شیر مردوں سے ہوا بیشۂ تحقیق تہی
(ڈاکٹر شمس بدایونی)
۲۶؍ فروری بروز اتوارصبح کے سات بجے تھے، میں سفر کے لیے تیار ہوکر پور ٹیکو کے قریب پہنچ چکاتھا، معاًفون کی گھنٹی بجی، میں واپس ہوا، ریسیور اٹھایا اُدھر سے آواز آئی ’’میں حنیف نقوی۔ رشید حسن خاں صاحب کا رات انتقال ہوگیا آپ ان کی تدفین میں شریک ہوسکتے ہیں‘‘۔ میں کسی اہم وجہ سے اپنے سفر کو ملتوی نہیں کرسکا اور تدفین میں شریک ہونے سے معذور رہا، مگراس دن ایک اضمحلال کی کیفیت طاری رہی، ان سے ملاقاتیں اور فون پر کی گئی باتیں یاد آتی رہیں، ان کی اعتماد ویقین سے بھرپور آواز، کاٹ دار جملے، بے تکلف لہجہ، کچھ خاص تکیہ کلام، ہاں بھائی، ارے بھئی، دیکھئے، یہ جو ہیں نا، ہاں بس ان کے لہجے اور بیان کا طنطنہ سماعت پر بار بار دستک دیتا رہا، میں کبھی محظوظ ہوتا رہا اور کبھی ملول، اب یہ آواز سننے کو کہا ملے گی؟ کون اس طرح دو ٹوک انداز میں پکارے گا؟۔
۱۔ ’’ہیلو۔ ارے بھئی! آپ کہاں ہیں؟ ایک ماہ ہوگیا آپ کا کوئی فون نہیں آیا دیکھئے شمس صاحب! کم از کم مہینے میں ایک بار ضرور فون کیجیے۔ یا پھر تعلق منقطع کرلیجیے‘‘۔
۲۔ ’’ہیلوجی میں شمس بول رہا ہوں۔ ہاں بھئی شمس صاحب کیسے ہیں آپ؟ آپ کے بچے کیسے ہیں؟ کیسی ہے ہماری بہو؟ اور ہمارے لطیف صاحب ٹھیک ہیں! کاروبار کیسا چل رہاہے آپ کا؟ کیا لکھ رہے ہیں آج کل آپ؟۔
دیکھئے شمس صاحب میں برابر سن رہا اور پڑھ رہاہوں کہ آپ لگاتار سمیناروں میں شرکت کررہے ہیں، یہ ٹھیک نہیں ہے، آپ کو جم کر سنجیدگی کے ساتھ کسی موضوع پر تین چار سال کام کرنا چاہیے، بس اگر آپ یہ نہیں کریں گے تو خود کو ضائع کردیں گے، ارے بھائی،...
The issue of the sacrifice of Abrahim’s son remain an important bone of contention among the followers of Abrahamic religions. The Jews and Christians believe that it is Ishaq while among the Muslims some opine in favour of Ismail while favours Ishaq. To a common man it seems to be not an important issue whether it is Ismail or Ishaq but when its implications are taken into account then it is of great value to Muslims, Jews and Christians that who was sacrificed? Ismail or Ishaq. In the following pages an effort is made to look the issue in the light of some contemporary researches conducted in the Indo-Pak Subcontinent in the first half of the 20th century. Different positions on the issue are evaluated with the Quran and other holy scriptures and in the contemporary western scholarships.
Embryonic stem cells are the pluripotent cells that act as a root of embryonic development to engender the specialized cells of the body. This property can be captured in vitro to cultivate indefinitely, providing a remarkable model to study early development and diseases. In vitro, mouse pluripotent embryonic stem cells (mESCs) exist in two different states, naïve and primed. The naïve state mimics in vivo inner cell mass of blastocyst with the pluripotency genes expressed more uniformly and have more developmental potential than the primed state. The primed state corresponds to a later embryonic developmental stage than the naïve state. Both states of cells express similar level of some key pluripotency genes but the signaling pathways that support their self-renewal and pluripotency are strikingly different. Mitochondrial metabolism, among others, is a major difference between the two states. The primed state has more mature mitochondria but doesn’t use them for ATP generation, which is generated solely through glycolysis. The naïve state however, has a bivalent metabolic state, i.e. uses both glycolysis and mitochondria to generate ATP. What role mitochondria play in these two states remains a very interesting and relevant question. Here in this study, we investigated the function of mitochondrial respiration in naïve mESCs by blocking the electron transport chain (ETC) with specific pharmacological inhibitors, Rotenone and Antimycin, and genetically with shRNAs against mitochondrial specific transcription factor A (TFAM) and a helicase, Twinkle. Both inhibitors and shRNAs resulted in blockade of cell proliferation and when released, the cells resumed self-renewal without affecting the pluripotency. The paused phenotype by ETC inhibition also appeared in the blastocysts cultured in vitro, which naturally die within 2-3 days of the development while Rotenone treatment extends survival of blastocysts for 3 more days. Moreover, the treated blastocysts were able to give live pups when injected back into surrogate mother, confirming a normal developmental potential. Upon ETC inhibition with either compounds or shTFAM, the mitochondrial mass and membrane potential increased and level of reactive oxygen species (ROS) decreased. The shRNAs against TFAM and Twinkle greatly reduced the mitochondrial DNA (mtDNA) copy number and expression of mtDNA encoded mRNA, leading to complete blockade of mitochondrial respiration. Paused mESCs stopped oxygen consumption and enhanced glycolysis instead to maintain a steady level of ATP generation, which is essential for the cells to be alive. Mechanistically, ETC inhibition induced pause is distinct from the pause induced through either mTOR or Myc inhibition. Neither pyruvate, aspartate nor nucleosides supplementation could rescue the self-renewal of mESCs which were shown to have the ability in other cell types upon ETC inhibition. The total non-targeted metabolomics showed that the ETC regulates the carbohydrates, proteins, lipid and nucleic acid metabolism. Specifically, lysosomal-related pathways are found to be significantly and commonly changed from both metabolomics and proteomic analyses. We could confirm the blockade of autophagy and lysosomal pathways in ETC inhibition-induced paused cells. These analyses suggest that an intimate link exists between mitochondria and lysosome in mESCs and highlights the potential important function of lysosomes for mESCs self-renewal. This work reported a new type of pause by ETC inhibition in mESCs and identified some unique metabolic roles of mitochondrial ETC for mESCs self-renewal. Furthermore this study first time shows the effect of Ursolic acid on mouse embryonic stem cells.