Heterotrimeric G Proteins and the Regulation of Microtubule Assembly

Microtubules (MTs), a major component of cell cytoskeleton, exhibit diverse cellular functions including cell motility, intracellular transport, cell division, and differentiation. These functions of MTs are critically dependent on their ability to polymerize and depolymerize. Although a significant progress has been made in identifying cellular factors that regulate microtubule assembly and dynamics, the role of signal transducing molecules in this process is not well understood. It has been demonstrated that heterotrimeric G proteins, which are components of G protein-coupled receptor (GPCR) signaling pathway, interact with microtubules and play important roles in regulating assembly/dynamics of this cytoskeletal filament. While α subunit of G proteins (Gα) inhibits microtubule assembly and accelerates microtubule dynamics, Gβγ promotes tubulin polymerization. In this chapter, we review the current status of G-protein modulation of microtubules and cellular and physiological aspects of this regulation. Molecular, biochemical, and cellular methodologies that have been used to advance this field of research are discussed. Emphasis has been given on G-protein-microtubule interaction in neuronal differentiation as significant progress has been made in this field. The outcome from this research reflects the importance of GPCRs in transducing extracellular signals to regulate a variety of microtubule-associated cellular events

Cypermethrin, deltamethrin and glyphosate affect the activity of the Ca2 +-ATPase from human erythrocyte

Abstract The extensive use of pesticides can cause many human health problems. However, the effects of pesticides on a biochemical level are still poorly understood. In this study we analyzed the effect of different pesticides on the plasma membrane Ca2+-ATPase (PMCA) and on the sarco/ endoplasmic reticulum Ca2+-ATPase (SERCA) activities. Different amounts of pesticides were added to the Ca2+- dependent ATPase assays in order to determine if they were affecting the ATPase activity. The results showed that PMCA activity was partially inhibited by deltamethrin to 51.85% ± 3.7 when its concentration in the reaction medium was 0.5 mM, while cypermethrin and glyphosate stimulated the PMCA activity at the lowest concentrations tested. The maximum stimulatory effect of cypermethrin was of 155% ± 9.0 at a concentration of 0.2 mM. In addition, the herbicide glyphosate stimulated the activity 111% ± 2.0 at a concentration of 0.2 mM. In conclusion, our results showed that PMCA activity was partially inhibited by deltamethrin, but cypermethrin and glyphosate stimulated their activity. Our findings suggest that cypermethrin and deltamethrin have different structure- activity relationships. However, SERCA was not sensitive to deltamethrin or glyphosate. These differences may be reflected in disturbs over cellular calcium regulation. Resumen Se ha observado que la exposición de personas a plaguicidas puede causar problemas a la salud. Sin embargo, el estudio del efecto de plaguicidas a un nivel bioquímico ha sido pobremente estudiado. En este estudio, analizamos el efecto de cipermetrina, deltametrina y glifosato sobre la actividad enzimática de las Ca2+- ATPasa de membrana plasmática (PMCA) y de retículo sarcoplásmico (SERCA). Diferentes concentraciones de estos pesticidas fueron añadidas a los experimentos de actividad enzimática como estrategia para determinar si estos compuestos eran capaces de afectar la actividad enzimática de PMCA. Nuestros resultados demuestran que la actividad enzimática de PMCA fue parcialmente inhibida por deltametrina en un 51.85% ± 3.7 cuando su concentración fue de 0.5 mM, mientras que cipermetrina y glifosato estimularon la actividad enzimática de PMCA a menores concentraciones. El máximo efecto estimulatorio de cipermetrina fue de 155% ± 9.0 cuando el compuesto alcanzó una concentración de 0.2 mM. Además, el herbicida glifosato fue capaz de estimular la actividad enzimática de PMCA en un 111% ± 2.0 a concentraciones de 0.1-0.2 mM. En conclusión, nuestros resultados demostraron que la actividad enzimática de PMCA fue también parcialmente inhibida con deltametrina, pero al contrario de cipermetrina y glifosato la estimularon. Nuestros resultados sugieren que las diferencias en las estructuras químicas de cipermetrina y deltametrina se ven reflejadas en el efecto provocado sobre PMCA. Sin embargo, una enzima similar, SERCA, no fue afectada ni por deltametrina ni glifosato. Estas diferencias se pudieran ver reflejadas en disturbios sobre la regulación celular del calcio. Palabras clave: PMCA (ATPasa de Ca2+ de membrana plasmática), SERCA (ATPasa de Ca2+ de retículo endo/sarcoplásmico), actividad enzimática, cipermetrina, deltametrina, glifosato

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

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

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO