Editorial

كلمة العدد (الإنجليزي)Editorial in Englis

Expression, purification et réévaluation du rôle de la protéine CGI-58 dans le métabolisme lipidique

Triglycerides (TG) hydrolysis in adipose tissue is initialized by the action of the adipose TG lipase (ATGL) and its cofactor, the CGI-58 protein. Mutations in the gene coding the CGI-58 or ATGL proteins are the cause of the syndrome of Chanarin-Dorfman and of neutral lipids storage disease, respectively. CGI-58 protein belongs to the a/ß-hydrolase family, harboring the catalytic triad Ser-Asp/Glu-His, characteristic of carboxylester hydrolases, as well as the HX4D motif, characteristic of acyltransferase activity. Nowadays, the role and the enzymatic activity of the CGI-58 protein, in mammalians and plants, are not quite clear. In order to better understand the function of CGI-58 protein in lipid metabolism, we developed a new strategy using a new set of plasmids that enabled us, with the use of pET28b(+) plasmid, to express and purify the CGI-58 protein of mice and plants as well as the murine ATGL. These proteins were expressed in different E. coli strains, to test in vitro their activity. In addition, we have set up, using the generated plasmids and different E. coli strains, a system that allowed us to test the in vivo acyltransferase activity (LPAAT and/or LPGAT) of the CGI-58 proteins expressed in E. coli. Using these techniques, we demonstrated in vivo and in vitro that both mice and plant CGI-58 proteins, are neither able to catalyze a LPAAT or a LPGAT reaction, and that the plant CGI-58 protein is devoid of TG lipase or phospholipase activity. However we have shown, by analyzing lipid extracts, by thin layer chromatography and by mass spectrometry of different E. coli strains expressing the CGI-58 protein, that the expression of the plant CGI-58 protein, but not the mice one, results in a decrease of phosphatidylglycerol (PG) content in the different strains tested. However the mutation of the serine or histidine residue of the putative catalytic triad restores the wild-typephenotype. These results allowed us to propose that plant CGI-58 protein is involved in the metabolism of PGL’hydrolyse des triglycérides (TG) du tissu adipeux est initialisée par l’action de l’adipocyte TG lipase (ATGL), activée par son cofacteur la protéine CGI-58. Des mutations du gène codant les protéines CGI-58 ou ATGL sont respectivement à l’origine du syndrome de Chanarin-Dorfmann et de maladies de stockagede lipides neutres. La protéine CGI-58 appartient à la famille des a/ß-hydrolases, elle en possède la triade catalytique Ser-Asp/Glu-His caractéristique des carboxylester hydrolases, ainsi que le motif HX4D, caractéristique d’une activité acyltransférase. A ce jour, le rôle de la protéine CGI-58, chez les mammifères ou chez les plantes, n’est pas totalement éclairci, de même que son activité enzymatique. Dans le but de mieux comprendre le rôle de cette protéine CGI-58 dans le métabolisme lipidique, nous avons développé une nouvelle stratégie, en générant notamment de nouveaux plasmides qui nous ont permis d’exprimer et de purifier la protéine CGI-58 de souris et de plantes, ainsi que l’ATGL murine, dans différents souches d’E. coli, pour tester l’activité in vitro de ces protéines. De plus, nous avons mis en place, en utilisant ces plasmides générés et différentes souches E. coli, un système qui nous a permis de tester in vivo, dans E. coli, l’activité acyltransférase (LPAAT et/ou LPGAT) de la protéine CGI-58. En utilisant ces différentes techniques, nous avons pu montrer, aussi bien in vivo qu’in vitro, que la protéine CGI-58 de plante, ainsique celle de mammifère, ne possède ni activité LPAAT ni activité LPGAT, et que la protéine CGI-58 de plante est dépourvue d’activité TG lipase ou phospholipase. Cependant, nous avons montré, en analysant, par chromatographie sur couche mince et par spectrométrie de masse, des extraits lipidiques des différentes souches d’E. coli exprimant la protéine CGI-58, que l’expression de la protéine de plante, et non celle de mammifère, aboutit à une diminution du taux de phosphatidylglycérol (PG) dans les différentes souchestestées, et a contrario nous avons montré que la mutation de la sérine, ainsi que la mutation de l’histidine de la triade catalytique potentielle, restaure le phénotype sauvage. Ces résultats nous ont permis de proposer que la protéine CGI-58 de plante est impliquée dans le métabolisme du P

The Journal of Quranic Studies published by SOAS London University: The Question of Objectivity and Prejudice

أهداف البحث: تصدر مجلة الدراسات القرآنية عن كرسي الملك فهد منذ عام 1990 والذي يتبع لقسم الدراسات الشرق أوسطية في جامعة لندن: المدرسة الشرقية الإفريقية. ويهدف هذا البحث أن يعرف القارئ بهذه المجلة وبأهميتها من الناحية العلمية، وتأثيرها في المجال الأكاديمي وفي الإثراء العلمي الذي تقدمه في حقل الدراسات القرآنية. ويبين البحث أيضا مدى التزام المجلة بالمنهج العلمي المحايد في عرضها لآراء متناقضة حول القرآن الكريم وعلومه من قبل الباحثين المسلمين والغربيين الذين ينشرون في المجلة.  منهج الدراسة: اعتمد الباحث كلا من المنهج الوصفي والاستقرائي في دراسة كل الأعداد الصادرة من عام 1999 وحتى تاريخ إجراء الدراسة عام 2018، حيث بلغت المقالات المنشورة حوالي 267 بحثا باللغات العربية والإنجليزية والفرنسية. وكذلك اعتمد الباحث على المنهج التحليلي في دراسة بعض الأبحاث التي قدمها مسلمون وغربيون. النتائج: هذه المجلة هي مجلة علمية دولية لها وزنها وأثرها الكبير لدى الباحثين في الغرب في مجال الدراسات القرآنية. وقد تضمنت المجلة أبحاثا رصينة وجديدة، إلا أن إشكالية الموضوعية والتحيز لم تستطع هذه المجلة تجاوزها أو وضع ميزان ضابط لها، فانحازت للكتاب الغربيين المعارضين للإسلام دون أخذ بعين الاعتبار لمشاعر المسلمين وعقائدهم بدعوى الحيادية، ولم تطرح موضوعات ناقدة للمنهج الغربي الذي يتناول القرآن الكريم بتحيز واضح. وأوصت الدراسة بضرورة إنشاء مجلة علمية دولية متخصصة بالقرآن الكريم وعلومه، تعرض آراء المسلمين والغربيين المنصفين بطريقة علمية منصفة.Purpose: The Journal of Qur'anic Studies has been published in the King Fahd Chair of Islamic Studies since 1990 and is affiliated with the Department of Middle Eastern Studies at the University of London: Oriental African school. This Study aims to familiarize the reader with this journal and its scientific importance, its impact in the academic field and the scientific enrichment it offers in the field of Quranic studies. The study also shows the extent to which the journal adheres to a neutral scientific approach in presenting contradictory views on the Quran and its Sciences by Muslim and Western researchers who publish in the journal. Methodology: The researcher adopts both descriptive and inductive approach in the study of all the issues from 1999 to the date of the study in 2018. The published articles amounted to about 267 articles in Arabic, English and French. The author also relied on the analytical approach to study some of the articles presented by Muslims and Westerners. Findings: This is an international scientific journal that has a significant weight and impact among researchers in the West in the field of Qur'anic studies. The journal includes solid and new study. Yet, this journal could not overcome or put a criteria that controls the problem of objectivity and bias. Thus, it sides with western writers opposed to Islam without taking into account the feelings and beliefs of Muslims under the pretext of neutrality, and does not raise topics critical of the Western approach that deals with the Holy Quran with a clear bias. The study recommends the need to establish an international scientific journal specialized in the Holy Quran and its Sciences, presenting the views of Muslims and fair Westerners in an unbiased scientific manner

Beyond Antimalarial Stock-outs: Implications of Health Provider Compliance on Out-of-Pocket Expenditure during Care-Seeking for Fever in South East Tanzania.

To better understand how stock-outs of the first line antimalarial, Artemisinin-based Combination Therapy (ACT) and other non-compliant health worker behaviour, influence household expenditures during care-seeking for fever in the Ulanga District in Tanzania. We combined weekly ACT stock data for the period 2009-2011 from six health facilities in the Ulanga District in Tanzania, together with household data from 333 respondents on the cost of fever care-seeking in Ulanga during the same time period to establish how health seeking behaviour and expenditure might vary depending on ACT availability in their nearest health facility. Irrespective of ACT stock-outs, more than half (58%) of respondents sought initial care in the public sector, the remainder seeking care in the private sector where expenditure was higher by 19%. Over half (54%) of respondents who went to the public sector reported incidences of non-compliant behaviour by the attending health worker (e.g. charging those who were eligible for free service or referring patients to the private sector despite ACT stock), which increased household expenditure per fever episode from USD0.14 to USD1.76. ACT stock-outs were considered to be the result of non-compliant behaviour of others in the health system and increased household expenditure by 21%; however we lacked sufficient statistical power to confirm this finding. System design and governance challenges in the Tanzanian health system have resulted in numerous ACT stock-outs and frequent non-compliant public sector health worker behaviour, both of which increase out-of-pocket health expenditure. Interventions are urgently needed to ensure a stable supply of ACT in the public sector and increase health worker accountability

CHARACTERIZATION OF THERMAL TREATED CLAYOBTAINED FROM LEBANESE LOCAL RESOURCES ASSUPPLEMENTARY CEMENTITIOUS MATERIALS

The purpose of this research was to evaluate a kaolin clay obtained from local Lebanese source after being subjected to thermal treatment. A sample of kaolin clay was collected from local resources and subjected to a treatment process for enhancing its pozzolanic properties. The treated sample was characterized through testing procedure as per ASTM C311. It was found that the physical and chemical properties were in compliance with the relevant ASTM C618 standard. This indicates that the proposed treatment succeeded in developing and exhibiting the pozzolanic activity of the end product. The activity index test of the treated samples was investigated to verify the quality and performance of the end product which was found to be satisfactory. Therefore, the treated product is accepted to be classified as natural Pozzolan as per ASTM C618. The potential of producing Metakolin in Lebanon is of high importance due to its availability in large quantities. Moreover, it might be used to replace part of the Portland cement to reduce the CO2 emi ssion and energy consumption resulting from the cement production

