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Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

The small ribosomal subunit protein uS9 (formerly called rpS16 in Saccharomyces cerevisiae), has a long protruding C-terminal tail (CTT) that extends towards the mRNA cleft of the ribosome. The last C-terminal residue of uS9 is an invariably conserved, positively charged Arg that is believed to enhance interaction of the negatively charged initiator tRNA with the ribosome when the tRNA is base-paired to the AUG codon in the P-site. In order to more fully characterize the role of the uS9 CTT in eukaryotic translation, we tested how truncations, extensions and substitutions within the CTT affect initiation and elongation processes in Saccharomyces cerevisiae. We found that uS9 C-terminal residues are critical for efficient recruitment of the eIF2•GTP•Met-tRNAiMet ternary complex to the ribosome and for its proper response to the presence of an AUG codon in the P-site during the scanning phase of initiation. These residues also regulate hydrolysis of the GTP in the eIF2•GTP•Met-tRNAiMet complex to GDP and Pi. In addition, our data show that uS9 CTT modulates elongation fidelity. Therefore, we propose that uS9 CTT is critical for proper control of the complex interplay of events surrounding accommodation of initiator and elongator tRNAs in the P- and A-sites of the ribosome.

Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

Many organizations in the world either commercial or service, started to adopt new information systems, such as Enterprise Resource Planning (ERP), in order to overcome challenges, keep surviving in the market and to gain donor’s confidence. Therefore, among these organizations, there are international and relief organizations, for example United Nations Relief and Works Agency (UNRWA), which considered the biggest relief agency taking care of Palestinian refugees. UNRWA started applying ERP (REACH) in April-2015 in all its operations areas (Syria, Lebanon, Jordan, West Bank and Gaza), in order to improve the efficiency of its processes, and to overcome the difficulties, which existed in the old system (RAMCO). This study aims to investigate the relationship between quality characteristics (system quality, service quality, information quality, compatibility, and complexity) and effectiveness of ERP in post implementation stage at UNRWA’s employees in Gaza Field, and to identify the impact of these characteristics on system usage (individual and organizational impact). The study followed the descriptive analytic approach, and used a comprehensive survey method through a developed questionnaire to measure the research variables. (184) questionnaires were distributed, (174) usable questionnaires were received. The study found that three of independent variables (system quality, information quality & compatibility) affect directly and positively on ERP effectiveness, also the study reveals that (system quality & information quality) affect directly and positively on individual usage. On the other hand, the study reveals that there was no significant difference among the respondents, toward each field due to gender, educational level, age, current job, level, and years of experience. The study recommends that, there is a need to increase the awareness about REACH usage benefits, enhance training, and facilitate effective communications to sort out REACH problems quickly and easily. توجهت العديد من المنظمات في العالم سواء الخدمية أو التجارية إلى تبني أنظمة معلومات حديثة، كنظام تخطيط الموارد المؤسسية ، من أجل مواجهة التحديات والمحافظة على وضعها في السوق وكسب ثقة المانحين ، لذا كان من ضمن هذه المنظمات، منظمات دولية وإغاثية كمنظمة الأونروا التي تعتبر أكبر مؤسسة إغاثية وخدمية تهتم بشئون اللاجئين الفلسطينيين. لقد قامت الأونروا بتطبيق نظام تخطيط الموارد المؤسسية (REACH) في أبريل 2015 في كافة مناطق العمليات الخمسة (سوريا – لبنان-الأردن-الضفة –غزة) من أجل تحسين كفاءة عملياتها والتغلب على الصعوبات التي كانت موجودة في النظام القديم. تهدف هذه الدراسة إلى فحص العلاقة بين خصائص الجودة (جودة النظام ، جودة الخدمة، جودة المعلومات، التوافقية، درجة التعقيد) وبين فعالية نظام تخطيط الموارد المؤسسية في مرحلة ما بعد التنفيذ (أثره على الفرد والمنظمة) على موظفي مكتب غزة الإقليمي فقط. استخدم الباحث منهج التحليل الوصفي من خلال إعداد استبانة مصممة خصيصا للتعامل مع متغيرات البحث ، تم القيام بمسح شامل لأفراد العينة ، حيث تم توزيع الاستبانة على (184) موظفاً داخل مكتب غزة الإقليمي ، تم استرداد (174) استبانة. أظهرت نتائج الدراسة أن ثلاثة من المتغيرات المستقلة (جودة النظام ، جودة المعلومات، التوافقية ) تؤثر بشكل مباشر وذات دلالة احصائية في فعالية النظام ، أيضاً كشفت الدراسة أن كلاً من (جودة النظام وجودة المعلومات) تؤثر بشكل مباشر على استخدام الفرد ،وأن كلاً من (جودة النظام والتوافقية) لها تأثير مباشر على الكفاءة التنظيمية، كذلك أظهرت النتائج عدم وجود فروقات ذات دلالة إحصائية في استجابة المبحوثين تعزى إلى كلٍ من الجنس، العمر، المؤهلات، التعليم، الوظيفة الحالية، وأيضا سنوات الخبرة باستخدام النظام. وأوصت الدراسة بضرورة زيادة الوعي حول فوائد استخدام نظام تخطيط الموارد المؤسسية (REACH) ، وتعزيز التدريب لهذا النظام ، وتسهيل عملية التواصل الفعّال من أجل حل مشاكل النظام بسرعة وبسهولة.