480 research outputs found

    Principal series of finite subgroups of SU(3)

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    We attempt to give a complete description of the "exceptional" finite subgroups Sigma(36x3), Sigma(72x3) and Sigma(216x3) of SU(3), with the aim to make them amenable to model building for fermion masses and mixing. The information on these groups which we derive contains conjugacy classes, proper normal subgroups, irreducible representations, character tables and tensor products of their three-dimensional irreducible representations. We show that, for these three exceptional groups, usage of their principal series, i.e. ascending chains of normal subgroups, greatly facilitates the computations and illuminates the relationship between the groups. As a preparation and testing ground for the usage of principal series, we study first the dihedral-like groups Delta(27) and Delta(54) because both are members of the principal series of the three groups discussed in the paper.Comment: 43 pages, no figures; typos corrected, clarifications and references added, version matches publication in J. Phys.

    Embelin binds to human neuroserpin and impairs its polymerisation

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    Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain

    Cardiogenesis with a focus on vasculogenesis and angiogenesis

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    The initial intraembryonic vasculogenesis occurs in the cardiogenic mesoderm. Here, a cell population of proendocardial cells detaches from the mesoderm that subsequently generates the single endocardial tube by forming vascular plexuses. In the course of embryogenesis, the endocardium retains vasculogenic, angiogenic and haematopoietic potential. The coronary blood vessels that sustain the rapidly expanding myocardium develop in the course of the formation of the cardiac loop by vasculogenesis and angiogenesis from progenitor cells of the proepicardial serosa at the venous pole of the heart as well as from the endocardium and endothelial cells of the sinus venosus. Prospective coronary endothelial cells and progenitor cells of the coronary blood vessel walls (smooth muscle cells, perivascular cells) originate from different cell populations that are in close spatial as well as regulatory connection with each other. Vasculo‐ and angiogenesis of the coronary blood vessels are for a large part regulated by the epicardium and epicardium‐derived cells. Vasculogenic and angiogenic signalling pathways include the vascular endothelial growth factors, the angiopoietins and the fibroblast growth factors and their receptors

    Π’Π›Π˜Π―ΠΠ˜Π• Π­ΠšΠ ΠΠΠžΠ’ НА Π ΠΠ‘ΠŸΠ Π•Π”Π•Π›Π•ΠΠ˜Π― Π˜ΠœΠŸΠ£Π›Π¬Π‘ΠΠ«Π₯ ΠœΠΠ“ΠΠ˜Π’ΠΠ«Π₯ ΠŸΠžΠ›Π•Π™ ПРИ Π’Π ΠΠΠ‘ΠšΠ ΠΠΠ˜ΠΠ›Π¬ΠΠžΠ™ ΠœΠΠ“ΠΠ˜Π’ΠΠžΠ™ Π‘Π’Π˜ΠœΠ£Π›Π―Π¦Π˜Π˜

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    The article is devoted to an experimental test on the distribution of the pulse magnetic field’s range and how various screens influence it.ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½ΠΎΠ΅ исслСдованиС распрСдСлСния Π°ΠΌΠΏΠ»ΠΈΡ‚ΡƒΠ΄Ρ‹ ΠΈΠΌΠΏΡƒΠ»ΡŒΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π³Π½ΠΈΡ‚Π½ΠΎΠ³ΠΎ поля ΠΈ влияниС Π½Π° Π½Π΅Π³ΠΎ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… экранов

    General symptom reporting in female fibromyalgia patients and referents: a population-based case-referent study

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    <p>Abstract</p> <p>Background</p> <p>Fibromyalgia is characterized by widespread musculoskeletal pain and palpation tenderness. In addition to these classic symptoms, fibromyalgia patients tend to report a number of other complaints. What these other complaints are and how often they are reported as compared with related referents from the general population is not very well known. We therefore hypothesized that subjects with fibromyalgia report more of a wide range of symptoms as compared with referents of the same sex and age from the general population.</p> <p>Methods</p> <p>138 women with diagnosed fibromyalgia in primary health care and 401 referents from the general population matched to the cases by sex, age and residential area responded to a postal questionnaire where information on marital status, education, occupational status, income level, immigrant status, smoking habits physical activity, height and weight history and the prevalence of 42 defined symptoms was sought.</p> <p>Results</p> <p>The cases had lower educational and income levels, were more often unemployed, on sick leave or on disability pension and were more often first generation immigrants than the referents. They were also heavier, shorter and more often had a history of excessive food intake and excessive weight loss. When these differences were taken into account, cases reported not only significantly more presumed fibromyalgia symptoms but also significantly more of general symptoms than the referents. The distribution of symptoms was similar in subjects with fibromyalgia and referents, indicating a generally higher symptom reporting level among the former.</p> <p>Conclusion</p> <p>Subjects with fibromyalgia had a high prevalence of reported general symptoms than referents. Some of these differences may be a consequence of the disorder while others may reflect etiological processes.</p

    Cardiomyocyte Specific Ablation of p53 Is Not Sufficient to Block Doxorubicin Induced Cardiac Fibrosis and Associated Cytoskeletal Changes

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    Doxorubicin (Dox) is an anthracycline used to effectively treat several forms of cancer. Unfortunately, the use of Dox is limited due to its association with cardiovascular complications which are manifested as acute and chronic cardiotoxicity. The pathophysiological mechanism of Dox induced cardiotoxicity appears to involve increased expression of the tumor suppressor protein p53 in cardiomyocytes, followed by cellular apoptosis. It is not known whether downregulation of p53 expression in cardiomyocytes would result in decreased rates of myocardial fibrosis which occurs in response to cardiomyocyte loss. Further, it is not known whether Dox can induce perivascular necrosis and associated fibrosis in the heart. In this study we measured the effects of acute Dox treatment on myocardial and perivascular apoptosis and fibrosis in a conditional knockout (CKO) mouse model system which harbours inactive p53 alleles specifically in cardiomyocytes. CKO mice treated with a single dose of Dox (20 mg/kg), did not display lower levels of myocardial apoptosis or reactive oxygen and nitrogen species (ROS/RNS) compared to control mice with intact p53 alleles. Interestingly, CKO mice also displayed higher levels of interstitial and perivascular fibrosis compared to controls 3 or 7 days after Dox treatment. Additionally, the decrease in levels of the microtubule protein Ξ±-tubulin, which occurs in response to Dox treatment, was not prevented in CKO mice. Overall, these results indicate that selective loss of p53 in cardiomyocytes is not sufficient to prevent Dox induced myocardial ROS/RNS generation, apoptosis, interstitial fibrosis and perivascular fibrosis. Further, these results support a role for p53 independent apoptotic pathways leading to Dox induced myocardial damage and highlight the importance of vascular lesions in Dox induced cardiotoxicity

    A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment

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    Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3β€²-iodohippuryl N-Ι›-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine. Β© 1999 Cancer Research Campaig

    Identification of Key Residues for pH Dependent Activation of Violaxanthin De-Epoxidase from Arabidopsis thaliana

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    Plants are often exposed to saturating light conditions, which can lead to oxidative stress. The carotenoid zeaxanthin, synthesized from violaxanthin by Violaxanthin De-Epoxidase (VDE) plays a major role in the protection from excess illumination. VDE activation is triggered by a pH reduction in the thylakoids lumen occurring under saturating light. In this work the mechanism of the VDE activation was investigated on a molecular level using multi conformer continuum electrostatic calculations, site directed mutagenesis and molecular dynamics. The pKa values of residues of the inactive VDE were determined to identify target residues that could be implicated in the activation. Five such target residues were investigated closer by site directed mutagenesis, whereas variants in four residues (D98, D117, H168 and D206) caused a reduction in enzymatic activity indicating a role in the activation of VDE while D86 mutants did not show any alteration. The analysis of the VDE sequence showed that the four putative activation residues are all conserved in plants but not in diatoms, explaining why VDE in these algae is already activated at higher pH. Molecular dynamics showed that the VDE structure was coherent at pH 7 with a low amount of water penetrating the hydrophobic barrel. Simulations carried out with the candidate residues locked into their protonated state showed instead an increased amount of water penetrating the barrel and the rupture of the H121–Y214 hydrogen bond at the end of the barrel, which is essential for VDE activation. These results suggest that VDE activation relies on a robust and redundant network, in which the four residues identified in this study play a major role
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