bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Association of the Replication Initiator and Transcription Factor DnaA with theBacillus subtilisChromosome during Replication Stress
Authors: Breier Adam M. , Grossman Alan D. 
Published: November 2008

ABSTRACTDnaA functions as both a transcription factor and the replication initiator in bacteria. We characterized the DNA binding dynamics of DnaA on a genomic level. Based on cross-linking and chromatin immunoprecipitation data, DnaA binds at least 17 loci, 15 of which are regulated transcriptionally in response to inhibition of replication (replication stress). Six loci, each of which has a cluster of at least nine potential DnaA binding sites, had significant increases in binding by DnaA when replication was inhibited, indicating that the association of DnaA with at least some of its target sites is altered after replication stress. When replication resumed fromoriCafter inhibition of replication initiation, these high levels of binding decreased rapidly at origin-proximal and origin-distal regions, well before a replication fork could pass through each of the regulated regions. These findings indicate that there is rapid signaling to decrease activation of DnaA during replication and that interaction between DnaA bound at each site and the replication machinery is not required for regulation of DnaA activity in response to replication stress.
The BlcC (AttM) Lactonase ofAgrobacterium tumefaciensDoes Not Quench the Quorum-Sensing System That Regulates Ti Plasmid Conjugative Transfer
Authors: Khan Sharik R. , Farrand Stephen K. 
Published: November 2008

ABSTRACTThe conjugative transfer ofAgrobacteriumplasmids is controlled by a quorum-sensing system consisting of TraR and its acyl-homoserine lactone (HSL) ligand. The acyl-HSL is essential for the TraR-mediated activation of the Ti plasmid Tra genes. Strains A6 and C58 ofAgrobacterium tumefaciensproduce a lactonase, BlcC (AttM), that can degrade the quormone, leading some to conclude that the enzyme quenches the quorum-sensing system. We tested this hypothesis by examining the effects of the mutation, induction, or mutational derepression ofblcCon the accumulation of acyl-HSL and on the conjugative competence of strain C58. The induction ofblcresulted in an 8- to 10-fold decrease in levels of extracellular acyl-HSL but in only a twofold decrease in intracellular quormone levels, a measure of the amount of active intracellular TraR. The induction or mutational derepression ofblcas well as a null mutation inblcChad no significant effect on the induction of or continued transfer of pTiC58 from donors in any stage of growth, including stationary phase. In matings performed in developing tumors, wild-type C58 transferred the Ti plasmid to recipients, yielding transconjugants by 14 to 21 days following infection.blcC-null donors yielded transconjugants 1 week earlier, but by the following week, transconjugants were recovered at numbers indistinguishable from those of the wild type. Donors mutationally derepressed forblcCyielded transconjugants in planta at numbers 10-fold lower than those for the wild type at weeks 2 and 3, but by week 4, the two donors showed no difference in recoverable transconjugants. We conclude that BlcC has no biologically significant effect on Ti plasmid transfer or its regulatory system.
CcpC-Dependent Regulation of Citrate Synthase Gene Expression inListeria monocytogenes
Authors: Mittal Meghna , Picossi Silvia , Sonenshein Abraham L. 
Published: November 2008

ABSTRACTCitrate synthase, the first and rate-limiting enzyme of the tricarboxylic acid branch of the Krebs cycle, was shown to be required for de novo synthesis of glutamate and glutamine inListeria monocytogenes. The citrate synthase (citZ) gene was found to be part of a complex operon with the upstream genes lmo1569 and lmo1568. The downstream isocitrate dehydrogenase (citC) gene appears to be part of the same operon as well. Two promoters were shown to drivecitZexpression, a distal promoter located upstream of lmo1569 and a proximal promoter located upstream of the lmo1568 gene. Transcription ofcitZfrom both promoters was regulated by CcpC by interaction with a single site; assays of transcription in vivo and assays of CcpC binding in vitro revealed that CcpC interacts with and represses the proximal promoter that drives expression of the lmo1568,citZ, andcitCgenes and, by binding to the same site, prevents read-through transcription from the distal, lmo1569 promoter. Expression of the lmo1568 operon was not affected by the carbon source but was repressed during growth in complex medium by addition of glutamine.
The Tail Sheath of Bacteriophage N4 Interacts with the
Escherichia coli
Receptor
Authors: McPartland Jennifer , Rothman-Denes Lucia B. 
Published: November 2008

