Assessment of pathological response to therapy using lipid mass spectrometry imaging.

In many cancers, the establishment of a patient's future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the 'pathological response' to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care

Structure–activity relationships in hydroxy-2,3-diarylxanthone antioxidants. Fast kinetics spectroscopy as a tool to evaluate the potential for antioxidant activity in biological systems

A structure–activity relationship has been established for eight hydroxy-2,3-diarylxanthones (XH) bearing hydroxy groups on the two aryl rings. One-electron oxidation by superoxide radical-anions (ΣO2 -) and ΣTrp radicals as well as reaction with ΣCCl3O2 and ΣCHCl2O2 radicals demonstrates that two OH groups are required for efficient antioxidant reactivity in cetyltrimethylammonium bromide micelles. Hydroxy groups at the meta and para positions on either of the two phenyl rings confer enhanced reactivity, but XH bearing an OH at the para position of either phenyl ring is unreactive. While oxidation is favoured by OH in both meta and para positions of 2-aryl xanthone substituents, addition of a third and/or fourth OH enhances electron-donating capacity. In Cu2+-induced lipid peroxidation of human LDL, the lag period preceding the commencement of lipid peroxidation in the presence of XH bearing OH at meta and para positions on the 3-phenyl ring is extended to twice that observed with a comparable concentration of quercetin, a reference antioxidant. These antioxidants are also superior to quercetin in protecting human skin keratinocytes against tert-butylhydroperoxideinduced oxidative stress. While XH antioxidant activity in model biological systems is consistent with the structure–activity relationship, their response is also modulated by the localization of XH and by structural factors.This is Document No. NDLR-4864 from the Notre Dame Radiation Laboratory which is supported by the Office of Basic Energy Sciences at the United States Department of Energy. This work was supported by the Franco-Portuguese exchange programs GRICES-INSERM 2005-2006 and Pessoa 07958NF. P. Filipe thanks the “Sociedade Portugesa de Dermatologia e Venerologia” for a travel grant. Thanks are due to the University of Aveiro, “Fundação para a Ciência e a Tecnologia” and FEDER for funding the Organic Chemistry Research Unit. Clementina M. M. Santos thanks the Calouste Gulbenkian Foundation for the award of a short period research grant (proc 87872)

The dependence of alpha-tocopheroxyl radical reduction by hydroxy-2,3-diarylxanthones on structure and micro-environment

The flavonoid quercetin is known to reduce the α-tocopheroxyl radical (˙TocO) and reconstitute α-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH), exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study repair of ˙TocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ˙TocO, though repair depends strongly on the micro-environment. In cationic cetyltrimethylammonium bromide (CTAB) micelles, 30% of ˙TocO radicals are repaired at a rate constant of ∼7.4 × 106 M−1 s−1 by XH9 compared to 1.7 × 107 M−1 s−1 by ascorbate. Water-soluble Trolox (TrOH) radicals (˙TrO) are restored by XH9 in CTAB (rate constant ∼3 × 104 M−1 s−1) but not in neutral TX100 micelles where only 15% of ˙TocO are repaired (rate constant ∼4.5 × 105 M−1 s−1). In basic aqueous solutions ˙TrO is readily reduced by deprotonated XH9 species leading to ionized XH9 radical species (radical pKa ∼10). An equilibrium is observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [˙X9,H+/XH9] couple at pH 11, lower than the 250 mV for the [˙TrO,H+/TrOH] couple. A comparable value (100 mV) has been determined by cyclic voltammetry measurements

Low Energy Analyzing Powers in Pion-Proton Elastic Scattering

Analyzing powers of pion-proton elastic scattering have been measured at PSI with the Low Energy Pion Spectrometer LEPS as well as a novel polarized scintillator target. Angular distributions between 40 and 120 deg (c.m.) were taken at 45.2, 51.2, 57.2, 68.5, 77.2, and 87.2 MeV incoming pion kinetic energy for pi+ p scattering, and at 67.3 and 87.2 MeV for pi- p scattering. These new measurements constitute a substantial extension of the polarization data base at low energies. Predictions from phase shift analyses are compared with the experimental results, and deviations are observed at low energies.Comment: 15 pages, 4 figure

