Divergent Tandem Acyl Carrier Proteins Necessitate In-Series Polyketide Processing in the Leinamycin Family.

The leinamycin family of polyketides are promising antitumor antibiotics, yet several aspects of their biosynthesis remain elusive. All leinamycin family members bear a sulfur-containing moiety which is essential for the anticancer activity exhibited by leinamycin. The key building blocks required for the incorporation of these functionalities are introduced in the final module of the polyketide synthase (PKS), which elegantly combines β-branching and thiocysteine incorporation to generate a diverse library of sulfur-based molecular scaffolds.

Prevalence of indoor air pollutants from First Nation homes in North Central British Columbia, Canada.

Poor indoor air quality poses significant health risks. This study addresses the gap in knowledge regarding the prevalence of indoor air pollutants in remote and rural First Nation communities in north-central British Columbia, Canada. Dust samples from 75 homes were collected and analysed for house dust mites, pet allergens, mould antigens, and bacterial endotoxins.

An Integrated Module Performs Selective 'Online' Epoxidation in the Biosynthesis of the Antibiotic Mupirocin.

The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges, and the timing and mechanisms of several key transformations remain elusive. Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid side chain required for biological activity.

Structure and Function of the α-Hydroxylation Bimodule of the Mupirocin Polyketide Synthase.

Mupirocin is a clinically important antibiotic produced by a -AT Type I polyketide synthase (PKS) in . The major bioactive metabolite, pseudomonic acid A (PA-A), is assembled on a tetrasubstituted tetrahydropyran (THP) core incorporating a 6-hydroxy group proposed to be introduced by α-hydroxylation of the thioester of the acyl carrier protein (ACP) bound polyketide chain. Herein, we describe an in vitro approach combining purified enzyme components, chemical synthesis, isotopic labelling, mass spectrometry and NMR in conjunction with in vivo studies leading to the first characterisation of the α-hydroxylation bimodule of the mupirocin biosynthetic pathway.

Structure and Function of the α-Hydroxylation Bimodule of the Mupirocin Polyketide Synthase.

Mupirocin is a clinically important antibiotic produced by a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens. The major bioactive metabolite, pseudomonic acid A (PA-A), is assembled on a tetrasubstituted tetrahydropyran (THP) core incorporating a 6-hydroxy group proposed to be introduced by α-hydroxylation of the thioester of the acyl carrier protein (ACP) bound polyketide chain. Herein, we describe an in vitro approach combining purified enzyme components, chemical synthesis, isotopic labelling, mass spectrometry and NMR in conjunction with in vivo studies leading to the first characterisation of the α-hydroxylation bimodule of the mupirocin biosynthetic pathway.

Programmed Iteration Controls the Assembly of the Nonanoic Acid Side Chain of the Antibiotic Mupirocin.

Mupirocin is a clinically important antibiotic produced by NCIMB 10586 that is assembled by a complex -AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown.

Programmed Iteration Controls the Assembly of the Nonanoic Acid Side Chain of the Antibiotic Mupirocin.

Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown.

Photovoice exploration of physical activity norms and values among rural and remote pulmonary rehabilitation participants in British Columbia, Canada.

Purpose: Individuals with chronic obstructive pulmonary disease (COPD) engage in less physical activity compared to the general population, which can lead to worsened symptoms. In pulmonary rehabilitation (PR) programs, participants learn strategies to complete activities more easily. For such strategies to be effective, however, PR clinicians must understand their clients' activity values and practices within their geocultural contexts.

Is Female Wellness Affected When Men Blame Them for Erectile Dysfunction?

Introduction: Several studies have investigated the association between erectile dysfunction (ED), its treatment, and female sexual dysfunction, but the impact of males blaming their female partners for their ED remains unknown.

Aims: To investigate whether women who are blamed by their male partners for their ED experience worse overall sexual function and satisfaction.

Methods: We performed a global, cross-sectional web-based survey to investigate female perceptions of ED.

Solution Structure and Conformational Dynamics of a Doublet Acyl Carrier Protein from Prodigiosin Biosynthesis.

The acyl carrier protein (ACP) is an indispensable component of both fatty acid and polyketide synthases and is primarily responsible for delivering acyl intermediates to enzymatic partners. At present, increasing numbers of multidomain ACPs have been discovered with roles in molecular recognition of trans-acting enzymatic partners as well as increasing metabolic flux. Further structural information is required to provide insight into their function, yet to date, the only high-resolution structure of this class to be determined is that of the doublet ACP (two continuous ACP domains) from mupirocin synthase.

SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein-thioesterase domains from a fungal nonreducing polyketide synthase.

Menisporopsin A is a fungal bioactive macrocyclic polylactone, the biosynthesis of which requires only reducing (R) and nonreducing (NR) polyketide synthases (PKSs) to guide a series of esterification and cyclolactonization reactions. There is no structural information pertaining to these PKSs. Here, we report the solution characterization of singlet and doublet acyl carrier protein (ACP and ACP -ACP )-thioesterase (TE) domains from NR-PKS involved in menisporopsin A biosynthesis.

