Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study.

Understanding potential provocations of haemorrhage is important in a range of clinical settings, and particularly for people with abnormal vasculature. Patients with hereditary haemorrhagic telangiectasia (HHT) can report haemorrhage from nasal telangiectasia in real time, and suggested dietary factors may precipitate nosebleeds. To examine further, nosebleed severity, dietary supplement use, and blood indices were evaluated in an unselected group of 50 HHT patients recruited from a specialist UK service. Using the validated Epistaxis Severity Score, nosebleed severity ranged from 0 to 9.1 out of 10 (median 3.9). Using a Food Frequency Questionnaire, 24/50 (48%) participants reported use of dietary supplements in the previous year. A third (18/50; 36%) had used self prescribed, non-iron containing dietary supplements, ingesting between 1 and 3 different supplements each day. Eight (16%) used fish oils. Despite having more severe epistaxis (p = 0.012), the 12 iron supplement users had higher serum iron concentrations, and were able to maintain their red blood cell indices. In contrast, there was no evident benefit for the participants using non iron supplements. Furthermore, platelet counts and serum fibrinogen tended to be lower in fish oil/supplement users, and one fish oil user demonstrated reduced in vitro platelet aggregation. In conclusion, in this small study, a third of HHT patients used non-iron dietary supplements, and one in six ingested fish oils, unaware of their known anti-platelet activity. The scale of use, and potential of these "natural health supplements" to exacerbate nosebleeds has not been appreciated previously in HHT

Temperature and Pressure Dependent Kinetics of QOOH Decomposition and Reaction with O2: Experimental and Theoretical Investigations of QOOH Radicals Derived from Cl + (CH3)3COOH

QOOH radicals are key species in autoignition, produced by internal isomerisations of RO2 radicals, and are central to chain branching reactions in low temperature combustion. The kinetics of QOOH radical decomposition and reaction with O2 have been determined as a function of temperature and pressure, using observations of OH radical production and decay following H-atom abstraction from tertiary-butyl hydroperoxide ((CH3)3COOH) by Cl atoms to produce QOOH (.CH2(CH3)2COOH) radicals. The kinetics of QOOH decomposition have been investigated as a function of temperature (251 to 298 K), and pressure (10 to 350 Torr), in helium and nitrogen bath gases, and those of the reaction between QOOH and O2 have been investigated as a function of temperature (251 to 304 K), and pressure (10 to 100 Torr) in He and N2. Decomposition of the QOOH radicals was observed to display temperature and pressure dependence, with a barrier height for decomposition of (44.7 ± 4.0) kJ mol-1 determined by master equation fitting to the experimental data. The rate coefficient for the reaction between QOOH and O2 was determined to be (5.6 ± 1.7) × 10-13 cm3 s-1 at 298 K, with no significant dependence on pressure, and can be described by the Arrhenius parameters A = (7.3 ± 6.8) × 10-14 cm3 s-1 and Ea = -(5.4 ± 2.1) kJ mol-1 in the temperature range 251 to 304 K. This work represents the first measurements of any QOOH radical kinetics as a function of temperature and pressure

RNA-Seq analysis identifies key genes associated with haustorial development in the root hemiparasite Santalum album

Santalum album (sandalwood) is one of the economically important plant species in the Santalaceae for its production of highly valued perfume oils. Sandalwood is also a hemiparasitic tree that obtains some of its water and simple nutrients by tapping into other plants through haustoria which are highly specialized organs in parasitic angiosperms. However, an understanding of the molecular mechanisms involved in haustorium development is limited. In this study, RNA sequencing (RNA-seq) analyses were performed to identify changes in gene expression and metabolic pathways associated with the development of the S. album haustorium. A total of 56,011 non-redundant contigs with a mean contig size of 618 bp were obtained by de novo assembly of the transcriptome of haustoria and non-haustorial seedling roots. A substantial number of the identified differentially expressed genes were involved in cell wall metabolism and protein metabolism, as well as mitochondrial electron transport functions. Phytohormone-mediated regulation might play an important role during haustorial development. Especially, auxin signaling is likely to be essential for haustorial initiation, and genes related to cytokinin and gibberellin biosynthesis and metabolism are involved in haustorial development. Our results suggest that genes encoding nodulin-like proteins may be important for haustorial morphogenesis in S. album. The obtained sequence data will become a rich resource for future research in this interesting species. This information improves our understanding of haustorium development in root hemiparasitic species and will allow further exploration of the detailed molecular mechanisms underlying plant parasitism

Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences.Comment: Table 9 in this article includes corrections for errata in the Table 9 published in 10.1371/journal.pone.0017244. Supporting information is attached at the end of the article, and a computer-readable dataset of the ML estimates of selective constraints is available from 10.1371/journal.pone.001724

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ. Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score. Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London Clinic

Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup.

Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup

Kinetics of the Reactions of Hydroxyl Radicals with Furan and its Alkylated Derivatives 2-Methyl Furan and 2,5-Dimethyl Furan

Furans are promising second generation biofuels with comparable energy densities to conventional fossil fuels. Combustion of furans is initiated and controlled to a large part by reactions with OH radicals, the kinetics of which are critical to understand the processes occurring under conditions relevant to low-temperature combustion. The reactions of OH radicals with furan (OH + F, R1), 2-methyl furan (OH + 2-MF, R2), and 2,5-dimethyl furan (OH + 2,5-DMF, R3) have been studied in this work over the temperature range 294 to 668 K at pressures between 5 mbar and 10 bar using laser flash photolysis coupled with laser-induced fluorescence (LIF) spectroscopy to generate and monitor OH radicals under pseudo-first-order conditions. Measurements at p ≤ 200 mbar were made in N2, using H2O2 or (CH3)3COOH radical precursors, while those at p ≥ 2 bar were made in He, using HNO3 as the radical precursor. The kinetics of the reactions R1-R3 were observed to display a negative dependence on temperature over the range investigated, indicating the dominance of addition reactions under such conditions, with no significant dependence on pressure observed. Master equation calculations are in good agreement with the observed kinetics, and a combined parameterisation of addition channels and abstraction channels for R1-R3 is provided on the basis of this work and previous shock tube measurements at higher temperatures. This work significantly extends the temperature range previously investigated for R1 and represents the first temperature-dependent measurements of R2 and R3 at temperatures relevant for atmospheric chemistry and low-temperature combustion

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON