Bone Marrow Allograft Rejection Mediated by a Novel Murine NK Receptor, NKG2I

Natural killer (NK) cells mediate bone marrow allograft rejection. However, the molecular mechanisms underlying such a rejection remain elusive. In previous analyses, it has been shown that NK cells recognize allogeneic target cells through Ly-49s and CD94/NKG2 heterodimers. Here, we describe identification and characterization of a novel murine NK receptor, NKG2I, belonging to the NKG2 family. NKG2I, which was composed of 226 amino acids, showed ∼40% homology to the murine NKG2D and CD94 in the C-type lectin domain. Flow cytometric analysis with anti-NKG2I monoclonal antibody (mAb) revealed that expression of NKG2I was largely confined to NK and NKT cells, but was not seen in T cells. Furthermore, anti-NKG2I mAb inhibited NK cell–mediated cytotoxicity, whereas cross-linking of NKG2I enhanced interleukin 2– and interleukin 12–dependent interferon-γ production. Similarly, the injection of anti-NKG2I mAb before the allogeneic bone marrow transfer in vivo impinged on the function of NKG2I, resulting in the enhanced colony formation in the spleen. NKG2I is a novel activating receptor mediating recognition and rejection of allogeneic target cells

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Huntington’s disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general

Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318-knockout mice

Zfp318, a mouse gene with a Cys2/His2 zinc finger motif, is mainly expressed in germ cells in the testis. It encodes two alternative transcripts, which regulate androgen receptor-mediated transcriptional activation or repression by overexpression of them. However, the role of Zfp318 is still obscure in vivo, especially in spermatogenesis. To elucidate the role of Zfp318 during gamete production, we established a knockout mouse line. Zfp318-null male mice exhibited infertility, whereas Zfp318-null female mice displayed normal fertility. ZFP318 was expressed during multiple stages of spermatogenesis, from spermatocytes to round spermatids. The nuclei of secondary spermatocytes showed high levels of expression. Histological analysis and quantitative analysis of DNA content showed decreased numbers of both spermatids in the seminiferous tubules and mature spermatozoa in the epididymides of Zfp318-null mice. These results suggest that Zfp318 is expressed as a functional protein in testicular germ cells and plays an important role in meiosis during spermatogenesis

Machi: Neighborhood and Small Town—The Foundation for Urban Transformation in Japan

The term machi, signifying both neighborhood and small town, is a key element for understanding Japanese urban form and city planning. After tracing the origins of the term, this article explores the historic and contemporary significance of the concept and its particular spatial and socioeconomic forms. The article then argues that the concept of machi influenced the ways in which Japanese planners picked up foreign concepts through the nineteenth and particularly the twentieth century, absorbing some ideas and rejecting others. Building on their perception of the city as composed of urban units that allowed for planning in patchwork patterns, leading Japanese planners carefully selected models—independently of international appreciation—making, for example, the book The New Town by the German planner Gottfried Feder a standard reference. The article concludes by arguing that foreign observers must understand the concept of machi to comprehend contemporary Japanese neighborhoods, city life, and urban forms

Stable Operation of a 300-m Laser Interferometer with Sufficient Sensitivity to Detect Gravitational-Wave Events within our Galaxy

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of $h\sim 5 \times 10^{-21} /\sqrt{\rm Hz}$, a signal-to-noise ratio (SNR) of 30 is expected for gravitational waves generated by a coalescence of 1.4 $M_\odot$-1.4 $M_\odot$ binary neutron stars at 10 kpc distance. %In addition, almost all noise sources which limit the sensitivity and which %disturb the stable operation have been identified. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.Comment: 5 pages, 4 figure