bluuebunny/crossref_metadata_2025 huggingface dataset:
Within-Species Flagellin Polymorphism inXanthomonas campestrispvcampestrisand Its Impact on Elicitation ofArabidopsis FLAGELLIN SENSING2–Dependent Defenses
Authors: Sun Wenxian , Dunning F. Mark , Pfund Christine , Weingarten Rebecca , Bent Andrew F.
Published: February 2006

Bacterial flagellins have been portrayed as a relatively invariant pathogen-associated molecular pattern. We have found within-species, within-pathovar variation for defense-eliciting activity of flagellins among Xanthomonas campestris pv campestris (Xcc) strains. Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a transmembrane leucine-rich repeat kinase, confers flagellin responsiveness. The flg22 region was the only Xcc flagellin region responsible for detectable elicitation of Arabidopsis defense responses. A Val-43/Asp polymorphism determined the eliciting/noneliciting nature of Xcc flagellins (structural gene fliC). Arabidopsis detected flagellins carrying Asp-43 or Asn-43 but not Val-43 or Ala-43, and it responded minimally for Glu-43. Wild-type Xcc strains carrying nonrecognized flagellin were more virulent than those carrying a recognized flagellin when infiltrated into Arabidopsis leaf mesophyll, but this correlation was misleading. Isogenic Xcc fliC gene replacement strains expressing eliciting or noneliciting flagellins grew similarly, both in leaf mesophyll and in hydathode/vascular colonization assays. The plant FLS2 genotype also had no detectable effect on disease outcome when previously untreated plants were infected by Xcc. However, resistance against Xcc was enhanced if FLS2-dependent responses were elicited 1 d before Xcc infection. Prior immunization was not required for FLS2-dependent restriction of Pseudomonas syringae pv tomato. We conclude that plant immune systems do not uniformly detect all flagellins of a particular pathogen species and that Xcc can evade Arabidopsis FLS2-mediated defenses unless the FLS2 system has been activated by previous infections.
BlindHomologousR2R3 MybGenes Control the Pattern of Lateral Meristem Initiation inArabidopsis
Authors: Müller Dörte , Schmitz Gregor , Theres Klaus
Published: February 2006

In seed plants, shoot branching is initiated during postembryonic development by the formation of secondary meristems. These new meristems, which are established between the stem and leaf primordia, develop into vegetative branches or flowers. Thus, the number of axillary meristems has a major impact on plant architecture and reproductive success. This study describes the genetic control of axillary meristem formation in Arabidopsis thaliana by a group of three R2R3 Myb genes, which are homologous to the tomato (Solanum lycopersicum) Blind gene and were designated REGULATORS OF AXILLARY MERISTEMS (RAX). rax mutants show new phenotypes that are characterized by defects in lateral bud formation in overlapping zones along the shoot axis. RAX genes are partially redundant in function and allow a fine-tuning of secondary axis formation. As revealed by monitoring of SHOOT MERISTEMLESS transcript accumulation, the RAX genes control a very early step of axillary meristem initiation. The RAX1 and RAX3 expression domains specifically mark a cell group in the center of the leaf axil from which the axillary meristem develops. Double mutant combinations of lateral suppressor and rax1-3 as well as expression studies suggest that at least two pathways control the initiation of axillary meristems in Arabidopsis.
Analysis of the Transcription Factor WUSCHEL and Its Functional Homologue inAntirrhinumReveals a Potential Mechanism for Their Roles in Meristem Maintenance
Authors: Kieffer Martin , Stern Yaniv , Cook Holly , Clerici Elena , Maulbetsch Christoph , Laux Thomas , Davies Brendan
Published: February 2006

One of the most significant features of plant development is the way in which it can be elaborated and modulated throughout the life of the plant, an ability that is conferred by meristems. The Arabidopsis thaliana  WUSCHEL gene (WUS), which encodes a homeodomain transcription factor, is required to maintain the stem cells in the shoot apical meristem in an undifferentiated state. The mechanism by which WUS prevents the differentiation of stem cells is unknown. We have characterized a meristem maintenance mutant in Antirrhinum majus and shown that it arises from a defect in the WUS orthologue ROSULATA (ROA). Detailed characterization of a semidominant roa allele revealed an essential role for the conserved C-terminal domain. Expression of either ROA or WUS lacking this domain causes a failure of meristem maintenance. The conserved domain mediates an interaction between WUS and two members of a small family of corepressor-like proteins in Arabidopsis. Our results suggest that WUS functions by recruiting transcriptional corepressors to repress target genes that promote differentiation, thereby ensuring stem cell maintenance.
Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis?: Table 1
Authors: Sinclair D , Spedding A , Young R
Published: February 2006

Background:Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by the presence of various laboratory abnormalities but the precise role of laboratory staff in initiating clinical referral and subsequent biopsy is not clear.

Objective:To examine the impact of laboratory abnormalities in the investigation of PBC.

Methods:In a retrospective study of laboratory results over nine years from 1996, computer records were reviewed to identify how many referrals for biopsy were initiated and subsequent diagnoses made as a result of clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM concentration, or positive mitochondrial antibodies accompanied by a clinical comment from the laboratory suggesting further action.

Results:22 diagnoses of PBC were confirmed by histopathology. Eleven had high ALP activity which had follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or both) and a comment added suggesting further investigation into the possibility of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM concentration which prompted the relevant follow on testing and comments. One had an earlier diagnosis made on serological/clinical grounds and the biopsy was a confirmatory measure. One had no liver related antibodies. One had a request by laboratory staff for follow on tests but these were not asked for in subsequent samples by the requesting clinician.

Conclusions:There is a positive role for laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity, positive mitochondrial antibodies, or raised IgM concentrations should be investigated more fully by laboratory staff and advice given to prompt a clinical referral for review and biopsy.
Serum HER-2 concentration in patients with primary breast cancer
Authors: Kong S-Y , Kang J H , Kwon Y , Kang H-S , Chung K-W , Kang S H , Lee D H , Ro J , Lee E S
Published: February 2006

Objective:To evaluate whether serum HER-2/neu (HER-2) concentration is a valid index of HER-2 status in women with primary breast cancer, and to establish a normal reference range for serum HER-2 concentration in Korean women.

Methods:Serum HER-2 concentration was measured and immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) carried out on tissue samples from 86 consecutive female patients. The results of the three datasets were compared. The cut off value of HER-2 concentration was determined from the mean +2SD values derived from the serum of 93 healthy volunteers.

Results:The IHC and FISH data were significantly correlated (p<0.01), but neither showed significant correlation with the serum HER-2 data. The cut off value of serum HER-2 was 10.2 μg/l, and the serum HER-2 concentration of patients with primary breast cancer ranged from 5.0 to 17.5 μg/l. Only five patients had a serum HER-2 value above the cut off value.

Conclusions:Serum HER-2 concentration cannot be substituted for IHC or FISH to evaluate HER-2 status, nor can it be used as a diagnostic tumour marker in primary breast cancer, considering the low prevalence of serum HER-2 elevation.
Ca2+source-dependent transcription of CRE-containing genes in vascular smooth muscle
Authors: Pulver-Kaste Renee A. , Barlow Christy A. , Bond Jeffery , Watson Anjanette , Penar Paul L. , Tranmer Bruce , Lounsbury Karen M.
Published: February 2006

Altered Ca2+handling has immediate physiological and long-term genomic effects on vascular smooth muscle function. Previously we showed that Ca2+entry through voltage-dependent Ca2+channels (VDCCs) or store-operated Ca2+channels (SOCCs) results in phosphorylation of the Ca2+/cAMP response element (CRE)-binding protein in cerebral arteries. Here, oligonucleotide array analysis was used to determine gene transcription profiles resulting from these two Ca2+entry pathways in human cerebrovascular smooth muscle cell cultures. Results were confirmed and expanded using quantitative RT-PCR, Western blot, and immunofluorescence. A distinct, yet overlapping, set of CRE-regulated genes was induced by VDCC activation using K+membrane depolarization vs. SOCC activation by thapsigargin (TG). Membrane depolarization selectively induced a sustained increase in early growth response-1 (Egr-1) mRNA and protein, which were inhibited by the VDCC blocker nimodipine and the SOCC inhibitor 2-aminoethoxydiphenylborate (2-APB). TG selectively induced a sustained increase in MAPK phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by 2-APB, but not by nimodipine. The physiological agonist ANG II also stimulated expression of Egr-1 and MKP-1. Coadministration of 2-APB prevented expression of Egr-1 and MKP-1, whereas nimodipine blocked only Egr-1 expression. TG and ANG II induced phosphorylation of ERK, which was sensitive to 2-APB and was selectively required for CRE-binding protein phosphorylation. Our findings thus indicate that Ca2+entry through VDCCs and store-operated Ca2+entry can differentially regulate CRE-containing genes in vascular smooth muscle and also imply that agonist-induced signals involved in modulation of gene transcription can be controlled by multiple sources of Ca2+.
Endothelial dysfunction and exercise performance in lone atrial fibrillation or associated with hypertension or diabetes: different results with cardioversion
Authors: Guazzi Marco , Belletti Sebastiano , Bianco Elisabetta , Lenatti Laura , Guazzi Maurizio D.
Published: February 2006

