China and North Korea a peculiar relationship

Since Beijing organized the six-party talks in 2003 and persuaded North Korea to participate, much of the international community has applauded China's leadership in attempting to stabilize the region. However, some U.S. policymakers and regional experts have mistaken China's preference for a nonnuclear Korea as indication that Beijing's policy goals are more similar to U.S. policy goals than is accurate. Some mistake China's policy priorities in the region and, therefore, do not understand why Beijing does not take a more hard-line stance against North Korea. Others overestimate China's ability to influence North Korea. The purpose of this thesis is to provide a clearer understanding of Beijing's short-term and long-term policies toward North Korea and the limits of Beijing's ability to influence Pyongyang's behavior, in order to assist U.S. policymakers in formulating realistic strategies toward interaction with China on Korean peninsula issues.http://archive.org/details/chinandnorthkore109455784Approved for public release; distribution is unlimited

SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling

The Linear UBiquitin chain Assembly Complex (LUBAC) regulates immune signaling and its function is regulated by the deubiquitinases OTULIN and CYLD that associate with the catalytic subunit HOIP. However, the mechanism through which CYLD interacts with HOIP is unclear. We here show that CYLD interacts with HOIP via spermatogenesis-associated protein 2 (SPATA2). SPATA2 interacts with CYLD through its non-canonical PUB domain that binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner. Significantly, SPATA2 binding activates CYLD-mediated hydrolysis of ubiquitin chains. SPATA2 also harbors a conserved PUB-interacting motif that selectively docks into the HOIP PUB domain. In cells, SPATA2 is recruited to the TNF Receptor 1 signaling complex, and is required for CYLD recruitment. Loss of SPATA2 increases ubiquitination of LUBAC substrates and results in enhanced NOD2 signaling. Our data reveal SPATA2 as a high-affinity binding partner of CYLD and HOIP, and regulatory component of LUBAC-mediated NF-NB signaling

A common antigenic motif recognized by naturally occurring human VH5–51/VL4–1 anti-tau antibodies with distinct functionalities

Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer’s Disease (AD). By interrogating IgG+ memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated VH5–51/VL4–1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of VH5–51 and VL4–1 recognizes a common Pro-Xn-Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD. Electronic supplementary material The online version of this article (10.1186/s40478-018-0543-z) contains supplementary material, which is available to authorized users