Rotating Stars in Relativity

Rotating relativistic stars have been studied extensively in recent years, both theoretically and observationally, because of the information one could obtain about the equation of state of matter at extremely high densities and because they are considered to be promising sources of gravitational waves. The latest theoretical understanding of rotating stars in relativity is reviewed in this updated article. The sections on the equilibrium properties and on the nonaxisymmetric instabilities in f-modes and r-modes have been updated and several new sections have been added on analytic solutions for the exterior spacetime, rotating stars in LMXBs, rotating strange stars, and on rotating stars in numerical relativity.Comment: 101 pages, 18 figures. The full online-readable version of this article, including several animations, will be published in Living Reviews in Relativity at http://www.livingreviews.org

Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum

Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some insight into the neuroadaptive potentials of the brain when repeatedly exposed to drugs of abuse

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Precision Electroweak Measurements on the Z resonance.

We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron–positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLD experiment using a polarised beam at SLC. The measurements include cross-sections, forward–backward asymmetries and polarised asymmetries. The mass and width of the Z boson, mZ and ΓZ, and its couplings to fermions, for example the ρ parameter and the effective electroweak mixing angle for leptons, are precisely measured: The number of light neutrino species is determined to be 2.9840±0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward–backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, , and the mass of the W boson, . These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of mt and mW, the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than at 95% confidence level

Recent progress in research on the pharmacological potential of mushrooms and prospects for their clinical application

International audienceFungi are considered one of the most diverse, ecologically significant, and economically important organisms on Earth. The edible and medicinal mushrooms have long been known by humans and were used by ancient civilizations not only as valuable food but also as medicines. Mushrooms are producers of high- and low-molecular-weight bioactive compounds (alkaloids, lectins, lipids, peptidoglycans, phenolics, polyketides, polysaccharides, proteins, polysaccharide-protein/peptides, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 different therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiplatelet, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, immunosuppressive, mitogenic/regenerative, etc.). The early record of Materia Medica shows evidence of using mushrooms for treatment of different diseases. Mushrooms were widely used in the traditional medicine of many countries around the world and became great resources for modern clinical and pharmacological research. However, the medicinal and biotechnological potential of mushrooms has not been fully investigated. This review discusses recent advances in research on the pharmacological potential of mushrooms and perspectives for their clinical application