Generation and analysis of expressed sequence tags from a cDNA library of the fruiting body of Ganoderma lucidum

<p>Abstract</p> <p>Background</p> <p>Little genomic or trancriptomic information on <it>Ganoderma lucidum </it>(<it>Lingzhi</it>) is known. This study aims to discover the transcripts involved in secondary metabolite biosynthesis and developmental regulation of <it>G. lucidum </it>using an expressed sequence tag (EST) library.</p> <p>Methods</p> <p>A cDNA library was constructed from the <it>G</it>. <it>lucidum </it>fruiting body. Its high-quality ESTs were assembled into unique sequences with contigs and singletons. The unique sequences were annotated according to sequence similarities to genes or proteins available in public databases. The detection of simple sequence repeats (SSRs) was preformed by online analysis.</p> <p>Results</p> <p>A total of 1,023 clones were randomly selected from the <it>G</it>. <it>lucidum </it>library and sequenced, yielding 879 high-quality ESTs. These ESTs showed similarities to a diverse range of genes. The sequences encoding squalene epoxidase (SE) and farnesyl-diphosphate synthase (FPS) were identified in this EST collection. Several candidate genes, such as <it>hydrophobin</it>, <it>MOB2</it>, <it>profilin </it>and <it>PHO84 </it>were detected for the first time in <it>G</it>. <it>lucidum</it>. Thirteen (13) potential SSR-motif microsatellite loci were also identified.</p> <p>Conclusion</p> <p>The present study demonstrates a successful application of EST analysis in the discovery of transcripts involved in the secondary metabolite biosynthesis and the developmental regulation of <it>G. lucidum</it>.</p

SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis

Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, SIRT6 has been shown to regulate insulin secretion in response to glucose stimulation. However, what roles SIRT6 play in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of high palmitate. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis

Perspectives and challenges of applying the water-food-energy nexus approach to lake eutrophication modelling

Embargo until August 4, 2023The water-food-energy (WFE) nexus is about balancing competing interests to secure the sustainability of services provided by interconnected sectors. Ignoring the interconnections could cause serious consequences. For example, eutrophication caused by overemphasizing on food production maximization could threaten water security. Worldwide eutrophication intensification is one of the most important causes of the lake water quality deteriorations. Water quality models are usually important decision making tools for policy makers. This study attempts to explore the possibilities of applying the WFE nexus concept into water quality models. We propose the most significant challenge is lack of a common modelling framework to streamline connections between up- and downstream models. As the most important water quality issue, eutrophication modeling should increase its visibility in the United Nations Sustainable Develop Goals.acceptedVersio

Study on the composition optimization method for improving the fluidity of cast Ti2_2AlNb alloy and its mechanism

In this paper, the effects of Al, Nb main elements, Fe, Mo, W, Co, B, Si and their contents on the fluidity of Ti-22Al-25Nb alloy were investigated. The composition that was beneficial to improve the fluidity was screened through the thermodynamic software calculating thermophysical parameters affecting the fluidity of Ti$_2$AlNb alloy, the numerical simulation test of its fluidity and the verification test of the fluidity of optimized alloys. Finally, the improvement mechanism of the alloy fluidity was discussed. Results showed that the appropriate reduction of Nb element was better than Al element for the improvement of fluidity. The addition of trace Fe, B and Si elements were beneficial to the improvement of fluidity, the improvement effect of B element was best, while the addition of trace Mo, W, Co were not conducive to the improvement of fluidity. The cessation mechanism of Ti$_2$AlNb alloy is the cessation mechanism of the alloy with a wide crystallization temperature range. The composition which was most beneficial to improve the fluidity was Ti-22Al-24Nb-0.1B. The main reasons for the improvement of the fluidity had two sides: on the one hand, the reduction of 1at% Nb and the addition of 0.1at% B not only increased the superheat and crystallization latent heat of the alloy, but also reduced the melt viscosity and thermal conductivity, thus improving the fluidity. On the other hand, the TiB phase refined the grains, the fine grains prevented the dendrite from growing into developed dendrite networks, inhibited the adverse effect of the increase in the width of the solidification zone on the fluidity, reduced the flow resistance of the molten metal, and further improved the fluidity of the alloy.Comment: 23 pages, 14 figures, research pape

