Immune Regulatory Function of Cancer-Associated Fibroblasts in Non-small Cell Lung Cancer

Background Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors

Environmental Health Studies in the Korean National Industrial Complexes (EHSNIC): Focus-Group Interviews

This study investigated the social outcomes of the Environmental Health Studies of National Industrial Complex (EHSNIC), which have been conducted by the National Institute of Environmental Research (NIER) in eight National Industrial Complex Areas (NICAs) since 2003. Eighteen sessions of focus-group interviews with 85 people were conducted from October 2016 to January 2017. Interviewees were stakeholders from eight NICAs and included resident representatives, environmental nongovernment organizations, local government officials, and environmental health and safety officers from companies. Interview results were divided into six categories: EHSNIC awareness, EHSNIC outcomes, EHSNIC limitations, EHSNIC continuation, EHSNIC improvement directions, and EHSNIC results use. They were then further indexed into 23 divisions. EHSNIC awareness varied across stakeholders. A major EHSNIC outcome is that a continued result database was established, which was used as a reference for environmental improvements. EHSNIC limitations included no proper healthcare actions taken during the EHSNIC study period, a lack of EHSNIC results disclosure, a failure to reflect local specificity, and a lack of validity in the results. Regarding EHSNIC continuation, all stakeholders said EHSNIC should be conducted continuously. EHSNIC improvement directions included conducting studies tailored to each NICA, identifying correlations between pollutant exposure and disease, increasing the sample size, and performing repeated studies. Regarding EHSNIC results use, respondents wanted to use the results as a reference to relocate residents, ensure distance between NICAs and residential areas, provide healthcare support, develop local government policies, and implement firms’ environmental controls. Since EHSNIC aims to identify the health effects of NICAs on residents and take appropriate actions, it should be continued in the future. Even during the study period, it is important to take steps to preventively protect residents’ health. EHSNIC also needs to reflect each NICA’s characteristics and conduct reliable research based on stakeholder participation and communication

A Pectate Lyase-Coding Gene Abundantly Expressed during Early Stages of Infection Is Required for Full Virulence in Alternaria brassicicola

We thank Fred Brooks for insightful discussions on the roles of PL1332 on pathogenesis mechanisms employed by A. brassicicola.Alternaria brassicicola causes black spot disease of Brassica species. The functional importance of pectin digestion enzymes and unidentified phytotoxins in fungal pathogenesis has been suspected but not verified in A. brassicicola. The fungal transcription factor AbPf2 is essential for pathogenicity and induces 106 genes during early pathogenesis, including the pectate lyase-coding gene, PL1332. The aim of this study was to test the importance and roles of PL1332 in pathogenesis. We generated deletion strains of the PL1332 gene, produced heterologous PL1332 proteins, and evaluated their association with virulence. Deletion strains of the PL1332 gene were approximately 30% less virulent than wild-type A. brassicicola, without showing differences in colony expansion on solid media and mycelial growth in nutrient-rich liquid media or minimal media with pectins as a major carbon source. Heterologous PL1332 expressed as fusion proteins digested polygalacturons in vitro. When the fusion proteins were injected into the apoplast between leaf veins of host plants the tissues turned dark brown and soft, resembling necrotic leaf tissue. The PL1332 gene was the first example identified as a general toxin-coding gene and virulence factor among the 106 genes regulated by the transcription factor, AbPf2. It was also the first gene to have its functions investigated among the 19 pectate lyase genes and several hundred putative cell-wall degrading enzymes in A. brassicicola. These results further support the importance of the AbPf2 gene as a key pathogenesis regulator and possible target for agrochemical development.Yeshttp://www.plosone.org/static/editorial#pee

Generation and analysis of large-scale expressed sequence tags (ESTs) from a full-length enriched cDNA library of porcine backfat tissue

BACKGROUND: Genome research in farm animals will expand our basic knowledge of the genetic control of complex traits, and the results will be applied in the livestock industry to improve meat quality and productivity, as well as to reduce the incidence of disease. A combination of quantitative trait locus mapping and microarray analysis is a useful approach to reduce the overall effort needed to identify genes associated with quantitative traits of interest. RESULTS: We constructed a full-length enriched cDNA library from porcine backfat tissue. The estimated average size of the cDNA inserts was 1.7 kb, and the cDNA fullness ratio was 70%. In total, we deposited 16,110 high-quality sequences in the dbEST division of GenBank (accession numbers: DT319652-DT335761). For all the expressed sequence tags (ESTs), approximately 10.9 Mb of porcine sequence were generated with an average length of 674 bp per EST (range: 200–952 bp). Clustering and assembly of these ESTs resulted in a total of 5,008 unique sequences with 1,776 contigs (35.46%) and 3,232 singleton (65.54%) ESTs. From a total of 5,008 unique sequences, 3,154 (62.98%) were similar to other sequences, and 1,854 (37.02%) were identified as having no hit or low identity (<95%) and 60% coverage in The Institute for Genomic Research (TIGR) gene index of Sus scrofa. Gene ontology (GO) annotation of unique sequences showed that approximately 31.7, 32.3, and 30.8% were assigned molecular function, biological process, and cellular component GO terms, respectively. A total of 1,854 putative novel transcripts resulted after comparison and filtering with the TIGR SsGI; these included a large percentage of singletons (80.64%) and a small proportion of contigs (13.36%). CONCLUSION: The sequence data generated in this study will provide valuable information for studying expression profiles using EST-based microarrays and assist in the condensation of current pig TCs into clusters representing longer stretches of cDNA sequences. The isolation of genes expressed in backfat tissue is the first step toward a better understanding of backfat tissue on a genomic basis

Genome-wide comparative analysis of the Brassica rapa gene space reveals genome shrinkage and differential loss of duplicated genes after whole genome triplication

Euchromatic regions of the Brassica rapa genome were sequenced and mapped onto the corresponding regions in the Arabidopsis thaliana genome

Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012–2014

AbstractBackgroundThis study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3–18 year-old Korean children and adolescents.Materials and methodsWe used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012–2014 and identified 2388 children and adolescents aged 3–18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father’s education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times.ResultsThe median levels of blood lead and mercury, as well as urinary cadmium were 1.23μg/dL, 1.80μg/L, and 0.40μg/L (95% CIs, 1.21–1.25, 1.77–1.83, and 0.39–0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010.ConclusionSociodemographic factors, including age, sex, and father’s education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population