Tau Decay Research Articles

Search for lepton-flavor-violating τ−→ μ−μ+μ− decays at Belle II

We present the result of a search for the charged-lepton-flavor violating decay τ− → μ−μ+μ− using a 424 fb−1 sample of data recorded by the Belle II experiment at the SuperKEKB e+e− collider. The selection of e+e− → τ+τ− events is based on an inclusive reconstruction of the non-signal tau decay, and on a boosted decision tree to suppress background. We observe one signal candidate, which is compatible with the expectation from background processes. We set a 90% confidence level upper limit of 1.9 × 10−8 on the branching fraction of the τ−→ μ−μ+μ− decay, which is the most stringent bound to date.

Impacts of DCM-linked gating pore currents on the electrophysiological characteristics of hiPSC-CM monolayers

BackgroundVariants of the SCN5A gene, which encodes the NaV1.5 cardiac sodium channel, have been linked to arrhythmic disorders associated with dilated cardiomyopathy (DCM). However, the precise pathological mechanisms remain elusive. The present study aimed to elucidate the pathophysiological consequences of the DCM-linked Nav1.5/R219H variant, which is known to generate a gating pore current, using patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in monolayers. MethodsVentricular- and atrial-like hiPSC-CM monolayers were generated from DCM patients carrying the R219H SCN5A variant as well as from healthy control individuals. CRISPR-corrected hiPSC-CMs served as isogenic controls. Simultaneous optical mapping of action potentials (APs) and calcium transients (CaTs) was employed to measure conduction velocities (CVs) and AP durations (APDs) and served as markers of electrical excitability. Calcium handling was evaluated by assessing CaT uptake (half-time to peak), recapture (tau of decay), and durations (TD50 and TD80). A multi-electrode array (MEA) analysis was conducted on hiPSC-CM monolayers to measure field potential (FP) parameters, including corrected Fridericia FP durations (FPDc). ResultsOur results revealed that CVs were significantly reduced by more than 50 % in both ventricular- and atrial-like hiPSC-CM monolayers carrying the R219H variant compared to the control group. APDs were also prolonged in the R219H group compared to the control and CRISPR-corrected groups. CaT uptake, reuptake, and duration were also markedly delayed in the R219H group compared to the control and CRISPR-corrected groups in both the ventricular- and the atrial-like hiPSC-CM monolayers. Lastly, the MEA data revealed a notably prolonged FPDc in the ventricular- and atrial-like hiPSC-CMs carrying the R219H variant compared to the control and isogenic control groups. ConclusionsThese findings highlight the impact of the gating pore current on AP propagation and calcium homeostasis within a functional syncytium environment and offer valuable insights into the potential mechanisms underlying DCM pathophysiology.

Discovery potential of the Glashow resonance in an air shower neutrino telescope* *Project Supported by the ``CUG Scholar'' Scientific Research Funds at China University of Geosciences (Wuhan) (2024014)

The in-ice or in-water Cherenkov neutrino telescope, such as IceCube, has already proved its power in measuring the Glashow resonance by searching for the bump around arising from the W-boson production. There are many proposals for the next few decades for observations of cosmic tau neutrinos with extensive air showers, also known as tau neutrino telescopes. The air shower telescope is, in principle, sensitive to the Glashow resonance via the channel followed by the tau decay in the air (e.g., TAMBO, which has a geometric area of approximately ). Using a thorough numerical analysis, we find that the discovery significance can be up to 90% with a TAMBO-like setup if PeV neutrinos primarily originate from neutron decays, considering the flux parameters measured by IceCube as the input. The presence of new physics affecting the neutrino flavor composition can also increase the significance. However, if ultrahigh-energy neutrinos are dominantly produced from meson decays, it will be statistically difficult for an advanced proposal such as TAMBO to discriminate the Glashow resonance induced by from the intrinsic background. We have identified several limitations for such advanced telescopes, in comparison with the in-ice or in-water telescope, when measuring resonances: (i) a suppressed branching ratio of 11% for the decay ; (ii) the smearing effect and reduced acceptance because the daughter neutrino takes away 75% of the energy from the W decay; and (iii) a large attenuation effect for Earth-skimming neutrinos with the resonance.

Global analysis and LHC study of a vectorlike extension of the standard model with extra scalars

We perform a global analysis of a vectorlike extension of the Standard Model, which also features additional doublet and singlet scalars. The usual Yukawa interactions are forbidden in this setup by an extra U(1) global symmetry and the masses of the second and third family quarks and leptons are generated via the mixing with the vectorlike sector. We identify three best-fit benchmark scenarios which satisfy the constraints imposed by the stability of the scalar potential, the perturbativity of the coupling constants, the measurement of the muon anomalous magnetic moment and the nonobservation of the flavor violating tau decays. We show that dominant contributions to the muon (g−2) originate in this model from the charged Higgs/neutral lepton one-loop diagrams, thus correcting an inaccurate statement than can be found in the literature. We also perform a detailed LHC analysis of the benchmark scenarios. We investigate the experimental constraints stemming from direct searches for vectorlike quarks, vectorlike leptons, and exotic scalars. While we show that the model is not currently tested by any collider experiment, we point out that decays of a heavy Higgs boson into two tau leptons may offer a smoking gun signature for the model verification in upcoming runs at the LHC. Published by the American Physical Society 2024

Up-regulated small-conductance calcium-activated potassium currents contribute to atrial arrhythmogenesis in high-fat feeding mice.

Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS. Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023). Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.

Effects of Kaluza-Klein neutrinos on RD and [formula omitted

Recent measurements of RD and RD⁎ by the LHCb collaboration show deviations from their respective Standard Model values. These semileptonic B meson decays, associated with b→cτν¯ transition, are pointing toward new physics beyond the Standard Model via leptonic flavor universality violation. In this paper, we show that such anomaly can be resolved by the cummulative Kaluza-Klein (KK) modes of singlet right-handed neutrino which propagates in the large extra dimensional space. We found that the number of extra dimension should be 2 to explain RD and RD⁎. We show that both RD and RD⁎ constraint the energy scale MF of this extra dimension which are compatible with the limits from lepton flavor violating tau decays. In contrast, our findings are in tension with the limits coming from the neutrino experiments which set the most stringent lower bound on MF. The future measurements of RD(⁎)exp with reduced uncertainties will exclude this extra dimensional model with right-handed neutrino propagating in the bulk, if the central values stay.

Abstract 16997: Cardiomyocyte-Autonomous and Microtubule Dependent Mechanisms Are Sufficient to Mediate Load-Dependent T-Tubule Remodeling

Background: Mechanical overload is an established contributor to T-tubule (TT) remodeling and associated dyssynchronous Ca 2+ release leading to abnormal excitation-contraction coupling in cardiomyopathies. We examined the induction of pathological TT remodeling in isolated cardiomyocytes and the involvement of microtubules (MT) in this process. Methods: Adult rat ventricular myocytes (aRVMs) were cultured with applied variable in vitro load for 48hrs at either physiological (10kPa) or pathological (50kPa) stiffness, using custom magnetorheological elastomers with tunable stiffness. Cells were stained with Di-8-ANEPPS and Fluo-4-AM and imaged using confocal microscopy. Field stimulation of cells allowed for Ca 2+ transient acquisition via line scans. Protein expression changes were determined via Western blotting. IF staining allowed for visualization of the MT network and relevant TT proteins (TCAP, JPH2, BIN1). MT and tyrosination state dependency of remodeling was investigated by 1μM nocodazole (MT depolymerizer), taxol (MT stabilizer), and tubulin tyrosine ligase (TTL) treatments to alter the MT network accordingly. Results: Compared to the physiological stiffness group, aRVMs subjected to pathologically increased stiffness exhibited a 14.7% decrease in density, 18.9% decrease in regularity, and a 26.6% increase in luminal dimension of the TT system, along with an increase in longitudinal elements (p<0.05). The changes in both Ca 2+ handling parameters and protein expression resembled those typical of the in vivo myopathic phenotype. This included a 21.7% decrease in amplitude, along with a 33.7%, 29.8% and 21.1% increase in time to peak (TTP), variance in TTP, and the signal decay tau, respectively (p<0.05). Treatment of pathologically loaded cells with taxol worsened TT remodeling, specifically with respect to TT density which decreased by 12.5% compared to nontreatment cells, and longitudinal elements which increased by 24%. Increased MT tyrosination through TTL treatment showed a 37% recovery in TT density in cells cultured at pathological stiffness compared to nontreatment cells (p<0.05). Conclusion: The results suggest that load-induced TT remodeling occurs via a cardiomyocyte autonomous, MT-dependent mechanism.

