Modes of Retrotransposition of Long Interspersed Element-1 by Environmental Factors

Approximately 42% of the human genome is composed of endogenous retroelements, and the major retroelement component, long interspersed element-1 (L1), comprises ∼17% of the total genome. A single human cell has more than 5 × 105 copies of L1, 80∼100 copies of which are competent for retrotransposition (RTP). Notably, L1 can induce RTP of other retroelements, such as Alu and SVA, and is believed to function as a driving force of evolution. Although L1-RTP during early embryogenesis has been highlighted in the literature, recent observations revealed that L1-RTP also occurs in somatic cells. However, little is known about how environmental factors induce L1-RTP. Here, we summarize our current understanding of the mechanism of L1-RTP in somatic cells. We have focused on the mode of L1-RTP that is dependent on the basic helix–loop–helix/per–arnt–sim (bHLH/PAS) family of transcription factors. Along with the proposed function of bHLH/PAS proteins in environmental adaptation, we discuss the functional linking of L1-RTP and bHLH/PAS proteins for environmental adaptation and evolution

トウガラシ（Capsicum baccatum）における カプサイシノイド含量の変異とその非辛味系統

The chili pepper (Capsicum) is both an important spice and fresh vegetable worldwide. C. baccatum is a lesser known domesticated species that is native to the Andean region. Fruit traits such as color, shape, and pungency markedly vary in this species. C. baccatum has potential as a bioresource for future chili pepper breeding programs. Although extensive studies have been conducted on the pungency of C. annuum, that of C. baccatum has not been examined in as much detail. In the present study, capsaicinoid contents were analyzed in 36 C. baccatum accessions. Capsaicinoid contents ranged between 0 and 4,258 μg/gDW. Furthermore, a negative relationship was observed between capsaicinoid contents and fruit weights. Although the pungency of C. baccatum is regarded as low-mild, very few non-pungent accessions were detected ; only one non-pungent accession (‘Kaleidoscope’) was identified among the C. baccatum accessions examined. In order to validate the stability of non-pungency in the accession, capsaicinoid contents were determined at different harvest dates, along with other accessions with different pungencies. Although capsaicinoid contents in other C. baccatum accessions changed with the picking date, capsaicinoid was not detected in ‘Kaleidoscope’ at any date. The non-pungent accession reported here may be useful for future C. baccatum pepper breeding programs.　トウガラシ（Capsicum 属）は世界的に重要な香辛料および野菜である．C. baccatum は南米原産のマイナーな栽培種であるが，果色，果形や辛味など果実形質に多様性が認められることから，トウガラシ遺伝資源として注目されている．トウガラシの辛味性についてはC. annuum 種において多くの研究が行われているが，C. baccatum 種においては十分研究されていない． 　本研究では，C. baccatum 36系統について辛味成分カプサイシノイドの含量を調査した．カプサイシノイド含量の幅は0 ～4,258 ㎍ /gDW であった．また果実重と辛味成分含量の間に負の相関が認められた．C. baccatum の辛味は低〜中程度であるが，非辛味系統はほとんど認められず，唯一1 系統（‘Kaleidoscope’）が非辛味であった．この非辛味の安定性を調査するために，辛味程度の異なる系統とともに異なる収穫時期におけるカプサイシノイド含量を調査した． 　他のC. baccatum 系統ではカプサイシノイド含量は収穫時期で変化したが，‘Kaleidoscope’ ではいずれの収穫時期でもカプサイシノイドは検出されなかった．本研究で見出された非辛味系統は将来のC. baccatum の育種において有用であろう

Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation

Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets

トウガラシ（Capsicum baccatum）における カプサイシノイド含量の変異とその非辛味系統

The chili pepper (Capsicum) is both an important spice and fresh vegetable worldwide. C. baccatum is a lesser known domesticated species that is native to the Andean region. Fruit traits such as color, shape, and pungency markedly vary in this species. C. baccatum has potential as a bioresource for future chili pepper breeding programs. Although extensive studies have been conducted on the pungency of C. annuum, that of C. baccatum has not been examined in as much detail. In the present study, capsaicinoid contents were analyzed in 36 C. baccatum accessions. Capsaicinoid contents ranged between 0 and 4,258 μg/gDW. Furthermore, a negative relationship was observed between capsaicinoid contents and fruit weights. Although the pungency of C. baccatum is regarded as low-mild, very few non-pungent accessions were detected ; only one non-pungent accession (‘Kaleidoscope’) was identified among the C. baccatum accessions examined. In order to validate the stability of non-pungency in the accession, capsaicinoid contents were determined at different harvest dates, along with other accessions with different pungencies. Although capsaicinoid contents in other C. baccatum accessions changed with the picking date, capsaicinoid was not detected in ‘Kaleidoscope’ at any date. The non-pungent accession reported here may be useful for future C. baccatum pepper breeding programs.　トウガラシ（Capsicum 属）は世界的に重要な香辛料および野菜である．C. baccatum は南米原産のマイナーな栽培種であるが，果色，果形や辛味など果実形質に多様性が認められることから，トウガラシ遺伝資源として注目されている．トウガラシの辛味性についてはC. annuum 種において多くの研究が行われているが，C. baccatum 種においては十分研究されていない． 　本研究では，C. baccatum 36系統について辛味成分カプサイシノイドの含量を調査した．カプサイシノイド含量の幅は0 ～4,258 ㎍ /gDW であった．また果実重と辛味成分含量の間に負の相関が認められた．C. baccatum の辛味は低〜中程度であるが，非辛味系統はほとんど認められず，唯一1 系統（‘Kaleidoscope’）が非辛味であった．この非辛味の安定性を調査するために，辛味程度の異なる系統とともに異なる収穫時期におけるカプサイシノイド含量を調査した． 　他のC. baccatum 系統ではカプサイシノイド含量は収穫時期で変化したが，‘Kaleidoscope’ ではいずれの収穫時期でもカプサイシノイドは検出されなかった．本研究で見出された非辛味系統は将来のC. baccatum の育種において有用であろう

Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice). After transplantation of human hematopoietic stem cells (HSCs), the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice) showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF), into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1), IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory/immunosuppressive myeloid cells

Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis

Lymph nodes (LNs) are at the center of adaptive immune responses. Various exogenous substances are transported into LNs and a series of immune responses ensue after recognition by antigen–specific lymphocytes. Although humanized mice have been used to reconstitute the human immune system, most lack LNs due to deficiency of the interleukin (IL)-2Rγ gene (cytokine common γ chain, γc). In this study, we established a transgenic strain, NOG-pRORγt-γc, in the NOD/shi-scid-IL-2Rγnull (NOG) background, in which the γc gene was expressed in a lymph-tissue inducer (LTi) lineage by the endogenous promoter of RORγt. In this strain, LN organogenesis was normalized and the number of human T cells substantially increased in the periphery after reconstitution of the human immune system by human hematopoietic stem cell transplantation. The distribution of human T cells differed between NOG-pRORγt-γc Tg and NOG-non Tg mice. About 40% of human T cells resided in LNs, primarily the mesenteric LNs. The LN-complemented humanized mice exhibited antigen-specific immunoglobulin G responses together and an increased number of IL-21+–producing CD4+ T cells in LNs. This novel mouse strain will facilitate recapitulation of human immune responses

Generation of Themis^−/− mice expressing mutant Themis proteins.

<p>(A) Schematic representation of the mutant Themis proteins. (B) Analysis of Themis protein expression by immunoblot using sorted CD69⁻ DP thymocytes from Themis^+/+, Themis^+/−, Themis^−/− and Themis^−/− mice expressing ΔPRS, ΔCore1, ΔCore2, ΔNLS, CAB2-1 mutant, or WT Themis. Data are representative of more than three independent experiments.</p