Endothelial dysfunction and underperfusion of exercising muscle contribute to exercise intolerance, hyperventilation, and breathlessness in atrial fibrillation (AF). Cardioversion (CV) improves endothelial function and exercise performance. We examined whether CV is equally beneficial in diabetes and hypertension, diseases that cause endothelial dysfunction and are often associated with AF. Cardiopulmonary exercise and pulmonary and endothelial (brachial artery flow-mediated dilation) function were tested before and after CV in patients with AF alone ( n = 18, group 1) or AF with hypertension ( n = 19, group 2) or diabetes ( n = 19, group 3). Compared with group 1, peak exercise workload, O2consumption (V̇o2), O2pulse, aerobic efficiency (ΔV̇o2/ΔWR), and ratio of brachial diameter changes to flow changes (Δ D/ΔF) were reduced in group 2 and, to a greater extent, in group 3; exercise ventilation efficiency (V̇e/V̇co2slope) and dead space-to-tidal volume ratio (Vd/Vt) were similar among groups. CV had less effect on peak workload (+7% vs. +18%), peak V̇o2(+12% vs. +17%), O2pulse (+33% vs. +50%), ΔV̇o2/ΔWR (+7% vs. +12%), V̇e/V̇co2slope (−6% vs. −12%), Δ D/ΔF (+7% vs. +10%), and breathlessness (Borg scale) in group 2 than in group 1 and was ineffective in group 3. The antioxidant vitamin C, tested in eight additional patients in each cohort, improved flow-mediated dilation in groups 1 and 2 before, but not after, CV and was ineffective in group 3, suggesting that the oxidative injury is least in lone AF, greater in hypertension with AF, and greater still in diabetes with AF. Comorbidities that impair endothelial activity worsen endothelial dysfunction and exercise intolerance in AF. The advantages of CV appear to be inversely related to the extent of the underlying oxidative injury.
Deletion of peroxisome proliferator-activated receptor-α induces an alteration of cardiac functions
Authors: Loichot Cécile , Jesel Laurence , Tesse Angela , Tabernero Antonia , Schoonjans Kristina , Roul Gérard , Carpusca Irina , Auwerx Johan , Andriantsitohaina Ramaroson
Published: February 2006

The peroxisome proliferator-activated receptor-α (PPARα) plays a major role in the control of cardiac energy metabolism. The role of PPARα on cardiac functions was evaluated by using PPARα knockout (PPARα −/−) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARα did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPARα −/− mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARα −/− mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARα −/− mice was lower compared with wild-type (PPARα +/+) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and β-adrenergic agonist-induced developed forces were significantly reduced in PPARα-null mice. In addition, Western blot analysis shows that the protein expression of β1-adrenergic receptor is reduced in hearts from PPARα −/− mice. Histological analysis showed that hearts from PPARα −/− but not PPARα +/+ mice displayed myocardial fibrosis. These results suggest that PPARα-null mice have an alteration of cardiac contractile performance under basal and under stimulation of β1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARα in maintaining cardiac functions.
Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability
Authors: Huang Ning , Khan Asim , Ashrafpour Homa , Neligan Peter C. , Forrest Christopher R. , Kontos Christopher D. , Pang Cho Y.
Published: February 2006

Skin ischemic necrosis due to vasospasm and/or insufficient vascularity is the most common complication in the distal portion of the skin flap in reconstructive surgery. This project was designed to test our hypothesis that preoperative subdermal injection of adenoviral vectors encoding genes for vascular endothelial growth factor-165 (Ad.VEGF-165) or endothelial nitric oxide (NO) synthase (Ad.eNOS) effectively augments skin viability in skin flap surgery and that the mechanism of Ad.VEGF-165 gene therapy involves an increase in synthesis/release of the angiogenic and vasodilator factor NO. PBS (0.5 ml) or PBS containing Ad.VEGF-165, Ad.eNOS, or adenovirus (Ad.Null) was injected subdermally into the distal half of a mapped rat dorsal skin flap (4 × 10 cm) 7 days preoperatively, and skin flap viability was assessed 7 days postoperatively. Local subdermal gene therapy with 2 × 107–2 × 1010 plaque-forming units of VEGF-165 increased skin flap viability compared with PBS- or Ad.Null-injected control ( P < 0.05). Subdermal Ad.VEGF-165 and Ad.eNOS gene therapies were equally effective in increasing skin flap viability at 5 × 108 plaque-forming units. Subdermal Ad.VEGF-165 therapy was associated with upregulation of eNOS protein expression, Ca2+-dependent NOS activity, synthesis/release of NO, and increase in capillary density and blood flow in the distal portion of the skin flap. Injection of the NOS inhibitor Nω-nitro-l-arginine (15 mg/kg im), but not the cyclooxygenase inhibitor indomethacin (5 mg/kg im), 45 min preoperatively completely abolished the increase in skin flap blood flow and viability induced by Ad.VEGF-165 injected subdermally into the mapped skin flap 7 days preoperatively. We have demonstrated for the first time that 1) Ad.VEGF-165 and Ad.eNOS mapped skin flap injected subdermally into the mapped skin flap 7 days preoperatively are equally effective in augmenting viability in the rat dorsal skin flap compared with control, 2) the mechanism of subdermal Ad.VEGF-165 gene therapy in augmenting skin flap viability involves an increase in NO synthesis/release downstream of upregulation of eNOS protein expression and Ca2+-dependent NOS activity, and 3) the vasodilating effect of NO may predominantly mediate subdermal Ad.VEGF gene therapy in augmenting skin flap blood flow and viability.
Significance of changes in TNF-α and IL-10 levels in the progression of heart failure subsequent to myocardial infarction
Authors: Kaur K. , Sharma A. K. , Singal P. K.
Published: February 2006

We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) correlates with the decrease in cardiac function in heart failure. It has been suggested that TNF-α plays a role in the progression of heart failure, and the effect of TNF-α in many tissues is modulated by IL-10. Any relation of these two cytokines to heart failure has never been examined. Cardiac function was assessed by echocardiographic and hemodynamic techniques in coronary artery-ligated rats at 1, 4, 8, and 16 wk after myocardial infarction (MI). Membrane-bound and soluble fractions of TNF-α and IL-10 proteins, the ratio of TNF-α to IL-10, and TNF-α and IL-10 mRNA levels were analyzed. Losartan was used to modify cardiac function in rats 4 wk after MI to further validate the relation between the IL-10-to-TNF-α ratio and cardiac function. Cardiac function deteriorated with time in all coronary artery-ligated groups, with severe failure at 16 wk after MI. Membrane-bound and soluble TNF-α protein fractions were increased 1 and 4 wk after MI, whereas TNF -α mRNA was increased 4 and 8 wk after MI. Membrane-bound IL-10 protein and mRNA levels were decreased 4, 8, and 16 wk after MI. The decrease in the IL-10-to-TNF-α protein ratio in all coronary artery-ligated groups correlated with the depressed cardiac function. Losartan improved cardiac function, membrane-bound and soluble TNF-α and IL-10 protein levels, the ratio of IL-10 to TNF-α, and IL-10 mRNA. This study suggests that a decrease in IL-10 and IL-10-to-TNF-α ratio correlates with depressed cardiac function.
Cyclic stretch attenuates effects of hyperoxia on cell proliferation and viability in human alveolar epithelial cells
Authors: McAdams Ryan M. , Mustafa Shamimunisa B. , Shenberger Jeffrey S. , Dixon Patricia S. , Henson Barbara M. , DiGeronimo Robert J.
Published: February 2006

The treatment of severe lung disease often requires the use of high concentrations of oxygen coupled with the need for assisted ventilation, potentially exposing the pulmonary epithelium to both reactive oxygen species and nonphysiological cyclic stretch. Whereas prolonged hyperoxia is known to cause increased cell injury, cyclic stretch may result in either cell proliferation or injury depending on the pattern and degree of exposure to mechanical deformation. How hyperoxia and cyclic stretch interact to affect the pulmonary epithelium in vitro has not been previously investigated. This study was performed using human alveolar epithelial A549 cells to explore the combined effects of cyclic stretch and hyperoxia on cell proliferation and viability. Under room air conditions, cyclic stretch did not alter cell viability at any time point and increased cell number after 48 h compared with unstretched controls. After exposure to prolonged hyperoxia, cell number and [3H]thymidine incorporation markedly decreased, whereas evidence of oxidative stress and nonapoptotic cell death increased. The combination of cyclic stretch with hyperoxia significantly mitigated the negative effects of prolonged hyperoxia alone on measures of cell proliferation and viability. In addition, cyclic stretch resulted in decreased levels of oxidative stress over time in hyperoxia-exposed cells. Our results suggest that cyclic stretch, as applied in this study, can minimize the detrimental effects of hyperoxia on alveolar epithelial A549 cells.
ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space
Authors: Basit Abdul , Reutershan Joerg , Morris Margaret A. , Solga Michael , Rose C. Edward , Ley Klaus
Published: February 2006

Neutrophil recruitment into lung constitutes a major response to airborne endotoxins. In many tissues endothelial intercellular adhesion molecule-1 (ICAM-1) interacts with lymphocyte function associated antigen-1 (LFA-1) on neutrophils, and this interaction plays a critical role in neutrophil recruitment. There are conflicting reports about the role of ICAM-1 in neutrophil recruitment into lungs. We studied neutrophil recruitment into alveolar space in a murine model of aerosolized LPS-induced lung inflammation. LPS induces at least a 100-fold increase in neutrophil numbers in alveolar space, as determined by flow cytometry of bronchoalveolar lavage fluid. Neutrophil recruitment was reduced by 54% in ICAM-1 null mice and by 45% in LFA-1 null mice. In wild-type mice treated with anti-ICAM-1 and anti-LFA-1 antibodies, there was 51 and 58% reduction in the neutrophil recruitment, respectively. In chimeric mice, generated by the transplantation of mixtures of bone marrows from LFA-1 null and wild-type mice, the normalized recruitment of LFA-1 null neutrophils was reduced by 60% compared with wild-type neutrophils. Neither the treatment of ICAM-1 null mice with a function-blocking antibody to LFA-1 nor the treatment of LFA-1 null mice with anti-ICAM-1 antibody resulted in further reduction in the recruitment compared with untreated ICAM-1 null and LFA-1 null mice. We conclude that ICAM-1 and LFA-1 play critical roles in the recruitment of neutrophils into the alveolar space in aerosolized LPS-induced lung inflammation, and LFA-1 serves as a ligand of ICAM-1 in the lung.
Ablation of the complement C3a anaphylatoxin receptor causes enhanced killing ofPseudomonas aeruginosain a mouse model of pneumonia
Authors: Mueller-Ortiz Stacey L. , Hollmann Travis J. , Haviland David L. , Wetsel Rick A.
Published: February 2006

The C3a anaphylatoxin is a 77-amino acid peptide that is generated by enzymatic cleavage of C3 during activation of the complement system. C3a mediates numerous biological functions on binding its receptor (C3aR), which is present on both myeloid and nonmyeloid cells. To investigate the biological impact of C3a-mediated effects during acute pneumonia caused by Pseudomonas aeruginosa, we subjected C3aR-deficient mice and matched wild-type (WT) mice to P. aeruginosa pulmonary infection. C3aR-deficient mice exhibited increased killing of P. aeruginosa in the lungs, less dissemination of bacteria into the bloodstream, and a decreased inflammatory response to P. aeruginosa pulmonary infection compared with WT mice. To examine whether the absence of C3aR would impact the humoral immune response to P. aeruginosa, we immunized WT and C3aR-deficient mice via intraperitoneal injection with live P. aeruginosa. Both groups of mice developed similar levels of antibody specific to P. aeruginosa. Immunized C3aR-deficient and WT mice were subjected to P. aeruginosa pulmonary infection, and C3aR-deficient mice again displayed increased killing of P. aeruginosa in the lungs, less dissemination of bacteria into the bloodstream, and a decreased inflammatory response in the lungs. Collectively, these data demonstrate that independently of antibody production, absence of C3aR causes enhanced killing of P. aeruginosa despite a diminished inflammatory response in a mouse model of pneumonia.
Nerve growth factor-enhanced airway responsiveness involves substance P in ferret intrinsic airway neurons
Authors: Wu Z.-X. , Dey R. D.
Published: February 2006

Nerve growth factor (NGF), a member of the neurotrophin family, enhances synthesis of neuropeptides in sensory and sympathetic neurons. The aim of this study was to examine the effect of NGF on airway responsiveness and determine whether these effects are mediated through synthesis and release of substance P (SP) from the intrinsic airway neurons. Ferrets were instilled intratracheally with NGF or saline. Tracheal smooth muscle contractility to methacholine and electrical field stimulation (EFS) was assessed in vitro. Contractions of isolated tracheal smooth muscle to EFS at 10 and 30 Hz were significantly increased in the NGF treatment group (10 Hz: 33.57 ± 2.44%; 30 Hz: 40.12 ± 2.78%) compared with the control group (10 Hz: 27.24 ± 2.14%; 30 Hz: 33.33 ± 2.31%). However, constrictive response to cholinergic agonist was not significantly altered between the NGF treatment group and the control group. The NGF-induced modulation of airway smooth muscle to EFS was maintained in tracheal segments cultured for 24 h, a procedure that causes a significant anatomic and functional loss of SP-containing sensory fibers while maintaining viability of intrinsic airway neurons. The number of SP-containing neurons in longitudinal trunk and superficial muscular plexus and SP nerve fiber density in tracheal smooth muscle all increased significantly in cultured trachea treated with NGF. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the NGF-induced increased contraction to EFS in cultured segments but had no effect in saline controls. These results show that the NGF-enhanced airway smooth muscle contractile responses to EFS are mediated by the actions of SP released from intrinsic airway neurons.
Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4
Authors: Qiao Jing , Huang Fei , Naikawadi Ram P. , Kim Kwang S. , Said Tamer , Lum Hazel
Published: February 2006

Abundant evidence indicates that lysophosphatidylcholine (LPC) is proinflammatory and atherogenic. In the vascular endothelium, LPC increases permeability and expression of proinflammatory molecules such as adhesion molecules and cytokines. Yet, mechanisms by which LPC mediates these activities remain unclear and controversial. Recent evidence implicates involvement of a novel subfamily of G protein-coupled receptors (GPR4, G2A, OGR1, and TDAG8) that are sensitive to lysolipids and protons. We previously reported that one of these receptors, GPR4, is selectively expressed by a variety of endothelial cells and therefore hypothesize that the LPC-stimulated endothelial barrier dysfunction is mediated through GPR4. We developed a peptide Ab against GPR4 that detected GPR4 expression in transfected COS 7 cells and endogenous GPR4 expression in endothelial cells by Western blot. Endothelial cells infected with a retrovirus containing small interference RNA (siRNA) to GPR4 resulted in 40–50% decreased GPR4 expression, which corresponded with partial prevention of the LPC-induced 1) decrease in transendothelial resistance, 2) stress fiber formation, and 3) activation of RhoA. Furthermore, coexpression of the siRNA-GPR4 with a siRNA-resistant mutant GPR4 fully restored the LPC-induced resistance decrease. However, extracellular pH of <7.4 did not alter baseline or LPC-stimulated resistances. The results provide strong evidence that the LPC-mediated endothelial barrier dysfunction is regulated by endogenous GPR4 in endothelial cells and suggest that GPR4 may play a critical role in the inflammatory responses activated by LPC.
East Germany's Jewish Question: The Return and Preservation of Jewish Sites in East Berlin and Potsdam, 1945–1989
Authors: Meng Michael
Published: February 2006

InSeptember 1950, Julius Meyer, head of the State Association of Jewish Communities in the German Democratic Republic (GDR), sent a letter to the Finance Ministry inquiring about the current state of Jewish communal property. Throughout the immediate postwar years, he and other Jewish leaders had requested, though with little success, the return of Jewish property and assistance to rebuild Jewish sites. With the occupation now over, Meyer hoped that the newly formed East German state might be sympathetic to the needs of theGemeinde(a religious community of Jews). He noted that the Jewish community had “still not acquired its own property” since most of it remained “under the control of the state” or in the hands of those who had seized it during the Nazi program of “Aryanization.” Meyer also pointed out that the Gemeinde needed money to reconstruct the numerous synagogues and Jewish cemeteries that had been damaged duringKristallnachtand World War II. “We ask,” he explained, “that you take into consideration the fact that the Jewish community, because of the extermination policy of the fascist state, finds itself in a situation like no other religious community.”
How to Become a Loyalist: Petitions, Self-Fashioning, and the Repression of Unrest (East Frisia, 1725–1727)
Authors: Luebke David M.
Published: February 2006

OnJanuary 21, 1727, several communes in the Nordbrookmerland region of East Frisia, a small principality located on the North Sea coast of Germany and hard by the Dutch border, were granted what amounted to immunity from prosecution for acts of rebellion. How and why this happened is a story that has a great deal to tell about the influence ordinary people could exert, through petitioning, on the practice of state power in early modern Europe. In the months and years before 1727, the prince of East Frisia, Georg Albrecht, had become embroiled in an increasingly hostile confrontation with the Estates of his province for control over the administration of taxes in the land. In their efforts to gain the upper hand, both the prince and the Estates had tried to forge alliances among the rural population and mobilized these networks against each other. The Nordbrookmerlanders tended to ally with the prince, but felt increasingly isolated and endangered. Throughout the autumn of 1726, they had been petitioning the chancellor, Enno R. Brenneysen, for protection against attacks perpetrated by the Estates' allies on their “wives and children, houses and farms.” In light of the chancellor's inability to preserve them from further destruction, the village elders asked that they be allowed to obey the Estates' commands until order was restored. Doing this, they pointed out, would force them to commit several “rebellious” acts, such as signing manifestos, supplying recruits for the rebels' militia, and paying an extraordinary war tax that had been levied by the Estates, the so-calledWochengeld.
Historical Evidence and Plausible History: Interpreting the Berlin Gestapo's Attempted “Final Roundup” of Jews (also known as the “Factory Action”)
Authors: Stoltzfus Nathan
Published: February 2006

Most historians who address it agree that the street protest by non-Jews for their Jewish family members constitutes the most plausible explanation for the Gestapo's release of intermarried Jews incarcerated at Berlin's Rosenstrasse. Had the women not protested, the Jews (or the overwhelming majority) most likely would have been deported to either death or labor camps. This view holds that regime leaders released the Jews for tactical reasons, not because it was cowed or had moral scruples. Although Wolf Gruner has characterized this long-established interpretation as “legend,’ his evidence on balance supports rather than challenges it.
Franz von Papen, the German Center Party, and the Failure of Catholic Conservatism in the Weimar Republic
Authors: Jones Larry Eugene
Published: February 2006

No one stood more directly in the eye of the storm that descended upon Germany in 1933 than Franz von Papen. Not only did Papen play a crucial role in overcoming Reich President Paul von Hindenburg's resistance to Adolf Hitler's appointment as chancellor, but his presence in the newly formed Hitler cabinet provided it with an aura of conservative legitimacy that helped mollify the fears that many Germans might otherwise have felt about the so-called Hitler solution. To complicate matters further, Papen proved utterly incapable of containing the dynamism of the Nazi movement and watched ineffectually from the sidelines as the Nazis unleashed a veritable revolution in the spring of 1933 that either swept Germany's conservative institutions aside or, what proved more likely, forcibly coordinated them into the organizational structure of the Third Reich. Nowhere, however, was Papen's ineffectiveness—or, for that matter, his lack of civil courage—more apparent than in the summer of 1934, when the Nazis ruthlessly murdered two of his closest associates, along with several other prominent conservatives, in a two-pronged strike against both the more militant elements within the Nazi movement and a clique of anti-Nazi conspirators within Papen's own vicechancery.
Biblical Interpretation in the Patristic Era, A 'Handbook of Patristic Exegesis' and Some Other Recent Books and Related Projects
Authors: van Oort Johannes
Published: February 2006

During the past ten years several books in the field of patristic exegesis have been published and some major projects have started. The aim of this article is to provide an introduction to this noticeably new trend of research and to evaluate some results.
"The Puzzle of the Last Four Books of Augustine's Confessions": An Illegitimate Issue?
Authors: Kotzé Annemaré
Published: February 2006

The most important point this article wants to make is that the expectations of the ancient reader, Augustine's contemporary, of a work like the Confessions may have been diametrically opposite to the expectations with which the work has been read for the past number of centuries. I contend that, even though they too would no doubt have recognized the novel and creative devices that characterize the work, ancient readers would not have been perplexed by the presence of the last four books of the Confessions. The whole issue surrounding the presence of these books is a problem created by the illegitimate assumptions later readers carried into their reading.
Post-Byzantine hermeneiai zographikes in the eighteenth century and their dissemination in the Balkans during the nineteenth century
Authors: Moutafov Emmanuel
Published: February 2006

This article focuses on the significance of the Orthodox painters’ manuals, called hermeneiai zographikes, in the development of post-Byzantine iconography and painting technology and techniques in the Balkans during the eighteenth and nineteenth centuries. Using a number of unpublished painters’ manuals (Greek and Slavonic) as primary sources for the study of Christian and Ottoman culture in the Balkan peninsula, it is possible to examine perceptions of Europe in the Balkans, in particular the principal routes for the transmission of ideas of the European Enlightenment, as well as the role of artists as mediators in the processes of ‘Europeanization'.
Determination of the cation exchange capacity of clays with copper complexes revisited
Authors: Ammann L. , Bergaya F. , Lagaly G.
Published: February 2006

The determination of the cation exchange capacity (CEC) of clays by exchange with the cationic copper complexes [Cu(en)2]2+ and [Cu(trien)]2+ is revisited. The procedures reported by Bergaya & Vayer (1997) and Meier & Kahr (1999) are modified slightly. The concentration of the copper complexes in the equilibrium solutions is measured by spectral photometry. Correct CEC values of the [Cu(en)2]2+ exchange are only obtained when a buffer (‘tris’, tris (hydroxymethyl) aminomethane, pH = 8) is added to the equilibrium solution after separation of the clay, because the molar extinction coefficient of this complex depends on the pH of the solution. A standard procedure is recommended as a reference method. In most cases, tris addition is not needed for the determination with [Cu(trien)]2+ cations. Nevertheless, tris addition is recommended in the standard procedure. Determination of CEC for 40 samples (kaolins, ‘common clays’, bentonites, montmorillonites and beidellite) shows a good agreement between measurements using [Cu(en)2]2+ and [Cu(trien)]2+ cations and with results by the ammonium acetate method.
Bentonites from Cabo de Gata, Almería, Spain: a mineralogical and geochemical overview
Authors: Caballero E. , Jiménez de Cisneros C. , Huertas F. J. , Huertas F. , Pozzuoli A. , Linares J.
Published: February 2006

The Neogene volcanic region of Cabo de Gata, Almería, SE Spain, is dotted with many outcrops of bentonite, some of them of significant economic interest. The bentonites have their origin in the hydrothermal alteration of pyroclastic rocks (15-7 Ma). The deposits are usually associated with fractures. The major mineral is a dioctahedral Fe- and Mg-smectite (89-75%) and this is accompanied by minor amounts of feldspars, quartz, amphiboles, pyroxenes, biotite, zeolites, disordered tridymite, calcite, etc. This paper describes the geological background, the general characteristics of the bentonites and major aspects of their formation, e.g. type of low-temperature hydrothermal solutions, mass balance, chemical evolutions of the smectites and geochemistry of trace elements. Finally, the characteristics of three of the most important deposits are described.
Hydraulic conductivity and imbibition speed of solid clay aggregates: two different approaches involving the tortuosity of pathways
Authors: Konta J.
Published: February 2006

Two different approaches used to express the tortuosity of water pathways in a solid clay body are known: (1) a static approach based on microscopic measurement in thin sections; and (2) a dynamic approach based on ‘imbibition’ speed. Each is expressed by a corresponding equation. The second method has the following advantages over the first: (a) it enables the testing of a much larger volume than that observed in a common thin section; (b) it measures the effects of all particles, including the finest fragments barely visible under optical microscope which also have influence on hydraulic conductivity or the imbibition speed of water; (c) in the case of expansible clays, the magnitude ofk(tortuosity of pathways including the shape of particles) can be compared withkfor non-expansible clays using a non-polar liquid, e.g. tetraline; (d) the measurement of the imbibition speed into the clay aggregate through a constant area is automated. Specific properties and processes important for sealing clays are discussed in the connection with the dynamic approach.
The relationship between zeolite (heulandite-clinoptilolite) content and the ammonium-exchange capacity of pyroclastic rocks in Gördes, Turkey
Authors: Esenli F. , Sirkecioğlu A.
Published: February 2006

Diagenetic alteration in two tuff horizons (the lower and upper tuff units) in the GoÈrdes region of Turkey led to the formation of mainly heulandite-clinoptilolite-type zeolites and also clay and silica minerals and K-feldspar. Possible variations in the climate and geological environment followed by variations in the hydrological system and the composition of the Miocene lake water and groundwater at that time resulted in the mineralogical facies. The lower tuffs are unaltered or slightly altered in the northern part and are more altered, particularly to zeolite (clinoptilolite) in the southern part of the study area. Heulandite and K-feldspar are mainly authigenic minerals in the upper tuff unit. The ammonium-exchange capacities of the 16 samples were investigated to understand the effects of the mineralogical composition on their ion-exchange capacities, which vary in the range 0.19-2.00 mEq/g. It is observed that the ion-exchange capacities are strongly dependent on the zeolite contents of the rocks. The correlation coefficient of this linear relation is 0.86. The most significant increase in ammonium-exchange capacity (from 0.2 to ~1.0 mEq/g) was observed when the zeolite contents increased from 0 to 30 wt.%. The second increase in exchange capacity was observed for samples containing >80 wt.% zeolite. Although there is no significant effect from the other authigenic minerals, smectite has a positive effect, and K-feldspar and opal-CT have almost no effect on the ion exchange capacities.
EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts
Authors: Li Ying Ji , Azuma Arata , Usuki Jiro , Abe Shinji , Matsuda Kuniko , Sunazuka Toshiaki , Shimizu Takako , Hirata Yukiyo , Inagaki Hirofumi , Kawada Tomoyuki , Takahashi Satoru , Kudoh Shoji , Omura Satoshi
Published: February 2006

Background

Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM) without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice.

Methods

Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL) fluid and for induction of messenger RNA (mRNA) of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT)-polymerase chainreaction (PCR) on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3) protein assay by western blotting in MLg2908.

Results

Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-β). The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-β, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-β.

Conclusion

These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-β signaling in lung fibroblasts.
Discovering semantic features in the literature: a foundation for building functional associations
Authors: Chagoyen Monica , Carmona-Saez Pedro , Shatkay Hagit , Carazo Jose M , Pascual-Montano Alberto
Published: February 2006

Background

Experimental techniques such as DNA microarray, serial analysis of gene expression (SAGE) and mass spectrometry proteomics, among others, are generating large amounts of data related to genes and proteins at different levels. As in any other experimental approach, it is necessary to analyze these data in the context of previously known information about the biological entities under study. The literature is a particularly valuable source of information for experiment validation and interpretation. Therefore, the development of automated text mining tools to assist in such interpretation is one of the main challenges in current bioinformatics research.

Results

We present a method to create literature profiles for large sets of genes or proteins based on common semantic features extracted from a corpus of relevant documents. These profiles can be used to establish pair-wise similarities among genes, utilized in gene/protein classification or can be even combined with experimental measurements. Semantic features can be used by researchers to facilitate the understanding of the commonalities indicated by experimental results. Our approach is based onnon-negative matrix factorization(NMF), a machine-learning algorithm for data analysis, capable of identifying local patterns that characterize a subset of the data. The literature is thus used to establish putative relationships among subsets of genes or proteins and to provide coherent justification for this clustering into subsets. We demonstrate the utility of the method by applying it to two independent and vastly different sets of genes.

Conclusion

The presented method can create literature profiles from documents relevant to sets of genes. The representation of genes as additive linear combinations of semantic features allows for the exploration of functional associations as well as for clustering, suggesting a valuable methodology for the validation and interpretation of high-throughput experimental data.
MassSorter: a tool for administrating and analyzing data from mass spectrometry experiments on proteins with known amino acid sequences
Authors: Barsnes Harald , Mikalsen Svein-Ole , Eidhammer Ingvar
Published: February 2006

Background

Proteomics is the study of the proteome, and is critical to the understanding of cellular processes. Two central and related tasks of proteomics are protein identification and protein characterization. Many small laboratories are interested in the characterization of a small number of proteins, e.g., how posttranslational modifications change under different conditions.

Results

We have developed a software tool called MassSorter for administrating and analyzing data from peptide mass fingerprinting experiments on proteins with known amino acid sequences. It is meant for small scale mass spectrometry laboratories that are interested in posttranslational modifications of known proteins. Several experiments can be compared simultaneously, and the matched and unmatched peak values are clearly indicated. The hits can be sorted according to m/z values (default) or according to the sequence of the protein. Filters defined by the user can mark autolytic protease peaks and other contaminating peaks (keratins, proteins co-migrating with the protein of interest, etc.). Unmatched peaks can be further analyzed for unexpected modifications by searches against a local version of the UniMod database. They can also be analyzed for unexpected cleavages, a highly useful feature for proteins that undergo maturation by proteolytic cleavage, creating new N- or C-terminals. Additional tools exist for visualization of the results, like sequence coverage, accuracy plots, different types of statistics, 3D models, etc. The program and a tutorial are freely available for academic users at http://www.bioinfo.no/software/massSorter.

Conclusion

MassSorter has a number of useful features that can promote the analysis and administration of MS-data.