bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Mammalian Target of Rapamycin Activity in PTEN-Inactive Prostate Cancer Cells by IκB Kinase α
Authors: Dan Han C. , Adli Mazhar , Baldwin Albert S. 
Published: July 2007

Abstract
The mammalian target of rapamycin (mTOR) is a mediator of cell growth, survival, and energy metabolism at least partly through its ability to regulate mRNA translation. mTOR is activated downstream of growth factors, insulin, and Akt-dependent signaling associated with oncoprotein expression or loss of the tumor-suppressor PTEN. In this regard, mTOR activity is associated with cancer cell growth and survival. Here, we have explored an involvement of the IκB kinase (IKK) pathway, associated with nuclear factor-κB activation, in controlling mTOR activity. The experiments show that IKKα controls mTOR kinase activity in Akt-active, PTEN-null prostate cancer cells, with less involvement by IKKβ. In these cells, IKKα associates with mTOR, as part of the TORC1 complex, in an Akt-dependent manner. Additionally, IKKα is required for efficient induction of mTOR activity downstream of constitutively active Akt expression. The results indicate a novel role for IKKα in controlling mTOR function in cancer cells with constitutive Akt activity. [Cancer Res 2007;67(13):6263–9]
Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms
Authors: Zhu Chaoyong , Silveira Angela , Hemdahl Anne-Louise , Hamsten Anders , Hedin Ulf , Swedenborg Jesper , Folkesson Maggie , Kazil Monsur , Eriksson Per 
Published: July 2007

SummaryIt has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture.The growth of theAAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase- 9 (MMP-9) and inhibit its degradation,thereby preserving enzymatic activity. Biopsies were obtained from thrombus- free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography,Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself.Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall.Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions.The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.
Association of specific haplotypes of GAS6 gene with stroke
Authors: Obach Víctor , de Frutos Pablo García , Chamorro Ángel , Muñoz Xavier , Hurtado Begoña , Sala Núria 
Published: July 2007

SummaryThe product of the growth arrest-specific gene 6 (GAS6),a ligand for tyrosine kinase receptors, is a vitamin K-dependent protein, structurally related to anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the cardiovascular system. In a preliminary study on GAS6 polymorphisms and atherothrombotic disease we found an association between the AA genotype of the c.834+7G>A GAS6 polymorphism and stroke. In order to further explore this association by considering GAS6 haplotypes and the main stroke subtypes,457 patients with ischemic stroke, 199 with hemorrhagic stroke and 150 asymptomatic controls were genotyped for eight GAS6 polymorphisms and other genetic markers in the same genome region. Association was measured by logistic regression analysis.The THESIAS program was used to measure linkage disequilibrium and haplotype frequencies. In univariate analysis, the GAS6 c.834+7AA genotype was found associated with decreased risk for stroke (OR: 0.59; 95%CI: 0.37–0.93).After adjustment for vascular risk factors, association was maintained when stroke subtypes affecting the microvasculature such as lacunar stroke and deep haemorrhage, were grouped together (OR: 0.44; 95%CI: 0.21–0.90). Furthermore, haplotype analysis revealed that association was even stronger when the c.834+7A allele was present in a specific haplotype (CACA) of four GAS6 polymorphisms. From these results we conclude that the A allele of the GAS6 c.834+7G>A polymorphism and more specifically, the CACA haplotype, is less prevalent in patients with stroke, suggesting a protective role for stroke of this haplotype.
Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot
Authors: Bagoly Zsuzsa , Haramura Gizella , Muszbek László 
Published: July 2007

