682 research outputs found
L008 DĂ©faut de diffĂ©renciation veino-lymphatique embyonnaire par modulation de lâARN interfĂ©rence
LâARN interfĂ©rence, mĂ©canisme de rĂ©gulation de lâexpression des gĂšnes, est mĂ©diĂ©e par les siARNs et les microARNs, ARN non-codants de 20 Ă 22 nuclĂ©otides affectant la rĂ©gulation post-transcriptionnelle dâARNm cibles avec lesquels ils sâapparient.La RNase DICER est une enzyme centrale de la biosynthĂšse des siARNs et microARNs. Les souris dont le gĂšne dicer est invalidĂ© ont un phĂ©notype complexe, et meurent trĂšs tĂŽt pendant le dĂ©veloppement, notamment Ă cause dâun dĂ©faut dâangiogenĂšse.Afin dâĂ©tudier lâARN interfĂ©rence au cours de lâangiogenĂšse embryonnaire, des souris dont le gĂšne dicer est floxĂ© (mutant conditionnel) sont croisĂ©es avec des souris exprimant la recombinase Cre, de maniĂšre constitutive, sous le contrĂŽle du promoteur du gĂšne tie2, dirigeant ainsi son expression dans les cellules endothĂ©liales (CE) et les cellules hĂ©matopiĂ©tiques.Nos rĂ©sultats montrent que lâinvalidation de dicer sous le contrĂŽle du promoteur du gĂšne tie2 entraine une mortalitĂ© embryonnaire suite Ă un ĆdĂšme et des hĂ©morragies au treiziĂšme jour du dĂ©veloppement (E13,5). Lâanalyse histologique montre des vaisseaux lymphatiques remplis de sang, suggĂ©rant une mauvaise sĂ©paration du rĂ©seau sanguin et lymphatique. Cette hypothĂšse est Ă©tudiĂ©e par marquage des vaisseaux lymphatiques (LYVE-1) et des vaisseaux sanguins (PECAM) sur embryon entier et peaux isolĂ©es Ă diffĂ©rents stades prĂ©cĂ©dant la mort.Ces embryons prĂ©sentent Ă©galement un problĂšme de dĂ©veloppement du foie, probablement dĂ» Ă lâactivitĂ© du promoteur tie2 dans les lignĂ©es hĂ©matopoiĂ©tiques. La mise en culture de ces foies fĆtaux Ă E13,5 rĂ©vĂšle une atteinte des prĂ©curseurs hĂ©matopoĂ©tiques.LâĂ©tude de ces prĂ©curseurs Ă des stades plus prĂ©coces (E8,5) est en cours au laboratoire.Nos rĂ©sultats dĂ©montrent donc un rĂŽle important de lâARN interfĂ©rence dans le contrĂŽle Ă©pigĂ©nĂ©tique de lâangiogenĂšse et de la lymphangiogenĂšse embryonnaire mais Ă©galement dans le dĂ©veloppement de lâhĂ©matopoiĂšse, suggĂ©rant son implication dans la diffĂ©renciation veino-lymphangiogenĂšse, dont les mĂ©canismes molĂ©culaires seront discutĂ©s
Is neutrophil gelatinase-associated lipocalin unaffected by convective continuous renal replacement therapy? Definitely ⊠maybe
Ethyl 4-{1-[(2,4-dinitroÂphenÂyl)hydrazono]ethÂyl}-5-(2-naphthylÂmethoxyÂmethÂyl)isoxazole-3-carboxylÂate
The title compound, C26H23N5O8, was prepared and its structure investigated to further develop a working hypothesis for the essential binding pharmacophore for ligands of the System Xc- transporter [Patel et al. (2004 â¶). Neuropharmacology, 46, 273â284]. The hydrazone group displays an E geometry and the isoxazole double bond and C=N group of the hydrazone are in an s-cis relationship. The secondary amino NH group forms an intraÂmolecular NâHâŻO hydrogen bond to a ring nitro group. There is a dihedral angle of 44.27â
(5)° between the isoxazole plane and the hydrazone group plane
Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release
Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands
Functional Analysis of Ficolin-3 Mediated Complement Activation
The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway
The lady vanishes: what's missing from the stem cell debate
Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponentsâ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in âthe stem cell warsâ is that women are equally invisible to both: âthe lady vanishesâ. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and womenâs reproductive labour as unimportant
Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications
This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis
The Intracellular Transport and Secretion of Calumenin-1/2 in Living Cells
Calumenin isoforms 1 and 2 (calu-1/2), encoded by the CALU gene, belong to the CREC protein family. Calu-1/2 proteins are secreted into the extracellular space, but the secretory process and regulatory mechanism are largely unknown. Here, using a time-lapse imaging system, we visualized the intracellular transport and secretory process of calu-1/2-EGFP after their translocation into the ER lumen. Interestingly, we observed that an abundance of calu-1/2-EGFP accumulated in cellular processes before being released into the extracellular space, while only part of calu-1/2-EGFP proteins were secreted directly after attaching to the cell periphery. Moreover, we found the secretion of calu-1/2-EGFP required microtubule integrity, and that calu-1/2-EGFP-containing vesicles were transported by the motor proteins Kif5b and cytoplasmic dynein. Finally, we determined the export signal of calu-1/2-EGFP (amino acid positions 20â46) and provided evidence that the asparagine at site 131 was indispensable for calu-1/2-EGFP stabilization. Taken together, we provide a detailed picture of the intracellular transport of calu-1/2-EGFP, which facilitates our understanding of the secretory mechanism of calu-1/2
GATE : a simulation toolkit for PET and SPECT
Monte Carlo simulation is an essential tool in emission tomography that can
assist in the design of new medical imaging devices, the optimization of
acquisition protocols, and the development or assessment of image
reconstruction algorithms and correction techniques. GATE, the Geant4
Application for Tomographic Emission, encapsulates the Geant4 libraries to
achieve a modular, versatile, scripted simulation toolkit adapted to the field
of nuclear medicine. In particular, GATE allows the description of
time-dependent phenomena such as source or detector movement, and source decay
kinetics. This feature makes it possible to simulate time curves under
realistic acquisition conditions and to test dynamic reconstruction algorithms.
A public release of GATE licensed under the GNU Lesser General Public License
can be downloaded at the address http://www-lphe.epfl.ch/GATE/
The role of bisphosphonates in breast cancer: The present and future role of bisphosphonates in the management of patients with breast cancer
At least 25% of patients with breast cancer develop skeletal metastases, with bone the site of disease producing the greatest morbidity. It is apparent that the bisphosphonates present an important component of the treatment strategy. They are now the treatment of choice in tumour-induced hypercalcaemia, and they can reduce bone pain and skeletal complications such as pathological fractures. In addition, bisphosphonates are being increasingly evaluated in the prevention of bone metastases and to prevent and treat cancer therapy-induced osteoporosis. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate
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