Physiological and pathological roles of LRRK2 in the nuclear envelope integrity

Mutations in LRRK2 cause autosomal dominant and sporadic Parkinson’s disease but the mechanisms involved in LRRK2 toxicity in PD are yet to be fully understood. We found that LRRK2 translocates to the nucleus by binding to seven in absentia homolog (SIAH-1), and in the nucleus it directly interacts with lamin A/C, independent of its kinase activity. LRRK2 knockdown caused nuclear lamina abnormalities and nuclear disruption. LRRK2 disease mutations mostly abolish the interaction with lamin A/C and, similar to LRRK2 knockdown, cause disorganization of lamin A/C and leakage of nuclear proteins. Dopaminergic neurons of LRRK2 G2019S transgenic and LRRK2 -/- mice display decreased circularity of the nuclear lamina and leakage of the nuclear protein 53BP1 to the cytosol. Dopaminergic nigral and cortical neurons of both LRRK2 G2019S and idiopathic PD patients exhibit abnormalities of the nuclear lamina. Our data indicate that LRRK2 plays an essential role in maintaining nuclear envelope integrity. Disruption of this function by disease mutations suggests a novel phosphorylation-independent loss of function mechanism that may synergize with other neurotoxic effects caused by LRRK2 mutations

Current density inhomogeneity throughout the thickness of superconducting films and its effect on their irreversible magnetic properties

We calculate the distribution of the current density $j$ in superconducting films along the direction of an external field applied perpendicular to the film plane. Our analysis reveals that in the presence of bulk pinning $j$ is inhomogeneous on a length scale of order the inter vortex distance. This inhomogeneity is significantly enhanced in the presence of surface pinning. We introduce new critical state model, which takes into account the current density variations throughout the film thickness, and show how these variations give rise to the experimentally observed thickness dependence of $$ and magnetic relaxation rate.Comment: RevTex, 9 PS figures. To appear in Phys. Rev.

Nuclear Interactions Of Super High Energy Cosmic-rays Observed In Mountain Emulsion Chambers

Here we present a summary of joint discussions on the results of three mountain experiments with large-scale emulsion chambers, at Pamir, Mt. Fuji and Chacaltaya. Observations cover gamma quanta, hadrons and their clusters (called "families"). The following topics are covered, concerning the characteristics of nuclear interactions the energy region 1014-1016 eV: (i) rapid dissipation seen in atmospheric diffusion of high-energy cosmic-rays; (ii) multiplicity and Pt increase in produced pi-mesons in the fragmentation region; (iii) existence of large-Pt jets, (iv) extremely hadron-rich family of the Centauro type; (v) exotic phenomena in the extremely high energy region beyond 1016 eV. © 1981.1911125(1977) Acta Univ. Lodz ser. II, (60)(1973) 13th Int. Cosmic-ray Conf., 3, p. 2228(1975) 14th Int. Cosmic-Ray Conf., 7, p. 2365(1979) AIP Conf. Proc. no. 49, p. 334(1979) 16th Int. Cosmic-ray Conf., 6, p. 344(1979) 16th Int. Cosmic-ray Conf., 7, p. 6816th Int. Cosmic-ray Conf. (1979) 16th Int. Cosmic-ray Conf., 7, p. 284(1979) 16th Int. Cosmic-ray Conf., 7, p. 294(1979) 16th Int. Cosmic-ray Conf., 13, p. 87(1979) 16th Int. Cosmic-ray Conf., 13, p. 92(1979) 16th Int. Cosmic-ray Conf., 13, p. 98(1979) AIP Conf. Proc. no. 49, p. 94(1979) AIP Conf. Proc. no. 49, p. 145(1979) AIP Conf. Proc. no. 49, p. 317(1979) 16th Int. Cosmic-ray Conf., 6, p. 350(1979) 16th Int. Cosmic-ray Conf., 6, p. 356(1979) 16th Int. Cosmic-ray Conf., 6, p. 362Nikolsky, Proc. 9th Int. High-energy Symp. (1978) CSSR, 21. , ToborMiyake, (1978) Proc. 19th Int. Conf. on High-energy physics, p. 433Vernov, (1977) Physica, 3, p. 1601Khristiansen, (1978) JETP Lett., 28, p. 124(1973) 13th Int. Cosmic-ray Conf., 3, p. 2219Izv. Acad. Nauk USSR, ser Phys. (1974) Izv. Acad. Nauk USSR, ser Phys., 38, p. 918(1975) 14th Int. Cosmic-ray Conf., 7, p. 2365(1979) 16th Int. Cosmic-ray Conf., 7, p. 68Dunaevsky, Urysson, Emelyanov, Shorin, Tashimov, (1975) FIAN preprint no. 150Dunaevsky, Urysson, Emelyanov, Shorin, Tashinov, (1979) Acta Univ. Lodz ser. II, (60), p. 199Ivanenko, Kanevskya, Roganova, (1978) JETP Lett., 40, p. 704Ivanenko, Kanevsky, Roganova, (1979) 16th Int. Cosmic-ray Conf., 7, p. 101Ivanenko, Kanevsky, Roganova, (1979) 16th Int. Cosmic-ray Conf., 7, p. 198Wrotniak, (1977) Acta Univ. Lodz ser. II, (60), p. 165Krys, Tomaszevski, Wrotniak, (1979) 16th Int. Cosmic-ray Conf., 7, p. 182Krys, Tomaszevski, Wrotniak, (1979) 16th Int. Cosmic-ray Conf., 7, p. 186Fomin, Kempa, Khristiansen, Levina, Piotrowska, Wdowczyk, (1977) 15th Int. Cosmic-ray Conf., 7, p. 248Fomin, Kempa, Khristiansen, Levina, Piotrowska, Wdowczyk, (1979) 16th Int. Cosmic-ray Conf., 13, p. 82Azimov, Mullazhanov, Yuldashbayev, (1979) 16th Int. Cosmic-ray Conf., 7, p. 262Azimov, Mullazhanov, Yuldashbayev, (1977) Acta Univ. Lodz ser. II, (60), p. 275Kasahara, Torri, Yuda, (1979) 16th Int. Cosmic-ray Conf., 13, p. 70Kasahara, Torii, Yuda, (1979) 16th Int. Cosmic-ray Conf., 13, p. 79Shibata, (1979) 16th Int. Cosmic-ray Conf., 7, p. 176H. Semba, T. Shibata and T. Tabuki, Suppl. Prog. Theor. Phys., to be publishedZhdanov, Roinishvilli, Smorodin, Tomaszevski, (1975) FIAN preprint no. 163Lattes, Fujimoto, Hasegawa, Hadronic interactions of high energy cosmic-ray observed by emulsion chambers (1980) Physics Reports, 65, p. 152Ellsworth, Gaisser, Yodh, (1981) Phys. Rev., 23 D, p. 764Baradzei, Smorodin, (1974) FIAN preprint nos. 103, 104Baradzei, Smorodin, (1977) Acta Univ. Lodz ser. II, (60), p. 51Zhdanov, (1980) FIAN preprint no. 140H. Semba, T. Shibata and T. Tabuki, Suppl. Prog. Theor. Phys., to be publishedShibata, (1980) Phys. Rev., 22 D, p. 100Slavatinsky, (1980) Proc. 7th European Symp. on Cosmic rays, , Leningrad, to be published(1979) AIP Conference Proc. no. 49, p. 145Azimov, Abduzhamilov, Chudakov, (1963) JETP (Sov. Phys.), 45, p. 40713th Int. Cosmic-ray Conf. (1973) 13th Int. Cosmic-ray Conf., 5, p. 326Acharya, Rao, Sivaprasad, Rao, (1979) 16th Int. Cosmic-ray Conf., 6, p. 289Ellsworth, Goodman, Yodh, Gaisser, Stanev, (1981) Phys. Rev., 23 D, p. 771Bariburina, Guseva, Denisova, (1980) Acta Univ. Lodz, 1, p. 9415th Int. Cosmic-ray Conf. (1977) 15th Int. Cosmic-ray Conf., 7, p. 184(1979) AIP Conf. Proc. no. 49, p. 33