Characterizing The Interactions Of Tropomyosin Receptor Kinases (Trks) In The Plasma Membrane

The three Tropomyosin Receptor Kinases, Trk-A, Trk-B, and Trk-C, belong to the second largest class of membrane proteins, the Receptor Tyrosine Kinases (RTKs). The Trks are important for the survival and the function of neurons in the central nervous system, and have been implicated in many cancers. Currently, the Trks are known to bind neurotrophins and get activated upon lateral dimerization, but there is no quantitative or mechanistic understanding of the dimerization process. This is one bottleneck in the development of Trk targeted therapies. The goal of this project is to characterize the interactions that control Trk activation in the plasma membrane using a FRET-based method. To determine the propensity for Trk dimerization in quantitative terms, I have characterized the dimerization of each Trk receptor over a broad range of concentrations in live cells. This has been done in the absence and in the presence of their ligands, the neurotrophins. I have found that the Trk receptors form dimers even in the absence of ligands, stabilized mainly via contacts in the transmembrane/intracellular domains, and binding of their cognate ligands stabilizes the dimers and induces changes in the conformations of the kinase dimers. I have also explored the mechanism of ligand functional selectivity for Trk-A and Trk-B. Ligand functional selectivity, or ligand biased signaling, is a phenomenon in which different ligands lead to different biological outcomes while interacting with the same receptor. I have shown that different ligand-bound Trk-A dimers have different stabilities, and that different ligand-bound Trk-B dimers exhibit both different stabilities and different intracellular conformations. These differences likely underlie the differential signaling in response to the different ligands. In the long run, this new basic knowledge about Trk interactions in the absence and presence of ligands may be used for the design of targeted Trk inhibitors, for the benefit of human health

Hindering and enabling factors towards ICT integration in schools: A developing country perspective

ICT in education has emerged as a widespread phenomenon and has been widely considered and explored. While remarkable achievement in ICT use in the teaching and learning process has been observed in the developed part of the world, schools in the developing countries still fail to do so. Pakistan, as a less developed country, has still been in its infancy stage of ICT integration in schools. The purpose of this paper was thus, to explore the existing state of affairs in relation to ICT integration in schools via reviewing both the hindering and enabling factors. The study employed a systemic review method to review the available research, conducted in Pakistan, in the last ten years. The results inform about several fundamental issues and provide a way forward towards effective ICT integration in the process of teaching and learning.

Efficacy of resomal versus low osmolar ORS in severe acute malnutrition children with diarrhea age 6 months to 59 months

Objective: To compare the efficacy of Resomal versus low Osmolar ORS in severe acute malnutrition in children with diarrhea age 6 months To 59 months.Methodology: This Randomized Control Trial was carried out at Nutrition stabilization Centre pediatrics Department, Liaquat university hospital, Hyderabad, with duration of one year from 1st April-2016- to 31st March-2017. All the children having severe acute Malnutrition were included. After admission, severity of diarrhea was assessed on clinical basis. After informed consent, patients of Severe Acute Malnutrition were divided into two groups i.e Group-A and Group-B on randomized selection. Group A was given Resomal and Group–B was given low Osmolar ORS. Electrolytes were sent on admission then again after 12 hours of giving rehydration solution, response of diarrhea was assessed on the basis of Laboratory investigations and clinical assessment.Results:  Mean age of the children was 20.83 months and standard deviation was 3.52 months. Female children were in the majority 172 as compared to males 152 out of 324 cases. No significant difference was found in Z-score of both groups, P-value 0.07. Acute diarrhea was the most common in both groups, Diarrhea frequency-1 was found significantly more in both groups, having p-value 0.001, while frequency 2 and 3 were found without significant difference in both groups.  Statistically there was a significant difference in pre rehydration electrolytes in both groups, having p-value 0.001.  After rehydration no significant difference was found in electrolytes in both groups.Conclusion: It was concluded that resomal and low osmolar ORS were similarly efficacious in the rehydration of severely malnourished children with diarrhea and dehydration after rehydration

Lipid Profiles and Its Association with Pre-Eclampsia and Eclampsia in Nulliparous Pregnant Women

