bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of VpsS, a Hybrid Sensor Kinase, Enhances Biofilm Formation in
Vibrio cholerae
Authors: Shikuma Nicholas J. , Fong Jiunn C. N. , Odell Lindsay S. , Perchuk Barrett S. , Laub Michael T. , Yildiz Fitnat H.
Published: June 2009

Vibrio cholerae
causes the disease cholera and inhabits aquatic environments. One key factor in the environmental survival of
V. cholerae
is its ability to form matrix-enclosed, surface-associated microbial communities known as biofilms. Mature biofilms rely on
Vibrio
polysaccharide to connect cells to each other and to a surface. We previously described a core regulatory network, which consists of two positive transcriptional regulators, VpsR and VpsT, and a negative transcriptional regulator HapR, that controls biofilm formation by regulating the expression of
vps
genes. In this study, we report the identification of a sensor histidine kinase, VpsS, which can control biofilm formation and activates the expression of
vps
genes. VpsS required the response regulator VpsR to activate
vps
expression. VpsS is a hybrid sensor histidine kinase that is predicted to contain both histidine kinase and response regulator domains, but it lacks a histidine phosphotransferase (HPT) domain. We determined that VpsS acts through the HPT protein LuxU, which is involved in a quorum-sensing signal transduction network in
V. cholerae
. In vitro analysis of phosphotransfer relationships revealed that LuxU can specifically reverse phosphotransfer to CqsS, LuxQ, and VpsS. Furthermore, mutational and phenotypic analyses revealed that VpsS requires the response regulator LuxO to activate
vps
expression, and LuxO positively regulates the transcription of
vpsR
and
vpsT
. The induction of
vps
expression via VpsS was also shown to occur independent of HapR. Thus, VpsS utilizes components of the quorum-sensing pathway to modulate biofilm formation in
V. cholerae
.
Transcriptional Profiling of Methyltransferase Genes during Growth of
Methanosarcina mazei
on Trimethylamine
Authors: Krätzer Christian , Carini Paul , Hovey Raymond , Deppenmeier Uwe
Published: June 2009

The genomic expression patterns of
Methanosarcina mazei
growing with trimethylamine were measured in comparison to those of cells grown with methanol. We identified a total of 72 genes with either an increased level (49 genes) or a decreased level (23 genes) of mRNA during growth on trimethylamine with methanol-grown cells as the control. Major differences in transcript levels were observed for the
mta
,
mtb
,
mtt
, and
mtm
genes, which encode enzymes involved in methane formation from methanol and trimethylamine, respectively. Other differences in mRNA abundance were found for genes encoding enzymes involved in isopentenyl pyrophosphate synthesis and in the formation of aromatic amino acids, as well as a number of proteins with unknown functions. The results were verified by in-depth analysis of methyltransferase genes using specific primers for real-time quantitative reverse transcription-PCR (RT-PCR). The monitored transcript levels of genes encoding corrinoid proteins involved in methyl group transfer from methylated C
1
compounds (
mta
C,
mtb
C,
mtt
C, and
mtm
C) indicated increased amounts of mRNA from the
mtaBC1
,
mtaBC2
, and
mtaBC3
operons in methanol-grown cells, whereas mRNA of the
mtb1-mtt1
operon was found in high concentrations during trimethylamine consumption. The genes of the
mtb1-mtt1
operon encode methyltransferases that are responsible for sequential demethylation of trimethylamine. The analysis of product formation of trimethylamine-grown cells at different optical densities revealed that large amounts of dimethylamine and monomethylamine were excreted into the medium. The intermediate compounds were consumed only in the very late exponential growth phase. RT-PCR analysis of key genes involved in methanogenesis led to the conclusion that
M. mazei
is able to adapt to changing trimethylamine concentrations and the consumption of intermediate compounds. Hence, we assume that the organism possesses a regulatory network for optimal substrate utilization.
LytM-Domain Factors Are Required for Daughter Cell Separation and Rapid Ampicillin-Induced Lysis inEscherichia coli
Authors: Uehara Tsuyoshi , Dinh Thuy , Bernhardt Thomas G.
Published: June 2009

Bacterial cytokinesis is coupled to the localized synthesis of new peptidoglycan (PG) at the division site. This newly generated septal PG is initially shared by the daughter cells. InEscherichia coliand other gram-negative bacteria, it is split shortly after it is made to promote daughter cell separation and allow outer membrane constriction to closely follow that of the inner membrane. We have discovered that the LytM (lysostaphin)-domain containing factors ofE. coli(EnvC, NlpD, YgeR, and YebA) are absolutely required for septal PG splitting and daughter cell separation. Mutants lacking all LytM factors form long cell chains with septa containing a layer of unsplit PG. Consistent with these factors playing a direct role in septal PG splitting, both EnvC-mCherry and NlpD-mCherry fusions were found to be specifically recruited to the division site. We also uncovered a role for the LytM-domain factors in the process of β-lactam-induced cell lysis. Compared to wild-type cells, mutants lacking LytM-domain factors were delayed in the onset of cell lysis after treatment with ampicillin. Moreover, rather than lysing from midcell lesions like wild-type cells, LytM−cells appeared to lyse through a gradual loss of cell shape and integrity. Overall, the phenotypes of mutants lacking LytM-domain factors bear a striking resemblance to those of mutants defective for theN-acetylmuramyl-l-alanine amidases: AmiA, AmiB, and AmiC.E. colithus appears to rely on two distinct sets of putative PG hydrolases to promote proper cell division.
Triacylglycerol Utilization Is Required for Regrowth of In Vitro Hypoxic Nonreplicating
Mycobacterium bovis
Bacillus Calmette-Guerin
Authors: Low Kai Leng , Rao P. S. Srinivasa , Shui Guanghou , Bendt Anne K. , Pethe Kevin , Dick Thomas , Wenk Markus R.
Published: June 2009

Mycobacteria store triacylglycerols (TGs) under various stress conditions, such as hypoxia, exposure to nitric oxide, and acidic environments. These stress conditions are known to induce nonreplicating persistence in mycobacteria. The importance of TG accumulation and utilization during regrowth is not clearly understood. Here we specifically determined the levels of accumulated TG and TG lipase activity in
Mycobacterium bovis
bacillus Calmette-Guerin (BCG) in various different physiological states (logarithmic growth, aerated stationary phase, hypoxia-induced dormancy, and regrowth from dormancy). We found extensive accumulation and degradation of TGs in the bacilli during entry into and exit from hypoxia-induced dormancy, respectively. These processes are accompanied by dynamic appearance and disappearance of intracellular TG lipid particles. The reduction in TG levels coincides with an increase in cellular TG lipase activity in the regrowing bacilli. Tetrahydrolipstatin, an inhibitor of TG lipases, reduces total lipase activity, prevents breakdown of TGs, and blocks the growth of mycobacteria upon resuscitation with air. Our results demonstrate that utilization of TGs is essential for the regrowth of mycobacteria during their exit from the hypoxic nonreplicating state.
Hydroxyl Radicals Are Involved in Cell Killing by the Bacterial Topoisomerase I Cleavage Complex
Authors: Liu I-Fen , Annamalai Thirunavukkarasu , Sutherland Jeanette H. , Tse-Dinh Yuk-Ching
Published: June 2009

Escherichia coli
expressing SOS-inducing mutant topoisomerase I was utilized to demonstrate that covalent protein-DNA complex accumulation results in oxidative damage. Hydroxyl radicals were detected following mutant topoisomerase induction. The presence of the Fe
2+
chelator 2,2′-dipyridyl and an
iscS
mutation affecting Fe-S cluster formation protect against topoisomerase I cleavage complex-mediated cell killing.
INFINITE STATISTICS, SYMMETRY BREAKING AND COMBINATORIAL HIERARCHY
Authors: SHEVCHENKO VLADIMIR
Published: June 2009

The physics of symmetry breaking in theories with strongly interacting quanta obeying infinite (quantum Boltzmann) statistics known as quons is discussed. The picture of Bose/Fermi particles as low energy excitations over nontrivial quon condensate is advocated. Using induced gravity arguments, it is demonstrated that the Planck mass in such low energy effective theory can be factorially (in number of degrees of freedom) larger than its true ultraviolet cutoff. Thus, the assumption that statistics of relevant high energy excitations is neither Bose nor Fermi but infinite can remove the hierarchy problem without necessity to introduce any artificially large numbers. Quantum mechanical model illustrating this scenario is presented.
TOPICS IN CHARM HADRON STUDIES AT BELLE
Authors: GOLOB BOŠTJAN
Published: June 2009

Studies of hadrons composed of charm quarks attend a growing attention in recent years due to both, experimental accessibility and theoretical motivation. In this paper we review selected results on charm hadron studies carried out with the Belle detector at the electron positron collider KEKB in Japan.
GRAVITY AS BF THEORY PLUS POTENTIAL
Authors: KRASNOV KIRILL
Published: June 2009

Spin foam models of quantum gravity are based on Plebanski's formulation of general relativity as a constrained BF theory. We give an alternative formulation of gravity as BF theory plus a certain potential term for the B-field. When the potential is taken to be infinitely steep one recovers general relativity. For a generic potential the theory still describes gravity in that it propagates just two graviton polarizations. The arising class of theories is of the type amenable to spin foam quantization methods, and, we argue, may allow one to come to terms with renormalization in the spin foam context.
NONCOMMUTATIVE SPHERICAL SYMMETRY VIA THE MONOPOLE
Authors: BURIĆ MAJA , MADORE JOHN
Published: June 2009

We analyze spherically symmetric static configurations of the noncommutative space-time and show that the monopole potential can be consistently included in the algebra of position operators.
HYBRID QUANTUM COSMOLOGY: COMBINING LOOP AND FOCK QUANTIZATIONS
Authors: MENA MARUGÁN G. A. , MARTÍN-BENITO M.
Published: June 2009

As a necessary step towards the extraction of realistic results from Loop Quantum Cosmology, we analyze the physical consequences of including inhomogeneities. We consider in detail the quantization of a gravitational model in vacuo which possesses local degrees of freedom, namely, the linearly polarized Gowdy cosmologies with the spatial topology of a three-torus. We carry out a hybrid quantization which combines loop and Fock techniques. We discuss the main aspects and results of this hybrid quantization, which include the resolution of the cosmological singularity, the polymeric quantization of the internal time, a rigorous definition of the quantum constraints and the construction of their solutions, the Hilbert structure of the physical states, and the recovery of a conventional Fock quantization for the inhomogeneities.
VERWEY TRANSITION (VT) BY PSEUDO-JOSEPHSON JUNCTIONS
Authors: KOO JE HUAN , KIM JUNG-HYUN , JEONG JONG-MUN , CHO GUANGSUP
Published: June 2009

We investigated pseudo-Josephson current effects in magnetite. Compared with the original Josephson junctions applied to superconductors, we obtained theoretical results that correlate well with experimental current data. Even though we applied a pseudo-Josephson junction to the current along the axis of energy (i.e. the momentum space), the theoretical form of DC-type currents was proportional to a tan function for the time parameter or a tanh function for the temperature parameter, which agrees with the experimental data. These pseudo-Josephson junctions occur in momentum space rather than in real space. The currents in magnetite are not primarily due to the electron–phonon interactions that induce a gap opening in band structures. We hypothesize that the Verwey Transition (VT) mechanism is pseudo-Josephson in nature.
PHOTOLYSIS AND LIFETIME OF NO2, N2O AND HNO3 USING ANALYTICAL SOFTWARE PROGRAM
Authors: AL-FAYDHI ANWAR MUSTAFA EZZAT
Published: June 2009

In this research photolysis of NO 2, N 2 O and HNO 3 for vast range of altitudes was investigated using the absorption cross-section data provided by NASA. The calculations were made using a special software computer program. Also the lifetimes of NO 2, N 2 O and HNO 3 were calculated. The investigation revealed that the lifetime due to photolysis will be nearly steady and short for NO 2, and will be as long (as there is no overlap with solar fluxes below 50 km altitude) for N 2 O . As for nitric acid HNO 3 the lifetime started to increase from 1 day at 25 km altitude to 10 days at the surface of the earth.
Parasympathetic effects on cardiac electrophysiology during exercise and recovery in patients with left ventricular dysfunction
Authors: Chicos Alexandru B. , Kannankeril Prince J. , Kadish Alan H. , Goldberger Jeffrey J.
Published: June 2009

Depressed parasympathetic activity has been proposed to be associated with an increased risk of sudden death. Parasympathetic effects (PE) on cardiac electrophysiology during exercise and recovery have not been studied in patients with left ventricular dysfunction. We performed noninvasive electrophysiological studies (NI-EPS) and characterized the electrophysiological properties of the sinus node, atrioventricular (AV) node, and ventricle in subjects with depressed left ventricular ejection fraction and dual-chamber defibrillators. NI-EPS were performed during rest, exercise, and recovery at baseline and after parasympathetic blockade with atropine to assess PE (the difference between parameter values in the 2 conditions). Ten subjects (9 men: age, 60 ± 9 yr; and left ventricular ejection fraction, 29 ± 8%) completed the study. All NI-EPS parameters decreased during exercise and trended toward rest values during recovery. PE at rest, during exercise, and during recovery, respectively, were on sinus cycle length, 320 ± 71 ( P = 0.0001), 105 ± 60 ( P = 0.0003), and 155 ± 82 ms ( P = 0.0002); on AV block cycle length, 137 ± 136 ( P = 0.09), 37 ± 19 ( P = 0.002), and 61 ± 39 ms ( P = 0.006); on AV interval, 58 ± 32 ( P = 0.035), 22 ± 13 ( P = 0.002), and 36 ± 20 ms ( P = 0.001); on ventricular effective refractory period, 15.8 ± 11.3 ( P = 0.02), 4.7 ± 15.2 ( P = 0.38), and 6.8 ± 15.5 ms ( P = 0.20); and on QT interval, 13 ± 12 ( P = 0.13), 3 ± 17 ( P = 0.6), and 20 ± 23 ( P = 0.04). In conclusion, we describe for the first time the changes in cardiac electrophysiology and PE during rest, exercise, and recovery in subjects with left ventricular dysfunction. PEs are preserved in these patients. Thus the role of autonomic changes in the pathophysiology of sudden death requires further exploration.
Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse
Authors: Fenton Richard A. , Komatsu Satoshi , Ikebe Mitsuo , Shea Lynne G. , Dobson James G.
Published: June 2009

Adenosine protects the heart from adrenergic overstimulation. This adenoprotection includes the direct anti-adrenergic action via adenosine A1receptors (A1R) on the adrenergic signaling pathway. An indirect A1R-induced attenuation of adrenergic responsiveness involves the translocation of PKC-ε to t-tubules and Z-line of cardiomyocytes. We investigated with sarcomere imaging, immunocytochemistry imaging, and coimmunoprecipitation (co-IP) whether A1R activation of PKC-ε induces the kinase translocation to receptor for activated C kinase 2 (RACK2) in isolated rat and mouse hearts and whether phospholipase C (PLC) is involved. Rat cardiomyocytes were treated with the A1R agonist chlorocyclopentyladenosine (CCPA) and exposed to primary PKC-ε and RACK2 antibodies with secondaries conjugated to Cy3 and Cy5 (indodicarbocyanine), respectively. Scanning confocal microscopy showed that CCPA caused PKC-ε to reversibly colocalize with RACK2 within 3 min. Additionally, rat and mouse hearts were perfused and stimulated with CCPA or phenylisopropyladenosine to activate A1R, or with phorbol 12-myristate 13-acetate to activate PKC. RACK2 was immunoprecipitated from heart extracts and resolved with SDS-PAGE. Western blotting showed that CCPA, phenylisopropyladenosine, and phorbol 12-myristate 13-acetate in the rat heart increased the PKC-ε co-IP with RACK2 by 186, 49, and >1,000%, respectively. The A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine prevented the CCPA-induced co-IP with RACK2. In mouse hearts, CCPA increased the co-IP of PKC-ε with RACK2 by 61%. With rat cardiomyocytes, the β-adrenergic agonist isoproterenol increased sarcomere shortening by 177%. CCPA reduced this response by 47%, an action inhibited by the PLC inhibitor U-73122 and 8-cyclopentyl-1,3-dipropylxanthine. In conclusion, A1R stimulation of the heart is associated with PLC-initiated PKC-ε translocation and association with RACK2.
Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone
Authors: Chawengsub Yuttana , Gauthier Kathryn M. , Campbell William B.
Published: June 2009

Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on LO metabolites of AA. Nitric oxide (NO)- and prostaglandin (PG)-independent vasodilatory responses to ACh and AA are reduced by inhibitors of LO and by antisense oligonucleotides specifically against 15-LO-1. Vasoactive 15-LO metabolites derived from the vascular endothelium include 15-hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-HEETA) that is hydrolyzed by soluble epoxide hydrolase to 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA). HEETA and THETA are endothelium-derived hyperpolarizing factors that induce vascular relaxations by activation of smooth muscle apamin-sensitive, calcium-activated, small-conductance K+channels causing hyperpolarization. In other arteries, the 12-LO metabolite 12-hydroxyeicosatetraenoic acid is synthesized by the vascular endothelium and relaxes smooth muscle by large-conductance, calcium-activated K+channel activation. Thus formation of vasodilator eicosanoids derived from LO pathways contributes to the regulation of vascular tone, local blood flow, and blood pressure.
Adenosine regulation of microtubule dynamics in cardiac hypertrophy
Authors: Fassett John T. , Xu Xin , Hu Xinli , Zhu Guangshuo , French Joel , Chen Yingjie , Bache Robert J.
Published: June 2009

There is evidence that endogenous extracellular adenosine reduces cardiac hypertrophy and heart failure in mice subjected to chronic pressure overload, but the mechanism by which adenosine exerts these protective effects is unknown. Here, we identified a novel role for adenosine in regulation of the cardiac microtubule cytoskeleton that may contribute to its beneficial effects in the overloaded heart. In neonatal cardiomyocytes, phenylephrine promoted hypertrophy and reorganization of the cytoskeleton, which included accumulation of sarcomeric proteins, microtubules, and desmin. Treatment with adenosine or the stable adenosine analog 2-chloroadenosine, which decreased hypertrophy, specifically reduced accumulation of microtubules. In hypertrophied cardiomyocytes, 2-chloroadenosine or adenosine treatment preferentially targeted stabilized microtubules (containing detyrosinated α-tubulin). Consistent with a role for endogenous adenosine in reducing microtubule stability, levels of detyrosinated microtubules were elevated in hearts of CD73 knockout mice (deficient in extracellular adenosine production) compared with wild-type mice (195%, P < 0.05). In response to aortic banding, microtubules increased in hearts of wild-type mice; this increase was exaggerated in CD73 knockout mice, with significantly greater amounts of tubulin partitioning into the cold-stable Triton-insoluble fractions. The levels of this stable cytoskeletal fraction of tubulin correlated strongly with the degree of heart failure. In agreement with a role for microtubule stabilization in promoting cardiac dysfunction, colchicine treatment of aortic-banded mice reduced hypertrophy and improved cardiac function compared with saline-treated controls. These results indicate that microtubules contribute to cardiac dysfunction and identify, for the first time, a role for adenosine in regulating cardiomyocyte microtubule dynamics.
Calcium/calmodulin-dependent protein kinase II mediates cardioprotection of intermittent hypoxia against ischemic-reperfusion-induced cardiac dysfunction
Authors: Yu Zhuo , Wang Zhi-Hua , Yang Huang-Tian
Published: June 2009

Intermittent high-altitude (IHA) hypoxia-induced cardioprotection against ischemia-reperfusion (I/R) injury is associated with the preservation of sarcoplasmic reticulum (SR) function. Although Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) and phosphatase are known to modulate the function of cardiac SR under physiological conditions, the status of SR CaMKII and phosphatase during I/R in the hearts from IHA hypoxic rats is unknown. In the present study, we determined SR and cytosolic CaMKII activity during preischemia and I/R (30 min/30 min) in perfused hearts from normoxic and IHA hypoxic rats. The left ventricular contractile recovery, SR CaMKII activity as well as phosphorylation of phospholamban at Thr17, and Ca2+/CaM-dependent SR Ca2+-uptake activity were depressed in the I/R hearts from normoxic rats, whereas these changes were prevented in the hearts from IHA hypoxic rats. Such beneficial effects of IHA hypoxia were lost by treating the hearts with a specific CaMKII inhibitor, KN-93. I/R also depressed cytosolic CaMKII and SR phosphatase activity, but these alterations remained unchanged in IHA hypoxic group. Furthermore, we found that the autophosphorylation at Thr287, which confers Ca2+/CaM-independent activity, was not altered by I/R in both groups. These findings indicate that preservation of SR CaMKII activity plays an important role in the IHA hypoxia-induced cardioprotection against I/R injury via maintaining SR Ca2+-uptake activity.
TGF-β through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation
Authors: Tsai Shirling , Hollenbeck Scott T. , Ryer Evan J. , Edlin Rachel , Yamanouchi Dai , Kundi Rishi , Wang Chunjie , Liu Bo , Kent K. Craig
Published: June 2009

