We found that most peripheral CD4 cells co-express a low density of CD8 alpha antigen in African green monkeys (AGM). Further, the cell surface expression of CD4 and the expression of CD4 mRNA underwent a decrease when purified CD4CD8low cells were cultured with mitogen and IL-2. These observations suggest that AGM CD4 cells are subject to loss of CD4 expression after lymphocyte activation. Part of the peripheral CD8 fraction exhibited a significant helper activity which suggested the phenotypic conversion in helper T cells from CD4+ to CD4- in vivo. Simian immunodeficiency virus (SIV) grew well in CD4 panning cells following SIV infection. In contrast, CD4CD8low cells were resistant to SIV infection after their conversion to CD4- cells.

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The fundamental approach to the biological control of Aedes albopictus requires the mass rearing of mosquitoes and the release of highly competitive adults in the field. As the fitness of adults is highly dependent on the development of immatures, we aimed to identify the minimum feeding regime required to produce viable and competitive adults by evaluating three response parameters: development duration, immature mortality, and adult wing length. Our study suggests at least 0.60 mg/larva/day of larval diet composed of dog food, dried beef liver, yeast, and milk powder in a weight ratio of 2:1:1:1 is required to maximize adult fitness. With standardized protocols in mass rearing, intensive studies can be readily conducted on mosquito colonies to facilitate comparisons across laboratories. This study also evaluated the differences in response of laboratory and field strains under different feeding regimes. We found that strain alone did not exert substantial effects on all response parameters. However, the field strain exhibited significantly lower immature mortality than the laboratory strain under the minimum feeding regime. Females and males of the laboratory strain had longer wing lengths under nutritional constraint due to the higher mortality that resulted in reduced interactions with the remaining larvae. Meanwhile, the field strain exhibited heterogeneous duration of immature development compared with the laboratory strain. The disparities demonstrated by the two strains in this study suggest the effect of inbreeding surfaced after a long term of laboratory colonization. Despite the trade-offs resulting from laboratory colonization, the competitiveness of the laboratory strain of Ae. albopictus is comparable to the field strain, provided the larvae are fed optimally. Journal of Vector Ecology 42 (1): 105-112. 2017.

CITED2 (Cbp/p300‐interacting transactivator, with Glu/Asp‐rich carboxy‐terminal domain, 2) is a member of the CITED family and is involved in various cellular functions during development and differentiation. Mounting evidence suggests the importance of CITED in the progression of human malignancies, but the significance of CITED2 protein has not yet been examined in breast carcinoma. Therefore, in the present study, we examined the clinical significance and the biological functions of CITED2 in breast carcinoma by immunohistochemistry and in vitro study. CITED2 immunoreactivity was detected in breast carcinoma tissues, and it was significantly higher compared to those in morphologically normal mammary glands. CITED2 immunoreactivity was significantly associated with stage, pathological T factor, lymph node metastasis, histological grade, HER2 and Ki‐67, and inversely correlated with estrogen receptor. Moreover, the immunohistochemical CITED2 status was significantly associated with increased incidence of recurrence and breast cancer‐specific death of the breast cancer patients, and multivariate analyses demonstrated CITED2 status as an independent worse prognostic factor for disease‐free and breast cancer‐specific survival. Subsequent in vitro experiments showed that CITED2 expression significantly increased proliferation activity and migration property in MCF‐7and S KBR‐3 breast carcinoma cells. Moreover, CITED2 caused chemoresistance to epirubicin and 5‐fluorouracil, but not paclitaxel, in these cells, and it inhibited p53 accumulation after 5‐fluorouracil treatment in MCF‐7 cells. These results suggest that CITED2 plays important roles in the progression and chemoresistance of breast carcinoma and that CITED2 status is a potent prognostic factor in breast cancer patients.

Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV-I). The hematological features and the evidence for monoclonal integration of provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like disease. The expression of surface markers on the leukemic cells indicated that they were defined as an activated CD8+ T cell subset. Together with the finding that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with human ATL. Finally, we assessed characteristics of the CD8 chains on these transformed cells. The result indicated that the leukemic cells expressed only the alpha chains but not the beta chains. However, in the case of in vitro-transformed cell lines the expression pattern of the CD8 chains varied in individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both alphaalpha+ and alphabeta+) T cells in AGMs.

A group of RNA methylation enzymes is currently of interest as a new target for cancer therapy. Alpha-ketoglutarate-dependent dioxygenase B (AlkB) homolog 5 ( ALKBH5) is an N 6 -methyladenosine (m 6 A) demethylation enzyme, and by high-throughput screening from pure small molecule compounds, we identified two novel inhibitors, Ena15 and Ena21, against it. Each compound showed either uncompetitive or competitive inhibition for 2-oxoglutarate (2OG). In addition, Ena21 had little inhibitory activity for fat mass and obesity-associated protein (FTO), which is another N 6 -methyladenosine demethylation enzyme, while Ena15 enhanced the demethylase activity of FTO. The predicted binding poses of both compounds with the crystal structure of ALKBH5 (PDB ID: 4NRO) were comparable with these observations pertaining to the interaction of the 2OG catalytic site in this enzyme kinetics. Furthermore, either knockdown of ALKBH5 or inhibition with Ena15 or Ena21 inhibited cell proliferation of glioblastoma multiforme-derived cell lines, decreased cell population in the synthesis phase of the cell cycle, increased m 6 A RNA level, and stabilized FOXM1 mRNA. Based on these results, Ena15 and Ena21 were found to be potential candidates that might help in further research into the biological function of ALKBH5.

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