Fatty Acid Oxidation in Peroxisomes: Enzymology, Metabolic Crosstalk with Other Organelles and Peroxisomal Disorders

Peroxisomes play a central role in metabolism as exemplified by the fact that many genetic disorders in humans have been identified through the years in which there is an impairment in one or more of these peroxisomal functions, in most cases associated with severe clinical signs and symptoms. One of the key functions of peroxisomes is the β-oxidation of fatty acids which differs from the oxidation of fatty acids in mitochondria in many respects which includes the different substrate specificities of the two organelles. Whereas mitochondria are the main site of oxidation of medium-and long-chain fatty acids, peroxisomes catalyse the β-oxidation of a distinct set of fatty acids, including very-long-chain fatty acids, pristanic acid and the bile acid intermediates di- and trihydroxycholestanoic acid. Peroxisomes require the functional alliance with multiple subcellular organelles to fulfil their role in metabolism. Indeed, peroxisomes require the functional interaction with lysosomes, lipid droplets and the endoplasmic reticulum, since these organelles provide the substrates oxidized in peroxisomes. On the other hand, since peroxisomes lack a citric acid cycle as well as respiratory chain, oxidation of the end-products of peroxisomal fatty acid oxidation notably acetyl-CoA, and different medium-chain acyl-CoAs, to CO2 and H2O can only occur in mitochondria. The same is true for the reoxidation of NADH back to NAD+. There is increasing evidence that these interactions between organelles are mediated by tethering proteins which bring organelles together in order to allow effective exchange of metabolites. It is the purpose of this review to describe the current state of knowledge about the role of peroxisomes in fatty acid oxidation, the transport of metabolites across the peroxisomal membrane, its functional interaction with other subcellular organelles and the disorders of peroxisomal fatty acid β-oxidation identified so far in humans

Qualitative study about the ways teachers react to feedback from resident evaluations

Contains fulltext : 127324.pdf (publisher's version ) (Open Access)BACKGROUND: Currently, one of the main interventions that are widely expected to contribute to teachers' professional development is confronting teachers with feedback from resident evaluations of their teaching performance. Receiving feedback, however, is a double edged sword. Teachers see themselves confronted with information about themselves and are, at the same time, expected to be role models in the way they respond to feedback. Knowledge about the teachers' responses could be not only of benefit for their professional development, but also for supporting their role modeling. Therefore, research about professional development should include the way teachers respond to feedback. METHOD: We designed a qualitative study with semi-structured individual conversations about feedback reports, gained from resident evaluations. Two researchers carried out a systematic analysis using qualitative research software. The analysis focused on what happened in the conversations and structured the data in three main themes: conversation process, acceptance and coping strategies. RESULTS: The result section describes the conversation patterns and atmosphere. Teachers accepted their results calmly, stating that, although they recognised some points of interest, they could not meet with every standard. Most used coping strategies were explaining the results from their personal beliefs about good teaching and attributing poor results to external factors and good results to themselves. However, some teachers admitted that they had poor results because of the fact that they were not "sharp enough" in their resident group, implying that they did not do their best. CONCLUSIONS: Our study not only confirms that the effects of feedback depend first and foremost on the recipient but also enlightens the meaning and role of acceptance and being a role model. We think that the results justify the conclusion that teachers who are responsible for the day release programmes in the three departments tend to respond to the evaluation results just like human beings do and, at the time of the conversation, are initially not aware of the fact that they are role models in the way they respond to feedback

Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

BACKGROUND: At the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment. METHODS: We conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m(2), overweight 25–29.9 kg/m(2) and obese ⩾30 kg/m(2)). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5–11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk. RESULTS: On crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant. CONCLUSIONS: Overweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM

Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

<p>Abstract</p> <p>Background</p> <p>Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients.</p> <p>Methods</p> <p>Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks.</p> <p>Results</p> <p>In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, <it>FADS1</it>, down-regulated, and <it>LEP </it>and <it>ANGPT1</it>, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of <it>CFH</it>). Interestingly, we found that the microRNA <it>MIRLET7A2 </it>was overexpressed in the PP adipose tissue of prostate cancer patients.</p> <p>Conclusions</p> <p>Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.</p