Theobromine enhances the conversion of white adipocytes into beige adipocytes in a PPARγ activation-dependent manner

The adipocytes play an important role in driving the obese-state—white adipose tissue (WAT) stores the excess energy as fat, wherein brown adipose tissue (BAT) is responsible for energy expenditure via the thermoregulatory function of uncoupling protein 1 (UCP1)—the imbalance between these two onsets obesity. Moreover, the anti-obesity effects of brown-like-adipocytes (beige) in WAT are well documented. Browning, the process of transformation of energy-storing into energy-dissipating adipocytes, is a potential preventive strategy against obesity and its related diseases. In the present study, to explore an alternative source of natural products in the regulation of adipocyte transformation, we assessed the potential of theobromine (TB), a bitter alkaloid of the cacao plant, inducing browning in mice (in vivo) and primary adipocytes (in vitro). Dietary supplementation of TB significantly increased skin temperature of the inguinal region in mice and induced the expression of UCP1 protein. It also increased the expression levels of mitochondrial marker proteins in subcutaneous adipose tissues but not in visceral adipose tissues. The microarray analysis showed that TB supplementation upregulated multiple thermogenic and beige adipocyte marker genes in subcutaneous adipose tissue. Furthermore, in mouse-derived primary adipocytes, TB upregulated the expression of the UCP1 protein and mitochondrial mass in a PPARγ ligand-dependent manner. It also increased the phosphorylation levels of PPARγ coactivator 1α without affecting its protein expression. These results indicate that dietary supplementation of TB induces browning in subcutaneous WAT and enhances PPARγ-induced UCP1 expression in vitro, suggesting its potential to treat obesity.ArticleThe Journal of Nutritional Biochemistry. 100: 108898 (2021)journal articl

Nd-ion Substitution Effect on f-electron Multipole Order of PrRu4P12

We studied the effect of magnetic Nd-ion substitution on the metal-nonmetal transition at a transition temperature of 63 K of PrRu4P12, which is characterized by antiferro-type electric multipole ordering of Pr-ion 4f electrons. The transition temperature of Pr1-xNdxRu4P12 depends weakly on the Nd concentration x as compared to Laand Ce-substituted compounds. Inelastic neutron-scattering measurements revealed that the energies and widths of crystalline field excitation peaks of Pr 4f 2 in Pr0.85Nd0.15Ru4P12 are very similar to those of PrRu4P12. These experimental results indicate that the ordered state is robust against the substitution of magnetic Nd ions as compared to the La and Ce substitutions. Magnetic interactions between the Pr ions and the Nd ions in Pr1-xNdxRu4P12 help stabilize the magnetic triplet ground state of the Pr ions that appears in the antiferro-type multipole ordered phase. Therefore, the nonmagnetic multipole ordered phase of PrRu4P12 is compatible with the magnetic perturbation.Conference : 20th International Conference on Magnetism, ICM 2015Location : Barcelona, SPAINDate : JUL 05-10, 201

Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration

<p>Abstract</p> <p>Background</p> <p>Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4⁺T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4⁺lymphocytes in such patients to investigate their clinical significance.</p> <p>Methods</p> <p>CD4⁺T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4⁺lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%.</p> <p>Results</p> <p>CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4⁺lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4⁺lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period.</p> <p>Conclusions</p> <p>The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4⁺T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.</p

A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J)

<p>Abstract</p> <p>Background</p> <p>A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial.</p> <p>Methods/Design</p> <p>In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years.</p> <p>Discussion</p> <p>Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters.</p> <p>Trial registration</p> <p>UMIN Clinical Trials Registry number, UMIN000000444. ClinicalTrials.gov number, NCT00736918.</p

Beam and SKS spectrometers at the K1.8 beam line

High-resolution spectrometers for both incident beams and scattered particles have been constructed at the K1.8 beam line of the Hadron Experimental Facility at J-PARC. A point-to-point optics is realized between the entrance and exit of QQDQQ magnets for the beam spectrometer. Fine-pitch wire chamber trackers and hodoscope counters are installed in the beam spectrometer to accept a high rate beam up to 107 Hz. The superconducting kaon spectrometer for scattered particles was transferred from KEK with modifications to the cryogenic system and detectors. A missing-mass resolution of 1.9 ± 0.1 MeV/c2 (FWHM) was achieved for the ∑ peaks of (π±, K+) reactions on a proton target in the first physics run of E19 in 2010

日本中部のウンシュウミカン園土壌からの亜酸化窒素，炭酸ガスの排出およびメタンの吸収 Emission of N_2O and CO_2 and uptake of CH_4 in soil from a Satsuma mandarin orchard under mulching cultivation in central Japan

The flux of nitrous oxide (N_2O), methane (CH_4) and carbon dioxide (CO_2) from brown lowland soils in a satsuma mandarin (Citrus unshiu Marcow, \u27Silverhill\u27, 31 years old) orchard located in Okitsu, central Japan facing the North Pacific Ocean, was measured once a week from March 2001 to February 2002 using the closed chamber method. Two categories of treatment, mulching and non-mulching, were used in the experimental field by covering the soil surface with a moisture-permeable and waterproof sheet in the latter half of fruit growing season from mid-September to mid-December in 2001. The annual N_2O emission and the amount of total nitrogen fertilized were 93mg N/m^2/year and 27.0g N/m^2/year for the non-mulching treatment and 55mg N/m^2/year and 18.9g N/m^2/year for the mulching treatment, respectively. No significant difference was found in the N_2O emission factor between mulching (0.34%) and non-mulching (0.29%) treatment. These emission factors were much lower than the average value (0.62%) for upland fields in Japan and the IPCC default value of 1.25%. On the other hand, a small amount of atmospheric methane was absorbed into the surface soils throughout the year. The annual uptake of CH_4 was 24 and 17mg CH_4/m^2/year for the non-mulching and mulching treatment, respectively, with no significant difference between the two treatments. Annual CO_2 emission with the non-mulching and mulching treatment was 1.45 and 0.89kg CO_2/m^2/year, respectively. The difference in the amount of each gas emission between the two treatments was discussed with respect to the soil temperature, water-filled pore space (WFPS), the timing and amount of nitrogen fertilized, and the effect of mulching