MALT1-deficient mice develop atopic-like dermatitis upon aging

MALT1 plays an important role in innate and adaptive immune signaling by acting as a scaffold protein that mediates NF-kappa B signaling. In addition, MALT1 is a cysteine protease that further fine tunes proinflammatory signaling by cleaving specific substrates. Deregulated MALT1 activity has been associated with immunodeficiency, autoimmunity, and cancer in mice and humans. Genetically engineered mice expressing catalytically inactive MALT1, still exerting its scaffold function, were previously shown to spontaneously develop autoimmunity due to a decrease in Tregs associated with increased effector T cell activation. In contrast, complete absence of MALT1 does not lead to autoimmunity, which has been explained by the impaired effector T cell activation due to the absence of MALT1-mediated signaling. However, here we report that MALT1-deficient mice develop atopic-like dermatitis upon aging, which is preceded by Th2 skewing, an increase in serum IgE, and a decrease in Treg frequency and surface expression of the Treg functionality marker CTLA-4

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. II: The Second Year (2009-2010)

As an extension of the project in Kato et al. (2009, arXiv:0905.1757), we collected times of superhump maxima for 61 SU UMa-type dwarf novae mainly observed during the 2009-2010 season. The newly obtained data confirmed the basic findings reported in Kato et al. (2009): the presence of stages A-C, as well as the predominance of positive period derivatives during stage B in systems with superhump periods shorter than 0.07 d. There was a systematic difference in period derivatives for systems with superhump periods longer than 0.075 d between this study and Kato et al. (2009). We suggest that this difference is possibly caused by the relative lack of frequently outbursting SU UMa-type dwarf novae in this period regime in the present study. We recorded a strong beat phenomenon during the 2009 superoutburst of IY UMa. The close correlation between the beat period and superhump period suggests that the changing angular velocity of the apsidal motion of the elliptical disk is responsible for the variation of superhump periods. We also described three new WZ Sge-type objects with established early superhumps and one with likely early superhumps. We also suggest that two systems, VX For and EL UMa, are WZ Sge-type dwarf novae with multiple rebrightenings. The O-C variation in OT J213806.6+261957 suggests that the frequent absence of rebrightenings in very short-Porb objects can be a result of sustained superoutburst plateau at the epoch when usual SU UMa-type dwarf novae return to quiescence preceding a rebrightening. We also present a formulation for a variety of Bayesian extension to traditional period analyses.Comment: 63 pages, 77 figures, 1 appendix, Accepted for publication in PASJ, data correctio

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1

The paracaspase mucosa-associated lymphoid tissue 1 (MALT1) is central to lymphocyte activation and lymphomagenesis. MALT1 mediates antigen receptor signalling to NF-kappa B by acting as a scaffold protein. Furthermore, MALT1 has proteolytic activity that contributes to optimal NF-kappa B activation by cleaving the NF-kappa B inhibitor A20. Whether MALT1 protease activity is involved in other signalling pathways, and the identity of the relevant substrates, is unknown. Here, we show that T-cell receptors (TCR) activation, as well as overexpression of the oncogenic API2-MALT1 fusion protein, results in proteolytic inactivation of CYLD by MALT1, which is specifically required for c-jun N-terminal kinase (JNK) activation and the inducible expression of a subset of genes. These results indicate a novel role for MALT1 proteolytic activity in TCR-induced JNK activation and reveal CYLD cleavage as the underlying mechanism

Amyloid Activates GSK-3β to Aggravate Neuronal Tauopathy in Bigenic Mice

The hypothesis that amyloid pathology precedes and induces the tau pathology of Alzheimer’s disease is experimentally supported here through the identification of GSK-3 isozymes as a major link in the signaling pathway from amyloid to tau pathology. This study compares two novel bigenic mouse models: APP-V717I × Tau-P301L mice with combined amyloid and tau pathology and GSK-3β × Tau-P301L mice with tauopathy only. Extensive and remarkable parallels were observed between these strains including 1) aggravation of tauopathy with highly fibrillar tangles in the hippocampus and cortex; 2) prolonged survival correlated to alleviated brainstem tauopathy; 3) development of severe cognitive and behavioral defects in young adults before the onset of amyloid deposition or tauopathy; and 4) presence of pathological phospho-epitopes of tau, including the characteristic GSK-3β motif at S396/S404. Both GSK-3 isozymes were activated in the brain of parental APP-V717I amyloid mice, even at a young age when cognitive and behavioral defects are evident but before amyloid deposition. The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons