329 research outputs found

    Base-Mediated Nitrophenyl Reductive Cyclization for the Synthesis of Hexahydro-2,6-methano-1-benzazocines

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    A Diels-Alder reaction leading to 4-nitrophenylcyclohexanones followed by a newly developed base-mediated reductive cyclization of the resulting ketone tethered to the nitrobenzene moiety gives access to the hexahydro-2,6-methano-1-benzazocine ring system present in several biologically interesting natural products such as aspernomine. The scope of the reaction was explored with eight substituted nitrobenzenes, obtaining yields of up to 87%. The highest cytotoxicity was observed in benzazocine 4h, bearing an enone moiety, which was active against eight cancer cell lines

    Single-channel transmission in gold one-atom contacts and chains

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    We induce superconductivity by proximity effect in thin layers of gold and study the number of conduction channels which contribute to the current in one-atom contacts and atomic wires. The atomic contacts and wires are fabricated with a Scanning Tunneling Microscope. The set of transmission probabilities of the conduction channels is obtained from the analysis of the I(V)I(V) characteristic curve which is highly non-linear due to multiple Andreev reflections. In agreement with theoretical calculations we find that there is only one channel which is almost completely open.Comment: 4 pages, 2 figures. To be published in Phys. Rev. B, Rapid Communications (2003

    Chemical composition, nutritional value, and biological evaluation of Tunisian okra pods (Abelmoschus esculentus L. moench)

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    The aim of this work was to perform an unprecedented in-depth study on the bioactive phytochemicals of Abelmoschus esculentus L. Moench Tunisian landrace (Marsaouia). For this purpose, its nutritional, aroma volatile, and phenolic profiles were characterized, and sundry biological activities were assessed in vitro. The approximate composition revealed that total dietary fiber as the most abundant macronutrient, mainly insoluble dietary fiber, followed by total carbohydrates and proteins. In addition, okra pods were rich in K, Ca, Mg, organic acids, tocopherols, and chlorophylls. Gas Chromatography-Electron Impact Mass Spectrometry (GC-EIMS) analysis showed that oxygenated monoterpenes, sesquiterpene hydrocarbons, and phenylpropanoids were the predominant essential volatile components in A. esculentus pods. A total of eight flavonols were detected by High-Performance Liquid Chromatography coupled to a DAD detector and mass spectrometry by electrospray ionization (HPLC-DAD-MS/ESI); with quercetin-3-O-glucoside being the majority phenolic component, followed by quercetin-O-pentosyl-hexoside and quercetin-dihexoside. This pioneering study, evidences that Tunisian okra display promising antioxidant and cytotoxic actions, in addition to relevant inhibitory effects against α-amylase and α-glucosidase enzymes, and interesting analgesic activity

    Grassroots Agency: Participation and Conflict in Buenos Aires Shantytowns seen through the Pilot Plan for Villa 7 (1971–1975)

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    open access articleIn 1971, after more than a decade of national and municipal policies aimed at the top-down removal of shantytowns, the Buenos Aires City Council approved the Plan Piloto para la Relocalización de Villa 7 (Pilot Plan for the Relocation of Shantytown 7; 1971–1975, referred to as the Pilot Plan hereinafter). This particular plan, which resulted in the construction of the housing complex, Barrio Justo Suárez, endures in the collective memory of Argentines as a landmark project regarding grassroots participation in state housing initiatives addressed at shantytowns. Emerging from a context of a housing shortage for the growing urban poor and intense popular mobilizations during the transition to democracy, the authors of the Pilot Plan sought to empower shantytown residents in novel ways by: 1) maintaining the shantytown’s location as opposed to eradication schemes that relocated the residents elsewhere, 2) formally employing some of the residents for the stage of construction, as opposed to “self-help” housing projects in which the residents contributed with unpaid labor, and 3) including them in the urban and architectural design of the of the new housing. This paper will examine the context in which the Pilot Plan was conceived of as a way of re-assessing the roles of the state, the user, and housing-related professionals, often seen as antagonistic. The paper argues that residents’ fair participation and state intervention in housing schemes are not necessarily incompatible, and can function in specific social and political contexts through multiactor proposals backed by a political will that prioritizes grassroots agency

