bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of annexin I with early endosomes is regulated by Ca2+ and requires an intact N-terminal domain.
Authors: Seemann J , Weber K , Osborn M , Parton R G , Gerke V
Published: August 2013

Annexin I is a member of a multigene family of Ca2+/phospholipid-binding proteins and a major substrate for the epidermal growth factor (EGF) receptor kinase, which has been implicated in membrane-related events along the endocytotic pathway, in particular in the sorting of internalized EGF receptors occurring in the multivesicular body. We analyzed in detail the intracellular distribution of this annexin by cell fractionation and immunoelectron microscopy. These studies used polyclonal as well as a set of species-specific monoclonal antibodies, whose epitopes were mapped to the lateral surface of the molecule next to a region thought to be involved in vesicle aggregation. Unexpectedly, the majority of annexin I was identified on early and not on multivesicular endosomes in a form that required micromolar levels of Ca2+ for the association. The specific cofractionation with early endosomes was also observed in transfected baby hamster kidney cells when the intracellular fate of ectopically expressed porcine annexin I was analyzed by using the species-specific monoclonal antibodies in Western blots of subcellular fractions. Interestingly, a truncation of the N-terminal 26, but not the N-terminal 13 residues of annexin I altered its intracellular distribution, shifting it from fractions containing early to those containing late and multivesicular endosomes. These findings underscore the regulatory importance of the N-terminal domain and provide evidence for an involvement of annexin I in early endocytotic processes.
Phorbol 12-myristate 13-acetate down-regulates Na,K-ATPase independent of its protein kinase C site: decrease in basolateral cell surface area.
Authors: Beron J , Forster I , Beguin P , Geering K , Verrey F
Published: August 2013

The effect of protein kinase C (PKC) stimulation on the pump current (Ip) generated by the Na,K-ATPase was measured in A6 epithelia apically permeabilized with amphotericin B. Phorbol 12-myristate 13-acetate (PMA) produced a decrease in Ip carried by sodium pumps containing the endogenous Xenopus laevis or transfected Bufo marinus alpha 1 subunits (approximately 30% reduction within 25 min, maximum after 40 min) independent of the PKC phosphorylation site (T15A/S16A). In addition to this major effect of PMA, which was independent of the intracellular sodium concentration and was prevented by the PKC inhibitor bisindolylmaleimide GF 109203X (BIM), another BIM-resistant, PKC site-independent decrease was observed when the Ip was measured at low sodium concentrations (total reduction approximately 50% at 5 mM sodium). Using ouabain binding and cell surface biotinylation, stimulation of PKC was shown to reduce surface Na,K-ATPase by 14 to 20% within 25 min. The same treatment stimulated fluid phase endocytosis sevenfold and decreased by 16.5% the basolateral cell surface area measured by transepithelial capacitance measurements. In conclusion, PKC stimulation produces a decrease in sodium pump function which can be attributed, to a large extent, to a withdrawal of sodium pumps from the basolateral cell surface independent of their PKC site. This reduction of the number of sodium pumps is parallel to a decrease in basolateral membrane area.
Association of syntaxin 3 and vesicle-associated membrane protein (VAMP) with H+/K(+)-ATPase-containing tubulovesicles in gastric parietal cells.
Authors: Peng X R , Yao X , Chow D C , Forte J G , Bennett M K
Published: August 2013

H+/K(+)-ATPase is the proton pump in the gastric parietal cell that is responsible for gastric acid secretion. Stimulation of acid secretion is associated with a reorganization of the parietal cells resulting in the incorporation of H+/K(+)-ATPase from a cytoplasmic membrane pool, the tubulovesicle compartment, into the apical canalicular membrane. To better characterize the role of membrane trafficking events in the morphological and physiological changes associated with acid secretion from parietal cells, we have characterized the expression and localization of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in these cells. Each of the six different SNARE proteins examined [syntaxins 1 through 4 of 25-kDa synaptosome-associated protein, and vesicle-associated membrane protein] were found to be expressed in parietal cells. Furthermore, two of these SNAREs, vesicle-associated membrane protein and syntaxin 3, were associated with H+/K(+)-ATPase-containing tubulovesicles while the remainder were excluded from this compartment. The expression of syntaxin 1 and synaptosome-associated protein of 25 kDa in parietal cells, two SNAREs previously thought to be restricted to neuroendocrine tissues, suggests that parietal cells may utilize membrane trafficking machinery that is similar to that utilized for regulated exocytosis in neurons. Furthermore, the localization of syntaxin 3, a putative target membrane SNARE, to the tubulovesicle compartment indicates that syntaxin 3 may have an alternative function. These observations support a role for intracellular membrane trafficking events in the regulated recruitment of H+/K(+)-ATPase to the plasma membrane after parietal cell stimulation.
Modification of annexin II expression in PC12 cell lines does not affect Ca(2+)-dependent exocytosis.
Authors: Graham M E , Gerke V , Burgoyne R D
Published: August 2013

The Ca2+/phospholipid/cytoskeletal-binding protein annexin II has been proposed to play an important role in Ca(2+)-dependent exocytosis; however, the evidence for this role is inconclusive. More direct evidence obtained by manipulating annexin II levels in cells is still required. We have attempted to do this by generating stably transfected PC12 cell lines expressing proteins which elevate or lower functional annexin II levels and using these cell lines to investigate Ca(2+)-dependent exocytosis. Three cell lines were generated: one expressing an annexin II mutant which aggregates annexin II in at least a proportion of the cells, thereby removing functional protein from the cell; a mixed clonal cell line constitutively overexpressing human annexin II; and a clonal cell line capable of over-expressing annexin II in the presence of sodium butyrate. After digitonin permeabilization, Ca(2+)-dependent dopamine release from these cell lines was compared with that from control nontransfected cells, and, in addition, release was compared in induced to uninduced cells. There were no significant differences in Ca(2+)-dependent exocytosis between any of the transfected cell lines before or after induction and the control cells. In addition, nontransfected PC12 cells treated with nerve growth factor, which elevates annexin II levels severalfold, failed to increase Ca(2+)-dependent exocytosis after digitonin permeabilization, compared with control cells. We conclude that annexin II is not an important regulator of Ca(2+)-dependent exocytosis in PC12 cells.
Fast receptor-induced formation of glycerophosphoinositol-4-phosphate, a putative novel intracellular messenger in the Ras pathway.
Authors: Falasca M , Carvelli A , Iurisci C , Qiu R G , Symons M H , Corda D
Published: August 2013

Glycerophosphoinositols are phosphoinositide metabolites whose levels are constitutively elevated in Ras-transformed cells. Here, we show that one of these compounds, glycerophosphoinositol-4-phosphate (GroPIns-4-P) responds acutely to the stimulation of the epidermal growth factor receptor, with a fast, massive and transient increase. The mechanism leading to GroPIns-4-P formation involves the activation of phosphoinositide-3 kinase and the small GTP-binding protein Rac, since GroPIns-4-P was neither formed in cells expressing the dominant negative form of Rac nor in cells treated with the phosphoinositide-3 kinase inhibitor wortmannin. GroPIns-4-P has been previously shown to inhibit adenylyl cyclase. Accordingly, epidermal growth factor also decreased the basal, cholera toxin-stimulated, and forskolin-stimulated cyclic AMP levels with kinetics similar to those of GroPIns-4-P formation, suggesting that GroPIns-4-P mediates this inhibitory effect. The hormone-induced formation of GroPIns-4-P was detected in several cell lines of various origin, suggesting that GroPIns-4-P is a novel intracellular messenger of the Ras pathway, possibly able to convey information from tyrosine kinase receptors to the cyclic AMP cascade.
A chimeric serine/threonine kinase receptor system reveals the potential of multiple type II receptors to cooperate with transforming growth factor-beta type I receptor.
Authors: Muramatsu M , Yan J , Eto K , Tomoda T , Yamada R , Arai K
Published: August 2013

Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.
Immunoisolation and partial characterization of endothelial plasmalemmal vesicles (caveolae).
Authors: Stan R V , Roberts W G , Predescu D , Ihida K , Saucan L , Ghitescu L , Palade G E
Published: August 2013

Plasmalemmal vesicles (PVs) or caveolae are plasma membrane invaginations and associated vesicles of regular size and shape found in most mammalian cell types. They are particularly numerous in the continuous endothelium of certain microvascular beds (e.g., heart, lung, and muscles) in which they have been identified as transcytotic vesicular carriers. Their chemistry and function have been extensively studied in the last years by various means, including several attempts to isolate them by cell fractionation from different cell types. The methods so far used rely on nonspecific physical parameters of the caveolae and their membrane (e.g., size-specific gravity and solubility in detergents) which do not rule out contamination from other membrane sources, especially the plasmalemma proper. We report here a different method for the isolation of PVs from plasmalemmal fragments obtained by a silica-coating procedure from the rat lung vasculature. The method includes sonication and flotation of a mixed vesicle fraction, as the first step, followed by specific immunoisolation of PVs on anticaveolin-coated magnetic microspheres, as the second step. The mixed vesicle fraction, is thereby resolved into a bound subfraction (B), which consists primarily of PVs or caveolae, and a nonbound subfraction (NB) enriched in vesicles derived from the plasmalemma proper. The results so far obtained indicate that some specific endothelial membrane proteins (e.g., thrombomodulin, functional thrombin receptor) are distributed about evenly between the B and NB subfractions, whereas others are restricted to the NB subfraction (e.g., angiotensin converting enzyme, podocalyxin). Glycoproteins distribute unevenly between the two subfractions and antigens involved in signal transduction [e.g., annexin II, protein kinase C alpha, the G alpha subunits of heterotrimeric G proteins (alpha s, alpha q, alpha i2, alpha i3), small GTP-binding proteins, endothelial nitric oxide synthase, and nonreceptor protein kinase c-src] are concentrated in the NB (plasmalemma proper-enriched) subfraction rather than in the caveolae of the B subfraction. Additional work should show whether discrepancies between our findings and those already recorded in the literature represent inadequate fractionation techniques or are accounted for by chemical differentiation of caveolae from one cell type to another.
Subcellular distribution and targeting of the intracellular chloride channel p64.
Authors: Redhead C , Sullivan S K , Koseki C , Fujiwara K , Edwards J C
Published: August 2013

p64 is an intracellular chloride channel originally identified in bovine kidney microsomes. Using a combination of immunofluorescent and electron microscopic technique, we demonstrate that p64 resides in the limiting membranes of perinuclear dense core vesicles which appear to be regulated secretory vesicles. Heterologous expression of p64 in PancI cells, a cell type which does not normally express p64, results in targeting to a similar compartment. Mutagenesis experiments demonstrate that both the N- and C-terminal domains of the protein independently contribute to subcellular distribution of the protein. The C-terminal domain functions to prevent expression of p64 on the plasma membrane and the N-terminal domain is necessary to deliver p64 to the appropriate membrane compartment.
A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant.
Authors: Tang Y , Ramakrishnan C , Thomas J , DeFranco D B
Published: August 2013

All steroid receptors possess a bipartite nuclear localization signal sequence (NLS) that localizes within the second zinc finger of their DNA-binding domain. Fine-structure mapping of the rat glucocorticoid receptor (rGS) NLS identified a composite signal composed of three distinct proto-NLSs that function effectively when present in unique pairs. At least one of the rGR proto-NLSs appears to influence receptor trafficking within the nucleus, as revealed by a unique nuclear staining pattern of receptors possessing a point mutation (i.e., arginine at position 496; R496), at proto-NLS, pNLS-2. Specifically, carboxyl-terminal-truncated rGRs possessing various point mutations at R496 localized within a limited number of large foci in nuclei of transiently transfected COS-1 cells. R496 mutations did not affect subnuclear targeting when present in full-length rGR, reflecting a protective effect of the receptor's ligand-binding domain that can be exerted in cis and in trans. The effects of rGR R496 mutations on subnuclear targeting were not autonomous because we also observed a coincident localization of hsp70, the 70-kDa heat shock protein, within nuclear foci that include r496 mutant receptors. The elimination of R496 mistargeting by overexpression of an hsp70 partner (i.e., the DnaJ homologue, HDJ-2/HSDJ) suggests that the hsp70/DnaJ chaperone system is mobilized to specific sites within the nucleus in response to inappropriate targeting or folding of specific mutant receptors. HDJ-2/HSDJ overexpression also corrects defective transactivation and transrepression activity of R496 mutant GRs. Thus, molecular chaperones, such as members of the hsp70 and DnaJ families, may survey the nucleus for misfolded proteins and actively participate in their refolding into biologically active conformational states.
Identification of detergent-resistant plasma membrane microdomains in dictyostelium: enrichment of signal transduction proteins.
Authors: Xiao Z , Devreotes P N
Published: August 2013

Unlike most other cellular proteins, the chemoattractant receptor, cAR1, of Dictyostelium is resistant to extraction by the zwitterionic detergent, CHAPS. We exploited this property to isolate a subcellular fraction highly enriched in cAR1 by flotation of CHAPS lysates of cells in sucrose density gradients. Immunogold electron microscopy studies revealed a homogeneous preparation of membrane bilayer sheets. This preparation, designated CHAPS-insoluble floating fraction (CHIEF), also contained a defined set of 20 other proteins and a single uncharged lipid. Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation. The cell surface phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase (ACA), were specifically localized in these structures, whereas the cell adhesion molecule gp80, most of the major cell surface membrane proteins, cytoskeletal components, the actin-binding integral membrane protein ponticulin, and G-protein alpha- and beta-subunits were absent. Overall, CHIFF represents about 3-5% of cell externally exposed membrane proteins. All of these results indicate that CHIFF is derived from specialized microdomains of the plasma membrane. The method of isolation is analogous to that of caveolae. However, we were unable to detect distinct caveolae-like structures on the cell surface associated with cAR1, which showed a diffuse staining profile. The discovery of CHIFF facilitates the purification of cAR1 and related signaling proteins and the biochemical characterization of receptor-mediated processes such as G-protein activation and desensitization. It also has important implications for the "fluid mosaic" model of the plasma membrane structures.
Mitogen-activated protein kinase/extracellular signal-regulated kinase 2 regulates cytoskeletal organization and chemotaxis via catalytic and microtubule-specific interactions.
Authors: Reszka A A , Bulinski J C , Krebs E G , Fischer E H
Published: August 2013

