Caractérisation du rôle de Citron Kinase durant la cytokinèse

La cytokinèse est un processus dont le but est une séparation de deux cellules soeurs en deux entités suite à une mitose. La cytokinèse nécessite la formation d’un anneau contractile (AC) qui va conduire un sillon de clivage vers une ingression à l’équateur de la cellule. L’une des étapes critiques de ce processus est la transition d’un AC dynamique vers une structure stable surnommée l’anneau du midbody (AM), organelle qui va guider la cellule vers l’abscision. La compréhension des mécanismes moléculaires impliqués dans cette transition nous permettrait de mieux comprendre les complexes protéiques impliqués autant au niveau de l’initiation qu’à la terminaison de la cytokinèse. Des défauts ayant lieu lors de cette transition mènent à la formation de cellules binucléées tétraploïdes qui sont observées dans plusieurs pathologies comme le cancer. Afin d’approfondir nos connaissances à ce sujet j’ai utilisé un modèle d’imagerie optique en temps réel dans un modèle cellulaire de Drosophila melanogaster : les cellules S2 de Schneider. Ces études ont mis l’emphase sur un nouveau mécanisme de maturation de la transition AC/AM. Nous avons pu démontrer que la kinase Citron, Sticky, et la septine, Peanut, agissent de manière opposée sur la protéine Anillin pour retenir ou éliminer, respectivement, la membrane plasmique lors de la transition AC/AM. En effet, la diminution d’expression de Sticky par ARNi engendre une perte de contrôle de rétention membranaire de l’AM. À l’inverse, la diminution d’expression de Peanut inhibe la maturation par excrétion membranaire de l’AM. La diminution d’expression simultanée de Sticky et de Peanut conduit l’AC vers des mouvements oscillatoires typiques d’une instabilité de l’AC suite à la perte de fonction de l’Anillin. Sticky est une protéine corticale lors de la cytokinèse dont le rôle et les partenaires d’interaction restent controversés. Pour approfondie nos connaissance de ce sujet, nous avons effectué une étude structurelle et fonctionnelle de Sticky. Cette étude démontre que Sticky possède deux mécanismes de localisation corticale. Le premier dépend de l’Anillin et le deuxième dépend de la petite GTPase Rho1, le régulateur maître de la cytokinèse. Sticky est capable de se localiser à l’AC en présence de l’un ou l’autre de ces deux mécanismes, mais chacun semble être essentiel pour la réussite de la cytokinèse. Le domaine minimal d’interaction entre la Sticky et l’Anillin a été identifié. Une version d’Anillin qui manque le site de liaison à la Sticky est incapable de supporter l’achèvement de la cytokinèse, et les cellules échouent la cytokinèse d’une manière semblable aux cellules dont l’expression de Sticky est diminuée. Similairement, les cellules exprimant une protéine Sticky mutée au site d’interaction avec Rho1-GTP, sont incapables de compléter la cytokinèse lorsque les niveaux endogènes de Sticky sont diminués par ARNi. Ceci suggère que Sticky agit avec Anillin et Rho1 au niveau du cortex pour guider la transition d’un AC dynamique vers un AM stable. Par la mise en évidence et la caractérisation d’un nouveau mécanisme moléculaire essentiel à la cytokinèse, cette thèse constitue des avancements importants au niveau de la cytokinèse.Cytokinesis is a multistep process that allows two sister cells to undergo complete separation following mitosis. Cytokinesis requires the formation of a contractile ring (CR) that will drive cleavage furrow ingression at the equator of the cell. One of the crucial steps in this process is the transition from a dynamic CR to a more stable structure named the midbody ring (MR), which directs the final separation or abscission. Our knowledge of the molecular mechanisms involved in the CR-to-MR transition would presumably improve our understanding of the molecular complexes involved throughout cytokinesis from initiation to abscission. Defects that occur during this transition can lead to the formation of bi-nucleate tetraploid cells that are often observed in pathological conditions such as cancer. I have used Drosophila melanogaster Schneider’s S2 cells to study the CR-to-MR transition. My findings have highlighted a previously uncharacterized maturation process essential for the transition. More specifically, I demonstrate that the Citron Kinase, Sticky, and the Septin, Peanut, have opposing actions on the scaffold protein Anillin to either retain or extrude, respectively, membrane-positive proteins during the CR-to-MR transition. Indeed, Sticky depletion by RNAi led to uncontrolled loss of membrane-associated Anillin at the MR. Conversely, Peanut depletion led to inhibition of MR maturation by membrane extrusion. Co-depletion of Sticky and Peanut led to oscillatory movements of the CR, typical of Anillin depletion. Sticky is a cortical protein during cytokinesis whose role and interacting partners are controversial. I have performed a structure/function analysis of Sticky to better define its role and regulation during cytokinesis. My work shows that Sticky has two mechanisms of cortical localization. The first is through an Anillin interaction and the second is through the small GTPase Rho1, a master regulator of cytokinesis. Sticky can localize to the cortex in the absence of either one of these mechanisms. However, loss of both inhibits its localization. Following the identification of the minimal interaction sites of Anillin and Sticky, I expressed an Anillin mutant that lacked part of this site and found that cells failed cytokinesis in a similar manner to cells depleted of Sticky. Mutation of the Rho1 binding site on Sticky produced similar cytokinesis failures. Altogether, the results suggest that Sticky interacts with Anillin and Rho1 at the cortex to guide the transition from dynamic CR to stable MR. This thesis advances our understanding of cytokinesis by highlighting a previously uncharacterized process of MR maturation and by defining the importance and regulation of Citron Kinase during this process

