692 research outputs found
Kinase Inhibitor Profile For Human Nek1, Nek6, And Nek7 And Analysis Of The Structural Basis For Inhibitor Specificity
Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Ă262-1258)-(T162A), Isogranulatimide for hNek6(S206A), and GSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the respective hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by molecular docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.20111761191Rubin, G.M., Yandell, M.D., Wortman, J.R., Gabor Miklos, G.L., Nelson, C.R., Hariharan, I.K., Fortini, M.E., Fleischmann, W., Comparative genomics of the eukaryotes (2000) Science, 287, pp. 2204-2215Johnson, L.N., Lowe, E.D., Noble, M.E., Owen, D.J., The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases (1998) FEBS Lett., 430, pp. 1-11Hanks, S.K., Eukaryotic protein kinases (1991) Curr. Opin. Struct. 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In situ short-term responses of Amazonian understory plants to elevated CO<sub>2</sub>
The response of plants to increasing atmospheric CO2 depends on the ecological context where the plants are found. Several experiments with elevated CO2 (eCO2) have been done worldwide, but the Amazonian forest understory has been neglected. As the central Amazon is limited by light and phosphorus, understanding how understory responds to eCO2 is important for foreseeing how the forest will function in the future. In the understory of a natural forest in the Central Amazon, we installed four open-top chambers as control replicates and another four under eCO2 (+250 ppm above ambient levels). Under eCO2, we observed increases in carbon assimilation rate (67%), maximum electron transport rate (19%), quantum yield (56%), and water use efficiency (78%). We also detected an increase in leaf area (51%) and stem diameter increment (65%). Central Amazon understory responded positively to eCO2 by increasing their ability to capture and use light and the extra primary productivity was allocated to supporting more leaf and conducting tissues. The increment in leaf area while maintaining transpiration rates suggests that the understory will increase its contribution to evapotranspiration. Therefore, this forest might be less resistant in the future to extreme drought, as no reduction in transpiration rates were detected.</p
Noether gauge symmetry for gravity in Palatini formalism
In this study, we consider a flat Friedmann-Robertson-Walker (FRW) universe
in the context of Palatini theory of gravity. Using the dynamical
equivalence between gravity and scalar-tensor theories, we construct a
point Lagrangian in the flat FRW spacetime. Applying {\em Noether gauge
symmetry approach} for this Lagrangian we find out the form of
and the exact solution for cosmic scale factor. It is shown that the resulting
form of yield a power-law expansion for the scale factor of the
universe.Comment: 7 pagese, no figures; Published in Astrophysics & Space Science. Some
minor corrections have been mad
Novos genes de resistĂŞncia Ă ferrugem-asiĂĄtica-da-soja: teste de alelismo para os locos Rpp2 e Rpp4
Anålise de diversidade genÊtica do gene da osteopontina em bovinos da raça girolando
Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV
Results are presented from a search for a W' boson using a dataset
corresponding to 5.0 inverse femtobarns of integrated luminosity collected
during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV.
The W' boson is modeled as a heavy W boson, but different scenarios for the
couplings to fermions are considered, involving both left-handed and
right-handed chiral projections of the fermions, as well as an arbitrary
mixture of the two. The search is performed in the decay channel W' to t b,
leading to a final state signature with a single lepton (e, mu), missing
transverse energy, and jets, at least one of which is tagged as a b-jet. A W'
boson that couples to fermions with the same coupling constant as the W, but to
the right-handed rather than left-handed chiral projections, is excluded for
masses below 1.85 TeV at the 95% confidence level. For the first time using LHC
data, constraints on the W' gauge coupling for a set of left- and right-handed
coupling combinations have been placed. These results represent a significant
improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe
Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV
A search for a Higgs boson decaying into two photons is described. The
analysis is performed using a dataset recorded by the CMS experiment at the LHC
from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an
integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross
section of the standard model Higgs boson decaying to two photons. The expected
exclusion limit at 95% confidence level is between 1.4 and 2.4 times the
standard model cross section in the mass range between 110 and 150 GeV. The
analysis of the data excludes, at 95% confidence level, the standard model
Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The
largest excess of events above the expected standard model background is
observed for a Higgs boson mass hypothesis of 124 GeV with a local significance
of 3.1 sigma. The global significance of observing an excess with a local
significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is
estimated to be 1.8 sigma. More data are required to ascertain the origin of
this excess.Comment: Submitted to Physics Letters
Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV
The Lambda(b) differential production cross section and the cross section
ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum
pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7
TeV using data collected by the CMS experiment at the LHC. The measurements are
based on Lambda(b) decays reconstructed in the exclusive final state J/Psi
Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and
Lambda to proton pion, using a data sample corresponding to an integrated
luminosity of 1.9 inverse femtobarns. The product of the cross section times
the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls
faster than that of b mesons. The measured value of the cross section times the
branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06
+/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for
anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are
statistical and systematic, respectively.Comment: Submitted to Physics Letters
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