University of Arizona

About: University of Arizona is a education organization based out in Tucson, Arizona, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 63805 authors who have published 155998 publications receiving 6854915 citations. The organization is also known as: UA & U of A.

The emerging role of the Nrf2–Keap1 signaling pathway in cancer

Abstract: The Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2])-Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1) signaling pathway is one of the most important cell defense and survival pathways. Nrf2 can protect cells and tissues from a variety of toxicants and carcinogens by increasing the expression of a number of cytoprotective genes. As a result, several Nrf2 activators are currently being tested as chemopreventive compounds in clinical trials. Just as Nrf2 protects normal cells, studies have shown that Nrf2 may also protect cancer cells from chemotherapeutic agents and facilitate cancer progression. Nrf2 is aberrantly accumulated in many types of cancer, and its expression is associated with a poor prognosis in patients. In addition, Nrf2 expression is induced during the course of drug resistance. Collectively, these studies suggest that Nrf2 contributes to both intrinsic and acquired chemoresistance. This discovery has opened up a broad spectrum of research geared toward a better understanding of the role of Nrf2 in cancer. This review provides an overview of (1) the Nrf2-Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.

Molecular genetic perspectives on cross‐talk and specificity in abiotic stress signalling in plants

Abstract: The perception of abiotic stresses and signal transduction to switch on adaptive responses are critical steps in determining the survival and reproduction of plants exposed to adverse environments. Plants have stress-specific adaptive responses as well as responses which protect the plants from more than one environmental stress. There are multiple stress perception and signalling pathways, some of which are specific, but others may cross-talk at various steps. Recently, progress has been made in identifying components of signalling pathways involved in salt, drought and cold stresses. Genetic analysis has defined the Salt-Overly-Sensitive (SOS) pathway, in which a salt stress-induced calcium signal is probably sensed by the calcium-binding protein SOS3 which then activates the protein kinase SOS2. The SOS3‐SOS2 kinase complex regulates the expression and activity of ion transporters such as SOS1 to reestablish cellular ionic homeostasis under salinity. The ICE1 (Inducer of CBF Expression 1)‐CBF (CRepeat Binding Protein) pathway is critical for the regulation of the cold-responsive transcriptome and acquired freezing tolerance, although at present the signalling events that activate the ICE1 transcription factor during cold stress are not known. Both ABAdependent and -independent signalling pathways appear to be involved in osmotic stress tolerance. Components of mitogen-activated protein kinase (MAPK) cascades may act as converging points of multiple abiotic as well as biotic stress signalling pathways. Forward and reverse genetic analysis in combination with expression profiling will continue to uncover many signalling components, and biochemical characterization of the signalling complexes will be required to determine specificity and crosstalk in abiotic stress signalling pathways.

The ages and metallicities of galaxies in the local universe

Abstract: We derive stellar metallicities, light-weighted ages and stellar masses for a magnitude-limited sample of 175 128 galaxies drawn from the Sloan Digital Sky Survey Data Release Two (SDSS DR2). We compute the median-likelihood estimates of these parameters using a large library of model spectra at medium‐high resolution, covering a comprehensive range of star formation histories. The constraints we derive are set by the simultaneous fit of five spectral absorption features, which are well reproduced by our population synthesis models. By design, these constraints depend only weakly on the α/Fe element abundance ratio. Our sample includes galaxies of all types spanning the full range in star formation activity, from dormant early-type to actively star-forming galaxies. By analysing a subsample of 44 254 high-quality spectra, we show that, in the mean, galaxies follow a sequence of increasing stellar metallicity, age and stellar mass at increasing 4000-A break strength. For galaxies of intermediate mass, stronger Balmer absorption at fixed 4000-A break strength is associated with higher metallicity and younger age. We investigate how stellar metallicity and age depend on total galaxy stellar mass. Low-mass galaxies are typically young and metal-poor, massive galaxies old and metalrich, with a rapid transition between these regimes over the stellar mass range 3 × 10 9 M ∗ 3 × 10 10 M� . Both high- and low-concentration galaxies follow these relations, but there is a large dispersion in stellar metallicity at fixed stellar mass, especially for low-concentration galaxies of intermediate mass. Despite the large scatter, the relation between stellar metallicity and stellar mass is similar to the correlation between gas-phase oxygen abundance and stellar mass for star-forming galaxies. This is confirmed by the good correlation between stellar metallicity and gas-phase oxygen abundance for galaxies with both measures. The substantial range in stellar metallicity at fixed gas-phase oxygen abundance suggests that gas ejection and/or accretion are important factors in galactic chemical evolution. Ke yw ords: galaxies: evolution ‐ galaxies: formation ‐ galaxies: stellar content.

Solar influences on climate

Abstract: The development of this review article has evolved from work carried out by an international team of the International Space Science Institute (ISSI), Bern, Switzerland, and from work carried out under the auspices of Scientific Committee on Solar Terrestrial Physics (SCOSTEP) Climate and Weather of the Sun‐Earth System (CAWSES‐1). The support of ISSI in providing workshop and meeting facilities is acknowledged, especially support from Y. Calisesi and V. Manno. SCOSTEP is acknowledged for kindly providing financial assistance to allow the paper to be published under an open access policy. L.J.G. was supported by the UK Natural Environment Research Council (NERC) through their National Centre for Atmospheric Research (NCAS) Climate program. K.M. was supported by a Marie Curie International Outgoing Fellowship within the 6th European Community Framework Programme. J.L. acknowledges support by the EU/FP7 program Assessing Climate Impacts on the Quantity and Quality of Water (ACQWA, 212250) and from the DFG Project Precipitation in the Past Millennium in Europe (PRIME) within the Priority Program INTERDYNAMIK. L.H. acknowledges support from the U.S. NASA Living With a Star program. G.M. acknowledges support from the Office of Science (BER), U.S. Department of Energy, Cooperative Agreement DE‐FC02‐97ER62402, and the National Science Foundation. We also wish to thank Karin Labitzke and Markus Kunze for supplying an updated Figure 13, Andrew Heaps for technical support, and Paul Dickinson for editorial support. Part of the research was carried out under the SPP CAWSES funded by GFG. J.B. was financially supported by NCCR Climate–Swiss Climate Research.

First Documented Rhythm and Clinical Outcome From In-Hospital Cardiac Arrest Among Children and Adults

Abstract: ContextCardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA.ObjectiveTo test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes.Design, Setting, and PatientsA prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (≥18 years) and 880 children (<18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded.Main Outcome MeasureSurvival to hospital discharge.ResultsThe rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P<.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P<.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32).ConclusionsIn this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.