282 research outputs found
The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate
Protein phosphatase 1 (PP1) binding proteins are quintessential regulators, determining substrate specificity and defining subcellular localization and activity of the latter. Here, we describe a novel PP1 binding protein, the nuclear membrane protein lamina associated polypeptide 1B (LAP1B), which interacts with the DYT1 dystonia protein torsinA. The PP1 binding domain in LAP1B was here identified as the REVRF motif at amino acids 55-59. The LAP1B:PP1 complex can be immunoprecipitated from cells in culture and rat cortex and the complex was further validated by yeast co-transformations and blot overlay assays. PP1, which is enriched in the nucleus, binds to the N-terminal nuclear domain of LAP1B, as shown by immunocolocalization and domain specific binding studies. PP1 dephosphorylates LAP1B, confirming the physiological relevance of this interaction. These findings place PP1 at a key position to participate in the pathogenesis of DYT1 dystonia and related nuclear envelope-based diseases.publishe
Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study
<p>Abstract</p> <p>Background</p> <p>It is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp) polymorphisms of the NOS3 gene were associated with resistant hypertension.</p> <p>Methods</p> <p>A prospective case-control observational study was performed. From a series of 950 consecutive patients followed up during 42 months, 48 patients with resistant hypertension were detected. 232 patients with controlled high blood pressure were also included.</p> <p>Results</p> <p>No differences were observed in the distribution of G894T (Glu298Asp) NOS3 genotypes between the resistant hypertension group and the controlled hypertension patients. However, genotype -786CC was more frequent in the group of patients with resistant hypertension (33.3%) than in the group of patients with controlled high blood pressure (17.7%) (p 0.03). Furthermore carriers of allele T (-786TC and -786TT) were more frequent in patients with controlled hypertension (82.3%) than those with resistant hypertension (66.7%) (Multivariate analysis; RR 2.09; 95% CI 1.03–4.24; p 0.004).</p> <p>Conclusion</p> <p>Our results indicate that genotype -786CC of the NOS3 gene increase the susceptibility to suffer resistant hypertension, which suggest that resistance to conventional therapy could be determined at the endothelial level.</p
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Final Pre-40S Maturation Depends on the Functional Integrity of the 60S Subunit Ribosomal Protein L3
Ribosomal protein L3 is an evolutionarily conserved protein that participates in the assembly of early pre-60S particles. We report that the rpl3[W255C] allele, which affects the affinity and function of translation elongation factors, impairs cytoplasmic maturation of 20S pre-rRNA. This was not seen for other mutations in or depletion of L3 or other 60S ribosomal proteins. Surprisingly, pre-40S particles containing 20S pre-rRNA form translation-competent 80S ribosomes, and translation inhibition partially suppresses 20S pre-rRNA accumulation. The GTP-dependent translation initiation factor Fun12 (yeast eIF5B) shows similar in vivo binding to ribosomal particles from wild-type and rpl3[W255C] cells. However, the GTPase activity of eIF5B failed to stimulate processing of 20S pre-rRNA when assayed with ribosomal particles purified from rpl3[W255C] cells. We conclude that L3 plays an important role in the function of eIF5B in stimulating 3′ end processing of 18S rRNA in the context of 80S ribosomes that have not yet engaged in translation. These findings indicate that the correct conformation of the GTPase activation region is assessed in a quality control step during maturation of cytoplasmic pre-ribosomal particles
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Design of Novel Relaxase Substrates Based on Rolling Circle Replicases for Bioconjugation to DNA Nanostructures
During bacterial conjugation and rolling circle replication, HUH endonucleases, respectively known as relaxases and replicases, form a covalent bond with ssDNA when they cleave their target sequence (nic site). Both protein families show structural similarity but limited amino acid identity. Moreover, the organization of the inverted repeat (IR) and the loop that shape the nic site differs in both proteins. Arguably, replicases cleave their target site more efficiently, while relaxases exert more biochemical control over the process. Here we show that engineering a relaxase target by mimicking the replicase target, results in enhanced formation of protein-DNA covalent complexes. Three widely different relaxases, which belong to MOBF, MOBQ and MOBP families, can properly cleave DNA sequences with permuted target sequences. Collaterally, the secondary structure that the permuted targets acquired within a supercoiled plasmid DNA resulted in poor conjugation frequencies underlying the importance of relaxase accessory proteins in conjugative DNA processing. Our results reveal that relaxase and replicase targets can be interchangeable in vitro. The new Rep substrates provide new bioconjugation tools for the design of sophisticated DNA-protein nanostructures.This work was financed by grants
BFU2014-55534-C2-1-P from the Spanish Ministry of
Economy and Competitiveness and 612146/FP7-ICT-
2013 and 282004/FP7-HEALTH.2011.2.3.1-2 from
the European Union Seventh Framework Programme
to FC and grant BFU2014-55534-C2-2-P from the
Spanish Ministry of Economy and Competitiveness to
GM. The funders had no role in study design, data
collection and analysis, decision to publish, or
preparation of the manuscript
Probabilistic fire spread forecast as a management tool in an operational setting
Background: An approach to predict fire growth in an operational setting, with the
potential to be used as a decision-support tool for fire management, is described and
evaluated. The operational use of fire behaviour models has mostly followed a deterministic
approach, however, the uncertainty associated with model predictions needs
to be quantified and included in wildfire planning and decision-making process during
fire suppression activities. We use FARSITE to simulate the growth of a large wildfire.
Probabilistic simulations of fire spread are performed, accounting for the uncertainty
of some model inputs and parameters. Deterministic simulations were performed for
comparison. We also assess the degree to which fire spread modelling and satellite
active fire data can be combined, to forecast fire spread during large wildfires events.
Results: Uncertainty was propagated through the FARSITE fire spread modelling system
by randomly defining 100 different combinations of the independent input variables
and parameters, and running the correspondent fire spread simulations in order
to produce fire spread probability maps. Simulations were initialized with the reported
ignition location and with satellite active fires. The probabilistic fire spread predictions
show great potential to be used as a fire management tool in an operational setting,
providing valuable information regarding the spatial–temporal distribution of burn
probabilities. The advantage of probabilistic over deterministic simulations is clear
when both are compared. Re-initializing simulations with satellite active fires did not
improve simulations as expected.
Conclusion: This information can be useful to anticipate the growth of wildfires
through the landscape with an associated probability of occurrence. The additional
information regarding when, where and with what probability the fire might be in the
next few hours can ultimately help minimize the negative environmental, social and
economic impacts of these firesinfo:eu-repo/semantics/publishedVersio
Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells:Comparison with human bone marrow and adipose-derived mesenchymal stem cells
We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair
Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women
<p>Abstract</p> <p>Background</p> <p>After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time.</p> <p>Objective</p> <p>The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women.</p> <p>Methods</p> <p>Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis.</p> <p>Results</p> <p>Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05).</p> <p>Conclusion</p> <p>In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time.</p
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