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Objective: Exposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes. Method: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme's function in adipocyte physiology. Results: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes. Conclusion: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.

Abstract Background Developing economically viable pathways to produce renewable energy has become an important research theme in recent years. Lignocellulosic biomass is a promising feedstock that can be converted into second-generation biofuels and bioproducts. Global warming has adversely affected climate change causing many environmental changes that have impacted earth surface temperature and rainfall patterns. Recent research has shown that environmental growth conditions altered the composition of drought-stressed switchgrass and directly influenced the extent of biomass conversion to fuels by completely inhibiting yeast growth during fermentation. Our goal in this project was to find a way to overcome the microbial inhibition and characterize specific compounds that led to this inhibition. Additionally, we also determined if these microbial inhibitors were plant-generated compounds, by-products of the pretreatment process, or a combination of both. Results Switchgrass harvested in drought (2012) and non-drought (2010) years were pretreated using Ammonia Fiber Expansion (AFEX). Untreated and AFEX processed samples were then extracted using solvents (i.e., water, ethanol, and ethyl acetate) to selectively remove potential inhibitory compounds and determine whether pretreatment affects the inhibition. High solids loading enzymatic hydrolysis was performed on all samples, followed by fermentation using engineered Saccharomyces cerevisiae. Fermentation rate, cell growth, sugar consumption, and ethanol production were used to evaluate fermentation performance. We found that water extraction of drought-year switchgrass before AFEX pretreatment reduced the inhibition of yeast fermentation. The extracts were analyzed using liquid chromatography–mass spectrometry (LC–MS) to detect compounds enriched in the extracted fractions. Saponins, a class of plant-generated triterpene or steroidal glycosides, were found to be significantly more abundant in the water extracts from drought-year (inhibitory) switchgrass. The inhibitory nature of the saponins in switchgrass hydrolysate was validated by spiking commercially available saponin standard (protodioscin) in non-inhibitory switchgrass hydrolysate harvested in normal year. Conclusions Adding a water extraction step prior to AFEX-pretreatment of drought-stressed switchgrass effectively overcame inhibition of yeast growth during bioethanol production. Saponins appear to be generated by the plant as a response to drought as they were significantly more abundant in the drought-stressed switchgrass water extracts and may contribute toward yeast inhibition in drought-stressed switchgrass hydrolysates.

Abstract Background There is insufficient knowledge about the systemic health effects of exposure to fine (PM2.5) and ultrafine particles emitted from typical indoor sources, including cooking and candlelight burning. We examined whether short-term exposure to emissions from cooking and burning candles cause inflammatory changes in young individuals with mild asthma. Thirty-six non-smoking asthmatics participated in a randomized controlled double-blind crossover study attending three exposure sessions (mean PM2.5 µg/m3 ; polycyclic aromatic hydrocarbons ng/m3): (a) air mixed with emissions from cooking (96.1; 1.1), (b) air mixed with emissions from candles (89.8; 10), and (c) clean filtered air (5.8; 1.0). Emissions were generated in an adjacent chamber and let into a full-scale exposure chamber where participants were exposed for five hours. Several biomarkers were assessed in relation to airway and systemic inflammatory changes; the primary outcomes of interest were surfactant Protein-A (SP-A) and albumin in droplets in exhaled air – novel biomarkers for changes in the surfactant composition of small airways. Secondary outcomes included cytokines in nasal lavage, cytokines, C-reactive protein (CRP), epithelial progenitor cells (EPCs), genotoxicity, gene expression related to DNA-repair, oxidative stress, and inflammation, as well as metabolites in blood. Samples were collected before exposure start, right after exposure and the next morning. Results SP-A in droplets in exhaled air showed stable concentrations following candle exposure, while concentrations decreased following cooking and clean air exposure. Albumin in droplets in exhaled air increased following exposure to cooking and candles compared to clean air exposure, although not significant. Oxidatively damaged DNA and concentrations of some lipids and lipoproteins in the blood increased significantly following exposure to cooking. We found no or weak associations between cooking and candle exposure and systemic inflammation biomarkers including cytokines, CRP, and EPCs. Conclusions Cooking and candle emissions induced effects on some of the examined health-related biomarkers, while no effect was observed in others; Oxidatively damaged DNA and concentrations of lipids and lipoproteins were increased in blood after exposure to cooking, while both cooking and candle emissions slightly affected the small airways including the primary outcomes SP-A and albumin. We found only weak associations between the exposures and systemic inflammatory biomarkers. Together, the results show the existence of mild inflammation following cooking and candle exposure.

Abstract Background One third of UK medical students undertake an intercalated degree, typically in traditional academic disciplines. It is less usual for students to undertake intercalated degrees that are directly aligned to a clinical speciality with longitudinal placements. This cross sectional survey aims to explore the self-reported experiences of students, alumni and supervisors associated with a clinically oriented intercalated degree in emergency care featuring a longitudinal placement in a hospital emergency department over a 9-month academic year. Themes for exploration include student clinical and academic development, effect on career choice, supervisor experience and the effect on host institutions. Methods Current students, previous alumni, and clinical placement supervisors associated with a single intercalated degree programme in urgent and emergency care since 2005 were identified from records and using social media. Separate online surveys were then developed and distributed to current students/ previous alumni and consultant physician supervisors, between May and August 2016. Results are presented using basic descriptive statistics and selected free text comments. Results Responses were obtained from 37 out of 46 contactable students, and 14 out of 24 supervisors (80 and 63%, respectively). Students self-reported increased confidence in across a range of clinical and procedural competencies. Supervisors rated student competence in clinical, inter-professional and academic writing skills to be commensurate with, or in many cases exceeding, the level expected of a final year medical student. Supervisors reported a range of benefits to their own professional and personal development from supervising students, which included improved teaching and mentoring skills, providing intellectual challenge, and helping with the completion of audits and service improvement projects. Conclusions Students report the acquisition of a range of clinical, academic, and inter-professional skills following their intercalated BSc year. A positive experience was reported by supervisors, extending to host institutions. Students reported feeling more enthusiastic about emergency medicine careers on completion. However, as students embarking on this degree naturally bring pre-existing interest in the area, it is not possible to attribute causation to these associations. Further investigation is also required to determine the longer term effect of clinically oriented intercalated degrees on career choice.

Solid organ malignancies involving breast, prostate, and lung frequently metastasize to the skeleton. However, the occurrence of Paget's disease and metastatic bone disease in the same patient is uncommon. We report a case of a 63-year-old man who presented with back pain and a lump in the right breast. He was earlier diagnosed to have Paget's disease of bone based on characteristic skeletal radiological features, 99mTc methylene diphosphonate bone scan and elevated alkaline phosphatase, and treated with bisphosphonates, and his disease was in remission. Further evaluation revealed an underlying skeletal metastatic disease secondary to a breast malignancy. He underwent radical mastectomy with axillary node clearance, radiotherapy, and chemotherapy. In addition, he also received parenteral bisphosphonates for his skeletal metastatic bone disease.