bluuebunny/crossref_metadata_2025 huggingface dataset:
A Singular Case of Prophage Complementation in Mutational Activation of
recET
Orthologs in
Salmonella enterica
Serovar Typhimurium
Authors: Lemire Sebastien , Figueroa-Bossi Nara , Bossi Lionello
Published: August 2008

A class of mutations that suppress the recombination defects of
recB
mutants in
Salmonella enterica
serovar Typhimurium strain LT2 activates the normally silent
recET
module of the Gifsy-1 prophage. Allele
sbcE21
is a 794-bp deletion within the immunity region of the prophage. Concomitant with activating
recET
,
sbcE21
stimulates Gifsy-1 excision, resulting in unstable suppression. Early studies found both
recB
suppression and its instability to depend on the presence of the related Gifsy-2 prophage elsewhere in the chromosome. In cells lacking Gifsy-2, the
sbcE21
allele became stable but no longer corrected
recB
defects. Here, we show that a single Gifsy-2 gene is required for Gifsy-1
recET
activation in the
sbcE21
background. This gene encodes GtgR, the Gifsy-2 repressor. Significantly, the
sbcE21
deletion has one end point within the corresponding gene in the Gifsy-1 genome,
gogR
, which in strain LT2 is a perfect duplicate of
gtgR
. The deletion truncates
gogR
and places the Gifsy-1 left operon, including the
recET
and
xis
genes, under the control of the
gogR
promoter. The ability of GtgR to
trans
-activate this promoter therefore implies that GtgR and GogR normally activate the transcription of their own genes. Consistent with the symmetry of the system, a similar deletion in Gifsy-2 results in a Gifsy-1-dependent
sbc
phenotype (
sbcF24
). Two additional Gifsy-1 deletions (
sbcE23
and
sbcE25
) were characterized, as well. The latter causes all but the last codon of the
gogR
gene to fuse, in frame, to the second half of
recE
. The resulting hybrid protein appears to function as both a transcriptional regulator and a recombination enzyme.
Paerucumarin, a New Metabolite Produced by the
pvc
Gene Cluster from
Pseudomonas aeruginosa
Authors: Clarke-Pearson Michael F. , Brady Sean F.
Published: August 2008

The
pvc
gene cluster from
Pseudomonas aeruginosa
has been linked to the biosynthesis of both the pyoverdine chromophore and pseudoverdine. Our reinvestigation of the role this gene cluster plays in
P. aeruginosa
secondary metabolite biosynthesis shows that its major product is actually paerucumarin, a novel isonitrile functionalized cumarin.
Regulation of the
Rhodobacter sphaeroides
2.4.1
hemA
Gene by PrrA and FnrL
Authors: Ranson-Olson Britton , Zeilstra-Ryalls Jill H.
Published: August 2008

Part of the oxygen responsiveness of
Rhodobacter sphaeroides
2.4.1 tetrapyrrole production involves changes in transcription of the
hemA
gene, which codes for one of two isoenzymes catalyzing 5-aminolevulinic acid synthesis. Regulation of
hemA
transcription from its two promoters is mediated by the DNA binding proteins FnrL and PrrA. The two PrrA binding sites, binding sites I and II, which are located upstream of the more-5′
hemA
promoter (P1), are equally important to transcription under aerobic conditions, while binding site II is more important under anaerobic conditions. By using phosphoprotein affinity chromatography and immunoblot analyses, we showed that the phosphorylated PrrA levels in the cell increase with decreasing oxygen tensions. Then, using both in vivo and in vitro methods, we demonstrated that the relative affinities of phosphorylated and unphosphorylated PrrA for the two binding sites differ and that phosphorylated PrrA has greater affinity for site II. We also showed that PrrA regulation is directed toward the P1 promoter. We propose that the PrrA component of anaerobic induction of P1 transcription is attributable to higher affinity of phosphorylated PrrA than of unphosphorylated PrrA for binding site II. Anaerobic activation of the more-3′
hemA
promoter (P2) is thought to involve FnrL binding to an FNR consensuslike sequence located upstream of the P2 promoter, but the contribution of FnrL to P1 induction may be indirect since the P1 transcription start is within the putative FnrL binding site. We present evidence suggesting that the indirect action of FnrL works through PrrA and discuss possible mechanisms.
Nitrogen Control in
Mycobacterium smegmatis
: Nitrogen-Dependent Expression of Ammonium Transport and Assimilation Proteins Depends on the OmpR-Type Regulator GlnR
Authors: Amon Johannes , Bräu Tanja , Grimrath Aletta , Hänβler Eva , Hasselt Kristin , Höller Martina , Jeβberger Nadja , Ott Lisa , Szököl Juraj , Titgemeyer Fritz , Burkovski Andreas
Published: August 2008

The effect of nitrogen regulation on the level of transcriptional control has been investigated in a variety of bacteria, such as
Bacillus subtilis, Corynebacterium glutamicum, Escherichia coli
, and
Streptomyces coelicolor
; however, until now there have been no data for mycobacteria. In this study, we found that the OmpR-type regulator protein GlnR controls nitrogen-dependent transcription regulation in
Mycobacterium smegmatis
. Based on RNA hybridization experiments with a wild-type strain and a corresponding mutant strain, real-time reverse transcription-PCR analyses, and DNA binding studies using cell extract and purified protein, the
glnA
(msmeg_4290) gene, which codes for glutamine synthetase, and the
amtB
(msmeg_2425) and
amt1
(msmeg_6259) genes, which encode ammonium permeases, are controlled by GlnR. Furthermore, since
glnK
(msmeg_2426), encoding a PII-type signal transduction protein, and
glnD
(msmeg_2427), coding for a putative uridylyltransferase, are in an operon together with
amtB
, these genes are part of the GlnR regulon as well. The GlnR protein binds specifically to the corresponding promoter sequences and functions as an activator of transcription when cells are subjected to nitrogen starvation.
Role of Phosphopantetheinyl Transferase Genes in Antibiotic Production by
Streptomyces coelicolor
Authors: Lu Ya-Wen , San Roman Adrianna K. , Gehring Amy M.
Published: August 2008

The phosphopantetheinyl transferase genes SCO5883 (
redU
) and SCO6673 were disrupted in
Streptomyces coelicolor
. The
redU
mutants did not synthesize undecylprodigiosin, while SCO6673 mutants failed to produce calcium-dependent antibiotic. Neither gene was essential for actinorhodin production or morphological development in
S. coelicolor
, although their mutation could influence these processes.
Identification of Residues Important for Cleavage of the Extracellular Signaling Peptide CSF of
Bacillus subtilis
from Its Precursor Protein
Authors: Lanigan-Gerdes Sara , Briceno Geraldine , Dooley Alek N. , Faull Kym F. , Lazazzera Beth A.
Published: August 2008

Extracellular Phr pentapeptides produced by gram-positive, spore-forming bacteria regulate processes during the transition from exponential- to stationary-phase growth. Phr pentapeptides are produced by cleavage of their precursor proteins. We determined the residues that direct this cleavage for the
Bacillus subtilis
Phr peptide, CSF, which is derived from the C terminus of PhrC. Strains expressing PhrC with substitutions in residues −1 to −5 relative to the cleavage site had a defect in CSF production. The mutant PhrC proteins retained a functional signal sequence for secretion, as assessed by secretion of PhrC-PhoA fusions. To determine whether the substitutions directly affected cleavage of PhrC to CSF, we tested cleavage of synthetic pro-CSF peptides that corresponded to the C terminus of PhrC and had an amino acid substitution at the −2, −3, or −4 position. The mutant pro-CSF peptides were cleaved less efficiently to CSF than the wild-type pro-CSF peptide whether they were incubated with whole cells, cell wall material, or the processing protease subtilisin or Vpr. To further define the range of amino acids that support CSF production, the amino acid at the −4 position of PhrC was replaced by the 19 canonical amino acids. Only four substitutions resulted in a >2-fold defect in CSF production, indicating that this position is relatively immune to mutational perturbations. These data revealed residues that direct cleavage of CSF and laid the groundwork for testing whether other Phr peptides are processed in a similar manner.
p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction
Authors: Xu Minlin , Remillard Carmelle V. , Sachs Benjamin D. , Makino Ayako , Platoshyn Oleksandr , Yao Weijuan , Dillmann Wolfgang H. , Akassoglou Katerina , Yuan Jason X.-J.
Published: August 2008

A member of the TNF receptor family, the p75 neurotrophin receptor (p75NTR) has been previously shown to play a role in the regulation of fibrin deposition in the lung. However, the role of p75NTRin the regulation of pulmonary vascular tone in the lung is unknown. In the present study, we evaluated the expression of p75NTRin mouse pulmonary arteries and the putative role of p75NTRin modulating pulmonary vascular tone and agonist responsiveness using wild-type (WT) and p75NTRknockout (p75−/−) mice. Our data indicated that p75NTRis expressed in both smooth muscle and endothelial cells within the pulmonary vascular wall in WT mice. Pulmonary artery rings from p75−/−mice exhibited significantly elevated active tension due to endothelin-1-mediated Ca2+influx. Furthermore, the contraction due to capacitative Ca2+entry (CCE) in response to phenylephrine-mediated active depletion of intracellular Ca2+stores was significantly enhanced compared with WT rings. The contraction due to CCE induced by passive store depletion, however, was comparable between WT and p75−/−rings. Active tension induced by serotonin, U-46619 (a thromboxane A2analog), thrombin, 4-aminopyridine (a K+channel blocker), and high extracellular K+in p75−/−rings was similar to that in WT rings. Deletion of p75NTRdid not alter pulmonary vasodilation to sodium nitroprusside (a nitric oxide donor). These data suggest that intact p75NTRsignaling may play a role in modulating pulmonary vasoconstriction induced by endothelin-1 and by active store depletion.
Theoretical model of metabolic blood flow regulation: roles of ATP release by red blood cells and conducted responses
Authors: Arciero Julia C. , Carlson Brian E. , Secomb Timothy W.
Published: August 2008

