bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia
Authors: Kupatt Christian , Horstkotte Jan , Vlastos Georgios A. , Pfosser Achim , Lebherz Corinna , Semisch Matthias , Thalgott Mark , Büttner Kerstin , Browarzyk Christian , Mages Jörg , Hoffmann Reinhard , Deten Alexander , Lamparter Mathias , Müller Fabian , Beck Heike , Büning Hildegard , Boekstegers Peter , Hatzopoulos Antonis K. 
Published: July 2005

ABSTRACTClonal embryonic endothelial progenitor cells (eEPCs) isolated from embryonic day 7.5 mice home specifically to hypoxic areas in mouse tumor metastases but spare normal organs and do not form carcinomas. Based on these results, we assessed the potential of eEPCs to enhance vascularization and limit organ dysfunction after ischemia in syngenic and xenotypic organisms. The angiogenic potential of eEPCs was evaluated in chronic ischemic rabbit hindlimbs after regional application by retroinfusion. eEPC treatment improved limb perfusion, paralleled by an increase in capillary density and collateral blood vessel number. Systemic eEPC infusion into mice after ischemic cardiac insult increased postischemic heart output measured by a marked improvement in left ventricle developed pressure and both systolic and diastolic functions. In vitro, eEPCs strongly induced vascular outgrowths from aortic rings. To address the molecular basis of this intrinsic angiogenic potential, we investigated the eEPC transcriptome. Genomewide Affymetrix GeneChip analysis revealed that the eEPCs express a wealth of secreted factors known to induce angiogenesis, tissue remodeling, and organogenesis that may contribute to the eEPC‐mediated beneficial effects. Our findings show that eEPCs induce blood vessel growth and cardioprotection in severe ischemic conditions providing a readily available source to study the mechanisms of neovascularization and tissue recovery.
Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response
Authors: Chan Shiu‐Wan , Egan Philip Anthony 
Published: July 2005

ABSTRACTUnfolded protein response (UPR) is a cellular adaptive response that functions to reduce stress caused by malfolded proteins in the endoplasmic reticulum (ER). UPR can be induced under physiological or pathological conditions and is responsible for the pathogenesis of many human diseases. Hepatitis C virus (HCV) is a single‐stranded, positive‐sense RNA virus causing chronic diseases. Its genome encodes two envelope proteins E1 and E2, which mature in the ER to form a noncovalently bound, native complex and disulfide aggregates and have previously been shown to induce expression of the molecular chaperone immunoglobulin heavy chain binding protein. In this study, we show that HCV envelope protein expression regulates another stress indicator CCAAT/enhancer‐binding protein‐homologous protein (CHOP). The ER‐stress element and the activating transcription factor 4 element in the CHOP promoter were activated to a similar extent by HCV envelope protein expression. Using mouse embryonic fibroblasts deficient in the ER stress kinase RNA‐activated protein kinase‐like ER‐resident kinase (PERK), we showed that PERK was necessary and sufficient for activating the CHOP promoter. Expression of HCV E1 and/or E2 also induced splicing of X‐box binding protein 1 and transactivation of the unfolded protein response element, leading to the speculation that HCV E1 and E2 not only regulate the UPR but also ER‐associated degradation.
Munich Information Center for Protein Sequences Plant Genome Resources. A Framework for Integrative and Comparative Analyses
Authors: Schoof Heiko , Spannagl Manuel , Yang Li , Ernst Rebecca , Gundlach Heidrun , Haase Dirk , Haberer Georg , Mayer Klaus F.X. 
Published: July 2005

Abstract
With several plant genomes sequenced, the power of comparative genome analysis can now be applied. However, genome-scale cross-species analyses are limited by the effort for data integration. To develop an integrated cross-species plant genome resource, we maintain comprehensive databases for model plant genomes, including Arabidopsis (Arabidopsis thaliana), maize (Zea mays), Medicago truncatula, and rice (Oryza sativa). Integration of data and resources is emphasized, both in house as well as with external partners and databases. Manual curation and state-of-the-art bioinformatic analysis are combined to achieve quality data. Easy access to the data is provided through Web interfaces and visualization tools, bulk downloads, and Web services for application-level access. This allows a consistent view of the model plant genomes for comparative and evolutionary studies, the transfer of knowledge between species, and the integration with functional genomics data.
The alc-GR System. A Modified alc Gene Switch Designed for Use in Plant Tissue Culture
Authors: Roberts Gethin R. , Garoosi G. Ali , Koroleva Olga , Ito Masaki , Laufs Patrick , Leader David J. , Caddick Mark X. , Doonan John H. , Tomsett A. Brian 
Published: July 2005

Abstract
The ALCR/alcA (alc) two-component, ethanol-inducible gene expression system provides stringent control of transgene expression in genetically modified plants. ALCR is an ethanol-activated transcription factor that can drive expression from the ALCR-responsive promoter (alcA). However, the alc system has been shown to have constitutive expression when used in plant callus or cell suspension cultures, possibly resulting from endogenous inducer produced in response to lowered oxygen availability. To widen the use of the alc system in plant cell culture conditions, the receptor domain of the rat glucocorticoid receptor (GR) was translationally fused to the C terminus of ALCR to produce ALCR-GR, which forms the basis of a glucocorticoid-inducible system (alc-GR). The alc-GR switch system was tested in tobacco (Nicotiana tabacum) Bright Yellow-2 suspension cells using a constitutively expressed ALCR-GR with four alternative alcA promoter-driven reporter genes: β-glucuronidase, endoplasmic reticulum-targeted green fluorescent protein, haemagglutinin, and green fluorescent protein-tagged Arabidopsis (Arabidopsis thaliana) Arath;CDKA;1 cyclin-dependent kinase. Gene expression was shown to be stringently dependent on the synthetic glucocorticoid dexamethasone and, in cell suspensions, no longer required ethanol for induction. Thus, the alc-GR system allows tight control of alcA-driven genes in cell culture and complements the conventional ethanol switch used in whole plants.
Metabolic Engineering of Isoflavonoid Biosynthesis in Alfalfa
Authors: Deavours Bettina E. , Dixon Richard A. 
Published: July 2005

Abstract
The potential health benefits of dietary isoflavones have generated considerable interest in engineering the synthesis of these phytoestrogens into plants. Genistein glucoside production (up to 50 nmol g−1 fresh weight) was engineered in alfalfa (Medicago sativa) leaves by constitutive expression of isoflavone synthase from Medicago truncatula (MtIFS1). Glucosides of biochanin A (4′-O-methylgenistein) and pratensein (3′-hydroxybiochanin A) also accumulated. Although MtIFS1 was highly expressed in all organs examined, genistein accumulation was limited to leaves. MtIFS1-expressing lines accumulated several additional isoflavones, including formononetin and daidzein, in response to UV-B or Phoma medicaginis, whereas the chalcone and flavanone precursors of these compounds accumulated in control lines. Enhanced accumulation of the phytoalexin medicarpin was observed in P. medicaginis-infected leaves of MtIFS1-expressing plants. Microarray profiling indicated that MtIFS1 expression does not significantly alter global gene expression in the leaves. Our results highlight some of the challenges associated with metabolic engineering of plant natural products, including tissue-specific accumulation, potential for further modification by endogenous enzyme activities (hydroxylation, methylation, and glycosylation), and the differential response of engineered plants to environmental factors.
OsPTF1, a Novel Transcription Factor Involved in Tolerance to Phosphate Starvation in Rice
Authors: Yi Keke , Wu Zhongchang , Zhou Jie , Du Liming , Guo Longbiao , Wu Yunrong , Wu Ping 
Published: July 2005

Abstract
We report here on a novel transcription factor with a basic helix-loop-helix domain for tolerance to inorganic phosphate (Pi) starvation in rice (Oryza sativa). The gene is designated OsPTF1. The expression of OsPTF1 is Pi starvation induced in roots while constitutively expressed in shoots, as shown by northern-blot analysis. Overexpression of OsPTF1 enhanced tolerance to Pi starvation in transgenic rice. Tillering ability, root and shoot biomass, and phosphorus content of transgenic rice plants were about 30% higher than those of the wild-type plants in Pi-deficient conditions in hydroponic experiments. In soil pot and field experiments, more than 20% increase in tiller number, panicle weight, and phosphorus content was observed in transgenic plants compared to wild-type plants at low-Pi levels. In Pi-deficient conditions, transgenic rice plants showed significantly higher total root length and root surface area, which results in a higher instantaneous Pi uptake rate over their wild-type counterparts. Microarray analysis for transgenic plants overexpressing OsPTF1 has been performed to investigate the downstream regulation of OsPTF1.
Effects of Calreticulin on Viral Cell-to-Cell Movement
Authors: Chen Min-Huei , Tian Guo-Wei , Gafni Yedidya , Citovsky Vitaly 
Published: July 2005

AbstractCell-to-cell tobacco mosaic virus movement protein (TMV MP) mediates viral spread between the host cells through plasmodesmata. Although several host factors have been shown to interact with TMV MP, none of them coresides with TMV MP within plasmodesmata. We used affinity purification to isolate a tobacco protein that binds TMV MP and identified it as calreticulin. The interaction between TMV MP and calreticulin was confirmed in vivo and in vitro, and both proteins were shown to share a similar pattern of subcellular localization to plasmodesmata. Elevation of the intracellular levels of calreticulin severely interfered with plasmodesmal targeting of TMV MP, which, instead, was redirected to the microtubular network. Furthermore, in TMV-infected plant tissues overexpressing calreticulin, the inability of TMV MP to reach plasmodesmata substantially impaired cell-to-cell movement of the virus. Collectively, these observations suggest a functional relationship between calreticulin, TMV MP, and viral cell-to-cell movement.
Control of Root Cap Formation by MicroRNA-Targeted Auxin Response Factors in Arabidopsis
Authors: Wang Jia-Wei , Wang Ling-Jian , Mao Ying-Bo , Cai Wen-Juan , Xue Hong-Wei , Chen Xiao-Ya 
Published: July 2005

AbstractThe plant root cap mediates the direction of root tip growth and protects internal cells. Root cap cells are continuously produced from distal stem cells, and the phytohormone auxin provides position information for root distal organization. Here, we identify the Arabidopsis thaliana auxin response factors ARF10 and ARF16, targeted by microRNA160 (miR160), as the controller of root cap cell formation. The Pro35S:MIR160 plants, in which the expression of ARF10 and ARF16 is repressed, and the arf10-2 arf16-2 double mutants display the same root tip defect, with uncontrolled cell division and blocked cell differentiation in the root distal region and show a tumor-like root apex and loss of gravity-sensing. ARF10 and ARF16 play a role in restricting stem cell niche and promoting columella cell differentiation; although functionally redundant, the two ARFs are indispensable for root cap development, and the auxin signal cannot bypass them to initiate columella cell production. In root, auxin and miR160 regulate the expression of ARF10 and ARF16 genes independently, generating a pattern consistent with root cap development. We further demonstrate that miR160-uncoupled production of ARF16 exerts pleiotropic effects on plant phenotypes, and miR160 plays an essential role in regulating Arabidopsis development and growth.
Actin-Related Protein2/3 Complex Component ARPC1 Is Required for Proper Cell Morphogenesis and Polarized Cell Growth inPhyscomitrella patens
Authors: Harries Phillip A. , Pan Aihong , Quatrano Ralph S. 
Published: July 2005

AbstractThe actin-related protein2/3 (Arp2/3) complex functions as a regulator of actin filament dynamics in a wide array of eukaryotic cells. Here, we focus on the role of the Arp2/3 complex subunit ARPC1 in elongating tip cells of protonemal filaments of the moss Physcomitrella patens. Using RNA interference (RNAi) to generate loss-of-function mutants, we show dramatic defects in cell morphology manifested as short, irregularly shaped cells with abnormal division patterns. The arpc1 RNAi plants lack the rapidly elongating caulonemal cell type found in wild-type protonemal tissue. The absence of this cell type prevents normal bud formation even in response to cytokinin treatment and results in filamentous colonies lacking leafy gametophores. In addition, arpc1 protoplasts show an increased sensitivity to osmotic shock and are defective in their ability to properly establish a polarized outgrowth during regeneration from a single cell. This failure of arpc1 protoplasts to undergo proper tip growth is rescued by ARPC1 overexpression and is phenocopied in wild-type protoplasts treated with Latrunculin B, a potent inhibitor of actin polymerization. We show in moss that ARPC1, and by inference the Arp2/3 complex, plays a critical role in controlling polarized growth and cell division patterning through its regulation of actin dynamics at the cell apex.
The Putative RNA-Dependent RNA PolymeraseRDR6Acts Synergistically withASYMMETRIC LEAVES1and2to RepressBREVIPEDICELLUSand MicroRNA165/166 in Arabidopsis Leaf Development
Authors: Li Hong , Xu Lin , Wang Hua , Yuan Zheng , Cao Xiaofeng , Yang Zhongnan , Zhang Dabing , Xu Yuquan , Huang Hai 
Published: July 2005

AbstractThe Arabidopsis thaliana ASYMMETRIC LEAVES1 (AS1) and AS2 genes are important for repressing class I KNOTTED1-like homeobox (KNOX) genes and specifying leaf adaxial identity in leaf development. RNA-dependent RNA polymerases (RdRPs) are critical for posttranscriptional and transcriptional gene silencing in eukaryotes; however, very little is known about their functions in plant development. Here, we show that the Arabidopsis RDR6 gene (also called SDE1 and SGS2) that encodes a putative RdRP, together with AS1 and AS2, regulates leaf development. rdr6 single mutant plants displayed only minor phenotypes, whereas rdr6 as1 and rdr6 as2 double mutants showed dramatically enhanced as1 and as2 phenotypes, with severe defects in the leaf adaxial-abaxial polarity and vascular development. In addition, the double mutant plants produced more lobed leaves than the as1 and as2 single mutants and showed leaf-like structures associated on a proportion of leaf blades. The abnormal leaf morphology of the double mutants was accompanied by an extended ectopic expression of a class I KNOX gene BREVIPEDICELLUS (BP) and high levels of microRNA165/166 that may lead to mRNA degradation of genes in the class III HD-ZIP family. Taken together, our data suggest that the Arabidopsis RDR6-associated epigenetic pathway and the AS1-AS2 pathway synergistically repress BP and MIR165/166 for proper plant development.
Safety and tolerability of antagonist anti‐human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease
Authors: KASRAN A. , BOON L. , WORTEL C. H. , van HOGEZAND R. A. , SCHREIBER S. , GOLDIN E. , DE BOER M. , GEBOES K. , RUTGEERTS P. , CEUPPENS J. L. 
Published: July 2005

SummaryBackground:  The ligation of CD40 by CD154 is a critical step in the interaction between APC and T cells. In animals, antagonizing CD40L‐CD40 has been shown to reduce the severity of several autoimmune and inflammatory disorders, including experimental colitis.Aim:  To investigate tolerability and safety of an antagonist chimeric monoclonal anti‐human CD40 antibody (ch5D12) for treatment of Crohn's disease.Method:  ch5D12 was administrated to 18 patients with moderate to severe Crohn's disease in a single dose, open‐label dose‐escalation phase I/IIa study.Results:  ch5D12 plasma concentrations increased dose‐dependently after infusion. Two patients developed an anti‐ch5D12 antibody response. Overall response and remission rates were 72 and 22%, respectively with no evidence for a dose–response effect. Treatment with ch5D12 reduced microscopic disease activity and intensity of the lamina propria cell infiltrate, but did not alter percentages of circulating T and B cells. ch5D12 was well tolerated, although some patients experienced headache, muscle aches, or joint pains, which may have been related to the study drug.Conclusions:  Antagonizing CD154–CD40 interactions with ch5D12 is a promising therapeutic approach for remission induction in Crohn's disease.
The impact of major depressive disorder on the short‐ and long‐term outcome of Crohn's disease treatment with infliximab
Authors: PERSOONS P. , VERMEIRE S. , DEMYTTENAERE K. , FISCHLER B. , VANDENBERGHE J. , VAN OUDENHOVE L. , PIERIK M. , HLAVATY T. , VAN ASSCHE G. , NOMAN M. , RUTGEERTS P. 
Published: July 2005

