1,539 research outputs found
Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets
<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3â38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div
Influencia de la EducaciĂłn FĂsica en jugadores de FĂștbol AsociaciĂłn Sub-13 y Sub-15
The present study aims to evaluate the lifestyles of association football players in the under-13 and under-15 categories. The sample consisted of two association football teamsâ under-13 (23 players) and under-15 (20 players) from the municipality of Alvarado, Veracruz, Mexico. The results obtained showed that; In food consumption habits, it was identified that 76% of athletes have high consumption of fruits, vegetables and water, while 24% do so poorly, therefore, by category it can be observed that the U-15 obtained higher percentage of healthy food consumption with 82% in contrast to the U-13 with 79%, on the other hand alcohol consumption is in a range of 3% -10% as well as tobacco 4% -10% For this reason, it is concluded that the practice of association football in the under-13 and under-15 categories is a means that allows acquiring healthy lifestyles in the intake of healthy foods, it is also a means to keep adolescents away of drug use.El presente estudio lleva por objetivo evaluar los estilos de vida que llevan los jugadores de fĂștbol asociaciĂłn de las categorĂas sub-13 y sub-15. La muestra fue constituida por dos equipos de fĂștbol asociaciĂłn sub-13 (23 jugadores) y sub-15 (20 jugadores) del municipio de Alvarado, Veracruz, MĂ©xico. Los resultados obtenidos arrojaron que; en los hĂĄbitos de consumo alimenticio se identificĂł que el 76% de los deportistas tienen alto consumo de frutas, verduras y agua, mientras que un 24% lo realiza de forma deficiente, por tanto, por categorĂa se puede observar que la Sub-15 obtuvo mayor porcentaje de consumo de alimentos saludable con el 82% a diferencia de la Sub-13 con un 79%, por otra parte el consumo de alcohol estĂĄ en un rango del 3%-10% asĂ como el del tabaco 4%-10%.Por tal motivo, se concluye que la prĂĄctica del futbol asociaciĂłn en las categorĂas sub-13 y sub-15 es un medio que permite adquirir estilos de vida saludable en la ingesta de alimentos saludables, asĂ mismo es un medio para alejar a los adolescentes del consumo de drogas.
 
Effect of family relatedness on characteristics of estimated IBD probabilities in relation to precision of QTL estimates
<p>Abstract</p> <p>Background</p> <p>A random QTL effects model uses a function of probabilities that two alleles in the same or in different animals at a particular genomic position are identical by descent (IBD). Estimates of such IBD probabilities and therefore, modeling and estimating QTL variances, depend on marker polymorphism, strength of linkage and linkage disequilibrium of markers and QTL, and the relatedness of animals in the pedigree. The effect of relatedness of animals in a pedigree on IBD probabilities and their characteristics was examined in a simulation study.</p> <p>Results</p> <p>The study based on nine multi-generational family structures, similar to a pedigree structure of a real dairy population, distinguished by an increased level of inbreeding from zero to 28% across the studied population. Highest inbreeding level in the pedigree, connected with highest relatedness, was accompanied by highest IBD probabilities of two alleles at the same locus, and by lower relative variation coefficients. Profiles of correlation coefficients of IBD probabilities along the marked chromosomal segment with those at the true QTL position were steepest when the inbreeding coefficient in the pedigree was highest. Precision of estimated QTL location increased with increasing inbreeding and pedigree relatedness. A method to assess the optimum level of inbreeding for QTL detection is proposed, depending on population parameters.</p> <p>Conclusions</p> <p>An increased overall relationship in a QTL mapping design has positive effects on precision of QTL position estimates. But the relationship of inbreeding level and the capacity for QTL detection depending on the recombination rate of QTL and adjacent informative marker is not linear.</p
Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP
Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/Bâ. Results also show that unstructured post- ranslationally modified C-terminal tails are
responsible for the dynamics of Sm-B/Bâ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)
Detection of Usutu virus infection in wild birds in the United Kingdom, 2020
In August 2020, as part of a long-term disease surveillance programme, Usutu virus was detected in five Eurasian blackbirds (Turdus merula) and one house sparrow (Passer domesticus) from Greater London, England. This was initially detected by reverse transcription-PCR and was confirmed by virus isolation and by immunohistochemical detection of flavivirus in tissues. Phylogenetic analysis identified Usutu virus African 3.2 lineage, which is prevalent in the Netherlands and Belgium, suggesting a potential incursion from mainland Europe
Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study
The last decade has seen an explosion in models that describe phenomena in
systems medicine. Such models are especially useful for studying signaling
pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to
showcase current mathematical and statistical techniques that enable modelers
to gain insight into (models of) gene regulation, and generate testable
predictions. We introduce a range of modeling frameworks, but focus on ordinary
differential equation (ODE) models since they remain the most widely used
approach in systems biology and medicine and continue to offer great potential.
We present methods for the analysis of a single model, comprising applications
of standard dynamical systems approaches such as nondimensionalization, steady
state, asymptotic and sensitivity analysis, and more recent statistical and
algebraic approaches to compare models with data. We present parameter
estimation and model comparison techniques, focusing on Bayesian analysis and
coplanarity via algebraic geometry. Our intention is that this (non exhaustive)
review may serve as a useful starting point for the analysis of models in
systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte
The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data
We present constraints on cosmological and astrophysical parameters from
high-resolution microwave background maps at 148 GHz and 218 GHz made by the
Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to
2010. A model of primary cosmological and secondary foreground parameters is
fit to the map power spectra and lensing deflection power spectrum, including
contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the
kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy
from unresolved infrared sources, radio sources, and the correlation between
the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal
SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000,
while the corresponding amplitude of the kinematic SZ power spectrum has a 95%
confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the
WMAP 7-year temperature and polarization power spectra, we find excellent
consistency with the LCDM model. We constrain the number of effective
relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56,
in agreement with the canonical value of Neff=3.046 for three massless
neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39
eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and
Hubble constant measurements. We constrain the amount of primordial helium to
be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure
constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We
also find no evidence for any running of the scalar spectral index, dns/dlnk =
-0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013)
and Dunkley et al. (2013). Matches published JCAP versio
Synthesis and Characterization of Core-shell ZrO2/PAAEM/PS Nanoparticles
This work demonstrates the synthesis of core-shell ZrO2/PAAEM/PS nanoparticles through a combination of solâgel method and emulsifier-free emulsion polymerizaiton. By this method, the modified nanometer ZrO2cores were prepared by chemical modification at a molecular level of zirconium propoxide with monomer of acetoacetoxyethylmethacrylate (AAEM), and then copolymerized with vinyl monomer to form uniform-size hybrid nanoparticles with diameter of around 250 nm. The morphology, composition, and thermal stability of the core-shell particles were characterized by various techniques including transmission electron microscopy (TEM), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal-gravimetry analyzer (TGA). The results indicate that the inorganicâorganic nanocomposites exhibit good thermal stability with the maximum decomposition temperature of ~447 °C. This approach would be useful for the synthesis of other inorganicâorganic nanocomposites with desired functionalities
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