mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype

Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses

Allozyme differentiation of two populations of the genus Neoplecostomus Eigenmann & Eigenmann, 1888 (Teleostei, Loricariidae) from the upper Paraná River basin, Brazil

Allozyme electrophoresis was used to examine 12 enzymatic systems in two populations of the genus Neoplecostomus from the Paraná River basin. Samples of Neoplecostomus sp. 1 were collected in Paraitinguinha stream of the Tietê River basin, in the municipality of Salesópolis, São Paulo State, and those of Neoplecostomus sp. 2 from São Domingos stream of the Rio Grande River basin, in the municipality of Muzambinho, Minas Gerais State. The genetic variability of the two populations was estimated by Nei’s expected heterozygosity and was considered lower than average for populations of freshwater fish. The proportion of polymorphic loci was low (only 5.26% for the locus Idh). The low frequency of heterozygosity for both populations revealed a high fixation of alleles for each locus. Homozygote excess was observed in both populations. The values of Nei’s genetic identity and the presence of loci with different allele frequencies in both populations may imply that the two populations belong to different species. The genetic variability between populations was compared to other data for loricariids

Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization.

We have previously demonstrated that Stat3 regulates lysosomal-mediated programmed cell death (LM-PCD) during mouse mammary gland involution in vivo. However, the mechanism that controls the release of lysosomal cathepsins to initiate cell death in this context has not been elucidated. We show here that Stat3 regulates the formation of large lysosomal vacuoles that contain triglyceride. Furthermore, we demonstrate that milk fat globules (MFGs) are toxic to epithelial cells and that, when applied to purified lysosomes, the MFG hydrolysate oleic acid potently induces lysosomal leakiness. Additionally, uptake of secreted MFGs coated in butyrophilin 1A1 is diminished in Stat3-ablated mammary glands and loss of the phagocytosis bridging molecule MFG-E8 results in reduced leakage of cathepsins in vivo. We propose that Stat3 regulates LM-PCD in mouse mammary gland by switching cellular function from secretion to uptake of MFGs. Thereafter, perturbation of lysosomal vesicle membranes by high levels of free fatty acids results in controlled leakage of cathepsins culminating in cell death.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (T.J.S. and B. L-L.) and a Cancer Research UK Cambridge Cancer Centre PhD studentship (H.K.R.).This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3043.html

Violence witnessing, perpetrating and victimization in medellin, Colombia: a random population survey

<p>Abstract</p> <p>Background</p> <p>The burden of injury from violence and the costs attributable to violence are extremely high in Colombia. Despite a dramatic decline in homicides over the last ten years, homicide rate in Medellin, Colombia second largest city continues to rank among the highest of cities in Latin America. This study aims to estimate the prevalence and distribution of witnesses, victims and perpetrators of different forms of interpersonal violence in a representative sample of the general population in Medellin in 2007.</p> <p>Methods</p> <p>A face-to-face survey was carried out on a random selected, non-institutionalized population aged 12 to 60 years, with a response rate of 91% yielding 2,095 interview responses.</p> <p>Results</p> <p>We present the rates of prevalence for having been a witness, victim, or perpetrator for different forms of violence standardized using the WHO truncated population pyramid to allow for cross-national comparison. We also present data on verbal aggression, fraud and deception, yelling and heavy pranks, unarmed aggression during last year, and armed threat, other severe threats, robbery, armed physical aggression, and sexual aggression during the lifetime, by age, sex, marital and socioeconomic status, and education. Men reported the highest prevalence of being victims, perpetrators and witnesses in all forms of violence, except for robbery and sexual violence. The number of victims per perpetrator was positively correlated with the severity of the type of violence. The highest victimization proportions over the previous twelve months occurred among minors. Perpetrators are typically young unmarried males from lower socio-economic strata.</p> <p>Conclusions</p> <p>Due to very low proportion of victimization report to authorities, periodic surveys should be included in systems for epidemiological monitoring of violence, not only of victimization but also for perpetrators. Victimization information allows quantifying the magnitude of different forms of violence, while data on factors associated with aggression and perpetrators are necessary to estimate risk and protective factors that are essential to sound policies for violence prevention formulation.</p

Using Biotic Interaction Networks for Prediction in Biodiversity and Emerging Diseases

Networks offer a powerful tool for understanding and visualizing inter-species ecological and evolutionary interactions. Previously considered examples, such as trophic networks, are just representations of experimentally observed direct interactions. However, species interactions are so rich and complex it is not feasible to directly observe more than a small fraction. In this paper, using data mining techniques, we show how potential interactions can be inferred from geographic data, rather than by direct observation. An important application area for this methodology is that of emerging diseases, where, often, little is known about inter-species interactions, such as between vectors and reservoirs. Here, we show how using geographic data, biotic interaction networks that model statistical dependencies between species distributions can be used to infer and understand inter-species interactions. Furthermore, we show how such networks can be used to build prediction models. For example, for predicting the most important reservoirs of a disease, or the degree of disease risk associated with a geographical area. We illustrate the general methodology by considering an important emerging disease - Leishmaniasis. This data mining methodology allows for the use of geographic data to construct inferential biotic interaction networks which can then be used to build prediction models with a wide range of applications in ecology, biodiversity and emerging diseases

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration