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The pathogenic mechanism(s) contributing to loss of dopamine neurons in Parkinson's disease (PD) remain obscure. Leucine-rich repeat kinase 2 (LRRK2) mutations are linked, as a causative gene, to PD. LRRK2 mutations are estimated to account for 10% of familial and between 1 % and 3 % of sporadic PD. LRRK2 proximate single nucleotide polymorphisms have also been significantly associated with idiopathic/sporadic PD by genome-wide association studies. LRRK2 is a multidomain-containing protein and belongs to the protein kinase super-family. We constructed two inducible dopaminergic cell lines expressing either human-LRRK2-wild-type or human-LRRK2-mutant (G2019S). Phenotypes of these LRRK2 cell lines were examined with respect to cell viability, morphology, and protein function with or without induction of LRRK2 gene expression. The overexpression of G2019S gene promoted (1) low cellular metabolic activity without affecting cell viability, (2) blunted neurite extension, and (3) increased phosphorylation at S910 and S935. Our observations are consistent with reported general phenotypes in LRRK2 cell lines by other investigators. We used these cell lines to interrogate the biological function of LRRK2, to evaluate their potential as a drug-screening tool, and to investigate screening for small hairpin RNA-mediated LRRK2 G2019S gene knockdown as a potential therapeutic strategy. A proposed LRRK2 kinase inhibitor (i.e., IN-1) decreased LRRK2 S910 and S935 phosphorylation in our MN9DLRRK2 cell lines in a dose-dependent manner. Lentivirus-mediated transfer of LRRK2 G2019S allele-specific small hairpin RNA reversed the blunting of neurite extension caused by LRRK2 G2019S overexpression. Taken together, these inducible LRRK2 cell lines are suitable reagents for LRRK2 functional studies, and the screening of potential LRRK2 therapeutics.

The possible ill effects of herbicides usage in agriculture have increased the interest of farming and researchers community to explore new ways of weed control. Bioherbicides (Allelochemicals) are considered as an available option for weed management. In order to test the potential of some allelopathic plant water extracts as a weed management tool in wheat crop, a field trial was carried out during winter 2011-12 at NDF, The University of Agriculture Peshawar Pakistan. The experimental design was RCBD having split plot arrangement. The main plots assigned to time of treatment application (pre emergence and post emergence) of plant extracts, while there were eight sub plots consisting of different weed control measures i.e. sorghum water extract {Sorghum bicolor (L.) Moench}, sunflower extract (Helianthus annuus L.), Parthenium extract (Parthenium hysterophorus L.), common reed extract {Phragmites australis (Cav) Trin}, Johnson grass extract {Sorghum halepense (L.) Pers}, Rice straw extract (Oryza sativa L.), herbicide (Logran Extra) and control. The results demonstrated that the pre emergence application of all the plant water extracts proved to be superior in action to their post application regarding weed control. Among the plant water extracts (treatments) the pre emergence application of both P. australis and H. annuus gave the minimum weed density of 89.50 and 113.50 m2 respectively compared to control plot (280.0 m2). Tallest (113.9 cm) plant height and outmost grains spike-1 (64) was computed for H. annuus. In addition, the P. australis and herbicide (Logran extra) both proved superior for 1000 grain weight, however the leaf area of wheat remained non-significant under all examined treatments. The present results suggest that P. australis and H. annuus could be successfully incorporated in weed management approaches in wheat. Currently allelopathy is passing through experimental stages. Thus, furthercomprehensive studies are suggested to explore the possibility and feasibility for commercializing the extracts of these two species. [ABSTRACT FROM AUTHOR]

