Steady Rotation of Micropolar Fluid Sphere in Concentric Spherical Container

AbstractThe problem of slow steady rotation of a micropolar fluid sphere in concentric spherical container filled with viscous fluid is studied. The appropriate boundary conditions are taken on the surface of the sphere. The hydrodynamic couple and wall correction factor exerted on the micropolar fluid sphere is obtained. The dependence of the wall correction factor on the micropolarity parameter and spin parameter is presented graphically and discussed. The hydrodynamic couple acting on a solid sphere in a cell model and on a solid sphere in an unbounded medium are obtained from the present analysis

A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals

AbstractTwo monoclonal antibodies (SPM-1 and SPM-2) immunoprecipitate brain N-type calcium channels. On immunoaffinity chromatography of digitonin extracts of bovine brain membranes on SPM-1- and SPM-2-Sepharose, proteins of 36 (syntaxins A and B), 28 and 19 kDa are specifically retained by both columns. Here we show that the 19 and 28 kDa bands contain VAMP/synaptobrevin-2, and rab3A/smg25A and SNAP-25, respectively. Since SPM-1 and SPM-2 recognize only syntaxins and the 28 kDa band (rab3A/smg25A and SNAP-25), respectively, the results indicate that all these proteins form a complex. Our results suggest tight linkage between the components involved in neurotransmitter release

高い変形能を示すチタン繊維編物内部への骨成長

Objectives: The objective of this study is to develop a Ti fibre knit block without sintering, and to evaluate its deformability and new bone formation in vivo. Material and Methods: A Ti fibre with a diameter of 150 μm was knitted to fabricate a Ti mesh tube. The mesh tube was compressed in a metal mould to fabricate porous Ti fibre knit blocks with three different porosities of 88%, 69%, and 50%. The elastic modulus and deformability were evaluated using a compression test. The knit block was implanted into bone defects of a rabbit’s hind limb, and new bone formation was evaluated using micro computed tomography (micro-CT) analysis and histological analysis. Results: The knit blocks with 88% porosity showed excellent deformability, indicating potential appropriateness for bone defect filling. Although the porosities of the knit block were different, they indicated similar elastic modulus smaller than 1 GPa. The elastic modulus after deformation increased linearly as the applied compression stress increased. The micro-CT analysis indicated that in the block with 50% porosity new bone filled nearly all of the pore volume four weeks after implantation. In contrast, in the block with 88% porosity, new bone filled less than half of the pore volume even 12 weeks after implantation. The histological analysis also indicated new bone formation in the block. Conclusions: The titanium fibre knit block with high porosity is potentially appropriate for bone defect filling, indicating good bone ingrowth after porosity reduction with applied compression

Positive association of AKT1 haplotype to Japanese methamphetamine use disorder

Recent evidence suggests that the AKT1-GSK3Β signalling cascade partially mediates dopaminedependentbehaviours. In relation to the pathophysiology of schizophrenia or methamphetamine (Meth)use disorder, AKT1 is a good candidate gene for such conditions. For schizophrenia, positive associationsof SNPs and AKT1 haplotypes were reported in US and Japanese samples. To evaluate the association between AKT1 and Meth-use disorder, we conducted a case-control study of Japanese samples (182 patients and 437 controls). A positive association between a SNP and haplotypes was found, and the ‘signal’ SNP was the same SNP found to be associated with US schizophrenia, but not with Japanese schizophrenia. Our results indicate that AKT1 may play a possible role in the development of Meth-use disorder. Further investigation of these associations, together with evidence from previous animal studies, may open the way to elucidation of the pathophysiology of this condition.</p

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Objective. Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. Method. A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. Results. Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-γ. Conclusion. This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted

Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms

AbstractMyeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as “driver” gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%–30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs) but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6–8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2—the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators—and examined the influence of single or double mutations on HSCs (Lineage−Sca-1+c-Kit+ cells (LSKs)) by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F–LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F–LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more highly expressed in double-mutant-LSKs than in JAK2V617F–LSKs. These altered gene expressions might partly explain the mechanisms of initiation and progression of MPNs which was observed in the functional analyses [9]. Here we describe gene expression profiles deposited at the Gene Expression Omnibus (GEO) under the accession number GSE62302 including experimental methods and quality control analyses

Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis

Shide, K., Kameda, T., Kamiunten, A. et al. Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis. Blood Cancer J. 9, 42 (2019). https://doi.org/10.1038/s41408-019-0202-

Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

成人T細胞白血病リンパ腫の多段階発がん分子メカニズムを解明 --難治性疾患の新規治療標的候補を複数同定--. 京都大学プレスリリース. 2021-09-07.Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1–infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell–restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis