1,281 research outputs found
NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.
The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6 mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer and aging in mice. Surprisingly, a mutation that compromises NSMCE2-dependent SUMOylation does not have a detectable impact on murine lifespan. In contrast, NSMCE2 deletion in adult mice leads to pathologies resembling those found in patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable impact on DNA replication, NSMCE2-deficient cells also present the cellular hallmarks of BS such as increased recombination rates and an accumulation of micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases recombination rates and is synthetic lethal due to severe chromosome mis-segregation. Our work reveals that SUMO- and BLM-independent activities of NSMCE2 limit recombination and facilitate segregation; functions of the SMC5/6 complex that are necessary to prevent cancer and aging in mice.The authors want to thank Jordi Torres and Mark O'Driscoll for comments on the manuscript. Work in OF laboratory related to this project was supported by Fundacion Botin, by Banco Santander through its Santander Universities Global Division and by grants from MINECO (SAF2011-23753 and SAF2014-57791-REDC), Howard Hughes Medical Institute, and the European Research Council (ERC-617840). Work in JM laboratory was funded by a grant from MINECO (BFU2013-49153P).S
Role of educational level in the relationship between Body Mass Index (BMI) and health-related quality of life (HRQL) among rural Spanish women
BACKGROUND: The impact of obesity on health-related quality of life (HRQL) has been little explored in rural areas. The goal of this study is to ascertain the association between obesity and HRQL among Spanish women living in a rural area, and the influence of their educational level. METHODS: Cross-sectional study with personal interview of 1298 women (aged 18 to 60) randomly selected from the electoral rolls of 14 towns in Galicia, a region in the north-west of Spain. HRQL was assessed using the SF-36 questionnaire. The association between body mass index (BMI) and suboptimal scores in the different HRQL dimensions was summarised using odds ratios (ORs), obtained from multivariate logistic regression models. Separate analyses were conducted for women who had finished their education younger than 16 years old and women with secondary education to assess differences in the relationship between BMI and HRQL according to educational level. RESULTS: Among women with primary or lower education, obesity was associated with a higher prevalence of suboptimal values in the following dimensions: Physical functioning (OR: 1.97; 95%CI: 1.22-3.18); Role-physical (OR: 1.81; 95%CI: 1.04-3.14); General health (OR: 1.76; 95%CI: 1.10-2.81); and Role-emotional (OR: 2.52; 95%CI: 1.27-5.03). In women with higher education, physical functioning was the only dimension associated with obesity (OR: 2.02: 95%CI 0.83-4.97). CONCLUSION: The impact of obesity on women's HRQL is greater among those with a lower educational level. This group registered higher prevalence of obesity and poorer self-perceived health.This study was funded by the Instituto de Salud Carlos III (grant 001/05).S
Transgenic nematodes as biosensors for metal stress in soil pore water samples
Caenorhabditis elegans strains carrying stress-reporter green fluorescent protein transgenes were used to explore patterns of response to metals. Multiple stress pathways were induced at high doses by most metals tested, including members of the heat shock, oxidative stress, metallothionein (mtl) and xenobiotic response gene families. A mathematical model (to be published separately) of the gene regulatory circuit controlling mtl production predicted that chemically similar divalent metals (classic inducers) should show additive effects on mtl gene induction, whereas chemically dissimilar metals should show interference. These predictions were verified experimentally; thus cadmium and mercury showed additive effects, whereas ferric iron (a weak inducer) significantly reduced the effect of mercury. We applied a similar battery of tests to diluted samples of soil pore water extracted centrifugally after mixing 20% w/w ultrapure water with air-dried soil from an abandoned lead/zinc mine in the Murcia region of Spain. In addition, metal contents of both soil and soil pore water were determined by ICP-MS, and simplified mixtures of soluble metal salts were tested at equivalent final concentrations. The effects of extracted soil pore water (after tenfold dilution) were closely mimicked by mixtures of its principal component ions, and even by the single most prevalent contaminant (zinc) alone, though other metals modulated its effects both positively and negatively. In general, mixtures containing similar (divalent) metal ions exhibited mainly additive effects, whereas admixture of dissimilar (e.g. trivalent) ions often resulted in interference, reducing overall levels of stress-gene induction. These findings were also consistent with model predictions
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Measurement of charm production at central rapidity in proton-proton collisions at TeV
The -differential production cross sections of the prompt (B
feed-down subtracted) charmed mesons D, D, and D in the rapidity
range , and for transverse momentum GeV/, were
measured in proton-proton collisions at TeV with the ALICE
detector at the Large Hadron Collider. The analysis exploited the hadronic
decays DK, DK, DD, and their charge conjugates, and was performed on a
nb event sample collected in 2011 with a
minimum-bias trigger. The total charm production cross section at TeV and at 7 TeV was evaluated by extrapolating to the full phase space
the -differential production cross sections at TeV
and our previous measurements at TeV. The results were compared
to existing measurements and to perturbative-QCD calculations. The fraction of
cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/307
A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE
In this small note we are concerned with the solution of Forward-Backward
Stochastic Differential Equations (FBSDE) with drivers that grow quadratically
in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem
is a comparison result that allows comparing componentwise the signs of the
control processes of two different qgFBSDE. As a byproduct one obtains
conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio
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