Chemical transport models are useful tools for evaluating source contributions and health impacts of PM2.5 in the atmosphere. We recently found that concentrations of PM2.5 compounds over Japan were ...much better reproduced by a volatility basis set model with an enhanced dry deposition velocity of HNO3 and NH3 compared with a two-product yield model. In this study, we evaluated the sensitivities to organic aerosol models of the simulated source contributions to PM2.5 concentrations and of PM2.5-related mortality. Overall, the simulated source contributions to PM2.5 were similar between the two models. However, because of the improvements associated with the volatility basis set model, the contributions of ammonia sources decreased, particularly in winter and spring, and contributions of biogenic and stationary evaporative sources increased in spring and summer. The improved model estimated that emission sources in Japan contributed 35%–48% of the PM2.5-related mortality in Japan. These values were higher than the domestic contributions to average PM2.5 concentrations in Japan (26%–33%) because the domestic contributions were higher in higher population areas. These results indicate that control of both domestic and foreign emissions is necessary to reduce health impacts due to PM2.5 in Japan.
Nortropine‐N‐oxyl (NNO) was synthesized in a single step from nortropine. The electrocatalytical activity of NNO was evaluated by cyclic voltammetry in pH7.0 phosphate buffer solution. The anodic ...peak current for ethanol, isopropanol and glucose was enhanced, showing these alcohols were oxidized by electrocatalytic effect of NNO. On the other hand, TEMPO derivative (4‐hydroxy‐2,2,6,6,‐terramethylpiperidine N‐oxyl free radical) could not oxidize the alcohols under the same condition. The electrochemical response of the NNO to glucose was investigated. The anodic peak current increased with an increase in the concentration of glucose. A linear response to the glucose concentration ranging from 0.1 to 10 mM was obtained.
Abstract
The circadian clock is an internal timekeeping system that governs about 24 h biological rhythms of a broad range of developmental and metabolic activities. The clocks in eukaryotes are ...thought to rely on lineage-specific transcriptional–translational feedback loops. However, the mechanisms underlying the basic transcriptional regulation events for clock function have not yet been fully explored. Here, through a combination of chemical biology and genetic approaches, we demonstrate that phosphorylation of RNA polymerase II by CYCLIN DEPENDENT KINASE C; 2 (CDKC;2) is required for maintaining the circadian period in Arabidopsis. Chemical screening identified BML-259, the inhibitor of mammalian CDK2/CDK5, as a compound lengthening the circadian period of Arabidopsis. Short-term BML-259 treatment resulted in decreased expression of most clock-associated genes. Development of a chemical probe followed by affinity proteomics revealed that BML-259 binds to CDKC;2. Loss-of-function mutations of cdkc;2 caused a long period phenotype. In vitro experiments demonstrated that the CDKC;2 immunocomplex phosphorylates the C-terminal domain of RNA polymerase II, and BML-259 inhibits this phosphorylation. Collectively, this study suggests that transcriptional activity maintained by CDKC;2 is required for proper period length, which is an essential feature of the circadian clock in Arabidopsis.
Abstract
The complex stratification of tropical forests is a key feature that directly contributes to high aboveground biomass (AGB) and species diversity. This study aimed to explore the vertical ...patterns of AGB and tree species diversity in the tropical forest of Pasoh Forest Reserve, Malaysia. To achieve this goal, we used a combination of field surveys and drone technology to gather data on species diversity, tree height (
H
), and tree diameter at breast height (
D
). As all trees in the 6 ha plot were tagged and identified, we used the data to classify the taxonomy and calculate species diversity indices. We used unmanned aerial vehicle-based structure-from-motion photogrammetry to develop a Digital Canopy Height Model to accurately estimate
H
. The collected data and previous datasets were then used to develop Bayesian height–diameter (HD) models that incorporate taxonomic effects into conventional allometric and statistical models. The best models were selected based on their performance in cross-validation and then used to estimate AGB per tree and the total AGB in the plot. Results showed that taxonomic effects at the family and genus level improved the HD models and consequent AGB estimates. The AGB was the highest in the higher layers of the forest, and AGB was largely contributed by larger trees, especially specific families such as Dipterocarpaceae, Euphorbiaceae, and Fabaceae. In contrast, species diversity was the highest in the lower layers, whereas functional diversity was the highest in the middle layers. These contrasting patterns of AGB and species diversity indicate different roles of forest stratification and layer-specific mechanisms in maintaining species diversity. This study highlights the importance of considering taxonomic effects when estimating AGB and species diversity in tropical forests. These findings underscore the need for a more comprehensive understanding of the complex stratification of tropical forests and its impact on the forest ecosystem.
During fasting, liver pivotally regulates blood glucose levels through glycogenolysis and gluconeogenesis. Kidney also produces glucose through gluconeogenesis. Gluconeogenic genes are transactivated ...by fasting, but their expression patterns are chronologically different between the two organs. We find that renal gluconeogenic gene expressions are positively correlated with the blood β-hydroxybutyrate concentration. Thus, we herein aim to investigate the regulatory mechanism and its physiological implications.
Gluconeogenic gene expressions in liver and kidney were examined in hyperketogenic mice such as high-fat diet (HFD)-fed and ketogenic diet-fed mice, and in hypoketogenic PPARα knockout (PPARα−/−) mice. Renal gluconeogenesis was evaluated by rise in glycemia after glutamine loading in vivo. Functional roles of β-hydroxybutyrate in the regulation of renal gluconeogenesis were investigated by metabolome analysis and RNA-seq analysis of proximal tubule cells.
Renal gluconeogenic genes were transactivated concurrently with blood β-hydroxybutyrate uprise under ketogenic states, but the increase was blunted in hypoketogenic PPARα−/− mice. Administration of 1,3-butandiol, a ketone diester, transactivated renal gluconeogenic gene expression in fasted PPARα−/− mice. In addition, HFD-fed mice showed fasting hyperglycemia along with upregulated renal gluconeogenic gene expression, which was blunted in HFD-fed PPARα−/− mice. In vitro experiments and metabolome analysis in renal tubular cells showed that β-hydroxybutyrate directly promotes glucose and NH3 production through transactivating gluconeogenic genes. In addition, RNA-seq analysis revealed that β-hydroxybutyrate-induced transactivation of Pck1 was mediated by C/EBPβ.
Our findings demonstrate that β-hydroxybutyrate mediates hepato–renal interaction to maintain homeostatic regulation of blood glucose and systemic acid-base balance through renal gluconeogenesis regulation.
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•Renal gluconeogenic gene expression is transactivated under ketogenic conditions.•Activated renal gluconeogenesis contributes to fasting hyperglycemia in obese mice.•β-hydroxybutyrate directly transactivates renal gluconeogenic gene expression.•β-hydroxybutyrate supplementation ameliorates fasting hypoglycemia in PPARα−/− mice.•β-hydroxybutyrate is a regulator of glucose and acid-base homeostasis in kidney.
Radiometric calibration utilizing the Moon as a reference source is termed as lunar calibration. It is a useful method for evaluating the performance of optical sensors onboard satellites orbiting ...the Earth. Lunar calibration provides sufficient radiometric calibration opportunities without requiring any special equipment, and is suitable for nano/microsatellites. This study applies lunar calibration to a multispectral sensor, Ocean Observation Camera (OOC), on board a microsatellite named Rapid International Scientific Experiment Satellite. Simulating the brightness of the Moon based on the RObotic Lunar Observatory and SELENE/Spectrum Profiler models, sensitivity degradation was proven to be negligible in any of the four spectral bands of the OOC with the sensor temperature correction. A bluing trend in the OOC's sensor sensitivity was revealed, indicating a shorter observation wavelength shows larger irradiance. Comparing the top-of-atmosphere reflectance of Railroad Valley Playa with the Radiometric Calibration Network dataset revealed that the derived calibration parameter from the lunar calibration was valid for correcting the bluing trend in the visible range. Although the lunar and vicarious calibration parameters for the infrared band were unexpectedly inconsistent, lunar calibration could potentially contribute toward estimating the contaminated background radiance in the Earth observation images.
Abstract
Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering ...effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
A new anti-GARP antibody that enhances antitumor immunity
Abstract
Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were ...expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions.
Objective:
Reports of hypothyroidism after hysterosalpingography (HSG) using lipiodol are emerging. The present study was designed to investigate the changes in serum iodine concentration (SIC), ...urinary iodine concentration/creatinine excretion (UI/Cr), and thyroid function before and after HSG using lipiodol.
Methods:
The prospective observation study included 22 infertile euthyroid women with no previous history of thyroid disease. All underwent HSG between April 2007 and August 2008 at our institution. We examined SIC, UI/Cr, and thyroid function before HSG, and at 4, 8, 12, and 24 weeks, and 9–12 months after HSG.
Results:
The median value of SIC and UI/Cr peaked at 4 weeks after HSG and remained at significantly high levels at 8, 12, and 24 weeks post-HSG compared with pre-HSG. In sync with the increase of iodine, the mean level of TSH significantly increased at 4, 8, 12, and 24 weeks post-HSG compared with pre-HSG. After 24 weeks, differences in SIC, UI/Cr, and TSH levels before and after HSG became nonsignificant. The mean value of free triiodothyronine and free thyroxine showed no significant difference at any of the time points compared with pre-HSG. Three cases (13.6%) showed transient high TSH (>5 μIU/L) with normal thyroid hormones at 4 or 8 weeks after HSG.
Conclusion:
Thyroid monitoring should be conducted in the first 4–8 weeks after HSG using lipiodol and attention to thyroid dysfunction should be paid for up to 6 months after the procedure due to the possibility of excess iodine.
Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, ...MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57‐year‐old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non‐keratinized squamous epithelium with small duct‐like structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3‐MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML‐2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.
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