Distribution by Scientific Domains

Kinds of XII

  • factor xii

  • Selected Abstracts

    Cyst-based toxicity tests XII,Development of a short chronic sediment toxicity test with the ostracod crustacean Heterocypris incongruens: Selection of test parameters

    Belgis Chial
    Abstract Experiments were carried out with neonates of the freshwater ostracod Heterocypris incongruens hatched from cysts in order to develop a new culture/maintenance-free solid-phase microbiotest for the toxicity assessment of contaminated sediments. Based on preliminary investigations, a number of test parameters were investigated for a short-chronic assay: hatching time, size of the cups of the multiwell test plates, feeding of the test organisms prior to the test, amount of supplemental algal food, volume of sediment, and duration of the test. On the basis of the findings, a test protocol was formulated for a 6-day assay in 12-cup multiwell plates with 10 organisms per cup and 3 replicates. The test organisms were collected 52 h after the start of the incubation of the cysts in standard freshwater at 25°C under continuous illumination after a 4-h prefeeding with 1.3 mg/mL Spirulina. The test biota in the cups were exposed to 300 ,L of test sediment in 2 mL of standard freshwater with 3 × 107 live algal cells (Raphidocelis subcapitata) as food supplement. Calibrated sand was used as a reference sediment. Mortality and growth of the ostracods were determined after 6 days' incubation at 25°C in darkness. The selected test parameters for the new microbiotest were found adequate for toxicity determination of natural sediments compared with the 10-day contact test with the amphipod Hyalella azteca. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 520,527, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10085 [source]

    Variability and divergence in Pongamia pinnata (L.) Pierre germplasm , a candidate tree for biodiesel

    GCB BIOENERGY, Issue 6 2009
    N. SUNIL
    Abstract Three explorations were undertaken in South East Coastal zone of India covering parts of Andhra Pradesh (AP) and Orissa states to collect Pongamia pinnata (L.) Pierre germplasm during March,June 2007. A total of 123 accessions were collected and seed data recorded were analyzed for morphometric traits viz., seed length, seed width, seed thickness, 100-seed weight and oil content. Variation in the collected germplasm was analyzed using anova, simple measures of variation and D2 statistics. Significant genetic variability between seed traits and oil content and association among the seed traits was recorded. Phenotypic variance was higher than genotypic variance for all the characters indicating dominant role of environment. High heritability (broad sense) for 100-seed weight (97.6%) and oil content (86.7%) indicated the reliability of these characters as selection criteria for plus trees. Genetic gain was maximum for 100-seed weight (62.6%) followed by oil content (30.5%). D2 analysis grouped the accessions into 12 clusters. Cluster XII and cluster IX were the most diverse based on the intercluster distance. Based on the observed diversity, Chittoor, Srikakulam and Adilabad districts of AP are most suitable for collecting diverse germplasm lines and also for in situ conservation. [source]

    Teaching and Learning Guide for: The Geopolitics of Climate Change

    Jon Barnett
    Author's Introduction Climate change is a security problem in as much as the kinds of environmental changes that may result pose risks to peace and development. However, responsibilities for the causes of climate change, vulnerability to its effects, and capacity to solve the problem, are not equally distributed between countries, classes and cultures. There is no uniformity in the geopolitics of climate change, and this impedes solutions. Author Recommends 1.,Adger, W. N., et al. (eds) (2006). Fairness in adaptation to climate change. Cambridge, MA: MIT Press. A comprehensive collection of articles on the justice dimensions of adaptation to climate change. Chapters discuss potential points at which climate change becomes ,dangerous', the issue of adaptation under the United Nations Framework Convention on Climate Change (UNFCCC), the unequal outcomes of adaptation within a society, the effects of violent conflict on adaptation, the costs of adaptation, and examples from Bangladesh, Tanzania, Botswana, and Hungary. 2.,Leichenko, R., and O'Brien, K. (2008). Environmental change and globalization: double exposures. New York: Oxford University Press. This book uses examples from around the world to show the way global economic and political processes interact with environmental changes to create unequal outcomes within and across societies. A very clear demonstration of the way vulnerability to environmental change is as much driven by social processes as environmental ones, and how solutions lie within the realm of decisions about ,development' and ,environment'. 3.,Nordås, R., and Gleditsch, N. (2007). Climate conflict: common sense or nonsense? Political Geography 26 (6), pp. 627,638. doi:10.1016/j.polgeo.2007.06.003 An up-to-date, systematic and balanced review of research on the links between climate change and violent conflict. See also the other papers in this special issue of Political Geography. 4.,Parry, M., et al. (eds) (2007). Climate change 2007: impacts adaptation and vulnerability. Contribution of Working Group II to the fourth assessment report of the intergovernmental panel on climate change. Cambridge, UK: Cambridge University Press. The definitive review of all the peer-reviewed research on the way climate change may impact on places and sectors across the world. Includes chapters on ecosystems, health, human settlements, primary industries, water resources, and the major regions of the world. All chapters are available online at http://www.ipcc.ch/ipccreports/ar4-wg2.htm 5.,Salehyan, I. (2008). From climate change to conflict? No consensus yet. Journal of Peace Research 45 (3), pp. 315,326. doi:10.1177/0022343308088812 A balanced review of research on the links between climate change and conflict, with attention to existing evidence. 6.,Schwartz, P., and Randall, D. (2003). An abrupt climate change scenario and its implications for United States national security. San Francisco, CA: Global Business Network. Gives insight into how the US security policy community is framing the problem of climate change. This needs to be read critically. Available at http://www.gbn.com/ArticleDisplayServlet.srv?aid=26231 7.,German Advisory Council on Global Change. (2007). World in transition: climate change as a security risk. Berlin, Germany: WBGU. A major report from the German Advisory Council on Global Change on the risks climate changes poses to peace and stability. Needs to be read with caution. Summary and background studies are available online at http://www.wbgu.de/wbgu_jg2007_engl.html 8.,Yamin, F., and Depedge, J. (2004). The International climate change regime: a guide to rules, institutions and procedures. Cambridge, UK: Cambridge University Press. A clear and very detailed explanation of the UNFCCC's objectives, actors, history, and challenges. A must read for anyone seeking to understand the UNFCCC process, written by two scholars with practical experience in negotiations. Online Materials 1.,Environmental Change and Security Program at the Woodrow Wilson International Center for Scholars http://www.wilsoncenter.org/ecsp The major website for information about environmental security. From here, you can download many reports and studies, including the Environmental Change and Security Project Report. 2.,Global Environmental Change and Human Security Project http://www.gechs.org This website is a clearing house for work and events on environmental change and human security. 3.,Intergovernmental Panel on Climate Change (IPCC) http://www.ipcc.ch/ From this website, you can download all the chapters of all the IPCC's reports, including its comprehensive and highly influential assessment reports, the most recent of which was published in 2007. The IPCC were awarded of the Nobel Peace Prize ,for their efforts to build up and disseminate greater knowledge about man-made (sic) climate change, and to lay the foundations for the measures that are needed to counteract such change'. 4.,Tyndall Centre for Climate Change Research http://www.tyndall.ac.uk The website of a major centre for research on climate change, and probably the world's leading centre for social science based analysis of climate change. From this site, you can download many publications about mitigation of and adaptation to climate change, and about various issues in the UNFCCC. 5.,United Nations Framework Convention on Climate Change http://unfccc.int/ The website contains every major document relation to the UNFCCC and its Kyoto Protocol, including the text of the agreements, national communications, country submissions, negotiated outcomes, and background documents about most key issues. Sample Syllabus: The Geopolitics of Climate Change topics for lecture and discussion Week I: Introduction Barnett, J. (2007). The geopolitics of climate change. Geography Compass 1 (6), pp. 1361,1375. United Nations Secretary General, Kofi Annan, address to the 12th Conference of Parties to the United Nations Framework Convention on Climate Change, Nairobi, 15 November 2006. Available online at http://www.unep.org/Documents.Multilingual/Default.asp?DocumentID=495&ArticleID=5424&l=en Week II: The History and Geography of Greenhouse Gas Emissions Topic: The drivers of climate change in space and time Reading Baer, P. (2006). Adaptation: who pays whom? In: Adger, N., et al. (eds) Fairness in adaptation to climate change. Cambridge, MA: MIT Press, pp. 131,154. Boyden, S., and Dovers, S. (1992). Natural-resource consumption and its environmental impacts in the Western World: impacts of increasing per capita consumption. Ambio 21 (1), pp. 63,69. Week III: The Environmental Consequences of climate change Topic: The risks climate change poses to environmental systems Reading Intergovernmental Panel on Climate Change. (2007). Climate change 2007: climate change impacts, adaptation and vulnerability: summary for policymakers. Geneva, Switzerland: IPCC Secretariat. Watch: Al Gore. The Inconvenient Truth. Weeks IV and V: The Social Consequences of Climate Change Topic: The risks climate change poses to social systems Reading Adger, W. N. (1999). Social vulnerability to climate change and extremes in coastal Vietnam. World Development 27, pp. 249,269. Comrie, A. (2007). Climate change and human health. Geography Compass 1 (3), pp. 325,339. Leary, N., et al. (2006). For whom the bell tolls: vulnerability in a changing climate. A Synthesis from the AIACC project, AIACC Working Paper No. 21, International START Secretariat, Florida. Stern, N. (2007). Economics of climate change: the Stern review. Cambridge, UK: Cambridge University Press (Chapters 3,5). Week VI: Mitigation of Climate Change: The UNFCCC Topic: The UNFCCC and the Kyoto Protocol Reading Najam, A., Huq, S., and Sokona, Y. (2003). Climate negotiations beyond Kyoto: developing countries concerns and interests. Climate Policy 3 (3), pp. 221,231. UNFCCC Secretariat. (2005). Caring for climate: a guide to the climate change convention and the Kyoto Protocol. Bonn, Germany: UN Framework Convention on Climate Change Secretariat. Weeks VII and VIII: Adaptation to Climate Change Topic: What can be done to allow societies to adapt to avoid climate impacts? Reading Adger, N., et al. (2007). Assessment of adaptation practices, options, constraints and capacity. In: Parry, M., et al. (eds) Climate change 2007: impacts, adaptation and vulnerability. Contribution of Working Group II to the fourth assessment report of the intergovernmental panel on climate change. Cambridge, UK: Cambridge University Press, pp. 717,744. Burton, I., et al. (2002). From impacts assessment to adaptation priorities: the shaping of adaptation policy. Climate Policy 2 (2,3), pp. 145,159. Eakin, H., and Lemos, M. C. (2006). Adaptation and the state: Latin America and the challenge of capacity-building under globalization. Global Environmental Change: Human and Policy Dimensions 16 (1), pp. 7,18. Ziervogel, G., Bharwani, S., and Downing, T. (2006). Adapting to climate variability: pumpkins, people and policy. Natural Resources Forum 30, pp. 294,305. Weeks IX and X: Climate Change and Migration Topic: Will climate change force migration? Readings Gaim, K. (1997). Environmental causes and impact of refugee movements: a critique of the current debate. Disasters 21 (1), pp. 20,38. McLeman, R., and Smit, B. (2006). Migration as adaptation to climate change. Climatic Change 76 (1), pp. 31,53. Myers, N. (2002). Environmental refugees: a growing phenomenon of the 21st century. Philosophical Transactions of the Royal Society 357 (1420), pp. 609,613. Perch-Nielsen, S., Bättig, M., and Imboden, D. (2008). Exploring the link between climate change and migration. Climatic Change (online first, forthcoming); doi:10.1007/s10584-008-9416-y Weeks XI and XII: Climate Change and Violent Conflict Topic: Will Climate change cause violent conflict? Readings Barnett, J., and Adger, N. (2007). Climate change, human security and violent conflict. Political Geography 26 (6), pp. 639,655. Centre for Strategic and International Studies. (2007). The age of consequences: the foreign policy and national security implications of global climate change. Washington, DC: CSIS. Nordås, R., and Gleditsch, N. (2007). Climate conflict: common sense or nonsense? Political Geography 26 (6), pp. 627,638. Schwartz, P., and Randall, D. (2003). An abrupt climate change scenario and its implications for United States national security. San Francisco, CA: Global Business Network. [online]. Retrieved on 8 April 2007 from http://www.gbn.com/ArticleDisplayServlet.srv?aid=26231 Focus Questions 1Who is most responsible for climate change? 2Who is most vulnerable to climate change? 3Does everyone have equal power in the UNFCCC process? 4Will climate change force people to migrate? Who? 5What is the relationship between adaptation to climate change and violent conflict? [source]

    Glomus jugulare tumor: Tumor control and complications after stereotactic radiosurgery

    Robert L. Foote MD
    Abstract Background We evaluated toxicity and long-term efficacy of stereotactic radiosurgery in patients with symptomatic or progressive glomus jugulare tumors. Methods Twenty-five consecutive patients (age, 30,88 years; 17 women, 8 men) who underwent stereotactic radiosurgery with the Leksell Gamma Knife (dose, 12,18 Gy) were prospectively followed. MRI and clinical examinations were performed at 6 months and 1, 2, and 3 years, and then every 2 years. Results None of the tumors increased in size, 17 were stable, and 8 decreased (median imaging follow-up, 35 months; range, 10,113 months). Symptoms subsided in 15 patients (60%); vertigo occurred in 1, but balance improved with vestibular training (median clinical follow-up, 37 months; range, 11,118 months). No other new or progressive neuropathy of cranial nerves V,XII developed. Conclusions Stereotactic radiosurgery can achieve excellent tumor control with low risk of morbidity in the treatment of glomus jugulare tumors. The lower cranial nerves can safely tolerate a radiosurgical dose of 12 to 18 Gy. © 2002 Wiley Periodicals, Inc. Head Neck 24: 332,339, 2002; DOI 10.1002/hed.10005 [source]

    Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix

    Stefan M. Willems
    Abstract Cellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and ECM. GNAS1 -activating mutations have been described in intramuscular myxoma, and lead to downstream activation of cFos. KRAS and TP53 mutations are commonly involved in sarcomagenesis whereby KRAS subsequently activates c-Fos. A well-documented series of intramuscular myxoma (three typical cases and seven cases of the more challenging cellular variant) and grade I myxofibrosarcoma (n= 10) cases were karyotyped, analyzed for GNAS1, KRAS and TP53 mutations and downstream activation of c-Fos mRNA and protein expression. ECM was studied by liquid chromatography mass spectrometry and expression of proteins identified was validated by immunohistochemistry and qPCR. Grade I myxofibrosarcoma showed variable, non-specific cyto-genetic aberrations in 83,5% of cases (n= 6) whereas karyotypes of intramuscular myxoma were all normal (n= 7). GNAS1 -activating mutations were exclusively found in 50% of intramuscular myxoma. Both tumour types showed over-expression of c-Fos mRNA and protein. No mutations in KRAS codon 12/13 or in TP53 were detected. Liquid chromatography mass spectrometry revealed structural proteins (collagen types I, VI, XII, XIV and decorin) in grade I myxofibrosarcoma lacking in intramuscular myxoma. This was confirmed by immunohistochemistry and qPCR. Intramuscular/cellular myxoma and grade I myxofibrosarcoma show different molecular genetic aberrations and different composition of their ECM that probably contribute to their diverse clinical behaviour. GNAS1 mutation analysis can be helpful to distinguish intramuscular myxoma from grade I myxofibrosarcoma in selected cases. [source]

    Elementary concepts of medicine: XII.

    Specialties of medicine, genuine, other

    Neural plasticity of neonatal hypoglossal nerve for effective suckling

    Nanae Fukushima
    Abstract The adaptive movement of the tongue after unilateral lesion of the hypoglossal (XII) nerve during the early postnatal days is essential for recovery of milk intake. The present study investigated the basic mechanisms underlying such adaptation, focusing on the neural plasticity that allows effective suckling. After resection of the ipsilateral XII nerve on P1, 1,1,-dioctadecyl-3,3,3,,3,-tetramethylindocarbocyanine perchlolate (DiI), a postmortem neuronal tracer, was applied to the contralateral uninjured XII nerve on P4 and P7. DiI-labeled fibers were traced successfully within the tongue and showed gradually increased extension over the XII nerve-injured side in the central core portion of the denervated tongue between P4 and P7. Systematic neuroanatomic experiments showed that contralateral axonal sprouting occurred as early as 1 day after nerve injury (P2), and that such axonal sprouting occurred exclusively from the medial branch of the XII nerve responsible for tongue protrusion, an essential movement for suckling. These findings provide direct evidence of functional neural plasticity that allows effective suckling in XII nerve-injured newborns with suckling disturbance. © 2007 Wiley-Liss, Inc. [source]

    Involvement of the contact phase and intrinsic pathway in herpes simplex virus-initiated plasma coagulation

    Summary.,Background:,A hemostatic response to vascular injury is initiated by the extrinsic pathway of coagulation and amplified by the intrinsic pathway. We previously reported that purified herpes simplex virus type-1 (HSV1) has constitutive extrinsic pathway tissue factor (TF) and anionic phospholipid on its surface derived from the host cell, and can consequently bypass strict cellular control of coagulation. Objective:,The current work addresses the hypothesis that HSV1-induced plasma coagulation also involves intrinsic pathway, factor VIII (FVIII), and upstream contact activation pathway, factor XII (FXII). Results:,HSV1-initiated clotting was accelerated when purified FVIII was added to FVIII-deficient plasma and in normal plasma attenuated by an inhibitory anti-FVIII antibody (Ab). High HSV1 concentrations predictably reduced the effect of FVIII due to the availability of excess viral TF. To further define TF-independent clotting mechanisms initiated by HSV1, the extrinsic pathway was disabled using factor VII-deficient plasma. The intrinsic pathway is triggered by activation of FXII associated with surface-bound kallikrein, which subsequently activates factor XI. Here we found that an inhibitor of activated FXII, corn trypsin inhibitor, and anti-FXII, anti-kallikrein and anti-FXI Abs inhibited HSV1-initiated clotting. HSV1-enhanced activation of purified FXII was confirmed by Western blot, but required prekallikrein. Conclusion:,The current work shows that HSV1 can trigger and amplify coagulation through the contact phase and intrinsic pathway, and suggests an additional mechanism that may contribute to vascular pathology. [source]

    Distinct C-terminus of the B subunit of factor XIII in a population-associated major phenotype: the first case of complete allele-specific alternative splicing products in the coagulation and fibrinolytic systems

    H. IWATA
    Summary.,Objectives: The purpose of this study was to elucidate the molecular bases of the heterogeneity of the B subunit of coagulation factor XIII (FXIII-B), classified by isoelectric focusing into its three population-associated major phenotypes. Methods and Results: By genetic sequencing and polymerase chain reaction (PCR),restriction fragment length polymorphism analyses, a C-to-G change was identified in intron K for the Asian-associated major phenotype FXIII-B*3. A transcript containing the novel exon XII, was detected by reverse transcription PCR using hepatocyte cell lines with this allele. The exclusive existence of a novel C-terminal peptide in a homozygote of FXIII-B*3 was also detected by matrix-assisted laser-desorption ionization time of flight mass spectrometry. The FXIII-B*3 isoform had a C-terminus 15 residues longer than the other isoforms, containing two additional basic amino acids and one extra acidic amino acid. Accordingly, the C-to-G nucleotide substitution created an efficient splice acceptor AG dinucleotide, which resulted in allele-specific alternative splicing in intron K. When compared with FXIII-B*1, the third major phenotype, FXIII-B*2, had an A-to-G change in exon III, converting His95 to Arg, and a rare phenotype, FXIII-B*4, had an A-to-T change in exon VII, converting Glu368 to Val. Conclusions: We found an extremely rare event of complete allele-specific alternative splicing for FXIII-B. The FXIII-B*3 isoform had a distinct C-terminal peptide, while the FXIII-B*2 and FXIII-B*4 isoforms had His95 to Arg and Glu368 to Val substitutions, respectively, which led to differential isoelectric points of these isoforms. Such variations in the amino acid sequence of FXIII-B may have profound effects on its structure,function relationship, plasma FXIII levels, and disease susceptibility. [source]

    Factor XI deficiency in animal models

    T. RENNÉ
    Summary., The blood coagulation system forms fibrin to limit blood loss from sites of injury, but also contributes to occlusive diseases such as deep vein thrombosis, myocardial infarction, and stroke. In the current model of a coagulation balance, normal hemostasis and thrombosis represent two sides of the same coin; however, data from coagulation factor XI-deficient animal models have challenged this dogma. Gene targeting of factor XI, a serine protease of the intrinsic pathway of coagulation, severely impairs arterial thrombus formation but is not associated with excessive bleeding. Mechanistically, factor XI may be activated by factor XII following contact activation or by thrombin in a feedback activation loop. This review focuses on the role of factor XI, and its deficiency states as novel target for prevention of thrombosis with low bleeding risk in animal models. [source]

