bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation of the Flavivirus Kunjin NS3 Gene in
cis
but Not Its RNA Sequence or Secondary Structure Is Essential for Efficient RNA Packaging
Authors: Pijlman Gorben P. , Kondratieva Natasha , Khromykh Alexander A.
Published: October 2006

Our previous studies using
trans
-complementation analysis of Kunjin virus (KUN) full-length cDNA clones harboring in-frame deletions in the NS3 gene demonstrated the inability of these defective complemented RNAs to be packaged into virus particles (W. J. Liu, P. L. Sedlak, N. Kondratieva, and A. A. Khromykh, J. Virol.
76:
10766-10775). In this study we aimed to establish whether this requirement for NS3 in RNA packaging is determined by the secondary RNA structure of the NS3 gene or by the essential role of the translated NS3 gene product. Multiple silent mutations of three computer-predicted stable RNA structures in the NS3 coding region of KUN replicon RNA aimed at disrupting RNA secondary structure without affecting amino acid sequence did not affect RNA replication and packaging into virus-like particles in the packaging cell line, thus demonstrating that the predicted conserved RNA structures in the NS3 gene do not play a role in RNA replication and/or packaging. In contrast, double frameshift mutations in the NS3 coding region of full-length KUN RNA, producing scrambled NS3 protein but retaining secondary RNA structure, resulted in the loss of ability of these defective RNAs to be packaged into virus particles in complementation experiments in KUN replicon-expressing cells. Furthermore, the more robust complementation-packaging system based on established stable cell lines producing large amounts of complemented replicating NS3-deficient replicon RNAs and infection with KUN virus to provide structural proteins also failed to detect any secreted virus-like particles containing packaged NS3-deficient replicon RNAs. These results have now firmly established the requirement of KUN NS3 protein translated in
cis
for genome packaging into virus particles.
Functions of the Stem Region of the Semliki Forest Virus Fusion Protein during Virus Fusion and Assembly
Authors: Liao Maofu , Kielian Margaret
Published: October 2006

Membrane fusion of the alphaviruses is mediated by the E1 protein, a class II virus membrane fusion protein. During fusion, E1 dissociates from its heterodimer interaction with the E2 protein and forms a target membrane-inserted E1 homotrimer. The structure of the homotrimer is that of a trimeric hairpin in which E1 domain III and the stem region fold back toward the target membrane-inserted fusion peptide loop. The E1 stem region has a strictly conserved length and several highly conserved residues, suggesting the possibility of specific stem interactions along the trimer core and an important role in driving membrane fusion. Mutagenesis studies of the alphavirus Semliki Forest virus (SFV) here demonstrated that there was a strong requirement for the E1 stem in virus assembly and budding, probably reflecting its importance in lateral interactions of the envelope proteins. Surprisingly, however, neither the conserved length nor any specific residues of the stem were required for membrane fusion. Although the highest fusion activity was observed with wild-type E1, efficient fusion was mediated by stem mutants containing a variety of substitutions or deletions. A minimal stem length was required but could be conferred by a series of alanine residues. The lack of a specific stem sequence requirement during SFV fusion suggests that the interaction of domain III with the trimer core can provide sufficient driving force to mediate membrane merger.
MODIFIED MATCHED ULNAR RESECTION FOR ARTHROSIS OF DISTAL RADIOULNAR JOINT IN RHEUMATOID ARTHRITIS
Authors: Srikanth K. N. , Shahane S. A. , Stilwell J. H.
Published: October 2006

The pain of distal radioulnar arthrosis in rheumatoid patients is often due to disease largely confined to the radioulnar rather than the ulnocarpal articulation. This is a retrospective study of 14 patients (14 wrists) who underwent selective shaving of the radial articulation of the ulnar head leaving the ulnocarpal articulation intact. The ulnar head is reduced to the circumference of its shaft and a dorsal retinacular flap is interposed between it and the distal radius. Average age of the patients and follow-up were 63.5 years and 31 months, respectively. All patients had rheumatoid arthritis. Pain improved in 14 out of 15 wrists. Overall results were 67% good to excellent and 33% fair based on the modified Mayo's wrist score. This novel procedure for DRUJ arthrosis produces predictable pain relief in low demand rheumatoid patient.
ANEURYSMAL BONE CYST OF THE HAND: A REPORT OF FOUR CASES
Authors: Başarir Kerem , Saǧlik Yener , Yildiz Yusuf , Tezen Engyn
Published: October 2006

Aneurysmal bone cysts are benign lesions that rarely occur in the bones of the hand. Curettage and bone grafting are the most common treatment modalities performed considering the possible functional loss after total excision. Four cases of aneurysmal bone cyst of the hand were identified. Three out of four cases were treated initially with curettage and bone grafting alone without any other local therapy. One had total excision of the lesion. There were two recurrences in the curettage group. Both were treated with excision and followed up for a minimum of 12 months. Curettage alone was associated with high recurrence rates. Total excision of the lesion was the most successful procedure employed. In view of the high recurrence rates following curettage alone and non-neoplastic nature of the lesion, adjuvant treatment modalities such as cryosurgery, electric cauterisation should be considered for initial treatment of ABC. Resection should be preserved for recurrent cases.
Copper and the Prion Protein: Methods, Structures, Function, and Disease
Authors: Millhauser Glenn L.
Published: October 2006

