Changes in motor synergies for tracking movement and responses to perturbations depend on task-irrelevant dimension constraints

We investigated the changes in the motor synergies of target-tracking movements of hands and the responses to perturbation when the dimensionalities of target positions were changed. We used uncontrolled manifold (UCM) analyses to quantify the motor synergies. The target was changed from one to two dimensions, and the direction orthogonal to the movement direction was switched from task-irrelevant directions to task-relevant directions. The movement direction was task-relevant in both task conditions. Hence, we evaluated the effects of constraints on the redundant dimensions on movement tracking. Moreover, we could compare the two types of responses to the same directional perturbations in one- and two-dimensional target tasks. In the one-dimensional target task, the perturbation along the movement direction and the orthogonal direction were task-relevant and -irrelevant perturbations, respectively. In the two-dimensional target task, the both perturbations were task-relevant perturbations. The results of the experiments showed that the variabilities of the hand positions in the two-dimensional target-tracking task decreased, but the variances of the joint angles did not significantly change. For the task-irrelevant perturbations, the variances of the joint angles within the UCM that did not affect hand position (UCM component) increased. For the task-relevant perturbations, the UCM component tended to increase when the available UCM was large. These results suggest that humans discriminate whether the perturbations were task-relevant or -irrelevant and then adjust the responses of the joints by utilizing the available UCM

Expression and localization of aquaporin 1b during oocyte development in the Japanese eel (Anguilla japonica)

To elucidate the molecular mechanisms underling hydration during oocyte maturation, we characterized the structure of Japanese eel (Anguilla japonica) novel-water selective aquaporin 1 (AQP1b) that thought to be involved in oocyte hydration. The aqp1b cDNA encodes a 263 amino acid protein that includes the six potential transmembrane domains and two Asn-Pro-Ala motifs. Reverse transcription-polymerase chain reaction showed transcription of Japanese eel aqp1b in ovary and testis but not in the other tissues. In situ hybridization studies with the eel aqp1b cRNA probe revealed intense eel aqp1b signal in the oocytes at the perinucleolus stage and the signals became faint during the process of oocyte development. Light microscopic immunocytochemical analysis of ovary revealed that the Japanese eel AQP1b was expressed in the cytoplasm around the yolk globules which were located in the peripheral region of oocytes during the primary yolk globule stage; thereafter, the immunoreactivity was observed throughout the cytoplasm of oocyte as vitellogenesis progressed. The immunoreactivity became localized around the large membrane-limited yolk masses which were formed by the fusion of yolk globules during the oocyte maturation phase. These results together indicate that AQP1b, which is synthesized in the oocyte during the process of oocyte growth, is essential for mediating water uptake into eel oocytes

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

同種移植後のHBV再活性化の後方視的検討

Reactivation of hepatitis B has been recognized as a careful adverse event after chemotherapies or immunosuppressive therapies because chronic hepatitis B leads to carcinoma and/or liver cirrhosis. Allogenic hematopoietic stem cell transplantation（allo-HSCT）against hematological diseases induces severe immunosuppression including reconstitution of naïve donor immunity against HBV-infected hepatocytes and we therefore need to follow-up HBV testing for a long term. In order to establish how to follow-up HBV-infected patients with receiving allo-HSCT, we retrospectively studied HBV serological markers and HBV-DNA in the HBV-infected patients, who received allo-HSCT and followed-up more than １ year in our single center. We detected ７ HBV-infected and allo-HSCT-received patients, and HBV reactivation was occurred in ３ patients with detecting HBV-DNA. No patients were died due to HBV reactivation. The HBV reactivation period after receiving allo-HSCT was １６，２０，７９ months, respectively. All the ３ patients received nucleoside analogues（NUCs）; however, the appearance of viral mutation was occurred in one patient who received lamivudine and already detected HBs-Ag before allo-HSCT. The HBV reactivation was controlled with addition of adefovir. Others were due to discontinuation of entecavir, which reason was poor medication-adherence after stopping immunosuppressive therapies. These two patients received tenofovir alafenamide in addition or retreated with entecavir, respectively, leading to disappearing of HBV-DNA. HBs-Ab were disappeared in ３１ months after allo-HSCT in one patient, and then the Ab was detected after occurring HBV reactivation, suggesting reconstitution of donor immunity. Taken together, our findings suggest that we need to follow-up immune-reconstitution and regularly evaluate HBV serological markers and HBV-DNA, in addition to maintain medication-adherence

Glycolysis Inhibition Inactivates ABC Transporters to Restore Drug Sensitivity in Malignant Cells

Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2), KG-1 (ABCB1) and HepG2 cells (ABCB1 and ABCG2). Interestingly, although side population (SP) cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells

Trastuzumab タンザイ リョウホウ ガ チョコウ シタ セツジョ フノウ シンコウ イガン ノ 1レイ

Trastuzumab, a humanized monoclonal antibody directed against human epidermal growth factor receptor２ （HER２）, has been shown to be active against metastatic gastric cancer that overexpress HER２. A ７８-year-old man presented with an edema in the lower legs. He was diagnosed as having advanced gastric cancers with multiple liver metastases in our hospital. Immunohistochemistry of the tumor cells revealed HER２ overexpression with an intensity of ３＋. The patient was treated with DS-T chemotherapy （Docetaxel＋S‐１＋Trastuzumab） because of the presence of renal dysfunction. Due to the adverse effect appeared with his skin, DS-T chemotherapy has been canceled and trastuzumab chemotherapy was continued. After １１ months of trastuzumab monotherapy, metastatic liver tumors were diminished. There is very few report of a positive response to trastuzumab in a patient with HER２‐overexpressing metastatic gastric cancer