bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial genetic structure of lowbush blueberry,Vaccinium angustifolium, in four fields in Maine
Authors: Bell Daniel J. , Rowland Lisa J. , Zhang Dapeng , Drummond Frank A.
Published: October 2009

Expressed sequence tag – polymerase chain reaction (EST-PCR) molecular markers were used to infer spatial genetic structure of four lowbush blueberry ( Vaccinium angustifolium Ait.) fields in Maine. Genetic structure was quantified at three spatial scales: (1) within apparent clones (intrapatch), (2) among clones within a field, and (3) among fields separated by as much as 65 km. Of five “clones” or putative individuals examined in the intrapatch study, two showed complete genetic homogeneity within the patch, while three showed some band differences at their edges compared with their interiors. These differences at the edges, however, matched adjacent clones (so-called “intruders”), from which it was concluded that lowbush blueberry exhibits a fairly tight, phalanx clonal architecture with no evidence of invasive seedling establishment within clones. No significant correlation between genetic and physical distance was found among clones within fields via several statistical approaches. Significant among-field genetic differentiation was found via AMOVA (ΦPT= 8.4%; p ≤ 0.01) based upon transect samples across four fields ranging from 12.5 to 65 km apart. Principal component analysis and spatial autocorrelation (SA) corroborated these findings. Significant positive SA was found at the within-field distance class of <350 m, but SA decreased to an insignificant value by the first interfield distance of 12.5 km. A special form of SA analysis was employed to detect “hotspots” of genetic similarity between pairs of adjacent clones in two fields. Results indicated that 5 of 23 pairs of clones (21.7%) were genetically similar to each other, while the majority of pairs (18 of 23; 78.3%) showed random, decreasing patterns of genetic similarity. Results are discussed in terms of clonal dynamics including architecture, seedling recruitment, and inferred pollen or seed dispersal distances.
Low soil temperature reduces the positive effects of high nutrient supply on the growth and biomass of white birch seedlings in ambient and elevated carbon dioxide concentrations
Authors: Ambebe Titus Fondo , Dang Qing-Lai , Marfo Jacob
Published: October 2009

To investigate the interactive effects of soil temperature (Tsoil) and nutrient supply on the responses of growth and biomass of white birch ( Betula papyrifera Marsh.) to atmospheric carbon dioxide concentration ([CO2]), seedlings were grown under two [CO2] (360 and 720 µmol·mol–1), three Tsoil (5, 15, and 25 °C initially, increased to 7, 17, and 27 °C one month later), and three nutrient regimes (Low: N–P–K = 4:1.8:3.3 mg·L–1; Intermediate: N–P–K = 80:35:66 mg·L–1; and High: N–P–K = 160:70:132 mg·L–1) for 4 months. Low Tsoil reduced leaf and total biomass at high nutrient supply and root biomass at intermediate and high nutrient supply. There were significant three-factor interactive effects on root collar diameter (RCD), stem biomass, and leaf mass ratio. Low Tsoil reduced RCD at high nutrient supply and stem biomass at intermediate and high nutrient supply in elevated [CO2] while intermediate and high Tsoil enhanced them. Values of leaf mass ratio were lowest at low Tsoil and low nutrient supply in elevated [CO2]. The effect of Tsoil was generally insignificant at low nutrient supply, but the responses of growth and biomass remained significantly higher under high than low nutrient supply at all Tsoil.
Tomato plant architecture as affected by salinity: Descriptive analysis and integration in a 3-D simulation model
Authors: Najla Safaa , Vercambre Gilles , Pagès Loïc , Grasselly Dominique , Gautier Hélène , Génard Michel
Published: October 2009

Limited information is available on the effect of salinity on plant architecture; not only on final plant height, number of leaves, and leaf area, but also on plant growth and development from the leaflet to the whole plant scale. Tomato plants ( Solanum lycopersicum L. ‘Marmara’) were grown in greenhouses at four salinity levels (4, 7, 10, and 13 mS·cm–1). Plant development (leaf and inflorescence initiation), leaf growth rate, and final leaf dimensions were measured along the stem according to leaf rank and treatment. A decrease in leaflet growth and in the number of leaflets per leaf was associated with a lower growth rate and longer growth period in salinity stressed plants. Stem internode length was also reduced by salinity. At the plant scale, plant height and leaf area decreased with an increase in salinity. These parameters were the main inputs of a 3-D model of plant architecture, which enabled a complete description of plant architecture from the elementary to the canopy scale. This model of plant architecture was evaluated by comparing hemi-spherical photos of the plant taken with a camera with those generated by the model. The model was used to estimate light interception which should be useful to calculate photosynthesis at the plant scale.
High stability ferric chelates result in decreased iron uptake by the green algaChlorella kessleriowing to decreased ferric reductase activity and chelation of ferrous iron
Authors: Weger Harold G. , Lam Jackie , Wirtz Nikki L. , Walker Crystal N. , Treble Ron G.
Published: October 2009

Cells of the green alga Chlorella kessleri Fott et Nováková use a reductive mechanism for iron acquisition. Iron-limited cells acquired iron more rapidly from a chelator with a lower stability constant for Fe3+(hydroxyethylethylenediaminetriacetic acid (HEDTA)) than from a chelator with a higher stability constant (N,N′-di[2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED)). Furthermore, iron uptake rates decreased with increasing chelator concentrations at constant iron concentration. The negative effects of elevated HBED levels on iron uptake could be partly alleviated by the addition of Ga3+, which suggests that iron-free chelator has a negative effect on iron acquisition by competing for Fe2+with the ferrous transport system. Furthermore, ferric reductase activity progressively decreased with increasing concentrations of both chelators (in the iron-free form). This effect was not alleviated by Ga3+addition and was apparently caused by the direct inhibition of the reductase. Overall, we conclude that chelators with high stability constants for Fe3+decrease iron acquisition rates by Strategy I organisms via three separate mechanisms.
The genus Bauhinia s.l. (Leguminosae): a phylogeny based on the plastid trnL–trnF region
Authors: Sinou Carole , Forest Félix , Lewis Gwilym P. , Bruneau Anne
Published: October 2009

As the largest genus in tribe Cercideae, the pantropical genus Bauhinia has been the subject of a number of regional treatments in which it has been recognized either as a single genus with several subgenera or as several distinct genera. With the aim to better understand the taxon relationships within Bauhinia and between it and related genera, we have sequenced the plastid trnL–trnF region for 85 species, which together are representative of the eight genera recognized within Bauhinia sensu lato by some workers. In addition, representative taxa were verified for the presence or absence of the plastid rpl2 intron, which previous studies indicated might be a marker for specific lineages within Bauhinia s.l. Both Bayesian and parsimony analyses indicate that Bauhinia s.l. is paraphyletic with the monospecific genus Brenierea clustered within it. This genus, usually described as sister to Bauhinia s.l., forms a clade with the genera Piliostigma and Bauhinia sensu stricto. The remaining genera ( Gigasiphon , Tylosema , Barklya , Phanera , Lasiobema , and Lysiphyllum ) form a second clade sister to the first. All of these segregate genera are monophyletic except for Phanera, which is divided into two lineages comprising the Asian Phanera species together with the genus Lasiobema , and the second comprising the American Phanera species. The relationship between the Brenierea – Bauhinia s. str. – Piliostigma clade, the Gigasiphon–Tylosema–Barklya–Phanera–Lasiobema–Lysiphyllum clade and the genus Griffonia is not well resolved, but Adenolobus is sister to this large monophyletic group and the genus Cercis is sister to all other Cercideae. Preliminary analyses of the rpl2 plastid region also support the Piliostigma – Brenierea – Bauhinia s. str. clade, suggesting a unique loss event of the intron prior to the diversification of this clade.
Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2
Authors: Spallarossa Paolo , Altieri Paola , Aloi Concetta , Garibaldi Silvano , Barisione Chiara , Ghigliotti Giorgio , Fugazza Giuseppina , Barsotti Antonio , Brunelli Claudio
Published: October 2009

Low or high doses of doxorubicin induce either senescence or apoptosis, respectively, in cardiomyocytes. The mechanism by which different doses of doxorubicin may induce different stress-response cellular programs is not well understood. A recent study showed that the level of telomere dysfunction may induce senescence or apoptosis. We investigated the pathways to both apoptosis and senescence in neonatal rat cardiomyocytes and in H9c2 cells exposed to a single pulsed incubation with low or high doses of doxorubicin. High-dose doxorubicin strongly reduces TRF2 expression while enhancing TRF1 expression, and it determines early apoptosis. Low-dose doxorubicin induces downregulation of both TRF2 and TRF1, and it also increases the senescence-associated-β-galactosidase activity, downregulates the checkpoint kinase Chk2, induces chromosomal abnormalities, and alters the cell cycle. The involvement of TRF1 and TRF2 with apoptosis and senescence was assessed by short interfering RNA interference. The cells maintain telomere dysfunction and a senescent phenotype over time and undergo late death. The increase in the phase >4N and the presence of micronuclei and anaphase bridges indicate that cells die by mitotic catastrophe. p38 modulates TRF2 expression, whereas JNK and cytoplasmic p53 regulate TRF1. Pretreatment with specific inhibitors of MAPKs and p53 may either attenuate the damage induced by doxorubicin or shift the cellular response to stress from senescence to apoptosis. In conclusion, various doses of doxorubicin induce differential regulation of TRF1 and TRF2 through p53 and MAPK, which is responsible for inducing either early apoptosis or senescence and late death due to mitotic catastrophe.
Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy
Authors: Zhang Lei , Liu Yan , Lu Xiao Ting , Wu Yi Ling , Zhang Cheng , Ji Xiao Ping , Wang Rong , Liu Chun Xi , Feng Jin Bo , Jiang Hong , Xu Xin Sheng , Zhao Yu Xia , Zhang Yun
Published: October 2009

This study was carried out to test the hypothesis that Tongxinluo (TXL) as a Chinese herbal medicine enhances stability of vulnerable plaque dose dependently via lipid-lowering and anti-inflammation effects, similar to a high-dose simvastatin therapy. After abdominal aortic balloon injury, 75 rabbits were fed a 1% cholesterol diet for 10 wk and were then divided into five groups for 8-wk treatment: control group, low-dose TXL group, moderate-dose TXL group, high-dose TXL group, and high-dose simvastatin group. At the end of week 16, an adenovirus containing p53 was injected into the abdominal aortic plaques. Two weeks later, plaque rupture was induced by pharmacological triggering. The incidence of plaque rupture in all treatment groups (14.3%, 7.1%, 7.7%, and 7.1%) was significantly lower than that in control group (73.3%; P > 0.01). TXL dose-dependently lowered serum lipid levels and inhibited systemic inflammation. Corrected acoustic intensity and fibrous cap thickness of the aortic plaques were significantly increased, whereas plaque area, plaque burden, vulnerable index, and expression of oxidized low-density lipoprotein (ox-LDL) receptor 1, matrix metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor of MMP 1, and NF-κB in plaques were markedly reduced in all treatment groups when compared with the control group. Similar to high-dose simvastatin group, high-dose TXL group exhibited a low serum level of low-density lipoprotein cholesterol and ox-LDL, a low expression level of systemic and local inflammatory factors and a low plaque vulnerability index, with no differences in the incidence of plaque rupture among all treatment groups. TXL dose-dependently enhances the stability of vulnerable plaques and prevents plaques from rupture. Simvastatin and TXL offer similar protection in terms of lipid-lowering, anti-inflammation, and antioxidation effects.
Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function
Authors: Basu Ratnadeep , Oudit Gavin Y. , Wang Xiuhua , Zhang Liyan , Ussher John R. , Lopaschuk Gary D. , Kassiri Zamaneh
Published: October 2009

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita ( Ins2WT/C96Y) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Yand their littermate control ( Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Ymice exhibited preserved cardiac systolic function compared with Ins2WT/WTmice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Ymice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WTmice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Ymyocardium. Consistent with the lack of fibrosis, expression of procollagen-α type I, procollagen-α type III, and fibronectin were not increased in these hearts. Ins2WT/C96Yhearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+pump) levels, elevated β-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Yhearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and β-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in the absence of interstitial fibrosis and hypertrophy.
Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms
Authors: Lim Chee Chew , Bryan Nathan S. , Jain Mohit , Garcia-Saura Maria F. , Fernandez Bernadette O. , Sawyer Douglas B. , Handy Diane E. , Loscalzo Joseph , Feelisch Martin , Liao Ronglih
Published: October 2009

The female sex has been associated with increased resistance to acute myocardial ischemia-reperfusion (I/R) injury. While enhanced antioxidant capacity has been implicated in female cardioprotection, there is little evidence to support this assumption. Previous studies have shown an important role of cellular glutathione peroxidase (GPx1) in protection of the myocardium from I/R injury. Whether GPx1 is mechanistic in the protection of female myocardium, post-I/R, has not been examined. We utilized a murine model with homozygous deletion of GPx1 and examined its impact on postischemic myocardial recovery in male and female mice. Following I/R, male GPx1(−/−) hearts were more susceptible to contractile and diastolic dysfunction, and this was associated with increased protein carbonyls, a marker of oxidative stress. In contrast, GPx1 deficiency in female hearts did not exacerbate dysfunction or oxidative stress post-I/R. Both wild-type and GPx1(−/−) female hearts exhibited reduced creatine kinase leakage and a more favorable ascorbate redox status compared with males. Following I/R, female GPx1(−/−) hearts showed a comparable decrease in glutathione redox status as their male counterparts; however, they exhibited a greater decrease in nitrate-to-nitrite ratio, suggesting a higher consumption of nitrate in female GPx1(−/−) hearts. Our findings demonstrate that GPx1 is critical for cardioprotection during I/R in male, but not female, mice. The maintenance of cardioprotection in female mice lacking GPx1 post-I/R may be due to an improved ascorbate redox homeostasis and enhanced nitrate-to-nitrite conversion, which would predictably be accompanied by enhanced production of cardioprotective nitric oxide.
Neuregulin-1 attenuated doxorubicin-induced decrease in cardiac troponins
Authors: Bian Yun , Sun Maoyun , Silver Marcy , Ho Kalon K. L. , Marchionni Mark A. , Caggiano Anthony O. , Stone James R. , Amende Ivo , Hampton Thomas G. , Morgan James P. , Yan Xinhua
Published: October 2009

Neuregulin-1 (NRG1) is a potential therapeutic agent for the treatment of doxorubicin (Dox)-induced heart failure. NRG1, however, activates the erbB2 receptor, which is frequently overexpressed in breast cancers. It is, therefore, important to understand how NRG1, via erbB2, protects the heart against Dox cardiotoxicity. Here, we studied NRG1-erbB2 signaling in Dox-treated mice hearts and in isolated neonatal rat ventricular myocytes (NRVM). Male C57BL/6 mice were treated with recombinant NRG1 before and daily after a single dose of Dox. Cardiac function was determined by catheterization. Two-week survival was analyzed by the Kaplan-Meier method. Cardiac troponins [cardiac troponin I (cTnI) and cardiac troponin T (cTnT)] and phosphorylated Akt protein levels were determined in mice hearts and in NRVM by Western blot analysis. Activation of caspases and ubiquitinylation of troponins were determined in NRVM by caspase assay and immunoprecipitation. NRG1 significantly improved survival and cardiac function in Dox-treated mice. NRG1 reduced the decrease in cTnI, cTnT, and cardiac troponin C (cTnC) and maintained Akt phosphorylation in Dox-treated mice hearts. NRG1 reduced the decrease in cTnI and cTnT mRNA and proteins in Dox-treated NRVM. Inhibition of erbB2, phosphoinositide 3-kinase (PI3K), Akt, and mTOR blocked the protective effects of NRG1 on cTnI and cTnT in NRVM. NRG1 significantly reduced Dox-induced caspase activation, which degraded troponins, in NRVM. NRG1 reduced Dox-induced proteasome degradation of cTnI. NRG1 attenuates Dox-induced decrease in cardiac troponins by increasing transcription and translation and by inhibiting caspase activation and proteasome degradation of troponin proteins. NRG1 maintains cardiac troponins by the erbB2-PI3K pathway, which may lessen Dox-induced cardiac dysfunction.
Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1
Authors: Zhou Guofei , Dada Laura A. , Wu Minghua , Kelly Aileen , Trejo Humberto , Zhou Qiyuan , Varga John , Sznajder Jacob I.
Published: October 2009

Patients with acute lung injury develop hypoxia, which may lead to lung dysfunction and aberrant tissue repair. Recent studies have suggested that epithelial-mesenchymal transition (EMT) contributes to pulmonary fibrosis. We sought to determine whether hypoxia induces EMT in alveolar epithelial cells (AEC). We found that hypoxia induced the expression of α-smooth muscle actin (α-SMA) and vimentin and decreased the expression of E-cadherin in transformed and primary human, rat, and mouse AEC, suggesting that hypoxia induces EMT in AEC. Both severe hypoxia and moderate hypoxia induced EMT. The reactive oxygen species (ROS) scavenger Euk-134 prevented hypoxia-induced EMT. Moreover, hypoxia-induced expression of α-SMA and vimentin was prevented in mitochondria-deficient ρ0 cells, which are incapable of ROS production during hypoxia. CoCl2 and dimethyloxaloylglycine, two compounds that stabilize hypoxia-inducible factor (HIF)-α under normoxia, failed to induce α-SMA expression in AEC. Furthermore, overexpression of constitutively active HIF-1α did not induce α-SMA. However, loss of HIF-1α or HIF-2α abolished induction of α-SMA mRNA during hypoxia. Hypoxia increased the levels of transforming growth factor (TGF)-β1, and preincubation of AEC with SB431542, an inhibitor of the TGF-β1 type I receptor kinase, prevented the hypoxia-induced EMT, suggesting that the process was TGF-β1 dependent. Furthermore, both ROS and HIF-α were necessary for hypoxia-induced TGF-β1 upregulation. Accordingly, we have provided evidence that hypoxia induces EMT of AEC through mitochondrial ROS, HIF, and endogenous TGF-β1 signaling.
The olfactory system is affected by steroid aerosol treatment in mice
Authors: Mucignat-Caretta C. , Bondí M. , Rubini A. , Calabrese F. , Barbato A.
Published: October 2009

Asthma needs continuous treatment often for years. In humans, some drugs are administered via aerosol, therefore they come in contact with both respiratory and olfactory mucosa. We explored the possibility that antiasthma corticosteroid treatment could influence the olfactory function by passage through the nose. A group of mice was exposed twice daily for 42 days to fluticasone propionate aerosol and was compared with a control group. Olfactory behavior, respiratory mechanics, histology, and immunoreactivity in the olfactory system were assessed. Fluticasone-treated mice were slower in retrieving a piece of hidden food, but both groups were similarly fast when the food was visible. When a clearly detectable odor was present in the environment, all mice behaved in a similar way. Respiratory mechanics indices were similar in all mice except for the viscose resistance, which was reduced in fluticasone-treated mice. Olfactory mucosa of fluticasone-treated mice was thicker than that of controls. Slight but consistent differences in staining were present for Olfactory Marker Protein but not for other proteins. A mild impairment of olfactory function is present in mice chronically treated with fluticasone aerosol, apparently accompanied by slight modifications of the olfactory receptor cells, and suggests monitoring of olfactory function modifications in long-term steroid users.
Tie2-mediated loss of peroxisome proliferator-activated receptor-γ in mice causes PDGF receptor-β-dependent pulmonary arterial muscularization
Authors: Guignabert C. , Alvira C. M. , Alastalo T.-P. , Sawada H. , Hansmann G. , Zhao M. , Wang L. , El-Bizri N. , Rabinovitch M.
Published: October 2009

Peroxisome proliferator-activated receptor (PPAR)-γ is reduced in pulmonary arteries (PAs) of patients with PA hypertension (PAH), and we reported that deletion of PPARγ in smooth muscle cells (SMCs) of transgenic mice results in PAH. However, the sequelae of loss of PPARγ in PA endothelial cells (ECs) are unknown. Therefore, we bred Tie2-Cre mice with PPARγflox/floxmice to induce EC loss of PPARγ (Tie2 PPARγ−/−), and we assessed PAH by right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and muscularized distal PAs in room air (RA), after chronic hypoxia (CH), and after 4 wk of recovery in RA (Rec-RA). The Tie2 PPARγ−/−mice developed spontaneous PAH in RA with increased RVSP, RVH, and muscularized PAs vs. wild type (WT); both genotypes exhibited a similar degree of PAH following chronic hypoxia, but Tie2 PPARγ−/−mice had more residual PAH compared with WT mice after Rec-RA. The Tie2 PPARγ−/−vs. WT mice in RA had increased platelet-derived growth factor receptor-β (PDGF-Rβ) expression and signaling, despite an elevation in the PPARγ target apolipoprotein E, an inhibitor of PDGF signaling. Inhibition of PDGF-Rβ signaling with imatinib, however, was sufficient to reverse the PAH observed in the Tie2 PPARγ−/−mice. Thus the disruption of PPARγ signaling in EC is sufficient to cause mild PAH and to impair recovery from CH-induced PAH. Inhibition of heightened PDGF-Rβ signaling is sufficient to reverse PAH in this genetic model.
Correlation of Autophagy Type in Podocytes with Histopathological Diagnosis of IgA Nephropathy
Authors: Sato S. , Yanagihara T. , Ghazizadeh M. , Ishizaki M. , Adachi A. , Sasaki Y. , Igarashi T. , Fukunaga Y.
Published: October 2009

Objective: IgA nephropathy (IgA-N) frequently leads to progressive renal failure, thus estimation of the degree of progression is important for patient management. Autophagy is a mechanism that facilitates clearance of waste products to preserve renal function. The aim of this study was to assess autophagy in podocytes in children with progressive IgA-N at initial diagnosis by electron microscopy and investigate the relationship between the types of autophagy and severity of the disease. Methods: Renal biopsies from 16 children with established progressive IgA-N were examined by light and transmission electron microscopy with reference to autophagy types in the podocytes and histopathological diagnosis of IgA-N. Results: Two autophagy types were found. Type I rarely transformed to autophagic vacuoles and did not dissolve, thus possibly impairing cell function. However, type II frequently transformed to autophagosomes and autophagic vacuoles thus facilitating protein and lipid clearance. Of the 16 children studied, 8 (50%) with type I autophagy at initial diagnosis showed focal proliferative glomerulosclerosis (GN) of mild type (3 cases, 37.5%), mild/moderate type (2 cases, 25%) and moderate type (3 cases, 37.5%). In contrast, the remaining 8 children with type II autophagy at initial diagnosis showed focal proliferative GN of mild type in 7 (87.5%) and mild/moderate type in 1 (12.5%) case. Conclusion: In IgA-N children, the occurrence of type I autophagy is correlated with histopathologically more progressive disease, possibly reflecting a tendency to a poorer prognosis.
Inflammatory Infiltrates and Neovessels Are Relevant Sources of MMPs in Abdominal Aortic Aneurysm Wall
Authors: Reeps Christian , Pelisek Jaroslav , Seidl Stefan , Schuster Tibor , Zimmermann Alexander , Kuehnl Andreas , Eckstein Hans-Henning
Published: October 2009

Objectives: Abdominal aortic aneurysm (AAA) wall is characterized by degradation of extracellular matrix through matrix metalloproteinases (MMPs), chronic inflammatory cell infiltration and extensive neovascularization. So far, MMP expression within AAA wall in association with infiltrates and neovascularization has not yet been studied. Methods: Vessel walls of 15 AAA patients and 8 organ donors were analyzed by immunohistochemistry for expression of various MMPs (MMP-1, -2, -3, -7, -8, -9, -12 and -13) in all cells located within the AAAs and correlated with infiltrates and neovascularization. Results: Luminal endothelial cells (ECs) were positive for MMP-1, -3 and -9, ECs of mature neovessels were furthermore positive for MMP-2. Immature neovessels expressed all MMPs tested except for MMP-13. Aortic medial smooth muscle cells (SMCs) expressed MMP-1, -2, -3 and -9, SMCs of mature neovessels, only MMP-1, -3 and -9. Inflammatory infiltrates expressed all MMPs tested except for MMP-2, macrophages expressed all MMPs. Infiltrates were composed mainly of B cells (58.5 ± 10.9%) and T lymphocytes (26.3 ± 9.5%). Furthermore, significant inverse correlations were found between the amounts of inflammatory cells, neovessels and collagen/elastin content of the aortic vessel wall (r = +0.806/p < 0.001, r = –0.650/p = 0.012, r = –0.63/p < 0.015; respectively). Conclusion: Inflammatory infiltrates and invading neovessels are relevant sources of MMPs in the AAA wall and may substantially contribute to aneurysm wall instability.
Effects of Passive Stretching on Muscle Injury and HSP Expression during Recovery after Immobilization in Rats
Authors: Inoue Takayuki , Suzuki Shigeyuki , Hagiwara Ryusuke , Iwata Masahiro , Banno Yasuhiro , Okita Minoru
Published: October 2009

