Therapeutic Effects of a Sodium Glucose Cotransporter 2 Inhibitor in Diabetic Patients with Chronic Kidney Disease

Multiple large-scale clinical trials have indicated that sodium glucose cotransporter 2（SGLT2）inhibitors reduce the incidence of cardiovascular events, deterioration of renal function and mortality. However, the therapeutic effects of SGLT2 inhibitors are supposed to be limited in patients with reduced renal function considering the mechanism of their action. In this study, a SGLT2 inhibitor, ipragliflozin was given to 30 type 2 diabetic patients with nephropathy whose estimated glomerular filtration rate（eGFR）was not lower than 30 mL/min/1.73 m2. After 12 to 16 weeks, hemoglobin A1c decreased by 0.6％（p＜0.001）, body weight was reduced by 1.8 kg（p＜0.01）and blood pressure was lowered by －10/－6 mmHg（p＜0.001/p ＜0.001）. This was accompanied by reductions in serum uric acid（－0.7 mg/dL, p＜0.001）, triglycerides （－25 mg/dL, p＝0.028）and g-glutamyl transferase（－8 U/L, p＝0.001）. On the other hand, plasma B-type natriuretic peptide also decreased by 12％（p＝0.020）and urinary albumin excretion was reduced by 23％ （p＝0.018）although the eGFR was not significantly changed. It is concluded that ipragliflozin is effective in lowering blood glucose even in patients with diabetic kidney disease and is beneficial in improving theaccompanying obesity and hypertension. In addition, ipragliflozin is thought to have favorable influences on the metabolisms of uric acid and lipids. These properties of ipragliflozin is expected to bring about protective effects against the progression of nephropathy and the development of cardiovascular disease resulting in the improvement of prognosis in diabetic patients with mild to moderate chronic kidney disease

Crosstalk between the Rb Pathway and AKT Signaling Forms a Quiescence-Senescence Switch

SummaryCell-cycle arrest in quiescence and senescence is largely orchestrated by the retinoblastoma (Rb) tumor-suppressor pathway, but the mechanisms underlying the quiescence-senescence switch remain unclear. Here, we show that the crosstalk between the Rb-AKT-signaling pathways forms this switch by controlling the overlapping functions of FoxO3a and FoxM1 transcription factors in cultured fibroblasts. In the absence of mitogenic signals, although FoxM1 expression is repressed by the Rb pathway, FoxO3a prevents reactive oxygen species (ROS) production by maintaining SOD2 expression, leading to quiescence. However, if the Rb pathway is activated in the presence of mitogenic signals, FoxO3a is also inactivated by AKT, thus reducing SOD2 expression and consequently allowing ROS production. This situation elicits senescence through irreparable DNA damage. We demonstrate that this pathway operates in mouse liver, indicating that this machinery may contribute more broadly to tissue homeostasis in vivo

The Far-Infrared Surveyor (FIS) for AKARI

The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and uses two kinds of array detectors. The FIS arrays and optics are designed to sweep the sky with high spatial resolution and redundancy. The actual scan width is more than eight arcmin, and the pixel pitch is matches the diffraction limit of the telescope. Derived point spread functions (PSFs) from observations of asteroids are similar to the optical model. Significant excesses, however, are clearly seen around tails of the PSFs, whose contributions are about 30% of the total power. All FIS functions are operating well in orbit, and its performance meets the laboratory characterizations, except for the two longer wavelength bands, which are not performing as well as characterized. Furthermore, the FIS has a spectroscopic capability using a Fourier transform spectrometer (FTS). Because the FTS takes advantage of the optics and detectors of the photometer, it can simultaneously make a spectral map. This paper summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the AKARI special issue of the Publications of the Astronomical Society of Japa

A Balanced Diet Is Necessary for Proper Entrainment Signals of the Mouse Liver Clock

BACKGROUND:The peripheral circadian clock in mice is entrained not only by light-dark cycles but also by daily restricted feeding schedules. Behavioral and cell culture experiments suggest an increase in glucose level as a factor in such feeding-induced entrainment. For application of feeding-induced entrainment in humans, nutrient content and dietary variations should be considered. PRINCIPAL FINDING:To elucidate the food composition necessary for dietary entrainment, we examined whether complete or partial substitution of dietary nutrients affected phase shifts in liver clocks of mice. Compared with fasting mice or ad libitum fed mice, the liver bioluminescence rhythm advanced by 3-4 h on the middle day in Per2::luciferase knock-in mice that were administered a standard mouse diet, i.e. AIN-93M formula [0.6-0.85 g/10 g mouse BW] (composition: 14% casein, 47% cornstarch, 15% gelatinized cornstarch, 10% sugar, 4% soybean oil, and 10% other [fiber, vitamins, minerals, etc.]), for 2 days. When each nutrient was tested alone (100% nutrient), an insignificant weak phase advance was found to be induced by cornstarch and soybean oil, but almost no phase advance was induced by gelatinized cornstarch, high-amylose cornstarch, glucose, sucrose, or casein. A combination of glucose and casein without oil, vitamin, or fiber caused a significant phase advance. When cornstarch in AIN-93M was substituted with glucose, sucrose, fructose, polydextrose, high-amylose cornstarch, or gelatinized cornstarch, the amplitude of phase advance paralleled the increase in blood glucose concentration. CONCLUSIONS:Our results strongly suggest the following: (1) balanced diets containing carbohydrates/sugars and proteins are good for restricted feeding-induced entrainment of the peripheral circadian clock and (2) a balanced diet that increases blood glucose, but not by sugar alone, is suitable for entrainment. These findings may assist in the development of dietary recommendations for on-board meals served to air travelers and shift workers to reduce jet lag-like symptoms

Binding a Universe: The Formation and Transmutations of the Best Japanese SF (Nenkan Nihon SF Kessakusen) Anthology Series

The annual science fiction anthology series The Best Japanese SF started publication in 2009 and showcases domestic writers old and new and from a wide range of publishing backgrounds. Although representative of the second golden era of Japanese science fiction in print in its diversity and with an emphasis on that year in science fiction, as the volumes progress the editors’ unspoken agenda has become more pronounced, which is to create a set of expectations for the genre and to uphold writers Project Itoh and EnJoe Toh as exemplary of this current golden era. This thesis analyzes the context of the anthology series’ publication, how the anthology is constructed, and these two writers’ contributions to the genre as integral to the anthologies and important to the younger generation of writers in the genre

Differential roles of breakfast only (one meal per day) and a bigger breakfast with a small dinner (two meals per day) in mice fed a high-fat diet with regard to induced obesity and lipid metabolism

<p>Abstract</p> <p>Background</p> <p>Recent studies on humans and rodents have suggested that the timing of food intake plays an important role in circadian regulation and metabolic health. Consumption of high-fat foods during the inactive period or at the end of the awake period results in weight gain and metabolic syndrome in rodents. However, the distinct effects of breakfast size and the breakfast/dinner size ratio on metabolic health have not yet been fully examined in mice.</p> <p>Methods</p> <p>We examined whether the parameters of metabolic syndrome were differentially affected in mice that consumed a large meal at the beginning of the awake period (breakfast; one meal group) and a relatively smaller meal at end of the awake period (dinner; two meals group). The mice of each group were provided equal food volume per day.</p> <p>Results</p> <p>Mice on one meal exhibited an increase in body weight gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression associated with β-oxidation in adipose tissue and liver compared with those on two meals. The circadian expression pattern of the <it>Clock</it> gene in mice on one meal was disturbed compared with those on two meals.</p> <p>Conclusions</p> <p>In conclusion, a bigger breakfast with a smaller dinner (two meals per day) but not breakfast only (one meal per day) helps control body weight and fat accumulation in mice on a high-fat meals schedule. The findings of this study suggest that dietary recommendations for weight reduction and/or maintenance should include information on the timing and quantity of dietary intake.</p