Association between CYP2E1 polymorphisms and risk of differentiated thyroid carcinoma

Differentiated thyroid carcinoma (DTC) results from complex interactions between genetic and environmental factors. Known etiological factors include exposure to ionizing radiations, previous thyroid diseases, and hormone factors. It has been speculated that dietary acrylamide (AA) formed in diverse foods following the Maillard's reaction could be a contributing factor for DTC in humans. Upon absorption, AA is biotransformed mainly by cytochrome P450 2E1 (CYP2E1) to glycidamide (GA). Considering that polymorphisms within CYP2E1 were found associated with endogenous levels of AA-Valine and GA-Valine hemoglobin adducts in humans, we raised the hypothesis that specific CYP2E1 genotypes could be associated with the risk of DTC. Analysis of four haplotype tagging SNPs (ht-SNPs) within the locus in a discovery case-control study (N = 350/350) indicated an association between rs2480258 and DTC risk. This ht-SNP resides within a linkage disequilibrium block spanning intron VIII and the 3'-untranslated region. Extended analysis in a large replication set (2429 controls and 767 cases) confirmed the association, with odds ratios for GA and AA genotypes of 1.24 (95 % confidence interval (CI) 1.03-1.48) and 1.56 (95 % CI, 1.06-2.30), respectively. Functionally, the minor allele was associated with low levels of CYP2E1 mRNA and protein expression as well as lower enzymatic activity in a series of 149 human liver samples. Our data support the hypothesis that inter-individual differences in CYP2E1 activity could modulate the risk of developing DTC suggesting that the exposure to specific xenobiotics, such as AA, could play a role in this process

Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide

Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test’s accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1,000 base pairs encompassing the minimal promoter region of the MSLN gene to identify expression quantitative trait loci (eQTL) that can affect SMRP. We assessed the association between four MSLN promoter variants and SMRP levels in a cohort of 72 MPM and 677 non-MPM subjects, and we carried out in vitro assays to investigate their functional role. Our results show that rs2235503 is an eQTL for MSLN associated with increased levels of SMRP in non-MPM subjects. Furthermore, we show that this polymorphic site affects the accuracy of SMRP, highlighting the importance of evaluating the individual’s genetic background and giving novel insights to refine SMRP specificity as a diagnostic biomarker

Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide.

Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test's accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1,000 base pairs encompassing the minimal promoter region of the MSLN gene to identify expression quantitative trait loci (eQTL) that can affect SMRP. We assessed the association between four MSLN promoter variants and SMRP levels in a cohort of 72 MPM and 677 non-MPM subjects, and we carried out in vitro assays to investigate their functional role. Our results show that rs2235503 is an eQTL for MSLN associated with increased levels of SMRP in non-MPM subjects. Furthermore, we show that this polymorphic site affects the accuracy of SMRP, highlighting the importance of evaluating the individual's genetic background and giving novel insights to refine SMRP specificity as a diagnostic biomarker

Jasmonic acid-induced volatiles of Brassica oleracea attract parasitoids: effects of time and dose, and comparison with induction by herbivores

Caterpillar feeding induces direct and indirect defences in brassicaceous plants. This study focused on the role of the octadecanoid pathway in induced indirect defence in Brassica oleracea. The effect of induction by exogenous application of jasmonic acid (JA) on the responses of Brussels sprouts plants and on host-location behaviour of associated parasitoid wasps was studied. Feeding by the biting–chewing herbivores Pieris rapae and Plutella xylostella resulted in significantly increased endogenous levels of JA, a central component in the octadecanoid signalling pathway that mediates induced plant defence. The levels of the intermediate 12-oxophyto-dienoic acid (OPDA) were significantly induced only after P. rapae feeding. Three species of parasitoid wasps, Cotesia glomerata, C. rubecula, and Diadegma semiclausum, differing in host range and host specificity, were tested for their behavioural responses to volatiles from herbivore-induced, JA-induced, and non-induced plants. All three species were attracted to volatiles from JA-induced plants compared with control plants; however, they preferred volatiles from herbivore-induced plants over volatiles from JA-induced plants. Attraction of C. glomerata depended on both timing and dose of JA application. JA-induced plants produced larger quantities of volatiles than herbivore-induced and control plants, indicating that not only quantity, but also quality of the volatile blend is important in the host-location behaviour of the wasps

