Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Density Variations in the NW Star Stream of M31

The Pan Andromeda Archeological Survey (PAndAS) CFHT Megaprime survey of the M31-M33 system has found a star stream which extends about 120 kpc NW from the center of M31. The great length of the stream, and the likelihood that it does not significantly intersect the disk of M31, means that it is unusually well suited for a measurement of stream gaps and clumps along its length as a test for the predicted thousands of dark matter sub-halos. The main result of this paper is that the density of the stream varies between zero and about three times the mean along its length on scales of 2 to 20 kpc. The probability that the variations are random fluctuations in the star density is less than 10^-5. As a control sample we search for density variations at precisely the same location in stars with metallicity higher than the stream, [Fe/H]=[0, -0.5] and find no variations above the expected shot noise. The lumpiness of the stream is not compatible with a low mass star stream in a smooth galactic potential, nor is it readily compatible with the disturbance caused by the visible M31 satellite galaxies. The stream's density variations appear to be consistent with the effects of a large population of steep mass function dark matter sub-halos, such as found in LCDM simulations, acting on an approximately 10Gyr old star stream. The effects of a single set of halo substructure realizations are shown for illustration, reserving a statistical comparison for another study.Comment: ApJ revised version submitte

PAndAS' progeny: extending the M31 dwarf galaxy cabal

We present the discovery of five new dwarf galaxies, Andromeda XXIII-XXVII, located in the outer halo of M31. These galaxies were found in the second year of data from the Pan-Andromeda Archaeological Survey (PAndAS) of the M31/M33 subgroup. This survey now provides an almost complete panoramic view of the M31 halo out to an average projected radius of ~150 kpc. The metal-poor stellar density map for this whole region serves, not only as an illustration of the discovery space for satellite galaxies, but also gives a birds-eye view of the ongoing assembly process of an L* disk galaxy. Four of the new dwarfs appear as well-defined spatial over-densities of stars lying on the expected locus of metal-poor red giant branch stars at the distance of M31. The fifth over-density, And XXVII, is embedded in an extensive stream of such stars and is possibly the remnant of a strong tidal disruption event. All five satellites have metallicities and luminosities typical of dwarf spheroidal galaxies and continue the trend whereby the brighter dwarf spheroidal satellites of M31 generally have much larger half-light radii than their Milky Way counterparts. With an extended sample of M31 satellite galaxies we also revisit the spatial distribution of this population and find that, within the current limits of the PAndAS survey, the surface density of satellites is essentially constant out to 150 kpc. This corresponds to a radial density distribution of satellites varying as 1/r, a result seemingly in conflict with the predictions of cosmological simulations. (Abridged)Comment: Accepted for publication in The Astrophysical Journal, 16 pages, 8 figure

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Arginase Activities and Global Arginine Bioavailability in Wild-Type and ApoE-Deficient Mice: Responses to High Fat and High Cholesterol Diets

Abstract Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE 2/2 and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE 2/2 mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE 2/2 mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease

The remnants of galaxy formation from a panoramic survey of the region around M31

In hierarchical cosmological models, galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach $10 - 100$ times the radius of the central disk. The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history, but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than $M_V < -6$ await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.Comment: Published in Nature. Supplementary movie available at https://www.astrosci.ca/users/alan/PANDAS/Latest%20news%3A%20movie%20of%20orbit.htm

Coal Use, Stove Improvement, and Adult Pneumonia Mortality in Xuanwei, China: A Retrospective Cohort Study

Background: In Xuanwei County, China, unvented indoor coal burning is strongly associated with increased risk of lung cancer and chronic obstructive pulmonary disease. However, the impact of coal burning and stove improvement on risk of pneumonia is not clear. Methods: We conducted a retrospective cohort study among all farmers born 1917 through 1951 and living in Xuanwei as of 1 January 1976. The analysis included a total of 42,422 cohort members. Follow-up identified all deaths in the cohort from 1976 through 1996. Ages at entry into and at exit from follow-up ranged from 24 to 59 years and from 25 to 80 years, respectively. The record search detected 225 deaths from pneumonia, and 32,332 (76%) were alive as of 31 December 1996. We constructed multivariable Cox models (time variable = age) to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Use of coal, especially smokeless coal, was positively associated with pneumonia mortality. Annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality. Stove improvement was associated with a 50% reduction in pneumonia deaths (smoky coal users: HR, 0.521; 95% CI, 0.340-0.798; smokeless coal users: HR, 0.449; 95% CI, 0.215-0.937). Conclusions: Our analysis is the first to suggest that indoor air pollution from unvented coal burning is an important risk factor for pneumonia death in adults and that improving ventilation by installing a chimney is an effective measure to decrease it.published_or_final_versio

Moray eels are more common on coral reefs subject to higher human pressure in the greater Caribbean

Proximity and size of the nearest market (‘market gravity’) have been shown to have strong negative effects on coral reef fish communities that can be mitigated by the establishment of closed areas. However, moray eels are functionally unique predators that are generally not subject to targeted fishing and should therefore not directly be affected by these factors. We used baited remote underwater video systems to investigate associations between morays and anthropogenic, habitat, and ecological factors in the Caribbean region. Market gravity had a positive effect on morays, while the opposite pattern was observed in a predator group subject to exploitation (sharks). Environmental DNA analyses corroborated the positive effect of market gravity on morays. We hypothesize that the observed pattern could be the indirect result of the depletion of moray competitors and predators near humans. Environmental science; ecology; biological sciences; zoology; animals; etholog

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The g-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergen