Autosomal recessive congenital ichthyosis (ARCI) is a genetically and phenotypically heterogeneous group of non-syndromic cornification disorders characterized primarily by generalized hyperkeratotic epidermal scales with or without erythroderma. So far, pathogenic variants in fourteen genes have been associated with ARCI most of which perturb lipid metabolism and localization during cornification, thereby disrupting the lipid envelope and thus barrier function. Research is in progress to reduce or treat the disease manifestations in affected individuals by enzyme replacement therapy and gene therapy. Moreover, gene expression studies and histopathological studies have been performed to discover more effective drug targets. However, a more precise genotype to phenotype correlation and a greater understanding of the pathophysiology would aid in developing more specific therapies. Therefore, the necessity is to elucidate the link between a defective gene and the resulting difference in expression of proteins in epidermis. In the current study whole exome sequencing (WES), Sanger sequencing and mass spectrometry were used to investigate four consanguineous Pakistani families (A, B, C, and D) affected with ARCI. WES identified a frameshift mutation c.364dupA (p.T122IfsX3) in SDR9C7 in family A, a nonsense mutation c.762C>G (p.Tyr254*) in PNPLA1 in family B, a missense mutation c.944G>A (p.R315H) in TGM1 in family C, and a missense mutation c.424 (p.R142C) in TGM1 in family D. Mass spectrometry of purified proteins isolated from epidermal corneocytes samples of the affected individuals confirmed the deleterious effects of the identified mutations. Combinatorial protein analysis of the three groups (PNPLA1, SDR9C7, and TGM1) identified common 20 proteins with altered expression in all the disease groups indicating their central role in ARCI pathology. Furthermore, a proteomic spectrum specific for each type of ARCI was also acquired. In conclusion, four families affected with ARCI were identified with mutations in SDR9C7, PNPLA1, and TGM1 along with the proteomic profiles that could aid in the genetic counseling and prenatal diagnosis of the families as well as devising improved diagnostic and therapeutic approaches for ARCI.
نواب ناظر یارجنگ نواب ناظر یارجنگ مرحوم ہماری پرانی بزم کی یادگار تھے، اس کی ساری خوبیاں ان میں جمع تھیں، وہ ایک بڑے باپ مولوی نظام الدین حسن مرحوم کے فرزند، خود حیدرآباد ہائیکورٹ کے جج اور اپنے اوصاف کے اعتبار سے بڑے آدمی تھے، وہ علی گڑھ کالج کے ابتدائی دور کے اولڈ بوائے تھے، اب شائد ہی ان کا کوئی معاصر زندہ ہو اور آخر تک ان کو اس سے وابستگی رہی، مدتوں مسلم یونیورسٹی کورٹ اور ایگزیکیٹو کونسل کے ممبر اور اس کے کاموں میں عملی حصہ لیتے رہے، ججی کے عہدے سے عرصہ ہوا ریٹائر ہوچکے تھے اور اپنا وقت حیدرآباد کے قومی و ملی کاموں میں صرف کرتے تھے، دارالمصنفین کی مجلس انتظامیہ کے پرانے رکن اور اس کے ہمدرد و ہوا خواہ تھے، ان سب سے بڑھ کر وہ عملاً مرد مومن تھے، ان کی موت سے ایک پرانی یادگار مٹ گئی، اﷲ تعالیٰ ان کی مغفرت فرمائے۔ (شاہ معین الدین ندوی،ستمبر ۱۹۶۶ء)
The present study work is about importance of plants in the light of Quran, A hadith and modern science Plants are an important means of survival. Without them, life is not only difficult but impossible. The very first tree was mention by Allah when the Hazrat Aadam Eli Hisslam was in the heaven a number of plant was mention by Quran o Hadith and other botanical books. Plants are main source of nutrition for human being, animals and curative plants are beauty of our planet. Their medicinal values are mention by Quran and Prophat Hazrat Muhammad صلى الله عليه وسلم proved by modern science. Many books and research paper have been written on plants with the passage of time the direction of research has also changed, as in the case of epidemics, likewise Corona has opened a new avenue of research that has resorted to herbal remedies, among other therapies. Such current research work is part of a series that sheds light on various aspects of plants.
Climate change poses profound risks to the livelihoods of vulnerable rural mountainous communities due to their higher dependence on natural resources which causing higher degradation. The current study had assessed the vulnerability due to climate change and livelihood practices of the Tehsil Balakot of Khyber Phuktoon Khawa (KPK), Pakistan and how these practices help to elate their adaptive capacity. Moreover, vulnerability of mountain forest in provision of forest services and land use changes were also determined.Based on mixed method approach including ten focus group discussions, survey of two hundred households and in-depth interviews with the locals; different hazards and their associated livelihood effects were explored. Wellbeing status of the community and resulting adaptation strategies were also analyzed. Temperature and rainfall data of last 30 years (1988 to 2017) was collected from the Pakistan Meteorological Department to validate people‟s perception of climate. Later the mapping of three integral ecosystem services as provisionary, regulatory, and cultural (recreation) through the local community‟s perception had been done. Carbon stock assessment as a climate regulatory service of the forest was carried out from the trees and the soil of Tehsil Balakot whereas livelihood vulnerability was evaluated through a composite indicator as Livelihood Vulnerability Index (LVI) and Livelihood Vulnerability Index of Intergovernmental Panel on Climate Change. Lastly land use change was analyzed using geographical information system (GIS). It was clearly depicted that the changing climate has significantly influenced the livelihoods of the local community through resource degradation, insufficient basic services, low agricultural productivity and social inequity. The poor people were facing additional burden due to their low adaptive capacity towards climate change. Furthermore, the analysis has shown that these forests provide myriad of services to their surrounding communities in form of the timber, fuelwood, climate regulation and recreation. The total carbon stock assessment for the Tehsil Balakot was determined as 243.79 t/ha. The average tree biomass as 207.41 t/ha and soil carbon was found as 36.38 t/ha. In the climatic trends, there was an overall decrease in mean minimum annual temperature by a factor of 0.0024 for each year whereas there had been an overall increase in mean maximum annual temperature by a factor of 0.0412 for each year. The mean annual rainfall of thirty years was 1471.27 mm. The comparative analysis within Tehsil Balakot showed that Union Council Balakot was more vulnerable with a LVI score of 0.41 than Kawai with an aggregate score of 0.35. The results of in-depth analysis of differential vulnerability showed that households in Balakot had the low adaptive capacity and higher exposure to natural disasters. The study has concluded that these forests are playing a vital role for the livelihood of the surrounding community as well contributes in climate change impacts mitigation. After working with communities, it is suggested that government policy should focus on those emergent issues which were identified relevant by communities and are most critical for their livelihoods. Developmental and community planners should also use such studies to assess the root causes of vulnerability to specify indigenous needs in policy making.