bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolvins and protectins: mediating solutions to inflammation
Authors: Kohli Payal , Levy Bruce D 
Published: July 2009

Resolution of inflammation has historically been viewed as a passive process, occurring as a result of the withdrawal of pro‐inflammatory signals, including lipid mediators such as leukotrienes and prostaglandins. Thus, most anti‐inflammatory drugs have traditionally targeted primarily mediator pathways that are engaged at the onset of inflammation. Only recently has it been established that inflammation resolution is an active process with a distinct set of chemical mediators. Several clinical and epidemiological studies have identified beneficial effects of polyunsaturated fatty acids (PUFAs) for a variety of inflammatory diseases, yet without mechanistic explanations for these beneficial effects. Resolvins and protectins are recently identified molecules that are generated from ω‐3 PUFA precursors and can orchestrate the timely resolution of inflammation in model systems. Dysregulation of pro‐resolving mediators is associated with diseases of prolonged inflammation, so designing pharmacological mimetics of naturally occurring pro‐resolving mediators offers exciting new targets for drug design. This review describes the discovery and synthesis of these novel lipid mediators, their receptors and mechanisms of action, and summarizes the studies to date that have uncovered roles for resolvins and protectins in disease states.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Molecular mechanisms for the persistent bronchodilatory effect of the β2‐adrenoceptor agonist salmeterol
Authors: Szczuka A , Wennerberg M , Packeu A , Vauquelin G 
Published: July 2009

Background: β2‐adrenoceptor agonists are effective bronchodilators.In vitrostudies demonstrated long‐lasting airway smooth muscle relaxation by salmeterol after washout, the quick disappearance of this effect in presence of antagonists and its recovery after antagonist removal. Current explanations invoke salmeterol accumulation in the membrane (‘diffusion microkinetic’ model) or the existence of salmeterol‐binding ‘exosites’. An alternative model based on ‘rebinding’ of a dissociated ligand to the receptor molecules also produces an apparent decrease in the ligand's dissociation rate in the absence of competing ligands.Purpose and approach: Computer‐assisted simulations were performed to follow the receptor‐occupation by a salmeterol‐like ligand and a competing ligand as a function of time. The aptness of the models to describe the abovein vitrofindings was evaluated.Key results: The ‘diffusion microkinetic’ model is sufficient to explain a long‐lasting β2‐adrenoceptor stimulation and reassertion as long as the membrane harbors a high concentration of the agonist. At lower concentration, ‘rebinding’ and, in second place, ‘exosite’ binding are likely to become operational.Conclusions and implications: The ‘rebinding’ and ‘exosite’ binding mechanisms take place at a sub‐cellular/molecular scale. Pending their demonstration by experiments on appropriate, simple models such as intact cells or membranes thereof, these mechanisms remain hypothetical in the case of salmeterol. Airway smooth muscle contraction could also be governed by additional mechanisms that are particular to this macroscopic approach.
Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon‐γ in HaCaT cells, a human keratinocyte cell line
Authors: Qi Xu‐Feng , Kim Dong‐Heui , Yoon Yang‐Suk , Li Jian‐Hong , Jin Dan , Teng Yung‐Chien , Kim Soo‐Ki , Lee Kyu‐Jae 
Published: July 2009