Comparing induction at an early and late step in signal transduction mediating indirect defence in Brassica oleracea

The induction of plant defences involves a sequence of steps along a signal transduction pathway, varying in time course. In this study, the effects of induction of an early and a later step in plant defence signal transduction on plant volatile emission and parasitoid attraction are compared. Ion channel-forming peptides represent a class of inducers that induce an early step in signal transduction. Alamethicin (ALA) is an ion channel-forming peptide mixture from the fungus Trichoderma viride that can induce volatile emission and increase endogenous levels of jasmonic acid (JA) and salicylic acid in plants. ALA was used to induce an early step in the defence response in Brussels sprouts plants, Brassica oleracea var. gemmifera, and to study the effect on volatile emission and on the behavioural response of parasitoids to volatile emission. The parasitoid Cotesia glomerata was attracted to ALA-treated plants in a dose-dependent manner. JA, produced through the octadecanoid pathway, activates a later step in induced plant defence signal transduction, and JA also induces volatiles that are attractive to parasitoids. Treatment with ALA and JA resulted in distinct volatile blends, and both blends differed from the volatile blends emitted by control plants. Even though JA treatment of Brussels sprouts plants resulted in higher levels of volatile emission, ALA-treated plants were as attractive to C. glomerata as JA-treated plants. This demonstrates that on a molar basis, ALA is a 20 times more potent inducer of indirect plant defence than JA, although this hormone has more commonly been used as a chemical inducer of plant defence

Context-dependent effects of induced resistance under co-infection in a plant–pathogen interaction

The ability of a parasite strain to establish and grow on its host may be drastically altered by simultaneous infection by other parasite strains, and dynamics under multiple infection have been suggested to be a major force driving pathogen evolution. Here, I studied whether hosts’ induced defenses mediate dynamics of multiple infection of the fungal pathogen, Podosphaera plantaginis, infecting Plantago lanceolata. A laboratory study of sequential infections, where interaction between pathogen strains was prevented, showed that ability to establish remained unaffected, but prior infection elevates the host's resistance to the degree that subsequent infection development is significantly reduced. However, when inoculated plants and their healthy controls were planted back into their natural populations, hosts with prior infection became more heavily infected by the subsequent infections than the initially healthy plants. Hence, a controlled short-term laboratory study is a poor predictor of the host's ability to mediate multiple infection during the course of natural epidemics. These results have applied implications for priming where the plants’ defenses are elicited to provide protection against further attack, highlighting the importance of testing priming under natural conditions for relevant time scales

Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines

Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25). Met5A cells were used as non-malignant mesothelial cell line. PDGFRB-silencing caused a decrease in the proliferation rate, and a reduced colony formation capacity, as well as an increase of the share of cells in sub-G1 and in G2 phase, and increased apoptotic rate of MPM cell lines. Loss of migration ability was also observed. Similar, or even further enhanced, results were obtained with crenolanib. Imatinib showed the least effective activity on the phenotype. In conclusion, our study highlights PDGFRB as target with a clear role in MPM tumorigenesis and provided a rationale to explore further the efficacy of crenolanib in MPM patients, with promising results

The impacts of risk and competition on bank profitability in China

Several rounds of banking reforms in China have aimed to increase the competitive condition and further enhance stability in the Chinese banking sector, while the joint effects of competition and risk-taking behaviour on the profitability in the banking sector have not been studied well enough so far in the literature. The current study contributes to the empirical literature by testing the impacts of risk and competition on profitability in the Chinese banking industry (state-owned, joint-stock and city commercial banks) over the period 2003-2011 under a one-step Generalized Method of Moments (GMM) system estimator. The results do not show any robust finding with regards to the impacts of competition and risk on bank profitability, while it is found that Chinese bank profitability is affected by taxation, overhead cost, labour productivity and inflation. The study provides policy implications to the Chinese banking industry and different ownership types of Chinese commercial banks

Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil

The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant’s dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs