807 research outputs found
Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms
Integrins are adhesion receptors that are crucial to the functions of multicellular organisms. Integrin-mediated adhesion is a complex process that involves both affinity
regulation and cytoskeletal coupling, but the molecular mechanisms behind this process have remained incompletely understood. In this study, we report that the phosphorylation
of each cytoplasmic domain of the leukocyte
function-associated antigen-1 integrin mediates different modes of integrin activation. Alpha Chain phosphorylation
on Ser1140 is needed for conformational changes in the integrin after chemokine- or integrin ligand-induced activation or after activation induced by active Rap1
(Rap1V12). In contrast, the beta chain Thr758 phosphorylation
mediates selective binding to 14-3-3 proteins in response to inside-out activation through the T cell receptor, resulting in cytoskeletal rearrangements. Thus, site-specific phosphorylation of the integrin cytoplasmic domains is important for the dynamic regulation of these complex receptors in cells
Risk factors and sib correlation in physiological neonatal jaundice
The effect of a number of explanatory variables on the degree of physiological jaundice in mature infants was evaluated by multiple regression analysis. The sampling was designed so that comparisons could be made between siblings. We found an effect of gestational age, gender, infant nutrition, ABO incompatibility and induction of labour. Taking these factors into account we still found a highly significant correlation between the peak bilirubin levels of siblings. Whether this correlation is genetically or environmentally determined is not clear.LR: 20061115; PUBM: Print; JID: 0000211; 635-65-4 (Bilirubin); ppublishSource type: Electronic(1
The TOTEM GEM telescope (T2) at the LHC
The TOTEM T2 telescope will measure inelastically produced charged particles in the forward region of the LHC Interaction Point 5. Each arm of the telescope consists in a set of 20 triple-GEM (Gas Electron Multiplier) detectors with tracking and t rigger capabilities. The GEM technology has been considered for the design of TOTEM very forward T2 telescopes thanks to its characteristics: large active areas, good position and timing resolution, excellent rate capability and radiation hardness. Each o f the four T2 half arms has been fully assembled and equipped with electronics at CERN and systematically tested in the SPS beam line H8 in 2008/09. After some optimization, the operation of the GEM chambers was fully satisfactory and the T2 telescopes we re installed and commissioned in their final positions at the LHC interaction point. During the first LHC run (December 2009) the T2 telescopes have collected data, at 900 GeV and 2.36 TeV. We will present here the performances of the detector and the pre liminary results obtained using the data collected
Proton-proton elastic scattering at the LHC energy of root s=7 TeV
-Proton-proton elastic scattering has been measured by the TOTEM experiment at the CERN Large Hadron Collider at root s = 7 TeV in dedicated runs with the Roman Pot detectors placed as close as seven times the transverse beam size (sigma(beam)) from the outgoing beams. After careful study of the accelerator optics and the detector alignment, |t|, the square of four-momentum transferred in the elastic scattering process, has been determined with an uncertainty of delta t = 0.1GeV root|t|. In this letter, first results of the differential cross-section are presented covering a |t|-range from 0.36 to 2.5GeV(2). The differential cross-section in the range 0.36 < |t| < 0.47 GeV(2) is described by an exponential with a slope parameter B = (23.6 +/- 0.5(stat) +/- 0.4(syst)) GeV(-2), followed by a significant diffractive minimum at |t| = (0.53 +/- 0.01(stat) +/- 0.01(syst)) GeV(2). For |t|-values larger than similar to 1.5GeV(2), the cross-section exhibits a power law behaviour with an exponent of -7.8 +/- 0.3(stat) +/- 0.1(syst). When compared to predictions based on the different available models, the data show a strong discriminative power despite th e small t-range covered. Copyright (C) EPLA, 201
First TOTEM measurement of large |t| proton proton elastic scattering at the LHC energy of √s = 7TeV
TOTEM has measured the differential cross-section for elastic proton-proton scattering at the LHC energy of √s = 7 TeV analysing data from runs with a standard β∗ = 1.5m optics. The differential cross section is measured over a |t|-range from 0.36 to 2.5GeV2. The differential cross-section shows a significant diffractive minimum at |t| = (0.53 ±0.01stat± 0.01syst) GeV2. For |t |-values larger than ∼ 1.5GeV2, the cross-section exhibits a power law behaviour with an exponent of -7.8 ± 0.3stat ±0.1syst. The data are compared to predictions based on different available models and show a strong discriminative power
Desenvolvimento de uma multiplex PCR para identificação das principais espécies de dermatófitos que acometem cães e gatos
Objetivou-se neste estudo padronizar uma reação do tipo multiplex PCR (mPCR) para detectar Microsporum canis, Microsporum gypseum e o complexo Trichophyton mentagrophytes em amostras de pelos e/ou crostas de cães e gatos. Foram analisadas 250 amostras por meio de exame direto e cultura; o DNA destas mesmas amostras foi extraído utilizando-se o kit de extração DNeasy Blood & Tissue (QIAGEN®, Hilden - Germany). Para a PCR foram desenhados primers para as espécies M. canis, M. gypseum e T. mentagrophytes e como controle positivo da reação utilizou-se o DNA extraído de colônias de M. canis (URM 6273), M. gypseum (URM 6921) e T. mentagrophytes (URM 6211), provenientes da Coleção de Culturas da Micoteca do Departamento de Micologia do Centro de Ciências Biológicas da Universidade Federal de Pernambuco. Padronizou-se uma PCR para detecção de M. canis e uma mPCR para detecção de M. canis, M. gypseum e o complexo T. mentagrophytes. Os protocolos padronizados neste estudo, a partir de primers desenhados, apresentaram boa sensibilidade e alta especificidade na detecção de M. canis, M. gypseum e T. mentagrophytes diretamente de amostras de pelos e/ou crostas de cães e gatos, viabilizando um diagnóstico mais rápido e específico, podendo ser empregados na rotina laboratorial como métodos para agilizar a detecção dos agentes estudados.The aim of this study was to standardize a multiplex PCR (mPCR) reaction to detect Microsporum canis, Microsporum gypseum and the Trichophyton mentagrophytes complex in fur and/or crusts samples of dogs and cats. 250 samples were analyzed by direct examination and culture; The DNA from these samples was extracted using the DNeasy Blood & Tissue extraction kit (QIAGEN®, Hilden-Germany). For the PCR, primers were designed for the M. canis, M. gypseum and T. mentagrophytes species and the DNA extracted from colonies of M. canis (URM 6273), M. gypseum (URM 6921) and T. mentagrophytes (URM 6211) from the Collection of Cultures of the Micoteca of the Mycology Department of the Biological Sciences Center of the Federal University of Pernambuco, were utilized as positive controls. A PCR for the detection of M. canis and an mPCR for the detection of M. canis, M. gypseum and the T. mentagrophytes complex was standardized. The protocols standardized in this study, from drawn primers, showed good sensitivity and high specificity in the detection of M. canis, M. gypseum and T. mentagrophytes directly from samples of fur and/or crusts of dogs and cats, making possible a faster and specificity in the results, can be used in the laboratory routine as methods capable of speeding the detection of the agents in question
BET Inhibition-Induced GSK3β Feedback Enhances Lymphoma Vulnerability to PI3K Inhibitors
The phosphatidylinositol 3 kinase (PI3K)-glycogen synthase kinase β (GSK3β) axis plays a central role in MYC-driven lymphomagenesis, and MYC targeting with bromodomain and extraterminal protein family inhibitors (BETi) is a promising treatment strategy in lymphoma. In a high-throughput combinatorial drug screening experiment, BETi enhance the antiproliferative effects of PI3K inhibitors in a panel of diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma cell lines. BETi or MYC silencing upregulates several PI3K pathway genes and induces GSK3β S9 inhibitory phosphorylation, resulting in increased β-catenin protein abundance. Furthermore, BETi or MYC silencing increases GSK3β S9 phosphorylation levels and β-catenin protein abundance through downregulating the E2 ubiquitin conjugating enzymes UBE2C and UBE2T. In a mouse xenograft DLBCL model, BETi decrease MYC, UBE2C, and UBE2T and increase phospho-GSK3β S9 levels, enhancing the anti-proliferative effect of PI3K inhibitors. Our study reveals prosurvival feedbacks induced by BETi involving GSK3β regulation, providing a mechanistic rationale for combination strategies. In this study, Derenzini et al. demonstrate that BET inhibitors enhance lymphoma vulnerability to PI3K inhibitors by inducing GSK3β feedback in a MYC-dependent manner and by downregulating E2-ubiquitin conjugating enzymes, which further enhance the feedback. These data provide the rationale for combining BET and PI3K inhibitors in lymphoma therapy
Shrub Consumption and Immediate Changes in Shrub Community and Spatial Patterns by Reintroduced Fire in Yosemite National Park, California, USA; Supplemental Information
Fire behavior in the Yosemite Forest Dynamics Plot during the Rim Fire as captured by the USFS Fire Behavior Assessment Team and reported in Ewell, C., D.F. Smith, M. Hilden, S. Greene, D. Coultrap, K. Robinson, N. Vaillant, A. Reiner, T. Norman. 2015. 2013 Rim Fire Stanislaus National Forest and Yosemite National Park Fire Behavior Assessment Team Summary Report. Each video was started based on a thermocouple trigger when the fire reached it
Measurement of proton-proton elastic scattering and total cross-section at = 7 TeV
At the LHC energy of = 7 TeV, under various beam and background conditions, luminosities, and Roman Pot positions, TOTEM has measured the differential cross-section for proton-proton elastic scattering as a function of the four-momentum transfer squared t. The results of the different analyses are in excellent agreement demonstrating no sizeable dependence on the beam conditions. Due to the very close approach of the Roman Pot detectors to the beam center ( around 5 beam) in a dedicated run with * = 90m, abs(t)-values down to 5 10**-3 GeV**2 were reached. The exponential slope of the differential elastic cross-section in this newly explored abs(t)-region remained unchanged and thus an exponential fit with only one constant B = (19.90+/-0.3)GeV-2 over the large abs(t)-range from 0.005 to 0.2GeV**2 describes the differential distribution well. The high precision of the measurement and the large fit range lead to an error on the slope parameter B which is remarkably small compared to previous experiments. It allows a precise extrapolation over the non-visible cross-section (only 9%) to t = 0. With the luminosity from CMS, the elastic cross-section was determined to be (25.4 +/- 1.1)mb, and using in addition the optical theorem, the total pp cross-section was derived to be (98.6 +/-2.2)mb. For model comparisons the t-distributions are tabulated including the large abs(t)-range of the previous measurement
Measurement of proton-proton elastic scattering and total cross-section at root s=7 TeV
At the LHC energy of root s = 7TeV, under various beam and background conditions, luminosities, and Roman Pot positions, TOTEM has measured the differential cross-section for proton-proton elastic scattering as a function of the four-momentum transfer squared t. The results of the different analyses are in excellent agreement demonstrating no sizeable dependence on the beam conditions. Due to the very close approach of the Roman Pot detectors to the beam center (approximate to 5 sigma(beam)) in a dedicated run with beta* = 90 m, vertical bar t vertical bar-values down to 5.10(-3) GeV2 were reached. The exponential slope of the differential elastic cross-section in this newly explored vertical bar t vertical bar-region remained unchanged and thus an exponential fit with only one constant B = (19.9+/-0.3) GeV-2 over the large vertical bar t vertical bar-range from 0.005 to 0.2 GeV2 describes the differential distribution well. The high precision of the measurement and the large fit range lead to an error on the slope parameter B which is remarkably small compared to previous experiments. It allows a precise extrapolation over the non-visible cross-section (only 9%) to t = 0. With the luminosity from CMS, the elastic cross-section was determined to be (25.4+/-1.1) mb, and using in addition the optical theorem, the total pp cross-section was derived to be (98.6 +/- 2.2) mb. For model comparisons the t-distributions are tabulated including the large vertical bar t vertical bar-range of the previous measurement (TOTEM Collaboration (ANTCHEV G. et al.), EPL, 95 (2011) 41001)
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