Background and purpose:  The macrophage‐derived chemokine (MDC/CCL22) is a prototypic Th2‐type chemokine intimately involved in Th2‐skewed allergic diseases, such as atopic dermatitis and asthma. The statins (3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase inhibitors) have been demonstrated to relieve allergic inflammation. However, the immunological effects and mechanisms of statins against atopic dermatitis remain unknown, at least in vitro. This study aimed to define how different statins affect MDC expression in HaCaT cells, a human keratinocyte cell line.Experimental approach:  To measure the effects of statins on MDC expression in HaCaT cells, we used a cell viability assay, reverse transcription‐polymerase chain reaction, enzyme‐linked immunosorbent assay and Western blotting analyses.Key results:  Fluvastatin, but not atorvastatin or simvastatin, inhibited MDC expression induced by interferon (IFN)‐γ and NF‐κB activation. A NF‐κB inhibitor, but not a STAT1 inhibitor, suppressed MDC expression in HaCaT cells. Further, inhibition of p38 mitogen‐activated protein kinases (MAPKs) significantly suppressed IFN‐γ‐induced MDC expression and NF‐κB activation. Interestingly, fluvastatin suppressed IFN‐γ‐induced NF‐κB activation in parallel with p38 MAPK phosphorylation.Conclusions and implications:  These results indicate that fluvastatin inhibited expression of the CC chemokine MDC induced by IFN‐γ in HaCaT cells, by inhibiting NF‐κB activation via the p38 MAPK pathway. This blockade of a Th2 chemokine by fluvastatin may suppress the infiltration of Th2 cells into skin lesions and lessen the skin inflammation seen in atopic dermatitis, suggesting a potential therapeutic use of fluvastatin for this condition.
Protective effects of mildronate in an experimental model of type 2 diabetes in Goto‐Kakizaki rats
Authors: Liepinsh Edgars , Vilskersts Reinis , Zvejniece Liga , Svalbe Baiba , Skapare Elina , Kuka Janis , Cirule Helena , Grinberga Solveiga , Kalvinsh Ivars , Dambrova Maija 
Published: July 2009

Background and purpose:  Mildronate [3‐(2,2,2‐trimethylhydrazinium) propionate] is an anti‐ischaemic drug whose mechanism of action is based on its inhibition of L‐carnitine biosynthesis and uptake. As L‐carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long‐term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto‐Kakizaki (GK) rats.Experimental approach:  GK rats were treated orally with mildronate at doses of 100 and 200 mg·kg−1 daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and β‐hydroxybutyrate, were assessed. L‐carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia‐reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail‐flick latency test.Key results:  Mildronate treatment significantly decreased L‐carnitine concentrations in rat plasma and gradually decreased both the fed‐ and fasted‐state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate‐treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%.Conclusions and implications:  These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L‐carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems.
Intracellular sequestration of amiodarone: role of vacuolar ATPase and macroautophagic transition of the resulting vacuolar cytopathology
Authors: Morissette G , Ammoury A , Rusu D , Marguery MC , Lodge R , Poubelle PE , Marceau F 
Published: July 2009

Background and purpose:  Tissue deposits of the anti‐arrhythmic drug amiodarone are a major source of side effects (skin discoloration, etc.). We addressed the mechanism of the concentration of amiodarone in cells, and characterized the resulting vacuolar cytopathology and its evolution towards macroautophagy.Experimental approach:  Sequestration of amiodarone in human cells (macrophages, smooth muscle cells, HEK 293a cells) was evaluated using its violet fluorescence and cytopathology using GFP‐conjugated subcellular markers. Autophagic signalling was probed by immunoblotting for the effector protein LC3. A patient biopsy of amiodarone‐induced blue‐gray skin discoloration was investigated for the presence of macroautophagy (immunofluorescence for LC3).Key results:  Most of the amiodarone (1–20 µM, 4–24 h) captured by cultured cells (macrophages were most avid) was present in enlarged vacuoles. The specific vacuolar ATPase (V‐ATPase) inhibitors, bafilomycin A1 or FR167356, prevented vacuolization and drug uptake. Vacuoles in HEK 293a cells were positive for markers of late endosomes and lysosomes (GFP‐Rab7, ‐CD63) and for an effector of macroautophagy, GFP‐LC3. The vacuoles accumulated endogenous LC3 and filled with lipids (Nile red staining) following longer amiodarone treatments (≥24 h). The electrophoretic mobility of both GFP‐LC3 and endogenous LC3 changed, showing activation in response to amiodarone. Paraffin tissue sections of the pigmented skin exhibited granular LC3 accumulation in superficial dermis macrophages.Conclusion and implications:  Vacuolar sequestration of amiodarone occurs at concentrations close to therapeutic levels, is mediated by V‐ATPase and evolves towards persistent macroautophagy and phospholipidosis. This cytopathology is not cell type specific, but tissue macrophages appear to be particularly susceptible.
Prevalence of cryoglobulinaemia in hepatitis C virus‐ and hepatitis C virus/human immunodeficiency virus‐infected individuals: implications for renal function
Authors: Lapinski Tadeusz Wojciech , Parfieniuk Anna , Rogalska‐Plonska Magdalena , Czajkowska Jolanta , Flisiak Robert 
Published: July 2009

AbstractBackground and aims: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV‐monoinfected and HCV/HIV‐coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated.Patients and methods: Seventy‐seven patients were enrolled in this study. Forty‐four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins were detected in the sera by electrophoresis and immunofixation. Serum urea and creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C concentration (CC) were analysed to evaluate renal function. The control group included 16 healthy individuals.Results: The occurrence of cryoglobulinaemia in HCV‐monoinfected patients was 55%, whereas in HCV/HIV‐coinfected patients it was 64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in 25%. The prevalence of cryoglobulinaemia was significantly higher in infection with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P<0.01). The most frequently occurring heavy chains were γ‐type (96%). Light chains, the κ‐type, were detected in all patients. The CC concentration was significantly higher in HCV/HIV‐coinfected patients compared with controls (718 vs. 392 ng/ml; P<0.005) or HCV‐monoinfected patients (508 ng/ml; P<0.007). There was correlation between the serum CC concentration and the incidence of cryoglobulinaemia (R=0.44; P<0.00015), which was particularly evident in HCV monoinfection (R=0.43; P<0.0034).Conclusions: Genotype‐1 infection is an important risk factor for cryoglobulinaemia. Standard renal function tests are not sufficient for the prediction of renal failure in HCV‐infected patients. Serum CC concentration allows to establish an early diagnosis of renal insufficiency related to cryoglobulinaemia.
Gadolinium‐Induced Nephrogenic Systemic Fibrosis Is Associated with Insoluble Gd Deposits in Tissues: In Vivo Transmetallation Confirmed by Microanalysis
Authors: Thakral Charu , Abraham Jerrold L. 
Published: July 2009

Background: Nephrogenic systemic fibrosis (NSF) is an extremely debilitating systemic fibrosing disorder affecting renal failure patients. The association of NSF with gadolinium (Gd) containing magnetic resonance contrast agents was noted in 2006. Gd deposition in skin biopsies was demonstrated shortly thereafter.Methods: We used automated scanning electron microscopy (SEM)/energy dispersive x‐ray spectroscopy for in situ quantitative analysis of insoluble Gd‐containing deposits, recording multi‐elemental composition and spatial distribution of detected features.Results: Gd was detected in all 29 patients (53 of 57 skin biopsies) with NSF, biopsied from 2 weeks to 3 years after Gd exposure. Gd concentration ranged from 1 to 2270 cps/mm2 and was detected predominantly in the deep dermis and subcutaneous fibrous septa. Gd was found associated with Ca, P and sometimes Fe or Zn. Patients with sequential biopsies showed persistence or increase of Gd in tissues (6 of 11). Transmission electron microscopy (TEM) identified the intracellular deposits in fibrocytes and macrophages.Conclusions: The demonstration of insoluble tissue deposits of Gd with co‐associated elements clearly confirms in vivo transmetallation and dissociation of soluble Gd‐chelates. Toxic Gd3+ may trigger fibrosis under permissive conditions, e.g., in renal insufficiency. Pathologists and clinicians need to be aware of this serious but preventable disease.
Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis
Authors: Terada Tadashi 
Published: July 2009

