Repeated Quinpirole Treatment: Locomotor Activity, Dopamine Synthesis and Effects of Selective Dopamine Antagonists

A report submitted by Bruce A. Mattingly the Research and Creative Productions Committee on the repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields

Neurochemical Correlates of Behavior Sensitization Following Repeated Apomorphine Treatment: Assessment of the Role of D1 Dopamine Receptor Stimulation

An article written by Bruce A. Mattingly and published in the Spring 1993 issue of Synapse

Repeated Quinpirole Treatment: Locomotor Activity, Dopamine Synthesis, and Effects of Selective Dopamine Antagonists

An article written by Bruce A. Mattingly and published in Synapse in 1995 on repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields

Neurochemical and Behavioral Effects of Acute and Chronic Treatment with Apomorphine in Rats

An article written by Bruce A. Mattingly and published by in the 1991 issue of Neuropharmacology, pages 191-197

Presence of C-type natriuretic peptide in human kidney and urine

Presence of C-type natriuretic peptide in human kidney and urine. The current study was undertaken to investigate the presence of CNP immunoreactivity in both human kidney and urine. Immunohistochemical staining with an indirect immunoperoxidase method utilizing an antibody which is 100% cross-reactive to both CNP-53 and CNP-22 was performed on five human kidney specimens (three biopsies of normal cadaveric donor kidneys and two of normal autopsy specimens). CNP immunoreactivity was positive in proximal, distal and medullary collecting duct tubular cells in a cytoplasmic and granular staining pattern. CNP immunoreactivity was also determined in the urine of five healthy volunteers utilizing a sensitive and specific double-antibody radioimmunoassay with a mean concentration of 10.8 ± 1.0 pg/ml. With the utilization of high pressure liquid chromatography, this immunoreactivity proved to be consistent with both the low molecular weight form, CNP-22, as well as the high molecular weight form, CNP-53. Urinary excretion of CNP was also measured in normal subjects (N = 5) and in patients with congestive heart failure (CHF, N = 6). CHF patients excreted over three times more CNP than normals (27.2 ± 2.8 vs. 8.7 ± 0.81 pg/min, P < 0.004) despite no difference between the two groups in plasma CNP concentrations (6.97 ± 0.28 vs. 8.08 ± 1.52 pg/ml, P = NS). This study demonstrates for the first time the presence of CNP immunoreactivity in human kidney and suggests that renal tubular cells may be an additional non-vascular site of synthesis for this cardiorenal acting peptide. This study also demonstrates an increase in urinary CNP excretion in congestive heart failure

Doxorubicin and Paclitaxel-Loaded Lipid-Based Nanoparticles Overcome Multidrug Resistance by Inhibiting P-Glycoprotein and Depleting ATP

To test the ability of nanoparticle (NP) formulations to overcome P-gp-mediated multidrug resistance (MDR), several different doxorubicin (Dox) and paclitaxel (PX)-loaded solid lipid NPs were prepared. Dox NPs showed 6-8-fold lower IC50 values in Pgp overexpressing human cancer cells than those of free Dox. The IC50 value of PX NPs was over 9-fold lower than that of Taxol® in P-gp-overexpressing cells. A series of in-vitro cell assays were used including quantitative studies on uptake and efflux, inhibition of calcein acetoxymethylester (Calcein AM) efflux, alteration of ATP levels, membrane integrity, mitochondrial membrane potential, apoptosis and cytotoxicity. Enhanced uptake and prolonged retention of Dox were observed with NP-based formulations in P-gp-overexpressing cells. Calcein AM and ATP assays confirmed that blank NPs inhibited P-gp and transiently depleted ATP. Intravenous injection of pegylated PX BTM NPs showed marked anticancer efficacy in nude mice bearing resistant NCI/ADR-RES tumors versus all control groups. NPs may be used to both target drug and biological mechanisms to overcome MDR via P-gp inhibition and ATP depletion

Space-based research in fundamental physics and quantum technologies

Space-based experiments today can uniquely address important questions related to the fundamental laws of Nature. In particular, high-accuracy physics experiments in space can test relativistic gravity and probe the physics beyond the Standard Model; they can perform direct detection of gravitational waves and are naturally suited for precision investigations in cosmology and astroparticle physics. In addition, atomic physics has recently shown substantial progress in the development of optical clocks and atom interferometers. If placed in space, these instruments could turn into powerful high-resolution quantum sensors greatly benefiting fundamental physics. We discuss the current status of space-based research in fundamental physics, its discovery potential, and its importance for modern science. We offer a set of recommendations to be considered by the upcoming National Academy of Sciences' Decadal Survey in Astronomy and Astrophysics. In our opinion, the Decadal Survey should include space-based research in fundamental physics as one of its focus areas. We recommend establishing an Astronomy and Astrophysics Advisory Committee's interagency ``Fundamental Physics Task Force'' to assess the status of both ground- and space-based efforts in the field, to identify the most important objectives, and to suggest the best ways to organize the work of several federal agencies involved. We also recommend establishing a new NASA-led interagency program in fundamental physics that will consolidate new technologies, prepare key instruments for future space missions, and build a strong scientific and engineering community. Our goal is to expand NASA's science objectives in space by including ``laboratory research in fundamental physics'' as an element in agency's ongoing space research efforts.Comment: a white paper, revtex, 27 pages, updated bibliograph

Renormalization-Scale-Invariant PQCD Predictions for R_e+e- and the Bjorken Sum Rule at Next-to-Leading Order

We discuss application of the physical QCD effective charge $\alpha_V$, defined via the heavy-quark potential, in perturbative calculations at next-to-leading order. When coupled with the Brodsky-Lepage-Mackenzie prescription for fixing the renormalization scales, the resulting series are automatically and naturally scale and scheme independent, and represent unambiguous predictions of perturbative QCD. We consider in detail such commensurate scale relations for the $e^+e^-$ annihilation ratio $R_{e^+e^-}$ and the Bjorken sum rule. In both cases the improved predictions are in excellent agreement with experiment.Comment: 13 Latex pages with 5 figures; to be published in Physical Review

Providing the Missing Link: the Exposure Science Ontology ExO

Environmental health information resources lack exposure data required to translate molecular insights, elucidate environmental contributions to diseases, and assess human health and ecological risks. We report development of an Exposure Ontology, ExO, designed to address this information gap by facilitating centralization and integration of exposure data. Major concepts were defined and the ontology drafted and evaluated by a working group of exposure scientists and other ontology and database experts. The resulting major concepts forming the basis for the ontology are exposure stressor , exposure receptor , exposure event , and exposure outcome . Although design of the first version of ExO focused on human exposure to chemicals, we anticipate expansion by the scientific community to address exposures of human and ecological receptors to the full suite of environmental stressors. Like other widely used ontologies, ExO is intended to link exposure science and diverse environmental health disciplines including toxicology, epidemiology, disease surveillance, and epigenetics

Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download