The objective of this study was to better understand the role of transforming growth factor-β (TGF-β) and its primary signaling protein Smad3 in the development of intimal hyperplasia. Male Sprague-Dawley rats underwent left carotid balloon injury followed by intra-arterial infection with adenovirus-expressing Smad3 (AdSmad3). In uninfected injured arteries, endogenous Smad3 was upregulated with the expression peaking at 14 days. Moreover, in arteries infected with AdSmad3, we observed an enhancement of intimal hyperplasia and increased vascular smooth muscle cell (VSMC) proliferation. The novel finding, that TGF-β/Smad3 stimulated rather than inhibited VSMC proliferation, was confirmed in cultured VSMCs infected with AdSmad3 and treated with TGF-β. To identify the mechanism underlying TGF-β/Smad3-mediated VSMC proliferation, we studied the cyclin-dependent kinase inhibitor p27. Although the upregulation of Smad3 in VSMCs had no significant effect on total p27 levels, Smad3 did stimulate the phosphorylation of p27 at serine-10 as well as the nuclear export of p27, events associated with cell proliferation. Furthermore, serine-10-phosphorylated p27 was also increased in AdSmad3-infected injured rat carotid arteries, demonstrating the existence of this same mechanism in vivo. In conclusion, our findings identify a novel mechanism for the effect of TGF-β on intimal hyperplasia. In the presence of elevated levels of Smad3 that develop in response to injury, TGF-β stimulates smooth muscle cell proliferation through a mechanism involving the phosphorylation and nuclear export of p27.
Oxidized α1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema
Authors: Li Zhenjun , Alam Sam , Wang Jicun , Sandstrom Caroline S. , Janciauskiene Sabina , Mahadeva Ravi
Published: June 2009

α1-Antitrypsin (AT) is a major elastase inhibitor within the lung. Oxidation of critical methionine residues in AT generates oxidized AT (Ox-AT), which has a greatly diminished ability to inhibit neutrophil elastase. This process may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD) by creating a functional deficiency of AT permitting lung destruction. We show here that Ox-AT promotes release of human monocyte chemoattractant protein-1 (MCP-1) and IL-8 from human lung type epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells. Native, cleaved, polymeric AT and secretory leukoproteinase inhibitor (SLPI) and oxidized conformations of cleaved, polymeric AT and SLPI did not have any significant effect on MCP-1 and IL-8 secretion. These findings were supported by the fact that instillation of Ox-AT into murine lungs resulted in an increase in JE (mouse MCP-1) and increased macrophage numbers in the bronchoalveolar lavage fluid. The effect of Ox-AT was dependent on NF-κB and activator protein-1 (AP-1)/JNK. These findings have important implications. They demonstrate that the oxidation of methionines in AT by oxidants released by cigarette smoke or inflammatory cells not only reduces the antielastase lung protection, but also converts AT into a proinflammatory stimulus. Ox-AT generated in the airway interacts directly with epithelial cells to release chemokines IL-8 and MCP-1, which in turn attracts macrophages and neutrophils into the airways. The release of oxidants by these inflammatory cells could oxidize AT, perpetuating the cycle and potentially contributing to the pathogenesis of COPD. Furthermore, these data demonstrate that molecules such as oxidants, antiproteinases, and chemokines, rather than act independently, are likely to interact to cause emphysema.
Environmental tobacco smoke exposure does not prevent corticosteroids reducing inflammation, remodeling, and airway hyperreactivity in mice exposed to allergen
Authors: Song Dae Jin , Min Myung Goo , Miller Marina , Cho Jae Youn , Broide David H.
Published: June 2009

The ability of corticosteroids to reduce airway inflammation and improve lung function is significantly reduced in asthmatics who are tobacco smokers compared with asthmatics who are nonsmokers. As not only high levels of tobacco smoke exposure in active smokers, but also significantly lower levels of tobacco smoke exposure from passive environmental tobacco smoke (ETS) exposure in nonsmokers can increase both asthma symptoms and the frequency of asthma exacerbations, we utilized a mouse model to determine whether corticosteroids can reduce levels of airway inflammation, airway remodeling, and airway hyperreactivity in mice exposed to the combination of chronic ETS and ovalbumin (OVA) allergen. Chronic ETS exposure alone did not induce increases in eosinophilic airway inflammation, airway remodeling, or airway hyperreactivity. Mice exposed to chronic OVA allergen had significantly increased levels of peribronchial fibrosis, increased thickening of the smooth muscle layer, increased mucus, and increased airway hyperreactivity, which was significantly enhanced by coexposure to the combination of chronic ETS and chronic OVA allergen. Administration of corticosteroids to mice exposed to chronic ETS and OVA allergen significantly reduced levels of eosinophilic airway inflammation, mucus production, peribronchial smooth muscle thickness, airway hyperreactivity, and the number of peribronchial TGF-β1+ cells. Overall, this study demonstrates that corticosteroids can significantly reduce levels of eosinophilic inflammation, mucus expression, airway remodeling, and airway hyperreactivity in chronic ETS-exposed mice challenged with allergen.
Functional Characterization of the Canine Heme-Regulated eIF2αKinase: Regulation of Protein Synthesis
Authors: Kanelakis Kimon C. , Pyati Jayashree , Wagaman Pamela C. , Chuang Jui Chang , Yang Young , Shankley Nigel P.
Published: June 2009

