Implication de la signalisation du BCR dans le ciblage thérapeutique des lymphomes folliculaires

Une des molécules clés des fonctions biologiques du lymphocyte B est le BCR (B Cell Receptor). Les connaissances concernant l'altération du signal BCR et son implication dans l'apparition des lymphopathies B ne cessent de s'élargir. De ce fait, le ciblage pharmacologique de cette molécule et de sa signalisation a constitué le centre d'intérêt de mes travaux de thèse. Ainsi nous avons montré que le Rituximab (anticorps thérapeutique anti-CD20) est capable d'inhiber le signal BCR à travers la diminution de son expression et que l'enzastaurine qui est un inhibiteur de protéines kinases situées en aval du BCR représente un potentiel anti-tumoral pour le lymphome folliculaire. Ainsi, ces travaux participent à la compréhension des mécanismes d'action de ces molécules thérapeutiques et démontrent l'importance du signal BCR dans la thérapie des lymphomes.Beside its central role in the recognition of antigen, the BCR (B Cell Receptor) controls a multitude of intracellular mechanisms that regulate B lymphocyte biology. Altered BCR signaling has been demonstrated in various types of B-cell lymphoma and some autoimmune diseases. Thus, therapeutic targeting of BCR signaling has been the focus of my PhD studies. We demonstrate that the monoclonal anti-CD20 antibody, Rituximab, inhibits BCR signaling at least by down-regulating BCR expression. Furthermore, enzastaurin (kinases inhibitor) exerts an anti-tumoral effect on follicular lymphoma cells by inhibiting downstream BCR signaling. Then, we characterized new mechanisms of action of Rituximab and enzastaurin and we focused on the importance of BCR signaling in lymphoma's therapy

Marine fouling community in the Eastern harbour of Alexandria, Egypt compared with four decades of previous studies

The aim of the present study is to compare the fouling communities between the years 1960 and 1999 in the Eastern harbour of Alexandria, Egypt and to study the main factors that may be controlling these communities. This comparison is based on monthly durations of panel immersion. By using roughened white polystyrene test panels (12.5x12.5 cm), monthly samples of marine fouling were collected from the harbour from October 1998 through September 1999. It is clear that a remarkable variation in number and diversity of fouling communities throughout the last four decades is evident. The minimum diversities were recorded during the studies of 1960 and 1970 (19 and 20 species respectively), while the maximum diversity (35 species) was achieved during the 1991 study. Moreover, a small shift among the four dominant groups (Polychaeta, Cirripedia, Bryozoa and Amphipoda) was noted during the four decades of the studies. The present comparison indicated that many factors may contribute to this variation, of which nutrient enrichment is the most important and the nature of the applied test panel is lees so

Background of Individual Education Plans (IEPs) Policy in Some Countries: A Review

This paper seeks to provide a cogent outline of the current policies that six separate countries have on Individual Education Plans (IEPs), identifying the key features in each system. The chosen countries are Australia (Queen Island), Canada (British Columbia), New Zealand, the United Kingdom, the United States of America, and Saudi Arabia. The aim of the paper was to have greater insights of the globalisation of IEPs at public schools in these above countries. It looked into a set of factors closely associated with each other; such as, to enable the exploration of how IEP policy is implemented at public schools in the same countries. The findings from the literature review showed a number of gaps in the current frameworks. Therefore, this has led the researcher to work further on these frameworks for the purpose of this paper. Keywords: IEPs in Australia, IEPs in Canada, IEPs in New Zealand, IEPs in United Kingdom, IEPs in United States of America, and IEPs in Saudi Arabia

Factors controlling marine fouling in some Alexandria Harbours, Egypt

The present work aims to relate the settlement of marine fouling organisms in three different harbours in Alexandria city which present a wide range of ecological/environmental variations. Theses are the Abu Qir, Eastern and El-Dekheila harbours. Monthly samples of marine fouling were collected from the three harbours by using white roughened polystyrene test panels (12.5x12.5 cm), as well as physicochemical, chemical and other biological data. Results were treated with multivariate statistical analysis (PCA). At the Abu Qir harbour, it was found that water temperature and salinity are the most important environmental factors controlling the temporal distribution of total fouling density, whereas water temperature and chlorophyll a are the most significant environmental factors controlling the total biomass. At the Eastern harbour it was demonstrated that ammonia and phosphate are the most significant environmental factors controlling the temporal distribution and total biomass of fouling organisms. Concerning El-Dekheila harbour, the total density and total biomass of fouling organisms were inversely correlated with the total zooplankton

A genome-wide regulatory network of INTS12 associated with pulmonary function

Genome-wide association studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3’end processing of small nuclear RNAs. An interrogation of bioinformatic datasets showed that in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighboring GSTCD expression. In contrast to the previous reports in other species, a minor alteration of small nuclear RNA processing was observed following INTS12 depletion. RNA sequencing analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, chromatin immunoprecipitation and sequencing experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, INTS12 regulome was defined which includes genes belonging to the protein synthesis pathways. INTS12 has functions beyond the canonical snRNA processing and evidence is presented showing that it regulates translation by directly controlling the expression of genes belonging to protein synthesis pathways. This thesis provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the understanding of biology behind the genetic association for lung function at the 4q24

Vascular endothelial growth factor receptor inhibition enhances chronic obstructive pulmonary disease picture in mice exposed to waterpipe smoke

