A Gauge-Mediation Model with a Light Gravitino of Mass O(10) eV and the Messenger Dark Matter

In the light of recent experimental data on gaugino searches, we revisit the direct-transmission model of dynamical supersymmery breaking with the gravitino mass m_{\tilde{G}}\leq 16 eV, which does not have any cosmological or astrophysical problems. We find that in the consistent regions of parameter space, the model predicts not only upper bounds on superparticle masses (1.1 TeV, 320 GeV, 160 GeV, 5 TeV, 1.5 TeV and 700 GeV for gluino, Wino, Bino, squarks, left-handed sleptons and right-handed sleptons, respectively), but also a mass of the lightest messenger particle in the range of 10-50 TeV. The lightest messenger particle can naturally be a messenger sneutrino. Therefore, this may suggest that the messenger sneutrino could be the dark matter, as proposed recently by Hooper and March-Russel to account for the gamma-ray spectrum from the galactic center observed by HESS experiment.Comment: 11 pages, 3 figure

Distinct regulatory mechanism of yeast GPX2 encoding phospholipid hydroperoxide glutathione peroxidase by oxidative stress and a calcineurin/Crz1-mediated Ca2+ signaling pathway

AbstractThe GPX2 gene encodes a homologue of mammalian phospholipid hydroperoxide glutathione peroxidase in Saccharomyces cerevisiae. Previously, we have reported that the oxidative stress-induced expression of GPX2 is strictly regulated by Yap1 and Skn7 transcription factors. Here, we found that the expression of GPX2 is induced by CaCl2 in a calcineurin (CN)/Crz1-dependent manner, and the CN-dependent response element was specified in the GPX2 promoter. Neither Yap1 nor Skn7 was required for Ca2+-dependent induction of GPX2, therefore, distinct regulation for the oxidative stress response and Ca2+ signal response for GPX2 exists in yeast cells

Neutrino-induced lepton flavor violation in gauge-mediated supersymmetry breaking

Gauge-mediated supersymmetry breaking is known to greatly suppress flavor changing neutral current effects. However, we show that gauge mediation in the context of leptogenesis implies potentially large lepton flavor violating signals. If the heavy right-handed neutrinos that participate in leptogenesis are lighter than the messenger scale of gauge mediation, they will induce flavor off-diagonal masses to the sleptons which in turn can induce large effects in mu to e gamma, tau to mu gamma, and mu-e conversion in nuclei. We demonstrate this result and compute numerically the lepton-flavor violating decay and conversion rates in scenarios of direct gauge mediation.Comment: 18 pages, 5 figure

Normal meal tolerance test is preferable to the glucagon stimulation test in patients with type 2 diabetes that are not in a hyperglycemic state: Comparison with the change of C-peptide immunoreactivity

Aims/Introduction: The aim of the present study was to evaluate the properties of the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in patients with type 2 diabetes. Materials and Methods: We enrolled 142 patients with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT using a calorie-controlled meal based on an intake of 30 kcal/kg ideal bodyweight/day. We calculated the change in C-peptide immunoreactivity (ΔCPR) by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection (GST) or 120 min after the meal (NMTT). Results: Mean ΔCPR for the GST was 2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater ΔCPR in the NMTT than the GST, and the mean ΔCPR was significantly greater in the NMTT than the GST (P < 0.05). To exclude any influence of antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents, and found the mean ΔCPR was significantly greater in the NMTT than the GST (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose toxicity, we carried out receiver operating characteristic analyses with fasting plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST ΔCPR to be larger than NMTT ΔCPR were fasting plasma glucose 147 mg/dL and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64, specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity 0.56, specificity 0.71, area under the curve 0.66). Conclusions: The NMTT is a reliable insulin secretion test in patients with type 2 diabetes, except for those in a hyperglycemic state

Associations of low-intensity light physical activity with physical performance in community-dwelling elderly Japanese: A cross-sectional study

BackgroundPhysical activity and physical performance relate to quality of life, mortality, and morbidity in elderly people. However, little is known about differences in physical performance related to low-intensity light physical activity (LLPA), high-intensity light physical activity (HLPA), and moderate-intensity physical activity (MPA) and how they are separated by sex in elderly populations.AimsThis study aimed to determine differences in LLPA, HLPA, MPA, and physical performance, and associations between these measures in community-dwelling elderly men and women.MethodsPhysical activity and physical performance such as timed-up-and-go test, one-leg standing time, and maximum gait speed were measured in 181 community-dwelling elderly men (mean age, 75.1 ± 5.3 years) and 109 women (mean age, 73.4 ± 4.8 years) in 2013. Physical activity was classified as LLPA (1.6~1.9 METs of physical activity), HLPA (2.0~2.9 METs of physical activity), and MPA (over 3 METs of physical activity). The association between the values of these three intensities of physical activity in the participants was assessed by Pearson’s correlation coefficients. Multiple linear regression analyses were used to assess the association of physical performance values with the three groups defined by accelerometer-measured physical activity intensity adjusted for sociographic, behavioral, and multiple diseases in the participants.ResultsMPA was beneficially associated with all physical performance indicators in the men (all P<0.05) and women (all P<0.05). Only HLPA showed significant associations with the timed-up-and-go test (P = 0.001) and maximum gait speed (P = 0.006) in women.DiscussionThese results may support the notion that not only HLPA in women but MPA in both sexes appears to improve physical performance in elderly populations.ConclusionThe present study findings provide novel epidemiological evidence for the potential benefits of HLPA in women and also reinforce the potential benefits of MPA in both sexes, which is the mainstay of public health recommendations

IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism

Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-α, and TGF-β were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases

Body mass index >= 23 is a risk factor for insulin resistance and diabetes in Japanese people: A brief report

Background: Screening for undiagnosed type 2 diabetes mellitus is recommended for Asian Americans with a body mass index ≥23. However, the optimal body mass index cut-off score for predicting the risk of diabetes mellitus in Japanese people is not well known. The aim of this study was to determine the best body mass index cut-off score for predicting insulin resistance and diabetes mellitus in the Japanese population. Methods: This study had two parts, a clinical investigation and a retrospective observational investigation. In the clinical part of the study, 58 participants (26 with type 2 diabetes mellitus and 32 non-diabetics) underwent a hyperinsulinemic-euglycemic clamp from which their glucose disposal rate was measured. For the retrospective part of the study, medical check-up data from 88,305 people in the Tottori Prefecture were analyzed for clinical evidence of diabetes mellitus. The optimal BMI cut-off scores for prediction of insulin resistance and diabetes mellitus were determined. Results: In the clamp study, the optimal body mass index cut-off score to predict insulin resistance in non-diabetic patients was 22.7. All participants with type 2 diabetes mellitus were insulin resistant, and the optimal body mass index cut-off score for prediction of severe insulin resistance was 26.2. When the data from the type 2 diabetic and the non-diabetic participants were combined, the optimal body mass index cut-off score for prediction of insulin resistance was 23.5. Analysis of 88,305 medical check-up records yielded an optimal body mass index cut-off score for prediction of diabetes mellitus of 23.6. Conclusions: These results suggest that having a body mass index ≥23 is a risk factor for insulin resistance and diabetes mellitus in the Japanese population

CPR-IR is an insulin resistance index that is minimally affected by hepatic insulin clearance-A preliminary research

Background: Increased hepatic insulin clearance (HIC) is important in the pathophysiology of type 2 diabetes mellitus (T2DM). The aim of this study is to analyze an effective insulin resistance (IR) index that is minimally affected by HIC. Methods: Our study involved 20 participants with T2DM and 21 healthy participants without diabetes (Non-DM). Participants underwent a meal tolerance test from which plasma glucose, insulin and serum C-peptide immunoreactivity (CPR) were measured, and HOMA-IR and HIC were calculated. Participants then underwent a hyperinsulinemic-euglycemic clamp from which the glucose disposal rate (GDR) was measured. Results: The index CPR-IR = 20/(fasting CPR × fasting plasma glucose) was correlated more strongly with GDR, than was HOMA-IR, and CPR-IR could be used to estimate GDR. In T2DM participants with HIC below the median, HOMA-IR and CPR-IR were equally well correlated with GDR. In T2DM with high HIC, CPR-IR correlated with GDR while HOMA-IR did not. In Non-DM, CPR-IR and HOMA-IR were equally well correlated with GDR regardless of HIC. The mean HIC value in T2DM was significantly higher than that of Non-DM. Conclusions: CPR-IR could be a simple and effective index of insulin resistance for patients with type 2 diabetes that is minimally affected by HIC

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes