Future Career Anxiety and its relationship to academic achievement among educational diploma students at University of Nizwa in the Sultanate of Oman in light of the Corona pandemic

هدفت الدراسة التعرف على علاقة قلـق المُـسـتقبل الـمهـني بالتحصيل الدراسي لدى طلبة دبلوم التأهيل التربوي والملتحقين في الدراسة بجامعة نزوى في سلطنة عُمان في ظل جائحة كرونا، واستخدمت الدراسة المنهج الوصفي، كما استخدم مقـياس قلـق المُـسـتقبل الـمهـني في جمع البيانات والمعلومات وتم تطبيقه على عينة مكونة من (61) طالبة. وتوصلت نتائج الدراسة إلى أن المتوسط العام لمستوى القلق وفقا لمجالاته الخمسة جاءت بين المتوسط والمتدني، كما أظهرت النتائج عدم وجـود فـروق ذات دلالة إحـصائية بين استـجابات أفـراد عينة الدراسـة من طلبة دبلوم التأهيل التربوي لمستوى قلـق المُـسـتقبل الـمهـني في جميع المحاور تُعـزى لمتغير التـخصص (علوم إنسانية، علوم تطبيقية)، كما أن معاملات الارتباط بين معدل الطلبة في البكالوريوس وقلق المسـتقبل جاءت بمستوى ضعيف. وتوصلت الدراسة الى مجموعة من التوصيات والمقترحات المتعلقة بدور مركز الإرشاد الطلابي لخفض القلق لدى الطلبة، وكذلك دور أولياء الأمور لعدم الضغط على أولادهم في قضية التوظيف والمسـتقبل الوظيفي لهم

Functional Characterization of Human Multidrug Resistance Atp-Binding Cassette Transporters

ABC (ATP-binding cassette) transporters comprise one of the largest class of transmembrane proteins. One of the most studied member of the human ABC transporters superfamily is ABCB1 which is also known as P-glycoprotein (P-gp) or multidrug resistance 1 (MDR1). Physiologically, P-gp protects the cells by exporting structurally and chemically unrelated substances out of the cell. P-gp also plays an important role in pharmacokinetics of drugs. Multidrug resistance (MDR) is a common phenomenon observed in cancer cells which is mediated by several molecular pumps including P-gp. Therefore, it is also called multidrug resistance transporter. A major problem in the treatment of diseases like cancer has been the development of resistance to chemotherapies. The present study comprises of three major sections. 1. In silico study for selection of interacting residues of human P-gp with benzophenone sulfonamide type of derivatives 2. Generation and functional characterization of mutants selected from in silico work 3. Screening of benzophenone sulfonamide derivatives for their P-gp inhibitory potential to see their effect on reversal of MDR. For in silico studies, two templates were used for molecular docking of a class of benzophenone sulfonamide derivatives in order to predict the residues in the binding pocket of human P-gp. The crystal structure of mouse P-gp (PDB: 4M1M) was used as a template to build the homology model of human P-gp. Benzophenone sulfonamides were initially docked into the modeled human P-gp. Additionally, the recently published CEM structure of humanmouse chimeric-P-gp was used to dock the same class. Docking results predicted certain important residues of the binding cavity involved in binding to benzophenone sulfonamide derivatives. Among the interacting residues tyrosine Y307 and Y310 were found directly interacting with active compounds of the benzophenone sulfonamide derivatives. Y310 was found in both the types of docking while Y307 was a major interacting partner in humanmouse chimeric structure and found in close vicinity in the modeled human P-gp structure. The second section of the thesis describes the generation of two arginine mutants Y307R and Y310R. Tyrosine Y307 and Y310 were selected for mutation on the basis of docking results. Both Y307 and Y310 were mutated to arginine to see if the mutant transporter showed any difference in transport of substrates and inhibitors including rhodamine 123, propafenone GPV31, verapamil and 3 novel benzonphenone sulfonamide derivatives. Y307R and Y310R mutants were expected to alter the binding of substrates or inhibitors and also affect the transport rate. As expected the two mutants Y307R and Y310R showed a decrease in transport of rhodamine123 which clearly demonstrated the importance of intact tyrosines at position 307 and 310 for transport activity of human P-gp for its renowned substrate rhodamine123. In addition, results with well-known inhibitor of P-gp verapamil and propafenone analogue showed that both mutants require low concentration of inhibitors to inhibit P-gp as compared to wild type transporter. When the inhibition experiments of P-gp were conducted using benzophenone sulfonamide derivatives again both mutants behaved like verapamil and propfenone analogue by showing lower IC50 values as compared to wild type transporter. It had been noticed that Y307R was equally expressed as that of wild type and Y310R showed a slight higher expression as that of P-gp which indicated that these two mutants did not mechanically alter the transporter.Third section of the thesis describes evaluation of benzophenone sulfonamide derivatives as inhibitors of P-gp. Such class of compounds were proven to be good inhibitors as they possess lower molecular weights and LopP values than the well-known inhibitor verapamil. IC50 values showing inhibitory activity of the active compounds (11, 13 and 14) in very low nanomolar range were found to be 0.029 µM ± 0.001, 0.07 µM ± 0.02 and 0.005 µM ± 0.002 respectively.