Background: Chronic obstructive pulmonary disease (COPD) is marked by destruction of alveolar architecture. Preclinical modelling for COPD is challenging. Chronic cigarette smoke exposure, the reference animal model of COPD, is time-inefficient, while exposure to waterpipe smoke (WPS), a surging smoking modality, was not fully tested for its histopathological pulmonary consequences. Since alveolar damage and pulmonary vascular endothelial dysfunction are integral to COPD pathology, lung histopathological effects of WPS were temporally evaluated, alone or in combination with vascular endothelial growth factor receptor (VEGFR) inhibition in mice.Materials and methods: Mice were exposed to WPS, 3 hours/day, 5 days/week, for 1, 2, 3, or 4 months. Another group of mice was exposed to WPS for 1 month, while being subjected to injections with the VEGFR blocker Sugen5416 (SU, 20 mg/kg) 3 times weekly. Control mice were exposed to fresh air in a matching inhalation chamber. Histopathological assessment of COPD was performed. Alveolar destructive index (DI) was counted as the percentage of abnormally enlarged alveoli with damaged septa per all alveoli counted. Mean linear intercept (MLI) was calculated as a measure of airspace enlargement.Results: Exposure to WPS resulted in significant increases in alveolar DI and MLI only after 4 months. Lung inflammatory score was minimal across all time-points. Importantly, combination of WPS and SU resulted in significantly increased DI, MLI, and inflammatory scores as early as 1 month post exposure.Conclusions: Combined exposure to WPS and SU results in COPD picture, highlighting the role of pulmonary vascular endothelial dysfunction in the disease

The effect of strict state measures on the epidemiologic curve of COVID-19 infection in the context of a developing country : a simulation from Jordan

COVID-19 has posed an unprecedented global public health threat and caused a significant number of severe cases that necessitated long hospitalization and overwhelmed health services in the most affected countries. In response, governments initiated a series of non-pharmaceutical interventions (NPIs) that led to severe economic and social impacts. The effect of these intervention measures on the spread of the COVID-19 pandemic are not well investigated within developing country settings. This study simulated the trajectories of the COVID-19 pandemic curve in Jordan between February and May and assessed the effect of Jordan’s strict NPI measures on the spread of COVID-19. A modified susceptible, exposed, infected, and recovered (SEIR) epidemic model was utilized. The compartments in the proposed model categorized the Jordanian population into six deterministic compartments: suspected, exposed, infectious pre-symptomatic, infectious with mild symptoms, infectious with moderate to severe symptoms, and recovered. The GLEAMviz client simulator was used to run the simulation model. Epidemic curves were plotted for estimated COVID-19 cases in the simulation model, and compared against the reported cases. The simulation model estimated the highest number of total daily new COVID-19 cases, in the pre-symptomatic compartmental state, to be 65 cases, with an epidemic curve growing to its peak in 49 days and terminating in a duration of 83 days, and a total simulated cumulative case count of 1048 cases. The curve representing the number of actual reported cases in Jordan showed a good pattern compatibility to that in the mild and moderate to severe compartmental states. The reproduction number under the NPIs was reduced from 5.6 to less than one. NPIs in Jordan seem to be effective in controlling the COVID-19 epidemic and reducing the reproduction rate. Early strict intervention measures showed evidence of containing and suppressing the disease

Prevalence of nicotine dependence among university students in Jordan: a cross-sectional study

Tobacco epidemic is one of the biggest public health threats the world has ever encountered. The objective of this study was to identify the prevalence of nicotine dependence among university students in Jordan and assess factors associated with this dependence.  A cross-sectional study using simple random sampling was conducted among university students from 3 public and 3 private universities selected for their convenience from central, middle, and east Jordan via administering a questionnaire between October 2016 and January 2017. The total number of participants was 892.  The overall nicotine dependence was 51.2%. Correlates to nicotine dependence were studying at an undergraduate level (OR=3.6; 95% CI: 1.4-8.1); studying humanities (OR=1.73; 95% CI: 1.2-2.1); existing of a smoking family member (OR=1.63; 95% CI: 1.5-1.9); starting smoking before age of 15 years (OR=1.60; 95% CI: 1.2-2.1); water pipe smoking (OR=1.48; 95% CI: 1.1-2.0); and studying at governmental universities (OR=1.36; 95% CI: 1.0-1.8).  Several socio-demographic characteristics had an impact on nicotine dependence. Future research is necessary to further improve our understanding of motives for smoking and dependence.&nbsp

Effectiveness of interactive teaching intervention on medical students' knowledge and attitudes toward stem cells, their therapeutic uses, and potential research applications

Background: Stem cell science is rapidly developing with the potential to alleviate many non-treatable diseases. Medical students, as future physicians, should be equipped with the proper knowledge and attitude regarding this hopeful field. Interactive teaching, whereby the teachers actively involve the students in the learning process, is a promising approach to improve their interest, knowledge, and team spirit. This study aims to evaluate the effectiveness of an interactive teaching intervention on medical students' knowledge and attitudes about stem cell research and therapy. Methods: A pre-post test study design was employed. A six-session interactive teaching course was conducted for a duration of six weeks as an intervention. Pre- and post-intervention surveys were used. The differences in the mean scores of students' knowledge and attitudes were examined using paired t-test, while gender differences were examined using an independent t-test. Results: Out of 71 sixth-year medical students from different nationalities invited to participate in this study, the interactive teaching course was initiated by 58 students resulting in a participation rate of 81.7%. Out of 58 students, 48 (82.8%) completed the entire course. The mean age (standard deviation) of students was 24 (1.2) years, and 32 (66.7%) were males. The results showed poor knowledge about stem cells among the medical students in the pre-intervention phase. Total scores of stem cell-related knowledge and attitudes significantly improved post-intervention. Gender differences in knowledge and attitudes scores were not statistically significant post-intervention. Conclusions: Integrating stem cell science into medical curricula coupled with interactive learning approaches effectively increased students' knowledge about recent advances in stem cell research and therapy and improved attitudes toward stem cell research and applications. Keywords: Arab; Attitudes; Education; Interactive teaching; Jordan; Knowledge; Medical curriculum; Stem cells; Students