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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 12.

Weight of Embalming Fluid - Did You Know?
I was reading an MSN article about how, if you donate your body to science, it may be rejected if you are overweight. The problem is a combination of lack ...Read Full Post
Source: About.com Chemistry - February 22, 2013 Category: Chemistry Source Type: news

Probing Glass Transitions in Thin and Ultrathin Polystyrene Films by Stick–Slip Behavior during Dynamic Wetting of Liquid Droplets on Their Surfaces
MacromoleculesDOI: 10.1021/ma3023734
Source: Macromolecules - February 22, 2013 Category: Chemistry Authors: Biao Zuo, Chao Qian, Donghuan Yan, Yingjun Liu, Wanglong Liu, Hao Fan, Houkuan Tian and Xinping Wang Source Type: research

Correction to Changes in Electronic Properties of Polymeric One-Dimensional {[M(CN)]−}n (M = Au, Ag) Chains Due to Neighboring Closed-Shell Zn(II) or Open-Shell Cu(II) Ions
Inorganic ChemistryDOI: 10.1021/ic400131c
Source: Inorganic Chemistry - February 22, 2013 Category: Chemistry Authors: François Baril-Robert, Xiaobo Li, Michael J. Katz, Andrew R. Geisheimer, Daniel B. Leznoff and Howard Patterson Source Type: research

Synthesis, Microwave Spectrum, and Conformational Properties of 2-Fluoroethyl Azide (FCH2CH2N3)
The Journal of Physical Chemistry ADOI: 10.1021/jp312227t
Source: Journal of Physical Chemistry A - February 22, 2013 Category: Chemistry Authors: Svein Samdal, Harald Møllendal and Jean-Claude Guillemin Source Type: research

Factors Affecting the Carboxylate Shift Upon Formation of Nonheme Diiron-O2 Adducts
Inorganic ChemistryDOI: 10.1021/ic302543n
Source: Inorganic Chemistry - February 22, 2013 Category: Chemistry Authors: Jonathan R. Frisch, Ryan McDonnell, Elena V. Rybak-Akimova and Lawrence Que Source Type: research

Thermally Conductive Aluminum Nitride–Multiwalled Carbon Nanotube/Cyanate Ester Composites with High Flame Retardancy and Low Dielectric Loss
Industrial & Engineering Chemistry ResearchDOI: 10.1021/ie3029569
Source: Industrial and Engineering Chemical Research - February 22, 2013 Category: Chemistry Authors: Ya-nan Mi, Guozheng Liang, Aijuan Gu, Feipeng Zhao and Li Yuan Source Type: research

The Particle Removing Characteristics in a Fixed Valve Tray Column
Industrial & Engineering Chemistry ResearchDOI: 10.1021/ie3027422
Source: Industrial and Engineering Chemical Research - February 22, 2013 Category: Chemistry Authors: Qingli Wang, Xueli Chen and Xin Gong Source Type: research

Vapor and Liquid Sorption in Matrimid Polyimide: Experimental Characterization and Modeling
Industrial & Engineering Chemistry ResearchDOI: 10.1021/ie3027873
Source: Industrial and Engineering Chemical Research - February 22, 2013 Category: Chemistry Authors: M. Minelli, G. Cocchi, L. Ansaloni, M. Giacinti Baschetti, M.G. De Angelis and F. Doghieri Source Type: research

Robust Dirac-Cone Band Structure in the Molecular Kagome Compound (EDT-TTF-CONH2)6[Re6Se8(CN)6]
Inorganic ChemistryDOI: 10.1021/ic302790m
Source: Inorganic Chemistry - February 22, 2013 Category: Chemistry Authors: Sandra Carlsson, Leokadiya Zorina, David R. Allan, J. Paul Attfield, Enric Canadell and Patrick Batail Source Type: research

Multiobjective optimization of biorefineries with economic and safety objectives
A new approach for the incorporation of safety criteria into the selection, location, and sizing of a biorefinery is introduced. In addition to the techno‐economic factors, risk metrics are used in the decision‐making process by considering the cumulative risk associated with key stages of the life cycle of a biorefinery that includes biomass storage and transportation, process conversion into biofuels or bioproducts, and product storage. The fixed cost of the process along with the operating costs for transportation and processing as well as the value of the product are included. An optimization formulation is develop...
Source: AIChE Journal - February 22, 2013 Category: Science Authors: Ali M. El‐Halwagi, Camilo Rosas, José María Ponce‐Ortega, Arturo Jiménez‐Gutiérrez, Mahboobul S. Mannan, Mahmoud M. El‐Halwagi Tags: Process Systems Engineering Source Type: research

Resonance-enhanced multiphoton ionization with circularly polarized light: chiral carbonyls.
Abstract An introduction to the principle and possibilities of the new method of circular dichroism laser mass spectrometry is given and its state of development is reviewed. This method allows enantiosensitive, mass-selective probing of chiral molecules. It is based on the combination of resonance-enhanced multiphoton ionization with circularly polarized light and specially modified time-of-flight mass spectrometry. As an example, application to carbonyls is presented. PMID: 23430178 [PubMed - as supplied by publisher]
Source: Analytical and Bioanalytical Chemistry - February 22, 2013 Category: Chemistry Authors: Boesl U, Bornschlegl A, Logé C, Titze K Tags: Anal Bioanal Chem Source Type: research

Comprehensive analysis of ß-lactam antibiotics including penicillins, cephalosporins, and carbapenems in poultry muscle using liquid chromatography coupled to tandem mass spectrometry.
Abstract A comprehensive method for the quantitative residue analysis of trace levels of 22 ß-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, in poultry muscle by liquid chromatography in combination with tandem mass spectrometric detection is reported. The samples analyzed for ß-lactam residues are hydrolyzed using piperidine in order to improve compound stability and to include the total residue content of the cephalosporin ceftifour. The reaction procedure was optimized using a full experimental design. Following detailed isotope labeling, tandem mass spectrometry studies and exact ...
Source: Analytical and Bioanalytical Chemistry - February 22, 2013 Category: Chemistry Authors: Berendsen BJ, Gerritsen HW, Wegh RS, Lameris S, van Sebille R, Stolker AA, Nielen MW Tags: Anal Bioanal Chem Source Type: research

Light from silicon nanocrystal LEDs
(Helmholtz Association of German Research Centres) Silicon nanocrystals have a size of a few nanometers and possess a high luminous potential. Scientists of KIT and the University of Toronto/Canada have now succeeded in manufacturing silicon-based light-emitting diodes. They are free of heavy metals and can emit light in various colors. The team of chemists, materials researchers, nanoscientists, and opto-electronic experts presents its development in the "Nano Letters" journal (DOI: 10.1021/nl3038689).
Source: EurekAlert! - Biology - February 22, 2013 Category: Biology Source Type: news

Regeneration and control of human fibroblast cell density by intermittently delivered pulsed electric fields
Abstract Proliferative scarring is a human disease with neither available effective treatment nor relevant animal model. One of the hypotheses for scar formation involves deregulation of fibroblast signaling and delayed apoptosis. Here, we introduce a new chemical‐free method for fibroblast density control in culture by intermittently delivered pulsed electric fields (IDPEF), which cause irreversible damage to cell membranes. Using 5–100 pulses with electric field strength of 150 V mm−1, pulse duration 70 µs, and frequency of 1 Hz, we investigated the effects of pulsed electric field application on growth, d...
Source: Biotechnology and Bioengineering - February 22, 2013 Category: Biomedical Science Authors: Alexander Golberg, Marianna Bei, Robert L. Sheridan, Martin L. Yarmush Tags: Article Source Type: research

Production of polymalic acid and malic acid by Aureobasidium pullulans fermentation and acid hydrolysis
Abstract Malic acid is a dicarboxylic acid widely used in the food industry and also a potential C4 platform chemical that can be produced from biomass. However, microbial fermentation for direct malic acid production is limited by low product yield, titer, and productivity due to end‐product inhibition. In this work, a novel process for malic acid production from polymalic acid (PMA) fermentation followed by acid hydrolysis was developed. First, a PMA‐producing Aureobasidium pullulans strain ZX‐10 was screened and isolated. This microbe produced PMA as the major fermentation product at a high titer equivalent to 87....
Source: Biotechnology and Bioengineering - February 22, 2013 Category: Biomedical Science Authors: Xiang Zou, Yipin Zhou, Shang‐Tian Yang Tags: Article Source Type: research

