bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia
Authors: Morris Amy E. , Liggitt H. Denny , Hawn Thomas R. , Skerrett Shawn J.
Published: October 2009

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and an important pathogen in patients with chronic lung disease, such as cystic fibrosis and bronchiectasis. The contribution of Toll-like receptor 5 (TLR5) to the innate immune response to this organism is incompletely understood. We exposed wild-type and TLR5-deficient ( Tlr5−/−) mice to aerosolized P. aeruginosa at low and high inocula and assessed bacterial clearance, lung inflammation, and cytokine production 4 and 24 h after infection. Bacterial clearance was impaired in Tlr5−/−mice after low-inoculum, but not high-inoculum, infection. Early bronchoalveolar accumulation of neutrophils was reduced in Tlr5−/−mice after low- and high-dose infection. Cytokine responses, including markedly impaired monocyte chemoattractant protein-1 production 4 h after low- and high-inoculum challenge, were selectively altered in Tlr5−/−mice. In contrast, there was no impairment of bacterial clearance, neutrophil recruitment, or monocyte chemoattractant protein-1 production in Tlr5−/−mice after infection with a nonflagellated isotypic strain of P. aeruginosa . Thus TLR5-mediated recognition of flagellin is involved in activating pulmonary defenses against P. aeruginosa and contributes to antibacterial resistance in a manner that is partially inoculum dependent. These data are the first to demonstrate a unique role for TLR5 in the innate immune response to P. aeruginosa lung infection.
Hypoxia promotes human pulmonary artery smooth muscle cell proliferation through induction of arginase
Authors: Chen Bernadette , Calvert Andrea E. , Cui Hongmei , Nelin Leif D.
Published: October 2009

Vascular remodeling and smooth muscle cell proliferation are hallmark pathogenic features of pulmonary artery hypertension (PAH). Alterations in the metabolism of l-arginine via arginase and nitric oxide synthase play a critical role in the endothelial dysfunction seen in PAH. l-arginine metabolism by arginase produces l-ornithine and urea. l-ornithine is a precursor for polyamine and proline synthesis, ultimately leading to an increase in cellular proliferation. Given the integral role of the smooth muscle layer in the pathogenesis of hypoxia-induced PAH, we hypothesized that hypoxia would increase cellular proliferation via arginase induction in human pulmonary artery smooth muscle cells (hPASMC). We found that arginase II mRNA and protein expression were significantly increased in cultured hPASMC exposed to 1% O2for 24 and 48 h, which coincided with an increase in arginase activity at 48 h. There were no hypoxia-induced changes in levels of arginase I mRNA or protein in cultured hPASMC. Exposure to hypoxia resulted in more than one and a half times as many viable cells after 120 h than normoxic exposure. The addition of the arginase inhibitor, S-(2-boronoethyl)-l-cysteine, completely prevented both the hypoxia-induced increase in arginase activity and proliferation in hPASMC. Furthermore, transfection of small interfering RNA (siRNA) targeting arginase II in hPASMC resulted in knockdown of arginase II protein levels and complete prevention of the hypoxia-induced cellular proliferation. These data support our hypothesis that hypoxia increases proliferation of hPASMC through the induction of arginase II.
Regulation of inflammation by Rac2 in immune complex-mediated acute lung injury
Authors: Dooley James L. , Abdel-Latif Dalia , St. Laurent Chris D. , Puttagunta Lakshmi , Befus Dean , Lacy Paige
Published: October 2009

Acute lung injury (ALI) is an inflammatory disorder associated with recruitment and activation of neutrophils in lungs. Rac2, a member of the Rho GTPase subfamily, is an essential regulator of neutrophil degranulation, superoxide release, and chemotaxis. Here, we hypothesized that Rac2 is important in mediating lung injury. Using a model of IgG immune complex-mediated ALI, we showed that injury was attenuated in rac2−/−mice compared with wild-type (WT) mice undergoing ALI, with significant decreases in alveolar leukocyte numbers, vascular leakage, and the inflammatory mediators, myeloperoxidase (MPO) and matrix metalloproteinases (MMPs). Reduced injury in rac2−/−mice was not associated with diminished cytokine and chemokine production, since bronchoalveolar lavage (BAL) levels of IL-17, TNF, CCL3, CXCL1, and CXCL2 were similarly increased in WT and rac2−/−mice with ALI compared with sham-treated mice (no ALI). BAL levels of MMP-2 and MMP-9 were significantly decreased in the airways of rac2−/−mice with ALI. Immunohistochemical analysis revealed that MMP-2 and MMP-9 expression was evident in alveolar macrophages and interstitial neutrophils in WT ALI. In contrast, MMP-positive cells were less prominent in rac2−/−mice with ALI. Chimeric mice showed that Rac2-mediated lung injury was dependent on hematopoietic cells derived from bone marrow. We propose that lung injury in response to immune complex deposition is dependent on Rac2 in alveolar macrophages and neutrophils.
Influence of Insulin and Muscle Fiber Type in Nε-(Carboxymethyl)-Lysine Accumulation in Soleus Muscle of Rats with Streptozotocin-Induced Diabetes Mellitus
Authors: Snow LeAnn M. , Thompson LaDora V.
Published: October 2009

Background: Nε-(carboxymethyl)-lysine (CML) is an advanced glycation end product (AGE), the accumulation of which has been implicated in the etiology of diabetes complications. Skeletal muscle in diabetes demonstrates altered function, and increased accumulation of CML has been found in several fast-twitch muscles of diabetic animals. Objective: This study aims to explore the accumulation of CML in soleus (a slow muscle) in diabetic animals, with and without insulin therapy. Methods: Twenty-one rats were randomly divided into control and diabetes groups (DNI: diabetes without insulin; DI: diabetes with insulin; C: control). Diabetes was induced by intravenous administration of streptozotocin. At the end of the 12-week experimental period the soleus muscle was excised and snap frozen in liquid nitrogen. Muscle cross-sections were immunolabeled for CML. The number of CML-labeled muscle fibers was quantified; fibers were also evaluated for fiber types and cross-sectional areas. Results: The percentage of myofibers immunolabeling for CML was highest in the DNI group (13.8 ± 2.5%), lower in the DI group (5.4 ± 1.1%) and lowest in the C group (2.1 ± 0.6%). Statistical analysis revealed that AGE accumulation was significantly greater in the DNI group than in both C and DI groups (p = 0.0002). There was no significant difference between C and DI groups. In the DNI animals, AGE-positive myofibers showed a higher percentage of fast fiber types than did the AGE-negative fibers (49.5 ± 6.9 vs. 13.7 ± 1.5%, p = 0.002). No differences existed in cross-sectional areas between AGE-positive and AGE-negative fibers within any group. Conclusion: The greatest accumulation of AGE was in the soleus of the DNI group, and was significantly less in the DI group. These findings may be linked to disordered glucose metabolism, increased oxidative stress and/or fiber type transformation in these muscles.
BCL-6 Oncoprotein in Breast Cancer: Loss of Expression in Disease Progression
Authors: Pinto António E. , André Saudade , Silva Giovani , Vieira Sara , Santos Ana C. , Dias Sérgio , Soares Jorge
Published: October 2009

Objective: To investigate the biological role of BCL-6 oncoprotein in breast cancer disease progression (recurrence and metastasis). Methods: The series consisted of 93 consecutive female patients with primary breast cancer and median follow-up of 10 years. BCL-6 expression was assessed in vivo by immunohistochemistry and real-time PCR. Breast cancer cell lines and some metastasis-related genes (CXCR4, Itgβ-3 and FLT-1) were also analysed by molecular techniques. Prognostic evaluation was performed by fitting a multivariate Cox regression model. Results: BCL-6 immunoexpression was positive in 22 (23.7%) tumours and negative in 71 (76.3%). All axillary lymph node metastases of 47 node-positive patients were negative, including 12 cases showing BCL-6-positive primary tumours. Likewise, in 9 recurrence cases, BCL-6 expression was similar or decreased compared with primary tumours. No correlation between immunoexpression and gene expression of BCL-6 was observed. BCL-6 was significantly reduced both in derived metastases of a breast cancer cell line (M435) and when the latter was treated with a demethylation agent (5-azacytidine). However, BCL-6-transfected breast cancer cell lines expressed significantly higher levels of CXCR4, Itgβ-3 and FLT-1. Co-expression of the 4 genes was found in 4 of 17 tumours evaluated, but lacking prognostic significance. BCL-6 oncoprotein revealed no significant influence on outcome. Conclusion: The results strongly suggest the loss of BCL-6 expression in breast cancer progression, which might be related with methylation status alterations of still unknown partner gene(s).
IGF-I and IGF-Binding Proteins in Articular Exudates of Children with Post-Traumatic Knee Damage and Juvenile Idiopathic Arthritis
Authors: Guszczyn Tomasz , Rzeczycka Justyna , Popko Janusz
Published: October 2009

Objective: IGF-I stimulates multiple functions of connective tissue cells and its activity is modulated by IGF-binding proteins (BPs). Some metalloproteinases are expected to modify IGF-I activity by digestion of IGF-BPs. It was decided to evaluate the concentration of IGF-I, IGF-BPs and the activity of gelatinases A and B in knee exudates of children with post-traumatic damage (PTD) and children with juvenile idiopathic arthritis (JIA) in comparison with those in the sera of the same patients. Methods: ELISA (for IGF-I assay), polyacrylamine gel electrophoresis following Western immunoblotting (for IGF-I and IGF-BPs expression), and zymography (for gelatinase detection) were used. Results: The knee exudates, especially those taken from patients with JIA, contained large amounts of IGF-I. The exudates of PTD and JIA patients contained some forms of IGF-BP-1 of molecular weight lower than those occurring in serum. Low expression BP-3 and high activity of gelatinase B were detected in the JIA exudates. Conclusions: The high gelatinase activities in exudates imply joint tissue damage. The cellular response to damage of this kind is an increase in IGF-I production, which stimulates repair processes. High proteolytic activities of gelatinase B in JIA patients may lower the amount of BP-3, possibly causing a relative decrease of IGF-I concentration and impairing the reparation processes stimulated by IGF-I.
The Impact of High Anxiety Level on Cellular and Humoral Immunity in Mice
Authors: Rammal Hassan , Bouayed Jaouad , Falla Jaïro , Boujedaini Naoual , Soulimani Rachid
Published: October 2009