    The antigenic binding site(s) of antibodies to factor XII associated with the antiphospholipid syndrome

    S. L. HARRIS
    Summary., Phospholipid binding proteins, including factor XII (FXII), are known to be targeted by antiphospholipid antibodies (aPA). Factor XII antibodies (FXIIab) have been described in some patients with the antiphospholipid syndrome (APS) and have been shown to lead to reduced levels of FXII. The antigenic binding site(s) and the pathophysiological effects of FXIIab are unknown. In an attempt to elucidate the binding site of these antibodies, immobilized plasma kallikrein was used to cleave FXII into its 52-kDa heavy-chain (HCFXII) and 28-kDa light-chain (LCFXII) components. Plasma samples from 12 female patients with definite APS and FXIIab were investigated for the presence of antibodies to FXII, HCFXII and LCFXII. All but one patient's plasma reacted to FXII, HCFXII and LCFXII in a similar manner. One patient gave markedly reduced positivity to HCFXII and LCFXII, suggesting that the FXIIab in this patient had a higher affinity for the intact FXII molecule. To further investigate the antigenic binding site(s) of FXII, 150 biotinylated peptides of the known FXII sequence were synthesized using a MultipinTM peptide synthesis procedure. The IgG and IgM fractions of the 12 patients' plasma were purified by affinity chromatography. The synthesized peptides were captured on streptavidin plates and individual patients' purified FXIIab assayed against the peptides in a modified enzyme-linked immunosorbent assay (ELISA). Two regions were identified as possible antigenic binding site(s) for FXIIab: one in the growth factor domain and the other in the catalytic domain. [source]

    Assessment of the role of heparan sulfate in high molecular weight kininogen binding to human umbilical vein endothelial cells

    L.P. Fernando
    Summary., The assembly and activation of the kinin forming system components on human umbilical vein endothelial cells (HUVEC) have been studied in great detail. Proteins such as gC1qR, cytokeratin-1 and u-PAR have been identified to be responsible for Zn2+ -dependent binding of high molecular weight kininogen (HK) to HUVEC. Heparan sulfate has also been shown to have a major role in Zn2+ -dependent binding of HK to the endothelial cell line, Ea.hy 926. In this study, we have analyzed the possible contribution of heparan sulfate to high molecular weight kininogen binding to HUVEC using multiple approaches. The presence of heparan sulfate on HUVEC was analyzed by staining with an antibody specific for heparan sulfate. Incubation of the cells with bacterial heparinases removed the heparan sulfate from the cell surface to the level seen with a control antibody, however, the Zn2+ -dependent binding of HK was not affected. Further, blocking of heparan sulfate with a specific antibody to heparan sulfate even after digestion with heparinases did not reduce HK binding whereas antibodies to the proteins gC1qR and cytokeratin-1 consistently reduced the binding of HK to the endothelial cells. The binding intensities of FITC-labeled HK were similar in heparinase-treated and -untreated HUVEC. The rate of kallikrein formation by the assembly of factor XII, HK and PK were similar in both heparinase-treated and non-treated HUVEC. All of these data indicate that heparan sulfate does not contribute significantly to HK binding to HUVEC. [source]

    Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasma

    H. Herwald
    Summary., Invasive and toxic infections caused by Streptococcus pyogenes are connected with high morbidity and mortality. Typical symptoms of these infections are hypotension, edema formation, tissue necrosis, and bleeding disorders. Here we report that components of the coagulation system including fibrinogen, factors V, XI, and XII, and H-kininogen, are assembled at the surface of S. pyogenes through specific interactions with bacterial surface proteins. In plasma environment, absorption of fibrinogen by S. pyogenes causes a hypocoagulatory state resulting in prolonged clotting times and impaired fibrin network formation. Moreover, the binding of coagulation factors and the subsequent activation of the coagulation system at the bacterial surface lead to the formation of a fibrin network covering S. pyogenes bacteria adhering to epithelial cells. The results suggest that interactions between S. pyogenes and components of the coagulation system contribute to some of the symptoms seen in severe infections caused by this important human pathogen. [source]