The extracellular signal-regulated kinases (ERKs) 1 and 2 are mitogen-activated protein kinases that act as key components in a signaling cascade linking growth factor receptors to the cytoskeleton and the nucleus. ERK2 mutants have been used to alter cytoskeletal regulation in Chinese hamster ovary cells without affecting cell growth or feedback signaling. Mutation of the unique loop L6 (residues 91-95), which is in a portion of the molecule that is cryptic upon the binding of ERK2 to the microtubules (MTs), generated significant morphological alterations. Most notable phenotypes were observed after expression of a combined mutant incorporating changes to both L6 and the TEY phosphorylation lip, including a 70% increase in cell spreading. Actin stress fibers in these cells, which normally formed a single broad parallel array, were arranged in three or more orientations or in fan-like arrays. MTs, which ordinarily extend longitudinally from the centrosome, spread radially, covering a larger surface area. Single, but not the double, mutations of the Thr and Tyr residues of the TEY phosphorylation lip caused a ca. 25% increase in cell spreading, accompanied by a threefold increase in chemotactic cell migration. Mutation of Lys-52 triggered a 48% increase in cell spreading but no alteration to chemotaxis. These findings suggest that wild-type ERK2 inhibits the organization of the cytoskeleton, the spreading of the cell, and chemotactic migration. This involves control of the orientation of actin and MTs and the positioning of focal adhesions via regulatory interactions that may occur on the MTs.
SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities.
Authors: Verma R , Feldman R M , Deshaies R J
Published: August 2013

Traversal from G1 to S-phase in cycling cells of budding yeast is dependent on the destruction of the S-phase cyclin/CDK inhibitor SIC1. Genetic data suggest that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the action of CDC34, CDC4, CDC53, SKP1, and CLN/CDC28. As a first step in defining the functions of the corresponding gene products, we have reconstituted SIC1 multiubiquitination in DEAE-fractionated yeast extract. Multiubiquitination depends on cyclin/CDC28 protein kinase and the CDC34 ubiquitin-conjugating enzyme. Ubiquitin chain formation is abrogated in cdc4ts mutant extracts and assembly restored by the addition of exogenous CDC4, suggesting a direct role for this protein in SIC1 multiubiquitination. Deletion analysis of SIC1 indicates that the N-terminal 160 residues are both necessary and sufficient to serve as substrate for CDC34-dependent ubiquitination. The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1.
Complexes between nascent polypeptides and their molecular chaperones in the cytosol of mammalian cells.
Authors: Eggers D K , Welch W J , Hansen W J
Published: August 2013

Folding of newly synthesized proteins in vivo is believed to be facilitated by the cooperative interaction of a defined group of proteins known as molecular chaperones. We investigated the direct interaction of chaperones with nascent polypeptides in the cytosol of mammalian cells by multiple methods. A new approach using a polyclonal antibody to puromycin allowed us to tag and capture a population of truncated nascent polypeptides with no bias as to the identity of the bound chaperones. In addition, antibodies that recognize the cytosolic chaperones hsp70, CCT (TRiC), hsp40, p48 (Hip), and hsp90 were compared on the basis of their ability to coprecipitate nascent polypeptides, both before and after chemical cross-linking. By all three approaches, hsp70 was found to be the predominant chaperone bound to nascent polypeptides. The interaction between hsp70 and nascent polypeptides is apparently dynamic under physiological conditions but can be stabilized by depletion of ATP or by cross-linking. The cytosolic chaperonin CCT was found to bind primarily to full-length, newly synthesized actin, and tubulin. We demonstrate and caution that nascent polypeptides have a propensity for binding many proteins nonspecifically in cell lysates. Although current models of protein folding in vivo have described additional components in contact with nascent polypeptides, our data indicate that the hsp70 and, perhaps, the hsp90 families are the predominant classes of molecular chaperones that interact with the general population of cytosolic nascent polypeptides.
A role for the SHP-2 tyrosine phosphatase in nerve growth-induced PC12 cell differentiation.
Authors: Wright J H , Drueckes P , Bartoe J , Zhao Z , Shen S H , Krebs E G
Published: August 2013