SummaryActivated clotting factors are down-regulated by two major mechanisms which involve protease inhibitors or proteolytic degradation. To date, no down-regulating mechanism for activated factor XIII (FXIIIa) has been demonstrated. As the hemostatic plug contains polymorphonuclear granulocytes (PMNs) rich in proteolytic enzymes, we tested if these proteases are released in fibrin clots, and become involved in the down-regulation of FXIIIa.The supernatant of stimulated granulocytes proteolytically degraded and inactivated FXIIIa. In the fibrin clot formed from fibrinogen solution elastase, cathepsin G and matrix metalloprotease-9 (MMP-9) were released from granulocytes without any external stimulus. PMN proteases released in fibrin clot exerted a fibrinolytic effect and almost completely de-graded both FXIII subunits.The elastase inhibitor, ONO 5046, partially inhibited the proteolytic degradation of FXIII in PMNsupplemented fibrin clots. Cathepsin G and MMP-9 inhibitors provided less protection; in these cases intermediate split products accumulated.The proteolytic degradation of FXIII by PMNs was also significant when the clot was made from whole plasma. The main plasma protease inhibitor, α1-antitrypsin, provided only partial protection. In the fibrin clot which contained α1-antitrypsin FXIIIa was degraded by PMN proteases significantly faster than cross-linked fibrin.The results suggest that the degradation of FXIII subunits by the concerted action of PMN proteases released within the clot represents a novel mechanism for the down-regulation of FXIIIa.
Regulation of hyaluronan synthesis by vasodilatory prostaglandins
Authors: Schrör Karsten , Fischer Jens 
Published: July 2007

SummaryHyaluronan (HA) is a macromolecular polysaccharide of the vascular extracellular matrix that confers both structural functions as well as signalling activity. HA is involved in a wide variety of biological processes, such as tissue morphogenesis, malignant growth and metastasis, wound healing and angiogenesis. In atherosclerosis, HA associates with leukocytes and vascular smooth muscle cells (VSMC) and is involved in vascular remodelling. HA is synthesized at the plasma membrane by three HAsynthase isoforms (HAS1–3). Human VSMC upregulate HAS1 and HAS2 in response to prostaglandins via Gs-coupled prostaglandin receptor subtypes IP and EP2. This review discusses the regulation of HA-synthesis by prostaglandins and the evidence for a central role of cyclooxygenase-2/PGE2 in regulation of HAsynthesis during atherogenesis.
Thrombin generation in plasma of healthy adults and children: Chromogenic versus fluorogenic thrombogram analysis
Authors: Devreese Katrien , Wijns Walter , Combes Isabelle , Vankerckhoven Soetkin , Hoylaerts Marc 
Published: July 2007

SummaryCoagulation tests and coagulation factor assays have been complemented recently with experimental tests to measure the total amount of thrombin formed.We have presently analyzed thrombin generation of healthy adult and paediatric plasma samples via a fluorogenic and a chromogenic method.The chromogenic method was performed on the fully automated Behring Coagulation System® (BCS®) and fluorogenic assays via Calibrated Automated Thrombography ® (CAT),after coagulation induction by various tissue factor (TF) concentrations.Sample distribution and variability were analyzed for the four main coagulation parameters, derived via computerized curve analysis in each method. Results for both methods were correlated.At the recommended TF concentration (300 pM), thrombin generation via BCS was less variable than via CAT (1–6 pM), but at comparable TF concentrations (1–6 pM), the CAT sensitivity was higher than that of BCS. Inhibition of intrinsic coagulation with the anti-factor VIII antibody BO2C11 revealed that the BCS detected extrinsic coagulation exclusively, at all TF concentrations tested. In contrast, at low TF concentrations (1 and 2.5 pM), via CAT, intrinsic coagulation pathway amplification was measured. At standardizedTF concentrations (300 pM in BCS vs. 2.5 pM in CAT), different reference values between adults and children were found, for all parameters, except Tmax. In adult samples, the best correlation between both methods was observed for ETPCAT versus ETPBCS and for Peak heightCAT versus CmaxBCS, when thrombin generation was exclusively extrinsic (300 pM in BCS vs. 6 pM in CAT). In conclusion, differential thrombin generation characteristics in BCS and CAT are relevant for their clinical applicability.
Exotericism after Lessing: The Enduring Influence of F. H. Jacobi on Leo Strauss
Authors: Altman William 
Published: July 2007

AbstractThis study shows that despite the fact that Leo Strauss published little about Jacobi, the misunderstood thinker about whom he wrote his doctoral dissertation exercised a crucial influence on what is often thought to be Strauss's most enduring achievement: his rediscovery of exotericism. A consideration of several of Strauss's writings that do mention Jacobi but remained unpublished at the time of his death—in particular his studies on Moses Mendelssohn, who was Jacobi's principal target in the Pantheismusstreit—reveal that Strauss considered Jacobi to be an exoteric writer. Appropriately enough, it is only a Straussian-style reading of Strauss's claims that exotericism lapsed after Lessing's death that reveals Jacobi's influence between the lines. Some consideration is given to the question of why Strauss wrote about Jacobi in this secretive way.
Terrorism as a War Crime
Authors: Jodoin Sébastien 
Published: July 2007

AbstractInternational humanitarian law (IHL) defines terrorism in a prima facie apolitical manner as acts or threats of violence committed by either States or non-States against certain non-combatants with the primary purpose of terrorizing them. It thus leaves some space for the use of violence by parties to a conflict, all the while holding them to respect certain fundamental principles. This distinctive brand of moral pragmatism is ideally suited to meeting the normative and moral challenge of terrorism and could prove useful to international efforts geared toward the suppression of terrorism through its influence over discourse and through direct prosecutions of the war crime of terrorism. To be effective though, certain limitations tied to the use of IHL must be overcome, relating notably to its scope of application. As the primary purpose of IHL is the limitation of chaos and human suffering, it has the potential to address the anarchy and anguish caused by terrorism.
LTR retrotransposons in rice (Oryza sativa, L.): recent burst amplifications followed by rapid DNA loss
Authors: Vitte Clémentine , Panaud Olivier , Quesneville Hadi 
Published: July 2007

Abstract

Background
LTR retrotransposons are one of the main causes for plant genome size and structure evolution, along with polyploidy. The characterization of their amplification and subsequent elimination of the genomes is therefore a major goal in plant evolutionary genomics. To address the extent and timing of these forces, we performed a detailed analysis of 41 LTR retrotransposon families in rice.

Results
Using a new method to estimate the insertion date of both truncated and complete copies, we estimated these two forces more accurately than previous studies based on other methods. We show that LTR retrotransposons have undergone bursts of amplification within the past 5 My. These bursts vary both in date and copy number among families, revealing that each family has a particular amplification history. The number of solo LTR varies among families and seems to correlate with LTR size, suggesting that solo LTR formation is a family-dependent process. The deletion rate estimate leads to the prediction that the half-life of LTR retrotransposon sequences evolving neutrally is about 19 My in rice, suggesting that other processes than the formation of small deletions are prevalent in rice DNA removal.

Conclusion
Our work provides insights into the dynamics of LTR retrotransposons in the rice genome. We show that transposable element families have distinct amplification patterns, and that the turn-over of LTR retrotransposons sequences is rapid in the rice genome.
EDR2 negatively regulates salicylic acid-based defenses and cell death during powdery mildew infections of Arabidopsis thaliana
Authors: Vorwerk Sonja , Schiff Celine , Santamaria Marjorie , Koh Serry , Nishimura Marc , Vogel John , Somerville Chris , Somerville Shauna 
Published: July 2007

Abstract

Background
The hypersensitive necrosis response (HR) of resistant plants to avirulent pathogens is a form of programmed cell death in which the plant sacrifices a few cells under attack, restricting pathogen growth into adjacent healthy tissues. In spite of the importance of this defense response, relatively little is known about the plant components that execute the cell death program or about its regulation in response to pathogen attack.