    Sulfamates and their therapeutic potential

    Jean-Yves Winum
    Abstract Starting from the very simple molecule sulfamic acid, O -substituted-, N -substituted-, or di-/tri-substituted sulfamates may be obtained, which show specific biological activities which were or started to be exploited for the design of many types of therapeutic agents. Among them, sulfamate inhibitors of aminoacyl-tRNA synthetases (aaRSs) were recently reported, constituting completely new classes of antibiotics, useful in the fight of drug-resistant infections. Anti-viral agents incorporating sulfamate moieties have also been obtained, with at least two types of such derivatives investigated: the nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitors, and the HIV protease inhibitors (PIs). In the increasing armamentarium of anti-cancer drugs, the sulfamates occupy a special position, with at least two important targets evidenced so far: the steroid sulfatases (STSs) and the carbonic anhydrases (CAs). An impressing number of inhibitors of STSs of the sulfamate type have been reported in the last years, with several compounds, such as 667COUMATE among others, progressing to clinical trials for the treatment of hormone-dependent tumors (breast and prostate cancers). This field is rapidly evolving, with many types of new inhibitors being constantly reported and designed in such a way as to increase their anti-tumor properties, and decrease undesired features (for example, estrogenicity, a problem encountered with the first generation such inhibitors, such as EMATE). Among the many isozymes of CAs, at least two, CA IX and CA XII, are highly overexpressed in tumors, being generally absent in the normal tissues. Inhibition of tumor-associated CAs was hypothesized to lead to novel therapeutic approaches for the treatment of cancer. Many sulfamates act as very potent (low nanomolar) CA inhibitors. The X-ray crystal structure of the best-studied isozyme, CA II, with three sulfamates (sulfamic acid, topiramate, and EMATE) has recently been reported, which allowed for a rationale drug design of new inhibitors. Indeed, low nanomolar CA IX inhibitors of the sulfamate type have been reported, although such compounds also act as efficient inhibitors of isozymes CA I and II, which are not associated with tumors. A large number of anti-convulsant sulfamates have been described, with one such compound, topiramate, being widely used clinically as anti-epileptic drug. By taking into consideration a side effect of topiramate, an anti-epileptic drug leading to weight loss in some patients, it has recently been proposed to use this drug and related sulfamates for the treatment of obesity. The rationale of this use is based on the inhibition of the mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were also shown to possess potent inhibitory activity against acyl coenzyme A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One such agent, avasimibe, is in advanced clinical trials for the treatment of hyperlipidemia and atherosclerosis. Thus, the sulfamate moiety offers very attractive possibilities for the drug design of various pharmacological agents, which are on one hand due to the relative ease with which such compounds are synthesized, and on the other one, due to the fact that biological activity of most of them is impressive. © 2004 Wiley Periodicals, Inc. [source]

    Diversity of staphylocoagulase and identification of novel variants of staphylocoagulase gene in Staphylococcus aureus

    Marie Kinoshita
    ABSTRACT Staphylocoagulase (SC) is a major phenotypic determinant of Staphylococcus aureus. Serotype of SC (coagulase type) is used as an epidemiological marker and 10 types (I,X) have been discriminated so far. To clarify genetic diversity of SC within a single and among different serotype(s), we determined approximately 1500 bp-nucleotide sequences of SC gene encoding D1, D2, and central regions (N-terminal half and central regions of SC; SCNC) for a total of 33 S. aureus strains comprising two to three strains from individual coagulase types (I,VIII, X) and 10 strains which were not determined as previously known SC serotypes (ND-strains). Amino acid sequence identities of SCNC among strains with a single coagulase type of II, III, IV, V, VI and X were extremely high (more than 99%), whereas lower identity (56,87%) was observed among different types. In contrast, within a single coagulase type of I, VII, or VIII, sequence divergence was found (lowest identity; 82%). SCNC sequences from the ND-strains were discriminated into two genetic groups with an identity of 71% to each other (tentatively assigned to genotypes [XI] and [XII]), and exhibited less than 86% sequence identities to those of most known coagulase types. All the types [XI] and [XII] strains were methicillin susceptible and belonged to different sequence types from those of coagulase types I,X strains reported so far by multilocus sequence typing. These findings indicated genetic heterogeneity of SC in coagulase types I, VII, and VIII strains, and the presence of two novel SC genotypes related to antigenicity of SC serotypes. [source]

    Expression of genes associated with allantois emergence in ovine and bovine conceptuses

    A.M. Ledgard
    Abstract In the development of ruminant embryos, the emergence and growth of the allantois is critical for the establishment of the chorioallantoic placenta. The allantoic membrane contributes to all the vasculature that perfuses the placental tissues and the fetal membranes. Using suppressive subtractive hybridization to compare mRNA from Day 13 ovine preimplantation conceptuses (prior to allantoic emergence) with Day 17 allantoic membrane, we identified nine genes whose expression was associated with the emergence of the allantoic sac. Collagen alpha 1 type XII, collagen alpha 2 type I, collagen alpha 2 type V, epsilon 4 beta-globin, osteonectin, and uroplakin were expressed at significantly greater levels in ovine Day 17 allantois compared to Day 13 conceptuses. These genes are associated with the extracellular matrix and most likely are involved in establishing and strengthening the structural integrity of the allantoic sac and in the development of the blood vessels. RalB expression increased with development although at significantly greater levels in the allantois only at Day 19. Hoxa-10 and RhoA showed no differential expression during this period. All these genes showed a similar temporal pattern of expression in bovine conceptuses at equivalent stages of development with significantly greater expression of all these genes, except for Hoxa-10, found in Day 24 allantois compared to Day 14 conceptuses. This suggests that the role they play in allantoic emergence, growth and function is conserved in both ruminant species and that their expression is regulated in a similar manner. The interactions and regulation of this process remains to be fully explained. Mol. Reprod. Dev. 1084,1093, 2006. © 2006 Wiley-Liss, Inc. [source]

    XII,The Argument from Resentment

    R. Jay Wallace
    Moral philosophers commonly deploy a strategy of hypothetical role reversal to show that morality is a source of reasons for everyone. Agents who are prepared to wrong another are invited to put themselves in their prospective victim's shoes; the agents concede that they would resent being treated in this way; and the conclusion is drawn that they themselves have reason not to wrong their prospective victims after all. The paper offers a reconstruction and defence of this argument from resentment. The argument, on the interpretation proposed, has an essentially deliberative structure; it does not attempt to extract a normative conclusion from metaethical premisses, but to elicit first-order normative convictions that are latent in the interlocutor's outlook. [source]