ABSTRACT

Unlike other characterized phages, the lytic coliphage N4 must inject the 360-kDa virion RNA polymerase (vRNAP), in addition to its 72-kbp genome, into the host for successful infection. The process of adsorption to the host sets up and elicits the necessary conformational changes in the virion to allow genome and vRNAP injection. Infection of suppressor and nonsuppressor strains,
Escherichia coli
W3350
supF
and
E. coli
W3350, with a mutant N4 isolate (N4am229) harboring an amber mutation in Orf65 yielded virions containing (N4gp65
+
) and lacking (N4gp65
−
) gp65, respectively. N4gp65
+
but not N4gp65
−
phage was able to adsorb to the host. Recombinant gp65 with a hexahistidine tag at the N terminus or hexahistidine and c-
myc
tags at the C terminus was able to complement N4gp65
−
virions in vivo and in vitro. Immunogold detection of gp65 in vivo complemented virions revealed its localization at the N4 tail. Finally, we show both in vitro and in vivo that gp65 interacts with the previously determined N4 outer membrane receptor, NfrA.
Extended perioperative thromboprophylaxis in patients with cancer
Authors: Terrenato Irene , Barba Maddalena , Sperati Francesca , Muti Paola , Schünemann Holger J. , Akl Elie A. 
Published: November 2008

SummaryWe systematically reviewed the literature to compare the relative efficacy and safety of extended versus limited duration heparin for perioperative thromboprophylaxis in patients with cancer. We followed the Cochrane Collaboration systematic review methodology and searched MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL. The outcomes of interest included mortality, symptomatic deep venous thrombosis (DVT), pulmonary embolism, and bleeding. We evaluated the quality of evidence by outcome using the GRADE approach. Of 3,986 identified citations, we included three randomized clinical trials using low-molecular-weight heparin (LMWH).The quality of evidence for mortality, DVT, and major bleeding was low. There was no significant difference between extended (4 weeks) and limited duration thromboprophylaxis in terms of death at three months (relative risk [RR]=0.49; 95% confidence interval [CI] 0.12–1.94), or major bleeding at four weeks (RR=2.94; 95% CI 0.12–71.85).An extended regimen was associated with a significantly lower risk of asymptomatic DVT (RR=0.21; 95% CI 0.05–0.94). No data was available for symptomatic DVT. In conclusion, there is limited and low-quality evidence that extended duration LMWH for perioperative thromboprophylaxis reduces DVT in patients with cancer undergoing major abdominal or pelvic surgery. More and better quality evidence is needed to justify extended regimens.
Altered bioavailability of platelet-derived factor VIII during thrombocytosis reverses phenotypic efficacy in haemophilic mice
Authors: Damon Andrea L. , Scudder Lesley E. , Gnatenko Dmitri V. , Sitaraman Varsha , Hearing Patrick , Jesty Jolyon , Bahou Wadie F. 
Published: November 2008

SummaryEctopic delivery of factor VIII (FVIII) to megakaryocytes (Mk) represents a viable approach for localized tenase generation by concentrating the FVIIIa/FIXa enzymecofactor complex onto activated platelet membranes. We utilized a core rat platelet factor 4 (PF4) promoter for Mk/platelet-restricted expression of human B-domain-deleted (hBDD) FVIII within the background of a haemophilia A mouse (rPF4/hBDD/FVIII-/-). Platelets from rPF4/hBDD/FVIII-/- mice contained ∼122 mU FVIII:C/1x109 platelets/ml with no detectable plasmatic FVIII:C,and with no effect on α-granule-derived platelet factorV/Va function.Paired tenase assays (± thrombin) confirmed that platelet (pt) FVIII (unlike platelet FV) required thrombin cleavage for complete activation. rPF4/hBDD/FVIII-/- mice exposed to a thrombocytotic stimulus (thrombopoietin, TPO) demonstrated a statistically-significant 66% reduction in molar ptFVIII activity with a non-significant reduction in total ptFVIII biomass. Decreased molar ptFVIII concentration correlated with loss of phenotypic correction as evaluated using a haemostatic tail-snip assay. Comparative studies using a transgenic mouse expressing human amyloid-β-precursor protein (hAβPP) from the rPF4 promoter confirmed diminished hAβPP expression without affecting endogenous α-granule PF4, establishing generalizability of these observations.While Mk/plateletreleased ptFVIII (unlike pFV) is proteolytically inactive, we also conclude that thrombocytotic stimuli negatively affect ptFVIII bioavailability and phenotypic efficacy, results which correlate best with molar ptFVIII concentration, and not systemically available ptFVIII.
Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)
Authors: Rømer Maria , Lademann Ulrik A. 
Published: November 2008

SummaryElevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase-type plasminogen activator (uPA) observed in tumours; however, several lines of evidence suggest that PAI-1 may contribute directly to the pathology of the disease. PAI-1 has been reported to have an effect on most of the basic cellular processes including cell adhesion, cell migration, cell invasion, and cell proliferation and increasing numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells.A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.
Antiphospholipid antibodies predict imminent vascular events independently from other risk factors in a prospective cohort
Authors: Kassis Jeannine , Solymoss Susan , Joseph Lawrence , Belisle Patrick , Levine Jerrold , Neville Carolyn , Rauch Joyce , Fortin Paul 
Published: November 2008

SummaryAntiphospholipid antibodies (aPL) are associated with vascular events, but the magnitude of this risk, alone, or in combination with other atherogenic and thrombophilic risk factors, remains unclear. A prospective cohort of 415 persons was studied for arterial and venous events (AE and VE) over a median time of 7.4 years. aPL and coagulation abnormalities were measured upon beginning of the study and annually for the first four years. Within the cohort, a nested case-control study was conducted to investigate the role of endothelial and inflammatory markers in predicting new vascular events. Forty-five individuals had new vascular events: 18 occurred during the first year of follow-up. The proportion of event-free survivors at eight years was 90% (95%CI = 87%, 94%) for aPL-negative and 72% (60%, 85%) for aPL-positive individuals, respectively. Predictors for new AE were previous AE (HR=5.7 [2.7, 12.0]), diabetes (5.6 [2.4, 13.2]), aPL positivity (2.6 ([1.2, 5.9]), and age (1.04 [1.01, 1.07]). New VE were predicted by previous VE (6.1 [1.9, 19.9]), anti-β2-glyco-protein I (aβ2GPI) positivity (5.8 [1.4, 24.1]), activated protein C resistance (APCR) (4.1 [1.1, 15.1]), and gender (3.7 [1.1, 12.9]). In the nested case-control study, similar predictors were observed for AE, while abnormal APCR (OR=5.5 [1.1, 26.6]) and elevated von Willebrand factor (vWF) (OR=5.0 [1.2, 19.8]) best predicted VE. We demonstrate that aPL independently predict new vascular events and discriminate between individuals with and without events in the first two years of follow-up, indicating that aPL are associated with a short-term risk of developing new and recurrent vascular events.
Compensatory anti-inflammatory response syndrome
Authors: Cavaillon Jean-Marc , Adib-Conquy Minou 
Published: November 2008

SummaryThe concept of ‘Compensatory anti-inflammatory response syndrome’ (CARS) was proposed in 1997 by Roger Bone (1941–1997) to qualify the consequences of the counter-regulatory mechanisms initiated to limit the overzealous inflammatory process in patients with infectious (sepsis) or non-infectious systemic inflammatory response syndrome (SIRS). One major consequence of CARS is the modification of the immune status that could favour the enhanced susceptibility of intensive care patients to nosocomial infections. Indeed, most animal ‘two-hit’ models illustrate an enhanced sensitivity to infection after a first insult. However, this observation is highly dependent on the experimental procedure. Numerous functions of circulating leukocytes are altered in sepsis and SIRS patients, as well as in animal models of sepsis or SIRS. However, this is rather a reprogramming of circulating leukocytes, since there is not a global defect of the immune cells functions. Furthermore, within tissues, leukocytes are rather primed or activated than immunosuppressed. Thus, CARS may be considered as an adapted compartmentalized response with the aim to silence some acute proinflammatory genes, and to maintain the possible expression of certain genes involved in the anti-infectious process.
Plasminogen activator inhibitor-1: The double-edged sword in apoptosis
Authors: Balsara Rashna D. , Ploplis Victoria A. 
Published: November 2008

SummaryPlasminogen activator inhibitor type-1 (PAI-1) is a multi-functional protein. It is a fast-acting inhibitor of plasminogen activators; urokinase-plasminogen activator and tissue type plasminogen activator, and also plays an important role in regulating cell proliferation, adhesion, migration, and signal transduction pathways.These biological events are important processes during angiogenesis and restenosis. PAI-1 has been shown to regulate proliferation, migration, and apoptosis of vascular smooth muscle cells and endothelial cells.The ability of PAI-1 to regulate cellular proliferation and migration has been attributed to its ability to control plasmin production, modify signaling pathways, and its inherent multifactorial ability to bind to vitronectin and lipoprotein receptor-related protein.However,the mechanism by which PAI-1 regulates the apoptotic pathway is not well understood. Evidence from the literature suggests that PAI-1 or its deficiency alters key signalling pathways, such as the PI3-k/Akt and the Jak/STAT pathways, and is involved in maintaining endothelial cell integrity thereby regulating cell death. Other investigators have demonstrated that PAI-1 directly binds to caspases as a mechanism of PAI-1-mediated cellular apoptosis. Moreover, results from studies assessing the role of PAI-1 in apoptosis have suggested that PAI-1 can exert pathogenic or protective effects, which may be related to the disease model or type of injury employed.
Rac-1 promotes pulmonary artery smooth muscle cell proliferation by upregulation of plasminogen activator inhibitor-1: Role of NFκB-dependent hypoxia-inducible factor-1α transcription
Authors: Diebold Isabel , Djordjevic Talija , Hess John , Görlach Agnes 
Published: November 2008

SummaryPulmonary vascular remodeling is commonly associated with pulmonary hypertension and is characterized by media thickening and disordered cellular proliferation, often accompanied by fibrin deposition and thrombosis in situ. However, the signaling pathways linking these different processes are not well understood. Since the GTPase Rac-1 has been suggested to act as a signaling relay in various cell types we investigated whether Rac-1 could be the link between thrombin signaling,plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrinolysis and promotes fibrin deposition, and proliferation of pulmonary artery smooth muscle cells (PASMC). Exposure to thrombin enhanced the levels of Rac-1 protein and increased PAI-1 mRNA and protein expression in dependence of the thrombin receptor PAR-1. Expression of dominant-negative Rac-1 (RacT17N) prevented thrombin-induced PAI-1 expression whereas constitutively active RacG12V enhanced PAI-1 levels. In the presence of RacT17N thrombin-induced PAI-1 promoter activity was abrogated whereas RacG12V increased PAI-1 promoter activity, and this response was essentially dependent on the transcription factor hypoxia-inducible factor-1 (HIF-1). Subsequently, RacG12V not only increased HIF transcriptional activity but also HIF-1α protein and mRNA levels, whereas RacT17N prevented these responses elicited by thrombin.In line,RacG12V enhanced HIF-1α promoter activity, and this response was dependent on nuclear factor-kappaB (NFκB) binding to the HIF-1α promoter. Finally, upregulation of PAI-1 by Rac-1 and HIF-1 was essential for thrombin-stimulated proliferation of PASMC.These findings indicate that Rac-1 is an important mediator of thrombin signaling and may contribute to pulmonary vascular remodeling via HIF-1-dependent upregulation of PAI-1 leading to enhanced proliferation of PASMC.
Risk of venous thromboembolism with rheumatoid arthritis
Authors: Matta Fadi , Singala Ravinder , Yaekoub Abdo , Najjar Reiad , Stein Paul 
Published: November 2008

