Biomedical subjects

G Lynch

Publications and source records attributed to G Lynch.

At least 109 records · Page 6Linked to original sources

PubMed2003

Study of the rare decays B0-->D(()+)(s)pi(-) and B0-->D(()-)(s)K+.

We report evidence for the decays B0-->D(+)(s)pi(-) and B0-->D(-)(s)K+ and the results of a search for B0-->D(*+)(s)pi(-) and B0-->D(*-)(s)K+ in a sample of 84 x 10(6) upsilon(4S) decays into BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. We measure the branching fractions B(B0-->D(+)(s)pi(-))=[3.2+/-0.9(stat)+/-1.0(syst)] x 10(-5) and B(B0-->D(-)(s)K+)=[3.2+/-1.0(stat)+/-1.0(syst)] x 10(-5). We also set 90% C.L. limits B(B0-->D(*+)(s)pi(-))<4.1 x 10(-5) and B(B0-->D(*-)(s)K+)<2.5 x 10(-5).

Journal Article↗

PubMed2003

Measurement of the Cabibbo-Kobayashi-Maskawa matrix element V(ub) with B-->rhoenu decays.

We present a measurement of the branching fraction for the rare decays B-->rhoenu and extract a value for the magnitude of V(ub), one of the smallest elements of the Cabibbo-Kobayashi-Maskawa quark-mixing matrix. The results are given for five different calculations of form factors used to para-metrize the hadronic current in semileptonic decays. Using a sample of 55 x 10(6) BB meson pairs recorded with the BABAR detector at the PEP-II e(+)e(-) storage ring, we obtain B(B0-->rho(-)e(+)nu)=(3.29+/-0.42+/-0.47+/-0.55) x 10(-4) and |V(ub)|=(3.64+/-0.22+/-0.25(+0.39)(-0.56)) x 10(-3), where the uncertainties are statistical, systematic, and theoretical, respectively.

Journal Article↗

PubMed2003

Long-term potentiation in the Eocene.

The first ten years of long-term potentiation (LTP) research are reviewed. Surprisingly, given the intensity of current interest, the discovery paper did not trigger a wave of follow-on experiments. Despite this, the initial work laid out what ultimately became standard questions and paradigms. The application of the then still novel hippocampal slice technique oriented LTP towards basic neuroscience, perhaps somewhat at the cost of lesser attention to its functional significance. The use of slices led to the discovery of the events that trigger the formation of LTP and provided some first clues about its extraordinary persistence. Signs of the intense controversy over the nature of LTP expression (release vs receptors) emerged towards the end of the first decade of work. What appears to be lacking in the literature of that time is a widespread concern about LTP and memory. This may reflect a somewhat different attitude that neurobiologists then had towards memory research and a perceived need to integrate the new potentiation phenomenon into the web of established science before advancing extended arguments about its contributions to behaviour.

Animals↗

PubMed2003

Measurement of the B0-->J/psipi+pi- branching fraction.

We present a measurement of the branching fraction for the decay of the neutral B meson into the final state J/psipi(+)pi(-). The data set contains approximately 56 x 10(6) BB pairs produced at the Upsilon(4S) resonance and recorded with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. The result of this analysis is B(B0-->J/psipi(+)pi(-))=(4.6+/-0.7+/-0.6) x 10(-5), where the first error is statistical and the second is systematic. In addition, we measure B(B0-->J/psirho(0))=(1.6+/-0.6+/-0.4) x 10(-5).

Journal Article↗

PubMed2003

Developmental and regional differences in the consolidation of long-term potentiation.

The alpha5beta1 integrin is present in high concentrations in the apical dendrites of pyramidal neurons in adult rats but is virtually absent in the basal dendrites. Moreover, alpha5beta1 does not appear in apical dendritic branches until the third post-natal week. Given that integrins contribute to the consolidation of synaptic plasticity, these results raise the possibility of developmental and regional differences in the stability of long-term potentiation (LTP). The present study tested this point using a LTP reversal paradigm in field CA1 of hippocampal slices. In accord with earlier reports, low-frequency afferent stimulation (5 Hz) introduced 30 s after theta burst stimulation (TBS) completely reversed LTP but was ineffective 30 min and 60 min later in slices from adult rats. The same low-frequency trains caused a partial reversal of LTP when applied 30 and 60 min post-TBS in slices from 21-day-old rats and a complete reversal at all time points in slices from 10-day-old rats. LTP in the basal dendrites of adult rats did not fully consolidate; i.e. potentiation was partially reversed by low-frequency stimulation even after delays of 30 or 60 min. Moreover, spaced (10 min) applications of 5- Hz pulses beginning at 30 min post-TBS completely erased LTP. The reversal effect in both apical and basal dendrites was blocked by N-methyl-D-aspartic acid receptor antagonists but an integrin antagonist had differential effects across the two dendritic domains. These results constitute evidence that the stability of LTP increases with age in the apical dendrites but remains incomplete even in adulthood in the basal dendrites. The possibilities that the developmental and regional variations in LTP consolidation are correlated with integrin expression and linked to different types of memory processing are discussed.

Animals↗

PubMed2003

Integrins regulate neuronal neurotrophin gene expression through effects on voltage-sensitive calcium channels.

Integrin adhesion receptors regulate gene expression during growth and differentiation in various cell types. Recent work, implicating integrins in functional synaptic plasticity, suggest they may have similar activities in adult brain. The present study tested if integrins binding the arginine-glycine-aspartate (RGD) matrix sequence regulate neurotrophin and neurotrophin receptor gene expression in cultured hippocampal slices. The soluble RGD-containing peptide glycine-arginine-glycine-aspartate-serine-proline (GRGDSP) increased neurotrophin mRNA levels in transcript- and subfield-specific fashions. Integrin ligand effects were greatest for brain-derived neurotrophic factor transcripts I and II and barely detectable for transcript III. In accordance with increased nerve growth factor mRNA levels, GRGDSP increased c-fos expression as well. In contrast, growth-associated protein-43, amyloid precursor protein and fibroblast growth factor-1 mRNAs were not elevated. Ligand effects on brain-derived neurotrophic factor transcript II and c-fos mRNA did not depend on the integrity of the actin cytoskeleton, neuronal activity, or various signaling pathways but were blocked by L-type voltage-sensitive calcium-channel blockers. These results indicate that in mature hippocampal neurons integrin engagement regulates expression of a subset of growth-related genes at least in part through effects on calcium influx. Accordingly, these synaptic adhesion receptors may play the same role in maintaining an adult, differentiated state in brain as they do in other tissues and changes in integrin activation and/or engagement may contribute to dynamic changes in neurotrophin expression and to neuronal calcium signaling.

Anesthetics, Local↗

PubMed2003

Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion.

It has been proposed that glutamatergic and dopaminergic systems are functionally opposed in their regulation of striatal output. The present study tested the effects of drugs that enhance AMPA-receptor-mediated glutamatergic transmission (ampakines) for their effects on dopamine-related alterations in cortical activity and locomotor behavior. Rats with unilateral 6-hydroxydopamine lesions of the ascending nigro-striatal dopamine system were sensitized to methamphetamine and then tested for methamphetamine-induced circling behavior in the presence and absence of ampakines CX546 and CX614. Both ampakines produced rapid, dose-dependent reductions in circling that were evident within 15 min and sustained through 1 h of behavioral testing. In situ hybridization maps of c-fos mRNA expression showed that in the intact hemisphere, ampakine cotreatment markedly increased c-fos expression in parietal, sensori-motor neocortex above that found in rats treated with methamphetamine alone. Ampakine cotreatment did not augment c-fos expression in frontal, sensori-motor cortex or striatum. Still larger ampakine-elicited effects were obtained in parietal cortex of the dopamine-depleted hemisphere where labeling densities were increased by approximately 60% above values found in methamphetamine-alone rats. With these effects, the hemispheric asymmetry of cortical activation was less pronounced in the ampakine-cotreatment group as compared with the methamphetamine-alone group. These results indicate that positive modulation of AMPA-type glutamate receptors 1) can offset behavioral disturbances arising from sensitized dopamine receptors and 2) increases aggregate neuronal activity in a regionally selective manner that is probably dependent upon behavioral demands.

Adrenergic Agents↗

PubMed2002

Measurements of branching fractions and CP-violating asymmetries in B0-->pi+pi-, K+pi-, K+K- decays.

We present measurements of branching fractions and CP-violating asymmetries for two-body neutral B meson decays to charged pions and kaons based on a sample of about 88x10(6) Upsilon(4S)-->BB decays. From a time-independent fit we measure the charge-averaged branching fractions B(B0-->pi+pi-)=(4.7+/-0.6+/-0.2)x10(-6), B(B0-->K+pi-)=(17.9+/-0.9+/-0.7)x10(-6), and the direct CP-violating charge asymmetry A(Kpi)=-0.102+/-0.050+/-0.016 [-0.188,-0.016], where the ranges in square brackets indicate the 90% confidence intervals. From a time-dependent fit we measure the B0-->pi+pi- CP-violating parameters S(pipi)=0.02+/-0.34+/-0.05 [-0.54,+0.58] and C(pipi)=-0.30+/-0.25+/-0.04 [-0.72,+0.12].

Journal Article↗

PubMed2002

Measurement of the CP asymmetry amplitude sin2beta with B0 mesons.

We present results on time-dependent CP asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 x 10(6) Upsilon(4S)-->B(-)B decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B(0) or B(-0) from its decay products. The amplitude of the CP asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta=0.741+/-0.067(stat)+/-0.034(syst) and |lambda|=0.948+/-0.051(stat)+/-0.030(syst). The magnitude of lambda is consistent with unity, in agreement with the standard model expectation of no direct CP violation in these modes.

Journal Article↗

PubMed2002

Measurement of the branching fraction and CP content for the decay B0-->D(+)D(-).

We report a measurement of the branching fraction of the decay B0-->D(*+)D(*-) and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4 fb (-1) collected at the Upsilon(4S) resonance during 1999-2000, we have reconstructed 38 candidate signal events in the mode B0-->D(*+)D(*-) with an estimated background of 6.2+/-0.5 events. From these events, we determine the branching fraction to be B(B0-->D(*+)D(*-))=[8.3+/-1.6(stat)+/-1.2(syst)]x10(-4). The measured CP-odd fraction of the final state is 0.22+/-0.18(stat)+/-0.03(syst).

Journal Article↗

PubMed2002

Measurement of the B(0) lifetime with partially reconstructed B(0)-->D(-)l(+)nu(l) decays.

The B(0) lifetime was measured with a sample of 23 million BB pairs collected by the BABAR detector at the PEP-II e(+)e(-) storage ring during 1999 and 2000. Events from the semileptonic decay B(0)-->D(*-)l(+)nu(l) have been selected with a partial reconstruction method in which only the charged lepton and the slow pi from the D*--->D(0)pi(-) decay are reconstructed. The result is tau(B(0)) = 1.529+/-0.012(stat)+/-0.029(syst) ps.

Journal Article↗

PubMed2002

Search for the rare decays B-->Kl(+)l(-) and B-->K(*)l(+)l(-).

We present results from a search for the flavor-changing neutral current decays B-->Kl(+)l(-) and B-->K(*)l(+)l(-), where l(+)l(-) is either an e(+)e(-) or mu(+)mu(-) pair. The data sample comprises 22.7 x 10(6) Upsilon(4S)-->B(-)B decays collected with the BABAR detector at the PEP-II B Factory. We obtain the 90% C.L. upper limits B(B-->Kl(+)l(-))<0.51 x 10(-6) and B(B-->K(*)l(+)l(-))<3.1 x 10(-6), close to standard model predictions for these branching fractions. We have also obtained limits on the lepton-family-violating decays B-->Ke+/-mu(-/+) and B-->K(*)e(+/-)mu(-/+).

Journal Article↗

PubMed2002

Measurement of B0-B-0 flavor oscillations in hadronic B0 decays.

Flavor oscillations of neutral B mesons have been studied in e+e- annihilation data collected with the BABAR detector at center-of-mass energies near the upsilon(4S) resonance. The data sample used for this purpose consists of events in which one B0 meson is reconstructed in a hadronic decay mode, while the flavor of the recoiling B0 is determined with a tagging algorithm that exploits the correlation between the flavor of the heavy quark and the charges of its decay products. From the time development of the observed mixed and unmixed final states, we determine the B0-B-0 oscillation frequency deltamd to be 0.516+/-0.016(stat)+/-0.010(syst) ps-1.

Journal Article↗

PubMed2002

Measurement of the B0-B-0 oscillation frequency with inclusive dilepton events.

The B0-B-0 oscillation frequency has been measured with a sample of 23 x 10(6) BB- pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives deltamd = 0.493+/-0.012(stat)+/-0.009(syst) ps-1.

Journal Article↗

PubMed2002

Search for T and CP violation in B0-B-0 mixing with inclusive dilepton events.

We report the results of a search for T and CP violation in B0-B-0 mixing using an inclusive dilepton sample collected by the BABAR experiment at the PEP-II B Factory. The asymmetry between l+l+ and l-l- events allows us to compare the probabilities for B-0-->B0 and B0-->B-0 oscillations and thus probe T and CP invariance. Using a sample of 23 x 10(6) BB- pairs, we measure a same-sign dilepton asymmetry of A(T/CP) = [0.5+/-1.2(stat)+/-1.4(syst)]%. For the modulus of the ratio of complex mixing parameters p and q, we obtain q/p = 0.998+/-0.006(stat)+/-0.007(syst).

Journal Article↗

PubMed2002

Measurement of B --> K*gamma branching fractions and charge asymmetries.

The branching fractions of the exclusive decays B0-->K(*0)gamma and B+-->K(*+)gamma are measured from a sample of (22.74+/-0.36)x10(6) BB decays collected with the BABAR detector at the PEP-II asymmetric e(+)e(-) collider. We find B (B0-->K(*0)gamma) = [4.23+/-0.40(stat)+/-0.22(syst)]x10(-5), B(B+-->K(*+)gamma) = [3.83+/-0.62(stat)+/-0.22(syst)]x10(-5) and constrain the CP-violating charge asymmetry to be -0.170 K(*)gamma)<0.082 at 90% C.L.

Journal Article↗

PubMed2002

Alpha3 integrin receptors contribute to the consolidation of long-term potentiation.

Several lines of evidence suggest that integrin receptors play a pivotal role in consolidation of long-term potentiation (LTP), but which of the many integrin dimers are involved remains to be discovered. The present study used an LTP reversal paradigm to test if alpha3 integrins make an important contribution. Function blocking alpha3 monoclonal antibodies or vehicle were locally infused into recording sites in field CA1 of rat hippocampal slices and LTP induced with theta burst stimulation. Low frequency trains of pulses were applied 30 min after the theta bursts. Previous work indicates that low frequency stimulation reverses LTP when applied immediately after induction but is largely ineffective after 30-45-min delays. If the antibodies were to block consolidation, then they should extend the period over which potentiation is vulnerable to disruption. There was no detectable difference between the two groups in the initial degree of LTP or within slice decay of potentiation 1-10 min after induction; a small but reliable decay occurred from 10 to 30 min with antibody treatment (P<0.01) but not in control slices. Percent potentiation was not statistically different for vehicle (55 +/- 19%, mean +/- S.D.) and anti-alpha3 (43 +/- 21%) slices at 30 min post-theta bursts. Five-Hz stimulation ("theta pulse" stimulation) 30 min after induction caused a reduction of LTP. The percent loss of potentiation after the 1-min trains was greater in the antibody-treated slices than in controls (98 +/- 4% vs. 62 +/- 28%, P<0.01, U-test) and correlated (r=0.84, alpha3 slices) with the percent LTP present prior to low frequency stimulation, as expected if the stimulation reversed potentiation. Recovery occurred in both groups but percent LTP was significantly smaller in experimental slices at 10 min post-theta pulses (5 +/- 11% vs. 36 +/- 15%, P<0.01). Recovery continued for 20 min after theta pulses and, in accordance with earlier work, was nearly complete for the control slices (50 +/- 19% vs 55 +/- 15%, 40 min post- vs. immediately pre-theta pulses). LTP remained depressed after 40 min of recovery in the anti-alpha3 slices (23 +/- 19% vs. 43 +/- 21%) at which point it was substantially less than that found in controls (P<0.01). Western blots with anti-alpha3 antibodies identified a polypeptide with the molecular mass (155 kDa) expected for the alpha3 subunit and further showed that it is broadly distributed in brain. Subcellular fractionation experiments demonstrated that alpha3 is concentrated in synaptic membranes over homogenates to about the same degree as the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor. From these results we suggest that alpha3-containing integrins are localized to synapses and are needed to stabilize a slowly decaying form of LTP. The findings also show that vulnerability to reversal can be used in place of extended recording sessions in studying consolidation.

Animals↗

PubMed2002

Uptake and pathogenic effects of amyloid beta peptide 1-42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists.

Many synapses contain two types of receptors - integrins and N-methyl-D-aspartate (NMDA) receptors - that have been implicated in peptide internalization. The present studies tested if either class is involved in the uptake of the 42-residue form of amyloid beta peptide (Abeta1-42), an event hypothesized to be of importance in the development of Alzheimer's disease. Cultured hippocampal slices were exposed to Abeta1-42 for 6 days in the presence or absence of soluble Gly-Arg-Gly-Asp-Ser-Pro, a peptide antagonist of Arg-Gly-Asp (RGD)-binding integrins, or the disintegrin echistatin. Abeta uptake, as assessed with immunocytochemistry, occurred in 42% of the slices incubated with Abeta peptide alone but in more than 80% of the slices co-treated with integrin antagonists. Uptake was also found in a broader range of hippocampal subfields in RGD-treated slices. Increased sequestration was accompanied by two characteristics of early stage Alzheimer's disease: elevated concentrations of cathepsin D immunoreactivity and activation of microglia. The selective NMDA receptor antagonist D-(-)-2-amino-5-phosphonovalerate completely blocked internalization of Abeta, up-regulation of cathepsin D, and activation of microglia. Our results identify two classes of receptors that cooperatively regulate the internalization of Abeta1-42 and support the hypothesis that characteristic pathologies of Alzheimer's disease occur once critical intraneuronal Abeta concentrations are reached.

2-Amino-5-phosphonovalerate↗