906 resultados para TERTIARY PHOSPHINES


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The archipelago of Cape Verde is made up of ten islands and nine islets and is located between latitudes 14º 28' N and 17º 12' N and longitudes 22º 40' W and 25º 22' W. It is located approximately 500 km from the Senegal coast in West Africa (Figure 1). The islands are divided into two groups: Windward and Leeward. The Windward group is composed of the islands of Santo Antão, São Vicente, Santa Luzia, São Nicolau, Sal and Boavista; and the Leeward group is composed of the islands Maio, Santiago, Fogo and Brava. The archipelago has a total land surface of 4,033 km2 and an Economic Exclusive Zone (ZEE) that extends for approximately 734,000 km2. In general, the relief is very steep, culminating with high elevations (e.g. 2,829 m on Fogo and 1,979 m on Santo Antão). The surface area, geophysical configuration and geology vary greatly from one island to the next. Cape Verde, due to its geomorphology, has a dense and complex hydrographical network. However, there are no permanent water courses and temporary water courses run only during the rainy season. These temporary water courses drain quickly towards the main watersheds, where, unless captured by artificial means, continue rapidly to lower areas and to the sea. This applies equally to the flatter islands. The largest watershed is Rabil with an area of 199.2 km2. The watershed areas on other islands extend over less than 70 km2. Cape Verde is both a least developed country (LDC) and a small island development state (SIDS). In 2002, the population of Cape Verde was estimated at approximately 451,000, of whom 52% were women and 48% men. The population was growing at an average 2.4% per year, and the urban population was estimated at 53.7 %. Over the past 15 years, the Government has implemented a successful development strategy, leading to a sustained economic growth anchored on development of the private sector and the integration of Cape Verde into the world economy. During this period, the tertiary sector has become increasingly important, with strong growth in the tourism, transport, banking and trade sectors. Overall, the quality of life indicators show substantial improvements in almost all areas: housing conditions, access to drinking water and sanitation, use of modern energy in both lighting and cooking, access to health services and education. Despite these overall socio-economic successes, the primary sector has witnessed limited progress. Weak performance in the primary sector has had a severe negative impact on the incomes and poverty risks faced by rural workers1. Moreover, relative poverty has increased significantly during the past decade. The poverty profile shows that: (i) extreme poverty is mostly found in rural areas, although it has also increased in urban areas; (ii) poverty is more likely to occur when the head of the household is a woman; (iii) poverty increases with family size; (iv) education significantly affects poverty; (v) the predominantly agricultural islands of Santo Antão and Fogo have the highest poverty rates; (vi) unemployment affects the poor more than the nonpoor; (vii) agriculture and fisheries workers are more likely to be poor than those in other sectors. Therefore, the fight against poverty and income inequalities remains one of the greatest challenges for Cape Verde authorities. The various governments of Cape Verde over the last decade have demonstrated a commitment to improving governance, notably by encouraging a democratic culture that guarantees stability and democratic changes without conflicts. This democratic governance offers a space for a wider participation of citizens in public management and consolidates social cohesion. However, there are some remaining challenges related to democratic governance and the gains must be systematically monitored. Finally, it is worth emphasizing that the country’s insularity has stimulated a movement to decentralized governance, although social inequalities and contrasts from one island to the next constitute, at the same time, challenges and opportunities.

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Na Europa e nas últimas décadas do Século XX, a emergência da Sociedade de Informação veio impor às organizações a necessidade de que, para além das inovações tecnológicas, haja uma preocupação relativamente aos bens intangíveis como a informação, as novas metodologias de trabalho e o know how (Batista, 2002). Paralelamente a estas inovações, as Instituições de Ensino Superior têm contribuído para a evolução do Capital Humano, como ativo intangível intrínseco ao Homem. Em Portugal e no contexto do Ensino/Formação a Distância parecem continuar a existir, ainda, em algumas instituições, problemas de identificação, e de descriminação das vantagens no que concerne à estrutura aberta e flexível, com o estudante/formando a ter algumas dificuldades em adaptar o seu perfil e interesses profissionais ao tipo de aprendizagem que mais se lhe adequa. O e-learning surge como um método de Ensino/Formação a Distância, só possível com a especificidade dos processos pedagógicos e em complementaridade com as Tecnologias de Informação e Comunicação (TIC), uma vez que são estas que lhe dão o suporte necessário à sua concretização. O e-learning ao proporcionar novas formas de comunicação, de interação e de confronto de ideias, permite uma aprendizagem baseada na partilha de saberes, tendo em consideração as experiências e os objetivos profissionais dos formandos. Dentro destes pressupostos, achámos importante fazer uma investigação a partir de Instituições de Ensino Superior Portuguesas, de modo a percebermos qual o papel e a influência que o e-learning desempenha nos objetivos das organizações académicas em geral e no Capital Humano dos seus Estudantes/Formandos em particular. A partir da questão da investigação foram definidos os objetivos e hipóteses de investigação de modo a que ao ser enunciada uma metodologia esta englobe fatores que foquem os elementos necessários à confirmação, ou não, dos pressupostos enunciados. Foi analisada documentação diversa, criado um questionário e conduzidas entrevistas, de modo a obter e potenciar a informação necessária e suficiente para o efeito. A recolha de dados para posterior análise e os resultados depois de interpretados, permitirão responder aos propósitos expressos desde o início da investigação.

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We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specimen showed a major disorganization of the neuromuscular junction, including changes in the nerve-terminal cytoskeleton and fragmentation of the synaptic gutters. Experiments performed in nonmuscle cells or in cultured C2C12 myotubes and using recombinant mini-agrin for the mutated and the wild-type forms showed that the mutated form did not impair the activation of MuSK or change the total number of induced acetylcholine receptor aggregates. A solid-phase assay using the dystrophin glycoprotein complex showed that the mutation did not affect the binding of agrin to alpha-dystroglycan. Injection of wild-type or mutated agrin into rat soleus muscle induced the formation of nonsynaptic acetylcholine receptor clusters, but the mutant protein specifically destabilized the endogenous neuromuscular junctions. Importantly, the changes observed in rat muscle injected with mutant agrin recapitulated the pre- and post-synaptic modifications observed in the patient. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.

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Cell surface receptors bind ligands expressed on other cells (in trans) in order to communicate with neighboring cells. However, an increasing number of cell surface receptors are found to also interact with ligands expressed on the same cell (in cis). These observations raise questions regarding the biological role of such cis interactions. Specifically, it is important to know whether cis and trans binding have distinct functional effects and, if so, how a single cell discriminates between interactions in cis versus trans. Further, what are the structural features that allow certain cell surface receptors to engage ligand both on the same as well as on an apposed cell membrane? Here, we summarize known examples of receptors that display cis-trans binding and discuss the emerging diversity of biological roles played by these unconventional two-way interactions, along with their structural basis.

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Introduction: Low cardiac output syndrome is frequent in childrenafter heart surgery for congenital heart disease and may result in pooroutcome and increased morbidity. In the adult population, preoperativebrain natriuretic peptide (BNP) was shown to be predictive of postoperative complications. In children, the value of preoperative BNP onpostoperative outcome is not so clear. The aim of this study was todetermine the predictive value of preoperative BNP on postoperativeoutcome and low cardiac output syndrome in children after heartsurgery for congenital heart disease.Methods: We examined, retrospectively, the postoperative course of97 pediatric patients (mean age 3.7 years, range 0-14 years old) whounderwent heart surgery in a tertiary care pediatric intensive caresetting. NTproBNP was measured preoperatively in all patients(median 412 pg/ml, range 12-35'000 pg/ml). Patients were divided intothree groups according to their NTproBNP levels (group 1: 0-300 pg/ml, group 2: 300-600 pg/ml, group 3: >600 pg/ml) and then,correlations with postoperative outcomes were examined.Results: We found that patients with a high preoperative BNP requiredmore frequently prolonged (>2 days) mechanical ventilation (33%vs 40% vs 61%, p = 0.045) and stayed more frequently longer than6 days in the intensive care unit (42% vs 50% vs 71%, p = 0.03).However, high preoperative BNP was not correlated with occurrenceof low cardiac output syndrome.Conclusion: Preoperative BNP cannot be used, in children, as areliable and sole predictor of postoperative low cardiac outputsyndrome. However it may help identify, before surgery, those patientsat risk of having a difficult postoperative course.

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Desmosomes are intercellular adhesive complexes that anchor the intermediate filament cytoskeleton to the cell membrane in epithelia and cardiac muscle cells. The desmosomal component desmoplakin plays a key role in tethering various intermediate filament networks through its C-terminal plakin repeat domain. To gain better insight into the cytoskeletal organization of cardiomyocytes, we investigated the association of desmoplakin with desmin by cell transfection, yeast two-hybrid, and/or in vitro binding assays. The results indicate that the association of desmoplakin with desmin depends on sequences within the linker region and C-terminal extremity of desmoplakin, where the B and C subdomains contribute to efficient binding; a potentially phosphorylatable serine residue in the C-terminal extremity of desmoplakin affects its association with desmin; the interaction of desmoplakin with non-filamentous desmin requires sequences contained within the desmin C-terminal rod portion and tail domain in yeast, whereas in in vitro binding studies the desmin tail is dispensable for association; and mutations in either the C-terminus of desmoplakin or the desmin tail linked to inherited cardiomyopathy seem to impair desmoplakindesmin interaction. These studies increase our understanding of desmoplakin-intermediate filament interactions, which are important for maintenance of cytoarchitecture in cardiomyocytes, and give new insights into the molecular basis of desmoplakin- and desmin-related human diseases.

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Several lines of evidences have suggested that T cell activation could be impaired in the tumor environment, a condition referred to as tumor-induced immunosuppression. We have previously shown that tenascin-C, an extracellular matrix protein highly expressed in the tumor stroma, inhibits T lymphocyte activation in vitro, raising the possibility that this molecule might contribute to tumor-induced immunosuppression in vivo. However, the region of the protein mediating this effect has remained elusive. Here we report the identification of the minimal region of tenascin-C that can inhibit T cell activation. Recombinant fragments corresponding to defined regions of the molecule were tested for their ability to inhibit in vitro activation of human peripheral blood T cells induced by anti-CD3 mAbs in combination with fibronectin or IL-2. A recombinant protein encompassing the alternatively spliced fibronectin type III domains of tenascin-C (TnFnIII A-D) vigorously inhibited both early and late lymphocyte activation events including activation-induced TCR/CD8 down-modulation, cytokine production, and DNA synthesis. In agreement with this, full length recombinant tenascin-C containing the alternatively spliced region suppressed T cell activation, whereas tenascin-C lacking this region did not. Using a series of smaller fragments and deletion mutants issued from this region, we have identified the TnFnIII A1A2 domain as the minimal region suppressing T cell activation. Single TnFnIII A1 or A2 domains were no longer inhibitory, while maximal inhibition required the presence of the TnFnIII A3 domain. Altogether, these data demonstrate that the TnFnIII A1A2 domain mediate the ability of tenascin-C to inhibit in vitro T cell activation and provide insights into the immunosuppressive activity of tenascin-C in vivo.

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Prior to their Alpine overprinting, most of the pre-Mesozoic basement areas in Alpine orogenic structures shared a complex evolution, starting with Neoproterozoic sediments that are thought to have received detrital input from both West and East Gondwanan cratonic sources. A subsequent Neoproterozoic-Cambrian active margin setting at the Gondwana margin was followed by a Cambrian-Ordovician rifting period, including an Ordovician cordillera-like active margin setting. During the Late Ordovician and Silurian periods, the future Alpine domains recorded crustal extension along the Gondwana margin, announcing the future opening of the Paleotethys oceanic domain. Most areas then underwent Variscan orogenic events, including continental subduction and collisions with Avalonian-type basement areas along Laurussia and the juxtaposition and the duplication of terrane assemblages during strike slip, accompanied by contemporaneous crustal shortening and the subduction of Paleotethys under Laurussia. Thereafter, the final Pangea assemblage underwent Triassic and Jurassic extension, followed by Tertiary shortening, and leading to the buildup of the Alpine mountain chain. Recent plate-tectonic reconstructions place the Alpine domains in their supposed initial Cambrian-Ordovician positions in the eastern part of the Gondwana margin, where a stronger interference with the Chinese blocks is proposed, at least from the Ordovician onward. For the Visean time of the Variscan continental collision, the distinction of the former tectonic lower-plate situation is traceable but becomes blurred through the subsequent oblique subduction of Paleotethys under Laurussia accompanied by large-scale strike slip. Since the Pennsylvanian, this global collisional scenario has been replaced by subsequent and ongoing shortening and strike slip under rising geothermal conditions, and all of this occurred before all these puzzle elements underwent the complex Alpine reorganization.

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Mutants were produced in the A-domain of HbpR, a protein belonging to the XylR family of σ(54)-dependent transcription activators, with the purpose of changing its effector recognition specificity from 2-hydroxybiphenyl (2-HBP, the cognate effector) to 2-chlorobiphenyl (2-CBP). Mutations were introduced in the hbpR gene part for the A-domain via error-prone polymerase chain reaction, and assembled on a gene circuitry plasmid in Escherichia coli, permitting HbpR-dependent induction of the enhanced green fluorescent protein (egfp). Cells with mutant HbpR proteins responsive to 2-CBP were enriched and separated in a flow cytometry-assisted cell-sorting procedure. Some 70 mutants were isolated and the A-domain mutations mapped. One of these had acquired true 2-CBP recognition but reacted hypersensitively to 2-HBP (20-fold more than the wild type), whereas others had reduced sensitivity to 2-HBP but a gain of 2-CBP recognition. Sequencing showed that most mutants carried double or triple mutations in the A-domain gene part, and were not located in previously recognized conserved residues within the XylR family members. Further selection from a new mutant pool prepared of the hypersensitive mutant did not result in increased 2-CBP or reduced 2-HBP recognition. Our data thus demonstrate that a one-step in vitro 'evolutionary' adaptation of the HbpR protein can result in both enhancement and reduction of the native effector recognition.

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Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ∼20 Å above the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels.

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Integrin adhesion receptors consist of non-covalently linked alpha and beta subunits each of which contains a large extracellular domain, a single transmembrane domain and a short cytoplasmic tail. Engaged integrins recruit to focal structures globally termed adhesion complexes. The cytoplasmic domain of the beta subunit is essential for this clustering. beta1 and beta3 integrins can recruit at distinct cellular locations (i.e. fibrillar adhesions vs focal adhesions, respectively) but it is not clear whether individual beta subunit cytoplasmic and transmembrane domains are by themselves sufficient to drive orthotopic targeting to the cognate adhesion complex. To address this question, we expressed full-length beta3 transmembrane anchored cytoplasmic domains and truncated beta3 cytoplasmic domains as GFP-fusion constructs and monitored their localization in endothelial cells. Membrane-anchored full-length beta3 cytoplasmic domain and a beta3 mutant lacking the NXXY motif recruited to adhesion complexes, while beta3 mutants lacking the NPXY and NXXY motifs or the transmembrane domain did not. Replacing the natural beta subunit transmembrane domain with an unrelated (i.e. HLA-A2 alpha chain) transmembrane domain significantly reduced recruitment to adhesion complexes. Transmembrane anchored beta3 and cytoplasmic domain constructs, however, recruited without discrimination to beta1- and beta3-rich adhesions complexes. These findings demonstrate that membrane anchorage and the NPXY (but not the NXXY) motif are necessary for beta3 cytoplasmic domain recruitment to adhesion complexes and that the natural transmembrane domain actively contributes to this recruitment. The beta3 transmembrane and cytoplasmic domains alone are insufficient for orthotopic recruitment to cognate adhesion complexes.

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OBJECTIVES: Kaposi's sarcoma (KS), invasive cervical carcinoma (ICC) and non-Hodgkin lymphoma (NHL) have been listed as AIDS-defining cancers (ADCs) by the Centers for Disease Control and Prevention since 1993. Despite this, HIV screening is not universally mentioned in ADC treatment guidelines. We examined screening practices at a tertiary centre serving a population where HIV seroprevalence is 0.4%. METHODS: Patients with KS, ICC, NHL and Hodgkin lymphoma (HL), treated at Lausanne University Hospital between January 2002 and July 2012, were studied retrospectively. HIV testing was considered part of the oncology work-up if performed between 90 days before and 90 days after the cancer diagnosis date. RESULTS: A total of 880 patients were examined: 10 with KS, 58 with ICC, 672 with NHL and 140 with HL. HIV testing rates were 100, 11, 60 and 59%, and HIV seroprevalence was 60, 1.7, 3.4 and 5%, respectively. Thirty-seven patients (4.2%) were HIV-positive, of whom eight (22%) were diagnosed at oncology work-up. All newly diagnosed patients had CD4 counts < 200 cells/μL and six (75%) had presented to a physician 12-236 weeks previously with conditions warranting HIV testing. CONCLUSIONS: In our institution, only patients with KS were universally screened. Screening rates for other cancers ranged from 11 to 60%. HIV seroprevalence was at least fourfold higher than the population average. As HIV-positive status impacts on cancer patient medical management, HIV screening should be included in oncology guidelines. Further, we recommend that opt-out screening should be adopted in all patients with ADCs and HL.

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The prevalence of cardiovascular diseases is high in the old age. These conditions have a negative impact on the quality of life and are associated with a high risk of disability. A marked increase in the number of affected individuals is likely, in coming decades, with population aging. Primary cardiovascular prevention, but also an early recognition of subclinical heart diseases and secondary and tertiary prevention will be of up most importance for individuals (quality of life) and for societies (burden of functional impairments) as the baby-boom generation reaches retirement age.

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P130 A HIGH-RESOLUTION 2D/3D SEISMIC STUDY OF A THRUST FAULT ZONE IN LAKE GENEVA SWITZERLAND M. SCHEIDHAUER M. BERES D. DUPUY and F. MARILLIER Institute of Geophysics University of Lausanne 1015 Lausanne, Switzerland Summary A high-resolution three-dimensional (3D) seismic reflection survey has been conducted in Lake Geneva near the city of Lausanne Switzerland where the faulted molasse basement (Tertiary sandstones) is overlain by complex Quaternary sedimentary structures. Using a single 48-channel streamer an area of 1200 m x 600 m was surveyed in 10 days. With a 5-m shot spacing and a receiver spacing of 2.5 m in the inline direction and 7.5 m in the crossline direction, a 12-fold data coverage was achieved. A maximum penetration depth of ~150 m was achieved with a 15 cu. in. water gun operated at 140 bars. The multi-channel data allow the determination of an accurate velocity field for 3D processing, and they show particularly clean images of the fault zone and the overlying sediments in horizontal and vertical sections. In order to compare different sources, inline 55 was repeated with a 30/30 and a 15/15 cu. in. double-chamber air gun (Mini GI) operated at 100 and 80 bars, respectively. A maximum penetration depth of ~450 m was achieved with this source.

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Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.