HPV E6 induces eIF4E transcription to promote the proliferation and migration of cervical cancer

AbstractIncreasing evidence has placed eukaryotic translation initiation factor 4E (eIF4E) at the hub of tumor development and progression. Several studies have reported that eIF4E is over-expressed in cervical cancer; however, the mechanism remains elusive. The results of this study further confirm over-expression of eIF4E in cervical cancer tumors and cell lines, and we have discovered that the transcription of eIF4E is induced by protein E6 of the human papillomavirus (HPV). Moreover, regulation of eIF4E by E6 significantly influences cell proliferation, the cell cycle, migration, and apoptosis. Therefore, eIF4E emerges as a key player in tumor development and progression and a potential target for CC treatment and prevention

Genome‑wide association analyses of leaf rust resistance in cultivated emmer wheat

Leaf rust, caused by Puccinia triticina (Pt), constantly threatens durum (Triticum turgidum ssp. durum) and bread wheat (Triticum aestivum) production worldwide. A Pt race BBBQD detected in California in 2009 poses a potential threat to durum production in North America because resistance source to this race is rare in durum germplasm. To find new resistance sources, we assessed a panel of 180 cultivated emmer wheat (Triticum turgidum ssp. dicoccum) accessions for seedling resistance to BBBQD and for adult resistance to a mixture of durum-specific races BBBQJ, CCMSS, and MCDSS in the field, and genotyped the panel using genotype-by-sequencing (GBS) and the 9 K SNP (Single Nucleotide Polymorphism) Infinium array. The results showed 24 and nine accessions consistently exhibited seedling and adult resistance, respectively, with two accessions providing resistance at both stages. We performed genome-wide association studies using 46,383 GBS and 4,331 9 K SNP markers and identified 15 quantitative trait loci (QTL) for seedling resistance located mostly on chromosomes 2B and 6B, and 11 QTL for adult resistance on 2B, 3B and 6A. Of these QTL, one might be associated with leaf rust resistance (Lr) gene Lr53, and two with the QTL previously reported in durum or hexaploid wheat. The remaining QTL are potentially associated with new Lr genes. Further linkage analysis and gene cloning are necessary to identify the causal genes underlying these QTL. The emmer accessions with high levels of resistance will be useful for developing mapping populations and adapted durum germplasm and varieties with resistance to the durum-specific races

Depdc5 deficiency exacerbates alcohol-induced hepatic steatosis via suppression of PPARα pathway

Alcohol-related liver disease (ALD), a condition caused by alcohol overconsumption, occurs in three stages of liver injury including steatosis, hepatitis, and cirrhosis. DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. In the current study, we found that aberrant activation of mTORC1 was likely attributed to the reduction of DEPDC5 in the livers of ethanol-fed mice or ALD patients. To further define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Hepatic Depdc5 ablation leads to mild hepatomegaly and liver injury and protects against diet-induced liver steatosis. In contrast, ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. Pharmacological intervention with Torin 1 suppressed mTORC1 activity and remarkably ameliorated ethanol-induced hepatic steatosis and inflammation in both control and Depdc5-LKO mice. The pathological effect of sustained mTORC1 activity in ALD may be attributed to the suppression of peroxisome proliferator activated receptor α (PPARα), the master regulator of fatty acid oxidation in hepatocytes, because fenofibrate (PPARα agonist) treatment reverses ethanol-induced liver steatosis and inflammation in Depdc5-LKO mice. These findings provide novel insights into the in vivo role of hepatic DEPDC5 in the development of ALD

Fasting plasma glucose is an independent predictor for severity of H1N1 pneumonia

<p>Abstract</p> <p>Background</p> <p>The pandemic influenza A (H1N1) virus emerged during 2009 and has spread worldwide. This virus can cause injuries to the lungs, liver, and heart. However, data regarding whether this influenza virus can affect pancreatic islets are limited. We investigated the effects of influenza A (H1N1) pneumonia on fasting plasma glucose (FPG) and islet function, and evaluated possible correlations between biochemical test results and the severity of H1N1 pneumonia.</p> <p>Methods</p> <p>We performed a retrospective analysis of patients either diagnosed with or suspected of having H1N1 pneumonia who were admitted to our hospital in 2009. Possible associations between FPG levels and H1N1 virus infection were assessed by logistic regression. Correlation and regression analyses were used to assess relationships between FPG and biochemical test results. Associations between admission days and significant data were assessed by single factor linear regression. To evaluate effects of H1N1 on pancreatic β-cell function, results of a resistance index (homa-IR), insulin function index (homa-β), and insulin sensitivity index (IAI) were compared between a H1N1 group and a non-H1N1 group by t-tests.</p> <p>Results</p> <p>FPG was significantly positively associated with H1N1 virus infection (OR = 1.377, 95%CI: 1.062-1.786; p = 0.016). FPG was significantly correlated with AST (r = 0.215; p = 0.039), LDH (r = 0.400; p = 0.000), BUN (r = 0.28; p = 0.005), and arterial Oxygen Saturation (SaO₂; r = -0.416; p = 0.000) in the H1N1 group. H1N1 patients who were hypoxemic (SaO₂<93%) had higher FPG levels than those who were not hypoxic (9.82 ± 4.14 vs. 6.64 ± 1.78; p < 0.05). FPG was negatively correlated with SaO₂in the H1N1 group with hypoxia (SaO₂<93; r = -0.497; p = 0.041). SaO₂levels in patients with high FPG levels (≥7 mmol/L) were significantly lower than those of H1N1 patients with low FPG levels (<5.6 mmol/L). There were no significant differences in homa-IR, homa-β, or IAI between the H1N1 and non-H1N1 groups after adjusting for age, sex, and BMI.</p> <p>Conclusions</p> <p>FPG on admission could be an independent predictor for the severity of H1N1 pneumonia. Elevated FPG induced by H1N1 pneumonia is not a result of direct damage to pancreatic β-cells, but arises from various factors' combinations caused by H1N1 virus infection.</p

The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice

BACKGROUND & AIMS: As a nicotinamide adenine dinucleotide-dependent deacetylase and a key epigenetic regulator, sirtuin 6 (SIRT6) has been implicated in the regulation of metabolism, DNA repair, and inflammation. However, the role of SIRT6 in alcohol-related liver disease (ALD) remains unclear. The aim of this study was to investigate the function and mechanism of SIRT6 in ALD pathogenesis. METHODS: We developed and characterized Sirt6 knockout (KO) and transgenic mouse models that were treated with either control or ethanol diet. Hepatic steatosis, inflammation, and oxidative stress were analyzed using biochemical and histological methods. Gene regulation was analyzed by luciferase reporter and chromatin immunoprecipitation assays. RESULTS: The Sirt6 KO mice developed severe liver injury characterized by a remarkable increase of oxidative stress and inflammation, whereas the Sirt6 transgenic mice were protected from ALD via normalization of hepatic lipids, inflammatory response, and oxidative stress. Our molecular analysis has identified a number of novel Sirt6-regulated genes that are involved in antioxidative stress, including metallothionein 1 and 2 (Mt1 and Mt2). Mt1/2 genes were downregulated in the livers of Sirt6 KO mice and patients with alcoholic hepatitis. Overexpression of Mt1 in the liver of Sirt6 KO mice improved ALD by reducing hepatic oxidative stress and inflammation. We also identified a critical link between SIRT6 and metal regulatory transcription factor 1 (Mtf1) via a physical interaction and functional coactivation. Mt1/2 promoter reporter assays showed a strong synergistic effect of SIRT6 on the transcriptional activity of Mtf1. CONCLUSIONS: Our data suggest that SIRT6 plays a critical protective role against ALD and it may serve as a potential therapeutic target for ALD. LAY SUMMARY: The liver, the primary organ for ethanol metabolism, can be damaged by the byproducts of ethanol metabolism, including reactive oxygen species. In this study, we have identified a key epigenetic regulator SIRT6 that plays a critical role in protecting the liver from oxidative stress-induced liver injury. Thus, our data suggest that SIRT6 may be a potential therapeutic target for alcohol-related liver disease