Summary
Background:  Major depressive disorder is the most common psychiatric diagnosis in Crohn's disease. In other chronic diseases, evidence suggests that depression influences the course of the disease. Strong evidence of such a mediating role of major depressive disorder in Crohn's disease has never been found.Aim:  To assess the relationship between major depressive disorder and outcome of treatment of luminal Crohn's disease with infliximab.Methods:  In this prospective study, 100 consecutive unselected patients underwent assessment of psychosocial, demographical disease‐related biological and clinical parameters at baseline and at 4 weeks after infliximab. Major depressive disorder was diagnosed using the Patient Health Questionnaire. Subsequently, the patients were followed up clinically until the next flare or during 9 months.Results:  The Crohn's disease responded in 75% of the patients, and remission was achieved in 60%. The presence of major depressive disorder at baseline predicted a lower remission rate (OR = 0.166, 95% CI = 0.049–0.567, P = 0.004). At follow‐up, 88% of the patients needed retreatment. At univariate regression analysis, major depressive disorder significantly decreased time to retreatment (P = 0.001). Multivariate Cox regression confirmed major depressive disorder as an independent determinant of active disease both at baseline and at re‐evaluation (hazard ratio = 2.271, 95% CI: 1.36–3.79, P = 0.002).Conclusion:  Major depressive disorder is a risk factor for failure to achieve remission with infliximab and for earlier retreatment in patients with active luminal Crohn's disease. Assessment and management of major depressive disorder should be part of the clinical approach to patients with Crohn's disease.
Upper gastrointestinal symptoms and therapies in elderly out‐patients, users of non‐selective NSAIDs or coxibs
Authors: PILOTTO A. , FRANCESCHI M. , VITALE D. F. , ZANINELLI A. , MASOTTI G. , RENGO F. ,   ON BEHALF OF F.I.R.I. (FONDAZIONE ITALIANA RICERCA SULL'INVECCHIAMENTO) AND THE SOFIA PROJECT INVESTIGATORS
Published: July 2005

SummaryBackground:  The association between coxib or non‐steroidal anti‐inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined.Aim:  To evaluate the association between non‐steroidal anti‐inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner.Materials:  The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2‐week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6‐month period were recorded.Results:  Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo‐skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non‐users of musculo‐skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid‐related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P < 0.01). The prescriptions of drugs for acid‐related disorders were significantly associated with the presence of upper gastrointestinal symptoms (OR = 1.7, 95% CI = 1.6–1.9), previous gastrointestinal disorders (OR = 1.1, 95% CI = 1.0–1.3) and NSAID use (OR = 1.5, 95% CI = 1.0–2.2), but no coxib use.Conclusion:  In this elderly population, upper gastrointestinal symptoms and prescriptions for gastroenterological drugs were higher in non‐steroidal anti‐inflammatory drug users than coxib users and non‐users of musculo‐skeletal drugs.
Impact of rising tropospheric ozone on potato: effects on photosynthesis, growth, productivity and yield quality
Authors: VANDERMEIREN K. , BLACK C. , PLEIJEL H. , DE TEMMERMAN L. 
Published: July 2005

ABSTRACTIn view of its importance for human nutrition, the European Commission funded a collaborative research programme (1998–99) to evaluate the impact of future increases in atmospheric ozone (O3) and carbon dioxide (CO2) concentrations on yield and tuber quality in potato (Solanum tuberosum L.). This was the first large‐scale open‐top chamber project to provide field‐based data spanning a wide range of European climatic conditions and ozone concentrations for a widely used cultivar, cv. Bintje. Intensive measurements of physiological and developmental effects were made throughout crop growth to improve the mechanistic understanding of the processes involved. Analysis of the experimental results and modelling work based on the extensive database revealed that the increasing tropospheric O3 concentrations predicted under future climatic scenarios in Europe are likely to reduce tuber yield in potato. However, season‐long exposure to elevated O3 had both beneficial and detrimental effects on tuber quality. Most of the significant physiological and growth effects occurred during the later stages of crop development, when elevated O3 reduced photosynthesis and promoted senescence. The observed changes in the quality and nutritional attributes of tubers, such as decreased content of reducing sugars and increased nitrogen concentrations, may be attributable to reduced carbohydrate allocation.