Elucidation of alkane metabolism in the filamentous fungi Ascocoryne sarcoides

Ph. D. ThesisAscocoryne sarcoides has been reported to produce a variety of secondary metabolites such as linear and cyclic alkanes that are suitable for biofuel applications. Alkanes and alkenes are important as they are fully compatible with current fuel infrastructure. The genetic and biochemical basis for the biosynthesis of linear alkanes in fungi is not known and routes for cyclic alkane biosynthesis in any domain remains to be established. In this thesis, A. sarcoides was able to grow robustly in chemically-defined media in which linear, but not cyclic, alkanes are the sole carbon source, providing evidence for fungal degradation of alkanes. To establish alkane metabolic pathways in A. sarcoides, the genome and metabolome of six publicly available A. sarcoides isolates were examined. The genomes of all six isolates were sequenced, assembled and annotated. For each isolate, over 10, 000 gene products were identified by combining expression data with Hidden Markov machine learning. Each genome and predicted proteome achieved over 90% complete annotation against BUSCO’s database, considered the threshold for a high-quality dataset. No homology to known alkane producing genes were detected in any A. sarcoides isolates. By integrating annotations, pathway mapping and gene ontology with comparative analysis, hypothetical pathways for alkane degradation (via ALK-like P450), linear alkane biosynthesis (via fdc1-mediated fatty acid decarboxylation/decarbonylation) and cyclic alkane biosynthesis (via lipid lyase route) are proposed. These findings provide candidate genes for downstream heterologous expression and have the potential to increase the available toolkit for advanced biofuel applications. Solvent extraction and stir bar sorptive methods coupled to GC/MS were used to screen for biogenic hydrocarbon metabolites. The solvent extraction method did not identified the presence of biogenic alkanes. Moreover, results from SBSE were inconclusive in establishing A. sarcoides as an alkane producer due to exogenic alkane contamination and will require further method development.BBSR

Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology

Background: Emerging evidence demonstrates that bone is an endocrine organ capable of influencing multiple physiological and pathological processes through the secretion of hormones. Recent research suggests complex crosstalk between the bone and other metabolic and cardiovascular tissues. It was uncovered that three of these bone-derived hormones—osteocalcin, lipocalin 2, and sclerostin—are involved in the endocrine regulations of cardiometabolic health and play vital roles in the pathophysiological process of developing cardiometabolic syndromes such as type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation is one of the hallmarks of cardiometabolic diseases and a major contributor to disease progression. Novel evidence also implicates important roles of bone-derived hormones in the regulation of chronic inflammation. Scope of review: In this review, we provide a detailed overview of the physiological and pathological roles of osteocalcin, lipocalin 2, and sclerostin in cardiometabolic health regulation and disease development, with a focus on the modulation of chronic inflammation. Major conclusions: Evidence supports that osteocalcin has a protective role in cardiometabolic health, and an increase of lipocalin 2 contributes to the development of cardiometabolic diseases partly via pro-inflammatory effects. The roles of sclerostin appear to be complicated: It exerts pro-adiposity and pro-insulin resistance effects in type 2 diabetes and has an anti-calcification effect during cardiovascular disease. A better understanding of the actions of these bone-derived hormones in the pathophysiology of cardiometabolic diseases will provide crucial insights to help further research develop new therapeutic strategies to treat these diseases

Traditional electrosurgery and a low thermal injury dissection device yield different outcomes following bilateral skin-sparing mastectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although a skin- and nipple-sparing mastectomy technique offers distinct cosmetic and reconstructive advantages over traditional methods, partial skin flap and nipple necrosis remain a significant source of post-operative morbidity. Prior work has suggested that collateral thermal damage resulting from electrocautery use during skin flap development is a potential source of this complication. This report describes the case of a smoker with recurrent ductal carcinoma <it>in situ </it>(DCIS) who experienced significant unilateral skin necrosis following bilateral skin-sparing mastectomy while participating in a clinical trial examining mastectomy outcomes with two different surgical devices. This unexpected complication has implications for the choice of dissection devices in procedures requiring skin flap preservation.</p> <p>Case presentation</p> <p>The patient was a 61-year-old Caucasian woman who was a smoker with recurrent DCIS of her right breast. As part of the clinical trial, each breast was randomized to either the standard of care treatment group (a scalpel and a traditional electrosurgical device) or treatment with a novel, low thermal injury dissection device, allowing for a direct, internally controlled comparison of surgical outcomes. Post-operative follow-up at six days was unremarkable for both operative sites. At 16 days post-surgery, the patient presented with a significant wound necrosis in the mastectomy site randomized to the control study group. Following debridement and closure, this site progressively healed over 10 weeks. The contralateral mastectomy, randomized to the alternative device, healed normally.</p> <p>Conclusion</p> <p>We hypothesize that thermal damage to the subcutaneous microvasculature during flap dissection may have contributed to this complication and that the use of a low thermal injury dissection device may be advantageous in select patients undergoing skin- and nipple-sparing mastectomy.</p