489 research outputs found
Ageing in the critical contact process: a Monte Carlo study
The long-time dynamics of the critical contact process which is brought
suddenly out of an uncorrelated initial state undergoes ageing in close analogy
with quenched magnetic systems. In particular, we show through Monte Carlo
simulations in one and two dimensions and through mean-field theory that
time-translation invariance is broken and that dynamical scaling holds. We find
that the autocorrelation and autoresponse exponents lambda_{Gamma} and lambda_R
are equal but, in contrast to systems relaxing to equilibrium, the ageing
exponents a and b are distinct. A recent proposal to define a non-equilibrium
temperature through the short-time limit of the fluctuation-dissipation ratio
is therefore not applicable.Comment: 18 pages, 7 figures, Latex2e with IOP macros; final for
Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARKAGE Study
Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players. In fact, TETs catalyze the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), driving the DNA demethylation process based on thymine DNA glycosylase (TDG)-mediated DNA repair pathway. The present paper reports the expression of DNA hydroxymethylation components, the levels of 5hmC and of its derivatives in peripheral blood mononuclear cells of age-stratified donors recruited in several European countries in the context of the EU Project ‘MARK-AGE’. The results provide evidence for an age-related decline of TET1, TET3 and TDG gene expression along with a decrease of 5hmC and an accumulation of 5caC. These associations were independent of confounding variables, including recruitment center, gender and leukocyte composition. The observed impairment of 5hmC-mediated DNA demethylation pathway in blood cells may lead to aberrant transcriptional programs in the elderly
Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study
Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated
Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling
Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO-), or using the ONOO- degradation catalyst FeTMPyP cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 mu M), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014, PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012]; FCT, Portugal [SERH/BPD/78901/2011, SERH/BD/38127/2007, SFRH/BD/77903/2011, SFRH/BD/79308/2011]info:eu-repo/semantics/publishedVersio
Defining needs and goals of post-ICU care for trauma patients: preliminary study
Background: The aim of this study was to assess the long-term physical and psychological disabilities and their economic impact in severe trauma survivors.
Methods: adult patients with injury severity score >15 and Abbreviated Injury Scale ≤3 admitted to the ICU of
a level 1 trauma centre in the lazio region and discharged alive from hospital underwent a structured interview 12-24 months after the event. self-reported somatic symptoms, autonomy, anxiety and depression were evaluated using a Likert-type Scale, Barthel Index and Hospital Anxiety and Depression Score (HADS), respectively. Patients’ working and economic status were also investigated.
Results: A total of 32/58 patients matching the inclusion criteria were included in the final analysis. eighteen patients (56%) reported at least a partial restriction in daily activities. Most common symptoms included muscle or joint pain, fatigue, and headache. All patients were receiving rehabilitation 1-2 years after the event. Fifty-eight percent of the patients spent more than €3600/year from their family budget for rehabilitation and medical care, however only 25% were receiving financial support from regional social services and 44% were unemployed at the time of the interview. thirty patients (94%) had HADS Depression Score≥11.
Conclusion: Survivors of severe trauma in our cohort had limited autonomy and need long-term rehabilitation. Most of them rely on private healthcare services with a significant financial impact on their family budget. Almost all patients had moderate to severe depression. Future post-ICU counseling services should facilitate access to rehabilitation and psychological support for these patient
Observation of CR Anisotropy with ARGO-YBJ
The measurement of the anisotropies of cosmic ray arrival direction provides
important informations on the propagation mechanisms and on the identification
of their sources. In this paper we report the observation of anisotropy regions
at different angular scales. In particular, the observation of a possible
anisotropy on scales between 10 and 30
suggests the presence of unknown features of the magnetic fields the charged
cosmic rays propagate through, as well as potential contributions of nearby
sources to the total flux of cosmic rays. Evidence of new weaker few-degree
excesses throughout the sky region R.A. is
reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich,
German
Quantum numbers of the state and orbital angular momentum in its decay
Angular correlations in decays, with , and , are used to measure
orbital angular momentum contributions and to determine the value of
the meson. The data correspond to an integrated luminosity of 3.0
fb of proton-proton collisions collected with the LHCb detector. This
determination, for the first time performed without assuming a value for the
orbital angular momentum, confirms the quantum numbers to be .
The is found to decay predominantly through S wave and an upper limit
of at C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure
Patient and physician perspectives on biological treatment in severe asthma: a Severe Asthma Network Italy survey
: Patients with severe asthma perceive beneficial effects of biologics and good self-reported adherence to treatment, even when self-administered at home https://bit.ly/48vP70w
The Atacama Cosmology Telescope: Microwave Intensity and Polarization Maps of the Galactic Center
We present arcminute-resolution intensity and polarization maps of the
Galactic center made with the Atacama Cosmology Telescope (ACT). The maps cover
a 32 deg field at 98, 150, and 224 GHz with ,
. We combine these data with Planck observations at
similar frequencies to create coadded maps with increased sensitivity at large
angular scales. With the coadded maps, we are able to resolve many known
features of the Central Molecular Zone (CMZ) in both total intensity and
polarization. We map the orientation of the plane-of-sky component of the
Galactic magnetic field inferred from the polarization angle in the CMZ,
finding significant changes in morphology in the three frequency bands as the
underlying dominant emission mechanism changes from synchrotron to dust
emission. Selected Galactic center sources, including Sgr A*, the Brick
molecular cloud (G0.253+0.016), the Mouse pulsar wind nebula (G359.23-0.82),
and the Tornado supernova remnant candidate (G357.7-0.1), are examined in
detail. These data illustrate the potential for leveraging ground-based Cosmic
Microwave Background polarization experiments for Galactic science.Comment: 26 pages, 14 figures, accepted for publication in Ap
Parp1 Localizes within the Dnmt1 Promoter and Protects Its Unmethylated State by Its Enzymatic Activity
Aberrant hypermethylation of CpG islands in housekeeping gene promoters and widespread genome hypomethylation are typical events occurring in cancer cells. The molecular mechanisms behind these cancer-related changes in DNA methylation patterns are not well understood. Two questions are particularly important: (i) how are CpG islands protected from methylation in normal cells, and how is this protection compromised in cancer cells, and (ii) how does the genome-wide demethylation in cancer cells occur. The latter question is especially intriguing since so far no DNA demethylase enzyme has been found.Our data show that the absence of ADP-ribose polymers (PARs), caused by ectopic over-expression of poly(ADP-ribose) glycohydrolase (PARG) in L929 mouse fibroblast cells leads to aberrant methylation of the CpG island in the promoter of the Dnmt1 gene, which in turn shuts down its transcription. The transcriptional silencing of Dnmt1 may be responsible for the widespread passive hypomethylation of genomic DNA which we detect on the example of pericentromeric repeat sequences. Chromatin immunoprecipitation results show that in normal cells the Dnmt1 promoter is occupied by poly(ADP-ribosyl)ated Parp1, suggesting that PARylated Parp1 plays a role in protecting the promoter from methylation.In conclusion, the genome methylation pattern following PARG over-expression mirrors the pattern characteristic of cancer cells, supporting our idea that the right balance between Parp/Parg activities maintains the DNA methylation patterns in normal cells. The finding that in normal cells Parp1 and ADP-ribose polymers localize on the Dnmt1 promoter raises the possibility that PARylated Parp1 marks those sequences in the genome that must remain unmethylated and protects them from methylation, thus playing a role in the epigenetic regulation of gene expression
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