SCUDO: a tool for signature-based clustering of expression profiles

SCUDO (Signature-based ClUstering for DiagnOstic purposes) is an online tool for the analysis of gene expression profiles for diagnostic and classification purposes. The tool is based on a new method for the clustering of profiles based on a subject-specific, as opposed to disease-specific, signature. Our approach relies on construction of a reference map of transcriptional signatures, from both healthy and affected subjects, derived from their respective mRNA or miRNA profiles. A diagnosis for a new individual can then be performed by determining the position of the individual's transcriptional signature on the map. The diagnostic power of our method has been convincingly demonstrated in an open scientific competition (SBV Improver Diagnostic Signature Challenge), scoring second place overall and first place in one of the sub-challenges

Involvement of lysine-88 of spinach ferredoxin-NADP+ reductase in the interaction with ferredoxin

AbstractA mutant of spinach ferredoxin-NADP+ reductase, in which Lys-88 has been changed to glutamine, has been obtained by site-directed mutagenesis. The mutant enzyme was fully active as a diaphorase, but partially impaired in ferredoxin-dependent cytochrome c reductase activity. By steady-state kinetics, the Km for ferredoxin of the K88Q enzyme was found to have increased 10-fold, whereas the kcat was unaffected by the amino acid replacement. The interaction between oxidized ferredoxin and the enzyme forms was also studied by spectrofluorimetric titration:Kd values of 110 and 10 nM were determined for the mutant and wild-type proteins, respectively. These data point out the importance of a positive charge at position 88 of the reductase for the interaction with ferredoxin, confirming previous cross-linking studies

Pair designing as practice for enforcing and diffusing design knowledge

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Exploring the Limitations of Peripheral Blood Transcriptional Biomarkers in Predicting Influenza Vaccine Responsiveness

Systems biology has been recently applied to vaccinology to better understand immunological responses to the influenza vaccine. Particular attention has been paid to the identification of early signatures capable of predicting vaccine immunogenicity. Building fromprevious studies, we employed a recently established algorithm for signature-based clustering of expression profiles, SCUDO, to provide new insights into why blood-derived transcriptome biomarkers often fail to predict the seroresponse to the influenza virus vaccination. Specifically, preexisting immunity against one or more vaccine antigens, which was found to negatively affect the seroresponse, was identified as a confounding factor able to decouple early transcriptome fromlater antibody responses, resulting in the degradation of a biomarker predictive power. Finally, the broadly accepted definition of seroresponse to influenza virus vaccine, represented by the maximum response across the vaccine-targeted strains, was compared to a composite measure integrating the responses against all strains. This analysis revealed that compositemeasures provide amore accurate assessment of the seroresponse to multicomponent influenza vaccines

C'est en forgeant qu'on devient forgeron : le développement d'une nouvelle banque de questions pour les étudiants en médecine gérée par les étudiants

Implication Statement The development of multiple-choice questions (MCQs) for undergraduate medical education study purposes is resource intensive. Commercially available question banks are typically expensive, only available in English, and may not be aligned with medical school learning objectives. Here, we introduce The Ottawa Question Bank: a student-led, bilingual study resource curated to a Canadian undergraduate medicine curriculum (www.theottawaquestionbank.ca). In total, 205 medical students wrote and edited 4438 original MCQs linked to objectives from the University of Ottawa undergraduate medical education curriculum. The project has received positive feedback from both developers and users. Our experience suggests that involving medical students in MCQ development is feasible and can result in the rapid creation of a low-cost, high-quality study resource curated to a program’s learning objectives. The platform outlined here can be used as a model for other medical schools and professional degree programs to develop their own question banks, including pharmacy, dentistry, nursing, and physiotherapy. Interested programs are encouraged to contact our team for collaborative opportunities.Énoncé des implications de la recherche L'élaboration de questions à choix multiples (QCM) dans le cadre de l'enseignement médical de premier cycle exige beaucoup de ressources. Les banques de questions disponibles dans le commerce sont généralement coûteuses, disponibles uniquement en anglais et ne correspondre pas forcément aux objectifs d'apprentissage des facultés de médecine. Nous présentons ici la Banque de questions d'Ottawa : une ressource d'étude bilingue dirigée par des étudiants et adaptée à un programme d'études de médecine de premier cycle au Canada (www.theottawaquestionbank.ca). Au total, 205 étudiants en médecine ont rédigé et édité 4438 QCM originaux liés aux objectifs du programme d'enseignement médical de premier cycle de l'Université d'Ottawa. Le projet a reçu des commentaires positifs de la part des développeurs et des utilisateurs. Notre expérience suggère qu'il est possible d'impliquer des étudiants en médecine dans le développement de QCM et de créer rapidement une ressource d'étude peu coûteuse et de haute qualité, adaptée aux objectifs d'apprentissage d'un programme. La plateforme décrite ici peut servir de modèle à d'autres facultés de médecine et programmes professionnels pour développer leurs propres banques de questions, y compris la pharmacie, l'odontologie, les soins infirmiers et la physiothérapie. Les programmes intéressés sont encouragés à contacter notre équipe pour des opportunités de collaboration

Cyclooxygenase-2 Induction after Oral Surgery Does Not Entirely Account for Analgesia after Selective Blockade of Cyclooxygenase 2 in the Preoperative Period

Background The administration of selective cyclooxygenase-2 inhibitors before surgery is regarded as an innovative option to manage postoperative pain. This study was designed to (1) examine the efficacy of preoperative cyclooxygenase-2 blockade on postoperative oral pain and (2) compare pain intensity with prostaglandin E2 (PGE2) production and cyclooxygenase isoform (cyclooxygenase-1, cyclooxygenase-2) messenger RNA (mRNA) expression at the surgical site during the postoperative period. Methods Sixty patients with impacted lower third molars were randomly allocated to three single-dose treatment groups--placebo, 50 mg rofecoxib, or 550 mg naproxen--1 h before extraction. Pain intensity was evaluated with categorical and visual analog scales every 30 min from 90 to 240 min after surgery. At these times, PGE2 production in the alveolar socket was also evaluated. Cyclooxygenase-1 and cyclooxygenase-2 mRNA expression was examined by reverse-transcription polymerase chain reaction in gingival specimens collected during tooth removal and 240 min after surgery. Results Pain intensity and PGE2 production in the placebo group increased throughout the observation period. Naproxen prevented pain and decreased PGE2 release at all time points. Rofecoxib reduced PGE2 production versus placebo from 150 min onward, while inducing analgesia through the whole observation period. mRNA assay in gingival specimens collected at tooth extraction revealed cyclooxygenase-1 expression, whereas cyclooxygenase 2 was undetectable. At the end of observation, cyclooxygenase-1 mRNA expression was unchanged, whereas cyclooxygenase-2 mRNA was significantly induced. Conclusions This study indicates that preoperative administration of a selective cyclooxygenase-2 inhibitor ensures effective control of postoperative pain. It is suggested that the selective blockade of inducible cyclooxygenase 2 at the surgical site does not entirely account for the analgesic action occurring in the postoperative period