The transmissible spongiform encephalopathies (TSEs) arise from conversion of the membrane-bound prion protein from PrPC to PrPSc. Examples of the TSEs include mad cow disease, chronic wasting disease in deer and elk, scrapie in goats and sheep, and kuru and Creutzfeldt-Jakob disease in humans. Although the precise function of PrPC in healthy tissues is not known, recent research demonstrates that it binds Cu(II) in an unusual and highly conserved region of the protein termed the octarepeat domain. This review describes recent connections between copper and PrPC, with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrPC function, and emerging connections between copper and prion disease.
Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells
Authors: Brueggemann Lioubov I. , Moran Christopher J. , Barakat John A. , Yeh Jay Z. , Cribbs Leanne L. , Byron Kenneth L.
Published: October 2006

[Arg8]-vasopressin (AVP), at low concentrations (10–500 pM), stimulates oscillations in intracellular Ca2+concentration (Ca2+spikes) in A7r5 rat aortic smooth muscle cells. Our previous studies provided biochemical evidence that protein kinase C (PKC) activation and phosphorylation of voltage-sensitive K+(Kv) channels are crucial steps in this process. In the present study, Kvcurrents ( IKv) and membrane potential were measured using patch clamp techniques. Treatment of A7r5 cells with 100 pM AVP resulted in significant inhibition of IKv. This effect was associated with gradual membrane depolarization, increased membrane resistance, and action potential (AP) generation in the same cells. The AVP-sensitive IKvwas resistant to 4-aminopyridine, iberiotoxin, and glibenclamide but was fully inhibited by the selective KCNQ channel blockers linopirdine (10 μM) and XE-991 (10 μM) and enhanced by the KCNQ channel activator flupirtine (10 μM). BaCl2(100 μM) or linopirdine (5 μM) mimicked the effects of AVP on K+currents, AP generation, and Ca2+spiking. Expression of KCNQ5 was detected by RT-PCR in A7r5 cells and freshly isolated rat aortic smooth muscle. RNA interference directed toward KCNQ5 reduced KCNQ5 protein expression and resulted in a significant decrease in IKvin A7r5 cells. IKvwas also inhibited in response to the PKC activator 4β-phorbol 12-myristate 13-acetate (10 nM), and the inhibition of IKvby AVP was prevented by the PKC inhibitor calphostin C (250 nM). These results suggest that the stimulation of Ca2+spiking by physiological concentrations of AVP involves PKC-dependent inhibition of KCNQ5 channels and increased AP firing in A7r5 cells.
Overexpression of arginase in the aged mouse penis impairs erectile function and decreases eNOS activity: influence of in vivo gene therapy of anti-arginase
Authors: Bivalacqua Trinity J. , Burnett Arthur L. , Hellstrom Wayne J. G. , Champion Hunter C.
Published: October 2006

Since both increased nitric oxide (NO) synthase (NOS) abundance and diminished NO signaling have been reported in the aging penis, the role of NO in the adaptations of aging remains controversial. Here we tested the hypothesis that arginase, an enzyme that competes with NOS for the substrate l-arginine, contributes to erectile dysfunction with advanced age in the B6/129 mouse strain. Arginase protein abundance, mRNA expression, and enzyme activity were elevated in aged compared with young penile endothelial cells. In addition, endothelial NOS (NOS3) protein abundance was greater in aged versus young penile endothelial cells, whereas NOS activity and cGMP levels were reduced. Calcium-dependent l-arginine-to-l-citrulline conversion and cGMP formation increased significantly in aged mouse penes in the presence of the arginase inhibitor 2( S)-amino-6-boronohexanoic acid (ABH). However, there was no effect on l-arginine-to-l-citrulline conversion or cGMP accumulation in the endothelium from young mouse penes. To assess the functional role of arginase in the inhibition of NOS pathway responsiveness in the penis, we evaluated the effects of ABH and an adeno-associated virus encoding an antisense sequence to arginase I (AAVanti-arginase) on erectile function in vivo. ABH and AAVanti-arginase enhanced endothelium-dependent erectile responses in the aged mice without altering endothelium-independent responses. Paralleling our in vitro observations, ABH or AAVanti-arginase did not affect vascular responses in the young mice. Inhibition of the arginase pathway improves endothelial function in the aging penile circulation, suggesting that the arginase pathway may be exploited to improve erectile dysfunction associated with aging.
Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction
Authors: Bivalacqua Trinity J. , Deng Weiwen , Kendirci Muammer , Usta Mustafa F. , Robinson Christine , Taylor Bradley K. , Murthy Subramanyam N. , Champion Hunter C. , Hellstrom Wayne J. G. , Kadowitz Philip J.
Published: October 2006

Mesenchymal stem cells (MSCs) can be used in adult stem cell-based gene therapy for vascular diseases. To test the hypothesis that MSCs alone or endothelial nitric oxide synthase (eNOS)-modified MSCs can be used for treatment of erectile dysfunction (ED), syngeneic rat MSCs (rMSCs) were isolated, ex vivo expanded, transduced with adenovirus containing eNOS, and injected into the penis of aged rats. Histological analysis demonstrated that rMSCs survived for at least 21 days in corporal tissue after intracavernous injection, and an inflammatory response was not induced. Intracavernous administration of eNOS-modified rMSCs improved the erectile response in aged rats at 7 and 21 days after injection. The increase in erectile function was associated with increased eNOS protein, NOS activity, and cGMP levels. rMSCs alone increased erectile function of aged rats at day 21, but not at day 7, with the transplanted cells exhibiting positive immunostaining for several endothelial and smooth muscle cell markers. This change in rMSC phenotype was accompanied by upregulation of penile eNOS protein expression/activity and elevated cGMP levels. These findings demonstrate that an adenovirus can be used to transduce ex vivo expanded rMSCs to express eNOS and that eNOS-modified rMSCs improve erectile function in the aged rat. Intracavernous injection of unmodified wildtype rMSCs improved erectile function 21 days after injection through mechanisms involving improved endothelium-derived NO/cGMP signaling and rMSC differentiation into penile cells expressing endothelial and smooth muscle markers. These data highlight the potential clinical use of adult stem cell-based therapy for the treatment of ED.
Evidence for reduced sympatholysis in leg resistance vasculature of healthy older women
Authors: Parker Beth A. , Smithmyer Sandra L. , Jarvis Sara S. , Ridout Samuel J. , Pawelczyk James A. , Proctor David N.
Published: October 2006

