Vortex Structure Around a Magnetic Dot in Planar Superconductors

The problem of the giant vortex state around a magnetic dot which is embedded in a superconducting film is investigated. The full non-linear, self-consistent Ginzburg-Landau equations are solved numerically in order to calculate the free energy, the order parameter of the host superconductor, the internal magnetic field due to the supercurrents, the corresponding current density, the magnetization probed in the vicinity of the dot, and the normal electron density as a function of the various parameters of the system. We find that, as we increase the magnetic moment of the dot, higher flux quanta vortex states become energetically more favorable, as they can better compete with the external magnetic field via the Meissner effect. In addition to that, they progressively become closer to each other in energy with direct experimental consequences, i.e. physical quantities like magnetization may fluctuate when measured, for example, as a function of a uniform external magnetic field.Comment: text 21 pages (REVTEX), 8 figures available upon reques

Effects of columnar disorder on flux-lattice melting in high-temperature superconductors

The effect of columnar pins on the flux-lines melting transition in high-temperature superconductors is studied using Path Integral Monte Carlo simulations. We highlight the similarities and differences in the effects of columnar disorder on the melting transition in YBa$_2$Cu$_3$O$_{7-\delta}$ (YBCO) and the highly anisotropic Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ (BSCCO) at magnetic fields such that the mean separation between flux-lines is smaller than the penetration length. For pure systems, a first order transition from a flux-line solid to a liquid phase is seen as the temperature is increased. When adding columnar defects to the system, the transition temperature is not affected in both materials as long as the strength of an individual columnar defect (expressed as a flux-line defect interaction) is less than a certain threshold for a given density of randomly distributed columnar pins. This threshold strength is lower for YBCO than for BSCCO. For higher strengths the transition line is shifted for both materials towards higher temperatures, and the sharp jump in energy, characteristic of a first order transition, gives way to a smoother and gradual rise of the energy, characteristic of a second order transition. Also, when columnar defects are present, the vortex solid phase is replaced by a pinned Bose glass phase and this is manifested by a marked decrease in translational order and orientational order as measured by the appropriate structure factors. For BSCCO, we report an unusual rise of the translational order and the hexatic order just before the melting transition. No such rise is observed in YBCO.Comment: 32 pages, 13 figures, revte

Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Rabies virus infects almost all mammals resulting in lethal disease. To date there is no treatment available for symptomatic rabies and there is an urgent need to develop treatment strategies that would prolong survival, thereby providing a window of opportunity for the host to mount a protective immune response. We hypothesized that both virus and excessive immune response contribute to disease and that interfering with both is necessary to prevent lethal disease. Here, we have inhibited the pro-inflammatory response associated with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on survival time. Our results confirm that some inflammatory responses may be involved in the pathogenesis of severe disease and the results suggest that effective intervention includes inhibition of virus and host response

Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves

Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines

Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1

Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials

Pan-cancer patterns of DNA methylation

The comparison of DNA methylation patterns across cancer types (pan-cancer methylome analyses) has revealed distinct subgroups of tumors that share similar methylation patterns. Integration of these data with the wealth of information derived from cancer genome profiling studies performed by large international consortia has provided novel insights into the cellular aberrations that contribute to cancer development. There is evidence that genetic mutations in epigenetic regulators (such as DNMT3, IDH1/2 or H3.3) mediate or contribute to these patterns, although a unifying molecular mechanism underlying the global alterations of DNA methylation has largely been elusive. Knowledge gained from pan-cancer methylome analyses will aid the development of diagnostic and prognostic biomarkers, improve patient stratification and the discovery of novel druggable targets for therapy, and will generate hypotheses for innovative clinical trial designs based on methylation subgroups rather than on cancer subtypes. In this review, we discuss recent advances in the global profiling of tumor genomes for aberrant DNA methylation and the integration of these data with cancer genome profiling data, highlight potential mechanisms leading to different methylation subgroups, and show how this information can be used in basic research and for translational applications. A remaining challenge is to experimentally prove the functional link between observed pan-cancer methylation patterns, the associated genetic aberrations, and their relevance for the development of cancer

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA