Development of Zein-Pectin Nanoparticle as Drug carrier

Recent years have witnessed tremendous growth of nanotechnology based drug delivery system which reduces drug toxicity and side effects and increases the therapeutic index of the drug. Aim of the study is to develop a biodegradable, non-toxic nanoparticle, solely from natural polymers. Zein – pectin nanoparticle comprising of a hydrophobic zein core and a hydrophilic pectin shell was developed by ultrasonication method. SEM images confirm the nanosize of the nanoparticle. UV- Visible and FT-IR spectroscopic results confirm the incorporation of zein, pectin and the encapsulation of the model drug quercetin in the nanoparticle. Zein is a prolamine class of protein found in wheat, maize etc and pectin is a polymer of galacturonic acid units found in plant cell wal

Draft genome sequence of Neurospora crassa strain FGSC 73

Citation: Baker, S. E., Schackwitz, W., Lipzen, A., Martin, J., Haridas, S., LaButti, K., . . . McCluskey, K. (2016). Draft genome sequence of Neurospora crassa strain FGSC 73. Genome Announcements, 3(2). doi:10.1128/genomeA.00074-15Citation: Baker, S., Schackwitz, W., Lipzen, A., . . . McCluskey, K. (2015). Draft Genome Sequence of Neurospora crassa Strain FGSC 73. Genome Announcements, 3(2), e00074-15. https://doi.org/10.1128/genomeA.00074-15We report the elucidation of the complete genome of the Neurospora crassa (Shear and Dodge) strain FGSC 73, a mat-a, trp-3 mutant strain. The genome sequence around the idiotypic mating type locus represents the only publicly available sequence for a mat-a strain. 40.42 Megabases are assembled into 358 scaffolds carrying 11,978 gene models. © 2015 Baker et al

Avicin D, a Plant Triterpenoid, Induces Cell Apoptosis by Recruitment of Fas and Downstream Signaling Molecules into Lipid Rafts

Avicins, a family of triterpene electrophiles originally identified as potent inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We previously showed that Jurkat cells, which express a high level of Fas, are very sensitive to treatment with avicins. Thus, we hypothesized that avicins may induce cell apoptosis by activation of the Fas pathway. By using a series of cell lines deficient in cell death receptors, we demonstrated that upon avicin D treatment, Fas translocates to the cholesterol- and sphingolipid-enriched membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid raft organization by using a cholesterol-depleting compound, methyl-β-cyclodextrin, not only prevents the clustering of Fas and its DISC complex but also reduces the sensitivity of the cells to avicin D. Avicin D activates Fas pathways independent of the association between extracellular Fas ligands and Fas receptors. A deficiency in Fas and its downstream signaling molecules leads to the resistance of the cells to avicin D treatment. Taken together, our results demonstrate that avicin D triggers the redistribution of Fas in the membrane lipid rafts, where Fas activates receptor-mediated cell death

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

Suzuki-Miyaura coupling under microwave enhanced conditions: Synthesis of 2-(hetero)aryl benzimidazoles

An expedient, palladium-mediated cross-coupling approach to functionalize the benzimidazole-based core under microwave-assisted conditions has been developed and is described. This protocol, which incorporates appendage diversity on this potential scaffold, is found to be compatible with a wide range of electronicallyand sterically-divergent (hetero)aryl boronic acids. The use of the PdCl2/(SPhos) catalytic system allows the formation of a stable and highly active LPd(0) species which was found to be critical for the successful synthesis of these novel, pharmacologically-relevant molecules. © AUTHOR(S).Russian Foundation for Basic Research, RFBR: 170300641AThe authors are thankful to SAIF, Indian Institute of Technology, Madras, for providing all the analytical data and spectra. Vasiliy A. Bakulev is thankful to Russian Foundation for Basic Research (Grant # 170300641A)

Fabrication and surface functionalization of electrospun polystyrene submicron fibers with controllable surface roughness

Polystyrene (PS) submicron fibers of 14 wt% concentration were fabricated by electrospinning using dimethylformamide (DMF)–tetrahydrofuran (THF) solvent system. The surface morphology of PS fibers was modified from smooth to rough by changing the mixing ratio of DMF and THF in the spinning solution. The electrospun PS fibers with smooth and rough surfaces were then amidomethylated by treating with N-hydroxymethyl-2-chloroacetamide. PS fibers with higher roughness incorporated more amidomethyl functional groups on their surface, as confirmed by XPS analysis. This observation was further supported by BET adsorption isotherm results which showed a significant increase in specific surface area of rough PS electrospun fibers. Interestingly, amidomethylation has altered rough electrospun PS submicron fibers from extremely hydrophobic to hydrophilic. These chemically modified electrospun PS fibers with controllable surface roughness and wettability may be utilized as a carrier for proteins, mainly enzymes and antibodies, by covalent linkage through amino groups attached to their surface

Mass dependence of light nucleus production in ultrarelativistic heavy ion collisions

Light nuclei can be produced in the central reaction zone via coalescence in relativistic heavy ion collisions. E864 at BNL has measured the production of ten light nuclei with nuclear number of A=1 to A=7 at rapidity $y\simeq1.9$ and $p_{T}/A\leq300MeV/c$. Data were taken with a Au beam of momentum of 11.5 A $GeV/c$ on a Pb or Pt target with different experimental settings. The invariant yields show a striking exponential dependence on nuclear number with a penalty factor of about 50 per additional nucleon. Detailed analysis reveals that the production may depend on the spin factor of the nucleus and the nuclear binding energy as well.Comment: (6 pages, 3 figures), some changes on text, references and figures' lettering. To be published in PRL (13Dec1999

MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism.

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global metabolic alterations in MUC16 knockdown pancreatic cancer cells, as compared to the controls. Specifically, glycolytic and nucleotide metabolite pools were significantly decreased. We observed similar metabolic alterations that correlated with MUC16 expression in primary tumor tissue specimens from human pancreatic adenocarcinoma cancer patients. Overall, our results demonstrate that MUC16 plays an important role in metabolic reprogramming of pancreatic cancer cells by increasing glycolysis and enhancing motility and invasiveness