Inhibition of a sympathetic stimulus (i.e., sympatholysis) during forearm exercise is reduced with age in women. This age-related alteration has not been characterized in the lower extremity vasculature of women, and the potential for blunting of the conduit artery dilatory response to a sudden increase in shear stress [flow-mediated dilation (FMD)] has not been examined in older adults of either sex. In the present study, we assessed popliteal artery diameter and velocity (Doppler ultrasound) in 16 young (23 ± 1 yr) and 14 older (69 ± 1 yr) women after 5 min of distal calf occlusion (FMD), 3 min of hand immersion in ice water [cold pressor test (CPT)], and 5 min of distal calf occlusion combined with hand immersion in ice water (FMD+CPT). Peak popliteal conductance after 5-min ischemia was not significantly different in young vs. older women. During the combined stimulus (FMD+CPT), the magnitude of vasoconstriction in the calf (reduction in peak popliteal artery conductance) was similar (5–8%), despite reduced resting adrenergic sensitivity to CPT [young (Y): −27.3 ± 3.8%; older (O): −15.8 ± 2.2%; P < 0.05] and blunted muscle sympathetic nerve activity responses to CPT (Y: 12.7 ± 3.6 bursts/min; O: 7.8 ± 2.5 bursts/min; P < 0.05) in older women. Popliteal FMD, normalized to the shear stimulus, was attenuated by 60–70% in older women. Peak popliteal diameter, measured during the combined stimulus (FMD+CPT), was blunted in young but not in older women (Y FMD: 5.5 ± 0.1 mm; Y FMD+CPT: 5.4 ± 0.1 mm; P = 0.03; O FMD: 5.8 ± 0.2 mm; O FMD+CPT: 5.8 ± 0.2 mm). These results confirm previous findings of diminished reactivity in the conduit arteries of older humans and provide the first evidence of reduced sympatholysis in the leg resistance vasculature of older women.
Cardiac-specific overexpression of diacylglycerol kinase ζ attenuates left ventricular remodeling and improves survival after myocardial infarction
Authors: Niizeki Takeshi , Takeishi Yasuchika , Arimoto Takanori , Takahashi Hiroki , Shishido Tetsuro , Koyama Yo , Goto Kaoru , Walsh Richard A. , Kubota Isao
Published: October 2006

Left ventricular (LV) remodeling, including cardiomyocyte necrosis, scar formation, LV geometric changes, and cardiomyocyte hypertrophy, contributes to cardiac dysfunction and mortality after myocardial infarction (MI). Although precise cellular signaling mechanisms for LV remodeling are not fully elucidated, Gq protein-coupled receptor signaling pathway, including diacylglycerol (DAG) and PKC, are involved in this process. DAG kinase (DGK) phosphorylates DAG and controls cellular DAG levels, thus acting as a negative regulator of PKC and subsequent cellular signaling. We previously reported that DGK inhibited angiotensin II and phenylephrine-induced activation of the DAG-PKC signaling and subsequent cardiac hypertrophy. The purpose of this study was to examine whether DGK modifies LV remodeling after MI. Left anterior descending coronary artery was ligated in transgenic mice with cardiac-specific overexpression of DGKζ (DGKζ-TG) and wild-type (WT) mice. LV chamber dilatation (4.12 ± 0.10 vs. 4.53 ± 0.32 mm, P < 0.01), reduction of LV systolic function (34.8 ± 8.3% vs. 28.3 ± 4.8%, P < 0.01), and increases in LV weight (95 ± 3.6 vs. 111 ± 4.1 mg, P < 0.05) and lung weight (160 ± 15 vs. 221 ± 25 mg, P < 0.05) at 4 wk after MI were attenuated in DGKζ-TG mice compared with WT mice. In the noninfarct area, fibrosis fraction (0.51 ± 0.04, P < 0.01) and upregulation of profibrotic genes, such as transforming growth factor-β1 ( P < 0.01), collagen type I ( P < 0.05), and collagen type III ( P < 0.01), were blocked in DGKζ-TG mice. The survival rate at 4 wk after MI was higher in DGKζ-TG mice than in WT mice (61% vs. 37%, P < 0.01). In conclusion, these results demonstrate the first evidence that DGKζ suppresses LV structural remodeling and fibrosis and improves survival after MI. DGKζ may be a potential novel therapeutic target to prevent LV remodeling after MI.
A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice
Authors: Jerebtsova Marina , Wong Edward , Przygodzki Ronald , Tang Pingtao , Ray Patricio E.
Published: October 2006

Pentosan polysulfate (PPS) is a heparin-like polysaccharide that can affect the binding interactions of fibroblast growth factor (FGF-2) with its high-affinity receptors. Patients with angiogenic tumors frequently show high levels of FGF-2 in the circulation. Since FGF-2 is a heparin-binding angiogenic growth factor, PPS has been used successfully to block its activity in patients with angiogenic tumors. However, because of its heparin-like activity, the major toxic effect of PPS is the development of bleeding disorders. The role that circulating FGF-2 plays in the pathogenesis of bleeding disorders in patients treated with PPS is currently unknown. Here we hypothesized that FGF-2 might play a physiological role in the pathogenesis of intestinal bleeding induced by PPS. This hypothesis is supported by previous studies showing that PPS is accumulated in the intestine and that circulating FGF-2 specifically binds to and modulates the angiogenic activity of intestinal submucosal endothelial cells. We used recombinant adenoviral vectors carrying a secreted form of FGF-2 and LacZ control vectors to determine whether high levels of circulating FGF-2 facilitate the development of intestinal bleeding disorders in FVB/N and C57BL/6J mice treated with PPS. We found that PPS, acting together with FGF-2, induced structural changes in intestinal vessels leading to the development of lethal intestinal hemorrhages. These findings might have wider clinical implications for the systemic use of PPS and other heparinoids in the treatment of patients with angiogenic diseases associated with high levels of circulating FGF-2.
Aberrant cytoplasmic sequestration of eNOS in endothelial cells after monocrotaline, hypoxia, and senescence: live-cell caveolar and cytoplasmic NO imaging
Authors: Mukhopadhyay Somshuvra , Xu Fang , Sehgal Pravin B.
Published: October 2006

We previously reported the disruption of caveolae/rafts, dysfunction of Golgi tethers, N-ethylmaleimide-sensitive factor-attachment protein (SNAP) receptor proteins (SNAREs), and SNAPs, and inhibition of anterograde trafficking in endothelial cells in culture and rat lung exposed to monocrotaline pyrrole (MCTP) as a prelude to the development of pulmonary hypertension. We have now investigated 1) whether this trafficking block affects subcellular localization and function of endothelial nitric oxide (NO) synthase (eNOS) and 2) whether Golgi blockade and eNOS sequestration are observed after hypoxia and senescence. Immunofluorescence data revealed that MCTP-induced “megalocytosis” of pulmonary arterial endothelial cells (PAEC) was accompanied by a loss of eNOS from the plasma membrane, with increased accumulation in the cytoplasm. This cytoplasmic eNOS was sequestered in heterogeneous compartments and partially colocalized with Golgi and endoplasmic reticulum (ER) markers, caveolin-1, NOSTRIN, and ER Tracker, but not Lyso Tracker. Hypoxia and senescence also produced enlarged PAEC, with dysfunctional Golgi and loss of eNOS from the plasma membrane, with sequestration in the cytoplasm. Live-cell imaging of caveolar and cytoplasmic NO with 4,5-diaminofluorescein diacetate (DAF-2DA) as probe showed a marked loss of caveolar NO after MCTP, hypoxia, and senescence. Although ionomycin stimulated DAF-2DA fluorescence in control PAEC, this ionophore decreased DAF-2DA fluorescence in MCTP-treated and senescent PAEC, suggesting localization of eNOS in an aberrant cytoplasmic compartment that was readily discharged by Ca2+-induced exocytosis. Thus monocrotaline, hypoxia, and senescence produce a Golgi blockade in PAEC, leading to sequestration of eNOS away from its functional caveolar location and providing a mechanism for the often-reported reduction in pulmonary arterial NO levels in experimental pulmonary hypertension, despite sustained eNOS protein levels.
PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries
Authors: Marrelli Sean P. , O'Neil Roger G. , Brown Rachel C. , Bryan Robert M.
Published: October 2006

We previously demonstrated that endothelium-derived hyperpolarizing factor (EDHF)-mediated dilations in cerebral arteries are significantly reduced by inhibitors of PLA2. In this study we examined possible mechanisms by which PLA2 regulates endothelium-dependent dilation, specifically whether PLA2 is involved in endothelial Ca2+ regulation through stimulation of TRPV4 channels. Studies were carried out with middle cerebral arteries (MCA) or freshly isolated MCA endothelial cells (EC) of male Long-Evans rats. Nitro-l-arginine methyl ester (l-NAME) and indomethacin were present throughout. In pressurized MCA, luminally delivered UTP produced increased EC intracellular Ca2+ concentration ([Ca2+]i) and MCA dilation. Incubation with PACOCF3, a PLA2 inhibitor, significantly reduced both EC [Ca2+]i and dilation responses to UTP. EC [Ca2+]i was also partially reduced by a transient receptor potential vanilloid (TRPV) channel blocker, ruthenium red. Manganese quenching experiments demonstrated Ca2+ influx across the luminal and abluminal face of the endothelium in response to UTP. Interestingly, PLA2-sensitive Ca2+ influx occurred primarily across the abluminal face. Luminal application of arachidonic acid, the primary product of PLA2 and a demonstrated activator of certain TRPV channels, increased both EC [Ca2+]i and MCA diameter. TRPV4 mRNA and protein was demonstrated in the endothelium by RT-PCR and immunofluorescence, respectively. Finally, application of 4α-phorbol 12,13-didecanoate (4αPDD), a TRPV4 channel activator, produced an increase in EC [Ca2+]i that was significantly reduced in the presence of ruthenium red. We conclude that PLA2 is involved in EC Ca2+ regulation through its regulation of TRPV4 channels. Furthermore, the PLA2-sensitive component of Ca2+ influx may be polarized to the abluminal face of the endothelium.
Hyperoxia modulates TGF-β/BMP signaling in a mouse model of bronchopulmonary dysplasia
Authors: Alejandre-Alcázar Miguel A. , Kwapiszewska Grazyna , Reiss Irwin , Amarie Oana V. , Marsh Leigh M. , Sevilla-Pérez Julia , Wygrecka Malgorzata , Eul Bastian , Köbrich Silke , Hesse Mareike , Schermuly Ralph T. , Seeger Werner , Eickelberg Oliver , Morty Rory E.
Published: October 2006