Idling Magnetic White Dwarf in the Synchronizing Polar BY Cam. The Noah-2 Project

Results of a multi-color study of the variability of the magnetic cataclysmic variable BY Cam are presented. The observations were obtained at the Korean 1.8m and Ukrainian 2.6m, 1.2m and 38-cm telescopes in 2003-2005, 56 observational runs cover 189 hours. The variations of the mean brightness in different colors are correlated with a slope dR/dV=1.29(4), where the number in brackets denotes the error estimates in the last digits. For individual runs, this slope is much smaller ranging from 0.98(3) to 1.24(3), with a mean value of 1.11(1). Near the maximum, the slope becomes smaller for some nights, indicating more blue spectral energy distribution, whereas the night-to-night variability has an infrared character. For the simultaneous UBVRI photometry, the slopes increase with wavelength from dU/dR=0.23(1) to dI/dR=1.18(1). Such wavelength dependence is opposite to that observed in non-magnetic cataclysmic variables, in an agreement to the model of cyclotron emission. The principal component analysis shows two (with a third at the limit of detection) components of variablitity with different spectral energy distribution, which possibly correspond to different regions of emission. The scalegram analysis shows a highest peak corresponding to the 200-min spin variability, its quarter and to the 30-min and 8-min QPOs. The amplitudes of all these components are dependent on wavelength and luminosity state. The light curves were fitted by a statistically optimal trigonometrical polynomial (up to 4-th order) to take into account a 4-hump structure. The dependences of these parameters on the phase of the beat period and on mean brightness are discussed. The amplitude of spin variations increases with an increasing wavelength and with decreasing brightnessComment: 30pages, 11figures, accepted in Cent.Eur.J.Phy

Strategies to augment non-immune system based defence mechanisms against gastrointestinal diseases in pigs

AbstractOur study addresses the first two weeks of the weaning period of piglets during which stressful physiological and environmental conditions experienced by the animals can promote the proliferation of pathogens in the digestive tract. The aim of the study was to identify new feeding strategies that result in boosting the gastrointestinal tract (GIT) microbiota of piglets and improve growth performance, reducing the negative impact of weaning. In order to identify a new synbiotic combination, 12 new putative probiotic strains of Bifidobacterium spp. and three non-digestible oligosaccharides [NDO] were screened in newly weaned piglets. The ability to increase the level of autochthonous bifidobacteria and improve growth performance were assessed. Bifidobacteria strains with a similar ability to develop in the hindgut showed a different effect on piglet performance depending on the dose in which they were provided. Our data support the idea that the presence of fructo-oligosaccharides would stimulate the occurrence of bifidobacteria in the caecum. It was shown that dietary intake of nitrate can generate salivary nitrite, which in turn is acidified in the stomach and could have antimicrobial activity against swallowed pathogens. The efficacy of the resulting synbiotic formula was improved by adding nitrate as antimicrobial. To enhance probiotic survival during gastric transit, a novel technology of microencapsulation was developed and applied to bacteria. The final synbiotic, containing the strain RA 18 of Bifidobacterium animalis subsp. lactis [1011cfu/day], the prebiotic Actilight® [4% of the diet], and nitrate [150mg KNO3/kg feed/day] was tested in organic weaned piglets reared under field conditions. Results show that the strain Ra 18 had a probiotic effect in organic weaned piglets, as it colonized and remained detectable in faecal samples until two weeks after addition. The use of our synbiotic formula improved weight gain, feed efficiency and health status of the weaned piglets

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic variation in the lion (Panthera leo)

Background Previous phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting. Results In this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations, as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail. Conclusions The results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management of ex situ populations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity.Environmental Biolog