A proposed mechanism for metabolic flow regulation involves the saturation-dependent release of ATP by red blood cells, which triggers an upstream conducted response signal and arteriolar vasodilation. To analyze this mechanism, a theoretical model is used to simulate the variation of oxygen and ATP levels along a flow pathway of seven representative segments, including two vasoactive arteriolar segments. The conducted response signal is defined by integrating the ATP concentration along the vascular pathway, assuming exponential decay of the signal in the upstream direction with a length constant of ∼1 cm. Arteriolar tone depends on the conducted metabolic signal and on local wall shear stress and wall tension. Arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model predicts that conducted responses stimulated by ATP release in venules and propagated to arterioles can account for increases in perfusion in response to increased oxygen demand that are consistent with experimental findings at low to moderate oxygen consumption rates. Myogenic and shear-dependent responses are found to act in opposition to this mechanism of metabolic flow regulation.
Cardiac-restricted overexpression of extracellular matrix metalloproteinase inducer causes myocardial remodeling and dysfunction in aging mice
Authors: Zavadzkas Juozas A. , Plyler Rebecca A. , Bouges Shenikqua , Koval Christine N. , Rivers William T. , Beck Christy U. , Chang Eileen I. , Stroud Robert E. , Mukherjee Rupak , Spinale Francis G.
Published: August 2008

The matrix metalloproteinases (MMPs) play a pivotal role in adverse left ventricular (LV) myocardial remodeling. The transmembrane protein extracellular MMP inducer (EMMPRIN) causes increased MMP expression in vitro, and elevated levels occur in patients with LV failure. However, the direct consequences of a prolonged increase in the myocardial expression of EMMPRIN in vivo remained unexplored. Cardiac-restricted EMMPRIN expression (EMMPRINexp) was constructed in mice using the full-length human EMMPRIN gene ligated to the myosin heavy chain promoter, which yielded approximately a twofold increase in EMMPRIN compared with that of the age/strain-matched wild-type (WT) mice; EMMPRINexp ( n = 27) and WT ( n = 33) mice were examined at 3.2 ± 0.1 or at 13.3 ± 0.5 mo of age ( n = 43 and 26, respectively). LV end-diastolic volume (EDV) was similar in young EMMPRINexp and WT mice (54 ± 2 vs. 57 ± 3 μl), but LV ejection fraction (EF) was reduced (51 ± 1 vs. 57 ± 1%; P < 0.05). In old EMMPRINexp mice, LV EDV was increased compared with WT mice values (76 ± 3 vs. 58 ± 3 μl; P < 0.05) and LV EF was significantly reduced (45 ± 1 vs. 57 ± 2%; P < 0.05). In EMMPRINexp old mice, myocardial MMP-2 and membrane type-1 MMP levels were increased by >50% from WT values ( P < 0.05) and were accompanied by a twofold higher collagen content ( P < 0.05). Persistent myocardial EMMPRINexp in aging mice caused increased levels of both soluble and membrane type MMPs, fibrosis, and was associated with adverse LV remodeling. These findings suggest that EMMPRIN is an upstream signaling pathway that can play a mechanistic role in adverse remodeling within the myocardium.
Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice
Authors: Bouhidel Omar , Pons Sandrine , Souktani Richard , Zini Roland , Berdeaux Alain , Ghaleh Bijan
Published: August 2008

Ischemic postconditioning (IPCD) significantly reduces infarct size in healthy animals and protects the human heart. Because obesity is a major risk factor of cardiovascular diseases, the effects of IPCD were investigated in 8- to 10-wk-old leptin-deficient obese ( ob/ob) mice and compared with wild-type C57BL/6J (WT) mice. All animals underwent 30 min of coronary artery occlusion followed by 24 h of reperfusion associated or not with IPCD (6 cycles of 10-s occlusion, 10-s reperfusion). Additional mice were killed at 10 min of reperfusion for Western blotting. IPCD reduced infarct size by 58% in WT mice (33 ± 1% vs. 14 ± 3% for control and IPCD, respectively, P < 0.05) but failed to induce cardioprotection in ob/ob mice (53 ± 4% vs. 56 ± 5% for control and IPCD, respectively). In WT mice, IPCD significantly increased the phosphorylation of Akt (+77%), ERK1/2 (+41%), and their common target p70S6K1 (+153% at Thr389 and +57% at Thr421/Ser424). In addition, the phosphorylated AMP-activated protein kinase (AMPK)-to-total AMPK ratio was also increased by IPCD in WT mice (+64%, P < 0.05). This was accompanied by decreases in phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MAP kinase phosphatase (MKP)-3, and protein phosphatase (PP)2C levels. In contrast, IPCD failed to increase the phosphorylation state of all these kinases in ob/ob mice, and the level of the three phosphatases was significantly increased. Thus, although IPCD reduces myocardial infarct size in healthy animals, its cardioprotective effect vanishes with obesity. The lack of enhanced phosphorylation by IPCD of Akt, ERK1/2, p70S6K1, and AMPK might partly explain the loss of cardioprotection in this experimental model of obese mice.
Inhibitor-2 prevents protein phosphatase 1-induced cardiac hypertrophy and mortality
Authors: Brüchert Nicole , Mavila Nirmala , Boknik Peter , Baba Hideo A. , Fabritz Larissa , Gergs Ulrich , Kirchhefer Uwe , Kirchhof Paulus , Matus Marek , Schmitz Wilhelm , DePaoli-Roach Anna A. , Neumann Joachim
Published: August 2008