Objectives: To access the lipid profiles and its association with pre-eclampsia and eclampsia in nulliparous pregnant women. Material and Methods: This cross-sectional study was performed on 234 nulliparous pregnant women with gestation period of  > 20 weeks and aged 15-45 years, from March to October 2014, in Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU), Peshawar, Pakistan with cooperation from gynecology and obstetrics departments of three tertiary-care hospitals of Peshawar & Khyber Medical College, Peshawar,  Khyber Pakhtunkhwa (KP), Pakistan. Subjects were assigned to three groups i.e., group A, group B and group C. For performing biochemical assays and lipid profiling, through ELISA, blood samples were collected from already subjects both with the disease and the controls. Results: Both subjects having pre-eclampsia and eclampsia showed significant elevated levels (p < 0.001) for low density lipoproteins cholesterols (LDL-c), high density lipoprotein cholesterol (HDL-c), total cholesterol (TC)/HDL-c and LDL-c/HDL-c ratio. But TC of pre-eclampsia subjects were found significantly elevated (p < 0.001) in relation to controls. LDL-c/HDL-c and TC/HDL-c also revealed an elevated significant change (p < 0.001) both for pre-eclamptic and eclamptic subjects. On the other hand, only TG/HDL-c in pre-eclamptic patients was found significantly higher (p<0.004) when compared to control group.  Conclusion: Serum lipid levels were observed higher in pre-eclampsia and eclampsia patients hence an early assessment is necessary to prevent complications in such patients

Protective effect of Parthenium hysterophorus against carbon tetrachloride- and paracetamol-induced hepatotoxicity in rabbits

Purpose: To investigate the possible hepatoprotective potential of Parthenium hysterophorus crude extract (Ph.Cr) against carbon tetrachloride (CCL4)- and paracetamol-induced hepatotoxicity in rabbits.Methods: Twenty rabbits were divided into five groups of four rabbits each. Group 1 served as normal control and received normal saline (5 mL/kg). Group 2 received normal saline followed by CCL4 (0.75 mL/kg p.o dose) after 1 h. Groups 3 and 4 received Ph.Cr at doses of 15 and 30 mg/kg po, respectively, for 7 days followed by one dose of CCL4, 2 h after the last extract dose (0.75 mL/kg, sc). Group 5 received silymarin as reference standard at a dose of 100 mg/kg orally for 7 days followed by one dose of CCL4 (0.75 mL/kg, sc), 2 h after the last drug dose. The effect of the extract on potassium (K+)- induced contractions in isolated rabbit jejenum was also evaluated. At the end of the study, the animals were sacrificed and their liver architecture examined microscopically.Results: Pre-treatment of rabbits with Ph.Cr reduced ALT, ALP and TB levels (p < 0.05, p < 0.01, p < 0.001) dose dependently. Hepatoprotective data indicate that Ph.Cr markedly reduced CCL4- and paracetamol-induced toxicity by preserving the histological architecture of the liver tissue at near normal. In isolated rabbit jejunum tissue, Ph.Cr relaxed high K+ (80 Mm)-induced contractions in a concentration-dependent (0.03 - 10 mg/mL) manner like that caused by silymarin.Conclusion: In the light of the results obtained, Parthenium hysterophorous  possesses hepatoprotective activity against CCL4- and paracetamol-induced  hepatic damage, possibly mediated via its antioxidant and Ca++ antagonist mechanisms.Keywords: Parthenium hysterophorus, Toxins, Hepatoprotection, Ca++ antagonist, Silymari

Analysis of Coverage and Area Spectral Efficiency under Various Design Parameters of Heterogeneous Cellular Network

As day by day the population is increasing, the use of mobile phones and different applications is increasing which requires high data rate for transmission. Homogeneous cellular network cannot fulfill the demand of mobile users, so creating a heterogeneous cellular network (HCN) is a better choice for higher coverage and capacity to fulfil the increasing demand of upcoming 5G and ultra-dense cellular networks. In this research, the impact of antenna heights and gains under varying pico to macro base stations density ratio from 2G to 5G and beyond on two-tier heterogeneous cellular network has been analyzed for obtaining optimum results of coverage and area spectral efficiency. Furthermore, how the association of UEs affects the coverage and ASE while changing the BSs antenna heights and gains has been explored for the two-tier HCN network model. The simulation results show that by considering the maximum macro BS antenna height, pico BS antenna height equal to user equipment (UE) antenna height and unity gains for both macro and pico tiers, the optimum coverage and area spectral efficiency (ASE) for a two-tier fully loaded heterogeneous cellular network can be obtained