MedWorm: Biochemistry

The Red Blood Cell Proteome and Interactome: An Update

Journal of Proteome Research — Fri, 20 Nov 2009 15:26:09 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

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Metabonomics in Ulcerative Colitis: Diagnostics, Biomarker Identification, And Insight into the Pathophysiology

Journal of Proteome Research — Fri, 20 Nov 2009 15:21:50 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Ceramide Kinase Profiling by Mass Spectrometry Reveals a Conserved Phosphorylation Pattern Downstream of the Catalytic Site

Journal of Proteome Research — Fri, 20 Nov 2009 15:21:50 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Enhancing Nitrite Reductase Activity of Modified Hemoglobin: Bis-tetramers and Their PEGylated Derivatives

Biochemistry — Fri, 20 Nov 2009 13:23:50 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

According To The Statistical Analysis Of Fossils 'Hobbits' Are A New Human Species

Biology / Biochemistry News From Medical News Today — Fri, 20 Nov 2009 08:00:00 +0100

Researchers from Stony Brook University Medical Center in New York have confirmed that Homo floresiensis is a genuine ancient human species and not a descendant of healthy humans dwarfed by disease. Using statistical analysis on skeletal remains of a well-preserved female specimen, researchers determined the "hobbit" to be a distinct species and not a genetically flawed version of modern humans. (Source: Biology / Biochemistry News From Medical News Today)

Bioactive caffeic acid esters from Glycyrrhiza glabra.

Natural Product Research — Fri, 20 Nov 2009 03:00:30 +0100

Authors: Dey S, Deepak M, Setty M, D'Souza P, Agarwal A, Sangli GK Thin layer chromatography bioautography (using DPPH spray reagent) guided fractionation of Glycyrrhiza glabra led to the isolation of two caffeic acid derivative esters, viz. eicosanyl caffeate (1) and docosyl caffeate (2). The two compounds exhibited potent elastase inhibitory activity, with IC(50) values of 0.99 microg mL(-1) and 1.4 microg mL(-1) for 1 and 2, respectively. The compounds also showed moderate antioxidant activity in DPPH and ABTS scavenging assays. The results indicate a possible role of caffeic acid derivatives, in addition to flavonoids in the anti-ulcer properties of G. glabra. PMID: 19921583 [PubMed - as supplied by publisher] (Source: Natural Product Research)

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A new xenicane norditerpene from the Indian marine gorgonian Acanthogorgia turgida.

Natural Product Research — Fri, 20 Nov 2009 03:00:27 +0100

Authors: Manzo E, Ciavatta ML, Gavagnin M, Villani G, Quaranta C, D'Souza L, Cimino G Chemical investigation of the liposoluble extract of the gorgonian Acanthogorgia turgida, from Indian coasts, led us to isolate a new xenicane-based norditerpene, isoacalycixeniolide-A (1), along with the known structurally related compounds 2-6. The structure of the norditerpene (1) was elucidated by spectral methods (mainly by NMR techniques), whereas the absolute stereochemistry was suggested by the application of circular dicroism methodology. PMID: 19921584 [PubMed - as supplied by publisher] (Source: Natural Product Research)

Clausmarin-C: a novel terpenoid coumarin from Clausena pentaphylla.

Natural Product Research — Fri, 20 Nov 2009 03:00:24 +0100

Authors: Raj K, Sharma M, Misra N A novel terpenoid coumarin, clausmarin-C (1), has been isolated from Clausena pentaphylla. Its structure has been established by extensive 1D- and 2D-NMR analysis and chemical transformation. PMID: 19921585 [PubMed - as supplied by publisher] (Source: Natural Product Research)

Studies on the anti-oedematogenic properties of a fraction rich in lonchocarpin and derricin isolated from Lonchocarpus sericeus.

Natural Product Research — Fri, 20 Nov 2009 03:00:21 +0100

Authors: Fontenele JB, Leal LK, Felix FH, Silveira ER, Viana GS The acute anti-inflammatory properties of a fraction rich in the chalcones lonchocarpin and derricin, from the roots of Lonchocarpus sericeus (HFLS), were studied for the first time, using a paw oedema model induced in rats by various stimuli. Results showed that HFLS (100 and 200 mg kg(-1), i.p.) was ineffective in inhibiting dextran-induced paw oedema. The HFLS (200 mg kg(-1), p.o. or i.p.) also failed to inhibit the bradykinin-induced oedema. In the yeast-elicited oedema, the HFLS (200 mg kg(-1), i.p.) caused inhibitions ranging from 42 to 59% in the first to fourth hours. Orally administered HFLS (200 mg kg(-1)) was active only in the second (27%) and fourth (32%) hours after yeast injection. It was observed that HFLS ...

Determination of flavonoid compounds from Saussurea involucrata by liquid chromatography electrospray ionisation mass spectrometry.

Natural Product Research — Fri, 20 Nov 2009 03:00:19 +0100

Authors: Xu YJ, Zhao DX, Fu CX, Cheng LQ, Wang NF, Han LJ, Ma FS Saussurea involucrata produces several bioactive flavonoids that are derived from the phenylpropanoid pathway. To determine these flavonoids, a sensitive high performance liquid chromatography electrospray ionisation mass spectrometry method (LC-ESI-MS) was developed. Chromatographic separation was then performed. The gradient elution was optimised to give high recoveries and satisfactory chromatographic resolution. Flavonoid detection was carried out using an ion trap as mass analyser. Parameters of the mass analyser were optimised. We used the validated LC-ESI-MS method to verify the identities of bioactive compounds, namely apigenin, luteolin, hispidulin, luteolin-7-O-glucoside and rutin. Calibration curves for these f...

The effect of triptolide on CD4+ and CD8+ cells in the Peyer's patch of DA rats with collagen induced arthritis.

Natural Product Research — Fri, 20 Nov 2009 03:00:16 +0100

In this study, we investigated the effect of triptolide on the CD4+ and CD8+ cell distribution in Peyer's patch cells and periphery lymphocytes and TGF-beta and IFN-gamma levels in periphery in collagen induced arthritis (CIA) in DA rats. CIA in the rat is a widely studied animal model of inflammatory polyarthritis, with similarities to RA, and the DA rat is one of most susceptible strains for CIA. Our data show that triptolide could lower the arthritic scores of CIA. The more CD8+ cells in the Peyer's patch, the more CD4+ cells in periphery. High level IFN-gamma and low level TGF-beta in periphery are observed in CIA rats, while the less CD4+ and CD8+ cells in the Peyer's patch, the less CD4+ cells in periphery. Low level IFN-gamma and high level TGF-beta in periphery are shown in triptol...

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In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines.

Natural Product Research — Fri, 20 Nov 2009 03:00:14 +0100

This study is aimed to evaluate the in vitro cytotoxicity of Senecio stabianus Lacaita (Asteraceae) against renal adenocarcinoma ACHN, hormone-dependent prostate carcinoma LNCaP, amelanotic melanoma C32 and human breast adenocarcinoma MCF-7 cell lines. The n-hexane extract showed an interesting activity with IC(50) values of 62.7 and 71.1 mug mL(-1) against C32 and LNCaP, respectively. Two compounds identified in the n-hexane extract, linalool and beta-caryophyllene, were found to be active against C32 cells (IC(50) values of 23.2 and 20.1 mug mL(-1), respectively). Among tested constituents, the highest activity was found when alpha-humulene was applied to LNCaP cells (IC(50) of 11.2 mug mL(-1)). In order to complete the phytochemical study on S. stabianus, which has not been investigated...

Synthesis, phytotoxic, cytotoxic, acetylcholinesterase and butrylcholinesterase activities of N,N'-diaryl unsymmetrically substituted thioureas.

Natural Product Research — Fri, 20 Nov 2009 03:00:11 +0100

Authors: Begum S, Choudhary MI, Khan KM Fourteen N,N'-diaryl unsymmetrically substituted thioureas were synthesised and their cytotoxic (in vitro), phytotoxic (in vitro), acetylcholinesterase and butrylcholinesterase activities were determined. Thiourea 16 exhibited high, and 1 and 3 showed significant phytotoxic activity. Thioureas 1, 3, 4, 6 and 10 showed significant activity and 2, 6 and 7 indicated moderate cytotoxic activities. Compound 12 exhibited butrylcholinesterase activity higher than a standard reference. PMID: 19921590 [PubMed - as supplied by publisher] (Source: Natural Product Research)

In vitro cytotoxic and antioxidative activity of Cornus mas and Cotinus coggygria.

Natural Product Research — Fri, 20 Nov 2009 03:00:08 +0100

Authors: Savikin K, Zdunic G, Jankovic T, Stanojkovic T, Juranic Z, Menkovic N Cytotoxicity and antioxidant properties of the methanol extracts of leaves and flowers of Cornus mas and Cotinus coggygria were studied, together with their chemical composition. Extracts of C. coggygria flowers and leaves showed better antioxidant activity in reaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical as well as in inhibition of lipid peroxidation (LP) than C. mas extracts. Preliminary results showed that all extracts possessed potential cytotoxic activity towards HeLa and LS174 human cancer cell lines in vitro, with stronger inhibition against growth of HeLa cell growth than against LS174 cell growth. Cytotoxic activity of C. coggygria extracts showed good correlation with their antioxidati...

Two new dioxin derivatives from the aerial parts of Lawsonia alba.

Natural Product Research — Fri, 20 Nov 2009 03:00:06 +0100

Authors: Siddiqui BS, Uddin N, Begum S From the aerial parts of Lawsonia alba two new dioxin derivatives, namely 12-[2'-(1', 4'-dioxin-5', 6'-dione)-8''E-undecenyl-dodecanoate (1) and 5-[1'-(docosa-2'E, 5'E-dienyl)]-1,4-dioxin-2,3-dione (2), were isolated and characterised on the basis of spectroscopic methods. PMID: 19921592 [PubMed - as supplied by publisher] (Source: Natural Product Research)

Insulin-stimulated phosphorylation of endothelial nitric oxide synthase at Ser615 contributes to nitric oxide synthesis

BJ Signal — Fri, 20 Nov 2009 00:00:00 +0100

Insulin stimulates endothelial nitric oxide synthesis via protein kinase B/Akt-mediated phosphorylation and activation of endothelial nitric oxide synthase at Ser1177. In previous studies, we have demonstrated that stimulation of endothelial nitric oxide synthase phosphorylation at Ser1177 may be required, yet is not sufficient for insulin-stimulated nitric oxide synthesis. We therefore investigated the role of phosphorylation of endothelial nitric oxide synthase at alternative sites to Ser1177 as candidate parallel mechanisms contributing to insulin-stimulated nitric oxide synthesis. Stimulation of human aortic endothelial cells with insulin rapidly stimulated phosphorylation of both Ser615 and Ser1177 on endothelial NO synthase, whereas phosphorylation of Ser114, Thr495 and Ser633 was un...

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AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10

BJ Energy — Fri, 20 Nov 2009 00:00:00 +0100

In this paper we characterise the properties of the potent MCT1 inhibitor, AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes were used to determine the Ki value and number of AR-C155858 binding sites (Et) on MCT1 and the transporter’s turnover number (Kcat). Derived values were 2.3 ± 1.4 nM, 1.29 ± 0.09 nmoles per ml packed cells and 12.2 ± 1.1 s-1 respectively. When expressed in Xenopus laevis oocytes MCT1 and MCT2 were potently inhibited by AR-C155858 whilst MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chi...

