Miller Fisher syndrome‐associated anti‐GQ1b ganglioside antibodies produce an acute complement‐dependent neuroexocytic effect at the mouse neuromuscular junction (NMJ) that closely resembles the ...effect of α‐latrotoxin (LTx). This pathophysiological effect is accompanied by morphological disruption of the nerve terminal involving the loss of major cytoskeletal components, including neurofilament. Both LTx and the membrane attack complex of complement form membrane pores that allow free ionic movement and we have previously hypothesized that Ca2+ ingress and the subsequent activation of Ca2+‐dependent proteases, calpains, may lead to substrate degradation resulting in structural disorganization of the terminal. Here, we treated mouse NMJs in hemidiaphragm preparations with anti‐GQ1b antibodies and complement, or with LTx in the presence and absence of extracellular Ca2+, and studied possible neuroprotective effects of the calpain inhibitors calpeptin and calpain inhibitor V. Both Ca2+ depletion and calpain inhibition protected the cytoskeleton from degradation, as assessed by immunohistological and ultrastructural analysis. Calpain inhibitors may therefore be useful therapeutically in limiting nerve terminal and axonal injury in autoimmune peripheral neuropathy and in human latrodectism.
Anti-disialoside antibodies (Abs) that bind NeuAc(α2–8) NeuAc epitopes on GQ1b and related gangliosides are found in human autoimmune neuropathy sera and are considered to be pathogenic. In a model ...system in mice, one mechanism by which anti-disialoside Abs have been demonstrated to induce paralysis is through a complement dependent blocking effect on transmitter release at the neuromuscular junction, similar to the effects of α-latrotoxin. Although direct targeting of presynaptic neuronal membranes occurs in this model, concomitant injury to perisynaptic Schwann cells (pSC) could indirectly contribute to this paralytic effect by influencing nerve terminal function and survival. To examine this possibility and the specific complement components that might mediate these effects, we exposed neuromuscular junctions in vivo and in vitro to an anti-disialoside Ab in conjunction with intact and selectively deficient complement sources. Using immuno-electron microscopy, we observed Ab deposits equally distributed on both neuronal and pSC membranes, and ultrastructural evidence of injury at both sites. Presynaptic neuronal injury was demonstrated functionally with microelectrode recordings and histologically as neurofilament loss. As hypothesized, concomitant pSC injury occurred, as indicated by abnormal uptake of ethidium dimer into pSC nuclei. The pSC and nerve terminal damage indicators correlated well with deposition of the pore-forming terminal complement component, membrane attack complex (MAC) in pSC and nerve terminal membranes. Furthermore, both neuronal and pSC injury were exacerbated in tissues from mice lacking the inhibitory complement regulator, CD59, where MAC formation is increased. These data demonstrate that both presynaptic neuronal membranes and pSCs are targets for anti-disialoside Abs, and that the injury to both sites is mediated by MAC and further regulated by CD59. This is the first demonstration that complement mediated pSC injury occurs in a model of autoimmune neuropathy and provides a rationale for investigating the possibility of pSC injury in equivalent conditions in man.
The only anticipated resonant contributions to B^{+}→D^{+}D^{-}K^{+} decays are charmonium states in the D^{+}D^{-} channel. A model-independent analysis, using LHCb proton-proton collision data ...taken at center-of-mass energies of sqrts=7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9 fb^{-1}, is carried out to test this hypothesis. The description of the data assuming that resonances only manifest in decays to the D^{+}D^{-} pair is shown to be incomplete. This constitutes evidence for a new contribution to the decay, potentially one or more new charm-strange resonances in the D^{-}K^{+} channel with masses around 2.9 GeV/c^{2}.
Results are reported from an amplitude analysis of the B+ → D+D− K+ decay. The analysis is carried out using LHCb proton-proton collision data taken at √s = 7, 8, and 13 TeV, corresponding to a total ...integrated luminosity of 9 fb−1. In order to obtain a good description of the data, it is found to be necessary to include new spin-0 and spin-1 resonances in the D−K+ channel with masses around 2.9 GeV/c2, and a new spin-0 charmonium resonance in proximity to the spin-2 χc2(3930) state.
