Hsp105 but not Hsp70 family proteins suppress the aggregation of heat-denatured protein in the presence of ADP

AbstractHsp105α and Hsp105β are mammalian members of the Hsp105/110 family, a diverged subgroup of the Hsp70 family. Here, we show that Hsp105α and Hsp105β bind non-native protein through the β-sheet domain and suppress the aggregation of heat-denatured protein in the presence of ADP rather than ATP. In contrast, Hsc70/Hsp40 suppressed the aggregation of heat-denatured protein in the presence of ATP rather than ADP. Furthermore, the overexpression of Hsp105α but not Hsp70 in COS-7 cells rescued the inactivation of luciferase caused by ATP depletion. Thus, Hsp105/110 family proteins are suggested to function as a substitute for Hsp70 family proteins to suppress the aggregation of denatured proteins in cells under severe stress, in which the cellular ATP level decreases markedly

Evaluation of muscle strength and its relation to exercise habits in Japanese

The aim of this study was to explore muscle strength and its relation to exercise habits in Japanese. We used data from 3,018 men and 6,881 women aged 20-69 years and not using medications in a cross-sectional study. Exercise habits and muscle strength, i.e. grip strength and leg strength, were measured. Age-related changes in muscle strength were noted. Exercise habits were found in 984 men (32.6%) and 1,664 women (24.2%). For subjects of both sexes over 50 years, grip strength was significantly decreased with age. However, the ratio of leg strength to body weight significantly decreased with age as early as 30 years in men and 40 years in women. Grip strength, leg strength and the ratio of leg strength to body weight in subjects with exercise habits were significantly higher than those without exercise habits after adjusting for age in both sexes. This standard mean value may provide a useful database for evaluating muscle strength in Japanese adult subjects.</p

ASTE Observations of Warm Gas in Low-mass Protostellar Envelopes: Different Kinematics between Submillimeter and Millimeter Lines

With the ASTE telescope, we have made observations of three low-mass protostellar envelopes around L483, B335, and L723 in the submillimeter CS ($J$=7--6) and HCN ($J$=4--3) lines. We detected both the CS and HCN lines toward all the targets, and the typical CS intensity ($\sim$ 1.0 K in T$_{B}$) is twice higher than that of the HCN line. Mapping observations of L483 in these lines have shown that the submillimeter emissions in the low-mass protostellar envelope are resolved, exhibit a western extension from the central protostar, and that the deconvolved size is $\sim$ 5500 AU $\times$ 3700 AU (P.A. = 78$^{\circ}$) in the HCN emission. The extent of the submillimeter emissions in L483 implies the presence of higher-temperature ($\gtrsim$ 40 K) gas at 4000 AU away from the central protostar, which suggests that we need to take 2-dimensional radiative transfer models with a flattened disklike envelope and bipolar cavity into account to explain the temperature structure inside the low-mass protostellar envelope. The position-velocity diagrams of these submillimeter lines in L483 and B335 exhibit different velocity gradients from those found in the previous millimeter observations. In particular, along the axis of the associated molecular outflow the sense of the velocity gradient traced by the submillimeter lines is opposite to that of the millimeter observations or the associated molecular outflow, both in L483 and B335. We suggest that expanding gas motions at the surface of the flattened disklike envelope around the protostar, which is irradiated from the central star directly, are the origin of the observed submillimeter velocity structure.Comment: 20 pages, 11 figure

Off-Policy Evaluation of Ranking Policies under Diverse User Behavior

Ranking interfaces are everywhere in online platforms. There is thus an ever growing interest in their Off-Policy Evaluation (OPE), aiming towards an accurate performance evaluation of ranking policies using logged data. A de-facto approach for OPE is Inverse Propensity Scoring (IPS), which provides an unbiased and consistent value estimate. However, it becomes extremely inaccurate in the ranking setup due to its high variance under large action spaces. To deal with this problem, previous studies assume either independent or cascade user behavior, resulting in some ranking versions of IPS. While these estimators are somewhat effective in reducing the variance, all existing estimators apply a single universal assumption to every user, causing excessive bias and variance. Therefore, this work explores a far more general formulation where user behavior is diverse and can vary depending on the user context. We show that the resulting estimator, which we call Adaptive IPS (AIPS), can be unbiased under any complex user behavior. Moreover, AIPS achieves the minimum variance among all unbiased estimators based on IPS. We further develop a procedure to identify the appropriate user behavior model to minimize the mean squared error (MSE) of AIPS in a data-driven fashion. Extensive experiments demonstrate that the empirical accuracy improvement can be significant, enabling effective OPE of ranking systems even under diverse user behavior.Comment: KDD2023 Research trac

Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis

The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-α) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6 (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance

Relationship between peak oxygen uptake and regional body composition in Japanese subjects

AbstractPurposeTo investigate the link between peak oxygen uptake and regional body composition by dual energy X-ray absorptiometry (DEXA) in Japanese subjects.MethodsA total of 93 men (42.2 ± 12.3 years old) and 106 women (43.5 ± 12.3 years old) were enrolled in this cross-sectional investigation study. Peak oxygen uptake was measured by the breath-by-breath method. Regional body composition i.e., body fat mass, lean body mass, and body fat percentage was evaluated using DEXA. In addition, metabolic risk parameters were also evaluated.ResultsPeak oxygen uptake was 37.6 ± 8.7 mL/kg/min in men and 31.1 ± 6.4 mL/kg/min in women, and decreased with age in both genders. Peak oxygen uptake was significantly correlated with total body fat percentage (men: r = −0.684, p < 0.0001; women: r = −0.681, p < 0.0001). These associations remained even after adjusting for age and total lean body mass. However, peak work rate was positively and significantly correlated with leg lean body mass.ConclusionPeak oxygen uptake was closely correlated with total body fat percentage in both genders. Aerobic exercise as well as leg resistance training might be useful for improving peak oxygen uptake in Japanese subjects

Comparison of muscle strength between Japanese men with and without metabolic syndrome

We compared muscle strength between Japanese men with and without metabolic syndrome. We used data for 323 Japanese men with metabolic syndrome and 893 Japanese men without the syndrome. Metabolic syndrome was defined by a new criterion in Japan, and the parameters for muscle strength, i.e. grip strength, leg strength were measured. Leg strength was found to be significantly higher in subjects with metabolic syndrome than in those without, while muscle strength per body weight was significantly lower in subjects with the syndrome. Lower muscle strength per body weight may be one of the characteristic features in subjects with metabolic syndrome.</p