Development of Optimized Inhibitor RNAs Allowing Multisite-Targeting of the HCV Genome

Abstract: Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs. The catalytic domain was preserved while the aptamer RNA domain was evolved to contain two binding sites, one mapping to the highly conserved IIIf domain of the HCV genome’s internal ribosome entry site (IRES), and the other either to IRES domain IV (which contains the translation start codon) or the essential linker region between domains I and II. These chimeric molecules efficiently and specifically interfered with HCV IRES-dependent translation in vitro (with IC50 values in the low µM range). They also inhibited both viral translation and replication in cell culture. These findings highlight the feasibility of using in vitro selection strategies for obtaining improved RNA molecules with potential clinical applications.This work was supported by the Spanish Ministerio de Economía y Competitividad [BFU2015-64359-P]. Work at our laboratory is partially supported by FEDER funds from the EU.Peer reviewe

Predictive Modelling Of Temperature And Water Activity (Solutes) On The In Vitro Radial Growth Of Botrytis Cinerea Pers

peer reviewe

بعض املرتكزات واألساسيات يف تقدمي القواعد للناطقني بغري العربية

Applied linguistic scholars agree that grammar is an essential aspect of teaching Arabic to a non-native speaker. Therefore, it is impossible to conduct any language to students without teaching its grammar, and it is challenging for the teachers. This research focuses on the overview of Arabic grammatical and its importance in teaching Arabic to non-native speakers. Additionally, it describes what aspects teachers should pay attention to in teaching grammar and offers several methods to be implemented based on academic research and teaching experience.

Tadris Maharah Al-Qiroah li An-Nathiqiin bi Ghairiha Al-Usus An-Nazhariah wa Al-Istiratijiyat At-Tathbiqiyah

This research paper highlights the reading skill in teaching Arabic to other speakers as a receptive skill (listening-reading) that contributes to enriching the learner's language ammunition. The research is made up of two parts: a theoretical part: it focuses on the importance of reading skill, while presenting its types and the purpose of its teaching. And a practical one which deals with the most important strategies used while presenting a reading lesson. This research paper is based on theoretical ideas derived from the heart of applied linguistics, as well as from applied study based on, on the one hand, an educational experience that I have gained while teaching non-Arabic speakers from different countries and nationalities, as well as benefiting from some training courses developed by academic specialists in Arabic language education for nonnative speakers of Arabic.  On the other hand, it benefits from specialized and varied linguistic sources and references.تروم هذه الورقة البحثية تسليط الضوء على مهارة القراءة في مجال تعليم اللغة العربية للناطقين بغيرها؛ باعتبارها من المهارات الاستقبالية (الاستماع- القراءة) التي تسهم في إغناء الذخيرة اللغوية لدى المتعلم. ويتكون البحث من شقين: شق نظري: تطرق لماهية القراءة وأهميتها، مع عرض أنواعها والهدف من تدريسها. وشق تطبيقي تم فيه عرض أهم الاستراتيجيات المتبعة في تقديم القراءة. تستند هذه الورقة البحثية إلى أفكار نظرية مستمدة من صميم اللسانيات التطبيقية، و وإلى دراسة تطبيقية ميدانية ترتكز – من جهة – على تجربة تربوية خضناها في تدريس الناطقين بغير العربية من دول وجنسيات مختلفة، فضلا عن استفادتي – حضوريا – من بعض الدورات التدريبية التي أطرها خبراء دوليون. وترتكز من جهة أخرى على مصادر ومراجع لسانية متخصصة ومتنوعة.

Prevalence, incidence and severity of apple powdery mildew infecting apple trees in the Fes-Meknes Region, Morocco

Apple powdery mildew, Podosphaera leucotricha (Ell. And Ev.), highly infects apple trees in the Fes-Meknes region in Morocco. A disease survey was carried out during fruit set stage of apples in late spring 2018. Three most popular cultivars in the region were assessed for the incidence and severity of the disease. It was obvious that the cultivars were highly susceptible to powdery mildew (Starking Delicious: 17.1%; Golden Delicious: 13.5% and Gala: 11.1%). The correlation between powdery mildew incidence and its severity was highly positive (r =0.90). We recorded the highest disease incidence in Tigrigra (21.5%) and the least in Sidi El Makhfi (4.1%). In view of ensuring good plant protection practices, we recommend that apple farmers carry out disease scouting and consider the action threshold before applying fungicide sprays. Keywords: Disease survey, Apple powdery mildew, Fes-Meknes regio

Management practices to improve the cocoa bean value chain in Sierra Leone

The cocoa bean value chain creates the largest source of employment and livelihood in the agricultural sector of Eastern Sierra Leone. The present review spans solutions to poor management practices, thereby improving the quality of cocoa beans and, by extension, the income of cocoa farmers. The major problems leading to the low yield of cocoa are unimproved varieties, low soil fertility, inadequate phytosanitary practices, climate change, aging of some plantations, and poor postharvest handling practices. The Sierra Leonean cocoa farmers adopt cocoa agroforestry systems. However, the typology of plantation management practices (climate-smart agriculture, organic agriculture, and conventional agriculture) that influence the cocoa quality parameters remains little known. Fairtrade, UTZ certified (Rainforest Alliance), Ecocert, and USDA Organic are the external certification organizations regulating the phytosanitary requirements of dried cocoa beans in Sierra Leone. The certifications influence the prices of cocoa bean export which remain vague to the farmers. The concise review helps recommend the conceptual framework of the cocoa bean value chain to all actors. There is a need for specific certification skills training courses in the country for proper inspection and audit of cocoa phytosanitary practices. Keywords: Cocoa production, postharvest handling practices, phytosanitary regulations, cocoa bean value chain, Sierra Leon