SummaryRheumatoid arthritis is not generally considered to be a risk factor for venous thromboembolism (VTE), although abnormalities of coagulation factors have been found in patients with rheumatoid arthritis. Sparse data in a few patients suggest that patients with rheumatoid arthritis may have higher rates of VTE. The purpose of this investigation was to determine if the incidences of pulmonary embolism (PE) and deep venous thrombosis (DVT) are increased in hospitalized patients with rheumatoid arthritis. The number of patients discharged from non-Federal short-stay hospitals throughout the United States from 1979 through 2005 with a discharge code for rheumatoid arthritis was obtained from the National Hospital Discharge Survey (NHDS). Among hospitalized patients with rheumatoid arthritis who did not have joint surgery, 41,000 of 4,818,000 (0.85%) had PE compared with 3,366,000 of 891,055,000 (0.38%) among patients who did not have rheumatoid arthritis and who did not have operations or joint surgery (relative risk =2.25). Deep venous thrombosis was diagnosed in 79,000 of 4,818,000 (1.64%) patients with rheumatoid arthritis and no joint operation, versus 7,681,000 of 891,055,000 (0.86%) who did not have rheumatoid arthritis or a joint operation (relative risk=1.90). The relative risk of venous thromboembolism (PE and/or DVT) in these patients was 1.99. The data suggest that rheumatoid arthritis is a risk factor for VTE in hospitalized medical patients. A heightened awareness of the risks for VTE and a lower threshold for evaluation of patients for possible DVT or PE would be appropriate in caring for hospitalized patients with rheumatoid arthritis.
Procedure before the ICJ: What is the Exact Date of the Closure of the Written Phase of Proceedings?
Authors: Quintana Juan 
Published: November 2008

AbstractDetermining the precise date on which the written phase in litigation before the International Court of Justice is closed and the case is “ready for hearing” is important for a number of reasons, including the application of the rules concerning the submission of “further” or “new” documents, and the filing of requests for permission to intervene under Article 62 of the Statute. While the instruments governing the Court's functioning are silent on the matter, conventional wisdom appears to support the notion that such a date is defined with sufficient clarity, as the written proceedings are to be closed “automatically” on the date of the deposit of the last pleading. The aim of this Note is to show that actual practice reveals that in most cases it will be difficult, if not outright impossible, to determine beforehand what this last pleading is going to be. As a result, the written phase will only be closed at a later stage, when the parties and the Court are certain that there will be no further pleadings, a circumstance that appears to conflict with the notion of “automatic closure”.
EC Visa Facilitation and Readmission Agreements: A New Standard EU Foreign Policy Tool?
Authors: Kruse Imke , Trauner Florian 
Published: November 2008

AbstractThis article offers an analysis of the objective, substance and political implications of EC visa facilitation and readmission agreements. These agreements have gained increasing importance in EU foreign policy making because the EU has started to view visa facilitation regimes not only as a necessary incentive for the signing of a readmission agreement, but also as a means for mitigating the negative side-effects of the Eastern Enlargement. In offering more relaxed travel conditions in exchange for endorsement of an EC readmission agreement and reforms in domestic justice and home affairs, the EU found a new way to pressure for reforms in neighbouring countries while meeting a major source of discontent in these countries. The analysis considers the broader implications of these agreements and argues that even if the facilitated travel opportunities are beneficial for the citizens of the target countries, the positive achievements are undermined by the Schengen enlargement which requires that the new member states tighten up their borders to their neighbours.
Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation
Authors: Jenq Robert R. , King Christopher G. , Volk Christine , Suh David , Smith Odette M. , Rao Uttam K. , Yim Nury L. , Holland Amanda M. , Lu Sydney X. , Zakrzewski Johannes L. , Goldberg Gabrielle L. , Diab Adi , Alpdogan Onder , Penack Olaf , Na Il-Kang , Kappel Lucy W. , Wolchok Jedd D. , Houghton Alan N. , Perales Miguel-Angel , van den Brink Marcel R. M. 
Published: November 2008

AbstractKeratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8+ T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8+ cells, as well as increased numbers of CD8+ cells producing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell–receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution.