Fibroblast phenotypes in different lung diseases

BACKGROUND: The “seed and soil” hypothesis emphasizes the importance of interactions between tumor cells and their microenvironment. CAFs (Cancer associated fibroblasts) are important components of the tumor microenvironment. They were widely involved in cancer cells growth and metastasis. Fibroblasts may also play a role in inflammatory disease. The phenotype conversion of fibroblasts in lung diseases has not been investigated previously. We hypothesized that fibroblasts phenotypes may vary among different types of lung disease. METHODS: The study included six types of lung tissues, ranging from normal lung to lung adenocarcinoma with lymphatic metastasis. Para-carcinoma tissues which were 2-cm-away from the tumor focus were also included in the analysis. The expression of target proteins including alpha-SMA (smooth muscle actin), FAP (fibroblast activation protein), vimentin, E-cadherin, and CK-19 (cytokeratin-19) were examined by immunohistochemistry. TGF-beta(transforming growth factor) and Twist were detected simultaneously in all samples. RESULTS: A progressive increase in the levels of alpha-SMA, vimentin and CK-19 was observed in correlation to the degree of malignancy from normal lung tissue to lung adenocarcinoma with lymphatic metastasis, whereas E-cadherin expression showed the opposite trend. TGF-beta and Twist were detected in cancer tissues and inflammatory pseudotumors. None of the proteins were detected in para-carcinoma tissues. CONCLUSIONS: Fibroblast phenotypes varied according to the type and degree of lung malignancy and fibroblasts phenotypic conversion occurs as a gradual process with specific spatiotemporal characteristics. Similar fibroblast phenotypes in inflammatory diseases and cancer tissues suggested a correlation between inflammation and cancer and implied a common mechanism underlying the formation of fibroblasts in inflammatory diseases and lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13019-014-0147-z) contains supplementary material, which is available to authorized users

Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq

Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)’s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated 14 013 757 sequence tags by H3K4me3 ChIP-Seq and obtained 17 322 358 paired end reads for mRNA, and 10 698 419 short reads for sRNA from the macaque brain. By integrating these data with genomic sequence features and extending and improving a state-of-the-art TSS prediction algorithm, we ab initio predicted and verified 17 933 of previously electronically annotated TSSs at 500-bp resolution. We also predicted approximately 10 000 novel TSSs. These provide an important rich resource for close examination of the species-specific transcript structures and transcription regulations in the Rhesus macaque genome. Our approach exemplifies a relatively inexpensive way to generate a reasonably reliable TSS map for a large genome. It may serve as a guiding example for similar genome annotation efforts targeted at other model organisms

(2R,3S)-2-Benzyl-3-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranos­yloxy)butanolide

The title compound, C25H30O12, which demonstrates a significant hepatoprotective effect, has comparable geometrical parameters to those of similar compounds. The absolute configuration of the title compound, viz. 2R,3S, was identified from the Flack parameter of 0.05 (17) and the Hooft parameter of 0.04 (6)

Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq

Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)’s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated 14 013 757 sequence tags by H3K4me3 ChIP-Seq and obtained 17 322 358 paired end reads for mRNA, and 10 698 419 short reads for sRNA from the macaque brain. By integrating these data with genomic sequence features and extending and improving a state-of-the-art TSS prediction algorithm, we ab initio predicted and verified 17 933 of previously electronically annotated TSSs at 500-bp resolution. We also predicted approximately 10 000 novel TSSs. These provide an important rich resource for close examination of the species-specific transcript structures and transcription regulations in the Rhesus macaque genome. Our approach exemplifies a relatively inexpensive way to generate a reasonably reliable TSS map for a large genome. It may serve as a guiding example for similar genome annotation efforts targeted at other model organisms

A System of Photocatalysis for NAD+ Regeneration of Product of (S)-1-Pheylethanol by Enzymic Catalysis

In this study, a system of photocatalysis for NAD+ regeneration of enzymatic catalysis was constructed. The optimal conditions for the coupling reaction of photocatalysis and biocatalysis were explored. Blue light was chosen for the efficient reaction and the optimal concentration of VB2 (vitamin B2, riboflavin) was determined. NAD+-dependent (R)-1-phenylethanol dehydrogenase was used in the reaction for transforming (R)-1-phenylethanol to acetophenone. The byproducts of the reaction were just H2O and O2 by means of catalase. The coupling reaction of catalysis and photocatalysis can be used for obtaining (S)-1-phenylethanol through racemization of 1-phenylethanol. Copyright © 2019 BCREC Group. All rights reserve

CRISPR/Cas9‐mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse

The X‐linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas‐mediated in situ genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies

Relationships Between Leaf Carbon and Macronutrients Across Woody Species and Forest Ecosystems Highlight How Carbon Is Allocated to Leaf Structural Function

Stoichiometry of leaf macronutrients can provide insight into the tradeoffs between leaf structural and metabolic investments. Structural carbon (C) in cell walls is contained in lignin and polysaccharides (cellulose, hemicellulose, and pectins). Much of leaf calcium (Ca) and a fraction of magnesium (Mg) were further bounded with cell wall pectins. The macronutrients phosphorus (P), potassium (K), and nitrogen (N) are primarily involved in cell metabolic functions. There is limited information on the functional interrelations among leaf C and macronutrients, and the functional dimensions characterizing the leaf structural and metabolic tradeoffs are not widely appreciated. We investigated the relationships between leaf C and macronutrient (N, P, K, Ca, Mg) concentrations in two widespread broad-leaved deciduous woody species Quercus wutaishanica (90 individuals) and Betula platyphylla (47 individuals), and further tested the generality of the observed relationships in 222 woody eudicots from 15 forest ecosystems. In a subsample of 20 broad-leaved species, we also analyzed the relationships among C, Ca, lignin, and pectin concentrations in leaf cell walls. We found a significant leaf C–Ca tradeoff operating within and across species and across ecosystems. This basic relationship was explained by variations in the share of cell wall lignin and pectin investments at the cell scale. The C–Ca tradeoffs were mainly driven by soil pH and mean annual temperature and precipitation, suggesting that leaves were more economically built with less C and more Ca as soil pH increased and at lower temperature and lower precipitation. However, we did not detect consistent patterns among C–N, and C–Mg at different levels of biological organization, suggesting substantial plasticity in N and Mg distribution among cell organelles and cell protoplast and cell wall. We observed two major axes of macronutrient differentiation: the cell-wall structural axis consisting of protein-free C and Ca and the protoplasm metabolic axis consisting of P and K, underscoring the decoupling of structural and metabolic elements inherently linked with cell wall from protoplasm investment strategies. We conclude that the tradeoffs between leaf C and Ca highlight how carbon is allocated to leaf structural function and suggest that this might indicate biogeochemical niche differentiation of species

Predicting Cherax quadricarinatus habitat distribution patterns through the usage of GIS and eDNA analysis in Terengganu, Malaysia

Cherax quadricarinatus (von Martens, 1868) is a highly invasive species that is resilient and highly adaptable to environmental conditions in new locations. Its presence brings along ecosystem imbalances and causes socioeconomic losses in invaded areas. Due to the destructive behaviour, it is important to conduct preliminary assessment methods and scientific studies especially on its behavioural and dispersal patterns. Thus, this study aims to determine the habitat distribution patterns of C. quadricarinatus based on the methods of GIS and environmental DNA (eDNA) analysis. The study was done at Felda Tenang, Terengganu, Malaysia. Based on the geographical features and climate conditions of the study area, we theorized that there are fewer and older C. quadricarinatus present at higher areas but more and younger C. quadricarinatus at lower areas. We found that 91.67% of the study area to be invaded, thus imploring the need for future mitigation plans to curb their dispersal into new areas. Future studies should also be done to determine the habitat distribution patterns of C. quadricarinatus in other areas

Life is beautiful: gay representation, moral panics, and South Korean television drama beyond Hallyu

Critical attention on Korean popular culture, particularly outside of Korea, has focused upon the Hallyu cultural phenomenon at the expense of sectors of the Korean creative industries that have sought to actively engage with their social and cultural environment and challenge the status quo. Politically charged, countercultural or just distinctive and/or original, non-Hallyu cultural artifacts have been and continue to be born out of a desire to be creative, to comment on or to create social change. This article focuses upon one such critically overlooked South Korean cultural artifact, the audacious and genuinely groundbreaking television drama "Life is Beautiful" (SBS 2010), which motivated an immense amount of critical and social reaction within Korea and yet has barely featured in English language analysis of Korean drama because it has not been classified as Hallyu. This is in spite of it being a finely produced and performed series and one written by the most prolific, longest serving and commercially successful of all Korean writers of Hallyu drama, Kim Soo-hyeon. In addition to its impressive production credentials, "Life is Beautiful" is also notable for being hugely controversial at the time of its broadcast due to its boldness in tackling the subject of Korean prejudice towards homosexuality