قانون کے ساتھ بڑے لوگو ں کا کھلواڑ
مصنف نے ایسے طبقے کا ذکر کیا ہے جو ان لوگوں کو راضی رکھنا فرض سمجھتے ہیں جن سے ان کو کام رہتا ہے۔زیادہ تر گورنمنٹ کو راضی کرنے کے لیے گاؤں کے لوگوں کو نواب اور ذیلدار خود ہی اپنے طور طریقے سے سنبھال لیتے ہیں اور اس بات کی خبر بھی گورنمنٹ کو لگنے نہیں دیتے۔ اس طرح کچھ کو تو انصاف مل جاتا مگر زیادہ تر لوگ اپنی بات کو دل میں ہی دبا کر صبر کرلیتے ہیں۔ نواب اور ذیلدار بھی اپنی اپنی ذات میں اتنے مگن ہوتے ہیں کہ اپنے ماتحت کام کرنے والوں کے سپرد اپنی رعایا کردیتے ہیں۔ اس طرح غریب کی آواز گورنمنٹ تو کیا خود نواب تک بھی نہیں پہنچ پاتی۔ مصنف نے اس درد کو محسوس کیا کہ لوگ کس طرح اپنے حق کے لیے بھی آواز نہیں اٹھا پاتے اور اپنے حق سے دستبردار ہو جاتے ہیں۔معاشرے میں مختلف طبقات کا ہونا بھی ایک حقیقت ہے۔ یہ ایک بہت بڑی سچائی ہیکہ دنیا اختلاف رائے پر قائم ہے۔ہر کوئی مختلف ہے رنگ، نسل، زبان، عقائد، امیر، غریب، چھوٹا، بڑا، مختلف رنگ و نسل سے تعلق رکھنے والے مختلف قبائل کے لوگ ریگستانوں، دریاؤں، پہاڑوں،میدانوں کے باسی اور سب سے اہم مختلف نظریات اور گروہوں کی شکل میں مختلف سیاسی پارٹیوں اور مختلف قائدین سے وابستہ لوگ۔اس سب کے باوجود ان کو جو چیز آپس میں ایک رکھتی ہے وہ ہے ان کاآپس میں اعتمادو یقین، اداریاور ملکی حکومت اس چیز کی ضامن ہوتی ہے کہ رویے انصاف پر مبنی ہوں اور یہی انصاف پر مبنی رویے ہی مضبوط معاشرے کی بنیاد بنتے ہیں۔ مگر وہاں جہاں کوئی ایک گروہ سرکش ہو جاتا ہے تو وہ اپنی اجارہ داری کی صورت میں سارا نظام...
اردو اور ہندی کا لسانی اشتراک و افتراق Initially was only language used to express human ideas. In every age, along with customs and traditions, language also went through stages of evaluation. That is why language of each region is unique. This uniqueness of languages is of its identity. Like human beings, languages also have their own families, and different languages grow as sub- branches of language family. They flourish and sometimes thrive and come to life through process of evolution. When some languages die out. Urdu and Hindi also belong to large languages families. They have a deep relationship. And speaking of same relationship, some tinkers do not separate them from each other. When it sometimes thinkers, there is difference between in the two. At a glance, we will mention the linguistic similarities and difference between Urdu and Hindi. Where are places and where there is difference between them, but all of them are mentioned here.