SHP-1 and SHP-2 are intracellular protein tyrosine phosphatases containing two adjacent src homology 2 domains that target these phosphatases to cell surface receptor signaling complexes and play a role in receptor signal transduction. In this report the PC12 cell system was used to investigate the potential roles of SHP-1 and SHP-2 in the induction of neuronal differentiation by nerve growth factor (NGF). By using neurite outgrowth as a marker for differentiation, the effects of transfected constructs of SHP-1 and SHP-2 were assessed. Overexpression of a catalytically inactive SHP-2, but not a catalytically inactive SHP-1, blocked NGF-stimulated neurite outgrowth. The mitogen-activated protein kinase (MAPK) signaling cascade is important for the morphological differentiation in PC12 cells, and both SHP-1 and SHP-2 have been implicated to act upstream of MAPK in other receptor signaling systems. A positive role for SHP-2 but not SHP-1 in the activation of MAPK by NGF was demonstrated by introduction of the SHP-2 phosphatase mutants along with hemagglutinin-tagged MAPK. Coexpression studies with the SHP-2 mutant along with mutant forms of MAPK kinase suggested that SHP-2 functions upstream of MAPK kinase and MAPK in NGF-induced neurite outgrowth.
Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells.
Authors: She H Y , Rockow S , Tang J , Nishimura R , Skolnik E Y , Chen M , Margolis B , Li W
Published: August 2013

Src homology domains [i.e., Src homology domain 2 (SH2) and Src homology domain 3 (SH3)] play a critical role in linking receptor tyrosine kinases to downstream signaling networks. A well-defined function of the SH3-SH2-SH3 adapter Grb2 is to link receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to the p21ras-signaling pathway. Grb2 has also been implicated to play a role in growth factor-regulated actin assembly and receptor endocytosis, although the underlying mechanisms remain unclear. In this study, we show that Grb2 interacts through its SH3 domains with the human Wiskott-Aldrich syndrome protein (WASp), which plays a role in regulation of the actin cytoskeleton. We find that WASp is expressed in a variety of cell types and is exclusively cytoplasmic. Although the N-terminal SH3 domain of Grb2 binds significantly stronger than the C-terminal SH3 domain to WASp, full-length Grb2 shows the strongest binding. Both phosphorylation of WASp and its interaction with Grb2, as well as with another adapter protein Nck, remain constitutive in serum-starved or epidermal growth factor-stimulated cells. WASp coimmunoprecipitates with the activated EGFR after epidermal growth factor stimulation. Purified glutathione S-transferase-full-length-Grb2 fusion protein, but not the individual domains of Grb2, enhances the association of WASp with the EGFR, suggesting that Grb2 mediates the association of WASp with EGFR. This study suggests that Grb2 translocates WASp from the cytoplasm to the plasma membrane and the Grb2-WASp complex may play a role in linking receptor tyrosine kinases to the actin cytoskeleton.
Uric acid and risk of heart failure: a systematic review and meta‐analysis
Authors: Huang He , Huang Baotao , Li Yulin , Huang Yan , Li Jing , Yao Hongmei , Jing Xianchao , Chen Jianrong , Wang Ji
Published: August 2013

Aims

We aimed to perform a systematic review and meta‐analysis to assess the association between serum uric acid and incident heart failure (HF)/prognosis of HF patients.

Methods and results

A systematic electronic literature search was conducted in Embase (Ovid SP, from 1974 to May 2013), Medline (Ovid SP, from 1946 to May 2013), and the Chinese Biomedical Literature Database (CBM, from 1978 to May 2013) to identify studies reporting on the association between serum uric acid and HF. Either a random effects model or a fixed effects model was used for pooling data. Five studies reporting on incident HF and 28 studies reporting on the adverse outcomes of HF patients were included. The results showed that hyperuricaemia was associated with an increased risk of incident HF [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.41–1.94], and the risk of all‐cause mortality (HR 2.15, 95% CI 1.64–2.83), cardiovascular mortality (HR 1.45, 95% CI 1.18–1.78), and the composite of death or cardiac events (HR 1.39, 95% CI 1.18–1.63) in HF patients. For every 1 mg/dL increase in serum uric acid, the odds of development of HF increased by 19% (HR 1.19, 95% CI 1.17–1.21), and the risk of all‐cause mortality and the composite endpoint in HF patients increased by 4% (HR 1.04, 95% CI 1.02–1.06) and 28% (HR 1.28, 95% CI 0.97–1.70), respectively. Subgroup analyses supported the positive association between serum uric acid and HF.

Conclusions

Elevated serum uric acid is associated with an increased risk of incident HF and adverse outcomes in HF patients.
Voltage-dependent intrinsic bursting in olfactory bulb Golgi cells
Authors: Pressler R. Todd , Rozman Peter A. , Strowbridge Ben W.
Published: August 2013

