The BRG1 chromatin remodeling enzyme links cancer cell metabolism and proliferation

Cancer cells reprogram cellular metabolism to meet the demands of growth. Identification of the regulatory machinery that regulates cancer-specific metabolic changes may open new avenues for anti-cancer therapeutics. The epigenetic regulator BRG1 is a catalytic ATPase for some mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is a well-characterized tumor suppressor in some human cancers, but is frequently overexpressed without mutation in other cancers, including breast cancer. Here we demonstrate that BRG1 upregulates de novo lipogenesis and that this is crucial for cancer cell proliferation. Knockdown of BRG1 attenuates lipid synthesis by impairing the transcription of enzymes catalyzing fatty acid and lipid synthesis. Remarkably, exogenous addition of palmitate, the key intermediate in fatty acid synthesis, rescued the cancer cell proliferation defect caused by BRG1 knockdown. Our work suggests that targeting BRG1 to reduce lipid metabolism and, thereby, to reduce proliferation, has promise for epigenetic therapy in triple negative breast cancer

Nanoscale Visualization of Elastic Inhomogeneities at TiN Coatings Using Ultrasonic Force Microscopy

Ultrasonic force microscopy has been applied to the characterization of titanium nitride coatings deposited by physical vapor deposition dc magnetron sputtering on stainless steel substrates. The titanium nitride layers exhibit a rich variety of elastic contrast in the ultrasonic force microscopy images. Nanoscale inhomogeneities in stiffness on the titanium nitride films have been attributed to softer substoichiometric titanium nitride species and/or trapped subsurface gas. The results show that increasing the sputtering power at the Ti cathode increases the elastic homogeneity of the titanium nitride layers on the nanometer scale. Ultrasonic force microscopy elastic mapping on titanium nitride layers demonstrates the capability of the technique to provide information of high value for the engineering of improved coatings

The GPI Anchor Signal Sequence Dictates the Folding and Functionality of the Als5 Adhesin from Candida albicans

Background: Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well? Methodology/Principal Findings: We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C. albicans, the C-terminal deletion of 20 amino acids (SS) results in a significant alteration in conformation and function of the mature protein. Conclusions/Significance: We propose that the locking of the conformation of the precursor protein in an alternate conformation from that of the mature protein is one probable strategy employed by the cell to control the behaviour an

Schimke immunoosseous dysplasia: defining skeletal features

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations

Stratification and delineation of gastric cancer signaling by in vitro transcription factor activity profiling and integrative genomics

10.1016/j.cellsig.2014.01.017Cellular Signalling265880-894CESI

Field Evaluation of Biorationals and Chemical Insecticides against Thrips parvispinus (Karny) (Thysanoptera: Thripidae), in Chrysanthemum

Field study was conducted to evaluate the efficacy of biorationals and chemical insecticides against black thrips, Thrips parvispinus (Karny) on chrysanthemum. Thrips population ranged from 15.33 to 13.89/flower before spraying. The efficacy of seven biorationals and seven chemical insecticides were evaluated against black thrips under field conditions. The application of pongamia soap @5g/lit and Spinosad 45% SC @ 0.2 ml/lit reduced the thrips incidence significantly among the biorational and chemical insecticides respectively. The mean per reduction of thrips incidence in pongamia soap @ 5 gm/lit application was 74.90%. This was followed by neem soap @ 5g/lit (72.25%), azadirachtin @10000ppm (71.10%), Beauveria bassiana (66.76%), Isaria fumosorosea (64.93%), Lecanicillium lecanii (63.72%), and Metarhizium anisopilae (62.46%). Among the chemical insecticides Spinosad 45%SC @ 0.2 ml/lt. stood first in the order of efficacy with 80.2% reduction in thrips population. The order of efficacy of chemical insecticides against black thrips in chrysanthemum are spinetoram 11.7%SC (76.245%) > cyantraniliprole 10%OD (73.92%) > fipronil 5% SC (72.24%) > thiamethoxam 25% WG (70.79%) > dinotefuran 20% WG (69.80%) > tolfenpyrad 15% EC (68.02%). The effective biorational and chemical insecticide can be included as a component in the Integrated pest management of thrips complex in chrysanthemum. The rotation of effective compounds will reduce the resistance development against insecticides in thrips associated with chrysanthemum and also reduces the thrips infestation

Assessing the Single and Combined Toxicity of Chlorantraniliprole with Bacillus thuringiensis against Maize Fall Armyworm Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) under Laboratory Conditions

Use of synthetic insecticides for the management of fall armyworm (FAW) Spodoptera frugiperda (J. E. Smith) for a longer period will led to development of insecticide resistance. Identification of an eco-friendly synergistic agent to enhance the toxicity potential and reduced pesticide use as well become mandatory in due process. Hence the present study was formulated to find the single and combined toxicity of chlorantraniliprole and Bacillus thuringiensis (Bt) against the 2nd and 3rd larval instars of S. frugiperda. Single toxicity of chlorantraniliprole against 2nd and 3rd larval instars were 0.87 and 1.52 ppm (LC25); 4.08 and 6.50 ppm (LC50), respectively. With respect to Bt, single toxicity against 2nd and 3rd larval instars were 474.39 and 693.48 ppm (LC25); 1008.62 and 1228.62 ppm (LC50), respectively. Combination effect of chlorantraniliprole with Bt revealed that 2nd instar of FAW showed supplemental synergism at LC50 of chlorantraniliprole + LC25 of Bt. In the case of LC50 of chlorantraniliprole + LC50 of Bt, LC25 of chlorantraniliprole + LC50 of Bt and LC25 of chlorantraniliprole + LC50 of Bt combinations, they showed sub additive synergism. In 3rd instar larvae, the combined toxicity results were similar for all the combinations of chlorantraniliprole + Bt except LC25 of chlorantraniliprole + LC50 of Bt where it showed an antagonistic synergism. Activity of Carboxyl Esterase (CarE), Mixed Function Oxidase (MFO) and Glutathione-S-Transferase (GST) were found to be lesser in chlorantraniliprole LC50 + Bt LC25 combinations than single toxicity treatments. Therefore, combined use of chlorantraniliprole with Bt at LC50 of chlorantraniliprole + LC25 of Bt had supplemental synergism on fall armyworm under laboratory condition

Nimesulide and celecoxib inhibits multiple oncogenic pathways in gastric cancer cells

10.4172/1948-5956.1000198Journal of Cancer Science and Therapy54126-13