Crystal structure and functional mapping of human ASMT,the last enzyme of the melatonin synthesis pathway

Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure of human N‐acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C‐terminal domain, which is typical of other SAM‐dependent O‐methyltransferases, and an N‐terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3‐dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.     

Contributing to an integrated profession: a model-based examination of the A-ONE

Yerxa’s [1] model of an integrated profession depicts a circular scholarly process whereby ideas formed in practice are subjected to research and then returned to practice through education. This knowledge-generating cycle supports occupational science and the development of our professional identity. The aim of this article is to demonstrate how Yerxa’s model was used to evaluate if three developmental cycles of the ADL-Focused Occupation-Based Neurobehavioral Evaluation (A-ONE) sufficiently represented all necessary model components required for implementation into practice. The three cycles were historical, educational and measurement. The necessary components included: (a) dilemmas in practice, (b) new ideas that emerged from those practice issues, (c) research to test those ideas and (d) education designed to integrate new knowledge into practice. The results of this analysis of the A-ONE supported adequate research related to ideas from practice being implemented back into practice. Through using the model of an integrated profession to reflect on ideas ignited within practice, and then implementing research to explore the potential contribution of those ideas to knowledge generation, we gain the power to influence the future development of occupational science and the profession.     

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

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HTA et précarité perçue en population précaire guadeloupéenne : l’enquête PHAPPG

ObjectiveTo assess the relationship between hypertension and perceived material insecurity in a disadvantaged Caribbean population.Patients and methodsWe used data from a cross-sectional study involving 2420 disadvantaged subjects aged 18–69 years, included consecutively at three Guadeloupian health centers. Hypertension was diagnosed over two consultations with a total of six blood pressure measurements. Perceived material insecurity was assessed using a closed-ended question.ResultsThe prevalence of hypertension was estimated at 17.7% among subjects who believed their material situation would improve in the future, at 28.2% among those who believed it would remain the same, and at 43.3% among those who believed it would deteriorate. A multivariate logistic regression analysis showed that hypertension risk more than doubled (OR: 2.35 – P: 0.002) among subjects who believed that their material situation would deteriorate in the future compared to those who believed that their situation would improve, with no significant sex-related differences. This relationship was especially strong among subjects aged 40 years or more (OR: 3.30 – P < 10^?3), and among subjects with low education level (OR: 3.81 – P: 0.003), but was independent of the other tested variables.ConclusionIn this disadvantaged population, perceived material insecurity is a psychosocial factor strongly associated with hypertension, independently of subjects’ risk behaviors. Subjects aged 40 years or more and subjects with a low education level seem the most vulnerable.     

Liver tumours in children: diagnostic and therapeutic approach in the Tropics

Liver tumours in children are rare and their prognosis are poor. Through a cross and retrospective study, we examined the epidemiological, clinical and therapeutic aspects on a number of patients in our hospital to try and improve the management of cases. This study involved 66 children admitted to the pediatric oncology unit of University Hospital of Treichville in Abidjan between 1991 and 2007. The average age of children was 7.2 years and the sex ratio of 1.4. 42 children lived in the countryside and 52 children were from disadvantaged areas. 63.2% of children were not vaccinated against hepatitis B. The abdominal mass was the primary sign of discovery and these tumours were dominated in both their primitive and secondary forms by the Burkitt's lymphoma.