Where To Buy Copper Sulfate Pentahydrate
Copper sulfate pentahydrate (also known as copper sulphate pentahydrate or simply copper sulfate or copper sulphate) is the chemical used to grow bright blue copper sulfate crystals. It's easy to ...Read Full Post
Source: About.com Chemistry - February 22, 2013 Category: Chemistry Source Type: news

Exploring potential chemical markers by metabolomics method for studying the processing mechanism of traditional Chinese medicine using RPLC-Q-TOF/MS: a case study of Radix Aconiti
Conclusions: The proposed strategy proves that RPLC-Q-TOF/MS-based metabolomic analysis does not only explore chemical markers but can also provide a comprehensive understanding of the transformation mechanisms underlying pao zhi.
Source: Chemistry Central Journal - February 22, 2013 Category: Chemistry Authors: Yubo LiYuming WangLina SuLixin LiYanjun Zhang Source Type: research

DSP-PP Cleavage Site [Enzymology]
Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G447↓D448 cleavage site in DSP-PP240 had dramatic effects on cleavage efficiency by the endogenous Sf9 cel...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Yang, R. T., Lim, G. L., Dong, Z., Lee, A. M., Yee, C. T., Fuller, R. S., Ritchie, H. H. Tags: Glycobiology and Extracellular Matrices Source Type: research

RabE1c Regulates PEX7 Function [Cell Biology]
In this study, we performed proteomic analysis to identify PEX7-binding proteins using transgenic Arabidopsis expressing green fluorescent protein (GFP)-tagged PEX7. Our analysis identified RabE1c, a small GTPase, as a PEX7 binding partner. In vivo analysis revealed that GTP-bound RabE1c binds to PEX7 and that a subset of RabE1c localizes to peroxisomes and interacts with PEX7 on the peroxisome membrane. Unlike endogenous PEX7, which is predominantly localized to the cytosol, GFP-PEX7 accumulates abnormally on the peroxisomal membrane and induces degradation of endogenous PEX7, concomitant with a reduction in import of PTS...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Cui, S., Fukao, Y., Mano, S., Yamada, K., Hayashi, M., Nishimura, M. Tags: Plant Biology Source Type: research

HP0892-HP0893 Is a Toxin-Antitoxin Pair of H. pylori [Microbiology]
In this study, we demonstrated that HP0892 binds to HP0893 strongly with a stoichiometry of 1:1, and HP0892-HP0893 interaction occurs mainly between the N-terminal secondary structure elements of HP0892 and the C-terminal region of HP0893. HP0892 cleaved mRNA in vitro, preferentially at the 5′ end of A or G, and the RNase activity of HP0892 was inhibited by HP0893. In addition, heterologous expression of HP0892 in Escherichia coli cells led to cell growth arrest, and the cell toxicity of HP0892 was neutralized by co-expression with HP0893. From these results and a structural comparison with other TA toxins, it is conclud...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Han, K.-D., Ahn, D.-H., Lee, S.-A., Min, Y.-H., Kwon, A.-R., Ahn, H.-C., Lee, B.-J. Tags: Protein Structure and Folding Source Type: research

Molecular Architecture of a PfEMP1{middle dot}ICAM-1 Complex [Microbiology]
The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from CIDR (cysteine-rich interdomain...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Brown, A., Turner, L., Christoffersen, S., Andrews, K. A., Szestak, T., Zhao, Y., Larsen, S., Craig, A. G., Higgins, M. K. Tags: Molecular Bases of Disease Source Type: research

K2P Extracellular Ion Pathway and pHo Gating [Protein Structure and Folding]
Proton-gated TASK-3 K+ channel belongs to the K2P family of proteins that underlie the K+ leak setting the membrane potential in all cells. TASK-3 is under cooperative gating control by extracellular [H+]. Use of recently solved K2P structures allows us to explore the molecular mechanism of TASK-3 cooperative pH gating. Tunnel-like side portals define an extracellular ion pathway to the selectivity filter. We use a combination of molecular modeling and functional assays to show that pH-sensing histidine residues and K+ ions mutually interact electrostatically in the confines of the extracellular ion pathway. K+ ions modula...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Gonzalez, W., Zuniga, L., Cid, L. P., Arevalo, B., Niemeyer, M. I., Sepulveda, F. V. Tags: Membrane Biology Source Type: research

