LYCOPENE PRODUCTION IN MYCOBACTERIUM SMEGMATIS BY EXPRESSION OF CRT GENES FROM MYCOBACTERIUM AURUM AND PROTECTIVE EFFECT OF LYCOPENE IN VIVO AND IN VITRO AGAINST UV RADIATION

Objective: The aim of the present study was to express in Mycobacterium smegmatis the clustered mycobacterial genes coding for lycopene synthesis and to investigate the protective properties of lycopene against ultraviolet (UV) irradiation.Methods: The genes, which encode the biogenesis of lycopene in Mycobacterium aurum A+, were introduced into Mycobacterium smegmatis by electroporation. The pigments produced were analyzed by thin layer chromatography, and the absorption spectra were determined. A survival test using UV irradiations was also performed.Results: The transformed Mycobacterium smegmatis were found to synthesize lycopene with important yield (1.41± 3.09 mg/g) and was more resistant to ultraviolet irradiation than non-pigmented strain (p<0.01). Furthermore, cells of M. smegmatis not transformed but coated with lycopene are more resistant to UV than those uncoated (p<0.01).Conclusion: M. smegmatis can form orange colonies on agar plates when it is transformed with the lycopene genes, and the transformants produces 1.41 mg/g (dry weight) of this carotene. Our findings strongly suggest that lycopene has antioxidant activities and prevent the lethal action of UV irradiation on bacterial cells in vivo and in vitro, and deserves further studies considering the amelioration of the production

Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate

AbstractNoonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate lay the groundwork for future molecular diagnosis research, and the development of novel treatment strategies

GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD) with an incidence of 1/3600 live births. This disorder was associated with mutations in the transcription factors involved in cardiogenesis, like Nk2 homeobox5 (NKX2-5), GATA binding protein4 (GATA4) and T-BOX1 (TBX1). GATA4 contributes particularly to heart looping and differentiation of the second heart field.Objectives: The aim of this study was to screen a Moroccan cohort with tetralogy of Fallot for GATA4 mutations, and to assess environmental risk factors that could be involved in the occurrence of this disorder.Methods: Thirty-one non-syndromic TOF patients, enrolled between 5th April 2014 and 18th June 2015, were screened for GATA4 mutations using direct sequencing of GATA4 coding exons. Statistical assessment of different risk factors, which is a retrospective study, was carried out using Chi-square and Fisher’s exact tests. Results: We identified seven exonic variants in nine patients (two missense and five synonymous variants); in addition of eight intronic variants. Assessment of environmental risk factors shows significant association of maternal passive smoking with TOF in the Moroccan population.Conclusion: The present study allowed, for the first time, the molecular and environmental characterisation of Moroccan TOF population. Our findings emphasise particularly the strong association of passive smoking with the emergence of tetralogy of Fallot.Keywords: Tetralogy of Fallot, GATA4, molecular screening, risk factors

GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD) with an incidence of 1/3600 live births. This disorder was associated with mutations in the transcription factors involved in cardiogenesis, like Nk2 homeobox5 (NKX2-5), GATA binding protein4 (GATA4) and T-BOX1 (TBX1). GATA4 contributes particularly to heart looping and differentiation of the second heart field. Objectives: The aim of this study was to screen a Moroccan cohort with tetralogy of Fallot for GATA4 mutations, and to assess environmental risk factors that could be involved in the occurrence of this disorder. Methods: Thirty-one non-syndromic TOF patients, enrolled between 5th April 2014 and 18th June 2015, were screened for GATA4 mutations using direct sequencing of GATA4 coding exons. Statistical assessment of different risk factors, which is a retrospective study, was carried out using Chi-square and Fisher\u2019s exact tests. Results: We identified seven exonic variants in nine patients (two missense and five synonymous variants); in addition of eight intronic variants. Assessment of environmental risk factors shows significant association of maternal passive smoking with TOF in the Moroccan population. Conclusion: The present study allowed, for the first time, the molecular and environmental characterisation of Moroccan TOF population. Our findings emphasise particularly the strong association of passive smoking with the emergence of tetralogy of Fallot

Antimycobacterial natural products from Moroccan medicinal plants: Chemical composition, bacteriostatic and bactericidal profile of Thymus satureioides and Mentha pulegium essential oils

Objective: To evaluate the susceptibility of Mycobacterium aurum and Mycobacterium smegmatis in vitro to the essential oils obtained from two medicinal plants: Thymus satureioides (T. satureioides) and Mentha pulegium (M. pulegium), and to study their chemical composition. Methods: The aerial parts of T. satureioides and M. pulegium (leaves and stems) were hydro-distillated using a Clevenger-type apparatus and essential oils were analyzed and identified by gas chromatography-mass spectrometry. Antimycobacterial screening of essential oils was performed on the basis of the inhibition zone diameter by disc diffusion method against two mycobacterial strains whereas the minimal inhibitory concentration and minimal bactericidal concentration were determined by using the micro-dilution method. Results: Chemical analysis of their aerial part's essential oils gave as major compounds, borneol (34.26%), carvacrol (31.21%) and thymol (3.71%) for T. satureioides and R(+)-pulegone (75.48%), carvone (6.66%) and dihydrocarvone (4.64%) for M. pulegium. Thereafter their antimycobacterial effect evaluation, using the micro-dilution method, indicated that minimal inhibitory concentration values of T. satureioides essential oil ranged from 0.062% to 0.015% (v/v) and from 0.125% to 0.031% (v/v) for M. pulegium respectively against Mycobacterium aurum and Mycobacterium smegmatis. Conclusions: It is clearly evident from the results obtained that the Moroccan medicinal plants have great potential to be used as anti-tuberculosis agents. These findings may help scientists to undertake several research projects to discover useful natural product as new anti-tuberculosis drug

Bifocal Intracanial Rosai-Dorfman Disease Mimicking Lymphoplasmacyte-Rich Meningioma: Diagnostic Pitfalls About a Case Report

Rosai-Dorfman disease (RDD) is a clonal histiocytic proliferation characterized by large S100 positive histiocytes with variable emperipolesis. Extranodal locations were confirmed with the central nervous system or the meninges involvement in less than 5% of cases, which is marked as a significant differential diagnosis of meningiomas in radiological and intra-operative pathological examination. Histopathology and immunohistochemistry are the keys to definitive diagnosis. We present a case of bifocal Rosai-Dorfman disease in a 26-year-old man, mimicking Lymphoplasmacyte-rich Meningioma. This case allows us to demonstrate the diagnosis pitfalls encountered in this localization