The author reports a very rare case of cutaneous metastasis of sarcomatoid carcinoma of the lung. The skin metastasis was an initial presentation. A 67‐year‐old man consulted our hospital because of left chest skin mass. An excisional biopsy was performed, and it showed proliferation of malignant sarcomatoid spindle and polygonal cells in the deep dermis and subcutis remote from the epidermis and appendages. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 7, CK 18, vimentin, p53, Ki‐67 (95%) and PDGFRA. They were negative for high molecular weight CK, CK 5/6, CK 14, CK 19, CK 20, epithelial membrane antigen, TTF‐1, CEA, desmin, S100 protein, α‐smooth muscle actin, p63, CD34, surfactant apoprotein A, chromogranin, synaptophysin, neuron‐specific enolase, CD68, CD56, D2‐40, calretinin and KIT. A pathological diagnosis of metastatic sarcomatoid carcinoma probably originating from the lung was made. Then, the patient was admitted to our hospital, and imaging modalities including compured tomography (CT) and magnetic resonance imaging (MRI) revealed a tumor in the left lung. No other tumors were detected in the imaging techniques. Lung biopsy was planned, but the patient suddenly died; the cause of death was unclear. Autopsy was not performed. The present report suggests that sarcomatoid carcinoma of the lung should be considered in cutaneous metastatic lesions.Terada T. Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis.
Translations of the Bible into Karaim
Authors: Jankowski Henryk 
Published: July 2009

AbstractThe aim of this paper is to present the state of research on Bible translations into Karaite Turkic, which in Turkic studies is called Karaim. The term Bible is employed in its narrower meaning, which designates the Hebrew Bible or Old Testament. This article tries to show how the translators approached the original text and gives a few samples to demonstrate differences between several selected translations.
Molecular modification of triacylglycerol accumulation by over-expression ofDGAT1to produce canola with increased seed oil content under field conditionsThis paper is one of a selection of papers published in a Special Issue from the National Research Council of Canada – Plant Biotechnology Institute.
Authors: Taylor David C. , Zhang Yan , Kumar Arvind , Francis Tammy , Giblin E. Michael , Barton Dennis L. , Ferrie James R. , Laroche André , Shah Saleh , Zhu Weiming , Snyder Crystal L. , Hall Linda , Rakow Gerhard , Harwood John L. , Weselake Randall J. 
Published: July 2009

The final step in the Kennedy pathway for seed oil synthesis is catalyzed by an acyl-CoA-dependent diacylglycerol acyltransferase, DGAT1 (EC. 2.3.1.20). We have cloned DGAT1 genes from both Arabidopsis thaliana (L.) Heynh ecotype Columbia and Brassica napus ‘Jet Neuf’ and over-expressed them in canola under the control of the seed-specific promoter, napin. DGAT1 from A. thaliana was inserted into B. napus ‘Quantum,’ whereas DGAT1 from B. napus was introduced into the B. napus double haploid breeding line DH12075. Both sets of transgenic plants exhibited increased seed oil content in both greenhouse and in field trial settings, ranging from 2.5% to 7% of dried mass on an absolute basis. The ‘Quantum’ transgenic lines were field-tested in plots at Watrous, Saskatchewan, in 2006 and 2007. Larger scale field trials of the DH12075 transgenics were carried out in 2007 at Ellerslie and Vegreville, Alberta. This is the first study wholly dedicated to DGAT1 over-expression and the resultant oil-content increases in transgenic canola under field conditions. Collectively, the field trial results strongly support the hypothesis that the level of DGAT1 activity during seed development in an oilseed crop can have a substantial effect on the flow of carbon into seed oil. Therefore, the over-expression of DGAT1 is a positive strategy for increasing oil content and cultivar performance in canola.
The role of diacylglycerol acyltransferase-1 and phospholipid:diacylglycerol acyltransferase-1 and -2 in the incorporation of hydroxy fatty acids into triacylglycerol in Arabidopsis thaliana expressing a castor bean oleate 12-hydroxylase geneThis paper is one of a selection of papers published in a Special Issue from the National Research Council of Canada – Plant Biotechnology Institute.
Authors: Dauk Melanie , Lam Patricia , Smith Mark A. 
Published: July 2009

