Study of the regulation of the phospholipid biosynthetic pathway in response to envelope stress in Escherichia coli

Chez E. coli, des enzymes localisées à la membrane interne assurent la synthèse des phospholipides (PL). La membrane lipidique, est une barrière entre l’environnement et le milieu intérieur, elle est soumise à différents stress. La synthèse des PL est sujette à une régulation fine en réponse à ces variations environnementales pour maintenir l’homéostasie de la membrane. La voie de synthèse des PL est bien étudiée, on sait peu de choses sur sa régulation transcriptionnelle. Des études transcriptomiques de la réponse au stress d’enveloppe par les facteurs sigmaE et le système CpxAR, ont montrées que les gènes des enzymes de synthèse des PL sont régulés par ces facteurs. De plus, il a été montré que le gène plsB, qui code pour la première enzyme de synthèse des PL, est induit par sigE et inhibée par le ppGpp. A partir de là, j’ai étudié la régulation en réponse au stress du gène psd, qui code pour la phosphatidyléthanolamine, le PL majoritaire d’E. coli. Pour commencer, j’ai confirmé que le premier promoteur de psd était induit par sigE, puis j’ai démontré que psd possédait un second promoteur induit par CpxR. Mon second projet a porté sur la caractérisation du gène clsB, qui code pour la cardiolipine synthase II qui synthétise de la cardiolipine (CL). clsB est en opéron avec les deux gènes de fonction inconnue ybhP et ybhN. Généralement, les produits des gènes en opéron œuvrent dans une voie commune, ont une fonction liée ou forment un seul complexe protéique. C’est pour cette raison que j’ai voulu déterminer le rôle de ybhP et ybhN dans la voie de synthèse de la CL et/ou dans la voie de synthèse des PL. La caractérisation de YbhP et YbhN est en cours.In E. coli, enzymes located on the inner membrane ensure the synthesis of phospholipids (PL). The lipid membrane is a barrier between the environment and the internal environment, it is subject to various stresses. PL synthesis is subject to fine regulation in response to these environmental variations to maintain membrane homeostasis. The pathway for PL synthesis is well studied, little is known about its transcriptional regulation. Transcriptomic studies of the envelope stress response by sigmaE factors and the CpxAR system have shown that genes for PL synthetic enzymes are regulated by these factors. In addition, it has been shown that the plsB gene, which codes for the first PL synthesis enzyme, is induced by sigE and inhibited by ppGpp. From there, I studied the stress response regulation of the psd gene, which encodes phosphatidylethanolamine, the major PL in E. coli. To begin with, I confirmed that the first promoter of psd was induced by sigE, then I demonstrated that psd had a second promoter induced by CpxR. My second project focused on the characterization of the clsB gene, which codes for cardiolipin synthase II which synthesizes cardiolipin (CL). clsB is in operon with the two genes of unknown function ybhP and ybhN. Usually, operon gene products work in a common pathway, have a related function, or form a single protein complex. It is for this reason that I wanted to determine the role of ybhP and ybhN in the pathway of LC synthesis and / or in the pathway of PL synthesis. The characterization of YbhP and YbhN is in progress

Dual Regulation of Phosphatidylserine Decarboxylase Expression by Envelope Stress Responses

International audienceBacteria adapt to versatile environments by modulating gene expression through a set of stress response regulators, alternative Sigma factors, or two-component systems. Among the central processes that must be finely tuned is membrane homeostasis, including synthesis of phospholipids (PL). However, few genetic regulations of this process have been reported. We have previously shown that the gene coding the first step of PL synthesis is regulated by σE and ppGpp, and that the BasRS (PmrAB) two component system controls the expression of the DgkA PL recycling enzyme. The gene coding for phosphatidylserine decarboxylase, the last step in phosphatidylethanolamine synthesis is another gene in the PL synthesis pathway susceptible of stress response regulation. Indeed, psd appears in transcriptome studies of the σE envelope stress Sigma factor and of the CpxAR two component system. Interestingly, this gene is presumably in operon with mscM coding for a miniconductance mechanosensitive channel. In this study, we dissected the promoter region of the psd-mscM operon and studied its regulation by σE and CpxR. By artificial activation of σE and CpxRA stress response pathways, using GFP transcriptional fusion and western-blot analysis of Psd and MscM enzyme production, we showed that the operon is under the control of two distinct promoters. One is activated by σE, the second is activated by CpxRA and also responsible for basal expression of the operon. The fact that the phosphatidylethanolamine synthesis pathway is controlled by envelope stress responses at both its first and last steps might be important for adaptation of the membrane to envelope perturbations

Role of baseline echocardiography prior to initiation of anthracycline-based chemotherapy in breast cancer patients

