Indicators of replicative damage in equine tendon fibroblast monolayers

<p>Background: Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it.</p> <p>Results: We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents.</p> <p>Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress.</p> <p>Conclusions: Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled.</p&gt

Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial

© 2020, The Author(s). Purpose: To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest. Methods: A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated \u3c 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1–2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes. Results: In total, 300 patients were analyzed and the proportion with CPC 1–2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95–3.85, p =.07. In patients with shockable rhythm, CPC 1–2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06–9.97, p =.04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12–4.62, p =.02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55–18.3, p =.008. Conclusions: In the whole study population, intra-arrest cooling initiated \u3c 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery

A longitudinal investigation of repressive coping and ageing

This is an Accepted Manuscript of an article published by Taylor & Francis in Aging & Mental Health on October 2016, available online: http://www.tandfonline.com/doi/full/10.1080/13607863.2015.1060941.Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults.Peer reviewedFinal Accepted Versio

COMPORTAMENTO HIDROLÓGICO DE ENCOSTA EM SUBSTRATO ROCHOSO GRANÍTICO SOB INFLUÊNCIA DE DESLIZAMENTO RASO - NOVA FRIBURGO, RIO DE JANEIRO

Tendo a água como principal agente deflagrador dos deslizamentos em regiões tropicais, este trabalho objetivou o estudo hidrológico de uma encosta com um cicatriz de deslizamento do tipo translacional raso, no evento extremo de chuva de Janeiro de 2011, Nova Friburgo-RJ. Para o entendimento da influência da água subterrânea na deflagração dos movimentos de massa, a área foi sondada e instrumenta, visando a caracterização física da encosta

Twenty five years after KLS: A celebration of non-equilibrium statistical mechanics

When Lenz proposed a simple model for phase transitions in magnetism, he couldn't have imagined that the "Ising model" was to become a jewel in field of equilibrium statistical mechanics. Its role spans the spectrum, from a good pedagogical example to a universality class in critical phenomena. A quarter century ago, Katz, Lebowitz and Spohn found a similar treasure. By introducing a seemingly trivial modification to the Ising lattice gas, they took it into the vast realms of non-equilibrium statistical mechanics. An abundant variety of unexpected behavior emerged and caught many of us by surprise. We present a brief review of some of the new insights garnered and some of the outstanding puzzles, as well as speculate on the model's role in the future of non-equilibrium statistical physics.Comment: 3 figures. Proceedings of 100th Statistical Mechanics Meeting, Rutgers, NJ (December, 2008

Alterations to nuclear architecture and genome behavior in senescent cells.

The organization of the genome within interphase nuclei, and how it interacts with nuclear structures is important for the regulation of nuclear functions. Many of the studies researching the importance of genome organization and nuclear structure are performed in young, proliferating, and often transformed cells. These studies do not reveal anything about the nucleus or genome in nonproliferating cells, which may be relevant for the regulation of both proliferation and replicative senescence. Here, we provide an overview of what is known about the genome and nuclear structure in senescent cells. We review the evidence that nuclear structures, such as the nuclear lamina, nucleoli, the nuclear matrix, nuclear bodies (such as promyelocytic leukemia bodies), and nuclear morphology all become altered within growth-arrested or senescent cells. Specific alterations to the genome in senescent cells, as compared to young proliferating cells, are described, including aneuploidy, chromatin modifications, chromosome positioning, relocation of heterochromatin, and changes to telomeres

Ginzburg-Landau functional for nearly antiferromagnetic perfect and disordered Kondo lattices

Interplay between Kondo effect and trends to antiferromagnetic and spin glass ordering in perfect and disordered bipartite Kondo lattices is considered. Ginzburg-Landau equation is derived from the microscopic effective action written in three mode representation (Kondo screening, antiferromagnetic correlations and spin liquid correlations). The problem of local constraint is resolved by means of Popov-Fedotov representation for localized spin operators. It is shown that the Kondo screening enhances the trend to a spin liquid crossover and suppresses antiferromagnetic ordering in perfect Kondo lattices and spin glass ordering in doped Kondo lattices. The modified Doniach's diagram is constructed, and possibilities of going beyond the mean field approximation are discussed.Comment: 18 pages, RevTeX, 7 EPS figures include

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

The Baikal Deep Underwater Neutrino Experiment: Results, Status, Future

We review the present status of the Baikal Underwater Neutrino Experiment and present results obtained with the various stages of the stepwise increasing detector: NT-36 (1993-95), NT-72 (1995-96) and NT-96 (1996-97). Results cover atmospheric muons, first clear neutrino events, search for neutrinos from WIMP annihilation in the center of the Earth, search for magnetic monopoles, and -- far from astroparticle physics -- limnology.Comment: Talk given at the Int. School on Nuclear Physics, Erice, Sept.199