In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods identified many other, nongranule cell types in the OB whose function remains mysterious. Within just the granule cell layer (GCL), Ramón y Cajal described multiple morphologically distinct subtypes of nongranule interneurons including large spiny Blanes cells which exhibit intrinsic persistent activity. Here, we define the intrinsic electrophysiology of a different nongranule interneuronal cell type in the GCL described by Ramón y Cajal, sparsely spiny Golgi cells in the rat OB. Golgi cells exhibit two distinct firing modes depending on the membrane potential: tonic firing and bursting. Golgi cells also generate rebound bursts following the offset of hyperpolarizing steps. We find that both low-threshold burst responses to depolarizing inputs and rebound bursts are blocked by nickel, an antagonist of T-type voltage-gated Ca2+ current. The state-dependent firing behavior we report in OB Golgi cells suggests that the function of these interneurons may dynamically shift from providing rhythmic potent inhibition of postsynaptic target neurons at sniffing frequencies to tonic, subtractive inhibition based on centrifugal modulatory input.
Methodological approaches to job satisfaction measurement in hospitality firms
Authors: Khalilzadeh Jalayer , Del Chiappa Giacomo , Jafari Jafar , Zargham Borujeni Hamid
Published: August 2013

Purpose

The purpose of this paper is to propose a new unbiased, reliable, exact, and systematic method of job satisfaction score estimation. The method considers affective and cognitive aspects simultaneously.

Design/methodology/approach

A questionnaire survey following the optimum allocation stratified sampling method was conducted in four up‐scale hotels of Tehran. Hotels' employees completed the questionnaires. Principal component analysis was used to identify facets, and the Friedman test was applied to examine their homogeneity. The Wilcoxon sign rank test and Pearson product‐moment correlation coefficients were employed to determine the most effective method among those investigated.

Findings

The weighted abridged job descriptive index (WAJDI) proposed in the study as a modified version of the job descriptive index seems to overcome the main limitations of the abridged job descriptive index (AJDI) and the perceived job satisfaction (PJS) methods when measuring job satisfaction in the hospitality sector.

Research limitations/implications

This paper encourages researchers to consider different methods to assess job satisfaction along with WAJDI. However, although a stratified sampling approach was used, it focused on a limited sociocultural and economic environment, which limits the generalizability of findings. WAJDI must be used in different conditions to prove its efficiency in measuring job satisfaction.

Originality/value

This study assesses and compares the power of the AJDI method, which is a cognitive‐based structure, with PJS as a global, single‐item scale to capture the affective aspects of job satisfaction. By introducing a new method of job satisfaction evaluation, this study contributes to the literature.
Consumers' evaluation of brief summary formats of print direct‐to‐consumer advertisements
Authors: Bhutada Nilesh , Deshpande Aparna , Menon Ajit , Perri Matthew
Published: August 2013

Purpose

The paper's aim is to measure the effect of various brief summary formats on consumers' drug‐related knowledge, evaluations of ad information, ad believability, attitudes towards the ad and brand, perceived product risk and intention to use ad information in making healthcare decisions.

Design/methodology/approach

Using mall‐intercept surveys, 307 US women, age 18‐50 years, were randomly assigned to one of the six different versions of brief summary formats for a birth control medicine. The six brief summary formats included: no brief summary, traditional (continuous prose) brief summary, risk information window, bulleted list, nutrition facts panel, and question‐answer format. The participants completed a closed‐ended questionnaire after reviewing the print ad.

Findings

MANOVA indicated presence of a multivariate main effect. However, univariate ANOVAs, performed to evaluate the effect of individual formats, revealed that the eight outcome variables did not vary significantly across the six brief summary formats. Nevertheless, respondents exhibited more positive evaluation of the newer brief summary formats compared to the traditional brief summary format, albeit there was no statistically significant difference among the newer formats.

Practical implications

Consumers clearly prefer newer brief summary formats to the traditional brief summary format.

Originality/value

This research provides additional insights about risk communication in direct‐to‐consumer ads and may assist the FDA in the development of a standardized regulatory structure for the future. Providing brief summary in a clearer, understandable, and consumer‐friendly manner can help consumers in deciding whether the drug is appropriate for their condition.
Learning to review submissions to peer reviewed journals: how do they do it?
Authors: Paltridge Brian
Published: August 2013

Purpose

The aim of this study is to examine how reviewers for academic journals learn to carry out the task of peer review and the issues they face in doing this.

Design/methodology/approach

A total of 45 reviewers completed a questionnaire which asked about their experience in doing peer reviews, how they had learnt to do them, and the issues they faced in doing these reviews. Follow up emails were also sent to reviewers in order to seek further elaboration on the answers they had provided in the questionnaire.

Findings

Over half of the reviewers had learnt to do reviews by reading reviews of their own submissions to peer‐reviewed journals. Others had learnt to write reviews by just doing them; that is, by practice. The most challenging aspect for the reviewers was writing reviewers' reports that were critical but still constructive. There was no consensus on the most straightforward aspects of writing peer reviews.

Practical implications

The study has implications for reviewer development, proposing an experiential, “learning by doing” approach to the training of reviewers rather than a didactic, information transmission style one.

Social implications

The study has implications for reviewer development, proposing an experiential, “learning by doing” approach to the training of reviewers rather than a didactic, information transmission style one.

Originality/value

The study provides insights into how reviewers learn to write peer reviews and the challenges they face in doing this. The paper also suggests strategies for improving reviewer development which can have benefits, especially for early career researchers.
Risks to auto sector recovery: bankruptcies of auto suppliers in East Asia and the USA
Authors: Platt Harlan , Platt Marjorie
Published: August 2013

Purpose

Early warning models are a widely employed development in modern finance. A good early warning model predicts with a high degree of accuracy the likelihood that a healthy company will either go bankrupt or become financially distressed. Now that B2B companies supply products worldwide, the risk of disruptions to business continuity due to supplier failure is international. This paper aims to focus on early warning models.

Design/methodology/approach

This paper extends the research comparing indicators of financial health to the subject of how industrial globalization affects early warning models. In specific, it considers models developed across two continents: North America and East Asia. The targets of the research are global auto suppliers, companies that deliver parts and equipment to original equipment auto manufacturers.

Findings

The findings are particularly important because of the collapse and resurrection of US original equipment manufacturers (OEMs). The modeling effort tested the ability of a single global model of financial distress to capture the determinants of auto supplier health on the two continents. Individual models for each continent proved to be superior to a single model.

Originality/value

This paper is the first to compare bankruptcy models for auto suppliers between China and the USA.
Performance indicators and terminology for value driven maintenance
Authors: Stenström Christer , Parida Aditya , Kumar Uday , Galar Diego
Published: August 2013

Purpose

Value driven maintenance (VDM) is a fairly new maintenance management methodology based on four maintenance value drivers and the formula of net present value (NPV) to calculate the value of different maintenance strategies. However, the dependability of the engineering assets needs to be assessed in order to make an estimation of the NPV. Therefore, the purpose of this paper is to critically analyse standardised indicators to find the most essential indicators for the four value drivers and for estimation of the NPV. Terminology containing performance drivers and killers are common in the field of asset management, but not many publications can be found for their detailed descriptions. One section in this paper is therefore dedicated to review these terms. A comprehensive description and classification of performance killers and drivers, and of indicators for VDM are presented in this paper.

Design/methodology/approach

Review of literature for technical terminology and review of standards for identification of indicators for maintenance performance measurement and NPV of maintenance.

Findings

Common description of technical terminology, as used by researchers, and identification of the most important indicators for maintenance performance measurement and the NPV of maintenance. Indicators classified under economic, technical, organizational and health, safety and environment (HSE) perspectives from EN 15341 standards are discussed and identified.

Originality/value

Description of emerging terminology in maintenance performance measurement adds to the consistency in communication of researchers and business stakeholders. Also, the identified maintenance performance indicators can facilitate performance measurement of organisations new to the process of measuring and analysing their performance.
Evaluation of milling characteristics of resin hybrid GFRP laminates using Taguchi approach
Authors: Jenarthanan M.P. , Jeyapaul R.
Published: August 2013

Purpose

The purpose of this paper is to report the preparation, characterisation and machinability of resin hybrid GFRP composites, which are made of glass fibre and the mixture of epoxy & polyester resin.

Design/methodology/approach

Resin hybrid GFRP laminates containing 0, 20 and 40wt% of polyester resin with the epoxy resin are prepared by conventional hand layup technique using glass fibre as the reinforcement. The variation of break load and shear strength for three different combinations of epoxy and polyester resin are studied by ASTM. A plan of experiment based on Taguchi was established with prefixed cutting parameters and the machining was performed. A stylus type profilometer to examine the surface roughness and shop microscope to examine the delamination of resin hybrid GFRP laminates were used. An analysis of variance (ANOVA) was performed to investigate the cutting characteristics of resin hybrid GFRP composite materials using solid carbide end mill. The correlation was obtained by multiple‐variable linear regression using Minitab 14 software.

Findings

Taguchi analysis reveals that the resin hybrid GFRP laminate provides better machinability in terms of surface roughness and delamination when compared to homogenous GFRP laminates (pure epoxy resin). Polyester resin enhances the machinability of the GFRP laminates.

Research limitations/implications

The machinability of the resin hybrid GFRP laminates can be improved further by modifying the polyester resin percentage.

Originality/value

The resin hybrid GFRP laminates so developed can be used in aircraft and aerospace applications to increase the shear and work of fracture properties.
Effect of temperature on coating properties of shellac‐novolac blends
Authors: Fahim Ansari Mohammad , Sarkhel Gautam , Nath Goswami Dipendra , Baboo Bangali
Published: August 2013

Purpose

The purpose of this paper is to improve the properties of shellac by blending with novolac and to study the thermal behaviour of the blends with an ultimate aim to use as surface coating material.

Design/methodology/approach

Novolac was synthesized by reaction of phenol with formaldehyde in a molar ratio of 1:0.8, in acidic condition. Blending of shellac with novolac was done in solution and films of the blends, prepared on glass slides and tin panels, were baked at 150°C for 15 minutes. Properties of the films were studied as per standard procedures.

Findings

Films of shellac‐novolac blends showed improvement in gloss and impact resistance compared to those of shellac alone. Gloss of blends increased with the increase in concentration of novolac and further increased on baking the films. Scratch hardness of shellac decreased on blending with novolac. Baked films of the blends showed resistance to heat and water. Films of shellac‐novolac blends were found to be more resistant to polar solvents compared to non‐polar solvents.

Research limitations/implications

Shellac, prepared from kusmi seedlac, was used in the study. Besides shellac, dewaxed decolorized lac (DDL), dewaxed lac (DL) and bleached lac (BL) could also be used for study on blending with novolac.

Practical implications

Blending of shellac with novolac improved the film properties of shellac. The study suggests that the compositions can be utilised in developing formulations of coating material with improved properties for metal surfaces.

Originality/value

The formulations based on modification of shellac with novolac and study of the film properties utilising various instruments are novel. The formulations based on shellac and novolac can find applications in the field of surface coating with desired purposes.
Radiation cured branched polyurethane for coatings
Authors: Manvi Gururaj N. , Jagtap Ramanand N.
Published: August 2013

Purpose

The purpose of this work is to develop flexible as well as rigid polyurethane coating by using mixed polyol. It is developed by using low cost reactant such as polyether and introducing branching in it.

Design/methodology/approach

Radiation curable branched polyurethanes were synthesised. In this work, branched polyol was synthesised by using trimethylol propane (TMP) and reacted with adipic acid (AA), neopentyl glycol (NPG) (polyester) and polypropylene glycol (PPG) (polyether). These branched polyols were developed by varying ratio of polyether to polyester from 20:80, 40:60 and 55:45. These branched polyols were further reacted with isophorane di isocyanate (IPDI) and hydroxy ethyl metha acrylate (HEMA) to get vinyl terminated prepolymer.

Findings

The branched polyol due to presence of polyether offers excellent flexibility and polyester which provides excellent scratch, adhesion, and tensile strength. Use of reactive diluents is avoided, and its role is compensated by polyether in all systems, which takes care of reducing viscosity and improves flow and levelling properties.

Practical implications

Synthesis of branched polyol using polyesters and polyethers is more beneficial as it offers advantage of its combined property.

Originality/value

The polyurethane acrylate due to its polyol combination, branching and cross linking offers enhanced coating properties and can be used for various coating applications.
Curriculum development resources for teachers and school librarians: a selection of resources
Authors: Wolven Robin
Published: August 2013

Purpose ‐ Curriculum development is a vital component in the educational process. Its scope is exceptionally broad, and it involves nearly everyone who is involved with teaching and learning, including teachers and librarians. Curriculum development resources offer guidance for lesson plan preparation that meets the educational standards set by each state. Resources for curriculum development for both teachers and librarians are abundant, with resources being offered both electronically and in print, freely available and for purchase. The purpose of this paper is to provide a selection of resources offered for teachers and those offered for librarians, electronically, in print, freely available, and for purchase. Design/methodology/approach ‐ Curriculum development resources were chosen based on the selection criteria included in the article, including: authority, accuracy, scope, appropriateness, and treatment. There were many resources for both teachers and librarians available, but only a few were selected. Those selected met the selection criteria and were outstanding and beneficial resources for curriculum development. Findings ‐ Resources for curriculum development for both teachers and librarians are abundant, with resources being offered both electronically and in print, freely available and for purchase. There are many resources for both teachers and librarians; however, teacher resources outnumber those for librarians. Perhaps in the upcoming years, as information literacy instruction becomes part of more institutions, further resources will be made available. Originality/value ‐ The function of curriculum development is to research, plan, and prepare the content and methods that will be taught during instruction to achieve the desired outcomes. State curriculum standards currently play a major role in schools and how the curriculum is developed. Curriculum development resources provide the necessary resources for teachers and librarians to plan and prepare curricula that can meet the standards set by each state.
Ambivalence, Political Engagement and Context
Authors: Johnson April A.
Published: August 2013

Scholars of American politics have generally found a negative relationship between ambivalence and political engagement. This study explores such conclusions and argues that the effect of ambivalence on engagement varies according to electoral context. Using a multi-level modeling strategy, I find that ambivalence has a significant overall effect on political engagement for citizens in the United States but a lesser overall impact for citizens in Great Britain. Yet by allowing the slope and the intercept of ambivalence to vary across parliamentary districts, I find that ambivalence has asymmetrical effects on political engagement within Britain. I conclude by arguing that ambivalence essentially operates in a differential manner across electoral contexts and provide preliminary evidence as to why this is.