RNase L mediates the insulin signalling pathway

Diabetes is characterized by hyperglycemia mainly due to defect in insulin secretion and/or action. Regulation of glucose transport and use by insulin is central to the maintenance of whole-body glucose homeostasis. One of the potential mechanisms associated with insulin sensitivity is the activation of insulin receptor (IR) and subsequently transduces the signal through phosphorylation of insulin receptor substrate1 (IRS1) and activation of the PI-3K/Akt pathway. RNase L, an interferon (IFN)-inducible enzyme, plays an important role in IFN functions against viral infection and cell proliferation. However, a direct link between RNase L and insulin sensitivity has yet to be clearly established. In this study, we found that RNase L plays an important role in glucose homeostasis through impacting IR which is a transmembrane receptor activated by insulin. The phosphorylation status of IR was significantly reduced in the cells deficient RNase L. As a result, activation of IRS1, the downstream substrate of IR, and the PI3K/AKT pathway was significantly inhibited in RNase L-/- cells. Further investigation of the molecular mechanism underlying the role of RNase L in mediating the activation of IR revealed that RNase L might regulate the cleavage of the precursor of IR via the ubiquitin/ proteasome system. Our results suggest that RNase L may be a novel target in the design of therapeutic strategies for diabetes.https://engagedscholarship.csuohio.edu/u_poster_2017/1020/thumbnail.jp

A Galactomannoglucan Derived from Agaricus brasiliensis: Purification, Characterization and Macrophage Activation via MAPK and IkappaB/NFkappaB Pathways

In this study, a novel galactomannoglucan named as TJ2 was isolated from Agaricus brasiliensis with microwave extraction, macroporous resin, ion exchange resin and high resolution gel chromatography. TJ2 is composed of glucose, mannose and galactose in the ratio 99.2:0.2:0.6. Infrared spectra (IR), methylation analysis and nuclear magnetic resonance spectra indicated that TJ2 mainly contained a b-(1?3) – linked glucopyranosyl backbone. Interestingly, TJ2 significantly promoted RAW264.7 cell proliferation, and was able to activate the cells to engulf E. coli. In addition, TJ2 induced the expression of Interleukin 1b (IL-1b), Interleukin 6 (IL-6), tumor necrosis factor a (TNF-a) and cyclooxygenase-2 (Cox-2) in the cells. TJ2 also promoted the production of nitric oxide (NO) by inducing the expression of inducible nitric oxide synthase (iNOS). Moreover, TJ2 is a potent inducer in activating the mitogen-activated protein kinase (MAPK) and inhibitor of nuclear factor-kappa B (IkappaB)/nuclear factor-kappa B (NFkappaB) pathways

A New Liquid Chromatography/Tandem Mass Spectrometry Method for Quantification of Gangliosides in Human Plasma

Gangliosides are a family of glycosphingolipids characterized by mono- or polysialic acid-containing oligosaccharides linked through 1,3- and 1,4-β glycosidic bonds with subtle differences in structure that are abundantly present in the central nervous systems of many living organisms. Their cellular surface expression and physiological malfunction are believed to be pathologically implicated in considerable neurological disorders, including Alzheimer and Parkinson diseases. Recently, studies have tentatively elucidated that mental retardation or physical stagnation deteriorates as the physiological profile of gangliosides becomes progressively and distinctively abnormal during the development of these typical neurodegenerative syndromes. In this work, a reverse-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay using standard addition calibration for determination of GM2, GM3, GD2, and GD3 in human plasma has been developed and validated. The analytes and internal standard were extracted from human plasma using a simple protein precipitation procedure. Then the samples were analyzed by reverse-phase ultra-performance liquid chromatography (UPLC)/MS/MS interfaced to mass spectrometry with electrospray ionization using a multiple reaction monitoring mode to obtain superior sensitivity and specificity. This assay was validated for extraction recovery, calibration linearity, precision, and accuracy. Our quick and sensitive method can be applied to monitor ganglioside levels in plasma from normal people and neurodegenerative patients

Identification of candidate genes and clarification of the maintenance of the green pericarp of weedy rice grains

The weedy rice (Oryza sativa f. spontanea) pericarp has diverse colors (e.g., purple, red, light-red, and white). However, research on pericarp colors has focused on red and purple, but not green. Unlike many other common weedy rice resources, LM8 has a green pericarp at maturity. In this study, the coloration of the LM8 pericarp was evaluated at the cellular and genetic levels. First, an examination of their ultrastructure indicated that LM8 chloroplasts were normal regarding plastid development and they contained many plastoglobules from the early immature stage to maturity. Analyses of transcriptome profiles and differentially expressed genes revealed that most chlorophyll (Chl) degradation-related genes in LM8 were expressed at lower levels than Chl a/b cycle-related genes in mature pericarps, suggesting that the green LM8 pericarp was associated with inhibited Chl degradation in intact chloroplasts. Second, the F2 generation derived from a cross between LM8 (green pericarp) and SLG (white pericarp) had a pericarp color segregation ratio of 9:3:4 (green:brown:white). The bulked segregant analysis of the F2 populations resulted in the identification of 12 known genes in the chromosome 3 and 4 hotspot regions as candidate genes related to Chl metabolism in the rice pericarp. The RNA-seq and sqRT-PCR assays indicated that the expression of the Chl a/b cycle-related structural gene DVR (encoding divinyl reductase) was sharply up-regulated. Moreover, genes encoding magnesium-chelatase subunit D and the light-harvesting Chl a/b-binding protein were transcriptionally active in the fully ripened dry pericarp. Regarding the ethylene signal transduction pathway, the CTR (encoding an ethylene-responsive protein kinase) and ERF (encoding an ethylene-responsive factor) genes expression profiles were determined. The findings of this study highlight the regulatory roles of Chl biosynthesis- and degradation-related genes influencing Chl accumulation during the maturation of the LM8 pericarp

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

RNase L mediates the insulin signalling pathway

Diabetes is characterized by hyperglycemia mainly due to defect in insulin secretion and/or action. Regulation of glucose transport and use by insulin is central to the maintenance of whole-body glucose homeostasis. One of the potential mechanisms associated with insulin sensitivity is the activation of insulin receptor (IR) and subsequently transduces the signal through phosphorylation of insulin receptor substrate1 (IRS1) and activation of the PI-3K/Akt pathway. RNase L, an interferon (IFN)-inducible enzyme, plays an important role in IFN functions against viral infection and cell proliferation. However, a direct link between RNase L and insulin sensitivity has yet to be clearly established. In this study, we found that RNase L plays an important role in glucose homeostasis through impacting IR which is a transmembrane receptor activated by insulin. The phosphorylation status of IR was significantly reduced in the cells deficient RNase L. As a result, activation of IRS1, the downstream substrate of IR, and the PI3K/AKT pathway was significantly inhibited in RNase L-/- cells. Further investigation of the molecular mechanism underlying the role of RNase L in mediating the activation of IR revealed that RNase L might regulate the cleavage of the precursor of IR via the ubiquitin/ proteasome system. Our results suggest that RNase L may be a novel target in the design of therapeutic strategies for diabetes.https://engagedscholarship.csuohio.edu/u_poster_2017/1020/thumbnail.jp

Environmental Regulation and Corporate Financing—Quasi-Natural Experiment Evidence from China

The Environmental Protection Law, which includes 70 articles and major changes in six aspects compared to the old law, is called in Chinese society the new Environment Protection Law. When the law was implemented in 2014, it was an important event in China that could be seen as a natural experiment. Based on a difference-in-differences model, this paper considers all of the listed heavily polluting enterprises between 2011 and 2016 as the experimental group and all of the other firms in the same industries listed on the Chinese stock market as the control group and examines the impact of the new Environmental Protection Law on the corporate financing of heavily polluting enterprises and its mechanisms. The results show that the strict environmental law caused Chinese listed enterprises to face higher environmental regulation costs, public pressure and environmental litigation. The financing capacity of heavily polluting enterprises has dropped significantly, especially in areas with higher regulatory intensity. Furthermore, since the new Environmental Protection Law was established, overinvestment by China’s heavily polluting enterprises has been significantly inhibited, and the decline in financing capacity exerts a mediating effect. The ultimate economic consequences of the new Environmental Protection Law are to decrease the corporate value of heavily polluting industries

Green Credit, Debt Maturity, and Corporate Investment—Evidence from China

Against the backdrop of working hard to build a beautiful country, this paper uses the promulgation of the “Green Credit Guidelines„ policy in China as a quasi-natural experiment. Based on a difference-in-differences (DID) model, the results show that, since the promulgation of the Green Credit Guidelines policy, financial institutions have significantly reduced the proportion of long-term debt to heavily polluting enterprises for reasons such as risk aversion and total credit constraints. Due to capital constraints and the restrictive terms of credit approval, the Green Credit Guidelines policy reduces the investment scale and overinvestment of heavily polluting enterprises. The dependency relationship of the debt maturity structure of heavily polluting enterprises with the investment scale and investment efficiency has been reduced. Furthermore, the negative net effect of the Green Credit Guidelines policy on long-term debt is more pronounced in heavily polluting enterprises that lack political connections. However, the promulgation of this policy inhibits the investment scale and the investment efficiency of heavily polluting enterprises (with or without political connections). To a certain extent, these results confirm the “supportive hand„ perspective towards political connections. The results of this research could help relevant government departments to understand the microeconomic consequences of the Green Credit Guidelines policy and could help improve and perfect China’s green credit policy

Root Traits and Soil Bacterial Composition Explain the Rhizosphere Effects along a Chronosequence of Rubber Plantations

Rubber tree plantations (Hevea brasiliensis) are expanding into the tropical regions of southwest China to ensure production to meet the growing demand for latex. The effects of long-term plantations on soil carbon processes are still unclear. Also, the effects of the plant’s rhizosphere on the decomposition of soil organic matter (SOM) play a crucial role in predicting soil carbon dynamics. The rhizosphere and soils corresponding to a chronosequence of ages (4, 15 and 30 years) of rubber plantations were collected and incubated to determine the effect of the rhizosphere (RE) on SOM decomposition. We also examined the soil physicochemical properties; bacterial community structure; and root morphological, chemical, and physiological traits to further explore the underlying mechanisms of the RE on SOM decomposition. The REs on SOM decomposition varied significantly in the different age classes of the rubber plantations, and the higher the REs on SOM decomposition in an older plantation might limit the accumulation of organic carbon in the soil. Root traits, including the specific root length, root nitrogen content, and root carbon/nitrogen ratio, varied significantly in response to the plantation age and explained more of the variance in the RE on SOM decomposition than the soil and microbial properties. Due to the changing root morphological and chemical traits along the age chronosequence, the rhizosphere bacterial community composition tended to shift the carbon utilisation strategy and the bulk soil nitrogen content decreased. These variations also affected the RE on SOM decomposition. Our results indicate that the development of rubber plantations would prevent soil carbon accumulation, especially in the rhizosphere, by increasing the RE on SOM decomposition, which would be predicated by root morphological and chemical traits