The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non-metals in biological tissues is of key interest in life science. Over the ...past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using double-focusing sector field (LA-ICP-SFMS) or quadrupole-based mass spectrometers (LA-ICP-QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA-ICP-QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA-ICP-MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal-containing proteins and also phosphoproteins. Metal-containing proteins were imaged in a two-dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA-ICP-MS imaging as a stand-alone technique and in combination with MALDI/ESI-MS for selected life science applications is summarized.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in ...thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.
Diagnostic Testing for the Novel Coronavirus Sharfstein, Joshua M; Becker, Scott J; Mello, Michelle M
JAMA : the journal of the American Medical Association,
04/2020, Letnik:
323, Številka:
15
Journal Article
Recenzirano
The technical and regulatory challenges that slowed down diagnostic testing for COVID-19 during the early spread of the pandemic in the U.S. are explained. The unintended consequences of making ...testing more widely available to the public, including testing errors and over-testing, are considered.
Mood disorders such as depression and anxiety are frequently observed in patients suffering from chronic pain. Over time, different tests and models have been developed in rodents to study the ...anxiodepressive‐like consequences of chronic pain. This review describes these preclinical tools (models and tests) used for studying behavioural aspects of the comorbid relationship between chronic pain and anxiety and/or major depressive disorder. Three major types of chronic pain strongly associated with anxiodepressive‐like comorbidity as well as their animal models are presented: neuropathic pain, inflammatory pain and fibromyalgia. After a description of chronic pain animal models and of the tests that allow determining nociceptive responses, this review presents and discusses the various behavioural tests that have been used to assess anxiety and depressive‐like behaviours in these models of chronic pain. Finally, this review highlights the progress that remains to be made to homogenize the results in the field of pain‐induced mood disorders and summarizes the recent advances achieved through these tests and models.
Chronic pain‐induced anxiodepressive‐like disorders can be modelled in rodents. This review describes models and tests frequently used for studying behavioural aspects of the anxiodepressive consequences of chronic pain.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département Neurobiologie et Génétique; Institut National de la Santé et de la Recherche Médicale U964; and Centre National de la ...Recherche Scientifique UMR7104, Illkirch; and Université de Strasbourg, Strasbourg, France
The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1 ) the latest data on the anatomy of the opioid system, 2 ) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3 ) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4 ) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was developed as a powerful analytical technique for metal imaging of 2D gels for the detection of metalloproteins in rat ...kidney after electrophoretic separation. Protein complexes, extracted with water, were separated in their native state in the first and second dimension by blue native gel electrophoresis (BN-PAGE). Essential and toxic metals, such as zinc, copper, iron, manganese and lead, were monitored by LA-ICP-MS after gel ablation by a focused laser beam in a way that the total surface of a selected fragment of the gel was totally ablated. The metal distribution of this part of the gel was then constructed by plotting the metal (isotope) signal intensity as a function of the x,y (isoelectric point, molecular mass) coordinates of the gel. The proteins at locations rich in metals were cut out, digested with trypsin and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
ABSTRACT
Understanding the transport of energetic cosmic rays belongs to the most challenging topics in astrophysics. Diffusion due to scattering by electromagnetic fluctuations is a key process in ...cosmic ray transport. The transition from a ballistic to a diffusive-propagation regime is presented in direct numerical calculations of diffusion coefficients for homogeneous magnetic field lines subject to turbulent perturbations. Simulation results are compared with theoretical derivations of the parallel diffusion coefficient’s dependences on the energy and the fluctuation amplitudes in the limit of weak turbulence. The present study shows that the widely used extrapolation of the energy scaling for the parallel diffusion coefficient to high turbulence levels predicted by quasi-linear theory does not provide a universally accurate description in the resonant-scattering regime. It is highlighted here that the numerically calculated diffusion coefficients can be polluted for low energies due to missing resonant interaction possibilities of the particles with the turbulence. Five reduced-rigidity regimes are established, which are separated by analytical boundaries derived in this work. Consequently, a proper description of cosmic ray propagation can only be achieved by using a turbulence-level-dependent diffusion coefficient and can contribute to solving the Galactic cosmic ray gradient problem.
ABSTRACT We present a systematic study of non-thermal electron-proton plasma and its emission processes in starburst galaxies in order to explain the correlation between the luminosity in the radio ...band and the recently observed gamma luminosity. In doing so, a steady state description of the cosmic-ray (CR) electrons and protons within the spatially homogeneous starburst is considered where continuous momentum losses are included as well as catastrophic losses due to diffusion and advection. The primary source of the relativistic CRs, e.g., supernova remnants, provides a quasi-neutral plasma with a power-law spectrum in momentum where we account for rigidity-dependent differences between the electron and proton spectrum. We examine the resulting leptonic and hadronic radiation processes by synchrotron radiation, inverse Compton scattering, Bremsstrahlung, and hadronic pion production. Finally, the observations of NGC 253, M82, NGC 4945, and NGC 1068 in the radio and gamma-ray bands as well as the observed supernova rate are used to constrain a best-fit model. In the case of NGC 253, M82, and NGC 4945 our model is able to accurately describe the data, showing that: (i) supernovae are the dominant particle accelerators for NGC 253, M82, and NGC 4945, but not for NGC 1068; (ii) all considered starburst galaxies are poor proton calorimeters in which for NGC 253 the escape is predominantly driven by the galactic wind, whereas the diffusive escape dominates in NGC 4945 and M82 (at energies >1 TeV); and (iii) secondary electrons from hadronic pion production are important to model the radio flux, but the associated neutrino flux is below the current observation limit.
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