Direct observation of an isopolyhalomethane O-H insertion reaction with water: Picosecond time-resolved resonance Raman (ps-TR 3) study of the isobromoform reaction with water to produce a CHBr 2OH product

The spectroscopic observation of an isopolyhalomethane O-H insertion reaction with water was obtained using picosecond time-resolved resonance Raman spectroscopy. It was observed that photolysis of low concentrations of bromoform in aqueous solution resulted in noticeable formation of HBr strong acid. It was shown by ab initio calculations that isobromoform can react with water to produce a CHBr 2(OH) O-H insertion reaction product and a HBr leaving group. The implications of the results for the phase dependent behavior of polyhalomethane photochemistry in the gas phase versus water solvated environments were discussed.published_or_final_versio

Comparison of the dehalogenation of polyhalomethanes and production of strong acids in aqueous and salt (NaCl) water environments: Ultraviolet photolysis of CH 2I 2

The ultraviolet photolysis of CH 2I 2 was studied in water and salt water solutions using photochemistry and picosecond time-resolved resonance Raman spectroscopy. Photolysis in both types of environments produces mainly CH 2(OH) 2 and HI products. However, photolysis of CH 2I 2 in salt water leads to the formation of different products/intermediates (CH 2ICl and Cl 2 -) not observed in the absence of salt in aqueous solutions. The amount of CH 2(OH) 2 and HI products appears to decrease after photolysis of CH 2I 2 in salt water compared to pure water. We briefly discuss possible implications of these results for photolysis of CH 2I 2 and other polyhalomethanes in sea water and other salt aqueous environments compared to nonsalt water solvated environments. © 2004 American Institute of Physics.published_or_final_versio

Unravelling the fast photocyclisation reaction mechanism(s) of 2-benzoylpyridine in aqueous solvent by time-resolved spectroscopy

Monday Poster Session: Time Resolved Raman (MP09) - Poster Number: 154A combined femtosecond transient absorption (fs-TA) and nanosecond time-resolved Resonance Raman (ns-TR3) spectroscopic investigation of the photoreaction of 2-benzoylpyridine in acetonitrile, neutral, basic and acidic aqueous solvents is reported. Some new species generated in the aqueous solvents observed for the first time and characterised by time-resolved vibrational spectroscopy in conjunction with results from DFT calculations. The detailed fast photocyclisation mechanism(s) of 2-benzoylpyridine in aqueous solvents after UV laser photolysis is obtained.postprintThe 22nd International Conference on Raman Spectroscopy (ICORS 2010), Boston, MA., 8-13 August 2010

Observation of a HI leaving group following ultraviolet photolysis of CH 2I 2 in water and an ab initio investigation of the O-H insertion/HI elimination reactions of the CH 2I-I isopolyhalomethane species with H 2O and 2H 2O

Ultraviolet/visible absorption and pH measurements that indicate significant production of H + and I - product following ultraviolet photolysis of CH 2I 2 in liquid water are presented. As such, the chemical reactivity of isodiiodomethane (CH 2I-I) with H 2O and 2H 2O is explored using ab initio calculations and compared to previous results. The CH 2I-I isopolyhalomethane species is found to react with water by an O-H insertion/HI elimination reaction mechanism that forms a HI leaving group.published_or_final_versio

A resonance Raman spectroscopic and CASSCF investigation of the Franck-Condon region structural dynamics and conical intersections of thiophene

Resonance Raman spectra were acquired for thiophene in cyclohexane solution with 239.5 and 266 nm excitation wavelengths that were in resonance with ∼240 nm first intense absorption band. The spectra indicate that the Franck-Condon region photodissociation dynamics have multidimensional character with motion mostly along the reaction coordinates of six totally symmetry modes and three nontotally symmetry modes. The appearance of the nontotally symmetry modes, the CS antisymmetry stretch +C-C=C bend mode v 21 (B 2) at 754 cm-1 and the H 7 C 3 C 4 H 8 twist 9 (A 2) at 906 cm -1, suggests the existence of two different types of vibronic-couplings or curve-crossings among the excited states in the Franck-Condon region. The electronic transition energies, the excited state structures, and the conical intersection points 1B 1/ 1A 1 and 1B 2 / 1A 1 between 2 1A 1 and 1 1B 2 or 1 1B 1 potential energy surfaces of thiophene were determined by using complete active space self-consistent field theory computations. These computational results were correlated with the Franck-Condon region structural dynamics of thiophene. The ring opening photodissociation reaction pathway through cleavage of one of the C-S bonds and via the conical intersection point 1B/ 1A 1 was revealed to be the predominant ultrafast reaction channel for thiophene in the lowest singlet excited state potential energy hypersurface, while the internal conversion pathway via the conical intersection point 1B 2 / 1A 1 was found to be the minor decay channel in the lowest singlet excited state potential energy hypersurface. © 2010 American Institute of Physics.published_or_final_versio

Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway

Objectives: Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour - stroma interaction. Methods: Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results: Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2 (+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 2003X microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions: TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.published_or_final_versio

Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Summary: Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size and structural immaturity of early-stage hiPSC-CMs. We developed a substrate nanopatterning approach to produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, and aligned myofibrils. We then isolated myofibrils from hiPSC-CMs and measured the tension and kinetics of activation and relaxation using a custom-built apparatus with fast solution switching. The contractile properties and ultrastructure of myofibrils more closely resembled human fetal myofibrils of similar gestational age than adult preparations. We also demonstrated the ability to study the development of contractile dysfunction of myofibrils from a patient-derived hiPSC-CM cell line carrying the familial cardiomyopathy MYH7 mutation (E848G). These methods can bring new insights to understanding cardiomyocyte maturation and developmental mechanical dysfunction of hiPSC-CMs with cardiomyopathic mutations. : In this article, Pioner and colleagues reported contractile properties of isolated myofibrils from hiPSC-CMs with highly mature morphology. This approach permits quantitative assessment of maturation and contractile properties of hiPSC-CMs and can be used to study the development of contractile dysfunction in genetically based cardiac diseases. The authors present a patient-derived cell line carrying a novel familial cardiomyopathy MYH7 mutation (E848G)

Practical Issues in Imputation-Based Association Mapping

Imputation-based association methods provide a powerful framework for testing untyped variants for association with phenotypes and for combining results from multiple studies that use different genotyping platforms. Here, we consider several issues that arise when applying these methods in practice, including: (i) factors affecting imputation accuracy, including choice of reference panel; (ii) the effects of imputation accuracy on power to detect associations; (iii) the relative merits of Bayesian and frequentist approaches to testing imputed genotypes for association with phenotype; and (iv) how to quickly and accurately compute Bayes factors for testing imputed SNPs. We find that imputation-based methods can be robust to imputation accuracy and can improve power to detect associations, even when average imputation accuracy is poor. We explain how ranking SNPs for association by a standard likelihood ratio test gives the same results as a Bayesian procedure that uses an unnatural prior assumption—specifically, that difficult-to-impute SNPs tend to have larger effects—and assess the power gained from using a Bayesian approach that does not make this assumption. Within the Bayesian framework, we find that good approximations to a full analysis can be achieved by simply replacing unknown genotypes with a point estimate—their posterior mean. This approximation considerably reduces computational expense compared with published sampling-based approaches, and the methods we present are practical on a genome-wide scale with very modest computational resources (e.g., a single desktop computer). The approximation also facilitates combining information across studies, using only summary data for each SNP. Methods discussed here are implemented in the software package BIMBAM, which is available from http://stephenslab.uchicago.edu/software.html

A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies

Genotype imputation methods are now being widely used in the analysis of genome-wide association studies. Most imputation analyses to date have used the HapMap as a reference dataset, but new reference panels (such as controls genotyped on multiple SNP chips and densely typed samples from the 1,000 Genomes Project) will soon allow a broader range of SNPs to be imputed with higher accuracy, thereby increasing power. We describe a genotype imputation method (IMPUTE version 2) that is designed to address the challenges presented by these new datasets. The main innovation of our approach is a flexible modelling framework that increases accuracy and combines information across multiple reference panels while remaining computationally feasible. We find that IMPUTE v2 attains higher accuracy than other methods when the HapMap provides the sole reference panel, but that the size of the panel constrains the improvements that can be made. We also find that imputation accuracy can be greatly enhanced by expanding the reference panel to contain thousands of chromosomes and that IMPUTE v2 outperforms other methods in this setting at both rare and common SNPs, with overall error rates that are 15%–20% lower than those of the closest competing method. One particularly challenging aspect of next-generation association studies is to integrate information across multiple reference panels genotyped on different sets of SNPs; we show that our approach to this problem has practical advantages over other suggested solutions

Breeding productivity, nest-site selection and conservation needs of the endemic Turkestan Ground-jay Podoces panderi

The Turkestan Ground-jay Podoces panderi, a corvid endemic to the deserts of Central Asia, is both understudied and under-protected. Using standardised nest-monitoring protocols and nest cameras, we estimated its breeding productivity for the first time as 0.586 fledglings per nesting attempt (inter-quartile range, IQR 0.413‒0.734), strongly constrained by a diverse set of predator species (accounting for 88% of failures), supporting the broad pattern that a wide spectrum of nest predators operate in arid environments. The probability of nest success for the 35 days from the start of incubation to fledging was low, 0.186 ± 0.06 se (N = 37), with no influence of season date, nest height or nest shrub species. However, pervasive shrub harvest severely limited availability of taller shrubs for nest-site selection, and thus our ability to detect any effect of height on nest survival. Mean clutch size was 4.8 ± 0.8 sd while hatching probability of an egg from a clutch surviving incubation was 0.800 ± 0.050 se and fledging probability was 0.824 ± 0.093 se for individual chicks in successful nests (i.e. that fledged one or more chicks). Two shrub genera, saxaul Haloxylon spp. and Calligonum spp., were used for nesting more frequently than expected (χ152 = 784.02, P < 0.001), highlighting their importance to breeding habitat suitability. This near-sole reliance on these taller shrub genera, both targeted for illegal cutting, indicates that habitat degradation may lead to increased predation and declines in productivity. Habitat conservation is, therefore, likely to be the most important management strategy for the species and other components of desert systems, as management of so diverse a set of nest predators would be both impractical and inappropriate