Background/Aims: In the present study, we aimed to examine whether a high anxiety level affects various parameters of immunity in mice. Methods: We used the behavioral light/dark choice test to evaluate whether high anxiety has an impact on various parameters of cellular (granulocytes, monocytes, total lymphocytes, TCD4+, TCD8+ and NK numbers) and humoral (IgA, E and G concentrations) immunity. Secondly, we investigated whether the cellular and humoral immune systems of mice with contrasting levels of anxiety responded differently to stressors (such as physical restraint) by monitoring blood markers of the both types of immunity. Results: High levels of anxiety inhibited part of the cellular and humoral immune systems by significantly decreasing total lymphocytes numbers (including TCD4+ and TCD8+) and immunoglobulin (A and E) concentrations. However, no significant changes in the number of granulocytes, monocytes or NK cells were observed. As a consequence, overall, our results suggest that high anxiety led to a decrease in the efficiency of the immune system of anxious mice. On the other hand, our findings also showed that restraint stress (acute and subacute) produced the same immunological profile as high anxiety in mice. This was independent of the animals’ anxiety status. At the same time, we observed that restraint stress produced significant increases in the levels of granulocytes and monocytes. Conclusions: High anxiety and restraint stress exerted adverse effects on cellular and humoral immunity in mice. While the effect of restraint stress was independent of the anxiety levels in mice, this stress led to an aggravation of the immune response from the high degree of anxiety. Therefore, anxious subjects could be more vulnerable to infections and inflammation, particularly when they are exposed to stressful situations.
Neuroendocrine and Immunological Correlates of Chronic Stress in ‘Strictly Healthy’ Populations
Authors: Moriguchi Jeckel Cristina M. , Lopes Rodrigo P. , Berleze Maria Cristina , Luz Clarice , Feix Leandro , Argimon Irani Iracema de Lima , Stein Lilian M. , Bauer Moisés E.
Published: October 2009

Background: Chronic stress has been associated with detrimental or maladaptive neuroendocrine and immunological changes. Objectives: We assessed the neuroendocrine and immunological correlates of a realistic chronic stress experienced by strictly healthy caregivers of Alzheimer’s disease patients and age-matched controls. Methods: We screened 330 caregivers and 206 non-caregivers according to the ‘strictly healthy’ conditions established by the SENIEUR protocol. Forty-one strictly healthy caregivers (60.56 ± 16.56 years) and 33 non-stressed controls (60.27 ± 14.11 years) were selected for this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at multiple points by radioimmunoassay. Peripheral T cell proliferation and cellular sensitivity to glucocorticoids (corticosterone and dexamethasone, DEX) were evaluated by colorimetric assays. We also examined the hypothalamic-pituitary-adrenal (HPA) axis response to the administration of a low-dose DEX in vivo. Results: The caregivers were significantly more stressed, anxious and depressed than non-caregivers (all p < 0.0001), in contrast to similar cortisol levels. Caregivers had reduced DHEAS levels (–32%, p < 0.0001), an increased cortisol/DHEAS ratio (39.7%, p < 0.0001) and impaired HPA axis response to DEX intake. Caregivers had a higher T cell proliferation (p < 0.0001) and increased sensitivity to glucocorticoids in vitro (p < 0.01) as compared to non-stressed controls. Conclusions: Our results suggest that the maintenance of health in chronically stressed populations may be associated with both protective and detrimental neuroendocrine and immunological changes.
Kainic Acid-Activated Microglia Mediate Increased Excitability of Rat Hippocampal Neurons in vitro and in vivo: Crucial Role of Interleukin-1beta
Authors: Zheng Honghua , Zhu Wei , Zhao Hu , Wang Xiaojing , Wang Wei , Li Zhengli
Published: October 2009

Objective: It is known that highly activated microglia and the consequent production of inflammatory cytokines were associated with neuroexcitotoxic injuries. The present study was carried out to explore whether interleukin-1β (IL-1β), a proinflammatory cytokine produced in abundance by activated microglia, mediates increased excitability of hippocampal neurons and the related molecular mechanisms. Methods: Primary cultured microglia were activated by kainic acid (KA), and the KA-treated microglial conditioned medium (KA-MCM) was collected. KA-MCM with or without anti-rat IL-1β monoclonal neutralizing antibody was then injected into the rat in the right cerebral ventricle, or primary cultured hippocampal neurons were treated with the above-mentioned KA-MCM. The population spike amplitude changes in the CA3 region were assessed by electrophysiological recording in vivo. Western blot and RT-PCR assay were performed to investigate the expression changes of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) and inducible nitric oxide synthase (iNOS) expression in hippocampal neurons. Results: Primary cultured microglia were significantly activated by KA with increased IL-1β levels. Interestingly, intracerebroventricular administration of KA-MCM to rats resulted in enhancement of population spike amplitude in the CA3 region and in upregulation of NMDAR1 and iNOS expression in the hippocampus, which was partially attenuated by anti-rat IL-1β antibody. Furthermore, the changes in NMDAR1 and iNOS expression in the rat hippocampus were verified by incubation of primary cultured hippocampal neurons with KA-MCM. Conclusion: This study provides evidence that KA-activated microglia mediate increased excitability of hippocampal neurons in vitro and in vivo and that IL-1β may be one of the main causes of this event.
Distribution of Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-α in the Peripheral Nervous System of Lewis Rats during Ascending Paresis and Spontaneous Recovery from Experimental Autoimmune Neuritis
Authors: De La Hoz Cristiane L.R. , Castro Fabiano R. , Santos Leonilda M.B. , Langone Francesco
Published: October 2009

Background: Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) are pleiotropic molecules with widespread action in autoimmune diseases. Objective: This study characterizes the distribution of iNOS and TNF-α in the spinal nerve roots, dorsal root ganglia and sciatic nerve of Lewis rats during experimental autoimmune neuritis (EAN). Methods: Macrophages and neutrophils were identified by immunofluorescence as cellular sources of iNOS and TNF-α at various stages of EAN induced by synthetic peptide 26. Results: As the disease progressed, iNOS- and TNF-α-bearing cells gradually infiltrated the cauda equina, dorsal root ganglia, Th12–L3 spinal roots, and the sciatic nerve. A severer EAN profile developed when more iNOS- and TNF-α-bearing cells were present, and the recovery from EAN was related to the disappearance of these cells and the regeneration of nerve fibers. Conclusions: This is the first report to show iNOS- and TNF-α-immunoreactive cells in dorsal root ganglia during EAN, suggesting an underlying pathology for the neuropathic pain behavior in EAN. Our results suggest that the cells bearing iNOS and TNF-α in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.
Low-Level Vagosympathetic Stimulation
Authors: Li Shuyan , Scherlag Benjamin J. , Yu Lilei , Sheng Xia , Zhang Ying , Ali Reza , Dong Yumei , Ghias Muhammad , Po Sunny S.
Published: October 2009

Background—

We used high-frequency stimulation delivered during the refractory period of the atrium and pulmonary veins (PVs) to induce focal firing and atrial fibrillation (AF). This study was designed to demonstrate that bilateral low-level vagosympathetic nerve stimulation (LL-VNS) could suppress high-frequency stimulation-induced focal AF at atrial and PV sites.

Methods and Results—

In 23 dogs anesthetized with Na-pentobarbital, electrodes in the vagosympathetic trunks allowed LL-VNS at 1 V below that which slowed the sinus rate or atrioventricular conduction. Multielectrode catheters were fixed at the right and left superior and inferior PVs and both atrial appendages. LL-VNS continued for 3 hours. At the end of each hour, the high-frequency stimulation algorithm consisting of a 40-ms train of stimuli (200 Hz; stimulus duration, 0.1 to 1.0 ms) was delivered 2 ms after the atrial pacing stimulus during the refractory period at each PV and atrial appendages site. The lowest voltage of high-frequency stimulation that induced AF was defined as the AF threshold. Five dogs without LL-VNS served as sham controls. Six dogs underwent LL-VNS after transection of bilateral vagosympathetic trunks. LL-VNS induced a progressive increase in AF threshold at all PV and atrial appendages sites, particularly significant (
P
<0.05) at the right superior PV, right inferior PV, left superior PV, and right atrial appendage. Bilateral vagosympathetic transection did not significantly alter the previous findings, and the 5 sham control dogs did not show changes in AF threshold at any site over a period of 3 hours.

Conclusions—

LL-VNS may prevent episodic AF caused by rapid PV and non-PV firing.
Vernakalant Hydrochloride for the Rapid Conversion of Atrial Fibrillation After Cardiac Surgery
Authors: Kowey Peter R. , Dorian Paul , Mitchell L. Brent , Pratt Craig M. , Roy Denis , Schwartz Peter J. , Sadowski Jerzy , Sobczyk Dorota , Bochenek Andrzej , Toft Egon
Published: October 2009

Background—

Postoperative atrial arrhythmias are common and are associated with considerable morbidity. This study was designed to evaluate the efficacy and safety of vernakalant for the conversion of atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery.

Methods and Results—

This was a prospective, randomized, double-blind, placebo-controlled trial of vernakalant for the conversion of AF or AFL after coronary artery bypass graft, valvular surgery, or both. Patients were randomly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo. If AF or AFL was present after a 15-minute observation period, then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given. The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing. In patients with AF, 47 of 100 (47%) who received vernakalant converted to SR compared with 7 of 50 (14%) patients who received placebo (
P
<0.001). The median time to conversion was 12 minutes. Vernakalant was not effective in converting postoperative AFL to sinus rhythm. Two serious adverse events occurred within 24 hours of vernakalant administration (hypotension and complete atrioventricular block). There were no cases of torsades de pointes, sustained ventricular tachycardia, or ventricular fibrillation. There were no deaths.

Conclusions—

Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery.

Clinical Trial Registration—

clinicaltrials.gov. Identifier: NCT00125320.
Bleeding Increases the Risk of Ischemic Events in Patients With Peripheral Arterial Disease
Authors: van Hattum Eline S. , Algra Ale , Lawson James A. , Eikelboom Bert C. , Moll Frans L. , Tangelder Marco J.D.
Published: October 2009

Background—

Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease.

Methods and Results—

All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7).

Conclusions—

In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.
Absence of Thrombospondin-2 Causes Age-Related Dilated Cardiomyopathy
Authors: Swinnen Melissa , Vanhoutte Davy , Van Almen Geert C. , Hamdani Nazha , Schellings Mark W.M. , D'hooge Jan , Van der Velden Jolanda , Weaver Matthew S. , Sage E. Helene , Bornstein Paul , Verheyen Fons K. , VandenDriessche Thierry , Chuah Marinee K. , Westermann Dirk , Paulus Walter J. , Van de Werf Frans , Schroen Blanche , Carmeliet Peter , Pinto Yigal M. , Heymans Stephane
Published: October 2009

Background—

The progressive shift from a young to an aged heart is characterized by alterations in the cardiac matrix. The present study investigated whether the matricellular protein thrombospondin-2 (TSP-2) may affect cardiac dimensions and function with physiological aging of the heart.

Methods and Results—

TSP-2 knockout (KO) and wild-type mice were followed up to an age of 60 weeks. Survival rate, cardiac function, and morphology did not differ at a young age in TSP-2 KO compared with wild-type mice. However, >55% of the TSP-2 KO mice died between 24 and 60 weeks of age, whereas <10% of the wild-type mice died. In the absence of TSP-2, older mice displayed a severe dilated cardiomyopathy with impaired systolic function, increased cardiac dilatation, and fibrosis. Ultrastructural analysis revealed progressive myocyte stress and death, accompanied by an inflammatory response and replacement fibrosis, in aging TSP-2 KO animals, whereas capillary or coronary morphology or density was not affected. Importantly, adeno-associated virus-9 gene–mediated transfer of TSP-2 in 7-week-old TSP-2 KO mice normalized their survival and prevented dilated cardiomyopathy. In TSP-2 KO animals, age-related cardiomyopathy was accompanied by increased matrix metalloproteinase-2 and decreased tissue transglutaminase-2 activity, together with impaired collagen cross-linking. At the cardiomyocyte level, TSP-2 deficiency in vivo and its knockdown in vitro decreased the activation of the Akt survival pathway in cardiomyocytes.

Conclusion—

TSP-2 expression in the heart protects against age-dependent dilated cardiomyopathy.
Environmental Mercury Exposure and Blood Pressure Among Nunavik Inuit Adults
Authors: Valera Beatriz , Dewailly Éric , Poirier Paul
Published: October 2009

Epidemiological evidence suggests a negative impact of methylmercury on the cardiovascular system, but findings regarding the effect on blood pressure (BP) are not consistent. We aimed to study the impact of mercury levels on BP among Nunavik Inuit adults. The health survey Qanuippitaa? was conducted in Nunavik (northern Quebec, Canada), and data were obtained from 732 Inuit ≥18 years of age. Anthropometric blood samples, as well as systolic BP and diastolic BP, were assessed. Pulse pressure (systolic BP−diastolic BP) was calculated. Mercury blood concentration was used as a biomarker of recent exposure. Simple relations between mercury and BP parameters were studied by using the Pearson correlation, whereas multiple regressions were performed to control for confounders. Mean age of the participants was 34.3 years (95% CI: 33.6 to 34.9 years). Systolic BP, diastolic BP, and pulse pressure means were 117 mm Hg (95% CI: 116 to 118 mm Hg), 73 mm Hg (95% CI: 72 to 74 mm Hg), and 43 mm Hg (95% CI: 42 to 44 mm Hg), respectively. Mercury mean was 50.2 nmol/L. In multivariable analyses, mercury was associated with systolic BP (β=2.14;
P
=0.0004), whereas the association with diastolic BP was near the significance level (β=0.96;
P
=0.069). In conclusion, mercury is associated with increasing BP and pulse pressure among Nunavik Inuit adults after considering the effect of fish nutrients (n-3 fatty acids and selenium) and other confounders.
Gospel Music as a Mirror of the Political and Socio-Economic Developments in Zimbabwe, 1980-2007
Authors: Gwekwerere Gadziro
Published: October 2009

This paper explores, analyses and discusses Zimbabwean gospel song themes from 1980 up to 2007 in relation to the Zimbabwean political and socio-economic situations in the country. The history of the socio-economic and political development of Zimbabwe during 1980-2007 would certainly be incomplete without including gospel music. Until about the mid-1980s, the general atmosphere in the newly-independent state of Zimbabwe was characterized by liberation euphoria and great optimism for the future. Equally so, local gospel music during this period was largely celebrative and conformist as far as the political and socio-economic dispensation was concerned. Socio-economic hardships crept in as a result of the government's implementation of neo-liberal economic reforms under the guidance of the World Bank and the International Monetary Fund (IMF) during the early 1990s. The ruling party soon found itself confronted by a multitude of gospel musicians criticizing its policies and malpractices. Works of various gospel artistes will be used as evidence but due to issues of space, it has not been possible to cover all Zimbabwean gospel artists.
Regional National Autonomy under Challenge: Law, Practice and Recommendations
Authors: Zhou Yong , Lundberg Maria
Published: October 2009

Regional national autonomy is claimed to be the "basic policy" of the Chinese Communist Party and a "basic political system" of the State to solve the minority nationalities' issues in China. Within the framework of "basic law", the Regional National Autonomy Law, the rights of the minority nationalities to administer their internal affairs shall be guaranteed. The present severe challenges to this system can be observed through its malfunctions in ethnic conflict solution, the maintenance of cultural diversity and the due regards of the interests of minorities in the quick the economic development. By developing its research methodology based on reviewing previous studies in this field, this article tries to describe this system in law and in practice through four essential elements, which include territory, group, organs of self-government and autonomous power of regional national autonomy. Taking into account the problems of implementation of law and the institutional design of regional national autonomy, this article briefly explores options to provide a meaningful autonomy for minority nationalities in China.
Portrait of an Institution: The US Embassy in London, 1945-53
Authors: Colman Jonathan
Published: October 2009

The US Embassy in London has long played a leading institutional role in the Anglo-American relationship, but few historians have examined that role. This article covers the early Cold War era of 1945-1953 — a formative period in the Anglo-American relationship — and considers issues such as the Embassy's organization, the range of work in which it participated and the contributions of the successive ambassadors. Prominent policy issues during this period included the European Recovery Plan and the Berlin Crisis. It is contended that the Embassy reached the peak of its peacetime importance under US Ambassador Lewis Douglas from 1947-1950, and that its most important role was in policy liaison. This liaison function stemmed from the need to coordinate British and US policies in the developing Cold War, and helped to lay the foundations for the long-term 'special relationship'. The article provides fresh insights into Anglo-American diplomatic bonds in a formative period.
Meridional Density Gradients Do Not Control the Atlantic Overturning Circulation
Authors: de Boer Agatha M. , Gnanadesikan Anand , Edwards Neil R. , Watson Andrew J.
Published: October 2009

A wide body of modeling and theoretical scaling studies support the concept that changes to the Atlantic meridional overturning circulation (AMOC), whether forced by winds or buoyancy fluxes, can be understood in terms of a simple causative relation between the AMOC and an appropriately defined meridional density gradient (MDG). The MDG is supposed to translate directly into a meridional pressure gradient. Here two sets of experiments are performed using a modular ocean model coupled to an energy–moisture balance model in which the positive AMOC–MDG relation breaks down. In the first suite of seven model integrations it is found that increasing winds in the Southern Ocean cause an increase in overturning while the surface density difference between the equator and North Atlantic drops. In the second suite of eight model integrations the equation of state is manipulated so that the density is calculated at the model temperature plus an artificial increment ΔT that ranges from −3° to 9°C. (An increase in ΔT results in increased sensitivity of density to temperature gradients.) The AMOC in these model integrations drops as the MDG increases regardless of whether the density difference is computed at the surface or averaged over the upper ocean. Traditional scaling analysis can only produce this weaker AMOC if the scale depth decreases enough to compensate for the stronger MDG. Five estimates of the depth scale are evaluated and it is found that the changes in the AMOC can be derived from scaling analysis when using the depth of the maximum overturning circulation or estimates thereof but not from the pycnocline depth. These two depth scales are commonly assumed to be the same in theoretical models of the AMOC. It is suggested that the correlation between the MDG and AMOC breaks down in these model integrations because the depth and strength of the AMOC is influenced strongly by remote forcing such as Southern Ocean winds and Antarctic Bottom Water formation.
Comparison of Aura MLS Water Vapor Measurements with GFS and NAM Analyses in the Upper Troposphere–Lower Stratosphere
Authors: Van Thien Le , Gallus William A. , Olsen Mark A. , Livesey Nathaniel
Published: October 2009

Water vapor mixing ratios in the upper troposphere and lower stratosphere measured by the Aura Microwave Limb Sounder (MLS) version 2.2 instrument have been compared with Global Forecast System (GFS) analyses at five levels within the 300–100-hPa layer and North American Mesoscale (NAM) model analyses at six levels within the 300–50-hPa layer over the two years of 2005 and 2006 at four analysis times (e.g., 0000, 0600, 1200, and 1800 UTC). Probability density functions of the vapor mixing ratios suggest that both analyses are often moister than Aura MLS values, but NAM model analyses agree somewhat better with Aura MLS measurements than GFS model analyses over the same North American domain at the five common levels. Examining five subsets of the global GFS domain, the GFS model analysis is moister than Aura MLS estimates everywhere but at 150 and 100 hPa in all regions outside of the tropics. NAM model analysis water vapor mixing ratios exceeded the Aura MLS values at all levels from 250 to 150 hPa in all four seasons of both years and some seasons at 100 and 50 hPa. Moist biases in winter and spring of both years were similar at all levels, but these moist biases in summer and fall were smaller in 2005 than in 2006 at all levels. These differences may be due to the change in the NAM from using the Eta Model to using the Weather Research and Forecasting model (WRF) in June 2006.
Comments on “Structure and Evolution of a Possible U.S. Landfalling Tropical Storm in 2006”
Authors: Beven John L. , Avila Lixion A. , Blake Eric S. , Cobb Hugh D. , Pasch Richard J.
Published: October 2009

