AS1949490, an inhibitor of 5'-lipid phosphatase SHIP2, promotes protein kinase C-dependent stabilization of brain-derived neurotrophic factor mRNA in cultured cortical neurons.

Brain-derived neurotrophic factor (BDNF), an essential factor for maintaining brain functions, has been reported to be reduced in various neurological diseases, including Alzheimer's disease and major depression. Therefore, new drugs to increase the BDNF expression need to be developed. Since phosphatidylinositol (3,4,5)-trisphosphate, a membrane signaling molecule produced by phosphoinositide 3 (PI3)-kinase in the BDNF signaling, is a candidate target of SH2 domain-containing inositol 5' phosphatase 2 (SHIP2, a 5'-lipid phosphatase), the present study examined the effect of a SHIP2 inhibitor AS1949490 on Bdnf expression in cultured cortical neurons. BDNF increased its own mRNA levels, and AS1949490 enhanced this positive feedback regulation. The effects of BDNF in combination with AS1949490 on the Bdnf mRNA levels were blocked by inhibitors of mitogen-activated protein kinase kinase (U0126), PI3-kinase (LY294002), phospholipase Cγ (U73122), and protein kinase C (bisindolylmaleimide I), whereas the effect of BDNF alone was inhibited only by U0126. The mRNA stability assay using actinomycin D demonstrated that AS1949490 reduced degradation of the self-amplified Bdnf mRNA levels, and this effect was disappeared in the presence of bisindolylmaleimide I. These results suggest that BDNF promoted the Bdnf mRNA stabilization in a protein kinase C-dependent manner only in the presence of AS1949490, thereby enhancing Bdnf expression. Furthermore, behavioral analyses indicated that central administration of AS1949490 caused memory-improving and anti-depressant effects in passive avoidance test and forced swim test, respectively. Therefore, inhibition of SHIP2 appears to be valuable therapeutic strategy against neurological disorders associated with insufficient BDNF functions.

[Activities of Japanese Occupational Health Service Centers].

OBJECTIVES: Although both occupational health centers and occupational health service centers (OHSCs) support small-scale enterprises in Japan, the activities of OHSCs are not well detailed. This survey aimed to clarify the activities and subjective evaluation by directors and coordinators of OHSCs, with a focus on improving occupational health services in small-scale enterprises. METHODS: The survey was conducted by mailing questionnaires to 377 directors and 507 coordinators at 344 OHSCs in Japan from September 2016 to January 2017. The survey items comprised questions about director and coordinator characteristics, OHSCs' systems and activities, and subjective evaluations of OHSCs' activities. RESULTS: Responses were obtained from 290 directors (76.9%) and 413 coordinators (81.5%) of OHSCs. Of the directors, 66.2% were occupational health directors of medical associations. The average number of years' experience for coordinators was 5.7 years, and 44.6% were specially qualified, most as health officers. The percentage of OHSC staff who were not coordinators was 22%, and 29.8% of OHSCs had a public health nurse. The Office of Labor Standard's guidance was most often cited as the reason why small-scale enterprises decided to use OHSCs. At least 90% of OHSC directors and coordinators evaluated OHSCs' activities as "good". Directors not consulted by a coordinator evaluated OHSCs' activities as "very good" significantly more often than directors who were consulted by a coordinator (p<.001). Similarly, directors not consulted by occupational health centers' members evaluated OHSCs' activities as "very good" significantly more often than directors who were consulted by occupational health centers' members (p<.006). Coordinators who were in charge of two or more regions medical associations evaluated OHSCs' activities as "very good" significantly more often than those who were in charge of only one regions medical association (p=.014).Coordinators who had qualification of occupational health evaluated OHSCs' activities as "very good" significantly more often than coordinators who had not (p=.007). Coordinators who conducted public relations activities evaluated OHSCs' activities as "very good" significantly more often than those who did not (p=.011). Similarly, coordinators who conducted public relations activities via email and homepage promotions evaluated OHSCs' activities as "very good" significantly more often than those who did not (p<.001). In addition, coordinators who used the consultation record evaluated OHSCs' activities as "very good" significantly more often than those who did not (p<.001), whereas coordinators who consulted with a director evaluated OHSCs' activities as "very good" significantly more often than those who did not (p=.028). Coordinators who thought doctors were fit for the OHSCs' activities had significantly higher percentages of qualifications than those who did not think this way (p=.032). Likewise, coordinators who conducted public relations activities had significantly higher percentages of qualifications than those who did not (p<.001), whereas coordinators who used the consultation record had significantly higher percentages of qualifications than those who did not (p=.006). CONCLUSIONS: This survey clarified OHSCs' activities and suggested that systems and activities are not the same across OHSCs. We found that coordinators need to master knowledge of occupational health and work support. In addition, improving the relationship between directors and coordinators, enhancing public relations activities, and utilizing tools such as a chart improved OHSCs' activities.

Exaptation of Bornavirus-Like Nucleoprotein Elements in Afrotherians.

Endogenous bornavirus-like nucleoprotein elements (EBLNs), the nucleotide sequence elements derived from the nucleoprotein gene of ancient bornavirus-like viruses, have been identified in many animal genomes. Here we show evidence that EBLNs encode functional proteins in their host. Some afrotherian EBLNs were observed to have been maintained for more than 83.3 million years under negative selection. Splice variants were expressed from the genomic loci of EBLNs in elephant, and some were translated into proteins. The EBLN proteins appeared to be localized to the rough endoplasmic reticulum in African elephant cells, in contrast to the nuclear localization of bornavirus N. These observations suggest that afrotherian EBLNs have acquired a novel function in their host. Interestingly, genomic sequences of the first exon and its flanking regions in these EBLN loci were homologous to those of transmembrane protein 106B (TMEM106B). The upstream region of the first exon in the EBLN loci exhibited a promoter activity, suggesting that the ability of these EBLNs to be transcribed in the host cell was gained through capturing a partial duplicate of TMEM106B. In conclusion, our results strongly support for exaptation of EBLNs to encode host proteins in afrotherians.

Immunochromatography for the rapid determination of cadmium concentrations in wheat grain and eggplant.

BACKGROUND: A simple and quick on-site test for trace levels of cadmium (Cd) in food is needed because of the human toxicity of this heavy metal. We developed an immunochromatography kit which uses the antigen-antibody complex reaction between the Cd-ethylenediaminetetraacetic acid (Cd-EDTA) complex and an anti-Cd-EDTA antibody. We previously reported the successful use of this kit to determine Cd concentrations in brown rice with respect to the international standard: 0.4 mg kg⁻¹. Here, we measured, using this immunochromatography kit, Cd concentrations in crops with lower international standards than rice. RESULTS: Cadmium extracted with 0.1 mol L⁻¹ HCl from wheat grain and fresh eggplant was purified sufficiently using an ion-exchange column treatment. Appropriate HCl extraction rates and dilution rates for the column eluate were selected; Cd concentrations in wheat grain and fresh eggplant were determined successfully by immunochromatography with respect to the international standards of 0.2 mg kg⁻¹ and 0.05 mg kg⁻¹ fresh weight, respectively. CONCLUSION: Approximate Cd concentrations in wheat grain and fresh eggplant can be monitored easily and quickly by this method at locations where facilities for acid digestion and precision analysis are not available.

Arachidonate 12-lipoxygenases with reference to their selective inhibitors.

Lipoxygenase is a dioxygenase recognizing a 1-cis,4-cis-pentadiene of polyunsaturated fatty acids. The enzyme oxygenates various carbon atoms of arachidonic acid as a substrate and produces 5-, 8-, 12- or 15-hydroperoxyeicosatetraenoic acid with a conjugated diene chromophore. The enzyme is referred to as 5-, 8-, 12- or 15-lipoxygenase, respectively. Earlier we found two isoforms of 12-lipoxygenase, leukocyte- and platelet-type enzymes, which were distinguished by substrate specificity, catalytic activity, primary structure, gene intron size, and antigenicity. Recently, the epidermis-type enzyme was found as the third isoform. Attempts have been made to find isozyme-specific inhibitors of 12-lipoxygenase, and earlier we found hinokitiol, a tropolone, as a potent inhibitor selective for the platelet-type 12-lipoxygenase. More recently, we tested various catechins of tea leaves and found that (-)-gallocatechin gallate was a potent and selective inhibitor of human platelet 12-lipoxygenase with an IC50 of 0.14 microM. The compound was much less active with 12-lipoxygenase of leukocyte-type, 15-, 8-, and 5-lipoxygenases, and cyclooxygenases-1 and -2.