74 research outputs found
Contribution of Majoron to Hubble tension in gauged U(1) Model
In this paper, we analyze parameter regions that can alleviate the Hubble
tension in the U(1) model with the broken lepton number
U(1) symmetry. As new particles, this model has a U(1)
gauge boson and a Majoron , which can affect the early universe and
the effective number of neutrino species . If and
simultaneously exist in the early universe, - interaction
processes such as occur. The
comparison of between the cases with and without the
- interaction processes shows that these processes make a small
contribution of to , and it does not need
to be considered for the alleviation of the Hubble tension. Based on these
facts, we calculated for various Majoron parameters without the
- interaction processes to search parameters that could alleviate
the Hubble tension. As a result, we found that the U(1)
gauge boson and Majoron can alleviate the Hubble tension in some parameter
regions, and there is a non-trivial synergy contribution between and
. Moreover, the parameter region with a lighter mass
MeV and a larger coupling is excluded because it
predicts too large , i.e. . The favored
and restricted regions of the Majoron parameters depend on the parameters
because of the presence of the contribution and synergy one.Comment: 24 pages, 4 figure
Model Building by Coset Space Dimensional Reduction Scheme Using Twelve-Dimensional Coset Spaces
We investigate the twelve-dimensional gauge-Higgs unification models with an
eight-dimensional coset space. For each model, we apply the coset space
dimensional reduction procedure and examine the particle contents of the
resulting four-dimensional theory. Then, some twelve-dimensional SO(18) gauge
theories lead to models of the SO(10)\times U(1) grand unified theory in four
dimensions, where fermions of the Standard Model appear in multiple generations
along with scalars that may break the electroweak symmetry. The representations
of the obtained scalars and fermions are summarized.Comment: 17 pages, 4 table
ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells
Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation
Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II
In addition to antigen presentation to CD4(+)T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of MHC-II, which was associated with decreased surface expression levels in murine dendritic cells (DCs) and resulted in impaired activation of CD4(+)T cells. However, the downstream signal that induces MHC-II endocytosis remains to be elucidated. In this study, we found that the crosslinking of MHC-II induced intracellular Ca(2+)mobilization, which was necessary for crosslinking-induced MHC-II endocytosis. We also found that these events were suppressed by inhibitors of Syk and phospholipase C (PLC). Treatments with a phorbol ester promoted MHC-II endocytosis, whereas inhibitors of protein kinase C (PKC) suppressed crosslinking-induced endocytosis of MHC-II. These results suggest that PKC could be involved in this process. Furthermore, crosslinking-induced MHC-II endocytosis was suppressed by inhibitors of clathrin-dependent endocytosis. Our results indicate that the crosslinking of MHC-II could stimulate Ca(2+)mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs
Discrimination of stock origin of spawning population of ayu Plecoglossus altivelis altivelis at the Ota River, Hiroshima Prefecture
太田川下流域で採集したアユ産卵群の由来判別を外部形態および耳石Sr:Ca比分析で行った。太田川にて放流された人工種苗の耳石Sr:Ca比のチャートパターンは耳石中心から300μmで減少が認められ,耳石中心から400μm以遠で比が減少する天然型と異なっていた。耳石Sr:Ca 比のチャートパターンに基づくと,産卵群への人工種苗の混入率は28%と考えられた。採集した産卵群の側線上方横列鱗数は13~26枚(n=173)で,側線上方横列鱗数が17枚以下を人工種苗,18枚以上を天然アユと仮定すると,産卵群への人工種苗の混入率は31%と見積もられた。太田川産卵群では概ね3割が放流された人工種苗であると考えられた。Stock discrimination in the spawning population of ayu, Plecoglossus altivelis altivelis in the Ota River, western Japan was conducted using number of scales above the lateral line and otolith Sr:Ca ratio. Chart pattern in otolith Sr:Ca ratio of hatchery-stocked ayu was different in amphidromous form. Based on chart pattern of otolith Sr:Ca ratio, mixing ratio of hatchery-stocked ayu to the spawning population was estimated at 28%. Number of scales above the lateral line of spawning population marked from 13 to 26 (n=173). Based on number of scales above the lateral line (hatchery-stocked ayu ≦ 17; amphidromous ≧ 18), the mixing ratio of hatchery-stocked ayu was estimated 31%. Consequently, the contribution ratio of hatchery-stocked ayu to the spawning population was around 30% at the Ota River
Fast deuteron diagnostics using visible light spectra of 3He produced by deuteron–deuteron reaction in deuterium plasmas
The fast deuteron (non-Maxwellian component) diagnostic method, which is based on the higher resolution optical spectroscopic measurement, has been developed as a powerful tool. Owing to a decrease in the D–H charge-exchange cross section, the diagnostic ability of conventional optical diagnostic methods should be improved for ∼MeV energy deuterons. Because the 3He–H charge-exchange cross section is much larger than that of D–H in the ∼MeV energy range, the visible light (VIS) spectrum of 3He produced by the dueteron–dueteron (DD) reaction may be a useful tool. Although the density of 3He is small because it is produced via the DD reaction, improvement of the emissivity of the VIS spectrum of 3He can be expected by using a high-energy beam. We evaluate the VIS spectrum of 3He for the cases when a fast deuteron tail is formed and not formed in the ITER-like beam injected deuterium plasma. Even when the beam energy is in the MeV energy range, a large change appears in the half width at half maximum of the VIS spectrum. The emissivity of the VIS spectrum of 3He and the emissivity of bremsstrahlung are compared, and the measurable VIS spectrum is obtained. It is shown that the VIS spectrum of 3He is a useful tool for the MeV beam deuteron tail diagnostics
Therapy for CKD-associated muscle dysfunction
Background
Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice.
Methods
The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups.
Results
In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level.
Conclusions
Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance
Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).
Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).
Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.
Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer
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