    Louis XII and the porcupine: transformations of a royal emblem

    N Hochner
    Louis XII, king of France (r. 1498,1515), inherited the emblem of the porcupine from his grandfather and maintained its symbolism of invincibility to particular effect in the circumstances of the Italian wars and the reconquest of the Milanese. However, the bellicose role of the porcupine within royal propaganda became increasingly less adequate to the image of a ,père du peuple' that Louis XII adopted in 1506. This study argues through detailed analysis of medals, royal entries, illuminated manuscripts, and other resource material that a certain disenchantment was felt towards the aggressive porcupine leading to its relative neglect in royal pageantry and iconography by the second half of Louis's reign. This shift is indicative of a deeper hesitancy between the image of paternal care , faithful to the duty of the Most Christian King , and the image of paternal care , faithful to the duty of the Most Christian King , and the image of glorious triumph , more suited to a bellicose warrior. The transformations undergone by the porcupine reveal the desire to redefine the very notion of the duty of kingship. [source]

    Preservation of segmental hindbrain organization in adult frogs

    Hans Straka
    Abstract To test for possible retention of early segmental patterning throughout development, the cranial nerve efferent nuclei in adult ranid frogs were quantitatively mapped and compared with the segmental organization of these nuclei in larvae. Cranial nerve roots IV,X were labeled in larvae with fluorescent dextran amines. Each cranial nerve efferent nucleus resided in a characteristic segmental position within the clearly visible larval hindbrain rhombomeres (r). Trochlear motoneurons were located in r0, trigeminal motoneurons in r2,r3, facial branchiomotor and vestibuloacoustic efferent neurons in r4, abducens and facial parasympathetic neurons in r5, glossopharyngeal motoneurons in r6, and vagal efferent neurons in r7,r8 and rostral spinal cord. In adult frogs, biocytin labeling of cranial nerve roots IV,XII and spinal ventral root 2 in various combinations on both sides of the brain revealed precisely the same rostrocaudal sequence of efferent nuclei relative to each other as observed in larvae. This indicates that no longitudinal migratory rearrangement of hindbrain efferent neurons occurs. Although rhombomeres are not visible in adults, a segmental map of adult cranial nerve efferent nuclei can be inferred from the strict retention of the larval hindbrain pattern. Precise measurements of the borders of adjacent efferent nuclei within a coordinate system based on external landmarks were used to create a quantitative adult segmental map that mirrors the organization of the larval rhombomeric framework. Plotting morphologically and physiologically identified hindbrain neurons onto this map allows the physiological properties of adult hindbrain neurons to be linked with the underlying genetically specified segmental framework. J. Comp. Neurol. 494:228,245, 2006. © 2005 Wiley-Liss, Inc. [source]

    Reckoning with Daniel J. Goldhagen's Views on the Roman Catholic Church, the Holocaust, and Pope Pius XII

    Vincent A. LapomardaArticle first published online: 1 DEC 200

    XII,Middle East, Asia, Australia, New Zealand and the Pacific Islands

    Siobhan Lambert-Hurley
    First page of article [source]

    2,4-Di­nitro­phenyl­hydrazones of 2,4-di­hydroxy­benz­aldehyde, 2,4-di­hydroxy­aceto­phenone and 2,4-di­hydroxy­benzo­phenone

    Russell G. Baughman
    In 2,4-di­hydroxy­benz­aldehyde 2,4-di­nitro­phenyl­hydrazone N,N -di­methyl­form­amide solvate {or 4-[(2,4-di­nitro­phenyl)­hydrazono­methyl]­benzene-1,3-diol N,N -di­methyl­form­amide solvate}, C13H10N4O6·C3H7NO, (X), 2,4-di­hydroxy­aceto­phenone 2,4-di­nitro­phenyl­hydrazone N,N -di­methyl­form­am­ide solvate (or 4-{1-[(2,4-di­nitro­phenyl)hydrazono]ethyl}benzene-1,3-diol N,N -di­methyl­form­amide solvate), C14H12N4O6·C3H7NO, (XI), and 2,4-di­hydroxy­benzo­phenone 2,4-di­nitro­phenyl­hydrazone N,N -di­methyl­acet­amide solvate (or 4-­{[(2,4-di­nitro­phenyl)hydrazono]phenyl­methyl}benzene-1,3-diol N,N -di­methyl­acet­amide solvate), C19H14N4O6·C4H9NO, (XII), the molecules all lack a center of symmetry, crystallize in centrosymmetric space groups and have been observed to exhibit non-linear optical activity. In each case, the hydrazone skeleton is fairly planar, facilitated by the presence of two intramolecular hydrogen bonds and some partial N,N double-bond character. Each molecule is hydrogen bonded to one solvent mol­ecule. [source]

    New insights into hereditary angio-oedema: Molecular diagnosis and therapy

    Nikoletta Nagy
    ABSTRACT Hereditary angio-oedema (HAE) is a rare but potentially life-threatening condition. Three types are now recognized. Types I and II HAE involve mutations in the C1NH (SERPING1) gene, encoding the C1 inhibitor protein, whereas type III HAE involves mutations in the F12 gene, encoding coagulation factor XII (Hageman factor). They share a common final pathway leading to increased bradykinin formation. HAE must be distinguished from acquired angio-oedema with C1 esterase inhibitor deficiency, angiotensin-converting enzyme inhibitor-induced angio-oedema and the much more common histaminergic angio-oedema, occurring with or without weals. Understanding the pathogenesis of HAE is leading to the introduction of new therapies that target the bradykinin receptor or inhibit kallikrein activity, innovations that will hopefully reduce morbidity and mortality in this group of severe genetic disease. [source]

    Oszillierende Weltmodelle versus Urknallmodelle.

