Under the influence of host immune pressures, human immunodeficiency virus (HIV) rapidly accumulates and selects mutations that confer survival advantage to the virus. The human leukocyte antigen (HLA) represents one of the major host selection pressures that drive the antigenic evolution of HIV. During the course of infection, the interplay of host and virus factors determines the eventual outcome of the disease as well as the repertoire of predominant viral mutants in a given host milieu. In global perspective, this cross-talk between the host and the virus is observed as population-specific amplification of particular HIV subtypes, recombinant forms, or mutation variants. This study focuses on the HIV immunogenic protein Gag to analyze; a) the association of host immunity and viral genetic variability with disease progression, b) HIV subtype A divergence and epitope evolution at global as well as at population level, and c) co-occurring epitope mutations in HIV Gag, using a new in-house bioinformatics tool. Methodology: In this study, a total of 1893 subtype A sequences, from mid-1980s to late 2000s, representing 19 different countries, were included for global analysis. For cohort study, 15 Afghan, 50 Kenyan and 74 Pakistani HIV positive samples were collected. Using a variety of bioinformatics software, the sequences from HIV-1 Gag region p24 and p2p7p1p6 were analyzed for mutations affecting genetic divergence and epitope evolution (predominantly V303 to T303 mutation in the Pakistani and Kenyan cohorts, respectively). Subsequently, the population-specific Gag mutations V303 and T303 were focused for in vitro analysis. Proteasomal assays followed by Mass Spectrometry were performed to evaluate the significance of V303 and T303 mutation in epitope processing. The HIV divergence was analyzed using phylogenetic networks and Bayesian Skyline plot, whereas, the genomic variability of Gag was measured in terms of GàA substitutions and Shannon entropy. Finally, a new Bioinformatics software, I-CAN (Identification of Co-occurring Amino acids and Nucleotides), was developed and used to analyze Gag epitope mutations co-occurring with the mutation V303T in Pakistani and Kenyan sequences. Results: In the Kenyan cohort, a linear trend between HIV genomic variability, and high viral load and low CD4 count was observed. Furthermore, certain Gag mutations unique to either Pakistani or Kenyan cohort were observed to affect the epitope processing in a population-specific manner. As a consequence of these mutations, epitope pattern in the two cohorts was uniquely altered. In the global analysis, it was observed that the HIV subtype A diverged around mid-90s from Kenya, exhibiting an upward trend in genomic variability that peaked in the last 5 years (2005-2010) of the analysis. A similar trend was also observed in Gag epitopes, where point mutations gave rise to novel Gag epitopes, evolving especially in the years 2005-2010. Finally, the results from the tool I-CAN, indicated a strong association in certain Gag co- occurring epitope mutations and the patient‟s HLA types. Conclusion: A pattern of population-specific Gag epitopes was observed that appeared to be evolving under selection pressures from the host HLA. Further investigation of these mutations will enhance the understanding of the evolution of HIV under host/population-specific selection pressures. This information may be helpful in designing vaccine and treatment strategies against HIV.
پروفیسر اصغر علی فیضی پروفیسر فیضی آکسفورڈ کے اعلیٰ تعلیم یافتہ تھے ان کااصل مضمون قانون تھا، مشرقی علوم وفنون میں بھی ان کودسترس تھی۔اسلامی قانون پران کی کتابیں حوالہ کی کتاب (Book of Reference)کی حیثیت رکھتی ہیں۔ عرصہ تک لاء کالج بمبئی کے پرنسپل رہے، انڈیا کے مصراور شام میں بھی سفیر رہے اورکشمیر یونیورسٹی کے وائس چانسلر بھی ہوئے۔ وزیٹنگ پروفیسر کی حیثیت سے کینیڈا، یورپ اورامریکہ کی متعدد یونیورسٹیوں میں لکچر دیے۔برہان کے خریدار شروع سے تھے اوراس کی بڑی قدر کرتے تھے، برہان کا کوئی مقالہ یانظرات ان کوزیادہ پسند آتاتھا تواس کی داد تحریراً دیتے تھے۔عرصہ سے ان کاکوئی خط نہیں آیاتھا۔بعض خانگی معاملات اورمسلسل ضعف وعلالت کے باعث سخت پریشان تھے۔ اب اچانک اخبارات میں ان کے انتقال کی خبر نظر سے گزری تودیرینہ تعلق کے باعث سخت صدمہ اورافسوس ہوا۔ اللھم اغفرلھما وارحمھما۔ [نومبر۱۹۸۱ء]
تسعى هذه الدراسة إلى التحديد التاريخي للنهضة العربية الإسلامية وسياقاتها وأسباب حدوثها، سواء منها السياسية أوالدينية أوالإصلاحية أو غيرها، والوقوف على أبرز روادها، ومناقشة أفكارهم، وتتبع مناهجهم، مع تدقيق النظر في المشاريع الإصلاحية التي قادوها في مراحل تاريخية حاسمة، هدفها استنهاض الأمة العربية والإسلامية من سباتها. وقد اعتمدت الدراسة على الجمع بين توليفة متكاملة من المناهج البحثية، خاصة منها المنهج الوصفي التحليلي والمنهج الاستقرائي والمنهج المقارن، وقد توصلت الدراسة إلى مجموعة من النتائج أهمها أن الأمة العربية والإسلامية لا زالت في نهضة وصحوة، ما دامت تسعى إلى تحقيق نفس الأهداف التي سعت إليها النهضة العربية السابقة، والتي لم تتحقق بعد، وقد أوصت الدراسة بمجموعة من التوصيات، تأتي على رأسها أهمية استجماع جهود الفاعل السياسي والمفكر والفاعل التربوي والمصلح الديني وعالم التقنية وغيرهم من الرواد، واشتغالهم بمنهج علمي واضح، قوامه استحضار مخرجات الإصلاحات السابقة دون الركون إليها، واستشراف المستقبل بتحدياته وآفاقه، لتخطيط مشاريع إصلاحية واقعية قابلة للتطبيق في البيئة العربية والمسلمة.
This study aimed at exploring teachers' perceptions of the actual and preferred leadership approaches of their principals in government and private schools in Karachi' Pakistan. The second aim was to compare whether teachers in government schools perceive leadership approaches (Actual and Preferred) of principals differently from teachers in Private schools or not. A survey tool Principal Leadership Approach Questionnaire (PLAQ) - developed by Pashiardis (1998), was adapted for this study. Questionnaires were sent to 450 teachers, randomly selected from government and private schools of three towns of Karachi. This sample teachers were asked to rate actual (PLAQ-A) and preferred (PLAQ-P) leadership approaches. Of 450 teachers, 333 completed the survey, providing a return rate of 74%. The results showed that the teachers perceived existing leadership approaches of principals as less democratic and less instructional than what they aspire for. The patterns remained consistent across systems of schools. However, the existing leadership approaches are perceived as more democratic in private schools than in their government counterparts. Further analysis revealed that teachers regardless of systems of schools perceived their principals as more efficient in the area of administration and fiscal management'. The government teachers wanted their headteachers to improve their leadership practices in the area of personnel management' and school leadership and management'. The private teachers wanted their principals to play a more active role in professional development in-service' and relations with parents and the community.' The study provides insight into an under-research area of teachers' perception about leadership approaches of principal in a developing country by using PLAQ, a questionnaire adapted for Pakistan as part of the current research. The results might prove useful to further the understanding of leadership and management practices in the context of the professional development of principals. The study also provides a foundation for further research and adds a measurement tool to the leadership and management literature.