Prematurely born infants who require oxygen therapy often develop bronchopulmonary dysplasia (BPD), a debilitating disorder characterized by pronounced alveolar hypoplasia. Hyperoxic injury is believed to disrupt critical signaling pathways that direct lung development, causing BPD. We investigated the effects of normobaric hyperoxia on transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in neonatal C57BL/6J mice exposed to 21% or 85% O2between postnatal days P1 and P28. Growth and respiratory compliance were significantly impaired in pups exposed to 85% O2, and these pups also exhibited a pronounced arrest of alveolarization, accompanied by dysregulated expression and localization of both receptor (ALK-1, ALK-3, ALK-6, and the TGF-β type II receptor) and Smad (Smads 1, 3, and 4) proteins. TGF-β signaling was potentiated, whereas BMP signaling was impaired both in the lungs of pups exposed to 85% O2as well as in MLE-12 mouse lung epithelial cells and NIH/3T3 and primary lung fibroblasts cultured in 85% O2. After exposure to 85% O2, primary alveolar type II cells were more susceptible to TGF-β-induced apoptosis, whereas primary pulmonary artery smooth muscle cells were unaffected. Exposure of primary lung fibroblasts to 85% O2significantly enhanced the TGF-β-stimulated production of the α1subunit of type I collagen (Iα1), tissue inhibitor of metalloproteinase-1, tropoelastin, and tenascin-C. These data demonstrated that hyperoxia significantly affects TGF-β/BMP signaling in the lung, including processes central to septation and, hence, alveolarization. The amenability of these pathways to genetic and pharmacological manipulation may provide alternative avenues for the management of BPD.
Complement levels and activity in the normal and LPS-injured lung
Authors: Bolger Molly S. , Ross DeAndre S. , Jiang Haixiang , Frank Michael M. , Ghio Andrew J. , Schwartz David A. , Wright Jo Rae
Published: October 2006

Complement, a complex protein system, plays an essential role in host defense through bacterial lysis, stimulation of phagocytosis, recruitment of immune cells to infected tissue, and promotion of the inflammatory response. Although complement is most well-characterized in serum, complement activity is also present in the lung. Here we further characterize the complement system in the normal and inflamed lung. By Western blot, C5, C6, and factor I were detected in bronchoalveolar lavage (BAL) at lower levels than in serum, whereas C2 was detected at similar levels in BAL and serum. C4 binding protein (C4BP) was not detectable in BAL. Exposure to lipopolysaccharide (LPS) elevated levels of C1q, factor B, C2, C4, C5, C6, and C3 in human BAL and C3, C5, and factor B in mouse and rat BAL. Message for C1q-B, C1r, C1s, C2, C4, C3, C5, C6, factor B, and factor H, but not C9 or C4BP, was readily detectable by RT-PCR in normal mouse lung. Exposure to LPS enhanced factor B expression, decreased C5 expression, and did not affect C1q-B expression in mouse and rat lung. BAL from rats exposed to LPS had a greater ability to deposit C3b onto bacteria through complement activation than did BAL from control rats. In summary, these data demonstrate that complement levels, expression, and function are altered in acute lung injury and suggest that complement within the lung is regulated to promote opsonization of pathogens and limit potentially harmful inflammation.
The C/A(−18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B
Authors: Steagall Wendy K. , Lin Jing-Ping , Moss Joel
Published: October 2006

Surfactant protein B (SP-B) is an essential component of surfactant that promotes adsorption and spreading of surfactant phospholipids and stabilizes the phospholipid monolayer. SP-B is essential for respiratory function in newborn humans and mice; adult mice with levels of SP-B below 25% of wild-type develop fatal respiratory distress syndrome. A potential regulatory function of the C/A(−18) single nucleotide polymorphism (SNP) in the promoter of the SP-B gene was examined. Transcriptional analysis and ELISA on bronchoalveolar lavage fluid revealed that the presence of the C allele correlated with more SP-B promoter activity and protein. There was approximately threefold difference in amounts of SP-B in bronchoalveolar lavage fluid from CA(−18) and AA(−18) individuals. By EMSA, Sp1 bound more tightly to the C allele sequence than to the A allele sequence, perhaps accounting for the differences in transcription. Genotyping of a normal volunteer population showed ∼31% of the population were AA homozygotes, suggesting that these individuals produce less SP-B. Differences in amounts of SP-B resulting from the promoter SNP could affect the clinical presentation of pulmonary disease.
IL-23 mediates inflammatory responses to mucoidPseudomonas aeruginosalung infection in mice
Authors: Dubin Patricia J. , Kolls Jay K.
Published: October 2006

Patients with cystic fibrosis (CF) develop chronic Pseudomonas aeruginosa lung infection with mucoid strains of P. aeruginosa; these infections cause significant morbidity. The immunological response in these infections is characterized by an influx of neutrophils to the lung and subsequent lung damage over time; however, the underlying mediators to this response are not well understood. We recently reported that IL-23 and IL-17 were elevated in the sputum of patients with CF who were actively infected with P. aeruginosa; however, the importance of IL-23 and IL-17 in mediating this inflammation was unclear. To understand the role that IL-23 plays in initiating airway inflammation in response to P. aeruginosa, IL-23p19−/−(IL-23 deficient) and wild-type (WT) mice were challenged with agarose beads containing a clinical, mucoid isolate of P. aeruginosa. Levels of proinflammatory cytokines, chemokines, bacterial dissemination, and inflammatory infiltrates were measured. IL-23-deficient mice had significantly lower induction of IL-17, keratinocyte-derived chemokine (KC), and IL-6, decreased bronchoalveolar lavage (BAL) neutrophils, metalloproteinase-9 (MMP-9), and reduced airway inflammation than WT mice. Despite the reduced level of inflammation in IL-23p19−/−mice, there were no differences in the induction of TNF and interferon-γ or in bacterial dissemination between the two groups. This study demonstrates that IL-23 plays a critical role in generating airway inflammation observed in mucoid P. aeruginosa infection and suggests that IL-23 could be a potential target for immunotherapy to treat airway inflammation in CF.
Estrogen in the Paraventricular Nucleus Attenuates
l
-Glutamate–Induced Increases in Mean Arterial Pressure Through Estrogen Receptor β and NO
Authors: Gingerich Sarah , Krukoff Teresa L.
Published: October 2006

Estrogen (E2) acts in the brain to decrease blood pressure (BP) responses to psychological stress. A likely site for the effects of E2 is the hypothalamic paraventricular nucleus (PVN), an important regulator of autonomic functions. We studied the effects of E2 in the PVN on BP and heart rate (HR) responses to
l
-glutamate injections into the PVN of male urethane-anesthetized rats. Microinjections of
l
-glutamate (50 nmol) into the PVN increased BP by 14±2.5 mm Hg and HR by 30±5.6 bpm. Microinjections of E2 (0.1, 1, and 10 pmol) into the PVN 30 minutes before
l
-glutamate dose-dependently attenuated the pressor response by 25%, 34%, and 59%, respectively, but did not affect HR. We determined that E2 receptor (ER) β mediates the effect of E2, because activation of ERβ with diarylpropionitrile (50 pmol) attenuated the response by 57%, whereas activation of ERα with propyl-pyrazole-triol (20 pmol) had no effect. Furthermore, inhibition of ERβ with R,R-tetrahydrochrysene (50 pmol) blocked the effect of E2, but inhibition of ERα with methyl-piperidino-pyrazole (1 nmol) did not. Finally, we found that the effect of E2 is mediated by NO, because the NO synthase (NOS) inhibitor,
N
G
-nitro-
l
-arginine methyl ester (2 nmol), the neuronal NOS inhibitor, 7-nitroindazole sodium salt (0.1 pmol), and the endothelial NOS inhibitor, N5-(1-iminoethyl)-
l
-ornithine (200 pmol) blocked the effect of E2. The effect was partially blocked with the γ-aminobutyric acid
A
receptor inhibitor bicuculline. Our results demonstrate that E2 in the PVN attenuates the
l
-glutamate–induced pressor response and that this effect is mediated by ERβ, NO produced by neuronal NO synthase and eNOS, and partly by γ-aminobutyric acid.
Role of Renal Medullary Heme Oxygenase in the Regulation of Pressure Natriuresis and Arterial Blood Pressure
Authors: Li Ningjun , Yi Fan , dos Santos Elisabete A. , Donley Dustin K. , Li Pin-Lan
Published: October 2006

Recent studies have demonstrated that inhibition of renal medullary heme oxygenase (HO) activity and carbon monoxide (CO) significantly decreases renal medullary blood flow and sodium excretion. Given the crucial role of renal medullary blood flow in the control of pressure natriuresis, the present study was designed to determine whether renal medullary HO activity and resulting CO production participate in the regulation of pressure natriuresis and thereby the long-term control of arterial blood pressure. In anesthetized Sprague-Dawley rats, increases in renal perfusion pressure induced significant elevations of CO concentrations in the renal medulla. Renal medullary infusion of chromium mesoporphyrin (CrMP), an inhibitor of HO activity, remarkably inhibited HO activity and the renal perfusion pressure-dependent increases in CO levels in the renal medulla and significantly blunted pressure natriuresis. In conscious Sprague-Dawley rats, continuous infusion of CrMP into the renal medulla significantly increased mean arterial pressure (129±2.5 mm Hg in CrMP group versus 118±1.6 mm Hg in vehicle group) when animals were fed a normal salt diet (1% NaCl). After rats were switched to a high-salt diet (8% NaCl) for 10 days, CrMP-treated animals exhibited further increases in mean arterial pressure compared with CrMP-treated animals that were kept on normal salt diet (152±4.1 versus 130±4.2 mm Hg). These results suggest that renal medullary HO activity plays a crucial role in the control of pressure natriuresis and arterial blood pressure and that impairment of this HO/CO-mediated antihypertensive mechanism in the renal medulla may result in the development of hypertension.
CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells
Authors: Kawamoto Atsuhiko , Iwasaki Hiroto , Kusano Kengo , Murayama Toshinori , Oyamada Akira , Silver Marcy , Hulbert Christine , Gavin Mary , Hanley Allison , Ma Hong , Kearney Marianne , Zak Victor , Asahara Takayuki , Losordo Douglas W.
Published: October 2006

Background—

We compared the therapeutic potential of purified mobilized human CD34
+
cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI).

Methods and Results—

CD34
+
cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5×10
5
CD34
+
cells/kg, 5×10
5
tMNCs/kg (low-dose MNCs [loMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5×10
5
CD34
+
cells/kg was transplanted intramyocardially 10 minutes after the induction of MI in athymic nude rats. Hematoxylin and eosin staining revealed that moderate to severe hemorrhagic MI on day 3 was more frequent in the hiMNC group than in the PBS and CD34
+
cell groups. Immunostaining for human-specific CD45 revealed abundant distribution of hematopoietic/inflammatory cells derived from transplanted cells in the ischemic myocardium of the hiMNC group. Capillary density on day 28 was significantly greater in the CD34
+
cell group (721.1±19.9 per 1 mm
2
) than in the PBS, loMNC, and hiMNC groups (384.7±11.0, 372.5±14.1, and 497.5±24.0 per 1 mm
2
) (
P
<0.01). Percent fibrosis area on day 28 was less in the CD34
+
cell group (15.6±0.9%) than in the PBS, loMNC, and hiMNC groups (26.3±1.2%, 27.5±1.8%, and 22.2±1.8%) (
P
<0.05). Echocardiographic fractional shortening on day 28 was significantly higher in the CD34
+
cell group (30.3±0.9%) than in the PBS, loMNC, and hiMNC groups (22.7±1.5%, 23.4±1.1%, and 24.9±1.7%;
P
<0.05). Echocardiographic regional wall motion score was better preserved in the CD34
+
cell group (21.8±0.5) than in the PBS, loMNC, and hiMNC groups (25.4±0.4, 24.9±0.4, and 24.1±0.6;
P
<0.05).

Conclusions—

CD34
+
cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.
Destructive Dynamics of Middle Management Intervention in Postmerger Processes
Authors: Meyer Christine B.
Published: October 2006

This article focuses on the dynamics of middle management intervention in post-merger processes. The literature on middle management intervention has focused on conflicts of interests between top and middle management in implementing strategic intent. The author suggests a more complex view of middle management intervention where the strategic intent is operationalized in the tension between groups of middle management driven by self-interests. The data and research generated in a merger between four Nordic partners show how the centralized support staff and operational management operationalized strategic intent in contradictory ways that led to implementation failure. These two middle management groups were given room for this destructive intervention for two reasons. First, the strategic intent gave unclear prescriptions for implementation and contained inherent contradictions between differentiation and integration. Second, the top management was largely absent in the implementation process and did not intervene until the merged corporation had persistent negative performance.
When the Forum Meets Interest Politics: Strategic Uses of Public Deliberation
Authors: Hendriks Carolyn M.
Published: October 2006

This article explores the interface between public deliberation and interest politics. It empirically examines how and when actors with vested interests support and oppose processes of direct citizen deliberation, such as citizens’ juries. An analysis of four cases finds that interest groups and activists respond to citizen deliberation in a variety of ways from cooperative engagement to disruptive disengagement. The research suggests that partisan actors are most likely to support citizens’ forums when the ideational and political context offers instrumental reasons to go public. The article explores what this strategic approach to public deliberation implies for the practice and theory of deliberative democracy.
A Parallel Fish Landscape Model for Ecosystem Modeling
Authors: Wang Dali , Berry Michael W. , Carr Eric A. , Gross Louis J.
Published: October 2006

Parallelization of a landscape fish population model (ALFISH) is an important effort towards high performance Across Tropic Level System Simulation (ATLSS) on a computing grid. ALFISH models the impacts of different water management strategies in the South Florida region on the freshwater fish population, providing estimates of the food resource available to wading birds. The parallel ALFISH model delivers similar results to those from a sequential implementation. Compared with the average simulation time of the sequential model, which is about 35 hours, the speed improvement of the parallel model on a symmetric multiprocessor (SMP) is substantial. Using 14 processors, the runtime of the parallel model with static partitioning is less than 4 hours, and that of the parallel model with dynamic load balancing is less than 3 hours.
Long-Term Influence of the Spatial Structure of an Initial State on the Dynamics of a Forest Growth Model: A Simulation Study Using the Capsis Platform
Authors: Goreaud F. , Alvarez I. , Courbaud B. , de Coligny F.
Published: October 2006

Spatially explicit individual-based models are used more often in forest modeling, especially because they take into account the influence of the spatial structure on the dynamics. However, they are potentially very sensitive to the initial spatial structure used for a simulation, which can be problematic if the initial state is not known or is simulated in an unrealistic way.The aim of this article is to study this sensitivity to initial spatial structure in the case of the “Mountain” model, an individual-based model of irregular spruce stands implemented in the Capsis platform.To characterize the influence of the initial spatial structure on the dynamics of the model, the authors simulated different initial spatial structures and compared the results of long-term simulations. They showed that the initial spatial structure can highly influence the dynamics of the model, not only during the first cycle of the evolution but also in the very long term in the evolution of the next generations. They also illustrated how some disturbances, such as a periodic gap opening through storms, can modify both the long-term dynamics of the stand and the duration of the influence of the initial spatial structure.
High Temperature Shape Memory Alloys Problems and Prospects
Authors: Firstov G. S. , Van Humbeeck J. , Koval Yu. N.
Published: October 2006

In this article, a review of the existing high temperature shape memory alloy (HTSMA) systems is given. Certain crucial disadvantages general to all HTSMAs and related to structural mechanisms of the martensitic transformation (MT) taking place at elevated temperatures are described. The perspectives of the HTSMA's application are also discussed.
Obesogenic environments: exploring the built and food environments
Authors: Lake Amelia , Townshend Tim
Published: October 2006

Obesity is a significant health and social problem which has reached pandemic levels. The obesogenicity of an environment has been defined as ‘the sum of influences that the surroundings, opportunities, or conditions of life have on promoting obesity in individuals or populations’.1 Prevention and treatment of obesity has focused on pharmacological, educational and behavioural interventions, with limited overall success. A novel and a longer-term approach would be to investigate the environments that promote high energy intake and sedentary behaviour; this has not yet been fully understood. The obesity epidemic has attracted attention at all levels, from general media interest to policy and practice from health and other professions including urban designers and planners. Shaping the environment to better support healthful decisions has the potential to be a key aspect of a successful obesity prevention intervention. Thus in order to develop effective environmental interventions, in relation to obesity, we need to understand how individuals, and different groups of individuals, interact with their environments in terms of physical activity and food intake.
Varieties of habitus and the embodiment of ballet
Authors: Wainwright Steven P. , Williams Clare , Turner Bryan S.
Published: October 2006

The overall aim of our research was to produce an ethnography of ballet as a social practice. We draw upon our fieldwork at the Royal Ballet (London) where we conducted 20 in-depth interviews with ballet staff, and observed ‘the company at work’, in class, rehearsal, and performance. We explored dancers’ ( n = 9) and ex-dancers’ (who are now administrators, teachers, and character dancers: n = 11) perceptions of their bodies, dancing careers, and the major changes that have occurred in the world of ballet over their professional lives. In this article, we draw upon Pierre Bourdieu’s notions of habitus, physical capital and cultural capital. The main focus of our article is an extended discussion of our threefold distinction between individual habitus, institutional habitus and choreographic habitus. Although our ethnography of the body is set within the elite cultural field of professional classical ballet, we hope that our research adds to debates on the interrelationships between individuals and institutions, the body and society, and on the salience of Bourdieu’s notion of habitus for understandings of the social world.
Antigone's Law
Authors: Nonet Philippe
Published: October 2006

Antigone's law is the same as Heidegger's law. The name of the first is φύσις, the name of the second is Ereignis. Both names are untranslatable. They signify the mutual belonging of being ( das Sein) and the essence of man. This law fulfills itself in the radiance of τò κάλλoς. It is the unsayable law of all law.
Humane wars? International law, Just War theory and contemporary armed humanitarian intervention
Authors: Mednicoff David M.
Published: October 2006

The contemporary international law of war is torn between the pressure to incorporate a doctrine to legitimize limited armed humanitarian intervention and its traditional concerns for nations' sovereignty. Especially because of its organic, interconnected nature, the theoretical tradition of just war theory, when concretized through explicit linkage to specific standards of contemporary human rights law, offers an approach to resolving this dilemma that does not unduly privilege war-making. This approach is both consistent with international law and useful as an example of the relevance of drawing on humanistic reasoning about justice in international jurisprudence. The argument is illustrated by reference to the cases of the failure of humanitarian intervention in Rwanda in 1994, the armed intervention in Kosovo in 1999 and the US-led wars in Iraq in 1991 and 2003.
Blacks and Rights: A Bittersweet Legacy
Authors: Darby Derrick
Published: October 2006

Some antebellum critics of the infamous Dred Scott “blacks have no rights” thesis suggested that this view resulted from a failure to appreciate that the humanity of blacks bestowed rights on them too. One plausible explanation for why many defenders of slavery and black subordination rejected this argument, which I shall develop in this paper, is that the prevailing political ideology of antebellum America contained a substantive conception of rights possession as well as well–entrenched allegations of black inferiority that were exploited to render the “blacks have no rights” thesis conceptually unproblematic. Elucidating the logic of arguments for and against the ‘blacks have no rights’ thesis will contribute to a broader understanding of the bittersweet legacy of rights discourse in American political thought.
Molecular polymorphism, differentiation and introgression in the period gene between Lutzomyia intermedia and Lutzomyia whitmani
Authors: Mazzoni Camila J , Souza Nataly A , Andrade-Coelho Claudia , Kyriacou Charalambos P , Peixoto Alexandre A
Published: October 2006

Background

Lutzomyia intermediaandLutzomyia whitmani(Diptera: Psychodidae) are important and very closely related vector species of cutaneous leishmaniasis in Brazil, which are distinguishable by a few morphological differences. There is evidence of mitochondrial introgression between the two species but it is not clear whether gene flow also occurs in nuclear genes.

Results

We analyzed the molecular variation within the clock geneperiod(per) of these two species in five different localities in Eastern Brazil. AMOVA and Fst estimates showed no evidence for geographical differentiation within species. On the other hand, the values were highly significant for both analyses between species. The two species show no fixed differences and a higher number of shared polymorphisms compared to exclusive mutations. In addition, some haplotypes that are "typical" of one species were found in some individuals of the other species suggesting either the persistence of old polymorphisms or the occurrence of introgression. Two tests of gene flow, one based on linkage disequilibrium and a MCMC analysis based on coalescence, suggest that the two species might be exchanging alleles at theperlocus.

Conclusion

Introgression might be occurring betweenL. intermediaandL. whitmaniinperiod, a gene controlling behavioral rhythms inDrosophila. This result raises the question of whether similar phenomena are occurring at other loci controlling important aspects of behavior and vectorial capacity.