Objective: Stretching exercise is known to induce muscle hypertrophy and is implicated in the modulation of muscle fiber behavior. We aim to determine whether stretching exercise is protective against reloading-induced muscle damage in immobilized rat soleus muscle. Methods: Rat hindlimbs in 54 eight-week-old male Wistar rats were immobilized by cast for 4 weeks, followed by reloading alone through normal ambulation in 24 (group NS) and after passive stretch in 25 rats (group S). Stretching exercise (30 min each day) lasted 6 days. To determine if passive stretching affects expression of heat shock proteins (HSPs) in rat soleus muscle during reloading following cast immobilization, the ratio of invading muscle fibers and HSPs expression were measured following cast removal. Results: The ratio of invading muscle fibers increased during the first and second days of reloading in group NS. Compared with reloading alone, stretching exercise reduced invading muscle fibers at most time points following cast removal (group S). Additionally, expression of HSP25 and HSP72 increased with time during reloading only in the group without passive stretch (group NS). Conclusion: Following immobilization, in the rat soleus muscle passive stretching exercise protects against injury induced by reloading. Furthermore, the protection provided by passive stretch is independent of HSPs.
Antisense Phosphorothioate Oligodeoxynucleic Acid for CD10 Suppresses Liver Metastasis of Colorectal Cancer
Authors: Luo Yi , Fujii Kiyomu , Ohmori Hitoshi , Sasahira Tomonori , Moriwaka Yukiko , Isobe Mamoru , Kuniyasu Hiroki
Published: October 2009

CD10 expression is associated with metastases of colorectal cancer (CRC). In the present study, we examined association of CD10 with liver metastasis of CRC cells to clarify the therapeutic significance of CD10. CD10-positive human colon cancer cell line, HT29 cells showed inhibition of growth, invasion and colony formation by treatment with CD10 antisense S-oligodeoxynucleotide (S-ODN). In the mouse liver metastasis mode, CD10 antisense S-ODN-treated HT29 cells made less embedded cells in the liver than control HT29 cells. Number and size of metastatic foci in nude mice liver were reduced in CD10 antisense S-ODN-treated HT29 cells. Treatment with CD10 antisense S-ODN decreased phosphorylation of ERK1/2 and EGFR in HT29 cells. Intraperitoneal administration of liposome-capsulated CD10 antisense S-ODN inhibited establishment of liver metastasis and growth of established metastasis in nude mice. These findings suggest that CD10 is associated substantially with liver metastasis of CRC cells and might be a molecular target of CRC treatment.
Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures
Authors: Lehtimäki Kai A. , Keränen Tapani , Palmio Johanna , Peltola Jukka
Published: October 2009

Background: Experimentally induced seizures are associated with increased production of inflammatory cytokines in the nervous system. Elevated cerebrospinal fluid levels of cytokine interleukin-6 (IL-6) have been found after a single generalized seizure in human patients. After prolonged seizures, levels of IL-6 have been shown to be even higher compared with single seizures. In the present study, we determined the levels of proconvulsive IL-1β and anticonvulsive IL-1ra in cerebrospinal fluid after single tonic-clonic seizures as well as after prolonged seizures. Methods: The levels of cytokines were measured using enzyme-linked immunosorbent assay. Results: We found that after single seizures, a slight increase in anticonvulsive IL-1ra levels was found; however, after prolonged partial or recurrent tonic-clonic seizures, the levels of IL-1ra were significantly elevated, together with decreased IL-1β levels. Conclusion: Our results indicate that after severe seizures, the balance between IL-1-type cytokines is changed towards a neuroprotective and anticonvulsive direction with an overproduction of IL-1ra with respect to potentially neurotoxic IL-1β. This reaction may serve as a defense mechanism of the nervous system against excitotoxic neuronal damage.
Effects of Methylprednisolone and Glatiramer Acetate on Nitric Oxide Formation of Cytokine-Stimulated Cells from the Rat Oligodendroglial Cell Line OLN-93
Authors: Holzknecht Christian , Röhl Claudia
Published: October 2009

Objectives: In multiple sclerosis, an autoimmune inflammatory disease, oligodendroglia are primarily affected and play an important role in the onset and process of the degeneration of neuronal axons. High-dose therapy with glucocorticoids like 6α-methylprednisolone (MP) as well as the application of immunomodulatory agents like glatiramer acetate (GA) are commonly used in the treatment of MS. The purpose of our study was to examine, in an adequate cell culture model, the effect of MP and GA on oligodendroglial activation induced by pro-inflammatory stimuli. Methods: In the present study, we measured the mRNA (real-time RT-PCR) and protein (Western blot) expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide (NO; Griess reagent) of rat oligodendroglial progenitor cell line OLN-93 after pro-inflammatory stimulation, and searched for influences of MP and GA on these parameters. OLN-93 cells were treated either with a combination of TNF-α and IFN-γ alone, or additionally with MP or GA. Cell viability and cell protein contents were determined in parallel. Results: Our results show that TNF-α and IFN-γ increased iNOS mRNA and protein expression and the NO production in OLN-93 cells. The elevated production of NO and iNOS protein was reduced in the presence of MP, whereas under treatment with GA, the cytokine-induced overproduction of NO did not change significantly. Conclusions: The presented data suggest an active role of oligodendroglial cells in inflammatory processes like multiple sclerosis and indicate different properties of MP and GA regarding immunosuppression.
Inflammatory Biomarkers in Patients with Posttraumatic Stress Disorder Caused by Myocardial Infarction and the Role of Depressive Symptoms
Authors: von Känel Roland , Begré Stefan , Abbas Chiara C. , Saner Hugo , Gander Marie-Louise , Schmid Jean-Paul
Published: October 2009

Objective: Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship. Methods: We investigated 15 patients with interviewer-rated PTSD caused by myocardial infarction (MI) and 29 post-MI patients with no PTSD. All patients completed the depression subscale of the Hospital Anxiety and Depression Scale and had blood collected to determine inflammatory markers of increased cardiovascular risk. Results: Controlling for demographic and medical covariates, patients with PTSD had higher leptin levels than patients with no PTSD (p = 0.038, explained variance 10.4%); this difference became nonsignificant when controlling for depressive symptoms. After controlling for depressive symptoms, PTSD patients had higher interleukin-6 (p = 0.041; explained variance 10%), lower C-reactive protein (p = 0.022, explained variance 12.1%), and lower soluble CD40 ligand (p = 0.016, explained variance 13.4%) than patients without PTSD. After controlling for PTSD status, depressive symptoms correlated with soluble CD40 ligand (r = 0.45, p = 0.002) and with C-reactive protein (r = 0.29, p < 0.07). Conclusions: The findings provide further evidence for altered inflammation in PTSD. Comorbid depressive symptoms ought to be considered to disentangle the unique associations of PTSD caused by MI and systemic inflammation.
Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood
Authors: Bernardi Maria M. , Kirsten Thiago B. , Matsuoka Suzana M. , Teodorov Elizabeth , Habr Soraya F. , Penteado Sandra H.W.N. , Palermo-Neto João
Published: October 2009

Objective: This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. Methods: For two experiments, pregnant rats were injected with LPS (250 μg/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6) and the dam’s open-field general activity (PND7) were evaluated. In the second experiment, the maternal pre- and postnatal parameters, the pup’s development, the offspring’s sexual behavior in adulthood, and the pup’s organ weights were assessed. Results: Compared to the control group, the LPS-treated dams presented reduced maternal behavior, decreased general activity, a smaller body weight difference between GD21 and PND1, a greater number of perinatal deaths, and smaller litters. For the male pups, LPS treatment resulted in a decreased body weight on PND2, whereas the anogenital distance and the day of testis descent were not modified. The male sexual behavior was impaired by prenatal LPS. Particularly the number of ejaculating animals was reduced. The testis weight was also lower in the prenatally LPS-treated rats than in the control rats. Conclusion: We propose that prenatal LPS exposure on GD21 acts as an imprinting factor that interferes with the programming of brain sexual determination in offspring.
Mutagenicity of Immunosuppressive Medications among Renal Transplant Recipients
Authors: Rath Thomas , Oliveira-Frick Vilma
Published: October 2009

Background: Immunosuppressive therapy is essential for patients after renal transplantation, but it may have mutagenic side effects. The frequency of micronuclei (MN) assessed by the cytokinesis block assay is well established in the diagnosis of DNA damage. Methods: We examined 79 patients before and after renal transplantation with the cytokinesis block assay. For MN evaluation, the criteria of the Human Micron Nucleus (HUMN) project were used. Results: Age and sex had no influence on the number of MN before transplantation. Patients with a shorter time on dialysis had fewer MN than patients with a longer time on dialysis. After 3 weeks of immunosuppressive therapy, the ability of cells to proliferate was reduced; therefore, only 36 patients could be analyzed. In these patients, MN frequency rose significantly. There was no linear relationship between MN after transplantation and age, sex, time on dialysis or graft function. The majority of patients (79%) were treated with cyclosporine A, mycophenolate mofetil and methylprednisolone when leaving the hospital. There was no difference between the different therapeutic schemes with regard to MN frequency after transplantation, but patients with mycophenolate mofetil showed less cellular proliferation. The function of the transplanted organ or the occurrence of rejection had no effect on MN frequency after transplantation. Conclusion: In patients with renal transplantation, immunosuppressive therapy intensifies the genotoxic damage of the preceding chronic renal failure.
Risperidone Treatment Increases CB1 Receptor Binding in Rat Brain
Authors: Secher Anna , Husum Henriette , Holst Birgitte , Egerod Kristoffer Lihme , Mellerup Erling
Published: October 2009

Background/Aims: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB1), the serotonin receptor 2C, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. Methods: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20% hydroxypropyl β-cyclodextrin) for 28 days. Expression of the aforementioned factors were examined together with plasma prolactin and ghrelin levels. Results: No difference in body weight gained during treatment was observed between risperidone and vehicle treated rats, but plasma risperidone levels positively correlated with visceral fat mass. Risperidone treatment increased CB1 receptor binding in the arcuate nucleus (40%), hippocampus (25–30%) and amygdala (35%) without concurrent alterations in the CB1 receptor mRNA. Risperidone treatment increased adiponectin mRNA. Conclusion: The present study showed that risperidone treatment altered CB1 receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB1 receptor density in brain regions involved in appetite and regulation of metabolic function.
Targeted SERCA2a Gene Expression Identifies Molecular Mechanism and Therapeutic Target for Arrhythmogenic Cardiac Alternans
Authors: Cutler Michael J. , Wan Xiaoping , Laurita Kenneth R. , Hajjar Roger J. , Rosenbaum David S.
Published: October 2009

Background—

Beat-to-beat alternans of cellular repolarization is closely linked to ventricular arrhythmias in humans. We hypothesized that sarcoplasmic reticulum calcium reuptake by SERCA2a plays a central role in the mechanism of cellular alternans and that increasing SERCA2a gene expression will retard the development of cellular alternans.

Methods and Results—

In vivo gene transfer of a recombinant adenoviral vector with the transgene for SERCA2a (Ad.SERCA2a) was performed in young guinea pigs. Isolated myocytes transduced with Ad.SERCA2a exhibited improved sarcoplasmic reticulum Ca
2+
reuptake (
P
<0.05) and were markedly resistant to cytosolic calcium alternans (
P
<0.05) under repetitive constant action potential clamp conditions (ie, when alternation of action potential duration was prevented), proving that sarcoplasmic reticulum Ca
2+
cycling is an important mechanism in the development of cellular alternans. Similarly, SERCA2a overexpression in the intact heart demonstrated significant resistance to alternation of action potential duration when compared with control hearts (heart rate threshold, 484�25 bpm versus 396�11 bpm,
P
<0.01), with no change in action potential duration restitution slope. Importantly, SERCA2a overexpression produced a 4-fold reduction in susceptibility to alternans-mediated ventricular arrhythmias (
P
<0.05).

Conclusions—

These data provide new evidence that sarcoplasmic reticulum Ca
2+
reuptake directly modulates susceptibility to cellular alternans. Moreover, SERCA2a overexpression suppresses cellular alternans, interrupting an important pathway to cardiac fibrillation in the intact heart.
Cardiac T2* Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Major
Authors: Kirk P. , Roughton M. , Porter J.B. , Walker J.M. , Tanner M.A. , Patel J. , Wu D. , Taylor J. , Westwood M.A. , Anderson L.J. , Pennell D.J.
Published: October 2009

Background—

The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major.

Methods and Results—

We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589;
P
<0.001) or serum ferritin (0.629;
P
<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514;
P
<0.001) or serum ferritin (0.518;
P
<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia.

Conclusions—

Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.
When Is Happiness About How Much You Earn? The Effect of Hourly Payment on the Money—Happiness Connection
Authors: DeVoe Sanford E. , Pfeffer Jeffrey
Published: October 2009

The authors argue that the strength of the relationship between income and happiness can be influenced by exposure to organizational practices, such as being paid by the hour, that promote an economic evaluation of time use. Using cross-sectional data from the United States, two studies found that income was more strongly associated with happiness for individuals paid by the hour compared to their non-hourly counterparts. Using panel data from the United Kingdom, Study 3 replicated these results for a multi-item General Health Questionnaire measure of subjective well-being. Study 4 showed that experimentally manipulating the salience of someone’s hourly wage rate caused non-hourly paid participants to evince a stronger connection between income and happiness, similar to those participants paid by the hour. Although there were highly consistent results across multiple studies employing multiple methods, overall the effect size was not large.
The Effects of Exclusion and Reintegration on the Evaluation of Deviant Opinion Holders
Authors: Chan Marc K. H. , Louis Winnifred R. , Hornsey Matthew J.
Published: October 2009

It seems likely that treatment of deviants within a group will be determined not just by the nature of their deviance but also by the history of their treatment. In two experiments, participants read cases in which group members advocated for change in a way that was non-normative for the group and were marginalized as a result. Participants were further informed that either the deviant was psychologically reintegrated or remained marginalized. Results showed that when deviants were reintegrated group members were more negative toward the deviant the more they identified with the group. Where the deviant remained excluded, this effect either disappeared or reversed. These effects were mediated by participants’ perceptions of the destructiveness of the deviant’s message, suggesting that ongoing exclusion can defuse threat. Reintegration into the group can have ironic costs in a person’s ability to communicate a deviant opinion successfully.