Radiative corrections and new physics tests in semileptonic tau decays

I review recent advances in the computation of radiative corrections in one- and two-meson tau decays and sketch their main applications in new physics tests: of lepton universality and CKM unitarity, as well as searching for non-standard interactions.

Electromagnetic corrections in hadronic tau decays

We revisit the isospin-breaking and electromagnetic corrections of some hadronic tau decays, which can also be employed to extract the Cabibbo-Kobayashi-Maskawa (CKM) matrix element Vus. We extend former analyses by Antonelli et al. working with ChPT with resonances. We find that going beyond the Low approximation, these corrections play an important role between the π− K0 and K− π0 modes. The K− K0 channel is also discussed.

Mathematical aspects of the asymptotic expansion in contour improved perturbation theory for hadronic tau decays

Mathematical aspects of the asymptotic expansion in contour improved perturbation theory for hadronic tau decays

Rare leptonic processes induced by massless dark photon

We introduce a dark photon considering a U(1) gauge extension of the standard model in particle physics. Provided that the extra U(1) symmetry is unbroken, the dark photon is massless and has no coupling to the standard electromagnetic current. Higher-dimensional operators describe interactions of the massless dark photon with particles in the standard model. We investigate the interactions of the massless dark photon with charged leptons via dipole operators, mainly focusing on the lepton family-violating processes. We present an improved constraint in the polarized two-body muon decay and a set of new bounds in tau decays. We also examine possible lepton family-violating signals of the massless dark photon in future lepton colliders.

Cardiac Protein Kinase D1 ablation alters the myocytes β-adrenergic response

β-adrenergic (β-AR) signaling is essential for the adaptation of the heart to exercise and stress. Chronic stress leads to the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase D (PKD). Unlike CaMKII, the effects of PKD on excitation-contraction coupling (ECC) remain unclear. To elucidate the mechanisms of PKD-dependent ECC regulation, we used hearts from cardiac-specific PKD1 knockout (PKD1 cKO) mice and wild-type (WT) littermates. We measured calcium transients (CaT), Ca2+ sparks, contraction and L-type Ca2+ current in paced cardiomyocytes under acute β-AR stimulation with isoproterenol (ISO; 100 nM). Sarcoplasmic reticulum (SR) Ca2+ load was assessed by rapid caffeine (10 mM) induced Ca2+ release. Expression and phosphorylation of ECC proteins phospholambam (PLB), troponin I (TnI), ryanodine receptor (RyR), sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) were evaluated by western blotting. At baseline, CaT amplitude and decay tau, Ca2+ spark frequency, SR Ca2+ load, L-type Ca2+ current, contractility, and expression and phosphorylation of ECC protein were all similar in PKD1 cKO vs. WT. However, PKD1 cKO cardiomyocytes presented a diminished ISO response vs. WT with less increase in CaT amplitude, slower [Ca2+]i decline, lower Ca2+ spark rate and lower RyR phosphorylation, but with similar SR Ca2+ load, L-type Ca2+ current, contraction and phosphorylation of PLB and TnI. We infer that the presence of PKD1 allows full cardiomyocyte β-adrenergic responsiveness by allowing optimal enhancement in SR Ca2+ uptake and RyR sensitivity, but not altering L-type Ca2+ current, TnI phosphorylation or contractile response. Further studies are necessary to elucidate the specific mechanisms by which PKD1 is regulating RyR sensitivity. We conclude that the presence of basal PKD1 activity in cardiac ventricular myocytes contributes to normal β-adrenergic responses in Ca2+ handling.

Pkd1 is necessary for full cardiac AngII-induced hypertrophy but not for full acute AngII-induced calcium handling changes.

The renin-angiotensin system (RAS) regulates blood pressure, extracellular fluid and electrolyte balance, cardiac inotropy, and vascular resistance. In the heart, angiotensin II (AngII) can induce hypertrophy directly by activating Protein Kinase D (PKD), a signaling kinase known to contribute to cardiac remodeling. Little is known, however, about the acute and chronic functional effects of AngII-induced PKD activation on calcium (Ca) handling. To investigate this, we used hearts from cardiac-specific PKD1 knockout (cKO) mice and their WT littermates. We measured Ca transients (CaT) and Ca spark (CaSp) frequencies in cardiomyocytes at 0.5 and 1 Hz pacing under acute and chronic AngII stimulation (100 nM in vitro and 3 mg/kg/day in osmotic minipump, respectively). Sarcoplasmic reticulum (SR) Ca load was assessed by rapid caffeine-induced Ca release. At baseline and after acute AngII treatment, CaT amplitude and tau decay, CaSp frequency and SR Ca load were similar in WT vs. PKD1 cKO. This was also the case for chronic exposure to AngII except that the tau decay was significantly slower in PKD1 cKO myocytes. In agreement with previous reports, echocardiographic measurements revealed that PKD1 cKO mice were also more resistant to chronic AngII-induced hypertrophy (LVPW increase 24.69 ± 2.74% vs. 54.73 ± 7.73 %) and ejection fraction reduction (4.08 ± 1.5% vs. 12.67 ± 0.52%). We conclude that despite PKD being necessary for the remodeling changes induced by chronic AngII, it does not alter the amplitude and kinetics of CaT and spontaneous Ca release, except for the slowed decay kinetics in the PKD1 cKO after chronic AngII treatment and decreased acute SR Ca load.

GNN-based end-to-end reconstruction in the CMS Phase 2 High-Granularity Calorimeter

We present the current stage of research progress towards a one-pass, completely Machine Learning (ML) based imaging calorimeter reconstruction. The model used is based on Graph Neural Networks (GNNs) and directly analyzes the hits in each HGCAL endcap. The ML algorithm is trained to predict clusters of hits originating from the same incident particle by labeling the hits with the same cluster index. We impose simple criteria to assess whether the hits associated as a cluster by the prediction are matched to those hits resulting from any particular individual incident particles. The algorithm is studied by simulating two tau leptons in each of the two HGCAL endcaps, where each tau may decay according to its measured standard model branching probabilities. The simulation includes the material interaction of the tau decay products which may create additional particles incident upon the calorimeter. Using this varied multiparticle environment we can investigate the application of this reconstruction technique and begin to characterize energy containment and performance.

