AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

Antimicrobial Activity and Genetic Profile of Enteroccoci Isolated from Hoopoes Uropygial Gland

Symbiotic microorganisms may be directly transferred from parents to offspring or acquired from a particular environment that animals may be able to select. If benefits for hosts vary among microbial strains, natural selection may favour hosts holding the most beneficial one. Enterococci symbionts living in the hoopoe (Upupa epops) uropygial gland are able to synthesise bacteriocins (antimicrobial peptides that inhibit the growth of competitor bacteria). We explored variability in genetic profile (through RAPD-PCR analyses) and antimicrobial properties (by performing antagonistic tests against ten bacterial indicator strains) of the different isolates obtained from the uropygial glands of hoopoe females and nestlings. We found that the genetic profile of bacterial isolates was related to antimicrobial activity, as well as to individual host identity and the nest from which samples were obtained. This association suggest that variation in the inhibitory capacity of Enterococci symbionts should be under selection.This work was financed by Ministerio de Ciencia e Innovación (Spanish National Government) and FEDER founds (projects CGL2010-19233-C03-01, and CGL2010-19233-C03-03), and Junta de Andalucía (P09-RNM-4557)

The role of the ubiquitination–proteasome pathway in breast cancer: Ubiquitin mediated degradation of growth factor receptors in the pathogenesis and treatment of cancer

Aberrant activity of growth factor receptors has been implicated in the pathogenesis of a wide variety of malignancies. The negative regulation of signaling by growth factor receptors is mediated in large part by the ubiquitination, internalization, and degradation of the activated receptor. Over the past few years, considerable insight into the mechanisms that control receptor downregulation has been gained. There are also data suggesting that mutations that lead to inhibition of downregulation of growth factor receptors could play a role in the pathogenesis of cancer. Therapies directed at enhancing the degradation of growth factor receptors offer a promising approach to the treatment of malignancies

Barriers to climate change adaptation in indigenous communities : a case study on the mohawk community of Kanesatake, Canada

202010 bcmaVersion of RecordPublishe

Routine versus ad hoc screening for acute stress following injury: who would benefit and what are the opportunities for prevention

Background: Screening for acute stress is not part of routine trauma care owing in part to high variability of acute stress symptoms in identifying later onset of posttraumatic stress disorder (PTSD). The objective of this pilot study was to assess the sensitivity, specificity, and power to predict onset of PTSD symptoms at 1 and 4 months using a routine screening program in comparison to current ad hoc referral practice. Methods Prospective cross-sectional observational study of a sample of hospitalized trauma patients over a four-month period from a level-I hospital in Canada. Baseline assessments of acute stress (ASD) and subsyndromal ASD (SASD) were measured using the Stanford Acute Stress Reaction Questionnaire (SASRQ). In-hospital psychiatric consultations were identified from patient discharge summaries. PTSD symptoms were measured using the PTSD Checklist-Specific (PCL-S). Post-discharge health status and health services utilization surveys were also collected. Results Routine screening using the ASD (0.43) and SASD (0.64) diagnoses were more sensitive to PTSD symptoms at one month in comparison to ad hoc referral (0.14) and also at four months (0.17, 0.33 versus 0.17). Ad hoc referral had greater positive predictive power in identifying PTSD caseness at 1 month (0.50) in comparison to the ASD (0.46) and SASD (0.43) diagnoses and also at 4 months (0.67 versus 0.25 and 0.29). Conclusions Ad hoc psychiatric referral process for acute stress is a more conservative approach than employing routine screening for identifying persons who are at risk of psychological morbidity following injury. Despite known limitations of available measures, routine patient screening would increase identification of trauma survivors at risk of mental health sequelae and better position trauma centers to respond to the circumstances that affect mental health during recovery.Population and Public Health (SPPH), School ofPsychiatry, Department ofSurgery, Department ofNon UBCMedicine, Faculty ofReviewedFacult

Shoulder terminal range eccentric antagonist/concentric agonist strength ratios in overhead athletes

Objective: The agonist-antagonist strength relationship for shoulder external rotation and internal rotation was formerly described by the relatively more functional ratios of eccentric external rotator to concentric internal rotator moments, and eccentric internal rotator to concentric external rotator moments for the entire range of motion. The aim of this study was to provide descriptive data for terminal range eccentric antagonist/concentric agonist rotator cuff strength in overhead athletes. Methods: The dominant and non-dominant shoulders of 40 asymptomatic military overhead athletes were tested through a range of 20 degrees of external rotation to 90 degrees of internal rotation using the Cybex NORM isokinetic dynamometer at a speed of 90 degrees/s. Differences between the dominant and non-dominant shoulders were assessed using the paired samples t-test. Results: The terminal range ratios during external rotation (20 degrees of internal rotation -10 degrees of external rotation) were found to be 2.09 and 1.58 for the dominant and non-dominant shoulders, respectively, whereas the terminal range ratios during internal rotation (60-90 degrees of internal rotation) were 1.03 and 1.19 for the dominant and non-dominant shoulders, respectively. These ratio differences between the dominant and non-dominant shoulders were significant (P < 0.01 for external and internal rotation). Conclusion: The muscle torque ratios of eccentric antagonist/concentric agonist are different between dominant and non-dominant shoulders of skilled overhead athletes at terminal ranges. This functional assessment of strength testing that reflects dynamic shoulder joint stability during the throwing activity at these specific ranges may provide valuable information either during preventive exercise programs or in the evaluation of the injured shoulder of the overhead athlete. We recommended functional exercises that improve eccentric external rotation strength on the dominant shoulder during the rehabilitation and prevention programs in overhead athletes