Dysregulated trophoblast-specific gene expression mediated by retroviral regulatory sequences contributes to preeclampsia (PE)

Präeklampsie (PE) ist eine Komplikation, die während der Schwangerschaft auftritt, fast 2-8% aller Schwangerschaften betrifft und human spezifisch ist. PE ist eine der Hauptursachen für den Tod von Mutter und Kind. Eine abnormale Plazentaentwicklung aufgrund einer verminderten Trophoblasteninvasion und einem gestörten Umbau der Spiralarterien trägt zur Pathogenese der PE bei. Klinisch wird die PE durch Bluthochdruck und Proteinurie, auftretendnach der 20. Schwangerschaftswoche, diagnostiziert und kann durch eine Funktionsstörung von Organen begleitet werden. Bei besonders schweren Verläufen ist die frühzeitige Endbindung die letzte Möglichkeit das Überleben der Mutter zu gewährleisten. Das Ziel dieser Studie ist es, weitere Gene zu identifizieren, die durch ERVs in der menschlichen Plazenta spezifisch reguliert werden und in PE dysreguliert sind. Um dieses Ziel zu erreichen, wurde das Transkriptom von primären menschlichen Trophoblastenzellen von 5 gesunden und 5 früh einsetzenden PE-Plazenten mittels RNA-Sequenzierung analysiert. Es wurden 335 Gene identifiziert, welche eine höhere Expression in den Trophoblastenzellen im Vergleich zu anderen Geweben aufwiesen. Zusätzlich zeigten einige der Gene (n=88) eine Co-Regulation der Expression durch retrovirale LTRs (10-kb 5‘ des transcription start side (TSS) des Gens). Hauptinteresse lag hierbei auf den Genen, welche ebenfalls eine Dysregulation in der PE aufwiesen (n = 16). Diese Studie identifizierte EPS8L1, das durch primaten-spezifisches ERV-LTR (MLT1G1) in Trophoblastenzellen reguliert wird, als einen wichtigen Faktor in der Entwicklung der menschlichen Plazenta. EPS8L1 ist in der PE Plazenta dysreguliert und involviert in mehrere Signalwege und die Funktionalität von Trophoblasten wie Invasion, Angiogenese und Redoxhomöostase. Hierdurch führt diese Arbeit zu einem besseren Verständnis der PE und deren human-spezifischer Natur.Preeclampsia (PE) is a complication that occurs during pregnancy and affects almost 2-8% of all pregnancies and is often regarded as a human-specific disorder.1,2 PE is one of the major causes of maternal and fetal death.1 Failure of the trophoblast cells to invade into the maternal decidua results in the improper remodeling of spiral arteries leading to PE pathogenesis. Clinically, it is diagnosed as a maternal syndrome, diagnosed by the new-onset of hypertension and proteinuria or other end-organ dysfunction after the 20th week of pregnancy. So far, the only effective treatment of the disorder is the removal of the placenta tissue and delivery of the infant. The aim of this study is to identify additional genes that are regulated by the human ERV-LTRs in the human placenta specifically, and are dysregulated in PE. To achieve this aim, the transcriptome of primary human trophoblast cells of 5 healthy and 5 early-onset PE placentas were analyzed by RNA sequencing (RNA-seq). RNA-seq analysis identified genes (n=335) with stronger expression in the trophoblast cells as compared to other human body tissues. Additionally, some of the genes (n=88) showed co-regulation of expression by the human ERV-LTRs in their vicinity (10-kb upstream of transcription start side (TSS) of the gene). Since my interest was to identify the new targets of PE pathogenesis, so I focused on genes (n=16) with dysregulated expression in women presented with PE. This study identified a new gene EPS8L1, regulated by primate-specific ERV-LTR in trophoblast cells that has a predominant role in the human placenta development and demonstrated that its dysregulation affected multiple pathways involved in trophoblast function like invasion, angiogenesis and maintenance of cell redox homeostasis. Furthermore, this study leads to the better understanding of the disease by explaining certain aspects of human-specific nature of PE

Impact of Climate Change on Crops’ Productivity across Selected Agro-ecological Zones in Pakistan

This study estimates the impact of major climate variables (temperature and rainfall) on crops’ productivity across four agro-ecological zones of Pakistan. The crops selected were rice, wheat, maize, cotton and sugarcane. The study used panel data from 1991 to 2010 and applied panel least square techniques. The results revealed that the effect of climatic variables on crops yield varied across agro climatic zone due to differences in their climate conditions. Temperature and rainfall were the important determinants affecting crops productivity across agro climatic zones of Pakistan. Wheat productivity has been impacted more in Northern Irrigated Plain-a by average temperature and in Northern Dry Mountains by rainfall than the other zones. Rice productivity has been impacted more in Dry Mountains by average temperature and in the Indus Delta by rainfall than other zones. Sugarcane productivity has been impacted more by average temperature and rainfall in Indus Delta than zone IV. Maize productivity has been impacted more by average temperature and rainfall in Northern Dry Mountains than other zones. Finally the study recommends proper mitigative and adaptative strategies to enhance the positive and lessen the adverse impact of climate change on crops productivity across agro climatic zones of Pakistan. JEL Classifications: Q15, Q54, Q57 Keywords: Climate Change, Agro-ecological Zones, Rainfall, Temperature, Productivit