An improved measurement of the decay $B^0_S$ → $μ^+μ^-$ and searches for the decays $B^0$ → $μ^+μ^+$ and $B^0_S$ → $μ^+μ^-γ$ are performed at the LHCb experiment using data collected in proton-proton ...collisions at $\sqrt{s}$ = 7, 8 and 13 TeV. corresponding to integrated luminosities of 1, 2 and 6 fb-1, respectively. The $B^0_S$ → $μ^+μ^-$ branching fraction and effective lifetime are measured to be $\mathscr{B}$($B^0_S$ → $μ^+μ^-$) = (3.09$^{(+0.46+0.15)}_{(-0.43-0.11)}$) x 10-9 and $τ(B^0_s →μ^+μ^-)$ = (2.07 ± 0.29 ± 0.03) ps, respectively, where the uncertainties include both statistical and systematic contributions. No significant signal for $B^0$ → $μ^+μ^-$ and $B^0_S$ → $μ^+μ^-γ$ decays is found and the upper limits $\mathscr{B}$($B^0$ → $μ^+μ^-$) < 2.6 x 10-10 and $B^0_S$ → $μ^+μ^-γ$ < 2.0 x 10-9 at 95% confidence level are determined, where the latter is limited to the range $m_{μμ}$ > 4.9 GeV/c2. Additionally, the ratio between the $B^0$ → $μ^+μ^-$ and $B^0_S$ → $μ^+μ^-$ branching fractions is measured to be $\mathscr{R}_{μ+μ-}$ < 0.095 at 95% confidence level. The results are in agreement with the Standard Model predictions.
Measurement of the W boson mass Ackernley, T.; Balagura, V.; Belyaev, I. ...
The journal of high energy physics,
2022, Letnik:
2022, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A
bstract
The
W
boson mass is measured using proton-proton collision data at
s
= 13 TeV corresponding to an integrated luminosity of 1.7 fb
−
1
recorded during 2016 by the LHCb experiment. With a ...simultaneous fit of the muon
q/p
T
distribution of a sample of
W
→
μν
decays and the
ϕ
*
distribution of a sample of
Z
→
μμ
decays the
W
boson mass is determined to be
m
w
=
80354
±
23
stat
±
10
exp
±
17
theory
±
9
PDF
MeV
,
where uncertainties correspond to contributions from statistical, experimental systematic, theoretical and parton distribution function sources. This is an average of results based on three recent global parton distribution function sets. The measurement agrees well with the prediction of the global electroweak fit and with previous measurements.
A study of the lineshape of the χc1 ( 3872 ) state is made using a data sample corresponding to an integrated luminosity of 3 fb−1 collected in p p collisions at center-of-mass energies of 7 and ...8 TeV with the LHCb detector. Candidate χc1 ( 3872 ) and ψ ( 2S ) mesons from b -hadron decays are selected in the J / ψ π+ π− decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the χc1 ( 3872 ) and ψ ( 2S ) states, Δm, and the width of the χc1 ( 3872 ) state, ΓBW, are determined to be ..., where the first uncertainty is statistical and the second systematic. Using a Flatté-inspired model, the mode and full width at half maximum of the lineshape are determined to be ... . An investigation of the analytic structure of the Flatté amplitude reveals a pole structure, which is compatible with a quasibound D0 D*0 state but a quasivirtual state is still allowed at the level of 2 standard deviations. (ProQuest: ... denotes formulae omited.).
Angular analysis of the rare decay Bs0→ ϕμ+μ Ackernley, T.; Balagura, V.; Belyaev, I. ...
The journal of high energy physics,
11/2021, Letnik:
2021, Številka:
11
Journal Article
Recenzirano
Odprti dostop
A
bstract
An angular analysis of the rare decay
B
s
0
→ ϕμ
+
μ
−
is presented, using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV, ...corresponding to an integrated luminosity of 8.4 fb
−
1
. The observables describing the angular distributions of the decay
B
s
0
→ ϕμ
+
μ
−
are determined in regions of
q
2
, the square of the dimuon invariant mass. The results are consistent with Standard Model predictions.
A
bstract
A combination of measurements sensitive to the
CP
violation angle
γ
of the Cabibbo-Kobayashi-Maskawa unitarity triangle and to the charm mixing parameters that describe oscillations between
...D
0
and
D
¯
0
mesons is performed. Results from the charm and beauty sectors, based on data collected with the LHCb detector at CERN’s Large Hadron Collider, are combined for the first time. This method provides an improvement on the precision of the charm mixing parameter
y
by a factor of two with respect to the current world average. The charm mixing parameters are determined to be
x
=
0.400
−
0.053
+
0.052
%
and
y
=
0.630
−
0.030
+
0.033
%
. The angle
γ
is found to be
γ
=
65.4
−
4.2
+
3.8
°
and is the most precise determination from a single experiment.
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