Results
We isolated the edr2-6 mutant, an allele of the previously described edr2 mutants. We found that edr2-6 exhibited an exaggerated chlorosis and necrosis response to attack by three pathogens, two powdery mildew and one downy mildew species, but not in response to abiotic stresses or attack by the bacterial leaf speck pathogen. The chlorosis and necrosis did not spread beyond inoculated sites suggesting that EDR2 limits the initiation of cell death rather than its spread. The pathogen-induced chlorosis and necrosis of edr2-6 was correlated with a stimulation of the salicylic acid defense pathway and was suppressed in mutants deficient in salicylic acid signaling. EDR2 encodes a novel protein with a pleckstrin homology and a StAR transfer (START) domain as well as a plant-specific domain of unknown function, DUF1336. The pleckstrin homology domain binds to phosphatidylinositol-4-phosphate in vitro and an EDR2:HA:GFP protein localizes to endoplasmic reticulum, plasma membrane and endosomes.

Conclusion

EDR2 acts as a negative regulator of cell death, specifically the cell death elicited by pathogen attack and mediated by the salicylic acid defense pathway. Phosphatidylinositol-4-phosphate may have a role in limiting cell death via its effect on EDR2. This role in cell death may be indirect, by helping to target EDR2 to the appropriate membrane, or it may play a more direct role.
Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study
Authors: Forceville Xavier , Laviolle Bruno , Annane Djillali , Vitoux Dominique , Bleichner Gérard , Korach Jean-Michel , Cantais Emmanuel , Georges Hugues , Soubirou Jean-Louis , Combes Alain , Bellissant Eric 
Published: July 2007

Abstract
Introduction
Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients.

Methods
A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded.

Results
Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups.

Conclusion
Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844.
Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system
Authors: Von Stetina Stephen E , Watson Joseph D , Fox Rebecca M , Olszewski Kellen L , Spencer W Clay , Roy Peter J , Miller David M 
Published: July 2007

AbstractBackgroundWith its fully sequenced genome and simple, well-defined nervous system, the nematodeCaenorhabditis elegansoffers a unique opportunity to correlate gene expression with neuronal differentiation. The lineal origin, cellular morphology and synaptic connectivity of each of the 302 neurons are known. In many instances, specific behaviors can be attributed to particular neurons or circuits. Here we describe microarray-based methods that monitor gene expression inC. elegansneurons and, thereby, link comprehensive profiles of neuronal transcription to key developmental and functional properties of the nervous system.ResultsWe employed complementary microarray-based strategies to profile gene expression in the embryonic and larval nervous systems. In the MAPCeL (Microarray ProfilingC. eleganscells) method, we used fluorescence activated cell sorting (FACS) to isolate GFP-tagged embryonic neurons for microarray analysis. To profile the larval nervous system, we used the mRNA-tagging technique in which an epitope-labeled mRNA binding protein (FLAG-PAB-1) was transgenically expressed in neurons for immunoprecipitation of cell-specific transcripts. These combined approaches identified approximately 2,500 mRNAs that are highly enriched in either the embryonic or larvalC. elegansnervous system. These data are validated in part by the detection of gene classes (for example, transcription factors, ion channels, synaptic vesicle components) with established roles in neuronal development or function. Of particular interest are 19 conserved transcripts of unknown function that are also expressed in the mammalian brain. In addition to utilizing these profiling approaches to define stage-specific gene expression, we also applied the mRNA-tagging method to fingerprint a specific neuron type, the A-class group of cholinergic motor neurons, during early larval development. A comparison of these data to a MAPCeL profile of embryonic A-class motor neurons identified genes with common functions in both types of A-class motor neurons as well as transcripts with roles specific to each motor neuron type.ConclusionWe describe microarray-based strategies for generating expression profiles of embryonic and larvalC. elegansneurons. These methods can be applied to particular neurons at specific developmental stages and, therefore, provide an unprecedented opportunity to obtain spatially and temporally defined snapshots of gene expression in a simple model nervous system.
Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes
Authors: Baart Gino JE , Zomer Bert , de Haan Alex , van der Pol Leo A , Beuvery E Coen , Tramper Johannes , Martens Dirk E 
Published: July 2007

Abstract
Background
Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years.

Results
Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures.

Conclusion
The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.