Joint mode selection and user association in D2D enabled multitier C-RAN

Cluster Computing - The device-to-device D-2-D Communication empowered Cloud Radio Access Network (CRAN) which is examined to be auspicious system model, gives energy efficiency and high data rate....     

CNS proteomes in alcohol and drug abuse and dependence

Drugs of abuse, including alcohol, can induce dependency formation and/or brain damage in brain regions important for cognition. 'High-throughput' approaches, such as cDNA microarray and proteomics, allow the analysis of global expression profiles of genes and proteins. These technologies have recently been applied to human brain tissue from patients with psychiatric illnesses, including substance abuse/dependence and appropriate animal models to help understand the causes and secondary effects of these complex disorders. Although these types of studies have been limited in number and by proteomics techniques that are still in their infancy, several interesting hypotheses have been proposed. Focusing on CNS proteomics, we aim to review and update current knowledge in this rapidly advancing area.     

Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum

Chronic alcohol exposure can adversely affect neuronal morphology, synaptic architecture and associated neuroplasticity. However, the effects of moderate levels of long-term alcohol intake on the brain are a matter of debate. The current study used 2-DE (two-dimensional gel electrophoresis) proteomics to examine proteomic changes in the striatum of male Wistar rats after 8 months of continuous access to a standard off-the-shelf beer in their home cages. Alcohol intake under group-housed conditions during this time was around 3–4 g/kg/day, a level below that known to induce physical dependence in rats. After 8 months of access rats were euthanased and 2-DE proteomic analysis of the striatum was conducted. A total of 28 striatal proteins were significantly altered in the beer drinking rats relative to controls. Strikingly, many of these were dopamine (DA)-related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis), pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP regulating phosphoprotein (a regulator of DA receptors and transporters), protein phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA uptake). Selected protein expression changes were verified using Western blotting. We conclude that long-term moderate alcohol consumption is associated with substantial alterations in the rat striatal proteome, particularly with regard to dopaminergic signaling pathways. This provides potentially important evidence of major neuroadaptations in dopamine systems with daily alcohol consumption at relatively modest levels.     

TGF-β1 re-programs TLR4 signaling in L. donovani infection: enhancement of SHP-1 and ubiquitin-editing enzyme A20

Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll-like receptor (TLR)-mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-1β in response to TLR stimulation. Overexpression of transforming growth factor (TGF)-β(1), but not IL-10, resulted in suppressed lipopolysaccharide (LPS)-induced production of TNF-α and downregulation of TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF-β(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain-containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase (IRAK)-1 activation. Addition of neutralizing TGF-β(1) antibody reversed these effects, and thus suggesting the pivotal role of TGF-β(1) in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF-β(1) induced tolerance in infected macrophages by reducing inhibitory protein (IκBα) degradation in a time-dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin-editing protein complex induced inhibitory activity of TGF-β(1) on LPS-mediated nuclear factor-κB activation. Thus, these findings suggest that TGF-β(1) promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active L. donovani infection.     

Fine discrimination in the recognition of individual species of phosphatidyl-myo-inositol mannosides from Mycobacterium tuberculosis by C-type lectin pattern recognition receptors

The Mycobacterium tuberculosis (M.tb) envelope is highly mannosylated with phosphatidyl-myo-inositol mannosides (PIMs), lipomannan, and mannose-capped lipoarabinomannan (ManLAM). Little is known regarding the interaction between specific PIM types and host cell C-type lectin pattern recognition receptors. The macrophage mannose receptor (MR) and dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells engage ManLAM mannose caps and regulate several host responses. In this study, we analyzed the association of purified PIM families (f, separated by carbohydrate number) and individual PIM species (further separated by fatty acid number) from M.tb H(37)R(v) with human monocyte-derived macrophages (MDMs) and lectin-expressing cell lines using an established bead model. Higher-order PIMs preferentially associated with the MR as demonstrated by their reduced association with MDMs upon MR blockade and increased binding to COS-1-MR. In contrast, the lower-order PIM(2)f associated poorly with MDMs and did not bind to COS-1-MR. Triacylated PIM species were recognized by MDM lectins better than tetra-acylated species and the degree of acylation influenced higher-order PIM association with the MR. Moreover, only higher-order PIMs that bind the MR showed a significant increase in phagosome-lysosome fusion upon MR blockade. In contrast with the MR, the PIM(2)f and lipomannan were recognized by DC-SIGN comparable to higher-order PIMs and ManLAM, and the association was independent of their degree of acylation. Thus, recognition of M.tb PIMs by host cell C-type lectins is dependent on both the nature of the terminal carbohydrates and degree of acylation. Subtle structural differences among the PIMs impact host cell recognition and response and are predicted to influence the intracellular fate of M.tb.     

Decline in ascorbate peroxidase activity--a prerequisite factor for tepal senescence in gladiolus

Flower senescence was studied in Gladiolus cv. "Snow Princess" over five arbitrarily divided developmental stages (stage 1, half bloom; stage 2, full bloom; stage 3, beginning of wilting; stage 4, 50% wilting; stage 5, complete wilting) in terms of changes in fresh weight, antioxidant enzymes (superoxide dismutase, SOD; ascorbate peroxidase, APX; glutathione reductase, GR) activities and membrane integrity. A significant decrease in tepal fresh weight was observed over the senescence period (after stage 2). Membrane integrity was studied by measuring lipid peroxidation [in terms of thiobarbituric acid reactive substances (TBARS) content] and membrane stability index (MSI) percentage. Maximum TBARS content was recorded in stage 4 (50% wilting). This increase in lipid peroxidation over the senescence period was in close association with high degree of membrane deterioration expressed as decrease in membrane stability index percentage. A significant decrease (two and half-fold) in MSI% in stage 5 (as compared to stage 1) indicates complete membrane deterioration. Progressive increase in endogenous H2O2 level was recorded over senescence period. Maximum H2O2 content (19.7+/-1.4 micromol g(-1) DW) was recorded at stage 5 (complete wilting). Three different patterns were observed in antioxidant enzymes behavior over the senescence period. APX activity was declined significantly as, the flower entered stage 3 (beginning of wilting) from full bloom condition (stage 2). Progressive and significant increase in SOD activity was measured as a function of time. Maximum SOD activity (24.2+/-0.8 U mg(-1) DW) was recorded in stage 5 (three-fold increase over stage 1). GR activity initially increased up to stage 4 (50% wilting) and declined significantly thereafter (approximately seven-fold). An increase in endogenous H2O2 level during senescence may be the result of a programmed down-regulation of APX enzyme activity, which seems to be the prerequisite factor for initiating senescence process in gladiolus tepal.     

Amino acid conjugated sophorolipids: A new family of biologically active functionalized glycolipids

Sophorolipids (SLs) are extra cellular glycolipids produced by Candida bombicola ATCC 22214 when grown in the presence of glucose and fatty acids. These compounds have a disaccharide head group connected to a long-chain hydroxyl-fatty acid by a glycosidic bond. To explore structure-activity of modified SLs, a new family of amino acid-SL derivatives was prepared. Synthesized analogs consist of amino acids linked by amide bonds formed between their alpha-amino moiety and the carboxyl group of ring-opened SL fatty acids. Their preparation involved the following: (i) hydrolysis of a natural SL mixture with aqueous alkali to give SL free acids, (ii) coupling of free acids to protected amino acids using dicarbodiimide, and (iii) removing amino acid carboxyl protecting groups. These conjugates were evaluated for their antibacterial, anti-HIV, and spermicidal activity. All tested analogs showed antibacterial activity against both gram +ve and gram -ve organisms. Leucine-conjugated SL was most efficient. For example, the minimum inhibitory concentrations (MIC) for Moraxella sp. and E. coli were 0.83 and 1.67 mg/mL, respectively. Among the alkyl esters of amino acid conjugated SLs, the ethyl ester of leucine-SLs was most active. Against Moraxella sp., S. sanguinis, and M. imperiale, MIC values are 7.62 x 10(-4), 2.28 x 10-(3) and 1.67 mg/mL, respectively. All compounds displayed virus-inactivating activity with 50% effective concentrations (EC50) below 200 microg/mL. The EC50 of leucine-SL ethyl ester was 24.1 microg/mL, showing that it is more potent than commercial spermicide nonoxynol-9 (EC50 approximately 65 microg/mL).     

The fission yeast ptr1+ gene involved in nuclear mRNA export encodes a putative ubiquitin ligase

Fission yeast ptr1-1 is one of the mRNA transport mutants that accumulate poly(A)+ RNA in the nuclei at the nonpermissive temperature. We found that the ptr1+ gene encodes a homolog of Saccharomyces cerevisiae Tom1p, a hect type ubiquitin ligase. In ptr1-1, a conserved amino acid in the hect domain of Ptr1p is mutated. The ptr1+ gene is essential for growth and its mutation did not affect nuclear protein export. A ptr1-1 rae1-167 double mutant showed a synthetic effect on a growth defect, indicating that Ptr1p functionally interacts with an essential mRNA export factor Rae1p. We also isolated a multi-copy suppressor for ptr1-1 and found that it is the mpd2+ gene isolated as a multi-copy suppressor of cdc7-PD1.     

Liposome-bilirubin interaction: a novel strategy to eliminate bilirubin from systemic circulation

In the present study, we established the role of liposomes in removal of bilirubin from systemic circulation of the hyperbilirubinemic rats. Bilirubin has been demonstrated to possess inherent tendency to interact with liposomes through ionic as well as hydrophobic interactions. The size as well as lamellarity of the liposomes does not seem to affect their binding with bilirubin. However, the charge on the surface of liposomes plays an important role in bilirubin-liposome interaction, e.g., bilirubin binds more extensively with positively charged liposomes as compared to the neutral or negatively charged liposomes. The present study further demonstrates that liposomes were effective in reducing the increased plasma bilirubin level in hyperbilirubinemic model animals as well. The results of the study suggest that positively charged liposome-mediated selective homing of excess plasma bilirubin to the hepatocytes seems to offer an important strategy in management of hyperbilirubinemic conditions.     

Fungal phyA gene expressed in potato leaves produces active and stable phytase

Fungal phyA gene from Aspergillus ficuum (niger) was cloned and expressed in potato leaves. The recombinant enzyme was stable and catalytically active. The expressed protein in the leaves of the dicotyledonous plant retained most physical and catalytic properties of the benchmark A. ficuum phytase. The expressed enzyme was, however, 15% less glycosylated than the native phytase. The usual bi-hump pH optima profile, which is characteristic of the fungal phytase, was altered; however, the pH optimum at 5.0 was unchanged for phytate and at 4.0 for synthetic substrate p-nitrophenyl phosphate. The temperature was, however, unchanged. The expressed phytase was found to be as sensitive as the native enzyme to the inhibitory action of pseudo substrate, myo-inositol hexasulfate, while losing about 90% of the activity at 20 microM inhibitor concentration. Similar to the benchmark phytase, the expressed phytase in leaves was completely inactivated by Arg modifier phenylglyoxal at 60 nM. In addition, the expressed phytase in the leaves was inhibited by antibody raised against a 20-mer internal peptide, which is present on the surface of the molecule as shown by the X-ray deduced 3D structure of fungal phytase. Taken together, the biochemical evidences indicate that fungal phytase when cloned and expressed in potato leaves produces a stable and active biocatalyst. 'Biofarming,' therefore, is an alternative way to produce functional hydrolytic enzymes as exemplified by the expression of A. ficuum (niger) phyA gene in potato leaf.