYP51 enzyme from Mycobacterium marinum was studied and compared to its counterpart from Mycobacterium tuberculosis to determine the degree of functional conservation between them. Spectroscopic analyses of substrate and inhibitor binding of the purified CYP51 enzymes from M.

Causal Relationships between Personal Networks and Health: A Comparison of Three Modeling Strategies.

Prior research documents associations between personal network characteristics and health, but establishing causation has been a long-standing research priority. To evaluate approaches to causal inference in egocentric network data, this article uses three waves from the University of California Berkeley Social Networks Study (N = 1,159) to investigate connections between nine network variables and two global health outcomes. We compare three modeling strategies: cross-sectional ordinary least squares regression, regression with lagged dependent variables (LDVs), and hybrid fixed and random effects models.

Management of transitions to adult services for young people with eating disorders: survey of current practice in England.

Aims And Method: The Royal College of Psychiatrists has published recommendations for managing transitions between child and adolescent mental health services (CAMHS) and adult services for eating disorders. A self-report questionnaire was designed to establish how many CAMHS teams meet these recommendations and was distributed to 70 teams providing eating disorders treatment in England.

Results: Of the 38 services that participated, 31 (81.

Network Support and Negative Life Events Associated With Chronic Cardiometabolic Disease Outcomes.

Introduction: Stress from negative life events may be an important risk factor for chronic cardiometabolic conditions, which are increasingly prevalent among young adults. Support from personal networks is known to buffer stress from negative life events. Yet, evidence for these relationships among both young and older adults remains unclear.

The Stereoselective Oxidation of para-Substituted Benzenes by a Cytochrome P450 Biocatalyst.

The serine 244 to aspartate (S244D) variant of the cytochrome P450 enzyme CYP199A4 was used to expand its substrate range beyond benzoic acids. Substrates, in which the carboxylate group of the benzoic acid moiety is replaced were oxidised with high activity by the S244D mutant (product formation rates >60 nmol.(nmol-CYP) .

Kinetic Evidence for an Induced Fit Mechanism in the Binding of the Substrate Camphor by Cytochrome P450.

Bacterial cytochrome P450 (P450) 101A1 (P450) has served as a prototype among the P450 enzymes and has high catalytic activity towards its cognate substrate, camphor. X-ray crystallography and NMR and IR spectroscopy have demonstrated the existence of multiple conformations of many P450s, including P450. Kinetic studies have indicated that substrate binding to several P450s is dominated by a conformational selection process, in which the substrate binds an individual conformer(s) of the unliganded enzyme.

Estimating the effect of selective border relaxation on COVID-19 in New Zealand.

Aims: We developed a model, updated daily, to estimate undetected COVID-19 infections exiting quarantine following selectively opening New Zealand's borders to travellers from low-risk countries.

Methods: The prevalence of infectious COVID-19 cases by country was multiplied by expected monthly passenger volumes to predict the rate of arrivals. The rate of undetected infections entering the border following screening and quarantine was estimated.

Rapid adaptation to human protein kinase R by a unique genomic rearrangement in rhesus cytomegalovirus.

Cytomegaloviruses (CMVs) are generally unable to cross species barriers, in part because prolonged coevolution with one host species limits their ability to evade restriction factors in other species. However, the limitation in host range is incomplete. For example, rhesus CMV (RhCMV) can replicate in human cells, albeit much less efficiently than in rhesus cells.

Characterization of human adrenal cytochrome P450 11B2 products of progesterone and androstenedione oxidation.

Cytochrome P450 (P450) 11B1 and 11B2 both catalyze the 11β-hydroxylation of 11-deoxycorticosterone and the subsequent 18-hydroxylation of the product. P450 11B2, but not P450 11B1, catalyzes a further C-18 oxidation to yield aldosterone. 11-Oxygenated androgens are of interest, and 11-hydroxy progesterone has been reported to be a precursor of these.

Functional interactions of adrenodoxin with several human mitochondrial cytochrome P450 enzymes.

Seven of the 57 human cytochrome P450 (P450) enzymes are mitochondrial and carry out important reactions with steroids and vitamins A and D. These seven P450s utilize an electron transport chain that includes NADPH, NADPH-adrenodoxin reductase (AdR), and adrenodoxin (Adx) instead of the diflavin NADPH-P450 reductase (POR) used by the other P450s in the endoplasmic reticulum. Although numerous studies have been published involving mitochondrial P450 systems, the experimental conditions vary considerably.

Direct and Moderating Causal Effects of Network Support on Sleep Quality: Findings From the UC Berkeley Social Network Study.

Background: Sleep is an important, restorative behavior for health, yet many adults report troubled sleep. The existence of a support network may be beneficial for sleep quality, including as a buffer for stressful events, yet few studies have examined these relationships longitudinally.

Purpose: To examine the causal effect of changes in personal network support on sleep quality both directly and as a buffer of negative life events among young and older adults.

A comparison of steroid and lipid binding cytochrome P450s from Mycobacterium marinum and Mycobacterium tuberculosis.

The steroid lipid binding cytochrome P450 (CYP) enzymes of Mycobacterium tuberculosis are essential for organism survival through metabolism of cholesterol and its derivatives. The counterparts to these enzymes from Mycobacterium marinum were studied to determine the degree of functional conservation between them. Spectroscopic analyses of substrate and inhibitor binding for the four M.

Multistep Binding of the Non-Steroidal Inhibitors Orteronel and Seviteronel to Human Cytochrome P450 17A1 and Relevance to Inhibition of Enzyme Activity.

Orteronel (TAK-700) is a substituted imidazole that was developed for the treatment of castration-resistant prostate cancer but was dropped in phase III clinical trials. Both enantiomers of this inhibitor of cytochrome P450 (P450) 17A1 show some selectivity in differentially blocking the 17α-hydroxylation and lyase activities of the enzyme. Although both enantiomers of this compound have sub-micromolar IC values and bind to the enzyme with a type II spectral change (indicative of nitrogen-iron bonding) and reported values of 56 and 40 nM ( and , respectively), the rates of binding to P450 17A1 were relatively slow.

Tracking your emotions: An eye-tracking study on reader's engagement with perspective during text comprehension.

An eye-tracking study explored perspective effects on eye-movements during reading. We presented texts that included either a personal perspective () or an onlooker perspective (he or she). We measured whether fixations on the pronouns themselves differed as a function of perspective, and whether fixations on pronouns were affected by the emotional valence of the text which was either positive or negative.

Personal networks and associations with psychological distress among young and older adults.

Objective: The aim of the study was to provide new tests of the argument that aspects of personal networks affect psychological distress and moderate the effects of negative life events, leveraging new, rich data on two different cohorts.

Method: The UCNets project measured psychological distress, life events, and various dimensions of personal networks for 673 50- to 70-year old adults and 485 21- to 30-year old adults. The project used stratified random address based sampling for all the older adults.

Socioeconomic Differences in Access to Neighborhood and Network Social Capital and Associations With Body Mass Index Among Black Americans.

Purpose: To examine associations between socioeconomic status and two forms of social capital, namely, neighborhood and network measures, and how these distinct forms of capital are associated with body mass index (BMI) among Black residents of low-income communities.

Design: Respondent-driven sampling was used to engage residents in a household survey to collect data on the respondents' personal network, perceptions about their neighborhood environment, and health.

Setting: Eight special emphasis neighborhoods in Greenville, South Carolina.