Growth Governance Nexus: A Case of Pakistan

Good governance has gained tremendous importance in the development agenda of developing economies since 1990s but growth literature gives mixed picture about the role of governance and institutional factors in explaining GDP growth. The present study is an attempt to provide empirical evidence on interlinks between governance and GDP growth. ADF and Johansen co-integration tests are applied for econometric testing of the hypothesis by using time series data from 1984 to 2010. All the variables turned out to be significant with ICRG (proxy used for governance) having positive and significant impact on GDP growth of Pakistan. Results of the study have shown that governance plays major role in determining GDP growth pattern of Pakistan. A complete reform of the political, economic system, judiciary, bureaucracy and a free media are recommended to improve governance and to achieve sustained GDP growth in Pakistan consequently

Quantum Movement Technique versus William Flexion Exercise on Pain and Walking Ability in Patients with Low Back Pain

OBJECTIVE: Our study aimed to compare between quantum movement technique (QMT) and William flexion exercise (WFE) in patients with low back pain (LBP) based on pain and walking ability. METHODS: Six-session QMT and WFE were provided for two groups of participants. The frequency of intervention was 6 times/week. Twenty patients (aged 25–65 years) with LBP were randomly assigned into the QMT group (n = 10) or the WFE group (n = 10). The primary outcome of the intervention was pain, measured using the numeric pain rating scale, while the secondary outcome was walking ability, measured using the Oswestry Disability Index. The measurements were conducted at baseline and the end of the intervention. RESULTS: Pain reduction was significantly shown in both groups (p < 0.05). However, QMT was shown more effective in reducing pain compared to WFE (p < 0.05). In addition, we found the significant improvement of walking ability in both groups following the intervention (p < 0.05), but no significant difference was shown between two groups (p > 0.05). CONCLUSIONS: QMT is more effective than WFE for reducing pain in patients with LBP

Integration of Requirement Engineering Challenges with Its Practices in Enterprise Resource Planning Systems

This study focuses on the problems and solutions that are useful and insightful evaluated. Requirement Engineering of the standard model of the process of life, in spite of the high degree of implementation, I know very little about the problems that arise and I make the process work better. And besides, many of these specific issues and discuss ways to improve them. I have tried to categorize the types of challenges because of their similarities are connected. And again, I talked about many of these general issues and their application to do so. Keywords: Requirement engineering challenges for Enterprise Resource Planning systems; Practices for Requirement engineering of Enterprise Resource Planning; Better Requirement Engineering model for Enterprise Resource Planning; Enterprise Resource Planning Requirement engineering integration; Categorized solutions to the challenges of Requirement engineering in Enterprise Resource Planning systems

Penentu ketidakpadanan pekerjaan dalam kalangan graduan: Kajian kes pekerja perkeranian di Lahore, Pakistan

Job mismatch among graduates reflects inefficiencies in the labor market. An imbalance between the demand and supply of graduates in the labor market leads to a horizontal mismatch. Nations make progress based on knowledge and education but despite obtaining higher education individuals are unable to find a job related to their field of study. This phenomenon occurs when educational institutes produce a large number of graduates while on the other hand, the supply of graduates exceeds the demand for graduates. This study aims to find out the determinants of horizontal mismatch and to analyze the reasons why workers have accepted the mismatched job. By using the worker’s self-assessment method required data is collected from the clerical workers of public and private sector universities at Lahore in 2019. These universities include the University of the Punjab, Lahore, and the University of Management and Technology, Lahore. Results of Logistic Regression analysis concluded that cost of job search, asymmetric information, and methods used to find a job are the most important determinants of job-mismatch. This study has also analyzed the reasons why workers have accepted their present mismatched job. Findings concluded that individuals accepted mismatched-job due to pay and promotion opportunities and a good working environment. This study suggested establishing linkages between educational institutes and industries to better formulate the policy that reduces the extent of horizontal mismatch.Ketidakpadanan pekerjaan mencerminkan ketidakcekapan dalam pasaran buruh. Ketidakseimbangan antara permintaan dan penawaran graduan dalam pasaran buruh membawa kepada ketidakpadanan mendatar. Negara maju berdasarkan pengetahuan dan Pendidikan tetapi walaupun memperoleh Pendidikan tinggi individu tidak dapat mencari pekerjaan yang berkaitan dengan bidang pengajian mereka. Fenomena ini berlaku apabila institut pendidikan mengeluarkan sejumlah besar graduan tetapi pasaran buruh tidak dapat menyerapnya dengan cekap kerana keterbatasan pekerjaan yang tersedia. Matlamat kajian ini adalah untuk mengetahuif aktor-faktor penentu ketidakpadanan mendatar dan menganalisis sebab-sebab pekerja telah menerima pekerjaan tidak sepadan. Dengan menggunakan kaedah penilaian kendiri pekerja, data yang diperlukan dikumpulkan daripada pekerjaper keranian universiti awam dan swasta di Lahore pada 2019. Universiti yang disasarkan termasuk Universiti Punjab, Lahore dan Universiti Pengurusan dan Teknologi. Keputusan analisis Regresi Logistik menunjukkan bahawa kos pencarian kerja, maklumat asimetri dan kaedah yang digunakan untuk mencari pekerjaan adalah penentu paling penting ketidakpadanan kerja. Kajian ini juga menganalisis sebab-sebab pekerja telah menerima pekerjaan mereka sekarang jika kerja itu tidak berkaitan dengan bidang pengajian mereka. Sebab-sebabini termasuk: disebabkan peluang gaji dan kenaikan pangkat, persekitaran kerja yang baik, lokasi pejabat, sekatan keluarga, perubahan minat kerjaya. Pekerjaan yang berkaitan dengan bidang pengajian tidak tersedia. Dapatan menyimpulkan bahawa individu menerima pekerjaan tidak sepadan kerana peluang gaji dan kenaikan pangkat serta persekitaran kerja yang baik. Kajian mencadangkan bahawa mesti ada hubungan yang kuku hantara institut pendidikan dan industri untuk merumuskan dasar yang lebih baik yang mengurangkan tahap ketidakpadanan mendatar

Development of Muscle Disuse Model in Rat: Effect of Denervation and Tenotomization on the Skeletal Muscle Mechanics

Denervation refers to the condition that represents loss of nerve connection with the muscle. The term tenotomization or tenotomy refers to the condition where the tendon of the skeletal muscle is damaged. Both these conditions lead towards muscle disuse and then deterioration. It may be caused by some diseases, chemical toxicity, physical injury or intentional surgical interruption. To observe the effects of denervation and tenotomy, it is important to develop an animal model with such pathological conditions for a better understanding and investigation of a possible cure. Current study was designed to develop an animal model in rat for denervation and tenotomy. The objectives were to optimize the anaesthetic dose for rats, to develop muscle disuse models in rats including denervation and tenotomization and to determine the mechanical and physiological properties of the gastrocnemius muscle of the animal model for muscle disuse. Gastrocnemius muscle of the rat was targeted for study. Models were developed by surgical procedures. We succeeded in developing the rat model for both conditions and it was verified by observing the changes in the physiological properties of muscles

A note on the fixed point theorem of F-contraction mappings in rectangular M-metric space

In this note, we show that the main result (Theorem 3.2) due to Asim et al. (Appl. Gen. Topol., 23(2), 363-376 (2022) https://doi.org/10.4995/agt.2022.17418) is still valid if we remove the assumption of continuity of the mapping

On the Utility of Parents\u27 Historical Data to Investigate the Causes of Autism Spectrum Disorder: A Data Mining-Based Framework

Objective: Autism Spectrum Disorder (ASD) is acknowledged as a challenge that influences the learning ability of adolescents and also negatively impacts their families. Autism may be caused due to environmental exposure or genetically inherited disorder, however, no definitive or universally customary reasons are known. This makes the issue fairly challenging. Material and methods: This work focuses on identifying the reasons of ASD utilizing computational methods. For this, data is collected that focuses on parental history for finding the trigged features by reviewing antenatal, perinatal, and infant hazard factors of ASD. Afterwards, ML techniques are applied on the collected instances to develop a predictive model and identify the reasons to ASD. While collecting the data, samples are obtained for ASD and non-ASD individuals both. A total of 115 features are obtained from each subject. The collected dataset has 47% samples of the subjects with ASD. Dimensionality reduction, and four feature selection methods are applied on the data to eliminate noise and least valued features. The data is verified using two clustering techniques, i.e., k-means and k-medoid. To validate the clustering results five clustering validation indices are used. Later, three classifiers, i.e. k-nearest neighbor (k-NN), Support Vector Machine (SVM), and Artificial Neural Network (ANN) are trained to predict cases with ASD. The frequent items mining technique and the descriptive analysis of the clustered data are utilized to identify the factors that may cause ASD. Results: The proposed framework enables to identify the features that may contribute towards ASD. Whereas, for the classification part, SVM classifier performs better than others do with an average accuracy of 98.34% in predicting the ASD cases. Conclusion: The results identified stress as the dominant feature and environmental factors, like frequent use of canned food and plastic/steel bottles during fertilization period that may contribute towards ASD