HAS1 Requires High Cellular UDP-GlcNAc Concentration [Glycobiology and Extracellular Matrices]
Mammals have three homologous genes encoding proteins with hyaluronan synthase activity (Has1–3), all producing an identical polymer from UDP-N-acetylglucosamine and UDP-glucuronic acid. To compare the properties of these isoenzymes, COS-1 cells, with minor endogenous hyaluronan synthesis, were transfected with human Has1–3 isoenzymes. HAS1 was almost unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3. This failure of HAS1 to synthesize hyaluronan was compensated by increasing the cellular content of UDP-N-acetyl glucosamine by ∼10-fold with 1 mm glucosamine in the growth medium. Hya...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Rilla, K., Oikari, S., Jokela, T. A., Hyttinen, J. M. T., Karna, R., Tammi, R. H., Tammi, M. I. Tags: Cell Biology Source Type: research

Ubiquitin-Proteasome-dependent Degradation of p300 by SIRT1 [Protein Synthesis and Degradation]
Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy. Here, we show that oral administration of resveratrol, which leads to activation of an NAD+-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice. The pro-hypertrophic co-activator p300 protein but not p300 mRNA was up-regulated in the mdx heart, and resveratrol administration down-regulated the p300 protein level. In cultured cardiomyocytes, cardiomyocyte hypertrophy induced by the α1-agonist phenylephrine was inhibited by the overexpression of SIRT1...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Kuno, A., Hori, Y. S., Hosoda, R., Tanno, M., Miura, T., Shimamoto, K., Horio, Y. Tags: Molecular Bases of Disease Source Type: research

SUMOylation of Glucokinase [Enzymology]
Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic β-cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissue-specific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how post-translational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cell...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Aukrust, I., B&jnodot;orkhaug, L., Negahdar, M., Molnes, J., Johansson, B. B., Muller, Y., Haas, W., Gygi, S. P., Sovik, O., Flatmark, T., Kulkarni, R. N., N&jnodot;olstad, P. R. Tags: Cell Biology Source Type: research

Mechanism of Collagen Fiber Degradation by Cathepsin K [Glycobiology and Extracellular Matrices]
Excessive cathepsin K (catK)-mediated turnover of fibrillar type I and II collagens in bone and cartilage leads to osteoporosis and osteoarthritis. However, little is known about how catK degrades compact collagen macromolecules. The present study is aimed to explore the structural and mechanical consequences of collagen fiber degradation by catK. Mouse tail type I collagen fibers were incubated with either catK or non-collagenase cathepsins. Methods used include scanning electron microscopy, protein electrophoresis, atomic force microscopy, and tensile strength testing. Our study revealed evidence of proteoglycan network ...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Panwar, P., Du, X., Sharma, V., Lamour, G., Castro, M., Li, H., Bromme, D. Tags: Enzymology Source Type: research

Crystal and Solution Structures of Tae4-Tai4 Complex [Microbiology]
The type VI secretion system (T6SS), a multisubunit needle-like apparatus, has recently been found to play a role in interspecies interactions. The Gram-negative bacteria harboring T6SS (donor) deliver the effectors into their neighboring cells (recipient) to kill them. Meanwhile, the cognate immunity proteins were employed to protect the donor cells against the toxic effectors. Tae4 (type VI amidase effector 4) and Tai4 (type VI amidase immunity 4) are newly identified T6SS effector-immunity pairs. Here, we report the crystal structures of Tae4 from Enterobacter cloacae and Tae4-Tai4 complexes from both E. cloacae and Sal...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Zhang, H., , Gao, Z.-Q., Wang, W.-J., Liu, G.-F., Xu, J.-H., Su, X.-D., Dong, Y.-H. Tags: Protein Structure and Folding Source Type: research

Oligomeric A{beta} and Apolipoprotein E/Amyloid-{beta} Complex as Potential Mechanistic Biomarkers for Alzheimer Disease♦ [Papers of the Week]
♦ See referenced article, J. Biol. Chem. 2013, 288, 5914–5926 Soluble oligomeric amyloid-β (oAβ) peptides produced from the proteolytic cleavage of the amyloid precursor protein are implicated in Alzheimer disease (AD). Apolipoprotein E (apoE) isoforms may specifically modulate soluble oAβ levels by forming complexes. Indeed, the primary genetic risk factor in sporadic AD is the APOE4 genotype. However, the apoE/Aβ complex is dynamic, and different detection methods have given inconsistent measurements. In this Paper of the Week, a team led by Mary Jo LaDu at the University of Illinois at Chicago established the ef...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Tags: Molecular Bases of Disease Source Type: research

APOE Genotype Effects on Soluble ApoE/A{beta} Complex Levels [Neurobiology]
In this study, soluble apoE/Aβ levels were lower in E4FAD mice compared with E2FAD and E3FAD mice, thus providing evidence that apoE/Aβ levels isoform-specifically modulate soluble oAβ clearance. Similar results were observed in soluble preparations of human cortical synaptosomes; apoE/Aβ levels were lower in AD patients compared with controls and lower with APOE4 in the AD cohort. In human CSF, apoE/Aβ levels were also lower in AD patients and with APOE4 in the AD cohort. Importantly, although total Aβ42 levels decreased in AD patients compared with controls, oAβ levels increased and were greater with APOE4 in the ...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., Van Eldik, L. J., Fardo, D. W., Estus, S., Bu, G., Gylys, K. H., LaDu, M. J. Tags: Molecular Bases of Disease Source Type: research

Signaling between V-ATPase and Cytohesin-2 [Membrane Biology]
Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1–17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interac...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Hosokawa, H., Dip, P. V., Merkulova, M., Bakulina, A., Zhuang, Z., Khatri, A., Jian, X., Keating, S. M., Bueler, S. A., Rubinstein, J. L., Randazzo, P. A., Ausiello, D. A., Gruber, G., Marshansky, V. Tags: Bioenergetics Source Type: research

Ca2+ Signaling Regulates Na+/H+ Exchange in C. elegans [Membrane Biology]
Membrane proton transporters contribute to pH homeostasis but have also been shown to transmit information between cells in close proximity through regulated proton secretion. For example, the nematode intestinal Na+/H+ exchanger NHX-7 causes adjacent muscle cells to contract by transiently acidifying the extracellular space between the intestine and muscle. NHX-7 operates during a Ca2+-dependent rhythmic behavior and contains several conserved motifs for regulation by Ca2+ input, including motifs for calmodulin and phosphatidylinositol 4,5-bisphosphate binding, protein kinase C- and calmodulin-dependent protein kinase typ...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Allman, E., Waters, K., Ackroyd, S., Nehrke, K. Tags: Signal Transduction Source Type: research

Lipid-Protein Interaction as Structure/Function Determinant [Lipids]
Energy-dependent uphill transport but not energy-independent downhill transport by lactose permease (LacY) is impaired when expressed in Escherichia coli cells or reconstituted in liposomes lacking phosphatidylethanolamine (PE) and containing only anionic phospholipids. The absence of PE results in inversion of the N-terminal half and misfolding of periplasmic domain P7, which are required for uphill transport of substrates. Replacement of PE in vitro by lipids with no net charge (phosphatidylcholine (PC), monoglucosyl diacylglycerol (GlcDAG), or diglucosyl diacylglycerol (GlcGlcDAG)) supported wild type transmembrane topo...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Vitrac, H., Bogdanov, M., Dowhan, W. Tags: Membrane Biology Source Type: research

H. irregulare GH7 Cellobiohydrolase Structure and Dynamics [Computational Biology]
Root rot fungi of the Heterobasidion annosum complex are the most damaging pathogens in temperate forests, and the recently sequenced Heterobasidion irregulare genome revealed over 280 carbohydrate-active enzymes. Here, H. irregulare was grown on biomass, and the most abundant protein in the culture filtrate was identified as the only family 7 glycoside hydrolase in the genome, which consists of a single catalytic domain, lacking a linker and carbohydrate-binding module. The enzyme, HirCel7A, was characterized biochemically to determine the optimal conditions for activity. HirCel7A was crystallized and the structure, refin...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Momeni, M. H., Payne, C. M., Hansson, H., Mikkelsen, N. E., Svedberg, J., Engstrom, A., Sandgren, M., Beckham, G. T., Stahlberg, J. Tags: Enzymology Source Type: research

Signaling through ARAP2 [Signal Transduction]
Focal adhesions (FAs) are dynamic structures that connect the actin cytoskeleton with the extracellular matrix. At least six ADP-ribosylation factor (Arf) GTPase-activating proteins (GAPs), including ARAP2 (an Arf6 GAP), are implicated in regulation of FAs but the mechanisms for most are not well defined. Although Rac1 has been reported to function downstream of Arf6 to control membrane ruffling and cell migration, this pathway has not been directly examined as a regulator of FAs. Here we test the hypothesis that ARAP2 promotes the growth of FAs by converting Arf6·GTP to Arf6·GDP thereby preventing the activation of the ...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Chen, P.-W., Jian, X., Yoon, H.-Y., Randazzo, P. A. Tags: Cell Biology Source Type: research

High-throughput Screen for Small Molecule PLC Inhibitors [Lipids]
Phospholipase C (PLC) isozymes are important signaling molecules, but few small molecule modulators are available to pharmacologically regulate their function. With the goal of developing a general approach for identification of novel PLC inhibitors, we developed a high-throughput assay based on the fluorogenic substrate reporter WH-15. The assay is highly sensitive and reproducible: screening a chemical library of 6280 compounds identified three novel PLC inhibitors that exhibited potent activities in two separate assay formats with purified PLC isozymes in vitro. Two of the three inhibitors also inhibited G protein-coupl...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Huang, W., Barrett, M., Hajicek, N., Hicks, S., Harden, T. K., Sondek, J., Zhang, Q. Tags: Signal Transduction Source Type: research

Proprotein Convertases Process and Inactivate FGE [Cell Biology]
Formylglycine-generating enzyme (FGE) post-translationally converts a specific cysteine in newly synthesized sulfatases to formylglycine (FGly). FGly is the key catalytic residue of the sulfatase family, comprising 17 nonredundant enzymes in human that play essential roles in development and homeostasis. FGE, a resident protein of the endoplasmic reticulum, is also secreted. A major fraction of secreted FGE is N-terminally truncated, lacking residues 34–72. Here we demonstrate that this truncated form is generated intracellularly by limited proteolysis mediated by proprotein convertase(s) (PCs) along the secretory pathwa...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Ennemann, E. C., Radhakrishnan, K., Mariappan, M., Wachs, M., Pringle, T. H., Schmidt, B., Dierks, T. Tags: Cell Biology Source Type: research

DDX6 Regulates VEGF Expression under Hypoxia [Protein Synthesis and Degradation]
Vascular endothelial growth factor A (VEGF) is a crucial proangiogenic factor, which regulates blood vessel supply under physiologic and pathologic conditions. The VEGF mRNA 5′-untranslated region (5′-UTR) bears internal ribosome entry sites (IRES), which confer sustained VEGF mRNA translation under hypoxia when 5′-cap-dependent mRNA translation is inhibited. VEGF IRES-mediated initiation of translation requires the modulated interaction of trans-acting factors. To identify trans-acting factors that control VEGF mRNA translation under hypoxic conditions we established an in vitro translation system based on human ade...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: de Vries, S., Naarmann-de Vries, I. S., Urlaub, H., Lue, H., Bernhagen, J., Ostareck, D. H., Ostareck-Lederer, A. Tags: RNA Source Type: research

Defective Conformational Transition Alters Na+ Pump Signaling [Cell Biology]
The α1 Na/K-ATPase possesses both pumping and signaling functions. Using purified enzyme we found that the α1 Na/K-ATPase might interact with and regulate Src activity in a conformation-dependent manner. Here we further explored the importance of the conformational transition capability of α1 Na/K-ATPase in regulation of Src-related signal transduction in cell culture. We first rescued the α1-knockdown cells by wild-type rat α1 or α1 mutants (I279A and F286A) that are known to be defective in conformational transition. Stable cell lines with comparable expression of wild type α1, I279A, and F286A were characterized....
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Ye, Q., Lai, F., Banerjee, M., Duan, Q., Li, Z., Si, S., Xie, Z. Tags: Membrane Biology Source Type: research

PAR2 and TRPV4 Coupling [Signal Transduction]
G protein-coupled receptors of nociceptive neurons can sensitize transient receptor potential (TRP) ion channels, which amplify neurogenic inflammation and pain. Protease-activated receptor 2 (PAR2), a receptor for inflammatory proteases, is a major mediator of neurogenic inflammation and pain. We investigated the signaling mechanisms by which PAR2 regulates TRPV4 and determined the importance of tyrosine phosphorylation in this process. Human TRPV4 was expressed in HEK293 cells under control of a tetracycline-inducible promoter, allowing controlled and graded channel expression. In cells lacking TRPV4, the PAR2 agonist st...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Poole, D. P., Amadesi, S., Veldhuis, N. A., Abogadie, F. C., Lieu, T., Darby, W., Liedtke, W., Lew, M. J., McIntyre, P., Bunnett, N. W. Tags: Neurobiology Source Type: research

Ebola VP40 Membrane Penetration [Molecular Biophysics]
In this study, we used an array of biophysical experiments and cellular assays along with mutagenesis of VP40 to investigate the role of membrane penetration in VP40 assembly and egress. Here we demonstrate that VP40 is able to penetrate specifically into the plasma membrane through an interface enriched in hydrophobic residues in its C-terminal domain. Mutagenesis of this hydrophobic region consisting of Leu213, Ile293, Leu295, and Val298 demonstrated that membrane penetration is critical to plasma membrane localization, VP40 oligomerization, and viral particle egress. Taken together, VP40 membrane penetration is an impor...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Adu-Gyamfi, E., Soni, S. P., Xue, Y., Digman, M. A., Gratton, E., Stahelin, R. V. Tags: Membrane Biology Source Type: research

Robustness in IDH Regulation [Enzymology]
In this study, we use extensive biochemical data and algebraic modeling to develop and analyze a model that shows how robust behavior arises in the isocitrate dehydrogenase (IDH) regulatory system of Escherichia coli, which was shown in 1985 to experimentally exhibit robustness. E. coli IDH is regulated by reversible phosphorylation catalyzed by the bifunctional isocitrate dehydrogenase kinase/phosphatase (IDHKP), and the level of IDH activity determines whether carbon flux is directed through the glyoxylate bypass (for growth on two-carbon substrates) or the full tricarboxylic acid cycle. Our model, which incorporates rec...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Dexter, J. P., Gunawardena, J. Tags: Computational Biology Source Type: research

Analysis of 5-HT3 Receptor Thermostability [Molecular Biophysics]
Pentameric ligand-gated ion channels (LGICs) play an important role in fast synaptic signal transduction. Binding of agonists to the β-sheet-structured extracellular domain opens an ion channel in the transmembrane α-helical region of the LGIC. How the structurally distinct and distant domains are functionally coupled for such central transmembrane signaling processes remains an open question. To obtain detailed information about the stability of and the coupling between these different functional domains, we analyzed the thermal unfolding of a homopentameric LGIC, the 5-hydroxytryptamine receptor (ligand binding, second...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Tol, M. B., Deluz, C., Hassaine, G., Graff, A., Stahlberg, H., Vogel, H. Tags: Protein Structure and Folding Source Type: research

Inhibitory Mechanism for Nuclear Export of Myocardin [Gene Regulation]
Myocardin (Mycd), a key factor in smooth muscle cell differentiation, is constitutively located in the nucleus, whereas myocardin-related transcription factors A and B (MRTF-A/B) reside mostly in the cytoplasm and translocate to the nucleus in a Rho-dependent manner. Here, we investigated the nuclear export of Mycd family members. They possess two leucine-rich sequences: L1 in the N terminus and L2 in the Gln-rich domain. Although L2 (but not L1) served as a CRM1-binding site for Mycd, CRM1-mediated nuclear export did not affect its subcellular localization. Serum response factor (SRF) competitively inhibited Mycd/CRM1 int...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Hayashi, K., Morita, T. Tags: Cell Biology Source Type: research

AMPK Activation by Emodin [Cell Biology]
AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [14C]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carb...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Song, P., Kim, J. H., Ghim, J., Yoon, J. H., Lee, A., Kwon, Y., Hyun, H., Moon, H.-Y., Choi, H.-S., Berggren, P.-O., Suh, P.-G., Ryu, S. H. Tags: Metabolism Source Type: research

Impact of p110{alpha} Inhibitors in Primary Lymphocytes [Signal Transduction]
Class IA phosphoinositide 3-kinase (PI3K) is essential for clonal expansion, differentiation, and effector function of B and T lymphocytes. The p110δ catalytic isoform of PI3K is highly expressed in lymphocytes and plays a prominent role in B and T cell responses. Another class IA PI3K catalytic isoform, p110α, is a promising drug target in cancer but little is known about its function in lymphocytes. Here we used highly selective inhibitors to probe the function of p110α in lymphocyte responses in vitro and in vivo. p110α inhibition partially reduced B cell receptor (BCR)-dependent AKT activation and proliferation, an...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: So, L., Yea, S. S., Oak, J. S., Lu, M., Manmadhan, A., Ke, Q. H., Janes, M. R., Kessler, L. V., Kucharski, J. M., Li, L.-S., Martin, M. B., Ren, P., Jessen, K. A., Liu, Y., Rommel, C., Fruman, D. A. Tags: Immunology Source Type: research

Assembly of Mitochondrial Complex I in Arabidopsis [Bioenergetics]
Subcomplexes of mitochondrial respiratory complex I (CI; EC 1.6.5.3) are shown to turn over in vivo, and we propose a role in an ancestral assembly pathway. By progressively labeling Arabidopsis cell cultures with 15N and isolating mitochondria, we have identified CI subcomplexes through differences in 15N incorporation into their protein subunits. The 200-kDa subcomplex, containing the ancestral γ-carbonic anhydrase (γ-CA), γ-carbonic anhydrase-like, and 20.9-kDa subunits, had a significantly higher turnover rate than intact CI or CI+CIII2. In vitro import of precursors for these CI subunits demonstrated rapid generati...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Li, L., Nelson, C. J., Carrie, C., Gawryluk, R. M. R., Solheim, C., Gray, M. W., Whelan, J., Millar, A. H. Tags: Plant Biology Source Type: research

Structure-Function Analysis of HMP-1/{alpha}-Catenin [Developmental Biology]
Stable intercellular adhesions formed through the cadherin-catenin complex are important determinants of proper tissue architecture and help maintain tissue integrity during morphogenetic movements in developing embryos. A key regulator of this stability is α-catenin, which connects the cadherin-catenin complex to the actin cytoskeleton. Although the C-terminal F-actin-binding domain of α-catenin has been shown to be crucial for its function, a more detailed in vivo analysis of discrete regions and residues required for actin binding has not been performed. Using Caenorhabditis elegans as a model system, we have characte...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Maiden, S. L., Harrison, N., Keegan, J., Cain, B., Lynch, A. M., Pettitt, J., Hardin, J. Tags: Cell Biology Source Type: research

SSRIs Inhibit {beta} Cell Function [Molecular Bases of Disease]
Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used for the treatment of mood and anxiety disorders. Here, we demonstrate that incubation (2 h) of murine islets or Min6 β cell line with the SSRIs paroxetine, fluoxetine, or sertraline inhibited insulin-induced Tyr phosphorylation of insulin receptor substrate (IRS)-2 protein and the activation of its downstream targets Akt and the ribosomal protein S6 kinase-1 (S6K1). Inhibition was dose-dependent with half-maximal effects at ∼15–20 μm. It correlated with a rapid dephosphorylation and activation of the IRS kinase GSK3β. Introduction of GSK3β siR...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Isaac, R., Boura-Halfon, S., Gurevitch, D., Shainskaya, A., Levkovitz, Y., Zick, Y. Tags: Signal Transduction Source Type: research

Mechanism of HCV NS3-NS4A Protease Inhibitor Resistance [Protein Structure and Folding]
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance ...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: O'Meara, J. A., Lemke, C. T., Godbout, C., Kukol&jnodot;, G., Lagace, L., Moreau, B., Thibeault, D., White, P. W., Llinas–Brunet, M. Tags: Molecular Bases of Disease Source Type: research

Analysis of PD-causing PINK1 Mutations [Molecular Bases of Disease]
Mutations in PINK1 (PTEN-induced putative kinase 1) are tightly linked to autosomal recessive Parkinson disease (PD). Although more than 50 mutations in PINK1 have been discovered, the role of these mutations in PD pathogenesis remains poorly understood. Here, we characterized 17 representative PINK1 pathogenic mutations in both mammalian cells and Drosophila. These mutations did not affect the typical cleavage patterns and subcellular localization of PINK1 under both normal and damaged mitochondria conditions in mammalian cells. However, PINK1 mutations in the kinase domain failed to translocate Parkin to mitochondria and...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Song, S., Jang, S., Park, J., Bang, S., Choi, S., Kwon, K.-Y., Zhuang, X., Kim, E., Chung, J. Tags: Neurobiology Source Type: research