Conformations within soluble oligomers and insoluble aggregates revealed by resonance energy transfer

Biopolymers — Fri, 20 Nov 2009 00:00:00 +0100

A fluorescently labeled 20-residue polyglutamic acid peptide E20 was used to study structural changes which occur in E20 as it co-aggregates with other unlabeled polyglutamic acid peptides. Resonance energy transfer was performed using an o-aminobenzamide donor at the N-terminus and 3-nitrotyrosine acceptor at the C-terminus of E20. Polyglutamic acid aggregates were not defined as amyloid, as they were non-fibrillar and did not bind Congo Red. Circular dichroism measurements indicate that polyglutamic acid aggregation involves a transition from [alpha]-helical monomers to aggregated [beta]-sheets. Soluble oligomers are also produced along with aggregates in the reaction, as determined through size exclusion chromatography. Time-resolved and steady state resonance energy transfer measuremen...

'Sulfo-click' for ligation as well as for site-specific conjugation with peptides, fluorophores, and metal chelators

Journal of Peptide Science — Fri, 20 Nov 2009 00:00:00 +0100

The 'sulfo-click' reaction, which is a chemoselective amidation reaction involving the reaction of an aminoethane sulfonyl azide with a thio acid, encompasses a new approach for ligation and conjugation. Detailed protocols are provided for decorating biologically active peptides or dendrimers with biophysical tags, fluorescent probes, metal chelators, and small peptides by using this reaction as a novel, metal-free 'sulfo-click' approach. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. (Source: Journal of Peptide Science)

An introduction to liquid chromatography-mass spectrometry instrumentation applied in plant metabolomic analyses

Phytochemical Analysis — Fri, 20 Nov 2009 00:00:00 +0100

Over the past decade the application of non-targeted high-throughput metabolomic analysis within the plant sciences has gained ever increasing interest and has truly established itself as a valuable tool for plant functional genomics and studies of plant biochemical composition. Whilst proton nuclear magnetic resonance (1H-NMR) spectroscopy is particularly appropriate for the analysis of bulk metabolites and gas chromatography mass spectrometry (GC-MS) to the analysis of volatile organic compounds (VOC's) and derivatised primary metabolites, liquid chromatography (LC)-MS is highly applicable to the analysis of a wide range of semi-polar compounds including many secondary metabolites of interest to plant researchers and nutritionists. In view of the recent developments in the separation sci...

Reactions of the Flavin Mononucleotide in Complex I: A Combined Mechanism Describes NADH Oxidation Coupled to the Reduction of APAD+, Ferricyanide, or Molecular Oxygen

Biochemistry — Thu, 19 Nov 2009 18:21:57 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

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Kinetic Analysis of Cysteine Desulfurase CD0387 from Synechocystis sp. PCC 6803: Formation of the Persulfide Intermediate

Biochemistry — Thu, 19 Nov 2009 16:56:36 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Evidence for the Involvement of Human DNA Polymerase N in the Repair of DNA Interstrand Cross-Links

Biochemistry — Thu, 19 Nov 2009 16:53:59 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Physical Instability of a Therapeutic Fc Fusion Protein: Domain Contributions to Conformational and Colloidal Stability

Biochemistry — Thu, 19 Nov 2009 14:17:22 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Post-Translational Modifications to Toxoplasma gondii α- and β-Tubulins Include Novel C-Terminal Methylation

Journal of Proteome Research — Thu, 19 Nov 2009 14:04:26 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Oligomeric Characterization of the Photosynthetic Apparatus of Rhodobacter sphaeroides R26.1 by Nondenaturing Electrophoresis Methods

Journal of Proteome Research — Thu, 19 Nov 2009 14:03:30 +0100

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Overexpression Of Sodium/Calcium Exchanger Protein Alone Did Not Cause Heart Failure

Biology / Biochemistry News From Medical News Today — Thu, 19 Nov 2009 11:00:00 +0100

Researchers from the Center for Translational Medicine at Thomas Jefferson University have found that the overexpression of a sodium/calcium exchanger, without changes in other ion transport pathways commonly observed in heart failure, does not by itself lead to contraction abnormalities in the heart. They presented the data from the study at the American Heart Association Scientific Sessions in Orlando, Fla. Led by Joseph Cheung, M.D., Ph.D. (Source: Biology / Biochemistry News From Medical News Today)

Scientific Link To Autism Identified

Biology / Biochemistry News From Medical News Today — Thu, 19 Nov 2009 11:00:00 +0100

During its research into the application of neuroscience in business, a New Jersey based think tank, The Center for Modeling Optimal Outcomes®, LLC (The Center) made an inadvertent and amazing discovery. The Center examined the neuroscientific dynamics of logic and emotion in decision making while researching neuroscience in business. They found unique corollary relationships between various brain chemicals (neurohormones, neurotransmitters, etc.). (Source: Biology / Biochemistry News From Medical News Today)

The novel ruthenium - [gamma]-linolenic complex [Ru2(aGLA)4Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential, increased reactive oxygen species generation and apoptosis in vitro

Cell Biochemistry and Function — Thu, 19 Nov 2009 00:00:00 +0100

The present study reports the synthesis of a novel compound with the formula [Ru2(aGLA)4Cl] according to elemental analyses data, referred to as Ru2GLA. The electronic spectra of Ru2GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru2GLA was synthesized with the aim of combining and possibly improving the anti-tumour properties of the two active components ruthenium and [gamma]-linolenic acid (GLA). The properties of Ru2GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru2GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru2GLA enters the cells and ICP-AES elemental...

Intermolecular cross-linking of monomers in H. pylori Na{+}/H{+} antiporter NhaA at dimer interface inhibits antiporter activity

BJ Energy — Thu, 19 Nov 2009 00:00:00 +0100

We previously showed that the Na+/H+ antiporter of Helicobacter pylori (HPNhaA) forms an oligomer in a native membrane of Escherichia coli, and conformational changes of oligomer occur between monomers of the oligomer during ion transport. In the current study, we use Blue Native PAGE to show that HPNhaA forms a dimer. Cysteine-scanning mutagenesis of residues 55 to 61 in a putative β-sheet region of loop1 and subsequent functional analyses revealed that the Q58C mutation resulted in an intermolecular disulfide bond. G56C, I59C, and G60C were found to be cross-linked by bifunctional cross-linkers. Furthermore, the Q58E mutant did not form a dimer, possibly due to electrostatic repulsion between monomers. These results imply that Gln58 and the flanking sequence in the p...

Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras mutated cancer cells

BJ Disease — Thu, 19 Nov 2009 00:00:00 +0100

Oncogenic Ras mutations render the protein constitutively active and promote tumourigenisis via chronic stimulation of effector pathways. In A549 lung adenocarcinoma approximately 50% of the total Ras population is constitutively active yet these cells display only weak activation of the effectors: ERK1/2 and Akt. In order to identify key negative regulators of oncogenic Ras signalling we performed a phosphatome RNAi screen in A549 cells and ranked their effects on phosphorylation of Ser473 of Akt. As expected, the tumour suppressor PTEN emerged as a leading hit – knockdown elevated Akt activation to 70% of maximal generated by acute EGF stimulation. Importantly, we identified other phosphatases with similar potencies including PTPN2 (TC-PTP) and PTPRJ (DEP-1/CD148). Potentiation of...

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MSK1 regulates the transcription of IL-1ra in response to TLR activation in macrophages.

BJ Disease — Thu, 19 Nov 2009 00:00:00 +0100

The activity of the pro-inflammatory cytokine IL-1 is closely regulated in vivo via a variety of mechanisms, including both the control of IL-1 production and secretion as well as naturally occurring inhibitors of IL-1 function such as IL-1ra. IL-1ra is homologous to IL-1, and is able to bind but not activate the IL-1 receptor. IL-1ra can be produced by a variety of cell types, and its production is stimulated by inflammatory signals. Here we show that in macrophages the TLR mediated induction of IL-1ra from both its proximal and distal promoters involves the p38 and ERK1/2 MAPK cascades. In addition we show that mitogen and stress activated kinase 1 (MSK1) and 2, kinases activated by either ERK1/2 or p38 in vivo, are required for the induction of both IL-1ra mRNA and protein. MSKs regulat...

CFTR fragments with the F508 deletion exert a dual allosteric control over the master kinase CK2.

BJ Disease — Thu, 19 Nov 2009 00:00:00 +0100

Cystic Fibrosis (CF) mostly follows a single F508 deletion in CFTR (ΔF508), thereby causing premature fragmentation of the nascent protein with concomitant alterations of diverse cellular functions. We show that CK2, the most pleiotropic protein kinase, undergoes allosteric control of its different cellular forms in the presence of short CFTR peptides encompassing the F508 deletion: these ΔF508 peptides drastically inhibit the isolated catalytic subunit (α) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non catalytic (β) subunits. Remarkable agreement between in silico docking and our biochemical data point to different sites for CFTR-ΔF peptide binding on isolated CK2α and on CK2β assembled into the holo...

The highly conserved synapsin domain E mediates synapsin dimerization and phospholipid vesicle clustering

BJ Cell — Thu, 19 Nov 2009 00:00:00 +0100

Synapsins are abundant synaptic vesicle (SV)-associated phosphoproteins that regulate synapse formation and function. The highly conserved COOH-terminal domain E was shown to contribute to several synapsin functions, ranging from formation of the SV reserve pool to regulation of the kinetics of exocytosis and SV cycling, although the molecular mechanisms underlying these effects are unknown. We used a synthetic 25-mer peptide encompassing the most conserved region of domain E (Pep-E) to analyze the role of domain E in regulating the interactions between synapsin I and liposomes mimicking the phospholipid composition of SVs (SV-liposomes) and other presynaptic protein partners. In affinity chromatography and cross-linking assays, Pep-E bound to endogenous and purified exogenous synapsin I a...

Paraoxonase 2 is downregulated by the Pseudomonas aeruginosa quorum sensing signal N-(3-oxododecanoyl)-L-homoserine lactone and attenuates oxidative stress induced by pyocyanin

BJ Cell — Thu, 19 Nov 2009 00:00:00 +0100

Two virulence factors produced by Pseudomonas aeruginosa are pyocyanin and N-(3-oxododecanoyl)-L-homoserine lactone (3OC12). Pyocyanin damages host cells by generating reactive oxygen species (ROS). 3OC12 is a quorum-sensing signaling molecule which regulates bacterial gene expression and modulates host immune responses. Paraoxonase-2 (PON2) is an esterase that inactivates 3OC12 and potentially attenuates P. aeruginosa virulence. Because increased intracellular calcium initiates the degradation of PON2 mRNA and protein and 3OC12 causes increases in cytosolic calcium, we hypothesized that 3OC12 would also downregulate PON2. 3OC12 and the calcium ionophore A23187 caused a rapid cytosolic calcium influx and downregulated PON2 mRNA, protein and hydrolytic activity in A549 and EA.hy 926 cells. ...

MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel Zn-finger protein, MCPIP

BJ Cell — Thu, 19 Nov 2009 00:00:00 +0100

We present evidence that MCP-1 causes death in cardiac myoblasts, H9c2, by inducing oxidative stress that causes ER stress leading to autophagy via a novel Zn-finger protein, MCP-1 induced protein (MCPIP). MCPIP expression caused cell death and knockdown of MCPIP attenuated MCP-1 induced cell death. It caused induction of iNOS, NADPH oxidase subunit phox47, its translocation from the cytoplasm to the membrane and production of reactive oxygen species (ROS), and induction of ER stress markers HSP40, PDI, GRP78 and IRE1α. It also caused autophagy as indicated by beclin-1 induction, cleavage of LC3 and autophagolysosome formation and apoptosis. Inhibitors of oxidative stress, inhibited ROS formation, ER stress, autophagy and cell death. Specific inhibitors of ER stress and knockdown of...

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Antioxidant activities of curcumin and combinations of this curcuminoid with other phytochemicals

Phytotherapy Research — Thu, 19 Nov 2009 00:00:00 +0100

In conclusion, curcumin is a potent antioxidant in a reaction that may be relevant to in vivo toxicity. In relation to two other well-known antioxidants, curcumin shows significantly greater synergism with resveratrol than with quercetin. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Phytotherapy Research)

Inhibitory effect of the cree traditional medicine wiishichimanaanh (Vaccinium vitis-idaea) on advanced glycation endproduct formation: identification of active principles

Phytotherapy Research — Thu, 19 Nov 2009 00:00:00 +0100

Like many aboriginal populations, First Nations communities such as the Cree of Eeyou Istchee are facing continuously increasing rates of diabetes and related complications. Advanced glycation endproducts (AGEs), which readily form and accumulate with sustained hyperglycemia, contribute to the development of diabetic complications and, as such, are considered a potential therapeutic target. In the present study, the inhibition of AGE formation by ethanolic extracts of the Cree medicinal plant Vaccinium vitis-idaea L. was assessed by fluorometric detection of fluorescent AGEs and immunodetection of N[egr]-(carboxymethyl)lysine adducts of albumin. Extracts from V. vitis-idaea berries demonstrated a concentration-dependent inhibition of AGE formation in both measures. High performance liquid ...

Effects of Athamanta turbith fruit essential oils on CCl4-induced hepatic failure in mice and their antioxidant properties

Phytotherapy Research — Thu, 19 Nov 2009 00:00:00 +0100

The effects of essential oils isolated from mature fruits of Athamanta turbith ssp. hungarica (Borbás) Tutin and A. turbith ssp. haynaldii (Borbás & Uechtr.) Tutin (Umbelliferae) on some liver biochemical parameters in mice intoxicated with carbon tetrachloride were investigated. Pretreatment with both essential oils extenuated the effects caused by carbon tetrachloride. In order to investigate in vitro antioxidant properties of the oils, three methods were applied: scavenging of both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radicals, as well as a test of inhibition of Fe2+/ascorbic-induced lipid peroxidation. Investigated essential oils exhibited modest antioxidant capacity. Therefore, their influence on biochemical parameters in intoxicated animals might be linked to the inhibition ...

Association of Phosphatidic Acid with the Bovine Mitochondrial ADP/ATP Carrier

Biochemistry — Wed, 18 Nov 2009 21:20:27 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Characterization of a Key Neutralizing Epitope on Pertussis Toxin Recognized by Monoclonal Antibody 1B7

Biochemistry — Wed, 18 Nov 2009 21:12:54 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

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Mansouramycins A−D, Cytotoxic Isoquinolinequinones from a Marine Streptomycete(1)

Journal of Natural Products — Wed, 18 Nov 2009 18:41:37 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

MSQuant, an Open Source Platform for Mass Spectrometry-Based Quantitative Proteomics

Journal of Proteome Research — Wed, 18 Nov 2009 17:54:23 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Insight into the Mechanism of Inactivation of Ribonucleotide Reductase by Gemcitabine 5′-Diphosphate in the Presence or Absence of Reductant

Biochemistry — Wed, 18 Nov 2009 17:46:34 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Distinct Pose of Discodermolide in Taxol Binding Pocket Drives a Complementary Mode of Microtubule Stabilization

Biochemistry — Wed, 18 Nov 2009 17:40:07 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Mechanism of Inactivation of Human Ribonucleotide Reductase with p53R2 by Gemcitabine 5′-Diphosphate

Biochemistry — Wed, 18 Nov 2009 17:37:08 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

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Heme Iron Nitrosyl Complex of MauG Reveals an Efficient Redox Equilibrium between Hemes with Only One Heme Exclusively Binding Exogenous Ligands

Biochemistry — Wed, 18 Nov 2009 16:31:07 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Functional Divergence of Helicobacter pylori Related to Early Gastric Cancer

Journal of Proteome Research — Wed, 18 Nov 2009 16:23:53 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Improving diffraction by humidity control: a novel device compatible with X-ray beamlines

Acta Crystallographica Section D — Wed, 18 Nov 2009 16:10:23 +0100

Dehydration of protein crystals is rarely used, despite being a post-crystallization method that is useful for the improvement of crystal diffraction properties, as it is difficult to reproduce and monitor. A novel device for hydration control of macromolecular crystals in a standard data-collection environment has been developed. The device delivers an air stream of precise relative humidity that can be used to alter the amount of water in macromolecular crystals. The device can be rapidly installed and is fully compatible with most standard synchrotron X-ray beamlines. Samples are mounted in cryoloops and the progress of dehydration can be monitored both optically and by the acquisition of diffraction images. Once the optimal hydration level has been obtained, cryocooling is easy to achi...

Th17: A New Participant in Gut Dysfunction in Mice Infected with Trichinella spiralis

Mediators of Inflammation — Wed, 18 Nov 2009 16:10:14 +0100

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. Our aim was to elucidate if Th17 cells were involved in the development of gastrointestinal hypermotility in this experimental model. Intestinal inflammation was observed by hematoxylin-eosin (HE) staining. Jejunal smooth muscle contractility was investigated in response to acetylcholine (Ach). The effects of IL-17 on jejunum smooth muscle contractility were explored. Flow cytometry was used to analyze the proportion of Th17 cells in jejunum. The levels of IL-17, IL-23, and TGF-β1 in jejunum were measured by Western blot. Our results showed that the inflammation in jejunum was severe at 2 weeks postinfection (PI), which was not discernible at 8 weeks PI. Jejunal ...

Direct One-Step18F-Labeling of Peptides via Nucleophilic Aromatic Substitution

Bioconjugate Chemistry — Wed, 18 Nov 2009 14:55:34 +0100

Bioconjugate Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Bioconjugate Chemistry)

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Global Genomic and Proteomic Analysis Identifies Biological Pathways Related to High-Risk Neuroblastoma

Journal of Proteome Research — Wed, 18 Nov 2009 14:53:32 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

The Caulerpa Pigment Caulerpin Inhibits HIF-1 Activation and Mitochondrial Respiration

Journal of Natural Products — Wed, 18 Nov 2009 14:51:07 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

Comparative Protein Profiling Reveals Minichromosome Maintenance (MCM) Proteins As Novel Potential Tumor Markers for Meningiomas

Journal of Proteome Research — Wed, 18 Nov 2009 14:50:41 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Evidence of Kinetic Control of Ligand Binding and Staged Product Release in MurA (Enolpyruvyl UDP-GlcNAc Synthase)-Catalyzed Reactions

Biochemistry — Wed, 18 Nov 2009 14:30:51 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Dissociation Kinetics of the GroEL−gp31 Chaperonin Complex Studied with Förster Resonance Energy Transfer

Biochemistry — Wed, 18 Nov 2009 14:27:10 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

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Snake Venomics of the Central American Rattlesnake Crotalus simus and the South American Crotalus durissus Complex Points to Neurotoxicity as an Adaptive Paedomorphic Trend along Crotalus Dispersal in South America

Journal of Proteome Research — Wed, 18 Nov 2009 12:53:23 +0100

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Coupling of the NMDA receptor to neuroprotective and neurodestructive events.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:37 +0100

Authors: Hardingham GE NMDA (N-methyl-D-aspartate) receptors are a subtype of ionotropic glutamate receptor with an important role in the physiology and pathophysiology of central neurons. Inappropriate levels of Ca(2+) influx through the NMDA receptor can contribute to neuronal loss in acute trauma such as ischaemia and traumatic brain injury, as well as certain neurodegenerative diseases such as Huntington's disease. However, normal physiological patterns of NMDA receptor activity can promote neuroprotection against both apoptotic and excitotoxic insults. As a result, NMDA receptor blockade can promote neuronal death outright or render neurons vulnerable to secondary trauma. Thus responses to NMDA receptor activity follow a classical hormetic dose-response curve: both too much and to...

Unique signal transduction of the VEGF family members VEGF-A and VEGF-E.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:32 +0100

Authors: Shibuya M Both VEGF (vascular endothelial growth factor)-A and Orf-virus-encoded VEGF-E bind and activate VEGFR (VEGF receptor)-2; however, only VEGF-A binds VEGFR-1. To understand the biological differences between VEGF-A and VEGF-E in vivo, we established transgenic mouse models. K14 (keratin-14)-promoter-driven VEGF-E transgenic mice showed a significant increase in mature blood vessels. However, K14-VEGF-A transgenic mice exhibited severe inflammation and oedema with increased angiogenesis, as well as lymphangiogenesis and lymph vessel dilatation. K14-VEGF-A transgenic mice deficient in VEGFR-1 signalling (K14-VEGF-A-tg/VEGFR-1 TK(-/-) mice) showed decreases in oedema and inflammation with less recruitment of macrophage-lineage cells, suggesting an involvement of VEGFR-1 i...

VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:30 +0100

Authors: Waltenberger J The action of VEGF (vascular endothelial growth factor) is essential to maintain proper endothelial and vascular function. VEGF stimulates virtually all aspects of endothelial function, namely proliferation, migration, permeability and nitric oxide production and release. In addition, the action of VEGF makes the endothelium anti-apoptotic. In turn, the inhibition of VEGF action is associated with endothelial dysfunction. Likewise, endothelial dysfunction can be found in the presence of several cardiovascular risk factors, including diabetes mellitus, hypercholesterolaemia and smoking. As circulating monocytes express functionally active VEGFR-1 (VEGF receptor 1) on their surface, monocytes and the related VEGFR-1-mediated signal transduction cascades have come ...

The role of neuropilins in cell signalling.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:27 +0100

Authors: Zachary IC, Frankel P, Evans IM, Pellet-Many C NRPs (neuropilins) are receptors for class 3 semaphorins, polypeptides essential for axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. While mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, little is known concerning the molecular mechanisms through which NRPs mediate the functions of their ligands in different cell types. NRP1 forms complexes with its co-receptors and is required for optimal function, but NRPs lack a clearly defined signalling domain and the role of NRP1 in receptor signalling and the function of the NRP1 cytosolic domain are unclear. Growing evidence indicates, however, that NRP1 plays a selective role in...

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Protease-activated receptors, cyclo-oxygenases and pro-angiogenic signalling in endothelial cells.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:24 +0100

Authors: Wheeler-Jones CP, Farrar C, Garonna E COX (cyclo-oxygenase)-2 and members of the PAR (protease-activated receptor) family (PARs 1-4) are highly overexpressed in a number of angiogenesis-dependent pathologies, including advanced atherosclerosis and cancer. An appreciation of the potential role(s) of PARs and COX enzymes in physiological angiogenesis is, however, currently lacking. Exposure of human endothelial cells to serine proteases (e.g. thrombin) or to PAR-selective agonist peptides leads to a wide range of cellular responses, including enhanced expression of COX-2, and we have shown that this induction depends on activation of classic pro-inflammatory signalling elements [e.g. MAPKs (mitogen-activated protein kinases) and NF-kappaB (nuclear factor kappaB)]. Our current st...

VEGF receptor trafficking in angiogenesis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:21 +0100

Authors: Scott A, Mellor H The intracellular trafficking of receptors provides a way to control the overall sensitivity of a cell to receptor stimulation. These sorting pathways are also used to shape the balance of signals that are generated in response to receptor activation. The major pro-angiogenic growth factor receptor is VEGFR2 (vascular endothelial growth factor 2). VEGFR2 activates a very similar set of signalling pathways to other RTKs (receptor tyrosine kinases); however, its intracellular trafficking is very different. Furthermore, VEGFR2 can form a complex with a range of different angiogenic regulators that in turn regulate the trafficking of VEGFR2 through the endosomal pathway. This regulated trafficking of VEGFR2 has important consequences for angiogenic signalling and...

A role for protein ubiquitination in VEGFR-2 signalling and angiogenesis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:18 +0100

Authors: Rahimi N Regulation of angiogenesis is often viewed as a balance between pro-angiogenic and anti-angiogenic factors, and when the balance shifts in favour of angiogenesis stimulators, an angiogenic switch turns on the normally inactive endothelial cells to grow new blood vessels. Recent studies have shown that PLCgamma1 (phospholipase Cgamma1), a major signalling substrate of VEGFR-2 (vascular endothelial growth factor receptor 2), undergoes c-Cbl-mediated ubiquitination. c-Cbl suppresses tyrosine phosphorylation of PLCgamma1 and with it VEGF (vascular endothelial growth factor)-induced endothelial cell proliferation and angiogenesis. Loss of c-Cbl in mice results in enhanced retinal neovascularization, VEGF- and tumour-induced angiogenesis. Notably, this observation suggests ...

VEGF-A-stimulated signalling in endothelial cells via a dual receptor tyrosine kinase system is dependent on co-ordinated trafficking and proteolysis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:15 +0100

Authors: Bruns AF, Bao L, Walker JH, Ponnambalam S The mammalian endothelium expresses two related but distinct receptor tyrosine kinases, VEGFR1 and VEGFR2 [VEGF (vascular endothelial growth factor) receptor 1 and 2], that regulate the vascular response to a key cytokine, VEGF-A. In the present review, we suggest a model for integrating the signals from these receptor tyrosine kinases by co-ordinating the spatial and temporal segregation of these membrane proteins linked to distinct signalling outputs associated with each intracellular location. Activation of pro-angiogenic VEGFR2 stimulates a programme of tyrosine phosphorylation, ubiquitination and proteolysis. This is linked to ESCRT (endosomal sorting complex required for transport)-mediated recognition of activated VEGFR2 and sor...

Gene therapy with vascular endothelial growth factors.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:12 +0100

Authors: Ylä-Herttuala S Therapeutic angiogenesis is a promising new concept for the treatment of myocardial and peripheral ischaemia. Members of the VEGF (vascular endothelial growth factor) family are among the most powerful modulators of angiogenesis. They regulate vascular growth and maintenance during embryogenesis and in adults. The present review summarizes the current status of therapeutic angiogenesis using VEGF, with special reference to preclinical studies. PMID: 19909246 [PubMed - in process] (Source: Biochemical Society Transactions)

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The heparin-binding domain confers diverse functions of VEGF-A in development and disease: a structure-function study.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:09 +0100

Authors: Krilleke D, Ng YS, Shima DT The longer splice isoforms of VEGF (vascular endothelial growth factor)-A, including VEGF(164(165)), contain a highly basic HBD (heparin-binding domain). This domain allows these isoforms to interact with and localize to the HS (heparan sulfate)-rich extracellular matrix, and bind to the co-receptor Nrp-1 (neuropilin-1). Heparin-binding VEGF-A isoforms are critical for survival: mice engineered to express exclusively the non-heparin-binding VEGF(120) have diminished vascular branching during embryonic development and die from postnatal angiogenesis defects shortly after birth. Although it is thought that the HBD contributes to the diverse functions of VEGF-A in both physiological and pathological processes, little is known about the molecular featur...

The anti-angiogenic isoforms of VEGF in health and disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:06 +0100

Authors: Qiu Y, Hoareau-Aveilla C, Oltean S, Harper SJ, Bates DO Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). Administration of recombinant VEGF(165)b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGF(xxx)b isoforms to the pro-angiogenic VEGF(xxx) isoforms, ...

Functionally defining the endothelial transcriptome, from Robo4 to ECSCR.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:02:03 +0100

Authors: Verissimo AR, Herbert JM, Heath VL, Legg JA, Sheldon H, Andre M, Swain RK, Bicknell R We have applied search algorithms to expression databases to identify genes whose expression is restricted to the endothelial cell. Such genes frequently play a critical role in endothelial biology and angiogenesis. Two such genes are the roundabout receptor Robo4 and the ECSCR (endothelial-cell-specific chemotaxis regulator). Endothelial cells express both Robo1 and Robo4, which we have knocked down using siRNA (small interfering RNA) and then studied the effect in a variety of in vitro assays. Both Robo4 and Robo1 knockdown inhibited in vitro tube formation on Matrigel. Transfection of Robo4 into endothelial cells increased the number of filopodial extensions from the cell, but failed to do...

Thymosin beta4 induces epicardium-derived neovascularization in the adult heart.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:58 +0100

Authors: Riley PR, Smart N The inability of the human heart to effectively repair itself after acute ischaemic injury has driven the search for efficacious means of promoting cardiac regenerative growth. Central to this has been the emergence of cell-based strategies to stimulate and augment both myocardial regeneration and neovascularization. Autologous cell transplantation of a variety of adult progenitor cells has been taken forward in clinical trials and, in parallel, investigators have begun to focus on the activation of resident cardiac cell populations as a means to stimulate endogenous repair. The latter approach depends on characterizing native progenitors with self-renewal, clonality, multipotency and arguably an analogous embryological counterpart. Recently, we have focused ...

Notch signalling in ischaemia-induced angiogenesis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:55 +0100

Authors: Zen AA, Madeddu P Notch signalling represents a key pathway essential for normal vascular development. Recently, great attention has been focused on the implication of Notch pathway components in postnatal angiogenesis and regenerative medicine. This paper critically reviews the most recent findings supporting the role of Notch in ischaemia-induced neovascularization. Notch signalling reportedly regulates several steps of the reparative process occurring in ischaemic tissues, including sprouting angiogenesis, vessel maturation, interaction of vascular cells with recruited leucocytes and skeletal myocyte regeneration. Further characterization of Notch interaction with other signalling pathways might help identify novel targets for therapeutic angiogenesis. PMID: 19909251 [P...

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Neuropilin ligands in vascular and neuronal patterning.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:52 +0100

Authors: Fantin A, Maden CH, Ruhrberg C Blood vessels and neurons share guidance cues and cell-surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 (neuropilin 1) is present on both blood vessels and nerves and binds two structurally diverse ligands, the class 3 semaphorin SEMA3A and an isoform of the vascular endothelial growth factor VEGF-A termed VEGF(165) (VEGF(164) in mice). In vitro, SEMA3A competes with VEGF(164) for binding to NRP1 to modulate the migration of endothelial cells and neuronal progenitors. It was therefore hypothesized that NRP1 signalling controls neurovascular co-patterning by integrating competing VEGF(164) and SEMA3A signals. However, SEMA3A, but not VEGF(164), is required for axon patterning of motor and sensory ne...

VEGFRs and Notch: a dynamic collaboration in vascular patterning.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:49 +0100

Authors: Jakobsson L, Bentley K, Gerhardt H ECs (endothelial cells) in the developing vasculature are heterogeneous in morphology, function and gene expression. Inter-endothelial signalling via Dll4 (Delta-like 4) and Notch has recently emerged as a key regulator of endothelial heterogeneity, controlling arterial cell specification and tip versus stalk cell selection. During sprouting angiogenesis, tip cell formation is the default response to VEGF (vascular endothelial growth factor), whereas the stalk cell phenotype is acquired through Dll4/Notch-mediated lateral inhibition. Precisely how Notch signalling represses stalk cells from becoming tip cells remains unclear. Multiple components of the VEGFR (VEGF receptor) system are regulated by Notch, suggesting that quantitative differenc...

Can the biology of VEGF and haem oxygenases help solve pre-eclampsia?

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:46 +0100

Authors: Ahmed A, Cudmore MJ Pre-eclampsia, a pregnancy-specific multi-organ syndrome characterized by widespread endothelial damage, is a new risk factor for cardiovascular disease. No therapies exist to prevent or treat this condition, even to achieve a modest improvement in pregnancy length or birth weight. Co-administration of soluble VEGFR-1 [VEGF (vascular endothelial growth factor) receptor-1; more commonly known as sFlt-1 (soluble Fms-like tyrosine kinase-1)] and sEng (soluble endoglin) to pregnant rats elicits severe pre-eclampsia-like symptoms. These two anti-angiogenic factors are increased dramatically prior to the clinical onset of pre-eclampsia and are quite possibly the 'final common pathway' responsible for the accompanying signs of hypertension and proteinuria as they ...

The DDAH/ADMA pathway in the control of endothelial cell migration and angiogenesis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:43 +0100

Authors: Fiedler LR, Wojciak-Stothard B ADMA (asymmetric dimethylarginine) is a cardiovascular risk factor and an endogenous inhibitor of NOS (nitric oxide synthase). ADMA is metabolized by DDAHs (dimethylarginine dimethylaminohydrolases). ADMA levels are increased in cardiovascular disorders associated with abnormal angiogenesis but the mechanisms are poorly understood. Recent studies show that altering ADMA metabolism in vivo and in vitro modulates the activity of Rho GTPases, key regulators of actin dynamics, endothelial cell motility and angiogenesis. In the present review, we consider this and other NO-dependent and -independent molecular mechanisms by which the DDAH/ADMA pathway regulates angiogenesis. PMID: 19909255 [PubMed - in process] (Source: Biochemical Society Transact...

Regulation of angiogenesis by ETS transcription factors.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:40 +0100

Authors: Randi AM, Sperone A, Dryden NH, Birdsey GM Transcription factors of the ETS family are important regulators of endothelial gene expression. Here, we review the evidence that ETS factors regulate angiogenesis and briefly discuss the target genes and pathways involved. Finally, we discuss novel evidence that shows how these transcription factors act in a combinatorial fashion with others, through composite sites that may be crucial in determining endothelial specificity in gene transcription. PMID: 19909256 [PubMed - in process] (Source: Biochemical Society Transactions)

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ERK5 and the regulation of endothelial cell function.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:37 +0100

Authors: Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ ERK5 (extracellular-signal-regulated kinase 5), also termed BMK1 [big MAPK1 (mitogen-activated protein kinase 1)], is the most recently discovered member of the MAPK family. It is expressed in a variety of tissues and is activated by a range of growth factors, cytokines and cellular stresses. Targeted deletion of Erk5 in mice has revealed that the ERK5 signalling cascade is critical for normal cardiovascular development and vascular integrity. In vitro studies have revealed that in endothelial cells, ERK5 is required for preventing apoptosis, mediating shear-stress signalling, regulating hypoxia, tumour angiogenesis and cell migration. This review focuses on our current understanding of the role of ERK5 in regulating endo...

Gene expression in neuronal disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:34 +0100

Authors: Wood IC, Gray NK, Jones L The brain is the most complex organ of the body and it contains the greatest diversity of cell types. Collectively, the cells within the brain express the greatest number of genes encoded within our genome. Inappropriate gene expression within these cells plays a fundamental role in many neuronal diseases. Illuminating the mechanisms responsible for gene expression is key to understanding these diseases. Because of the complexity, however, there is still much to understand about the mechanisms responsible for gene expression in the brain. There are many steps required for a protein to be generated from a gene, and groups who focus on gene expression normally study a single step such as regulation of transcription, mechanisms of RNA processing or contr...

Unravelling neurogenetic networks implicated in developmental language disorders.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:31 +0100

Authors: Vernes SC, Fisher SE Childhood syndromes disturbing language development are common and display high degrees of heritability. In most cases, the underlying genetic architecture is likely to be complex, involving multiple chromosomal loci and substantial heterogeneity, which makes it difficult to track down the crucial genomic risk factors. Investigation of rare Mendelian phenotypes offers a complementary route for unravelling key neurogenetic pathways. The value of this approach is illustrated by the discovery that heterozygous FOXP2 (where FOX is forkhead box) mutations cause an unusual monogenic disorder, characterized by problems with articulating speech along with deficits in expressive and receptive language. FOXP2 encodes a regulatory protein, belonging to the forkhead b...

Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:29 +0100

Authors: Bithell A, Johnson R, Buckley NJ HD (Huntington's disease) is a late onset heritable neurodegenerative disorder that is characterized by neuronal dysfunction and death, particularly in the cerebral cortex and medium spiny neurons of the striatum. This is followed by progressive chorea, dementia and emotional dysfunction, eventually resulting in death. HD is caused by an expanded CAG repeat in the first exon of the HD gene that results in an abnormally elongated polyQ (polyglutamine) tract in its protein product, Htt (Huntingtin). Wild-type Htt is largely cytoplasmic; however, in HD, proteolytic N-terminal fragments of Htt form insoluble deposits in both the cytoplasm and nucleus, provoking the idea that mutHtt (mutant Htt) causes transcriptional dysfunction. While a number of ...

Whole genome expression as a quantitative trait.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:26 +0100

Authors: Hardy J, Trabzuni D, Ryten M Surprisingly, whole genome analyses of complex human neurological and psychiatric disorders have revealed that many genetic risk factors are likely to influence gene expression rather than alter protein sequences. Previous analyses of neurological diseases have shown that genetic variability in gene expression levels of deposited proteins influence disease risk. With this background, we have embarked on a comprehensive project to determine the effects of common genetic variability on whole genome gene expression. PMID: 19909261 [PubMed - in process] (Source: Biochemical Society Transactions)

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High-throughput sequencing methods to study neuronal RNA-protein interactions.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:24 +0100

Authors: Ule J UV-cross-linking and RNase protection, combined with high-throughput sequencing, have provided global maps of RNA sites bound by individual proteins or ribosomes. Using a stringent purification protocol, UV-CLIP (UV-cross-linking and immunoprecipitation) was able to identify intronic and exonic sites bound by splicing regulators in mouse brain tissue. Ribosome profiling has been used to quantify ribosome density on budding yeast mRNAs under different environmental conditions. Post-transcriptional regulation in neurons requires high spatial and temporal precision, as is evident from the role of localized translational control in synaptic plasticity. It remains to be seen if the high-throughput methods can be applied quantitatively to study the dynamics of RNP (ribonucleop...

Pathogenic mechanisms of myotonic dystrophy.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:21 +0100

Authors: Lee JE, Cooper TA DM (myotonic dystrophy) is a dominantly inherited genetic disorder that is the most common cause of muscular dystrophy in adults affecting 1 in 8500 individuals worldwide. Different microsatellite expansions in two loci cause different forms of the disease that share similar features: DM1 (DM type 1) is caused by a tri- (CTG) nucleotide expansion within the DMPK (dystrophia myotonica protein kinase) 3'-untranslated region and DM2 (DM type 2) is caused by a tetra- (CCTG) nucleotide expansion within intron 1 of the ZNF9 (zinc finger 9) gene. The pathogenic mechanism of this disease involves the RNA transcribed from the expanded allele containing long tracts of (CUG)(n) or (CCUG)(n). The RNA results in a toxic effect through two RNA-binding proteins: MBNL1 (musc...

Gene expression networks: competing mRNA decay pathways in mammalian cells.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:18 +0100

We describe how a factor that is common to both pathways results in their competition. We also explain how competition between the two pathways contributes to the differentiation of C2C12 myoblasts to multinucleated myotubes. PMID: 19909264 [PubMed - in process] (Source: Biochemical Society Transactions)

eEF1A2 and neuronal degeneration.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:16 +0100

Authors: Abbott CM, Newbery HJ, Squires CE, Brownstein D, Griffiths LA, Soares DC Translation elongation factor eEF1A (eukaryotic elongation factor 1A) exists as two individually encoded variants in mammals, which are 98% similar and 92% identical at the amino acid level. One variant, eEF1A1, is almost ubiquitously expressed, the other variant, eEF1A2, shows a very restricted pattern of expression. A spontaneous mutation was described in 1972, which gives rise to the wasted phenotype: homozygous wst/wst mice develop normally until shortly after weaning, but then lose muscle bulk, acquire tremors and gait abnormalities and die by 4 weeks. This mutation has been shown to be a deletion of 15 kb that removes the promoter and first exon of the gene encoding eEF1A2. The reciprocal pattern of...

Protein synthesis and its control in neuronal cells with a focus on vanishing white matter disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:13 +0100

Authors: Pavitt GD, Proud CG Protein synthesis (also termed mRNA translation) is a key step in the expression of a cell's genetic information, in which the information contained within the coding region of the mRNA is used to direct the synthesis of the new protein, a process that is catalysed by the ribosome. Protein synthesis must be tightly controlled, to ensure the right proteins are made in the right amounts at the right time, and must be accurate, to avoid errors that could lead to the production of defective and potentially damaging proteins. In addition to the ribosome, protein synthesis also requires proteins termed translation factors, which mediate specific steps of the process. The first major stage of mRNA translation is termed 'initiation' and involves the recruitment of ...

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Splicing, cis genetic variation and disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:10 +0100

Authors: Jensen CJ, Oldfield BJ, Rubio JP Splicing is a post-transcriptional modification of RNA during which introns are removed and exons are joined. Most of the mammalian genes undergo constitutive and alternative splicing events. In addition to the strong signals of the splice sites, splicing is influenced at a distance by a range of trans factors that interact with cis regulatory elements and influence the spliceosome. The intention of the present mini-review is to give some insights into the complexity of this interaction and to introduce the consequences of some kinds of detrimental genetic variation on alternative splicing and disease. PMID: 19909267 [PubMed - in process] (Source: Biochemical Society Transactions)

Neuronal Glutamate and GABA(A) Receptor Function in Health and Disease.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:06 +0100

Authors: Moult PR Glutamate and GABA (gamma-aminobutyric acid) are the predominant excitatory and inhibitory neurotransmitters in the mammalian CNS (central nervous system) respectively, and as such have undergone intense investigation. Given their predominance, it is no wonder that the reciprocal receptors for these neurotransmitters have attracted so much attention as potential targets for the promotion of health and the treatment of disease. Indeed, dysfunction of these receptors underlies a number of well-characterized neuropathological conditions such as anxiety, epilepsy and neurodegenerative diseases. Although intrinsically linked, the glutamatergic and GABAergic systems have, by and large, been investigated independently, with researchers falling into the 'excitatory' or 'inhib...

Fractionating spatial memory with glutamate receptor subunit-knockout mice.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:03 +0100

Authors: Bannerman DM In recent years, the contribution that different glutamate receptor subtypes and subunits make to spatial learning and memory has been studied extensively using genetically modified mice in which key proteins are knocked out. This has revealed dissociations between different aspects of spatial memory that were not previously apparent from lesion studies. For example, studies with GluA1 AMPAR [AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor] subunit-knockout mice have revealed the presence of a GluA1-dependent, non-associative short-term memory mechanism that is important for performance on spatial working memory tasks, and a GluA1-independent, long-term associative memory mechanism which underlies performance on spatial reference memory ta...

Role of GABA(A) receptors in cognition.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:01:01 +0100

Authors: Möhler H Complex brains have developed specialized mechanisms for the grouping of principal cells into temporal coalitions of local or distant networks: the inhibitory interneuron 'clocking' networks. They consist of GABAergic (where GABA is gamma-aminobutyric acid) interneurons of a rich diversity. In cortical circuits, these neurons control spike timing of the principal cells, sculpt neuronal rhythms, select cell assemblies and implement brain states. On the basis of these considerations, the deficits in cognition, emotion and perception in psychiatric disorders such as anxiety, depression or schizophrenia are considered to manifest themselves through a dysregulation of the inhibitory interneuron 'clocking' network as a final common denominator, irrespective of the dive...

The physiological properties and therapeutic potential of alpha(5)-GABA(A) receptors.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:58 +0100

Authors: Martin LJ, Bonin RP, Orser BA The notion that drug treatments can improve memory performance has moved from the realm of science fiction to that of serious investigation. A popular working hypothesis is that cognition can be improved by altering the balance between excitatory and inhibitory neurotransmission. This review focuses on the unique physiological and pharmacological properties of GABA(A)Rs [GABA (gamma-aminobutyric acid) subtype A receptors] that contain the alpha(5) subunit (alpha(5)-GABA(A)R), as these receptors serve as candidate targets for memory-enhancing drugs. PMID: 19909271 [PubMed - in process] (Source: Biochemical Society Transactions)

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Use of concatamers to study GABA(A) receptor architecture and function: application to delta-subunit-containing receptors and possible pitfalls.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:55 +0100

Authors: Sigel E, Kaur KH, Lüscher BP, Baur R Many membrane proteins, including the GABA(A) [GABA (gamma-aminobutyric acid) type A] receptors, are oligomers often built from different subunits. As an example, the major adult isoform of the GABA(A) receptor is a pentamer built from three different subunits. Theoretically, co-expression of three subunits may result in many different receptor pentamers. Subunit concatenation allows us to pre-define the relative arrangement of the subunits. This method may thus be used to study receptor architecture, but also the nature of binding sites. Indeed, it made possible the discovery of a novel benzodiazepine site. We use here subunit concatenation to study delta-subunit-containing GABA(A) receptors. We provide evidence for the formation of d...

Locating GABA in GABA receptor binding sites.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:53 +0100

Authors: Lummis SC The Cys-loop family of ligand-gated ion channels contains both vertebrate and invertebrate members that are activated by GABA (gamma-aminobutyric acid). Many of the residues that are critical for ligand binding have been identified in vertebrate GABA(A) and GABA(C) receptors, and specific interactions between GABA and some of these residues have been determined. In the present paper, I show how a cation-pi interaction for one of the binding site residues has allowed the production of models of GABA docked into the binding site, and these orientations are supported by mutagenesis and functional data. Surprisingly, however, the residue that forms the cation-pi interaction is not conserved, suggesting that GABA occupies subtly different locations even in such closely re...

Single-channel properties of N-methyl-D-aspartate receptors containing chimaeric GluN2A/GluN2D subunits.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:50 +0100

Authors: O'Leary T, Wyllie DJ Subtypes of NMDARs (N-methyl-D-aspartate receptors) display differences in their pharmacological and biophysical properties. The differences are, to a large extent, determined by the identities of the GluN2 (glutamate-binding) NMDAR subunits that are co-expressed with GluN1 (glycine-binding) subunits, which form the final tetrameric NMDAR assembly. Of the four GluN2 subunits that exist (termed A-D), NMDARs composed of GluN1/GluN2A and GluN1/GluN2D subunits display the greatest differences in their sensitivities to a variety of agonists, antagonists and channel blockers as well as showing marked differences in their single-channel conductances and deactivation kinetics. Here, we describe a series of experiments where we have generated and studied two chimae...

The role of GABA(A)R phosphorylation in the construction of inhibitory synapses and the efficacy of neuronal inhibition.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:47 +0100

Authors: Vithlani M, Moss SJ GABA(A)Rs [GABA (gamma-aminobutyric acid) type-A receptors] are heteropentameric chloride-selective ligand-gated ion channels that mediate fast inhibition in the brain and are key therapeutic targets for benzodiazepines, barbiturates, neurosteroids and general anaesthetics. In the brain, most of the benzodiazepine-sensitive synaptic receptor subtypes are assembled from alpha(1-3), beta(1-3) and gamma(2) subunits. Although it is evident that the pharmacological manipulation of GABA(A)R function can have profound effects on behaviour, the endogenous mechanisms that neurons use to promote sustained changes in the efficacy of neuronal inhibition remain to be documented. It is increasingly clear that GABA(A)Rs undergo significant rates of constitutive endocytosi...

Neuronal calcium sensors and synaptic plasticity.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:45 +0100

Authors: Amici M, Doherty A, Jo J, Jane D, Cho K, Collingridge G, Dargan S Calcium entry plays a major role in the induction of several forms of synaptic plasticity in different areas of the central nervous system. The spatiotemporal aspects of these calcium signals can determine the type of synaptic plasticity induced, e.g. LTP (long-term potentiation) or LTD (long-term depression). A vast amount of research has been conducted to identify the molecular and cellular signalling pathways underlying LTP and LTD, but many components remain to be identified. Calcium sensor proteins are thought to play an essential role in regulating the initial part of synaptic plasticity signalling pathways. However, there is still a significant gap in knowledge, and it is only recently that evidence for t...

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Regulation of glutamate receptor trafficking by leptin.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:42 +0100

Authors: Moult PR, Harvey J It is well established that leptin is a circulating hormone that enters the brain and regulates food intake and body weight via its hypothalamic actions. However, it is also known that leptin receptors are widely expressed in the CNS (central nervous system), and evidence is accumulating that leptin modulates many neuronal functions. In particular, recent studies have indicated that leptin plays an important role in the regulation of hippocampal synaptic plasticity. Indeed leptin-insensitive rodents display impairments in hippocampal synaptic plasticity and defects in spatial memory tasks. We have also shown that leptin facilitates the induction of hippocampal LTP (long-term potentiation) via enhancing NMDA (N-methyl-D-aspartate) receptor function and that l...

Regulation of NMDA receptor Ca(2+) signalling and synaptic plasticity.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:40 +0100

Authors: Lau CG, Takeuchi K, Rodenas-Ruano A, Takayasu Y, Murphy J, Bennett MV, Zukin RS NMDARs (N-methyl-D-aspartate receptors) are critical for synaptic function throughout the CNS (central nervous system). NMDAR-mediated Ca(2+) influx is implicated in neuronal differentiation, neuronal migration, synaptogenesis, structural remodelling, long-lasting forms of synaptic plasticity and higher cognitive functions. NMDAR-mediated Ca(2+) signalling in dendritic spines is not static, but can be remodelled in a cell- and synapse-specific manner by NMDAR subunit composition, protein kinases and neuronal activity during development and in response to sensory experience. Recent evidence indicates that Ca(2+) permeability of neuronal NMDARs, NMDAR-mediated Ca(2+) signalling in spines and inductio...

Activity-dependent gene transcription as a long-term influence on receptor signalling.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:37 +0100

Authors: McDade DM, Conway AM, James AB, Morris BJ The regulation of synaptic glutamate receptor and GABA(A)R (gamma-aminobutyric acid subtype A receptor) levels is a key component of synaptic plasticity. Most forms of neuronal plasticity are associated with the induction of the transcription factor zif268 (egr1). Hence, it is predicted that zif268 may regulate transcription of genes associated with glutamate receptors and/or GABA(A)Rs. It turns out that receptor regulation by zif268 tends to be indirect. Induction of zif268 in neurons leads to altered expression of proteasome subunit and proteasome-regulatory genes, thereby changing the capacity of the neuron to degrade synaptic proteins, including receptors and receptor subunits. In addition, zif268 alters the transcription of genes ...

Plasticity of the alpha(4)betadelta GABA(A) receptor.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:34 +0100

Authors: Shen H, Smith SS The GABAR [GABA(A) (gamma-aminobutyric acid type A) receptor], which mediates most inhibition in the brain, is regulated homoeostatically to maintain an optimal level of neuronal excitability. In particular, the alpha(4)betadelta subtype of the GABAR plays a pivotal role in this regulation. This receptor, which is expressed extrasynaptically on the dendrites, normally has low expression in the brain, but displays a remarkable degree of plasticity. It can also be a sensitive target for endogenous neurosteroids such as THP (3alpha-hydroxy-5[alpha]beta-pregnan-20-one (allo-pregnanolone); a neurosteroid and positive modulator of the GABAR), which is released during stress, although the effect of the steroid is polarity-dependent, such that it increases inward curr...

Spare respiratory capacity, oxidative stress and excitotoxicity.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:32 +0100

Authors: Nicholls DG Chronic exposure to glutamate (glutamate excitotoxicity) exacerbates neuronal damage in the aftermath of stroke and is implicated in a variety of neurodegenerative disorders. Mitochondria play a central role in the survival or death of the exposed neuron. Calcium, oxidative stress and ATP insufficiency play closely interlocked roles that may be investigated with primary neuronal cultures. PMID: 19909281 [PubMed - in process] (Source: Biochemical Society Transactions)

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Rapid dendritic and axonal responses to neuronal insults.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:29 +0100

Authors: Mizielinska SM, Greenwood SM, Tummala H, Connolly CN Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system playing critical roles in basal synaptic transmission and mechanisms of learning and memory. Under normal conditions, glutamate is sequestered within synaptic vesicles (~100 mM) with extracellular glutamate concentrations being limited (<1 muM), via retrieval by plasma-membrane transporters on neuronal and glial cells. In the case of central nervous system trauma, stroke, epilepsy, and in certain neurodegenerative diseases, increased concentrations of extracellular glutamate (by vesicular release, cell lysis and/or decreased glutamate transporter uptake/reversal) stimulate the overactivation of local ionotropic glutamate receptors t...

Positive allosteric activation of GABA(A) receptors bi-directionally modulates hippocampal glutamate plasticity and behaviour.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:26 +0100

Authors: Shen G, Mohamed MS, Das P, Tietz EI Long-term BZ (benzodiazepine) anxiolytic therapy increases the risk of physical dependence manifested as withdrawal anxiety. BZ-induced potentiation of GABA(A)R (gamma-aminobutyric acid type-A receptor) function by 1-week oral administration of FZP (flurazepam) bi-directionally modulates excitatory glutamatergic synaptic transmission in hippocampal CA1 neurons during drug withdrawal. Previous electrophysiological studies on acutely isolated and intact CA1 neurons, as well as immunofluorescence and post-embedding immunogold electron microscopy studies, suggest increased synaptic insertion of GluR (glutamate receptor) 2-lacking AMPARs (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors) in 2-day FZP-withdrawn rats. Preliminary ...

RNA editing and its impact on GABA(A) receptor function.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:24 +0100

Authors: Daniel C, Ohman M A-to-I (adenosine-to-inosine) RNA editing catalysed by the ADARs (adenosine deaminases that act on RNA) is a post-transcriptional event that contributes to protein diversity in metazoans. In mammalian neuronal ion channels, editing alters functionally important amino acids and creates receptor subtypes important for the development of the nervous system. The excitatory AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate glutamate receptors, as well as the inhibitory GABA(A) [GABA (gamma-aminobutyric acid) type A] receptor, are subject to A-to-I RNA editing. Editing affects several features of the receptors, including kinetics, subunit assembly and cell-surface expression. Here, we discuss the regulation of editing during brain maturati...

RDL receptors.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:21 +0100

Authors: McGonigle I, Lummis SC RDL receptors are invertebrate members of the Cys-loop family of ligand-gated ion channels. They are GABA (gamma-aminobutyric acid)-activated chloride-selective receptors that are closely related to their vertebrate orthologues, the GABA(A) receptors, as well as other Cys-loop receptors such as the ionotropic glycine, nicotinic acetylcholine and 5-HT(3) receptors. RDL receptors are widely expressed throughout the insect CNS (central nervous system) and are important in inhibitory neurotransmission. They are therefore a major insecticidal target site. PMID: 19909285 [PubMed - in process] (Source: Biochemical Society Transactions)

Ca(2+)-dependent modulation of GABA(A) and NMDA receptors by extracellular ATP: implication for function of tripartite synapse.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:18 +0100

Authors: Lalo U, Andrew J, Palygin O, Pankratov Y The importance of communication between neuronal and glial cells for brain function is recognized by a modern concept of 'tripartite synapse'. Astrocytes enwrap synapses and can modulate their activity by releasing gliotransmitters such as ATP, glutamate and D-serine. One of the regulatory pathways in the tripartite synapse is mediated by P2X purinoreceptors. Release of ATP from synaptic terminals and astrocytes activates Ca(2+) influx via P2X purinoreceptors which co-localize with NMDA (N-methyl-D-aspartate) and GABA (gamma-aminobutyric acid) receptors and can modulate their activity via intracellular cascades which involve phosphatase II and PKA (protein kinase A). PMID: 19909286 [PubMed - in process] (Source: Biochemical Society ...

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Cortical excitability and post-stroke recovery.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:14 +0100

Authors: Clarkson AN, Carmichael ST Stroke is the leading cause of adult disability. Recent studies show that the brain can engage in a limited process of neural repair after stroke: re-mapping of sensory and motor function and sprouting of new connections in peri-infarct cortex surrounding the stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. The central cellular process in these events is alteration in neuronal response to incoming inputs - manipulations that increase neuronal firing to a given input are likely to induce changes in neuronal structure and alterations in cortical maps. Because post-stroke neural repair and recovery also involves neuronal sprouting and re-mapping of cortical sensory and m...

GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:12 +0100

Authors: Chen J, Tsang SY, Zhao CY, Pun FW, Yu Z, Mei L, Lo WS, Fang S, Liu H, Stöber G, Xue H The SCZ (schizophrenia)-associated GABA(A) receptor (gamma-aminobutyric acid type A receptor) beta(2) subunit gene GABRB2 was recently associated with BPD (bipolar disorder). Although weaker than its association with SCZ, significant association of GABRB2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071-rs187269 and rs1816072-rs187269 for which the M-M variants showed higher frequency in disease than the control. Significant genotype-dependent reduction in GABRB2 expression was shown for BPD, but to a lesser extent than that for SCZ. Temporal effects on GABRB2 expression were observed. Moreover, for the homozygous major genotypes of rs1816071, rs1816...

Potential role for ligand-gated ion channels after seizure-induced neurogenesis.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:09 +0100

Authors: Swijsen A, Hoogland G, Rigo JM Epileptic seizures result in an increased generation of new neurons in the dentate gyrus of the adult mammalian hippocampus. The role of these seizure-induced newborn neurons in the process of epileptogenesis remains largely unknown. Recent work, however, suggests an aberrant incorporation of newborn cells into the existing hippocampal network in such a way that they promote hippocampal hyperexcitability. In the present review, we discuss current knowledge about the possible role of seizure-induced newly generated neurons and the putative involvement of ligand-gated ion channels in the process of epileptogenesis. PMID: 19909289 [PubMed - in process] (Source: Biochemical Society Transactions)

Inhibition of recombinant GluN1/GluN2A and GluN1/GluN2B N-methyl-D-aspartate receptors by single malt whiskies.

Biochemical Society Transactions — Wed, 18 Nov 2009 05:00:06 +0100

Authors: Otton HJ, Janssen A, Wyllie DJ NMDARs (N-methyl-D-aspartate receptors) are considered to be a target for the inhibitory actions of ethanol. While profound inhibition of both native and recombinant NMDARs can be observed following the application of high concentrations of ethanol the levels of inhibition seen with lower concentrations of ethanol are more modest. Here, we report the effects of inhibiting NMDAR-mediated responses with ethanol concentrations that are experienced during the social consumption of alcohol comparing levels of inhibition seen with 'pure' ethanol with those produced by ethanol contained in three popular single malt whiskies. PMID: 19909290 [PubMed - in process] (Source: Biochemical Society Transactions)

Novel analogues of arginine vasopressin containing [alpha]-2-indanylglycine enantiomers in position 2

Journal of Peptide Science — Wed, 18 Nov 2009 00:00:00 +0100

Continuing our efforts to obtain potent and selective analogues of AVP we synthesized and pharmacologically evaluated ten new compounds modified at position 2 with [alpha]-2-indanylglycine or its D-enantiomer (Igl or D-Igl, respectively). All the peptides were tested for pressor, antidiuretic, and in vitro uterotonic activities. We also determined the binding affinity of these compounds to human OT receptor. The Igl2 substitution resulted in a significant change of the pharmacological profile of the peptides. The new analogues were moderate or potent OT antagonists (pA2 values ranging from 7.19 to 7.98) and practically did not interact with V1a and V2 receptors. It is worth emphasizing that these new peptides were exceptionally selective. On the other hand, the D-Igl2 substituted counterpa...

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On the use of N-dicyclopropylmethyl aspartyl-glycine synthone for backbone amide protection

Journal of Peptide Science — Wed, 18 Nov 2009 00:00:00 +0100

To prevent aspartimide formation and related side products in Asp-Xaa, particularly Asp-Gly-containing peptides, usually the 2-hydroxy-4-methoxybenzyl (Hmb) backbone amide protection is applied for peptide synthesis according to the Fmoc-protocols. In the present study, the usefulness of the recently proposed acid-labile dicyclopropylmethyl (Dcpm) protectant was analyzed. Despite the significant steric hindrance of this bulky group, N-terminal H-(Dcpm)Gly-peptides are quantitatively acylated by potent acylating agents, and alternatively the dipeptide Fmoc-Asp(OtBu)-(Dcpm)Gly-OH derivative can be used as a building block. In contrast to the Hmb group, Dcpm is inert toward acylations, but is readily removed in the acid deprotection and resin-cleavage step. Copyright © 2009 European Peptide ...

Microbial Fed-batch Production of 1,3-Propanediol Using Raw Glycerol with Suspended and Immobilized Klebsiella pneumoniae.

Applied Biochemistry and Biotechnology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Jun SA, Moon C, Kang CH, Kong SW, Sang BI, Um Y The production of 1,3-propanediol (1,3-PD) was investigated with Klebsiella pneumoniae DSM 4799 using raw glycerol without purification obtained from a biodiesel production process. Fed-batch cultures with suspended cells revealed that 1,3-PD production was more effective when utilizing raw glycerol than pure glycerol (productivity after 47 h of fermentation, 0.84 g L(-1) h(-1) versus 1.51 g L(-1) h(-1) with pure and raw glycerol, respectively). In addition, more than 80 g/L of 1,3-PD was produced using raw glycerol; this is the highest 1,3-PD concentration reported thus far for K. pneumoniae using raw glycerol. Repeated fed-batch fermentation with cell immobilization in a fixed-bed reactor was performed to enhance 1,3-PD product...

Simulated Microgravity Affects Growth of Escherichia coli and Recombinant beta-D: -Glucuronidase Production.

Applied Biochemistry and Biotechnology — Wed, 18 Nov 2009 00:00:00 +0100

In this study growth of E. coli BL21 (DE3) cells transformed with pET-28a (+)-pgus in double-axis clinostat that could model low shear SMG environment and the recombinant beta-D: -glucuronidase (PGUS) expression have been investigated. Results showed that the cell dry weights in SMG were 16.47%, 38.06%, and 28.79% more than normal gravity (NG) control, and the efficiency of the recombinant PGUS expression in SMG were 18.33%, 19.36%, and 33.42% higher than that in NG at 19 degrees C, 28 degrees C, and 37 degrees C, respectively (P < 0.05). PMID: 19921492 [PubMed - as supplied by publisher] (Source: Applied Biochemistry and Biotechnology)

Bioflocculant Exopolysaccharide Production by Azotobacter indicus Using Flower Extract of Madhuca latifolia L.

Applied Biochemistry and Biotechnology — Wed, 18 Nov 2009 00:00:00 +0100

This study suggests that use of M. latifolia L. flowers can be a potential alternative bioresource for production of exopolysaccharide. PMID: 19921493 [PubMed - as supplied by publisher] (Source: Applied Biochemistry and Biotechnology)

CSD mRNA expression in rat testis and the effect of taurine on testosterone secretion.

Amino Acids — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Yang J, Wu G, Feng Y, Sun C, Lin S, Hu J In the present study, the cysteine sulfinate decarboxylase (CSD) mRNA expression was detected in rat testis by RT-PCR. The results showed that CSD mRNA was expressed in rat testis, and the putative encoded-amino acid sequence was exactly the same as that in rat liver which was already known. At the same time, the effects of taurine on testosterone secretion were investigated both in vivo and in vitro. In vivo, taurine were administered to male rats by tap water. The results showed that taurine obviously stimulated the secretion of FSH, LH and testosterone in serum, but showed no significant effect on the secretion of estradiol. Taurine administered in water could significantly increase the concentration of taurine in the blood and testi...

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Insoluble and Flexible Silk Films Containing Glycerol.

Biomacromolecules — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Lu S, Wang X, Lu Q, Zhang X, Kluge JA, Uppal N, Omenetto F, Kaplan DL We directly prepared insoluble silk films by blending with glycerol and avoiding the use of organic solvents. The ability to blend a plasticizer like glycerol with a hydrophobic protein like silk and achieve stable material systems above a critical threshold of glycerol is an important new finding with importance for green chemistry approaches to new and more flexible silk-based biomaterials. The aqueous solubility, biocompatibility, and well-documented use of glycerol as a plasticizer with other biopolymers prompted its inclusion in silk fibroin solutions to assess impact on silk film behavior. Processing was performed in water rather than organic solvents to enhance the potential biocompatibility of these ...

On-chip coupling of free-solution transient ITP and CGE for highly efficient separation of dsDNA with variable sample loading amounts

Electrophoresis — Wed, 18 Nov 2009 00:00:00 +0100

We developed an on-chip DNA analysis method, in which free-solution transient isotachophoresis (FstITP) were coupled with CGE. Using chloride ions in the sample matrix and HEPES in the background electrolyte, respectively, as the leading and terminating ions, dsDNAs were isotachophoretically preconcentrated in free-solution and then separated in sieving polymer. The coupling of FstITP and CGE enabled higher separation efficiency due to higher preconcentration rate in free-solution. The FstITP-CGE analysis offered adjustable signal intensities by varying sample injection time. With the maximum sample loading volume, the LOD of the FstITP-CGE analysis was determined to be 0.24 ng/mL by confocal laser-induced fluorescence detection. The FstITP-CGE method is simple, robust and flexible, thus w...

Capillary electrochromatography with packed bead beds in microfluidic devices

Electrophoresis — Wed, 18 Nov 2009 00:00:00 +0100

Microchip-based bead-packed columns for electrochromatography are described for several types of stationary phases. Chromatography columns 2 mm in length were used for the separation of proteins and peptides by size- and ion-exchange modes of separation, respectively. In size-exclusion electrochromatograpgy, FITC-IgG and FITC-insulin were baseline resolved in less than 10 s, with efficiencies of up to 139,000 plates/m for FITC-insulin. In strong cation-exchange electrochromatography, a mixture of three fluorescently labeled peptides was baseline resolved in less than 40 s, with efficiencies up to 400,000 plates/m. The RSD for the analytes retention times were (Source: Electrophoresis)

Continuous fractionation of a two-component mixture by zone electrophoresis

Electrophoresis — Wed, 18 Nov 2009 00:00:00 +0100

Synchronized continuous-flow zone electrophoresis is a recently demonstrated tool for performing electrophoretic fractionation of a complex sample. The method resembles free flow electrophoresis, but unlike in that technique, no mechanical fluid pumping is required. Instead, fast electrokinetic flow switching is used to produce complex stream patterns, which results in lateral separation of components in a separation chamber. Here a solution is presented which allows for simultaneous collection of two fractions in synchronized continuous-flow zone electrophoresis. The method is demonstrated on a model mixture, with subsequent evaluation of the collected fractions purity by MCE. The necessary theoretical background is provided including both steering schemes and calculations of optimum oper...

Polymer microchip CE of proteins either off- or on-chip labeled with chameleon dye for simplified analysis

Electrophoresis — Wed, 18 Nov 2009 00:00:00 +0100

Microchip CE of proteins labeled either off- or on-chip with the "chameleon" CE dye 503 using poly(methyl methacrylate) microchips is presented. A simple dynamic coating using the cationic surfactant CTAB prevented nonspecific adsorption of protein and dye to the channel walls. The labeling reactions for both off- and on-chip labeling proceeded at room temperature without requiring heating steps. In off-chip labeling, a 9 ng/mL concentration detection limit for BSA, corresponding to a [sim]7 fg (100 zmol) mass detection limit, was obtained. In on-chip tagging, the free dye and protein were placed in different reservoirs of the microchip, and an extra incubation step was not needed. A 1 [mu]g/mL concentration detection limit for BSA, corresponding to a [sim]700 fg (10 amol) mass detection l...

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GDP-Mannose pyrophosphorylase is essential in the bloodstream form of Trypanosoma brucei

BJ Disease — Wed, 18 Nov 2009 00:00:00 +0100

A putative guanidine diphosphomannose pyrophophosphorylase (GDP-Man PP) gene from Trypanosoma brucei was identified in the genome and subsequently cloned, sequenced, and recombinantly expressed and shown to be a catalytically active dimer. Kinetic analysis revealed a Vmax of 0.34 μmol / min/ mg and Km’s of 67 μM and 12 μM for GTP and mannose-1-phosphate respectively. Further kinetic studies showed GDP-Man was a potent product feedback inhibitor. RNAi of the cytosolic TbGDP-Man PP showed mRNA levels were reduced to ~20% of wild type levels, causing the cells to die after 3-4 days, demonstrating TbGDP-Man PP is essential in the bloodstream form of T.brucei and thus a potential drug target. The RNAi induced parasites have a greatly reduced capability to form GDP-M...

Interaction of [alpha]-gliadin with polyanions: Design considerations for sequestrants used in supportive treatment of celiac disease

Biopolymers — Wed, 18 Nov 2009 00:00:00 +0100

This study provides insight into design considerations for polymer sequestrants used in the supportive treatment of celiac disease. © 2009 Wiley Periodicals, Inc. Biopolymers, 2009 (Source: Biopolymers)

Tau as a potential novel therapeutic target in ischemic stroke

Journal of Cellular Biochemistry — Wed, 18 Nov 2009 00:00:00 +0100

Stroke is associated with high mortality and major disability burdens worldwide, but there are few effective and widely available therapies. Tau plays an important role in promoting microtubule assembly and stabilizing microtubule networks with phosphorylation regulating these functions. Based on the "ischemia-reperfusion theory" of Alzheimer's disease, some previous studies have focused on the relationship of tau and Alzheimer lesions in experimental brain ischemia. Thus, we hypothesize that the alterations in phosphorylation of tau are critical to microtubule dynamics and metabolism, and contribute to the pathophysiologic mechanisms during brain ischemia and/or reperfusion processes. We infer that regulation of phosphorylation of tau may be considered as a potential new therapeutic targe...

Age-related effects of DHEA on peripheral markers of oxidative stress

Cell Biochemistry and Function — Wed, 18 Nov 2009 00:00:00 +0100

Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10-20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto-oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month-old. In the 13 month-old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione-S-transferase and catalase activities when compared to the other age groups. DHEA p...

Diketopiperazines from the Cordyceps-Colonizing Fungus Epicoccum nigrum

Journal of Natural Products — Tue, 17 Nov 2009 20:07:01 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

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Pyrrolidinones from the Ascomycete Fungus Albonectria rigidiuscula

Journal of Natural Products — Tue, 17 Nov 2009 20:04:21 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

Cytotoxic Constituents of the Lichen Diploicia canescens

Journal of Natural Products — Tue, 17 Nov 2009 20:03:05 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

Long-Chain Acyl-Homoserine Lactones from Methylobacterium mesophilicum: Synthesis and Absolute Configuration

Journal of Natural Products — Tue, 17 Nov 2009 20:02:21 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

Antineoplastic Agents. 556. Isolation and Structure of Coprinastatin 1 from Coprinus cinereus†,(1)

Journal of Natural Products — Tue, 17 Nov 2009 20:01:00 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

Antimycobacterial Flavonoids from the Leaf Extract of Galenia africana

Journal of Natural Products — Tue, 17 Nov 2009 20:00:59 +0100

Journal of Natural Products, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Natural Products)

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Gallium-67-Labeled Lactam Bridge-Cyclized α-Melanocyte Stimulating Hormone Peptide for Primary and Metastatic Melanoma Imaging

Bioconjugate Chemistry — Tue, 17 Nov 2009 20:00:33 +0100

Bioconjugate Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Bioconjugate Chemistry)

Tamoxifen−Poly(ethylene glycol)−Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment

Bioconjugate Chemistry — Tue, 17 Nov 2009 19:59:40 +0100

Bioconjugate Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Bioconjugate Chemistry)

Cellular Uptake Mechanism of Molecular Umbrella

Bioconjugate Chemistry — Tue, 17 Nov 2009 19:59:20 +0100

Bioconjugate Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Bioconjugate Chemistry)

Proteomic Analyses of the Developing Chicken Cardiovascular System

Journal of Proteome Research — Tue, 17 Nov 2009 19:51:14 +0100

Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Proteome Research)

Quassinoids from Eurycoma longifolia

Journal of Natural Products — Tue, 17 Nov 2009 19:44:58 +0100

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Apo and Nickel-Bound Forms of the Pyrococcus horikoshii Species of the Metalloregulatory Protein: NikR Characterized by Molecular Dynamics Simulations

Biochemistry — Tue, 17 Nov 2009 15:00:28 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Influence of Proline upon the Folding and Geometry of the WALP19 Transmembrane Peptide

Biochemistry — Tue, 17 Nov 2009 14:45:33 +0100

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Interaction between Na+ Ion and Carboxylates of the PomA−PomB Stator Unit Studied by ATR-FTIR Spectroscopy

Biochemistry — Tue, 17 Nov 2009 14:44:48 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

The Heparin Binding Motif of Endostatin Mediates Its Interaction with Receptor Nucleolin

Biochemistry — Tue, 17 Nov 2009 14:43:46 +0100

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Bolaamphiphile-Class Surfactants Can Stabilize and Support the Function of Solubilized Integral Membrane Proteins

Biochemistry — Tue, 17 Nov 2009 13:51:56 +0100

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Betaglycan has Two Independent Domains Required for High Affinity TGF-β Binding: Proteolytic Cleavage Separates the Domains and Inactivates the Neutralizing Activity of the Soluble Receptor

Biochemistry — Tue, 17 Nov 2009 13:50:55 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Molecularly Defined Antibody Conjugation through a Selenocysteine Interface

Biochemistry — Tue, 17 Nov 2009 13:50:47 +0100

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

Lyme Disease-Causing Microbes Seen Moving In Ticks

Biology / Biochemistry News From Medical News Today — Tue, 17 Nov 2009 12:00:00 +0100

Lyme disease is caused by the microbe Borrelia burgdorferi, which is transmitted to humans from feeding ticks. Justin Radolf and colleagues, at the University of Connecticut Health Center, Farmington, have now visualized the microbe moving through the feeding tick and determined that it has a biphasic mode of dissemination. (Source: Biology / Biochemistry News From Medical News Today)

Plant Cell and Tissue Culture-A Tool in Biotechnology: Basics and Application by Neumann, Karl-Hermann, Kumar, Ashwani, and Imani, Jafargholi : 2009, IX, 333 pp. 153 illustrations, hardcover. Publisher: Springer, ISBN: 978-3-540-93882-8; e-ISBN: 978-3-540-93883-5.

Applied Biochemistry and Biotechnology — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Basu SK, Goyal A PMID: 19921469 [PubMed - as supplied by publisher] (Source: Applied Biochemistry and Biotechnology)

Synthesis of orthogonally protected L: -threo-beta-ethoxyasparagine.

Amino Acids — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Spengler J, Pelay M, Tulla-Puche J, Albericio F Orthogonally protected L: -threo-beta-ethoxyasparagine (Fmoc-EtOAsn(Trt)-OH, 1) was synthesized from diethyl (2S,3S)-2-azido-3-hydroxysuccinate 2 in eight steps as a building block for solid-phase peptide synthesis. The starting material is easily available in multi-gram scale from D: -diethyltartrate. The transformation steps reported here are robust and scalable. Thus, a significant amount of 1 (1.8 g) was obtained in 21% overall yield. The synthesis reported is also expected to be useful for the preparation of other O-substituted L: -threo-beta-hydroxyasparagine derivatives. PMID: 19921395 [PubMed - as supplied by publisher] (Source: Amino Acids)

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The effects of a low protein diet on amino acids and enzymes in the serine synthesis pathway in mice.

Amino Acids — Tue, 17 Nov 2009 00:00:00 +0100

In this study, the levels of amino acids and enzymes in the L: -serine biosynthetic pathway were examined in the forebrain, cerebellum, liver, and kidney after the exposure of mice to protein-restricted diets. The levels of L: -serine, D: -serine, and L: -serine-O-phosphate were quantified by HPLC and quantitative Western blotting was used to measure changes in protein levels of five enzymes in the pathway. The L: -serine biosynthetic enzyme phosphoserine phosphatase was strongly upregulated, while the serine degradative enzymes serine racemase and serine dehydratase were downregulated in the livers and kidneys of mice fed low (6%) or very low (2%) protein diets for 2 weeks compared with mice fed a normal diet (18% protein). No changes in these enzymes were seen in the brain. The levels of...

Injectable, Highly Flexible, and Thermosensitive Hydrogels Capable of Delivering Superoxide Dismutase.

Biomacromolecules — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Li Z, Wang F, Roy S, Sen CK, Guan J Injectable hydrogels are attractive for cell and drug delivery. In this work, we synthesized a family of injectable, biodegradable, fast gelling and thermosensitive hydrogels based on N-isopropylacrylamide (NIPAAm), acrylic acid (AAc), dimethyl-gamma-butyrolactone acrylate (DBA), and 2-hydroxyethyl methacrylate-poly(trimethylene carbontate) (HEMAPTMC) macromer. Type I collagen was composited with the hydrogels to improve their biocompatibility. The hydrogel copolymer solutions were readily injectable at 4 degrees C. The solutions exhibited thermal transition temperatures ranging from 23.6 to 24.5 degrees C and were capable of gelation within 7 s at 37 degrees C to form highly flexible and soft hydrogels with moduli from 39 to 119 KPa and bre...

Enzyme-Catalyzed Polycondensation of Polyester Macrodiols with Divinyl Adipate: A Green Method for the Preparation of Thermoplastic Block Copolyesters.

Biomacromolecules — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Dai S, Xue L, Zinn M, Li Z Enzyme-catalyzed polycondensation for the synthesis of block copolymers was reported for the first time. Thermoplastic block copolyesters containing poly[(R)-3-hydroxybutyrate] (PHB) and poly[(R)-3-hydroxyoctanoate] (PHO) blocks were enzymatically prepared by one- or two-step lipase-catalyzed polycondensation. Novozym 435-catalyzed reaction of PHB-diol (M(n) of 3100 g/mol, GPC), PHO-diol (M(n) of 3200 g/mol, GPC), and divinyl adipate gave block poly(HB-co-HO) (M(n) of 9800 g/mol, GPC) with randomly arranged blocks in 55% yield. In two-step polycondensations, Novozym 435-catalyzed reaction of PHB-diol and divinyl adipate afforded 73% of PHB containing two vinyl ester end groups (M(n) of 2700 g/mol, GPC), which was further reacted with PHO-diol in the ...

Preparation of Thermoresponsive Anionic Copolymer Brush Surfaces for Separating Basic Biomolecules.

Biomacromolecules — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Nagase K, Kobayashi J, Kikuchi A, Akiyama Y, Kanazawa H, Annaka M, Okano T Poly(N-isopropylacrylamide-co-acrylic acid-co-N-tert-butylacrylamide) (poly(IPAAm-co-AAc-co-tBAAm) brush grafted silica beads were prepared through a surface-initiated atom transfer radical polymerization (ATRP) with CuCl/CuCl(2)/Me(6)TREN catalytic system in 2-propanol at 25 degrees C for 4 h. The prepared beads were characterized by chromatographic analysis. Basic analytes, catecholamine derivatives, and angiotensin peptides could be separated by a short column length containing the beads because of its high densely grafted copolymer structure. Chromatograms for catecholamine derivatives were obtained with high resolution peaks due to their electrostatic and hydrophobic interactions to the densely gra...