Cardiac-specific overexpression of the catalytic subunit of protein phosphatase type 1 (PP1) in mice results in hypertrophy, depressed contractility, propensity to heart failure, and premature death. To further address the role of PP1 in heart function, PP1 mice were crossed with mice that overexpress a functional COOH-terminally truncated form of PP1 inhibitor-2 (I-2140). Protein phosphatase activity was increased in PP1 mice but was normalized in double transgenic (DT) mice. The maximal rates of contraction (+dP/d t) and of relaxation (−dP/d t) were reduced in catheterized PP1 mice but normalized in DT mice. Similar contractile abnormalities were observed in isolated, perfused work-performing hearts and in whole animals by means of echocardiography. The increased absolute and relative heart weights observed in PP1 mice were normalized in DT mice. Histological analyses indicated that PP1 mice had significant cardiac fibrosis, which was absent in DT mice. Furthermore, PP1 mice exhibited an age-dependent increase in mortality, which was abrogated in DT mice. These results indicate that I-2 overexpression prevents the detrimental effects of PP1 overexpression in the heart and further underscore the fundamental role of PP1 in cardiac function. Therefore, PP1 inhibitors such as I-2 could offer new therapeutic options to ameliorate the deleterious effects of heart failure.
Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension
Authors: Goodwill Adam G. , James Milinda E. , Frisbee Jefferson C.
Published: August 2008

This study determined if altered vascular prostacyclin (PGI2) and/or thromboxane A2 (TxA2) production with reduced Po2 contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po2 under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po2. Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI2 production with reduced Po2 was similar between strains, although TxA2 production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH2/TxA2 receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA2, which competes against the vasodilator influences of PGI2. These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA2 production and may blunt vascular sensitivity to PGI2.
Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration
Authors: Yokoyama Utako , Minamisawa Susumu , Quan Hong , Akaike Toru , Jin Meihua , Otsu Koji , Ulucan Coskun , Wang Xu , Baljinnyam Erdenechimeg , Takaoka Minoru , Sata Masataka , Ishikawa Yoshihiro
Published: August 2008

Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2′- O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2′- O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury.
Long-term exposure to LPS enhances the rate of stimulated exocytosis and surfactant secretion in alveolar type II cells and upregulates P2Y2receptor expression
Authors: Garcia-Verdugo Ignacio , Ravasio Andrea , de Paco Elvira Garcia , Synguelakis Monique , Ivanova Nina , Kanellopoulos Jean , Haller Thomas
Published: August 2008

Bacterial LPS is a potent proinflammatory molecule. In the lungs, LPS induces alterations in surfactant pool sizes and phospholipid (PL) contents, although direct actions of LPS on the alveolar type II cells (AT II) are not yet clear. For this reason, we studied short- and long-term effects of LPS on basal and agonist-stimulated secretory responses of rat AT II by using Ca2+microfluorimetry, a microtiter plate-based exocytosis assay, by quantitating PL and3H-labeled choline released into cell supernatants and by using quantitative PCR and Western blot analysis. Long term, but not short term, exposures to LPS led to prolonged ATP-induced Ca2+signals and an increased rate in vesicle fusions with an augmented release of surfactant PL. Most notably, the stimulatory effect of LPS was ATP-dependent and may be mediated by the upregulation of the purinergic receptor subtype P2Y2. Western blot analysis confirmed higher levels of P2Y2, and suramin, a P2Y receptor antagonist, was more effective in LPS-treated cells. From these observations, we conclude that LPS, probably via Toll-like receptor-4, induces a time-dependent increase in P2Y2receptors, which, by yet unknown mechanisms, leads to prolonged agonist-induced Ca2+responses that trigger a higher activity in vesicle fusion and secretion. We further conclude that chronic exposure to endotoxin sensitizes AT II to increase the extracellular surfactant pool, which aids in the pulmonary host defense mechanisms.
Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione
Authors: Baglole Carolyn J. , Sime Patricia J. , Phipps Richard P.
Published: August 2008

Fibroblasts are key structural cells that can be damaged by cigarette smoke. Cigarette smoke contains many components capable of eliciting oxidative stress, which may induce heme oxygenase (HO)-1, a cytoprotective enzyme. There are no data on HO-1 expression in primary human lung fibroblasts after cigarette smoke extract (CSE) exposure. We hypothesized that human lung fibroblasts exposed to cigarette smoke would increase HO-1 though changes in intracellular glutathione (GSH). Primary human lung fibroblasts were exposed to CSE, and changes in HO-1 expression and GSH levels were assessed. CSE induced a time- and dose-dependent increase in expression of HO-1, but not HO-2 or biliverdin reductase, in two different primary human lung fibroblast strains, a novel finding. This induction of HO-1 paralleled a decrease in intracellular GSH, and a sustained reduction in GSH resulted in a dramatic increase in HO-1. Treatment with the antioxidants N-acetyl-l-cysteine or GSH reduced the expression of HO-1 induced by CSE. We also examined the signal transduction mechanism responsible for HO-1 induction. Nuclear factor erythroid-derived 2, like 2 (Nrf2) was not involved in HO-1 induction by CSE. Activator protein-1 (AP-1) is a redox-sensitive transcription factor shown in other systems to regulate HO-1 expression. CSE exposure resulted in nuclear accumulation of c-Fos and c-Jun, two key AP-1 components. Reduction of c-Fos and c-Jun nuclear translocation by SP-600125 attenuated the CSE-induced expression of HO-1. These data support the concept that changes in the cellular redox status brought on by cigarette smoke induce HO-1 in fibroblasts. This increase in HO-1 may help protect against cigarette smoke-induced inflammation and/or cell death.
Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation
Authors: Birukova Anna A. , Moldobaeva Nurgul , Xing Junjie , Birukov Konstantin G.
Published: August 2008

Mechanical ventilation at high tidal volumes compromises the blood-gas barrier and increases lung vascular permeability, which may lead to ventilator-induced lung injury and pulmonary edema. Using pulmonary endothelial cell (ECs) exposed to physiologically [5% cyclic stretch (CS)] and pathologically (18% CS) relevant magnitudes of CS, we evaluated the potential protective effects of hepatocyte growth factor (HGF) on EC barrier dysfunction induced by CS and vascular endothelial growth factor (VEGF). In static culture, HGF enhanced EC barrier function in a Rac-dependent manner and attenuated VEGF-induced EC permeability and paracellular gap formation. The protective effects of HGF were associated with the suppression of Rho-dependent signaling triggered by VEGF. Five percent CS promoted HGF-induced enhancement of the cortical F-actin rim and activation of Rac-dependent signaling, suggesting synergistic barrier-protective effects of physiological CS and HGF. In contrast, 18% CS further enhanced VEGF-induced EC permeability, activation of Rho signaling, and formation of actin stress fibers and paracellular gaps. These effects were attenuated by HGF pretreatment. EC preconditioning at 5% CS before HGF and VEGF further promoted EC barrier maintenance. Our data suggest synergistic effects of HGF and physiological CS in the Rac-mediated mechanisms of EC barrier protection. In turn, HGF reduced the barrier-disruptive effects of VEGF and pathological CS via downregulation of the Rho pathway. These results support the importance of HGF-VEGF balance in control of acute lung injury/acute respiratory distress syndrome severity via small GTPase-dependent regulation of lung endothelial permeability.
Neuraminidase-1 is required for the normal assembly of elastic fibers
Authors: Starcher Barry , d'Azzo Alessandra , Keller Patrick W. , Rao Gottipati K. , Nadarajah Deepa , Hinek Alexsander
Published: August 2008

The assembly of elastic fibers in tissues that undergo repeated cycles of extension and recoil, such as the lungs and blood vessels, is dependent on the proper interaction and alignment of tropoelastin with a microfibrillar scaffold. Here, we describe in vivo histopathological effects of neuraminidase-1 (Neu1) deficiency on elastin assembly in the lungs and aorta of mice. These mice exhibited a tight-skin phenotype very similar to the Tsk mouse. Normal septation of Neu1-null mice did not occur in neonatal mice, resulting in enlarged alveoli that were maintained in adults. The abnormal development of elastic fibers was remarkable under electron microscopy and confirmed by the overlapping distribution of elastin, fibrillin-1, fibrillin-2, and fibulin-5 (Fib-5) by the light microscopy immunostainings. Fib-5 fibers appeared diffuse and unorganized around the alveolar walls and the apex of developing secondary septal crests. Fibrillin-2 deposition was also abnormal in neonatal and adult lungs. Dispersion of myofibroblasts appeared abnormal in developing lungs of Neu1-null mice, with a random distribution of myofibroblast around the alveolar walls, rather than concentrating at sites of elastin synthesis. The elastic lamellae in the aorta of the Neu1-null mice were thinner and separated by hypertrophic smooth muscle cells that were surrounded by an excess of the sialic acid-containing moieties. The concentration of elastin, as measure by desmosine levels, was significantly reduced in the aorta of Neu1-null mice. Message levels for tropoelastin and Fib-5 were normal, suggesting the elastic fiber defects in Neu1-null mice result from impaired extracellular assembly.
P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus
Authors: Kwong Kevin , Kollarik Marian , Nassenstein Christina , Ru Fei , Undem Bradley J.
Published: August 2008

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to α,β-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to α,β-methylene ATP (30 μM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of α,β-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.
Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects
Authors: Briggs Laura E. , Takeda Morihiko , Cuadra Adolfo E. , Wakimoto Hiroko , Marks Melissa H. , Walker Alexandra J. , Seki Tsugio , Oh Suk P. , Lu Jonathan T. , Sumners Colin , Raizada Mohan K. , Horikoshi Nobuo , Weinberg Ellen O. , Yasui Kenji , Ikeda Yasuhiro , Chien Kenneth R. , Kasahara Hideko
Published: August 2008

Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5 knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by reduction in ventricular expression of the cardiac voltage-gated Na
+
channel pore-forming α-subunit (Na
v
1.5-α), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca
2+
for contraction (conduction–contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca
2+
is released from sarcoplasmic reticulum, was substantially reduced in Nkx2-5 knockout mice. These results indicate that Nkx2-5 function is critical not only during cardiac development but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction.
Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis
Authors: Kisucka Janka , Chauhan Anil K. , Patten Ian S. , Yesilaltay Ayce , Neumann Carola , Van Etten Richard A. , Krieger Monty , Wagner Denisa D.
Published: August 2008

The peroxiredoxin (Prdx) family of antioxidant enzymes uses redox-active cysteines to reduce peroxides, lipid hydroperoxides, and peroxynitrites. Prdx1 is known to be important to protect red blood cells against reactive oxygen species and in tumor prevention. In this study, the role of Prdx1 in inflammation, thrombosis, and atherosclerosis was investigated. Using intravital microscopy, we showed that the number of leukocytes rolling per minute in unstimulated veins was increased by 2.5-fold in
Prdx
1
−/−
compared to
Prdx
1
+/+
mice. In
Prdx
1
−/−
mice, 50% of leukocytes rolled at a velocity <10 μm/sec compared with 10% in
Prdx
1
+/+
mice, suggesting that adhesion molecule density on the endothelium may have been increased by Prdx1 deficiency. Indeed, endothelial P-selectin, soluble P-selectin, and von Willebrand factor in plasma were increased in
Prdx
1
−/−
mice compared to
Prdx
1
+/+
mice, indicating elevated Weibel–Palade body release. In contrast to this excessive endothelial activation,
Prdx
1
−/−
platelets showed no sign of hyperreactivity, and their aggregation both in vitro and in vivo was normal. We also examined the role of Prdx1 in the
apoE
−/−
murine spontaneous model of atherosclerosis.
Prdx
1
−/−
/
apoE
−/−
mice fed normal chow developed larger, more macrophage-rich aortic sinus lesions than
Prdx
1
+/+
/
apoE
−/−
mice, despite similar amounts and size distributions of cholesterol in their plasma lipoproteins. Thus, Prdx1 protects against excessive endothelial activation and atherosclerosis, and the
Prdx
1
−/−
mice could serve as an animal model susceptible to chronic inflammation.
Social Capital and College Planning
Authors: Farmer-Hinton Raquel L.
Published: August 2008

Through analyses of focus group transcripts, the author highlights key school-based supports and resources students viewed as helpful in their college-planning activities and explores the challenges students' expressed about being exposed to school-based social capital while living in disadvantaged community contexts. The findings suggest the importance of intersecting dosages of school-based social capital such as high expectations and experiential learning to help students complete their college-planning activities as well as the need for coping strategies for the psychological barriers of being college-bound within contexts where college access is not widely available.
Tensions in Multicultural Teacher Education Research
Authors: Furman Jim S.
Published: August 2008

This article builds on the results of an analysis of reviews of data-based research literature in the field of multicultural teacher education. The author discusses two examples of major findings from the seven reviews considered: the amount and quality of research and the hidden curriculum of teacher education. Limitations of the reviews are also discussed and particular attention is paid to the issues of defining multiculturalism and building a theoretical argument. The author describes, in detail, two major tensions that are evident in the field: the demographic tension and the effectiveness tension. In addition, the article suggests ways in which the field might move forward by establishing a strong theoretical rationale for its investigations.
Princes Shall Come out of Egypt
Authors: Walker Aswad
Published: August 2008

Marcus Garvey left substantial documentation regarding his beliefs about the nature of God, humanity, and salvation and the role of religion, positioning him as a theologian of considerable merit. Yet Garvey's contributions to the religious discourse have been widely ignored in academic circles, even though his theological ideas found tangible expression in his programs and institutions founded and in movements espousing solidarity to Garvey's race first agenda. One such movement is the Shrine of the Black Madonna of the Pan African Orthodox Christian Church (PAOCC). Founded in 1953 by the late Reverend Albert B. Cleage Jr., considered by many to be the father of Black liberation theology, the PAOCC embodies many of Garvey's beliefs. In this article, the author explores the similarities and differences in Garvey's and Cleage's theologies and their organizational expressions via the Universal Negro Improvement Association and the African Orthodox Church, and the PAOCC, respectively.
Family Structure and Children's Psychosocial Outcomes
Authors: Zheng Wu  , Feng Hou  , Schimmele Christoph M.
Published: August 2008

This article examines the influence of family structure on children's short-term psychosocial behavioral outcomes, including emotional disorder, conduct disorder, and prosocial behavior. The analysis uses five waves of data (1994-2003) from Canada's National Longitudinal Survey of Children and Youth to model how living in a cohabitational household (two biological parents) and how experiencing cohabitation dissolution influence children's behaviors, comparing these effects to outcomes observed in children from married biological-parent households. The findings indicate that growing up in a married biological-parent household does not offer a clear advantage. Most differences in behavioral problems across family structure associate with household demographics, low-income status, family dysfunction, and parental nurturance. As such, this study contributes two important findings. First, the results do not support the hypothesis that nonmarital cohabitation represents an undesirable child-rearing environment. Second, cohabitation dissolution has a nonsignificant effect on children's behaviors, which is surprising considering that divorce has a well-established harmful effect.
Social Loafing on Group Projects
Authors: Aggarwal Praveen , O'Brien Connie L.
Published: August 2008

To respond to the expectations of the industry and business school accreditation bodies, marketing faculty have been making extensive use of group projects in their curricula. A common problem with the use of student groups, however, is that of social loafing. In this study, we identify some easy-to-implement project set-up factors and examine their impact on reducing the incidence of social loafing. We find that the incidence of social loafing increases with the scope of the project and the size of the student group assigned to the project. We also find that having multiple peer evaluations during the course of the project reduces social loafing. We study the impact of social loafing on students' satisfaction with group members' contribution and the perceived fairness of the project grade. Recommendations for reducing social loafing and increasing students' satisfaction with group projects are also discussed.
Divergent Thinking and Interview Ratings
Authors: Batey Mark , Rawles Richard , Furnham Adrian
Published: August 2008

This study examined divergent thinking (DT) test scores of applicants taking part in a selection procedure for an undergraduate psychology degree ( N = 370). Interviewers made six specific (creative intelligence, motivation, work habits, emotional stability, sociability, and social responsibility) and one overall recommendation rating on each candidate. Results show that trained interviewers could identify which applicants would receive greater scores for originality for DT test scores. The implications for the use of DT tests in selection are considered.
Autumn Leaves: Excellence in Design Development Using Draping Techniques, 2006
Authors: Schactler Carolyn
Published: August 2008

The purpose of this project was to make a gown that glorifies the colors and shapes of fall leaves. The plan was to exhibit replica leaves of fabric by sandwiching them between layers of satin and tulle. The top layer of tulle was necessary to inhibit the abrasion of the raw fabric edges and to create the composite fabric. Inspiration came from the leaves themselves that displayed so many interesting shapes and brilliant autumn colors.
Clothing Invention
Authors: Peteu Mihaela Cornelia , Helvenston Gray Sally
Published: August 2008

Historians have increasingly used patents to better understand historical antecedents for modern functional attire. This study examined 1,126 patents from the U.S. Patent and Trademark Office “Nether Garments/Skirts” class to investigate skirt function from 1846 to 1920. Thematic content analysis was used to determine a primary purpose for each patent; purposes were then grouped into (a) fashion (primarily shaping devices), (b) wearability, (c) use, and (d) manufacturing. Wearability-related purposes outnumbered those devoted to fashion almost twofold, which emphasizes difficulties women encountered in wearing fashionable skirts. Two major thrusts were determined: (a) between 1846 and 1890, inventors attempted to overcome dysfunctional aspects of wearing fashionable skirt silhouettes, and (b) after 1890 attention turned to skirts designed for sports and professional activities and to meet the special requirements of women's unique physiology (maternity and sanitary protection). Shaping devices followed the generally accepted timeline for fashionable silhouettes, indicating market demand as a patent incentive.
A Rich-Media Solution for Distance Education
Authors: Vasu Michael L. , Ozturk Ali O.
Published: August 2008

MediaSite by Sonic Foundry is a web communication and content management system that automatically webcasts lectures and presentations. These presentations can be viewed as a live stream or as an archive over the Internet. MediaSite is frequently used to supplement traditional classes and distance education applications. In this review, the authors share their experience in using a rich-media tool MediaSite that added a great teaching quality and affectivity to an undergraduate survey methodology course within distance education format. Their experience leads them to believe that this technology can enhance a methods course such as survey research by providing visual reinforcement of what are otherwise textbook lectures. This is also true with respect to the expectations of assignments and reviews for final exams.
What's on Wikipedia, and What's Not . . . ?
Authors: Royal Cindy , Kapila Deepina
Published: August 2008

The World Wide Web continues to grow closer to achieving the vision of becoming the repository of all human knowledge, as features and applications that support user-generated content become more prevalent. Wikipedia is fast becoming an important resource for news and information. It is an online information source that is increasingly used as the first, and sometimes only, stop for online encyclopedic information. Using a method employed by Tankard and Royal to judge completeness of Web content, completeness of information on Wikipedia is assessed. Some topics are covered more comprehensively than others, and the predictors of these biases include recency, importance, population, and financial wealth. Wikipedia is more a socially produced document than a value-free information source. It reflects the viewpoints, interests, and emphases of the people who use it.
Streptococcus pneumoniae: An Update on Resistance Patterns in the United States
Authors: Starr Jessica A. , Fox Georgia W. , Clayton Jennifer K.
Published: August 2008

Streptococcus pneumoniae represents an important pathogen in numerous community-acquired respiratory infections. Penicillin resistance to Streptococcus pneumoniae in the United States has approached 35%. Additionally, there has been a significant increase in Streptococcus pneumoniae resistance among many other antimicrobial agents such as cephalosporins, macrolides, trimethoprim–sulfamethoxazole, clindamycin, tetracyclines, and chloramphenicol. Several nationwide surveillance programs have been implemented to quantify the prevalence of Streptococcus pneumoniae resistance in the United States. Overall, beta-lactam, macrolide, trimethoprim–sulfamethoxazole, and tetracycline resistance has increased over the past decade while later generation fluoroquinolones (levofloxacin and moxifloxacin) resistance has remained low. Controlling the spread of resistant pneumococcal isolates and preventing the development of both fluoroquinolone and multidrug resistant isolates will require a multidisciplinary approach involving physicians, pharmacists, microbiologists, and epidemiologists.
Management and Treatment Considerations for Infections Caused by Methicillin-Resistant Staphylococcus aureus
Authors: Wargo Kurt A. , Eiland Edward H. , Eiland Lea S.
Published: August 2008

Infections caused by methicillin-resistant Staphylococcus aureus have been documented since the 1960s. Four decades later, this microorganism has evolved from a pathogen found primarily in the health care environment to a major pathogen of community-acquired infections. Interestingly, the community-acquired methicillin-resistant Staphylococcus aureus isolates tend to be genetically distinct from their health-care–acquired relatives, have a propensity to be more virulent, yet be susceptible to more antibiotics. Furthermore, infections caused in the pediatric population have a susceptibility pattern that differs from those found in adults. With an increase in infections caused by methicillin-resistant Staphylococcus aureus, empiric therapy should contain an agent with activity against this microorganism. Currently several options exist for the treatment of skin and skin structure infections, yet very few options are available for the treatment of more invasive diseases caused by methicillin-resistant Staphylococcus aureus. This article will review the history of methicillin-resistant Staphylococcus aureus, Staphylococcus aureus economic considerations, and the current plus future treatment options for these infections.
Social Work Education: Status Quo or Change?
Authors: Sowers Karen M. , Dulmus Catherine N.
Published: August 2008

The authors believe that Stoesz and Karger did not go far enough in their critique. The struggling state of the profession and of social work education is symptomatic of a much larger and fundamental systemic problem that cannot be addressed solely by fixing the Council on Social Work Education or increasing requirements for Social Science Citation Index publications. Social work must build a broad-based capacity for rigorous scientific inquiry and train the next generation of faculty researchers and practitioners to carry on this essential work.
Suicidality and Self-Harm Among Sexual Minorities in Japan
Authors: DiStefano Anthony S.
Published: August 2008

In this study, I used ethnographic methods to examine suicidality and nonsuicidal self-harm among gay, lesbian, bisexual, and transgender persons in Japan. Participants ( N = 84) indicated that suicidality and self-harm are serious problems among sexual minorities and tend to be driven by (a) a homophobic/transphobic environment and the negative consequences of sexual minorities either disclosing their true selves or remaining hidden and silent within such an environment; (b) various antecedents to poor mental health; and (c) factors not directly related to being a sexual minority, particularly unemployment and debt in the context of a protracted national economic decline in Japan prior to the study period of 2003–2004. Participants also perceived a potentially higher risk for suicidality and self-harm among sexual minority adolescents and persons in their early 20s; those who work in the entertainment, bar, or sex industries; and survivors of violence perpetrated by intimate partners or family members.