The heme-regulated inhibitor (HRI) negatively regulates protein synthesis by phosphorylating eukaryotic initiation factor-2α(eIF2α) thereby inhibiting protein translation. The importance of HRI in regulating hemoglobin synthesis in erythroid cells makes it an attractive molecular target in need of further characterization. In this work, we have cloned and expressed the canine form of the HRI kinase. The canine nucleotide sequence has 86%, 82%, and 81% identity to the human, mouse, and rat HRI, respectively. It was noted that an isoleucine residue in the ATP binding site of human, rat, and mouse HRI is replaced by a valine in the canine kinase. The expression of canine HRI protein by in vitro translation using wheat germ lysate or in Sf9 cells using a baculovirus expression system was increased by the addition of hemin. Following purification, the canine protein was found to be 72 kD and showed kinase activity determined by its ability to phosphorylate a synthetic peptide substrate. Quercetin, a kinase inhibitor known to inhibit mouse and human HRI, inhibits canine HRI in a concentration-dependent manner. Additionally, quercetin is able to increase de novo protein synthesis in canine reticulocytes. We conclude that the canine is a suitable model species for studying the role of HRI in erythropoiesis.
On Multiple Interpolation Functions of the Nörlund‐Type q‐Euler Polynomials
Authors: Acikgoz Mehmet , Simsek Yilmaz
Published: June 2009

In (2006) and (2009), Kim defined new generating functions of the Genocchi, Nörlund‐type q‐Euler polynomials and their interpolation functions. In this paper, we give another definition
of the multiple Hurwitz type q‐zeta function. This function interpolates Nörlund‐type q‐Euler polynomials at negative integers. We also give some identities related to these polynomials
and functions. Furthermore, we give some remarks about approximations of Bernoulli and
Euler polynomials.
Clinical Significance of Skin Toxicity due to EGFR-Targeted Therapies
Authors: Giovannini Monica , Gregorc Vanesa , Belli Carmen , Roca Elisa , Lazzari Chiara , Viganò Maria Grazia , Serafico Anna , Villa Eugenio
Published: June 2009

Many small molecules and monoclonal antibodies blocking the activity of Epidermal Growth factor receptor (EGFR) have been developed and have shown clinical activity in patients with non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer (CRC), and are in clinical development for a range of other solid tumors. The toxicity profile of such agents is characterized by a typical pattern of cutaneous reactions. In this paper we reviewed the current available data regarding the clinical significance of skin reaction due to EGFR targeted agents. We show that skin toxicity can be considered as predictive marker of response to such drugs and that it is not disease specific; however its potential prognostic value is still to be proven.
Cell-Cell Adhesion in the Prelaminar Region of the Optic Nerve Head: A Possible Target for Ionic Stress
Authors: Carreras Francisco Javier , Porcel David , Alaminos Miguel , Garzón Ingrid
Published: June 2009

Purpose: This paper aims to study the anterior surface of the optic nerve in relation to its ability to support a source of stress acting from the vitreous cavity. The intercellular junctions of the lining astrocytes mediated by cellular adhesion molecules (CAMs) may be the main targets for ionic stress. Methods: The optic nerve of the domestic pig was prepared for light, confocal laser and transmission electron microscopy. Immunostaining was performed for antibodies against glial fibrillary acidic protein, neural cadherin (N-cadherin) and neural CAM (N-CAM). Results: Only 1 type of intercellular junction was found among the bordering astrocytes, which was characterized as a zonula adherens. Unions between lining cells showed a positive immunogold effect and immunofluorescence against N-cadherin in the zonula adherens and membrane apposition. N-CAM was also present in areas of nonjunctional cellular adhesion. Conclusion: The stability of intercellular junctions of the nerve-vitreous boundary is sensitive to altered concentrations of Ca2+. Since aqueous humor has half the Ca2+ concentration of plasma, any contact of aqueous humor with the optic nerve head can interfere with the ionic concentration of calcium in the extracellular spaces. This mechanism may contribute to age-related changes and some types of glaucoma.
Effects of Chronic Intracerebral Prolactin on the Oxytocinergic and Vasopressinergic System of Virgin Ovariectomized Rats
Authors: Donner Nina , Neumann Inga D.
Published: June 2009

Chronic intracerebroventricular (icv) infusion of prolactin (PRL) into the cerebral ventricles and mimicking central hyperprolactinemia in lactation has recently been shown to reduce anxiety and neuronal as well as neuroendocrine responses to acute stressor exposure. Here, we studied the effects of icv PRL on the activity of the oxytocin (OXT) and arginine vasopressin (AVP) systems of virgin female, ovariectomized, estradiol-substituted Wistar rats. Ovine PRL was delivered via osmotic minipumps at 0.01, 0.1 or 1 μg/h for 5 days. Under basal conditions, both plasma OXT and AVP concentrations were increased after chronic PRL treatment (1 μg/h). At hypothalamic level, this was accompanied by an increased c-fos and OXT mRNA expression within the supraoptic nucleus, the main source of plasma OXT, whereas AVP mRNA levels remained unchanged. No effect of PRL on c-fos or on nonapeptide mRNA expression was found in the hypothalamic paraventricular nucleus. Moreover, chronic PRL abolished the rise in plasma OXT induced by acute exposure to 30 min restraint stress in vehicle-treated rats. However, restraint stress did not significantly alter OXT or AVP mRNA expression in the hypothalamus of either vehicle- or PRL-treated animals. From these results we conclude that brain hyperprolactinemia alters the synthetic activity of OXT neurons and the secretory performance of OXT and AVP neurons within the hypothalamus, resulting in elevated plasma concentrations of both hormones under basal conditions. These changes are comparable to adaptations seen in the female peripartum period.
Functional Variant Disrupts Insulin Induction of USF1
Authors: Naukkarinen Jussi , Nilsson Emma , Koistinen Heikki A. , Söderlund Sanni , Lyssenko Valeriya , Vaag Allan , Poulsen Pernille , Groop Leif , Taskinen Marja-Riitta , Peltonen Leena
Published: June 2009

Background—

The upstream transcription factor 1 (
USF1
) gene is associated with familial combined hyperlipidemia, the most common genetic dyslipidemia in humans, as well as with various dyslipidemic changes in numerous other studies. Typical of complex disease-associated genes, neither the explicit mutations have been described nor the functional consequences for risk allele carriers been reported at the cellular or tissue level.

Methods and Results—

In this study, we aimed at describing the molecular mechanism through which the strongest associating intronic single-nucleotide polymorphism variant in
USF1
is involved in the development of dyslipidemia. The effects of the risk variant on gene expression were studied in 2 relevant human tissues, fat and muscle. Global transcript profiles of 47 fat biopsies ascertained for carriership of the risk allele were tested for differential expression of known USF1 target genes as well as for broader effects on the transcript profile. Allelic imbalance of
USF1
in fat was assessed using a quantitative sequencing approach. The possible allele-specific effect of insulin on the expression of
USF1
was studied in 118 muscle biopsies before and after a euglycemic hyperinsulinemic clamp. The risk allele of single-nucleotide polymorphism rs2073658 seems to eradicate the inductive effect of insulin on the expression of
USF1
in muscle and fat. The expression of numerous target genes is in turn perturbed in adipose tissue.

Conclusions—

In risk allele carriers, a defective response of
USF1
to insulin results in the suboptimal response of relevant target genes that contributes to the enhanced risk of developing dyslipidemia and coronary heart disease.
Working Time on Mars
Authors: Mirmalek Zara
Published: June 2009

The constancy of clock time as an effective work support technology has made it almost impossible to imagine a modern organization where time, specifically standard clock time, is not a component of the organizational infrastructure. Demonstrating the degree to which clock time has become embedded within the organizational sphere are the ways in which clock time operates as though it were a natural phenomenon, rather than a human-built technology (Adam, 1990; Anderson, 1964; Bluedorn, 2002; de Grazia, 1964; Zerubavel, 1981). The naturalization of clock time within organizations is evidenced by the reified assumption technology of clock time is fixed and cannot be modified to support contextually based temporal rhythms of work. The opportunity to challenge particular notions about the relationship between time and work is found in the organization of NASA's Mars Exploration Rovers mission (MER). In addition to standard clock time, the MER mission employed an extra-terrestrial version of standard clock time, known as “Mars time,” to track the presence and absence of sunlight on Mars. Drawing on empirical data, I foreground the inadequacies of the time support technologies that led me to question the use of standard clock time as a way of ordering the experience of time on Mars. I argue that the naturalization of clock time within post-industrial organizations contributed to this occasion in which the scientific exploration of Mars was conducted according to an agrarian era temporal rhythm but for which work support was organized around an industrial era time/work relationship.
Diurnally Asymmetric Trends of Temperature, Humidity, and Precipitation in Taiwan
Authors: Shiu Chein-Jung , Liu Shaw Chen , Chen Jen-Ping
Published: June 2009

In this work, 45 years (1961–2005) of hourly meteorological data in Taiwan, including temperature, humidity, and precipitation, have been analyzed with emphasis on their diurnal asymmetries. A long-term decreasing trend for relative humidity (RH) is found, and the trend is significantly greater in the nighttime than in the daytime, apparently resulting from a greater warming at night. The warming at night in three large urban centers is large enough to impact the average temperature trend in Taiwan significantly between 1910 and 2005. There is a decrease in the diurnal temperature range (DTR) that is largest in major urban areas, and it becomes smaller but does not disappear in smaller cities and offshore islands. The nighttime reduction in RH is likely the main cause of a significant reduction of fog events over Taiwan. The smaller but consistent reductions in DTR and RH in the three off-coast islands suggests that, in addition to local land use changes, a regional-scale process such as the indirect effect of anthropogenic aerosols may also contribute to these trends. A reduction in light precipitation (<4 mm h−1) and an increase in heavy precipitation (>10 mm h−1) are found over Taiwan and the offshore islands. The changes in precipitation are similar to the changes of other areas in Asia, but they are different from those of the United States, Europe, and the tropical oceans. The latter do not show any reduction in light precipitation.
Automatic Identification of Ramie and Cotton Fibers Using Characteristics in Longitudinal View, Part II: Fiber Stripes Analysis
Authors: Wang Rong Wu , Wu Xiong Ying , Wang Shan Yuan , Xu Bugao
Published: June 2009

Based on the analysis of stripes on fiber surfaces, a new method for cotton and ramie fiber identification is introduced in this paper. The stripes of a fiber surface were extracted by segmentation, edge detection, and thinning, and then they were orthogonally projected along the curving skeleton of the fiber. In addition, six characteristic parameters for identification were obtained, and based on the method of maximum probability, equations for identification were established on the six probability distribution curves of the characteristic parameters. Finally, weight coefficients of the equations were obtained from self-adapting identification tests. The experiments showed that the overall tolerance for false identification of cotton or ramie fiber was under 7%.
A Cage of Voices
Authors: Fu Diana
Published: June 2009

“I have a stomach full of words, but I just can’t say them” is a statement often uttered by migrant women in contemporary China. Using this as a point of entry, this article explores the paradoxical role that the Dagongmei’s Home, a Beijing women’s organization that promotes the rights and interests of female migrants, plays in producing identities for its members and in channeling their voices into the public arena. The Dagongmei’s Home is both a site of articulation and a cage that limits and contains the marginal voices of migrant women. By “hailing” its members into subjectivity as the dagongmei (working sister), the organization empowers these women to speak in otherwise closed spaces. However, since the women can only speak as dagongmei, they end up reproducing the state’s discourse of modernization. Nevertheless, a community-based drama workshop set up by a British woman in collaboration with the Home becomes an unlikely site of resistance as migrant women break the script of strong women sacrificing for the nation’s economic development, thus doing dagongmei subversively.
A Case Study in the Applied Philosophy of Imaging: The Synaptic Vesicle Debate
Authors: Rosenberger Robert
Published: June 2009

Thinkers from a variety of fields analyze the roles of imaging technologies in science and consider their implications for many issues, from our conception of selfhood to the authority of science. In what follows, I encourage scholars to develop an applied philosophy of imaging, that is, to collect these analyses of scientific imaging and to reflect on how they can be made useful for ongoing scientific work. As an example of this effort, I review concepts developed in Don Ihde’s phenomenology of technology and refigure them for use in the analysis of scientific practice. These concepts are useful for drawing out the details of the interpretive frameworks scientists bring to laboratory images. Next, I apply these ideas to a contemporary debate in neurobiology over the interpretation of images of neurons which have been frozen at the moment of transmitter release. This reveals directions for further thought for the study of neurotransmission.
Buckets of Resistance: Standards and the Effectiveness of Citizen Science
Authors: Ottinger Gwen
Published: June 2009

In light of arguments that citizen science has the potential to make environmental knowledge and policy more robust and democratic, this article inquires into the factors that shape the ability of citizen science to actually influence scientists and decision makers. Using the case of community-based air toxics monitoring with ‘‘buckets,’’ it argues that citizen science’s effectiveness is significantly influenced by standards and standardized practices. It demonstrates that, on one hand, standards serve a boundary-bridging function that affords bucket monitoring data a crucial measure of legitimacy among experts. On the other hand, standards simultaneously serve a boundary-policing function, allowing experts to dismiss bucket data as irrelevant to the central project of air quality assessment. The article thus calls attention to standard setting as an important site of intervention for citizen science-based efforts to democratize science and policy.
Male Adolescent Sexual Behavior
Authors: Collins Jennifer L. , Champion Jane Dimmitt
Published: June 2009

There is a need to involve sexual partners when addressing sexual behavior of high-risk adolescent women. This study explored men’s perceptions of their role in sexual relationships with adolescent women with a history of sexually transmitted infection (STI) and abuse. The AIDS risk reduction model was used to assess sexual risk behaviors of these men for development of cognitive behavioral risk reduction interventions for themselves and partner. Qualitative interviews were conducted with African and Mexican American men ( n = 14; ages 18 to 21 years), recruited via adolescent women enrolled in a control-randomized trial of behavioral interventions for reduction of unintended pregnancy, abuse, substance use, and STI. Participants varied in their perceptions of personal susceptibility to STI or HIV, access to informational resources regarding sexual behavior, and level of adult support for safer sexual behavior. These men shared perceptions of inadequate sexual health preparation, including education concerning risk, ultimately contributing to adverse outcomes of sexual behavior.
Nabilone produces marked impairments to cognitive function and changes in subjective state in healthy volunteers
Authors: Wesnes KA , Annas P , Edgar CJ , Deeprose C , Karlsten R , Philipp A , Kalliomäki J , Segerdahl M
Published: June 2009

This was a double-blind, randomised, placebo-controlled, crossover study of the acute cognitive and subjective effects of nabilone 1—3 mg in healthy male volunteers. The Cognitive Drug Research computerised system (CDR system) was used to assess changes in attention, working and episodic memory. In addition, a number of self-ratings were conducted including those of mood, alertness and perceived drug effects. Impairments to attention, working and episodic memory and self-ratings of alertness were evident. Volunteers also experienced a number of subjective drug effects. These data demonstrate that acute doses of nabilone in the range 1—3 mg produce clear cognitive and subjective effects in healthy volunteers, and therefore they may be used as reference data in the future study of peripherally acting cannabinoids believed to be free from such effects.
Effect of Risk Communication Formats on Risk Perception Depending on Numeracy
Authors: Keller Carmen , Siegrist Michael
Published: June 2009

Objective. To examine the influence of numeracy on interpreting various risk communication formats. Design. A random sample of women (N = 266) completed a questionnaire assessing numeracy and risk perception of prenatal test results and results of colon cancer screening tests. The authors examined the relationships between risk level (high v. low) and format of risk presentation (ratio, pictogram, or Paling Perspective Scale) and whether these relationships differed based on the numeracy skills of the participant. Results. The authors identified a significant (P <0.001) 3-way interaction between format, risk level, and numeracy: high-numerate participants in the low-risk group perceived the test results as less risky compared with participants in the high-risk group (P < 0.001) with the Paling Perspective Scale but not with the other formats. For low-numerate participants, they did not observe differences between low- and high-risk scenarios for any of the 3 formats. The results were similar for the Down syndrome and colon cancer scenarios. Overall, the pictogram resulted in significantly lower risk ratings compared with the Paling Perspective Scale and the ratio with numerator 1 (P < 0.001). Conclusion. Different communication formats may produce different risk perceptions, but the effect is qualified by patients' numeracy skills.