    Quantum Conductance in Semimetallic Bismuth Nanocontacts

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    Electronic transport properties of bismuth nanocontacts are analyzed by means of a low temperature scanning tunneling microscope. The subquantum steps observed in the conductance versus elongation curves give evidence of atomic rearrangements in the contact. The underlying quantum nature of the conductance reveals itself through peaks in the conductance histograms. The shape of the conductance curves at 77 K is well described by a simple gliding mechanism for the contact evolution during elongation. The strikingly different behaviour at 4 K suggests a charge carrier transition from light to heavy ones as the contact cross section becomes sufficiently small.Comment: 5 pages including 4 figures. Accepted for publication in Phys. Rev. Let

    Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

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    During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus

    Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction

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    Limfòcits b; Metilació de l'ADN; GenomaLinfocitos b; Metilación de ADN; GenomaB-lymphocytes; DNA methylation; GenomeActivation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which ∼25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis indicates that AID is not directly involved. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns.Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R to E.B.]; cofunded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe. E.B is supported by Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program); P.L. and C.P. are supported by the German Cancer Aid project CO-CLL [70113869]; B.G. is funded by the Deutsche Forschungsgemeinschaft [GR1617/14-1/iPAD, SFB1160/2_B5, RESIST–EXC 2155–Project ID 390874280, CIBSS–EXC-2189–Project ID 390939984]; BMBF [GAIN 01GM1910A]. Funding for open access charge: Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R]

    Nitrogen transfer from forage legumes to nine neighbouring plants in a multi-species grassland

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    Legumes play a crucial role in nitrogen supply to grass-legume mixtures for ruminant fodder. To quantify N transfer from legumes to neighbouring plants in multi-species grasslands we established a grass-legume-herb mixture on a loamy-sandy site in Denmark. White clover (Trifolium repens L.), red clover (Trifolium pratense L.) and lucerne (Medicago sativa L.) were leaf-labelled with 15N enriched urea during one growing season. N transfer to grasses (Lolium perenne L. and xfestulolium), white clover, red clover, lucerne, birdsfoot trefoil (Lotus corniculatus L.), chicory (Cichorium intybus L.), plantain (Plantago lanceolata L.), salad burnet (Sanguisorba minor L.)and caraway (Carum carvi L.) was assessed. Neighbouring plants contained greater amounts of N derived from white clover (4.8 gm-2) compared with red clover (2.2 gm-2) and lucerne (1.1 gm-2). Grasses having fibrous roots received greater amounts of N from legumes than dicotyledonous plants which generally have taproots. Slurry application mainly increased N transfer from legumes to grasses. During the growing season the three legumes transferred approximately 40 kg N ha-1 to neighbouring plants. Below-ground N transfer from legumes to neighbouring plants differed among nitrogen donors and nitrogen receivers and may depend on root characteristics and regrowth strategies of plant species in the multi-species grassland

    Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition

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    Embryonic development is defined by the hierarchical dynamical process that translates genetic information (genotype) into a spatial gene expression pattern (phenotype) providing the positional information for the correct unfolding of the organism. The nature and evolutionary implications of genotype–phenotype mapping still remain key topics in evolutionary developmental biology (evo-devo). We have explored here issues of neutrality, robustness, and diversity in evo-devo by means of a simple model of gene regulatory networks. The small size of the system allowed an exhaustive analysis of the entire fitness landscape and the extent of its neutrality. This analysis shows that evolution leads to a class of robust genetic networks with an expression pattern characteristic of lateral inhibition. This class is a repertoire of distinct implementations of this key developmental process, the diversity of which provides valuable clues about its underlying causal principles
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