Mathematical Creativity: The Unexpected Links

Creativity in mathematics is identified in many forms or we can say is made up of many components. One of these components is The Unexpected Links where one tries to solve a mathematical problem in a nontraditional manner that requires the formation of hidden bridges between distinct mathematical domains or even between seemingly far ideas within the same domain. In this article, we design problems that express unexpected links in mathematics and suit students of intermediate and secondary levels. We prove their feasibility through teachers’ testimonies and through introducing them in classrooms and collecting students’ attitudes with respect to understanding and interest. Results confirm that students can sense such component and that designed problems had caught teachers’ and students’ interest

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Maintaining Service Quality in Remote Teaching Environment: Case of Lebanese International University

Purpose: The shift from traditional face-to-face classes to virtual classrooms in response to Covid 19 pandemic has affected the higher education sector worldwide, including Lebanon. Among all private universities in Lebanon, the Lebanese International University (LIU) is the largest in terms of enrolment, which enroll 30% of higher education students in the country. Therefore, this study evaluates the LIU experience in remote teaching. After completing three consecutive online semesters, it was essential to measure to which extent did the remote instructor performance affected the educational service quality at LIU. Methodology: By the end of the Fall 2021 semester, a cross-sectional online survey was conducted among students at the School of Business and a total of 450 usable responses pertaining to undergraduate students were considered for data analysis. Findings: Using SPSS Software, the validity and reliability of the questionnaire has been verified and results showed that remote instructors’ performance has a significant and strong positive correlation with all dimensions of service quality; highest for reliability and lowest for tangible. Moreover, regression analysis results showed that 81.5 % of the variance in service quality scores can be predicted from the remote instructors’ performance. Suggestions: Future studies could collect data in a longitudinal manner and include a more representative student sample of the university students

Multi-stage appointment scheduling for outpatient chemotherapy unit: a case study

This paper deals with a multi stage hybrid flow-shop problem (HFSP) that arises in a privately Chemotherapy clinic. It aims to optimize the makespan of the daily chemotherapy activity. Each patient must respect the cyclic nature of chemotherapy treatment plans made by his referent on- cologist while taking into account the high variability in resource requirements (treatment time, nurse time, pharmacy time). The problem requires the assignment of chemotherapy patients to oncologists, pharmacists, chemotherapy beds or chairs and nurses over a 1-day period. We provided a Mixed Integer Program (MIP) to model this issue, which can be considered as a five-stage hybrid flow-shop scheduling problem with additional resources, dedicated machines, and no-wait constraints. Since this problem is known to be NP-hard, we provided a lower bound expression and developed an approximated solving algorithm: a tabu search inspired metaheuristic based on a constructive heuristic that can quickly reach satisfying results. To assess the empirical performance of the proposed approach, we conducted experi- ments on randomly generated instances based on real-world data of a Tunisian private clinic: Clinique Ennasr. Computational experiments show the efficiency of the proposed procedures: The mathematical model provided optimal solutions in reasonable computational time only for small instances (up to 10 patients). Meta-heuristic’s results demonstrate, also, that the proposed approach offers good results in terms of solution quality and computational times with an average relative gap to the MIP solution equal to 3.13% and to the lower bound equal to 5.37% for small instances (up to 15 patients). The same gap to the lower bound increases to 25% for medium and large size instances (20–50 patients)

BLEPal: Bluetooth Trace Synchronization and Merging Python Tool

Obsolete versio

Optimization of Partially Hydrolyzed Polyacrylamide (HPAM) Utilized in Water-Based Mud While Drilling

International audienceWater-soluble polymers are becoming increasingly important in various applications, such as stabilizer fluids and drilling muds. These materials are used as viscosifiers and filtration control agents, flocculants, and deflocculants due to their superior properties in increasing viscosity and gelling ability in the presence of crosslinkers. In general, studying the rheological behavior of drilling fluids is of paramount importance to ensure successful well drilling operations. Partially hydrolyzed polyacrylamide is one of the polymers widely used in water-based muds. The main objective of this study is to optimize the rheological properties of drilling muds through a characterization study of various parameters, including rheological behavior, viscosity, temperature (23 degrees C, 40 degrees C, and 60 degrees C), salinity using KCl and NaCl contents, aging, pH, solubility, and structural analysis using infrared of partially hydrolyzed polyacrylamide. The study aims to demonstrate the importance of using polymers in drilling muds. The findings revealed that a rate of 3% of HPAM gave better rheological behavior, the influence of KCl (1.5%, 3%, and 4.5%) was greater than that of NaCl (1.5%, 3%, and 4.5%) on polymers, and the aging test showed that the different formulations are stable and maintain their behavior up to 110 degrees C. The solubility test results confirmed the maximum amount absorbed by polyacrylamide ([C-HPAM] = 66.42 g/L) in order to avoid aggregation, gelification, and enhance the drilling mud by utilizing the prescribed contents