Dysregulation of microtubule stability impairs morphofunctional connectivity in primary neuronal networks

Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number and strength of synaptic connections is tightly regulated. Synapse function relies on the microtubule (MT) cytoskeleton, the dynamics of which are in turn controlled by a plethora of MT-associated proteins, including the MT-stabilizing protein Tau. Although mutations in the Tau-encodingMAPT gene underlie a set of neurodegenerative disorders, termed tauopathies, the exact contribution of MT dynamics and the perturbation thereof to neuronal network connectivity has not yet been scrutinized. Therefore, we investigated the impact of targeted perturbations of MT stability on morphological (e.g., neurite- and synapse density) and functional (e.g., synchronous calcium bursting) correlates of connectivity in networks of primary hippocampal neurons. We found that treatment with MT-stabilizing or -destabilizing compounds impaired morphofunctional connectivity in a reversible manner. We also discovered that overexpression of MAPT induced significant connectivity defects, which were accompanied by alterations in MT dynamics and increased resistance to pharmacological MT depolymerization. Overexpression of a MAPT variant harboring the P301L point mutation in the MT-binding domain did far less, directly linking neuronal connectivity with Tau's MT binding affinity. Our results show that MT stability is a vulnerable node in tauopathies and that its precise pharmacological tuning may positively affect neuronal network connectivity. However, a critical balance in MT turnover causes it to be a difficult therapeutic target with a narrow operating window

Limits on Lorentz violation in neutral-Kaon decay

The KLOE collaboration recently reported bounds on the directional dependence of the lifetime of the short-lived neutral kaon K_S with respect to the cosmic microwave background dipole anisotropy. We interpret their results in a general framework developed to probe Lorentz violation in the weak interaction. In this approach a Lorentz-violating tensor \chi_{\mu\nu} is added to the standard propagator of the W boson. We derive the K_S decay rate in a naive tree-level model and calculate the asymmetry for the lifetime. By using the KLOE data the real vector part of \chi_{\mu\nu} is found to be smaller than 10^-2. We briefly discuss the theoretical challenges concerning nonleptonic decays.Comment: Presented at the Sixth Meeting on CPT and Lorentz Symmetry, Bloomington, Indiana, June 17-21, 2013

Testing Lorentz invariance in orbital electron capture

Searches for Lorentz violation were recently extended to the weak sector, in particular neutron and nuclear $\beta$ decay [1]. From experiments on forbidden $\beta$-decay transitions strong limits in the range of $10^{-6}$-$10^{-8}$ were obtained on Lorentz-violating components of the $W$-boson propagator [2]. In order to improve on these limits strong sources have to be considered. In this Brief Report we study isotopes that undergo orbital electron capture and allow experiments at high decay rates and low dose. We derive the expressions for the Lorentz-violating differential decay rate and discuss the options for competitive experiments and their required precision.Comment: accepted for publication as a Brief Report in Physical Review

Symmetry violations in nuclear and neutron β\beta decay

The role of $\beta$ decay as a low-energy probe of physics beyond the Standard Model is reviewed. Traditional searches for deviations from the Standard Model structure of the weak interaction in $\beta$ decay are discussed in the light of constraints from the LHC and the neutrino mass. Limits on the violation of time-reversal symmetry in $\beta$ decay are compared to the strong constraints from electric dipole moments. Novel searches for Lorentz symmetry breaking in the weak interaction in $\beta$ decay are also included, where we discuss the unique sensitivity of $\beta$ decay to test Lorentz invariance. We end with a roadmap for future $\beta$-decay experiments.Comment: Accepted for publication in Rev. Mod. Phys. 86 pages, 13 figure

Cell proliferation, cell shape, and microtubule and cellulose microfibril organization of tobacco BY-2 cells are not altered by exposure to near weightlessness in space

The microtubule cytoskeleton and the cell wall both play key roles in plant cell growth and division, determining the plant’s final stature. At near weightlessness, tubulin polymerizes into microtubules in vitro, but these microtubules do not self-organize in the ordered patterns observed at 1g. Likewise, at near weightlessness cortical microtubules in protoplasts have difficulty organizing into parallel arrays, which are required for proper plant cell elongation. However, intact plants do grow in space and therefore should have a normally functioning microtubule cytoskeleton. Since the main difference between protoplasts and plant cells in a tissue is the presence of a cell wall, we studied single, but walled, tobacco BY-2 suspension-cultured cells during an 8-day space-flight experiment on board of the Soyuz capsule and the International Space Station during the 12S mission (March–April 2006). We show that the cortical microtubule density, ordering and orientation in isolated walled plant cells are unaffected by near weightlessness, as are the orientation of the cellulose microfibrils, cell proliferation, and cell shape. Likely, tissue organization is not essential for the organization of these structures in space. When combined with the fact that many recovering protoplasts have an aberrant cortical microtubule cytoskeleton, the results suggest a role for the cell wall, or its production machinery, in structuring the microtubule cytoskeleto