An experiment was conducted on effect of tillage and mulching on emergence, weed population and yield components of maize crop in district Peshawar under Semi arid environment during 2012. The experiment was laid out in factorial experiment with randomized complete block design having nine treatments and four replications. Three tillage practices (Cultivator 4 times followed by planking, mould board plough followed by rotavator and cultivator twice followed by planking) and three mulching levels (wheat mulch, barseem mulch and control) were used. Tillage practices were alloted to main plots and mulching levels to subplots. Tillage practices had a significant effect on harvest index (%), weed population (m-2) while showing no significant effect on number of cobs plant-1 and days to emergence. Maximum number of cobs plant-1(1), harvest index (22.71 %), weed population (39.50m-2) and days to emergence (5.07). Similarly, mulching have also showed no significant effect on number of cob plant-1 (1), and days to emergence (5.08) while showed significant effect onharvest index (22.20%) and weed population (33.08m-2). It was concluded that the combination of wheat straw mulch and mould board plough followed by rotavator were proved fruitful for increasing yield components of maize crop and reducing weed population under semiarid environment. [ABSTRACT FROM AUTHOR]

An experiment was conducted at the New Developmental Farm of The University of Agriculture Peshawar Pakistan during 2014 to determine the effect of different drying treatments on the essential oil contents of the flower of a medicinal plant, Matricaria chamomilla. Matricaria chamomilla was dried through various methods such as Flat plate solar dryer (FPSD), direct sunlight, shade and oven drying at 30° C, 40° C, 50° C, 60° C and 70° C.The essential oil contents were extracted from the dried flower of Matricaria chamomilla, by water distillation using Clevenger type apparatus. Three parameters were studied such as essential oil contents, drying period, and moisture content in dried product. Data were analyzed statistically under completely randomized design (CRD). Maximum essential oil was obtained 0.29% under shade drying and 0.28% by Flat Plate Solar drying (FPSD), oven drying at 30° C and 40° C, however these methods were non-significant from each other. High temperature and direct sun drying significantly decreased essential oil content. Maximum period consumed under drying at shade, sun and oven drying at 30° C were 288, 504, and 168 hours, respectively, and their dried sample having high moisture contents (11.91%, 10.91%, 11.79%), as compared to Flat plate solar drying and Oven drying at 50° C, 60° C and 70° C. [ABSTRACT FROM AUTHOR]

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Within the last two decades, genomics and bioinformatics have profoundly impacted our understanding of the molecular mechanisms of Parkinson's disease (PD). From the description of the first PD gene in 1997 until today, we have witnessed the emergence of new technologies that have revolutionized our concepts to identify genetic mechanisms implicated in human health and disease. Driven by the publication of the human genome sequence and followed by the description of detailed maps for common genetic variability, novel applications to rapidly scrutinize the entire genome in a systematic, cost-effective manner have become a reality. As a consequence, about 30 genetic loci have been unequivocally linked to the pathogenesis of PD highlighting essential molecular pathways underlying this common disorder. Herein we discuss how neurogenomics and bioinformatics are applied to dissect the nature of this complex disease with the overall aim of developing rational therapeutic interventions.

At various stages during embryogenesis and cancer cells are exposed to tension, compression and shear stress; forces that can regulate cell proliferation and differentiation. In the present study, we show that shear stress blocks cell cycle progression in colon cancer cells and regulates the expression of genes linked to the Wnt/beta-catenin, mitogen-activated protein kinase (MAPK) and NFkappaB pathways. The shear stress-induced increase of the secreted Wnt inhibitor DKK1 requires p38 and activation of NFkappaB requires IkappaB kinase-beta. Activation of beta-catenin, important in Wnt signaling and the cause of most colon cancers, is inhibited by shear stress through a pathway involving laminin-5, alpha6beta4 integrin, phosphoinositide 3-kinase (PI 3-kinase) and Rac1 coupled with changes in the distribution of dephosphorylated beta-catenin. These data show that colon cancer cells respond to fluid shear stress by activation of specific signal transduction pathways and genetic regulatory circuits to affect cell proliferation, and indicate that the response of colon cancers to mechanical forces such as fluid shear stress should be taken into account in the management of the disease.