Expression of oleate 12-hydroxylase genes in Arabidopsis results in the accumulation of hydroxy fatty acids in seed triacylglycerol (TAG). The pathways by which these unusual fatty acids become incorporated into TAG are not well understood. We expressed a fatty acid hydroxylase cDNA in Arabidopsis mutant lines to assess the role of three enzymes implicated in TAG assembly in this species. Plants deficient in the expression of phospholipid:diacylglycerol acyltransferase-1 or -2 accumulated hydroxy fatty acids and showed no differences to equivalent transformed wild-type plants. Plants lacking diacylglylcerol acyltransferase activity were also able to accumulate hydroxy fatty acids in seed neutral lipids. Triacylglycerol species containing one and two hydroxy fatty acids were abundant, and small amounts of trihydroxy-TAG were detected. These results indicate that individually, the three enzymes do not play a major role in the incorporation of hydroxy fatty acids into TAG.
Metabolic and hormonal processes associated with the induction of secondary dormancy inBrassica napusseedsThis paper is one of a selection of papers published in a Special Issue from the National Research Council of Canada – Plant Biotechnology Institute.
Authors: Fei Houman , Ferhatoglu Yurdagul , Tsang Edward , Huang Daiqing , Cutler Adrian J. 
Published: July 2009

Polyethylene glycol treatment induces secondary seed dormancy in Brassica napus L. cultivar ‘AC Excel’ (ACE), but not in ‘DH12075’ (DH). Gene expression, metabolite profiles, and hormone profiles were obtained from seeds of both cultivars following polyethylene glycol 8000 treatment. ACE seeds were more transcriptionally active: 28 genes were up-regulated in both cultivars and 10 and 158 genes were specifically up-regulated in DH and ACE, respectively. Nontargeted metabolite analyses combined with gene expression analyses showed significant differences in lipid, sugar, and phenylpropanoid metabolism between the cultivars. Abscisic acid (ABA) levels were higher and many ABA-inducible genes were expressed more in ACE. An association of ABA with secondary dormancy was supported by the observation that secondary dormancy was induced by polyethylene glycol 8000 in Arabidopsis wild-type seeds, but was reduced in ABA-deficient and ABA-insensitive mutants. Therefore, secondary dormancy appears to be realized through an active ABA-related mechanism that may involve changes in primary and secondary metabolism.
A Hirnantian (latest Ordovician) reefal bryozoan fauna from Anticosti Island, eastern Canada: taxonomy and chemostratigraphy
Authors: Ernst Andrej , Munnecke Axel 
Published: July 2009

The Natiscotec outcrop on Anticosti Island, Canada (Ellis Bay Formation, Laframboise Member, Hirnantian, Late Ordovician), exposes a patch reef some 20–30 m in diameter, 2–3 m thick, with abundant rugose corals, as well as favositids and heliolitids. Reef capping and flanking sediments include typical Hirnantian brachiopods, such as Hirnantia , Hindella , and Eospirigerina . Within the reef peloidal microbialites encrusting bryozoan colonies are common. The bryozoan fauna includes three cystoporates, seven trepostomes, and three phylloporines. Two genera and two species are new: the cystoporate Natiscotecella tenuis n. gen. and n. sp. and the phylloporine Dilaminocladia natiscotecensis n. gen. and n. sp. Three more species are also new: the cystoporates Ceramopora clara n. sp. and Acanthoceramoporella spinigera n. sp. and the trepostome Revalotrypa honguedensis n. sp. Furthermore, we identify the three trepostomes Atactoporella aff. ortoni (Nicholson, 1874), Hallopora elegantula (Hall, 1852), and Monotrypella cf. aequalis Ulrich, 1882, and a phylloporine Parachasmatopora porkunensis Lavrentjeva, 1985. Four species are identified at generic level and in open nomenclature: the three trepostomes Lioclemella sp., Calloporella sp., and Trepostomata sp. and a phylloporine ? Ralfinella sp. The bryozoan fauna shows some affinities with the Late Ordovician fauna of Scandinavia. Stable carbon isotope investigations from brachiopod shells of the same outcrop yield values for δ13C of up to +6.7‰, which represent the highest values reported from the Anticosti succession so far. This indicates that the stratigraphic position of the outcrop is at or close to the peak of the globally recognized Hirnantian δ13C excursion.