Background: Anthracycline adjuvant therapy has taken a particular role in the treatment of early stage breast cancer with an associated decrease in rates of both relapse and death. Their success however has been limited by their myelosuppression and their well-established risk of cardiac dysfunction. Guidelines have emerged that would limit the maximum lifetime dose of anthracyclines and make a baseline assessment and periodic monitoring of cardiac function part of the routine practice, which could be cumbersome, and may condemn the patient to an unwarranted modification of his/her regimen. Our study aimed at assessing the incidence of abnormal baseline echocardiography in asymptomatic women with breast cancer prior to anthracycline therapy and establishing risk criteria associated with abnormal echocardiograms at baseline. Methods: 220 Patients seen at AUBMC (American University of Beirut Medical Center) who had non- metastatic breast cancer, and had an echocardiography performed before starting anthracycline chemotherapy were chosen. Data about demographic characteristics, tumor characteristics, baseline echocardiography results, and change in clinical decision was collected. Patients with suboptimal (less than 50%) ejection fraction (EF) on baseline echocardiography were analyzed for the prevalence of cardiac risk factors. Results were compared to those among the overall study group using Fisher's Exact test. A p- value of = < 0.05 was used as reference for statistical significance. Results: All 220 of our patients had received a baseline echo prior to initiation of anthracycline therapy. 6.7% of these patients had already some abnormality in wall motion but only 2.7% had a suboptimal ejection fraction. 1.3% had a change in chemotherapy regimen based on ejection fraction. The patients with depressed EF had higher rates of CAD (coronary artery disease), diabetes, hypertension and dyslipidemia than the overall study group but without statistical significance. Conclusions: Our study, as well as the previous contingent studies raise the question about routine echocardiography prior to anthracycline therapy and might eventually lead to a modification of current practice guidelines.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Perspective of Lebanese oncologists on the symptom burden among adult cancer patients

Background :Proper approach to symptom control in cancer patients requires a good understanding of the prevalence of the various symptoms these patients have. Aim: This study aims at assessing the Lebanese oncologists' point of view concerning the symptom burden among cancer patients of Lebanon and comparing their opinions to the real complaints of patients themselves. Methods: A cross-sectional study was conducted among a representative sample of the Lebanese medical oncologists. Thirty-six physicians filled out a questionnaire regarding their demographics as well as the symptom profile of their patients. Those results were compared to the ones obtained from our previous study about symptom profile as reported by patients. Results: Fatigue was the symptom most our patients suffered from according to their physicians (64.167%). Also, a good percentage of physicians agreed that patients suffer from appetite loss, pain, weight loss, and nausea. When compared to the patients' reports of their own symptoms, a statistically significant difference existed between the two profiles for the majority of symptoms (14 out of 19). Also, for the majority of symptoms, physicians were found to underestimate the percentage of patients suffering from each symptom. Conclusion: This study shows that there is a statistically significant difference between the physicians' and the patients' perspectives on most of the common distressing symptoms. This entails more detailed questioning of the cancer patients about their distressing symptoms.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Pavillonnaires de la banlieue Nord. Une ethnographie des petites mobilités sociales.: Rapport à la Mission à l'ethnologie (ministère de la culture).

Rapport de recherch

Barriers to mammography screening: How to overcome them

Background: Screening mammography is an established intervention that leads to early breast cancer detection and reduced mortality. The Lebanese Ministry of Health has initiated yearly awareness campaigns and provided free mammography in multiple centers around the country. Methods: The study took place in two major areas of Lebanon - Beirut and South Lebanon. This cross-sectional survey aimed to assess knowledge about breast cancer screening and screening behaviors in the Lebanese population. The primary outcome of the study was to assess the reasons that prevented women from performing screening mammography based on our categories of questions: lack of knowledge about breast cancer, lack of access to screening facilities, failure of primary care physician to encourage screening behavior, and other reasons. Results: The major barriers to seek screening that had statistically significant P-values, in order of prevalence, included: lack of knowledge about breast cancer, followed by social reasons and lack of access. Conclusion: Given the prevalence of breast cancer in our population, it is important to understand the pitfalls that we experience in promoting awareness. Our study is the first study to reach out to the community to assess perceived barriers against screening and provide solutions for such barriers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Práticas econômicas e formas ordinárias de cálculo

Este artigo parte da hipótese da existência de uma pluralidade de cenas sociais em que os indivíduos interagem e as ações individuais adquirem sentido. A cada cena social correspondem racionalidades práticas diferentes. O exame das práticas de mensuração e contabilidade permite distinguir essas cenas e compreender como se articulam entre si. Para mostrar a diversidade de raciocínios nativos, utiliza-se primeiro a diversidade das unidades de medida usadas por horticultores amadores. Em seguida, examinam-se os quadros rituais de diversas transações e mostra-se que o consumidor racional &shy; no sentido da teoria utilitarista &shy; pode não recorrer a nenhum cálculo explícito, pois o ethos ascético encontra-se inscrito nas rotinas corporais. Para concluir, o artigo convida a um estudo sistemático da socialização econômica e propõe três pistas para a pesquisa: a descrição da diversidade de cenas sociais, a análise dos quadros rituais das transações, e o estudo das percepções dos constrangimentos e das práticas de autocontrole nas diversas classes sociais. O artigo sugere que, dessa forma, se poderiam definir domínios de validade para as formalizações matemáticas das condutas humanas elaboradas pelos economistas.<br>This article proceeds from the hypothesis that a plurality of social scenes exist in which individuals interact and individual actions acquire meaning. Each social scene corresponds to different practical rationalities. Examining the practices involved in measuring and counting allows us to distinguish these scenes and comprehend how they are mutually interconnected. As a demonstration of the diversity of native reasoning, the article first turns to the wide variety of units of measurement used by amateur horticulturists. Next, it examines the ritual settings of various transactions and shows that the rational consumer &shy; in the sense expounded by utilitarian theory &shy; need not rely on any explicit calculation, since the ascetic ethos can be found inscribed in body routines. In conclusion, the article calls for a systematic study of economic socialization and outlines three leads for such research: description of the diversity of social scenes, analysis of the ritual settings of transactions, and study of the perceptions of constraints and the practices of self-control among the various social classes. The author suggests such an approach may enable us to define domains of validity for the mathematical formalizations of human behaviours developed by economists