28 research outputs found

    p14–MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis

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    The extracellular signal-regulated kinase (ERK) cascade regulates proliferation, differentiation, and survival in multicellular organisms. Scaffold proteins regulate intracellular signaling by providing critical spatial and temporal specificity. The scaffold protein MEK1 (mitogen-activated protein kinase and ERK kinase 1) partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in mice, we now demonstrate that the p14–MP1-MEK1 signaling complex regulates late endosomal traffic and cellular proliferation. This function its essential for early embryogenesis and during tissue homeostasis, as revealed by epidermis-specific deletion of p14. These findings show that endosomal p14–MP1-MEK1 signaling has a specific and essential function in vivo and, therefore, indicate that regulation of late endosomal traffic by extracellular signals is required to maintain tissue homeostasis

    Membrane Recruitment of Scaffold Proteins Drives Specific Signaling

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    Cells must give the right response to each stimulus they receive. Scaffolding, a signaling process mediated by scaffold proteins, participates in the decoding of the cues by specifically directing signal transduction. The aim of this paper is to describe the molecular mechanisms of scaffolding, i.e. the principles by which scaffold proteins drive a specific response of the cell. Since similar scaffold proteins are found in many species, they evolved according to the purpose of each organism. This means they require adaptability. In the usual description of the mechanisms of scaffolding, scaffold proteins are considered as reactors where molecules involved in a cascade of reactions are simultaneously bound with the right orientation to meet and interact. This description is not realistic: (i) it is not verified by experiments and (ii) timing and orientation constraints make it complex which seems to contradict the required adaptability. A scaffold protein, Ste5, is used in the MAPK pathway of Saccharomyces Cerevisiae for the cell to provide a specific response to stimuli. The massive amount of data available for this pathway makes it ideal to investigate the actual mechanisms of scaffolding. Here, a complete treatment of the chemical reactions allows the computation of the distributions of all the proteins involved in the MAPK pathway when the cell receives various cues. These distributions are compared to several experimental results. It turns out that the molecular mechanisms of scaffolding are much simpler and more adaptable than previously thought in the reactor model. Scaffold proteins bind only one molecule at a time. Then, their membrane recruitment automatically drives specific, amplified and localized signal transductions. The mechanisms presented here, which explain how the membrane recruitment of a protein can produce a drastic change in the activity of cells, are generic and may be commonly used in many biological processes

    Evaluation of Fermi Read-out of the ATLAS Tilecal Prototype

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    Prototypes of the \fermi{} system have been used to read out a prototype of the \atlas{} hadron calorimeter in a beam test at the CERN SPS. The \fermi{} read-out system, using a compressor and a 40 MHz sampling ADC, is compared to a standard charge integrating read-out by measuring the energy resolution of the calorimeter separately with the two systems on the same events. Signal processing techniques have been designed to optimize the treatment of \fermi{} data. The resulting energy resolution is better than the one obtained with the standard read-out

    A digital Front-End and Readout MIcrosystem for calorimetry at LHC

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    % RD-16 A Digital Front-End and Readout Microsystem for Calorimetry at LHC \\ \\Front-end signal processing for calorimetric detectors is essential in order to achieve adequate selectivity in the trigger function of an LHC experiment, with data identification and compaction before readout being required in the harsh, high rate environment of a high luminosity hadron machine. Other crucial considerations are the extremely wide dynamic range and bandwidth requirements, as well as the volume of data to be transferred to following stages of the trigger and readout system. These requirements are best met by an early digitalization of the detector information, followed by integrated digital signal processing and buffering functions covering the trigger latencies.\\ \\The FERMI (Front-End Readout MIcrosystem) is a digital implementation of the front-end and readout electronic chain for calorimeters. It is based on dynamic range compression, high speed A to D converters, a fully programmable pipeline/digital filter chain, local storage and trigger functions. FERMI also acts as the interface to the Trigger and DAQ systems.\\ \\In the current demonstrator design six parallel acquisition channels consisting of a non-linear or switched multi-gain amplifier for 16/17 bit to 12 bit dynamic range compression. The signals are then sampled and digitised by 40~MHz, 12-bit ADCs. After linearisation and absolute calibration in look-up tables or add-multiply processes, the data are stored in dual port memories until the decision is taken by the first level trigger.\\ \\For the level-1 trigger, the data from all enabled channels are discriminated, added and summed over time to emulate pulse integration. The readout logic provides full time frames, up to 16~samples long, and/or digitally filtered data to the second and third level stages.\\ \\An integration of FERMI into a multi-chip Silicon-on-Silicon module (MCM-D) has been done using the flip-chip ASIC mounting technology. This solution allows a very high level of integration of complex functions with an excellent flexibility in mixing technologies for the different functional blocks.\\ \\Since FERMI is designed to be mounted in the immediate vicinity of the calorimeter, it incorporates a high degree of fault-tolerant circuitry and programmability, as well as the possible use of a rad-hard or rad-tolerant technologies.\\ \\Tests have been done together with detector prototypes for the ATLAS LAr and Tiles as well as with CMS crystal ECAL, and the results show that FERMI provides more than adequate performances for these detectors.\\ \

    Analysis of Meiosis in Nonmodel Tropical Plants: The Case of Carica papaya Linn

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    Este protocolo facilitará el desarrollo de variedades más productivas y resistentes de papaya, un cultivo de gran importancia nutricional en países tropicales.To develop plants that are more tolerant to drought, marginal soil fertility, and diseases and that satisfy demands for high yield, new cultivars of the tropical fruit papaya (Carica papaya L.) are needed. Nonetheless,in many cases, these traits are available in only wild relatives found throughout Latin America. Understanding meiotic progression may facilitate the introgression of desirable traits into commercial cultivars that maintain high fertility. In this protocol, we describe a practical and simple method to effectively isolate male meiocytes in order to document the behavior of papaya meiotic chromosomes.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM

    Evaluation of Fermi read-out of the Atlas Tilecal prototype

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    Prototypes of the FERMI system have been used to read out a prototype of the ATLAS hadron calorimeter in a beam test at the CERN SPS. The FERMI read-out system, using a compressor and a sampling ADC, is compared to a standard charge integrating read-out by measuring the energy resolution of the calorimeter separately with the two systems on the same events.http://www.sciencedirect.com/science/article/B6TJM-3SYVH5K-41/1/c7deb04cd1c94e28ecafdeda8aea0d1
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