XRCC2, XRCC3 and RAD51 are the main molecules of the homologous recombinant repair (HRR) pathway related to thyroid cancer. Polymorphisms in these genes have been reported frequently in literature and are known to show diverse patterns in different populations. The present study was designed to screen these genes in thyroid cancer patients and controls at the DNA, mRNA and protein levels. A total of 456 pathologically confirmed thyroid cancer patients and 400 healthy controls were recruited. ARMS-PCR was used for genetic analysis followed by sequencing. In this study, various reported polymorphisms were analysed in HRR pathway genes at the germline level in thyroid cancer patients. Significant association of these SNPs were observed with age of diagnosis, gender, smoking, staging, histological subtype and treatment strategies of cancer. Significant association of these functional, promoter based and non-coding polymorphisms in HRR pathway genes and associations of these SNPs with important risk factors highlights their possible role in thyroid carcinogenesis. Further haplotype analysis revealed that most of the haplotypes in XRCC2, XRCC3 and RAD51 are linked with a significant increase in thyroid cancer risk. While some of the haplotypes were associated with a significant reduced thyroid cancer risk. RAD51 SNP, rs1801321 were observed consistent in reduced risk of thyroid cancer in association with risk factors analysed in this study. HRR pathway genes were further investigated at mRNA and protein expression levels. Thyroid cancer samples (n=102) along with equal numbers of un-involved tissues as controls were used for expression analysis. Quantitative real time PCR was used for determination of mRNA expression levels and immunohistochemistry was performed to analyse the protein expression of these genes. Expression analysis of XRCC2, XRCC3, RAD51 and proliferation marker Ki67 at mRNA level revealed significant deregulations. Significant downregulation (p<0.01) of XRCC2 and up-regulations of XRCC3 (p<0.01), RAD51 (p<0.001) and proliferation marker Ki67 (p<0.001) were observed in the expression profile of HRR molecules. These were significantly correlated (negatively and positively) with an up-regulated expression profile of the tumor proliferation marker, Ki67. XRCC3 and RAD51 expression was up-regulated in higher stages and aggressive tumor stages. Immunohistochemical analysis of HRR molecules revealed that among 102 tumor samples, 87% samples showed down- regulation of XRCC2 (p<0.0001), 75% samples showed up-regulation of XRCC3 (p<0.001), 76% samples showed up-regulation of RAD51 (p<0.0001) and 82% samples showed up-regulation (p<0.0001) of proliferation marker, Ki67. These IHC analysis results support our qPCR findings. Polymorphisms in HRR genes and abnormal expression at transcription and translation levels besides defective DNA damage may suggest that HRR pathway genes are correlated with thyroid tumorigenesis and aggressive proliferative behaviour of thyroid cancer in the Pakistani population. Furthermore, the role of XRCC2 and XRCC3 genes were explored in a thyroid cancer cell line (8505C) cells using in-vitro experiments. Effects of genetic modifications were observed for XRCC2 and XRCC3 in thyroid cancer cells by CRISPR-Cas9. These two genes were expressed using lentivirus having GFP, Cas9 and guide RNA. Gene knockouts for these genes were observed after single cell isolation. A gene cleavage assay showed successful genetic modifications and altered behaviour of these genes in thyroid cancer cells. Therefore, potential knockout of these genes gave an insight into molecular mechanism of thyroid cancer. XRCC3 gene function was further explored in the thyroid cancer cell line. Gene knockdown was produced by siRNA technology and successful knockdowns were confirmed using western blots. XRCC3 knockdown cells of anaplastic thyroid cancer (8505C) cell line showed decreased cell growth (p<0.01) as well as decreased cell proliferation after cell colony forming assay (p<0.001) when compared to controls. Decreased invasion (p<0.001), increased adhesion ability (p<0.001) and decreased migration abilities (i.e. wound closure for XRCC3 with siRNA knockdown was 86%) of the cells migrated for wound closure after 24 hours compared to ~98% cell migration of control cells. XRCC3 siRNA knockdown showed significant genetic alterations after treatment with topoisomerase inhibitor drugs (i.e. camptothecin, phleomycin and etoposide). Effect of these drugs on XRCC3 knockdowns were observed by colony PCR and metaphase analysis. Therefore overexpression of XRCC3 caused significant increase in cancerous characteristics of thyroid cancer which is in accordance with observed results at the mRNA and protein levels of expression. For a better insight into these genes in thyroid carcinogenesis, further work is needed to explore the interesting domains playing important role in carcinogenesis. Study of different factors affecting the thyroid cancer will not only assist in understanding thyroid cancer disease progression but will also help to establish future personalized cancer risk prediction.