Structure of the Human Cation-Independent Mannose 6-Phosphate/IGF2 Receptor Domains 7-11 Uncovers the Mannose 6-Phosphate Binding Site of Domain 9.

The cation-independent mannose 6-phosphate (M6P)/Insulin-like growth factor-2 receptor (CI-MPR/IGF2R) is an ∼300 kDa transmembrane protein responsible for trafficking M6P-tagged lysosomal hydrolases and internalizing IGF2. The extracellular region of the CI-MPR has 15 homologous domains, including M6P-binding domains (D) 3, 5, 9, and 15 and IGF2-binding domain 11. We have focused on solving the first structures of human D7-10 within two multi-domain constructs, D9-10 and D7-11, and provide the first high-resolution description of the high-affinity M6P-binding D9.

A Priming Cassette Generates Hydroxylated Acyl Starter Units in Mupirocin and Thiomarinol Biosynthesis.

Mupirocin, a commercially available antibiotic produced by NCIMB 10586, and thiomarinol, isolated from the marine bacterium sp. SANK 73390, both consist of a polyketide-derived monic acid homologue esterified with either 9-hydroxynonanoic acid (mupirocin, 9HN) or 8-hydroxyoctanoic acid (thiomarinol, 8HO). The mechanisms of formation of these deceptively simple 9HN and 8HO fatty acid moieties in and , respectively, remain unresolved.

Attachment, Parenting, and Obesogenic Behavior: A Dyadic Perspective.

Pediatric obesity is a growing health concern afflicting the United States. The treatment for pediatric obesity, as a health epidemic, costs billions of dollars to our nation, leaving providers and researchers searching for effective and sustainable ways to better manage the biological, psychological, and social health of individuals and families. While many assessments and interventions continue to emerge, researchers have predominately focused on intra-individual concerns among white non-Hispanic populations.

Evaluation of Indicators of Female Sexual Dysfunction in Adult Entertainers.

Introduction: Female sexual dysfunction (FSD) incorporates a wide range of sexual issues within the female population; however, it has not been evaluated among female adult entertainers.

Aim: To evaluate the prevalence of FSD in women working in the adult entertainment industry.

Methods: A 53-question online survey was distributed to female adult entertainers via e-mail through collaboration with the Free Speech Coalition, the North American Trade Association of the Adult Industry.

The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA.

Toxin-antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species.

Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics.

Background: Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi-disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist.

Improvements to the Vulva, Vestibule, Urethral Meatus, and Vagina in Women Treated With Ospemifene for Moderate to Severe Dyspareunia: A Prospective Vulvoscopic Pilot Study.

Introduction: Ospemifene, an oral selective estrogen receptor modulator approved for the treatment of mild to moderate dyspareunia from menopause, has been shown to moderate sexual pain and vaginal epithelial cell characteristics. However, no prospective vulvoscopic studies have been performed.

Aim: To examine, in menopausal women taking ospemifene 60 mg daily, changes to the vulva, vestibule, urethral meatus, and vaginal region over 20 weeks using vulvoscopy in a prospective open-label pilot study.

Treatment Effects of WST11 Vascular Targeted Photodynamic Therapy for Urothelial Cell Carcinoma in Swine.

Purpose: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model.

Bilateral adrenal hemorrhage due to heparin-induced thrombocytopenia following partial nephrectomy - a case report.

Heparin-induced thrombocytopenia (HIT) can cause severe life-threatening events such as bilateral adrenal hemorrhage (BAH). A 48-year-old female developed a pulmonary embolus (PE) following partial nephrectomy. The anticoagulation treatment for her PE was complicated by HIT and subsequent BAH.

Androgen deficiency and metabolic syndrome in men.

Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population.

Automated camera-phone experience with the frequency of imaging necessary to capture diet.

Camera-enabled cell phones provide an opportunity to strengthen dietary recall through automated imaging of foods eaten during a specified period. To explore the frequency of imaging needed to capture all foods eaten, we examined the number of images of individual foods consumed in a pilot study of automated imaging using camera phones set to an image-capture frequency of one snapshot every 10 seconds. Food images were tallied from 10 young adult subjects who wore the phone continuously during the work day and consented to share their images.

Eight self-administered 24-hour dietary recalls using the Internet are feasible in African Americans and Whites: the energetics study.

Objective: To support research and to provide food and nutrition practitioners with a strong foundation for nutrient-based counseling, there is a need for affordable automated 24-hour dietary recalls. Multiple days of intake, along with repeated reports over time, are needed to achieve stable indicators of individual intakes and to support evaluation of success in meeting dietary goals because of intraindividual intake variability. Little information has been published on subject responses, participation rates, and the perceived subject burden of repeated 24-hour recalls.