    Das oszillierende Weltmodell Friedmanns, die Ablehnung der Anfangssingularität durch russische Kosmologen und die Zustimmung der katholischen Kirche zur Urknalltheorie Lemaîtres und Hawkings
    Abstract The Russian mathematician and physicist Friedmann and the Belgian priest and physicist Lemaître were the first to consider non-static world models in the framework of Einstein's general theory of relativity. Friedmann seemed to favour a periodic, oscillating cosmological model. His investigations were taken up by Russian cosmologists in the 1960s. They stated that the singularities present in many of the Friedmann-Lemaître cosmological models seemed to be artificial and were ascribed to the assumption of a highly symmetric distribution of cosmic matter. Their disapproval of singularities seems to be in accord with Soviet ideological requirements during that time like atheism and dialectic materialism. They had to retract their statements after Hawking had proved his singularity theorems and after the microwave background had been discovered. Hawking followed the line of thought which was initiated by Lemaître in the early 1930s. Lemaître had combined for the first time quantum physics and relativistic cosmology and had developed his idea of the primeval atom, a beginning of the universe in a dense state with just one quantum containing the whole mass of the universe. Pope Pius XII brought together this primeval atom and God as the Creator of the universe and declared in 1951 that big bang cosmology is compatible with the Bible. Not surprisingly Hawking was awarded the Pius XI medal by the Vatican in 1975 for his contributions to big bang cosmology. [source]

    Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII

    D. W. Jones
    Antibodies to factor XII (FXII) have previously been identified in some patients who were lupus anti-coagulant-positive. The relationship between these antibodies and FXII levels appeared to be variable. The aim of the present study was to confirm the presence of antibodies to FXII in patients with well characterized antiphospholipid syndrome (APS) and to establish their potential effect on levels of FXII. Forty-two patients with APS were studied; 21 patients were found to have either immunoglobulin (Ig)G or IgM antibodies to FXII by enzyme-linked immunosorbent assay (ELISA) using a highly purified preparation of FXII (> 99% pure). Levels of FXII were statistically significantly lower (P = 0·02) in patients with antibodies to FXII when compared with patients without antibodies to FXII (median = 91 ,/dl, s.d. = 39·1, median = 122 ,/dl, s.d. = 41·1 respectively). Four of the 21 patients with antibodies to FXII were found to have FXII levels below the laboratory normal range. Antibodies to FXII are present in significant numbers of patients with APS and may lead to acquired FXII deficiency. [source]

    ChemInform Abstract: 3,5-Disubstituted 6H-Pyrrolo[1,2-c][1,2,3]triazoles (VII), (XII) from Morita,Baylis,Hillman Adducts of Propargyl Aldehydes.

    CHEMINFORM, Issue 39 2010
    Sun Pil Park
    No abstract is available for this article. [source]

    ChemInform Abstract: Polarity and Chirality in Uranyl Borates: Insights into Understanding the Vitrification of Nuclear Waste and the Development of Nonlinear Optical Materials.

    CHEMINFORM, Issue 33 2010
    Shuao Wang
    Abstract The compounds (IV,VII) and (IX,XII) are synthesized with various Na(Tl):U:B molar ratios using H3BO3 as a reactive flux, and their structures are determined by single crystal XRD. [source]

    ChemInform Abstract: Unprecedented SnCl2×2H2O-Mediated Intramolecular Cyclization of Nitroarenes via C,N Bond Formation: A New Entry to the Synthesis of Cryptotackieine (XII) and Related Skeletons.

    CHEMINFORM, Issue 11 2009
    Sunil Sharma
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

    Synthesis and Antimicrobial Activity of 5-Amino-2,7-diaryl-6-cyano-3-isonicotinamidothiazolo [4,5-b]-2,3,4,7-tetrahydropyridines (VIII), 2,7-Diaryl-6-cyano-3-isonicotinamidothiazolo [4,5-b]-2,3,4,5,6,7-hexahydropyrid-5-ones (X), 2,7-Diaryl-5-amino-3-isonicotinamidothiazolo[4,5-d][1,3-]thiazines (XII) and 2,6-Diaryl-3-isonicotinamidthiazolo[4,5-c]pyrazolines (XIII).

    CHEMINFORM, Issue 22 2007
    Mukhtar Hussain Khan
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]

    Transformation of 4-Aryl(heteryl)-2,6-diamino-3,5-dicyano-4H-thiopyrans into Substituted Acrylonitriles (III), (VI), 1,4-Dihydropyridines (X), 2,3,4,7-Tetrahydrothiazolo[3,2-a]pyridine (XII), and 4,7-Dihydrothieno[2,3-b]pyridine (XV).

    CHEMINFORM, Issue 43 2006
    V. D. Dyachenko
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]