Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells

AbstractDendritic cells (DCs) play a major role in in vivo pathogenesis of HIV-1 infection. Therefore, DCs may provide a promising strategy to control and eventually overcome the fatal infection. Especially, immature DCs express all CD1s, the non-MHC lipid antigen -presenting molecules, and HIV-1 Nef down-regulates CD1 expression besides MHC. Moreover, CD1d-restricted CD4+ NKT cells are infected by HIV-1, reducing the number of these cells in HIV-1-infected individuals. To understand the exact role of DCs and CD1-mediated immune response during HIV-1 infection, Nef down-regulation of CD1a-restricted lipid/glycolipid Ag presentation in iDCs was analyzed. We demonstrated the involvement of the association of Nef with hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2), and that Hck, which is expressed strongly in iDCs, augmented this mutual interaction. Hck might be another therapeutic target to preserve the function of HIV-1 infected DCs, which are potential reservoirs of HIV-1 even after antiretroviral therapy

シコウ カウンセリング ニオケル セラピスト フォーカシング ノ イミ

It is extremely important for the psychotherapists to examine own psychological process as well as understanding the client. “Therapist focusing” is a method of urging promotion of the experience process to be caused by touching the charge of the case with the therapist and own felt sense. One session of the therapist focusing was presented, the meaning of “Therapist focusing” in beginner psychotherapist “Trial counseling” was examined by turning around by the talk form. As a result, two points were suggested. the first point is that the process of “Close examination of the felt sense” of the therapist focusing is approximated with the understanding of the counter transference and relativity of “Therapist focusing” and assessment of client

Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression.

Folliculin-interacting protein 1 and 2 (FNIP1 and FNIP2) play critical roles in preventing renal malignancy through their association with the tumor suppressor FLCN. Mutations in FLCN are associated with Birt-Hogg-Dubé (BHD) syndrome, a rare disorder with increased risk of renal cancer. Recent studies indicated that FNIP1/FNIP2 double knockout mice display enlarged polycystic kidneys and renal carcinoma, which phenocopies FLCN knockout mice, suggesting that these two proteins function together to suppress renal cancer. However, the molecular mechanism functionally linking FNIP1/FNIP2 and FLCN remains largely elusive. Here, we demonstrated that FNIP2 protein is unstable and subjected to proteasome-dependent degradation via β-TRCP and Casein Kinase 1 (CK1)-directed ubiquitination in a nutrition-dependent manner. Degradation of FNIP2 leads to lysosomal dissociation of FLCN and subsequent lysosomal association of mTOR, which in turn promotes the proliferation of renal cancer cells. These results indicate that SCFβ-TRCP negatively regulates the FLCN complex by promoting FNIP degradation and provide molecular insight into the pathogenesis of BHD-associated renal cancer.福岡歯科大学2016年

Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205+ dendritic cells

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1+ and DEC-205+ DCs. Using anti-33D1-specific monoclonal antibody, 33D1+ DCs were successfully depleted from C57BL/6 mice. When 33D1+ DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be mediated by the remaining DEC-205+ DCs was markedly enhanced, which may induce Th1 dominancy upon TLR signaling. The 33D1+ DC-depleted mice, implanted with syngeneic Hepa1-6 hepatoma or B16-F10 melanoma cells into the dermis, showed apparent inhibition of already established tumor growth in vivo when they were subcutaneously (sc) injected once or twice with LPS after tumor implantation. Moreover, the development of lung metastasis of B16-F10 melanoma cells injected intravenously was also suppressed when 33D1+ DC-deleted mice were stimulated twice with LPS in a similar manner, in which the actual cell number of NK1.1+CD3− NK cells in lung tissues was markedly increased. Furthermore, intraperitoneal (ip) administration of a very small amount of melphalan (l-phenylalanine mustard; l-PAM) (0.25 mg/kg) in LPS-stimulated 33D1+ DC-deleted mice helped to induce H-2Kb-restricted epitope-specific CD8+ cytotoxic T lymphocytes (CTLs) among tumor-infiltrating lymphocytes against already established syngeneic E.G7-OVA lymphoma. These findings indicate the importance and effectiveness of selective targeting of a specific subset of DCs, such as DEC-205+ DCs alone or with a very small amount of anticancer drugs to activate both CD8+ CTLs and NK effectors without externally added tumor antigen stimulation in vivo and provide a new direction for tumor immunotherapy

Postoperative Course of Crohn\u27s Disease -In regard to Recurrence and Residual Disease at Anastomosis -

Twenty-seven patients with Crohn\u27s disease who were operated on at the First Department of Surgery, Nagasaki University School of Medicine and followed-up after surgery were reviewed. Involved portion of intestinal tract were 10 in small bowel only, 14 in both small and large bowels, and 3 in large bowel. Major indication for surgery were obstruction, fistula, peritonitis and intractability of medical therapy. Twenty-two patients underwent radical resection and the other 5 patients had the disease left behind at anastomosis. The recurrence rate was 25.9% (7 out of 22), and early recurrence was found in small bowel diseases with longitudinal ulcerations or multiple aphthoid ulcers. Initial recurrence occured near the suture line, which showed no wide spreading in subsequent periods. Two cases with both small and large bowel disease required reoperation over 5 years after initial surgery because of stenosis. Three out of five cases with residual disease at the intestinal resection margin had a good condition, but the other three cases with skip sigmoid disease were intractable for medical therapy. Most suture line recurrence and residual disease at anastomosis were sufficiently managed by postoperative medication for long periods of time. Long-term follow-up study showed a good quality of life in about 75% of these cases. In conclusion, conservative resection rather than the sacrifice of normal bowel should be recommended for an extended disease of small bowel

Achievements of Hinode in the first eleven years

Hinode is Japan’s third solar mission following Hinotori (1981–1982) and Yohkoh (1991–2001): it was launched on 2006 September 22 and is in operation currently. Hinode carries three instruments: the Solar Optical Telescope, the X-Ray Telescope, and the EUV Imaging Spectrometer. These instruments were built under international collaboration with the National Aeronautics and Space Administration and the UK Science and Technology Facilities Council, and its operation has been contributed to by the European Space Agency and the Norwegian Space Center. After describing the satellite operations and giving a performance evaluation of the three instruments, reviews are presented on major scientific discoveries by Hinode in the first eleven years (one solar cycle long) of its operation. This review article concludes with future prospects for solar physics research based on the achievements of Hinode

Achievements of Hinode in the first eleven years

Hinode is Japan’s third solar mission following Hinotori (1981–1982) and Yohkoh (1991–2001): it was launched on 2006 September 22 and is in operation currently. Hinode carries three instruments: the Solar Optical Telescope, the X-Ray Telescope, and the EUV Imaging Spectrometer. These instruments were built under international collaboration with the National Aeronautics and Space Administration and the UK Science and Technology Facilities Council, and its operation has been contributed to by the European Space Agency and the Norwegian Space Center. After describing the satellite operations and giving a performance evaluation of the three instruments, reviews are presented on major scientific discoveries by Hinode in the first eleven years (one solar cycle long) of its operation. This review article concludes with future prospects for solar physics research based on the achievements of Hinode

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

SARS-CoV-2オミクロンBA.2.75株（通称ケンタウロス）のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5