EUSO-SPB2: A balloon experiment for UHECR and VHE neutrino observation

The Extreme Universe Space Observatory on a Super Pressure Balloon 2 (EUSO-SPB2) experiment will make new measurements from suborbital space as a precursor for future space missions that will address the challenge of the extremely low fluxes of ultra-high energy cosmic rays (UHECR) and very high energy (VHE) neutrinos. The EUSO-SPB2 detector is comprised of two 1m diameter aperture telescopes. The Fluorescence Telescope (FT) will point in nadir and will record fluorescence light from cosmic ray EAS with energies above 1 EeV in its field of view of 36 by 12 degrees. The Cherenkov Telescope (CT) features a silicon photomultiplier focal surface with a field of view of 12 by 6 degrees. The CT will switch between two observation modes: one which points the CT above the limb to measure the Cherenkov emission of cosmic ray EAS with energies above 1 PeV and one which points the CT below the limb to record the Cherenkov emission produced by PeV scale EAS initiated by neutrino-sourced tau decay. As it is the first time such an instrument has been flown, one of the priorities of the CT will be the study of the optical background for observing neutrinos in this way. EUSO-SPB2 is undergoing the final integration steps for launch on a NASA super pressure balloon payload in the spring of 2023 from Wanaka NZ. The CT was field-tested in March 2022 and the FT in August - September 2022. The data collected during the EUSO-SPB2 mission will be essential to advancing the development of a space-based multi-messenger observatory such as the Probe of Extreme Multi-Messenger Astrophysics (POEMMA). In this contribution, we discuss the EUSO-SPB2 science goals, the instruments, the expected performance and the current status.

Indirect constraints on lepton-flavor-violating quarkonium decays

Within an effective-field-theory framework, we present a model-independent analysis of the potential of discovering new physics by searching for lepton flavor violation in heavy quarkonium decays and, more in general, we study the phenomenology of lepton-flavor-violating (LFV) 2 quark-2 lepton ($2q2\ensuremath{\ell}$) operators with two charm or bottom fields. We compute the constraints from LFV muon and tau decays on the new-physics operators that can induce LFV processes involving $c\overline{c}$ and $b\overline{b}$ systems, thus providing a comprehensive list of indirect upper limits on processes such as $J/\ensuremath{\psi}\ensuremath{\rightarrow}\ensuremath{\ell}{\ensuremath{\ell}}^{\ensuremath{'}}$, $\mathrm{\ensuremath{\Upsilon}}(nS)\ensuremath{\rightarrow}\ensuremath{\ell}{\ensuremath{\ell}}^{\ensuremath{'}}$, $\mathrm{\ensuremath{\Upsilon}}(nS)\ensuremath{\rightarrow}\ensuremath{\ell}{\ensuremath{\ell}}^{\ensuremath{'}}\ensuremath{\gamma}$ etc., which can be sought at BESIII, Belle II, and the proposed super tau-charm factory. We show that such indirect constraints are so stringent that they prevent the detection of quarkonium decays into $e\ensuremath{\mu}$. In the case of decays of quarkonia into $\ensuremath{\ell}\ensuremath{\tau}$ ($\ensuremath{\ell}=e$, $\ensuremath{\mu}$), we find that an improvement by 2-3 orders of magnitude on the current sensitivities is in general required in order to discover or further constrain new physics. However, we show that cancellations among different contributions to the LFV tau decay rates are possible, such that $\mathrm{\ensuremath{\Upsilon}}(nS)\ensuremath{\rightarrow}\ensuremath{\ell}\ensuremath{\tau}$ can saturate the present experimental bounds. We also find that, interestingly, searches for LFV $Z$ decays, $Z\ensuremath{\rightarrow}\ensuremath{\ell}\ensuremath{\tau}$, at future ${e}^{+}{e}^{\ensuremath{-}}$ colliders are complementary probes of $2q2\ensuremath{\ell}$ operators with third generation quarks.

Tension between e+e−→ηπ−π+ and τ−→ηπ−π0ντ data and nonstandard interactions

We show the discrepancy between the isospin-rotated $e^+e^-\to\eta\pi^-\pi^+$ cross-section -- measured by various collaborations -- and the Belle $\tau^-\to\eta\pi^-\pi^0\nu_\tau$ spectrum, which cannot be explained by heavy new physics non-standard interactions. We give for the first time the framework needed to study these beyond the standard model contributions in three-meson tau decays.

Multi-photon Monte Carlo event generator KKMCee for lepton and quark pair production in lepton colliders

We present the KKMCee 5.00.2 Monte Carlo event generator for lepton and quark pair production for the high energy electron-positron annihilation process. It is still the most sophisticated event generator for such processes. Its entire source code is re-written in the modern C++ language. It reproduces all features of the older KKMC code in Fortran 77. However, a number of improvements in the Monte Carlo algorithm are also implemented. Most importantly, it is intended to be a starting point for the future improvements, which will be mandatory for the future high precision lepton collider projects. As in the older version, in addition to higher order QED corrections, it includes so-called O(α1.5) genuine weak corrections using a version of the classic DIZET library and polarized τ decays using TAUOLA program. Both DIZET and TAUOLA external libraries are still in Fortran 77. In addition, a HEPMC3 interface to other MC programs, like parton showers and detector simulation, replaces the older HepEvt interface. The HEPMC3 interface is also exploited in the implementation of the additional photon final state emissions in τ decays using an external PHOTOS library rewritten in C. Program summaryProgram title:KKMCee 5.00.2CPC Library link to program files:https://doi.org/10.17632/7drvvhbw92.1Licensing provisions: GPL-3.0Programming languages:C++, FORTRAN77External routines:CERN ROOT library, PHOTOS, HepMC v.3.0, TAUOLA, PHOTOS, FOAM, HEPMC3Nature of the problem: Fermion pair production is and will be used as an important data source for precise tests of the standard electroweak theory at a high luminosity future circular collider near the Z resonance and above and/or at the future linear lepton colliders of higher energies than those at LEP. The QED corrections to fermion pair production (especially τ leptons) have to be known to at least second order, including spin polarization effects, with 4-5 digit precision. The Standard Model predictions at the sub-permille precision level, taking into account multiple emission of photons for realistic experimental acceptances, can only be obtained using a Monte Carlo event generator. The realistic and precise simulation of τ lepton decays taking into account spin effects is an indispensable ingredient in the Monte Carlo event generator for the fermion pair production process.Solution method: Monte Carlo methods are used to simulate most of the two-fermion final-state processes in e+e− collisions in the presence of multiphoton initial and final state radiation. The multiphoton effects are described in the framework of coherent exclusive exponentiation (CEEX) extending/upgrading the older Yennie–Frautschi–Suura exclusive exponentiation (EEX) scheme. CEEX treats correctly to infinite order not only infrared cancellations but also QED interferences, including suppression of initial-final state interferences for narrow resonances. The matrix element according to the older YFS exponentiation is also implemented for the testing purpose. For τ leptons, the appropriate simulation of a very rich spectrum of the decays is included. Beam polarization and spin effects, both longitudinal and transverse, in tau decays are properly taken into account. Gaussian beam spread and an arbitrary spectrum of the beamstrahlung are also optionally simulated. The present version of the program is rewritten to C++ but in many respects corresponds to its FORTRAN predecessor KKMC v.4.13 [1] with later minor modifications in v. 4.32 [2].Additional comments including restrictions and unusual features: In the present version, electron (Bhabha) and t-quark final states are not included. (It is planned for a future version.) Third-order QED corrections in the leading-logarithmic approximation are included only in the auxiliary older YFS/EEX matrix element. The electroweak corrections should not be trusted above the t-quark threshold. The total cross section for light quarks for s<10 GeV (including narrow resonances) requires an improvement using experimental data. The program does not provide any handles for the beyond the Standard Model (BSM) physics, for instance in the Born Z boson couplings or in the electroweak (EW) formfactors.Running time depends on the CMS energy, final fermion type, upper phase space limit of the photon energy, and whether variable weight events or WT=1 events are generated. On a PC/Linux with a 2.2 GHz processor, producing 100k variable weight events at s=MZ takes 25 sec. of CPU time for μ-pairs and 30 sec. for τ-pairs including decays. At s=189 GeV 100k events with WT=1 costs 1200 sec. for μ-pairs and 830 sec. for τ-pairs (less hard photons).

Empagliflozin attenuates arrhythmogenesis via inhibition of O-GlcNAcylation in diastolic phase of diabetic cardiomyopathy

Abstract Background Diabetic cardiomyopathy is an important complication of diabetes mellitus (DM) and reported to increase the risk of fatal ventricular arrhythmias. Recent clinical trials showed that empagliflozin (EMPA), a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, improved cardiovascular outcomes regardless of the presence of diabetes and the traditional cardiovascular risk factors. Despite the promising benefit of EMPA on heart failure treatment, its beneficial effect in the context of anti-arrhythmic therapy has not been fully examined. We therefore aimed to examine anti-arrhythmic effect of acute EMPA treatment especially onto calcium (Ca2+) handling in diabetic cardiomyocytes. Methods We assessed echocardiography, hemodynamic study, electrophysiology, Ca2+ handling and protein expression in C57BLKS/J-leprdb/db mice (db/db mice), a leptin receptor-deficient model of obesity and Type 2 diabetes, and their non-diabetic lean heterozygous Leprdb/+ littermates (db/+ mice). Results The 16-week-old db/db mice had preserved systolic function but exhibited diastolic dysfunction. In arrhythmia induction using ex-vivo Langendorff-perfused hearts, db/db mice showed a significantly increased premature ventricular complex (PVC) by 2x Ca2+ and 1μM isoproterenol load than control, which was attenuated by EMPA perfusion (1 μM). Diabetic cardiomyocytes showed an increased frequency of spontaneous Ca2+ sparks and waves, and decreased Ca2+ transient amplitude and sarcoplasmic reticulum (SR) Ca2+ content. Ca2+ transient decay tau and time to 50% decay were significantly prolonged in diabetic cardiomyocytes. These data indicating the impaired Ca2+ handling in diabetic cardiomyocytes were normalized by acute administration of EMPA (1 μM), while the administration of NHE inhibitor (Cariporide 10 μM) did not show significant differences. In the protein expression analysis, CaMKII Thr287 autophosphorylation and CaMKII-dependent RyR2 S2814 phosphorylation were significantly increased in diabetic hearts, which were inhibited by short-term (30 min) perfusion of EMPA (1 μM). The expressions of SERCA2a and phospholamban were not significantly different among three groups. Lastly, whole hearts O-GlcNAcylation, one of the important post translational modifications, was significantly reduced by EMPA treatment. Conclusion EMPA improved intracellular Ca2+ handling and attenuated arrhythmogenesis in mice with diabetic cardiomyopathy at the diastolic dysfunction phase, suggesting that EMPA may exhibit this anti-arrhythmic effect by normalization of intracellular calcium handling via inhibiting O-GlcNAcylation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boehringer Ingelheim

Prospects for a flavour violating Z^prime explanation of Delta a_{mu ,e}

The apparent tensions emerging from the comparison of experimental data of the anomalous magnetic moments of the muon and electron to the Standard Model predictions (Delta a_{mu ,e}) could be interpreted as a potential signal of New Physics. Models encompassing a light vector boson have been known to offer a satisfactory explanation to Delta a_{mu }, albeit subject to stringent experimental constraints. Here we explore a minimal extension of the Standard Model via a leptophilic vector boson Z^prime , under the hypothesis of strictly flavour-violating couplings of the latter to leptons. The most constraining observables to this ad-hoc construction emerge from lepton flavour universality violation (in Z and tau decays) and from rare charged lepton flavour violating transitions. Once these are accommodated, one can saturate the tensions in Delta a_{mu }, but Delta a_{e} is predicted to be Standard Model-like. We infer prospects for several observables, including leptonic Z decays and several charged lepton flavour violating processes. We also discuss potential signatures of the considered Z^prime at a future muon collider, emphasising the role of the mu ^+mu ^- rightarrow tau ^+tau ^- forward-backward asymmetry as a key probe of the model.