Deoxygenative perfluoroalkylthiolation of carboxylic acids with benzothiazolium reagents

Deoxygenative perfluoroalkylthiolation reactions of readily available carboxylic acid derivatives have been developed using a series of 2-(perfluoroalkylthio)benzothiazolium (BT-SRF) reagents as convenient sources of perfluoroalkylthiolate anions. This method avoids pre-activation of the substrates and delivers rarely reported perfluoroalkyl thioesters featuring SRF groups up to C6F13. A survey of carboxylic acid substrates with the pentafluoroethylthiolating reagent BT-SC2F5 also revealed the generality of the approach as a method for accessing underexplored fluorinated compounds

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts

Biological maturation, relative age and self-regulation in male professional academy soccer players: A test of the underdog hypothesis

ObjectivesThe main and interactive effects of biological maturity status and relative age upon self-regulation in male academy soccer players are considered. Consistent with the ‘underdog’ hypothesis, whereby relatively younger players may benefit from competitive play with older peers, it was predicted later maturing and/or relatively younger players would report more adaptive self-regulation.DesignCross-sectional study.MethodPlayers (n = 171, aged 11–16 years) from four English professional soccer academies completed the modified Soccer Self-Regulation Scale. Date of birth, height, weight and parental height were obtained. Relative age was based on birth quarter for the selection year. Maturity status was based upon percentage of predicted adult height attained.ResultsLinear regression models showed later maturation was inversely associated with adaptive self-regulation, while relative age was unrelated to self-regulation.ConclusionsIn partial support of the underdog hypothesis, later maturing players appear to possess a psychological advantage

Elevated Plasma IL-6 Associates with Increased Risk of Advanced Fibrosis and Cholangiocarcinoma in Individuals Infected by Opisthorchis viverrini

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection

Liver Fluke Induces Cholangiocarcinoma

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma

Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini

The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts

Biological maturation, relative age and self-regulation in male professional academy soccer players: A test of the underdog hypothesis

ObjectivesThe main and interactive effects of biological maturity status and relative age upon self-regulation in male academy soccer players are considered. Consistent with the ‘underdog’ hypothesis, whereby relatively younger players may benefit from competitive play with older peers, it was predicted later maturing and/or relatively younger players would report more adaptive self-regulation.DesignCross-sectional study.MethodPlayers (n = 171, aged 11–16 years) from four English professional soccer academies completed the modified Soccer Self-Regulation Scale. Date of birth, height, weight and parental height were obtained. Relative age was based on birth quarter for the selection year. Maturity status was based upon percentage of predicted adult height attained.ResultsLinear regression models showed later maturation was inversely associated with adaptive self-regulation, while relative age was unrelated to self-regulation.ConclusionsIn partial support of the underdog hypothesis, later maturing players appear to possess a psychological advantage

Evaluation of liver fluke recombinant cathepsin B-1 protease as a serodiagnostic antigen for human opisthorchiasis

A cathepsin B-like cysteine protease belonging to family C1 is abundantly expressed in the transcriptome and proteome of the carcinogenic liver fluke of humans, Opisthorchis viverrini. This enzyme is present in excretory/secretory (ES) products released by parasites cultured in vitro. This study evaluated the performance of recombinant O. viverrini cathepsin B1 (rOv-CB-1) as an antigen for immunodiagnosis of opisthorchiasis. The full length Ov-CB-1 cDNA was cloned and recombinant protein was produced in catalytically active form in Pichia pastoris. The recombinant Ov-CB-1 (rOv-CB-1) was affinity purified via nickel-NTA chromatography and tested in enzyme-linked immunosorbent assays (ELISA) with human sera from an opisthorchiasis endemic area. Sera from egg-positive O. viverrini infections produced a strong IgG antibody response to rOv-CB-1 both in ELISA and immunoblot analysis. The sensitivity and specificity of the ELISA test was 67% and 81%, respectively. These findings support the feasibility of using recombinant Ov-CB-1 in ELISA for the serodiagnosis of human opisthorchiasis