232 research outputs found

    Effective Interaction of Electroweak-Interacting Dark Matter with Higgs Boson and Its Phenomenology

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    We study phenomenology of electroweak-interacting fermionic dark matter (DM) with a mass of O(100)\mathcal{O}(100) GeV. Constructing the effective Lagrangian that describes the interactions between the Higgs boson and the SU(2)L_L isospin multiplet fermion, we evaluate the electric dipole moment (EDM) of electron, the signal strength of Higgs boson decay to two photons and the spin-independent elastic-scattering cross section with proton. As representative cases, we consider the SU(2)L_L triplet fermions with zero/nonzero hypercharges and SU(2)L_L doublet fermion. It is found that the electron EDM gives stringent constraints on those model parameter spaces. In the cases of the triplet fermion with zero hypercharge and the doublet fermion, the Higgs signal strength does not deviate from the standard model prediction by more than a few % once the current DM direct detection constraint is taken into account, even if the CP violation is suppressed. On the contrary, O(10\mathcal{O}(10-20)20) % deviation may occur in the case of the triplet fermion with nonzero hypercharge. Our representative scenarios may be tested by the future experiments.Comment: 13 pages, 5 figures. Version accepted for publication in Phys. Lett.

    HIV-1 Derivatives in Rhesus Macaques

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    A major issue for present HIV-1 research is to establish model systems that reflect or mimic viral replication and pathogenesis actually observed in infected humans. To this end, various strategies using macaques as infection targets have long been pursued. In particular, experimental infections of rhesus macaques by HIV-1 derivatives have been believed to be best suited, if practicable, for studies on interaction of HIV-1 and humans under various circumstances. Recently, through in vitro genetic manipulations and viral cell-adaptations, we have successfully generated a series of HIV-1 derivatives with CXCR4-tropism or CCR5-tropism that grow in macaque cells to various degrees. Of these viruses, those with best replicative potentials can grow comparably with a pathogenic SIVmac in macaque cells by counteracting major restriction factors TRIM5, APOBEC3, and tetherin proteins. In this study, rhesus macaques were challenged with CXCR4-tropic (MN4/LSDQgtu) or CCR5-tropic (gtu + A4CI1) virus. The two viruses were found to productively infect rhesus macaques, being rhesus macaque-tropic HIV-1 (HIV-1rmt). However, plasma viral RNA was reduced to be an undetectable level in infected macaques at 5–6 weeks post-infection and thereafter. While replicated similarly well in rhesus peripheral blood mononuclear cells, MN4/LSDQgtu grew much better than gtu + A4CI1 in the animals. To the best of our knowledge, this is the first report demonstrating that HIV-1 derivatives (variants) grow in rhesus macaques. These viruses certainly constitute firm bases for generating HIV-1rmt clones pathogenic for rhesus monkeys, albeit they grow more poorly than pathogenic SIVmac and SHIV clones reported to date

    Giant geometry modulation on magnetic proximity effect observed in isomeric oxide heterostructures

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    Magnetic proximity effect (MPE) is generally considered to occur at the magnetic-nonmagnetic material interface within a short-range space domain, while the structural geometry modulation on such an interface effect has not been explored. Here, we fabricate isomeric paramagnetic metallic IrO2 with rutile and anatase structures, respectively, on a ferrimagnetic insulating CoFe2O4, and study the MPE-induced magnetism by anomalous Hall effect (AHE) measurements. The rutile phase with layered structure shows a conventional AHE and identical coercive-field with CoFe2O4, indicating a concomitant magnetic switching as a result of a strong magnetic coupling at the interface. In contrast, the anatase phase with tetrahedral structure exhibits an unconventional AHE with negative coercive-field at low temperatures. Further analyses indicate that in anatase, the contribution that strongly couples with CoFe2O4 is dramatically suppressed while a giant frustration-like response emerges. Our findings reveal that the MPE-induced spin orders can be pronouncedly modulated by structural geometry

    Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

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    <p>Abstract</p> <p>Background</p> <p>Adult T-cell leukemia/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component of <it>Brassica </it>vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>In the <it>in vitro </it>study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G<sub>1</sub>/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose) polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally), but not the vehicle control.</p> <p>Conclusion</p> <p>Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.</p

    Histidine-rich glycoprotein as a prognostic biomarker for sepsis

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    Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n=16) than in survivors (n=83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] mu g/ml; p<0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p<0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis

    Boson peak, elasticity, and glass transition temperature in polymer glasses : Effects of the rigidity of chain bending

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    UTokyo FOCUS Press releases掲載「プラスチックの硬さに潜むシンプルな性質を世界で初めて明らかに。 ―高分子ガラスにおける分子振動の正体とは?― 」<研究成果> URI: https://www.u-tokyo.ac.jp/focus/ja/press/z0109_00290.htm

    GABA-A and GABA-B Receptors in Filial Imprinting Linked With Opening and Closing of the Sensitive Period in Domestic Chicks (Gallus gallus domesticus)

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    Filial imprinting of domestic chicks has a well-defined sensitive (critical) period lasting in the laboratory from hatching to day 3. It is a typical model to investigate the molecular mechanisms underlying memory formation in early learning. We recently found that thyroid hormone 3,5,3′-triiodothyronine (T3) is a determinant of the sensitive period. Rapid increases in cerebral T3 levels are induced by imprinting training, rendering chicks imprintable. Furthermore, the administration of exogenous T3 makes chicks imprintable on days 4 or 6 even after the sensitive period has ended. However, how T3 affects neural transmission to enable imprinting remains mostly unknown. In this study, we demonstrate opposing roles for gamma-aminobutyric acid (GABA)-A and GABA-B receptors in imprinting downstream of T3. Quantitative reverse transcription polymerase chain reaction and immunoblotting showed that the GABA-A receptor expression increases gradually from days 1 to 5, whereas the GABA-B receptor expression gradually decreases. We examined whether neurons in the intermediate medial mesopallium (IMM), the brain region responsible for imprinting, express both types of GABA receptors. Immunostaining showed that morphologically identified putative projection neurons express both GABA-A and GABA-B receptors, suggesting that those GABA receptors interact with each other in these cells to modulate the IMM outputs. The roles of GABA-A and GABA-B receptors were investigated using various agonists and antagonists. Our results show that GABA-B receptor antagonists suppressed imprinting on day 1, while its agonists made day 4 chicks imprintable without administration of exogenous T3. By contrast, GABA-A receptor agonists suppressed imprinting on day 1, while its antagonists induced imprintability on day 4 without exogenous T3. Furthermore, both GABA-A receptor agonists and GABA-B receptor antagonists suppressed T3-induced imprintability on day 4 after the sensitive period has ended. Our data from these pharmacological experiments indicate that GABA-B receptors facilitate imprinting downstream of T3 by initiating the sensitive period, while the GABA-A receptor contributes to the termination of the sensitive period. In conclusion, we propose that opposing roles of GABA-A and GABA-B receptors in the brain during development determine the induction and termination of the sensitive period
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