The Best Track Change Committee of the National Hurricane Center evaluates proposed changes to the Hurricane Database (HURDAT) in the Atlantic and eastern North Pacific basins. In the companion paper, Gruskin documents a possible tropical cyclone that affected portions of the eastern United States on 27–28 June 2006 and proposes that it be added to HURDAT. The committee reviewed the aircraft, radar, rawinsonde, satellite, and surface data available on this system and found it to be a challenging and complex system. A reconnaissance aircraft flying in the system in real time failed to find a closed circulation before landfall, and kinematic parameters suggest the system was more likely to have the structure of an open wave, with any surface circulation at best being poorly defined. Because of the lack of conclusive evidence regarding the existence of a closed surface circulation before landfall, the committee has decided not to add this system to HURDAT as a tropical cyclone.
The Use of Prompts, Increased Accessibility, Visibility, and Aesthetics of the Stairwell to Promote Stair Use in a University Building
Authors: van Nieuw-Amerongen M.E. , Kremers S.P.J. , de Vries N.K. , Kok G.
Published: October 2009

Physical activity in the form of consistently opting for stair use instead of elevator use can have important health benefits. The article discusses a study assessing whether increasing the attractiveness and accessibility of a stairwell had an impact on stair use among students and employees of Maastricht University, the Netherlands. The intervention involves multiple environmental changes, including prompts and enhanced aesthetics, visibility, and accessibility of the stairwell. Stair and elevator use by students and employees of Maastricht University are observed using video cameras. Data are collected continuously during 1 week before and 4 weeks after the implementation of the intervention. A total of 21,786 observations are made. Findings reveal that total stair use increased significantly, by 8.2% and that effects remain stable over the 4-week postintervention period. Stair use can be positively and continuously influenced by improving the stairwell environment.
On the Social-Communicative Function of Justice: The Influence of Communication Goals and Personal Involvement on the Use of Justice Assertions
Authors: Wijn Remco , van den Bos Kees
Published: October 2009

This article reveals how people strategically use justice assertions when attempting to persuade others. In three studies participants communicated about a negative situation they or someone else had experienced and did so in a persuasive manner (Studies 1-3), an accurate manner (Study 1), by asking for an opinion (Study 2), or without a communication goal (Studies 1 and 3). Communicators who had a persuasion goal used more justice-related words than communicators who had a goal to be accurate, asked for an opinion, or had no goal. This was particularly the case when communications were about someone else rather than the participants themselves and for those high in self-monitoring whose identities were known (vs. anonymous). The article concludes that people use justice-related words in attempts to persuade others, but only when they know there is no doubt about their personal involvement. Implications are discussed.
Characterization of Fibrodysplasia in the Dog Following Inhibition of Metalloproteinases
Authors: Westwood Russell , Scott Robert C. , Somers Rebecca L. , Coulson Michelle , Maciewicz Rose A.
Published: October 2009

Musculoskeletal side effects are a widely reported consequence of administration of particular matrix metalloproteinase inhibitors (MMPi) in clinical trials. We describe here histopathological findings during dog studies with a fairly selective MMPi AZM551248, that are consistent with these human clinical changes. They were characterized by a dose-and time-dependent formative connective tissue alteration we have termed “fibrodysplasia.” The most sensitive site was the subcuticular connective tissue, although musculoskeletal tissues were also extensively involved. In the subcutis, changes occurred initially around pre-existing blood vessels, but then more diffusely. There was proliferation of cells showing myofibroblast differentiation identified by elevated levels of alpha-smooth muscle actin, fibronectin, and transforming growth factor β, and the deposition of collagen type III with a lesser quantity of collagen type I. On longer-term administration at lower doses, there was evidence of active fibrodysplasia arising and resolving during the dosing period, resulting in the multifocal deposition of mature collagen. Although there was organ specificity, essentially identical changes occurred at multiple connective tissue sites. We conclude that MMPi-induced fibrodysplasia in animals and, by inference, musculoskeletal side effects in humans are potentially diffuse connective tissue disorders.
Remote sensing of soil surface properties
Authors: Anderson K. , Croft H.
Published: October 2009

Remote sensing is now in a strong position to provide meaningful spatial data for use in soil science investigations. In the last 10 years, advancements in remote sensing techniques and technologies have given rise to a wealth of exciting new research findings in soil-related disciplines. This paper provides a critical insight into the role played by remote sensing in this field, with a specific focus on soil surface monitoring. Two key soil properties are considered in this review, soil surface roughness and moisture, because these two variables have benefited most from recent cutting-edge advances in remote sensing. Of note is the fact that the major recent advancements in spatial assessment of soil structure have emerged from optical remote sensing, while the soil moisture community has benefited from advancements in microwave systems, justifying the focus of this paper in these specific directions. The paper considers the newest techniques within active, passive, optical and microwave remote sensing and concludes by considering future challenges, multisensor approaches and the issue of scale — which is a key cross-disciplinary research question of relevance to soil scientists and remote sensing scientists alike.
A review of satellite meteorology and climatology at the start of the twenty-first century
Authors: Kidd Chris , Levizzani Vincenzo , Bauer Peter
Published: October 2009

The observation of the atmosphere by satellite instrumentation was one of the first uses of remotely sensed data nearly 50 years ago. Since then a range of satellites have carried many different meteorological sensors capable of monitoring the dynamics of the atmosphere and the capture and retrieval of information about atmospheric parameters for use in meteorological and climatological applications. The utilization of satellite observations for meteorology and climatology is essential since the atmosphere is a global feature, and conventional observations of it are primarily land-based. Satellites, with their synoptic view, provide much information benefiting numerical weather prediction models to improve weather forecasting and the ability to monitor weather systems, in particular those that pose a threat to humankind, over the entire Earth. Development of new observational capabilities has led to new insights into atmospheric processes and their interaction, allowing the consequences of anthropogenic activities, such as climate change, to be monitored.
Remote sensing and the future of landscape ecology
Authors: Newton Adrian C. , Hill Ross A. , Echeverría Cristian , Golicher Duncan , Rey Benayas José M. , Cayuela Luis , Hinsley Shelley A.
Published: October 2009

Landscape ecology focuses on the analysis of spatial pattern and its relationship to ecological processes. As a scientific discipline, landscape ecology has grown rapidly in recent years, supported by developments in GIS and spatial analysis techniques. Although remote sensing data are widely employed in landscape ecology research, their current and potential roles have not been evaluated critically. To provide an overview of current practice, 438 research papers published in the journal Landscape Ecology for the years 2004—2008 were examined for information about use of remote sensing. Results indicated that only 36% of studies explicitly mentioned remote sensing. Of those that did so, aerial photographs and Landsat satellite sensor images were most commonly used, accounting for 46% and 42% of studies, respectively. The predominant application of remote sensing data across these studies was for thematic mapping purposes. This suggests that landscape ecologists have been relatively slow to recognize the potential value of recent developments in remote sensing technologies and methods. The review also provided evidence of a frequent lack of key detail in studies recently published in Landscape Ecology , with 75% failing to provide any assessment of uncertainty or error relating to image classification and mapping. It is suggested that the role of remote sensing in landscape ecology might be strengthened by closer collaboration between researchers in the two disciplines, by greater integration of diverse remote sensing data with ecological data, and by increased recognition of the value of remote sensing beyond land-cover mapping and pattern description. This is illustrated by case studies drawn from Latin America (focusing on forest loss and fragmentation) and the UK (focusing on habitat quality for woodland birds). Such approaches might improve the analytical and theoretical rigour of landscape ecology, and be applied usefully to issues of outstanding societal interest, such as the impacts of environmental change on biodiversity and ecosystem services.
The T Allele of the 677C>T Polymorphism of Methylenetetrahydrofolate Reductase Gene is Associated With an Increased Risk of Ischemic Stroke in Polish Children
Authors: Zak Iwona , Sarecka-Hujar Beata , Kopyta Ilona , Emich-Widera Ewa , Marszal Elzbieta , Wendorff Janusz , Jachowicz-Jeszka Joanna
Published: October 2009

Ischemic stroke is a very rare and multifactorial disease in children. The aim of the study was to analyze the relationship between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and stroke in Polish children and to observe whether there is any significant transmission of MTHFR alleles from heterozygous parents to their affected offspring. We analyzed 64 patients with stroke, 122 parents, and 59 healthy children. The MTHFR polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. The T allele was more frequent in the stroke group (38%) than in controls (25%, P = .029, odds ratio = 1.84). We also found higher frequency of T allele in male patients compared to male controls (46% vs. 25%, P = .009, odds ratio = 2.53). The number of T allele carriers was again more prevalent in boys with stroke (71%) than in healthy boys (45%, P = .023, odds ratio = 3.09). The T allele was significantly transmitted in male patients (P < .019). We conclude that the MTHFR 677C>T polymorphism may be considered as a genetic risk factor of childhood stroke, especially in boys.
Perceptions of Regional Economic Development: Can Win—Lose Become Win—Win?
Authors: Gordon Victoria
Published: October 2009

This study extends previous research that explored the perceptions of economic development decision makers in Illinois regarding regional economic development competition and cooperation.This research project further contributes to an understanding of the interlocal cooperative interactions that exist between and among local governments.The author uses a qualitative approach using in-depth interviews conducted in 2006-2007 of participants within selected regions of Missouri, Indiana, Kentucky, and Tennessee. In 2002, communities participated in cooperative efforts, understood the benefits of cooperation, and expressed a willingness to cooperate in regional economic development efforts, however, the myriad obstacles to cooperation significantly curtailed cooperative efforts; now, the communities examined in Missouri, Indiana, Kentucky, and Tennessee have moved to actual cooperative action. Interviewees recognize that they must cooperate to be successful in economic development efforts— suggesting perhaps that economic development previously perceived as an inherently win—lose game has become a win—win arrangement.