Impact of different quantity of Zinc oxide nanoparticles on growth and hematology of Mrigal Cirrhinus mrigala

Zinc is essential for aquatic biota including fishes at a lower concentration, but when it reaches higher concentration it becomes toxic. The objectives of the present work were related to the impact of different quantities of zinc oxide nanoparticles on the growth and hematology of Mrigal Cirrhinus mrigala. The zinc oxide nanoparticles were synthesized by chemical precipitation method and characterized using by UV-VIS, SEM, EDAX, FTIR and XRD. Different quantity of zinc oxide nanoparticles such as 0, 5,10,15,20 and 25mg/100g were prepared by using a fish meal, groundnut oil cake, wheat flour, and tapioca flour. Feed utilization and hematological parameters of Mrigal were estimated after 21 days of feeding. UV-visible adsorption spectra show that the peak absorbance of ZnO nanoparticles was observed 500 nm. SEM shows that nanoparticles formed are clustered because of the adhesive nature of flower-shaped appearance. EDAX shows that the zinc oxide nanoparticles and the peaks are located between 1.0Kev and 8.5Kev. The FTIR spectrum of zinc oxide nanoparticles was analyzed in the range of 400-4000cm-1 and spectral bands were observed. The XRD results were viewed as the crystalline nature and average size of zinc oxide nanoparticles. Survival rate indicated that all Mrigal were healthy during the period of 21 days except in feed II,IV, and V. The feed utilization and growth parameters are higher in feed IV. Hematological parameters such as hemoglobin, RBC, Hematocrit, MCV, MCH, MCHC of Mrigal progressively increased and WBC and platelets decreased with increase in the quantity of Zinc Oxide nanoparticles

A simple characterization of special matchings in lower Bruhat intervals

We give a simple characterization of special matchings in lower Bruhat intervals (that is, intervals starting from the identity element) of a Coxeter group. As a byproduct, we obtain some results on the action of special matchings.Comment: accepted for publication on Discrete Mathematic

Unique motifs identify PIG-A proteins from glycosyltransferases of the GT4 family

<p>Abstract</p> <p>Background</p> <p>The first step of GPI anchor biosynthesis is catalyzed by PIG-A, an enzyme that transfers <it>N</it>-acetylglucosamine from UDP-<it>N</it>-acetylglucosamine to phosphatidylinositol. This protein is present in all eukaryotic organisms ranging from protozoa to higher mammals, as part of a larger complex of five to six 'accessory' proteins whose individual roles in the glycosyltransferase reaction are as yet unclear. The PIG-A gene has been shown to be an essential gene in various eukaryotes. In humans, mutations in the protein have been associated with paroxysomal noctural hemoglobuinuria. The corresponding PIG-A gene has also been recently identified in the genome of many archaeabacteria although genes of the accessory proteins have not been discovered in them. The present study explores the evolution of PIG-A and the phylogenetic relationship between this protein and other glycosyltransferases.</p> <p>Results</p> <p>In this paper we show that out of the twelve conserved motifs identified by us eleven are exclusively present in PIG-A and, therefore, can be used as markers to identify PIG-A from newly sequenced genomes. Three of these motifs are absent in the primitive eukaryote, <it>G. lamblia</it>. Sequence analyses show that seven of these conserved motifs are present in prokaryote and archaeal counterparts in rudimentary forms and can be used to differentiate PIG-A proteins from glycosyltransferases. Using partial least square regression analysis and data involving presence or absence of motifs in a range of PIG-A and glycosyltransferases we show that (i) PIG-A may have evolved from prokaryotic glycosyltransferases and lipopolysaccharide synthases, members of the GT4 family of glycosyltransferases and (ii) it is possible to uniquely classify PIG-A proteins versus glycosyltransferases.</p> <p>Conclusion</p> <p>Besides identifying unique motifs and showing that PIG-A protein from <it>G. lamblia </it>and some putative PIG-A proteins from archaebacteria are evolutionarily closer to glycosyltransferases, these studies provide a new method for identification and classification of PIG-A proteins.</p

Regulation of ATM and ATR by SMARCAL1 and BRG1 [preprint]

The G2/M checkpoint is activated on DNA damage by the ATM and ATR kinases that are regulated by post-translational modifications. In this paper, the transcriptional co-regulation of ATM and ATR by SMARCAL1 and BRG1, both members of the ATP-dependent chromatin remodeling protein family, is described. SMARCAL1 and BRG1 co-localize on the promoters of ATM and ATR; downregulation of SMARCAL1/BRG1 results in transcriptional repression of ATM/ATR and therefore, overriding of the G2/M checkpoint leading to mitotic abnormalities. On doxorubicin-induced DNA damage, SMARCAL1 and BRG1 are upregulated and in turn, upregulate the expression of ATM/ATR. Phosphorylation of ATM/ATR is needed for the transcriptional upregulation of SMARCAL1 and BRG1, and therefore, of ATM and ATR on DNA damage. The regulation of ATM/ATR is rendered non-functional if SMARCAL1 and/or BRG1 are absent or if the two proteins are mutated such that they are unable to hydrolyze ATP, as in for example in Schimke Immuno-Osseous Dysplasia and Coffin-Siris Syndrome. Thus, an intricate transcriptional regulation of DNA damage response genes mediated by SMARCAL1 and BRG1 is present in mammalian cells

Targeting the chromatin remodeling enzyme BRG1 increases the efficacy of chemotherapy drugs in breast cancer cells

Brahma related gene product 1 (BRG1) is an ATPase that drives the catalytic activity of a subset of the mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is overexpressed in most human breast cancer tumors without evidence of mutation and is required for breast cancer cell proliferation. We demonstrate that knockdown of BRG1 sensitized triple negative breast cancer cells to chemotherapeutic drugs used to treat breast cancer. An inhibitor of the BRG1 bromodomain had no effect on breast cancer cell viability, but an inhibitory molecule that targets the BRG1 ATPase activity recapitulated the increased drug efficacy observed in the presence of BRG1 knockdown. We further demonstrate that inhibition of BRG1 ATPase activity blocks the induction of ABC transporter genes by these chemotherapeutic drugs and that BRG1 binds to ABC transporter gene promoters. This inhibition increased intracellular concentrations of the drugs, providing a likely mechanism for the increased chemosensitivity. Since ABC transporters and their induction by chemotherapy drugs are a major cause of chemoresistance and treatment failure, these results support the idea that targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy for breast cancer

Elucidating the mechanism of DNA-dependent ATP hydrolysis mediated by DNA-dependent ATPase A, a member of the SWI2/SNF2 protein family

The active DNA-dependent ATPase A domain (ADAAD), a member of the SWI2/SNF2 family, has been shown to bind DNA in a structure-specific manner, recognizing DNA molecules possessing double-stranded to single-stranded transition regions leading to ATP hydrolysis. Extending these studies we have delineated the structural requirements of the DNA effector for ADAAD and have shown that the single-stranded and double-stranded regions both contribute to binding affinity while the double-stranded region additionally plays a role in determining the rate of ATP hydrolysis. We have also investigated the mechanism of interaction of DNA and ATP with ADAAD and shown that each can interact independently with ADAAD in the absence of the other. Furthermore, the protein can bind to dsDNA as well as ssDNA molecules. However, the conformation change induced by the ssDNA is different from the conformational change induced by stem-loop DNA (slDNA), thereby providing an explanation for the observed ATP hydrolysis only in the presence of the double-stranded:single-stranded transition (i.e. slDNA)

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

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