Temperature effects on the design parameters of a geothermal pile

In geotechnical engineering, geostructures with thermo-active functions establish direct thermal exchange between the ground and buildings. They can transfer energy from or into the ground to heat or cool a building. However, adapting foundation piles, completely or in part, to produce energy piles results in heat exchange with the soil, which changes the temperature of the soil and could thereby and affects the geotechnical properties and load bearing capacity of the geostructure. Most calculations of the bearing capacities of deep foundations conducted in France are currently based on in-situ testing results using a pressuremeter. Using finite element method to model the pressuremetric behaviour of a compacted soil subjected to thermo-mechanical variations is the main motivation for this work. In this study, several pressuremeter tests were conducted on a compacted illitic soil in a laboratory tank at temperatures between 1° and 40°C. The impact of temperature variation on the limit pressure (Pl), the creep pressure (Pf) and the Ménard pressuremeter modulus (EM) were determined. The results showed a significant decrease for both limit pressure (Pl) and creep pressure (Pf) with the increase of temperature. Numerical simulations of these tests were used to calibrate a bilinear constitutive model, taking into account temperature effects on soil compressibility within a coupled thermo-mechanical framework. Thereafter, a case study of a heat exchanger pile was simulated using the proposed approach

Efficacy, persistence and vector susceptibility to pirimiphos-methyl (Actellic® 300CS) insecticide for indoor residual spraying in Zanzibar

Background Indoor residual spraying (IRS) of households with insecticide is a principal malaria vector control intervention in Zanzibar. In 2006, IRS using the pyrethroid lambda-cyhalothrine was introduced in Zanzibar. Following detection of pyrethroid resistance in 2010, an insecticide resistance management plan was proposed, and IRS using bendiocarb was started in 2011. In 2014, bendiocarb was replaced by pirimiphos methyl. This study investigated the residual efficacy of pirimiphos methyl (Actellic® 300CS) sprayed on common surfaces of human dwellings in Zanzibar. Methods The residual activity of Actellic 300CS was determined over 9 months through bioassay tests that measured the mortality of female Anopheles mosquitoes, exposed to sprayed surfaces under a WHO cone. The wall surfaces included; mud wall, oil or water painted walls, lime washed wall, un-plastered cement block wall and stone blocks. Insecticide susceptibility testing was done to investigate the resistance status of local malaria vectors against Actellic 300CS using WHO protocols; Anopheline species were identified using PCR methods. Results Baseline tests conducted one-day post-IRS revealed 100 % mortality on all sprayed surfaces. The residual efficacy of Actellic 300CS was maintained on all sprayed surfaces up to 8 months post-IRS. However, the bioassay test conducted 9 months post-IRS showed the 24 h mortality rate to be ≤80 % for lime wash, mud wall, water paint and stone block surfaces. Only oil paint surface retained the recommended residual efficacy beyond 9 months post-IRS, with mortality maintained at ≥97 %. Results of susceptibility tests showed that malaria vectors in Zanzibar were fully (100 %) susceptible to Actellic 300CS. The predominant mosquito vector species was An. arabiensis (76.0 %) in Pemba and An. gambiae (83.5 %) in Unguja. Conclusion The microencapsulated formulation of pirimiphos methyl (Actellic 300CS) is a highly effective and appropriate insecticide for IRS use in Zanzibar as it showed a relatively prolonged residual activity compared to other products used for the same purpose. The insecticide extends the residual effect of IRS thereby making it possible to effectively protect communities with a single annual spray round reducing overall costs. The insecticide proved to be a useful alternative in insecticide resistance management plans

Expression of DLK1 and MEG3 genes in porcine tissues during postnatal development

The Drosophila-like homolog 1 (DLK1), a transmembrane signal protein similar to other members of the Notch/Delta/Serrate family, regulates the differentiation process in many types of mammalian cells. Callipyge sheep and DLK1 knockout mice are excellent examples of a fundamental role of the gene encoding DLK1 in muscle growth and fat deposition. DLK1 is located within co-regulated imprinted clusters (the DLK1/DIO3 domain), along with other imprinted genes. Some of these, e.g. the RNA coding MEG3 gene, presumedly interfere with DLK1 transcription. The aim of our study was to analyze DLK1 and MEG3 gene expression in porcine tissues (muscle, liver, kidney, heart, brain stem) during postnatal development. The highest expression of both DLK1 and MEG3 variant 1 (MEG3 var.1) was observed in the brain-stem and muscles, whereas that of MEG3 variant 2 (MEG3var.2) was the most abundant in muscles and the heart. During development (between 60 and 210 days of age) expression of analyzed genes was down-regulated in all the tissues. An exception was the brain- stem, where there was no significant change in MEG3 (both variants) mRNA level, and relatively little decline (2-fold) in that of DLK1 transcription. This may indicate a distinct function of the DLK1 gene in the brain-stem, when compared with other tissues

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London