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  • National Academy of Sciences  (7)
  • Blackwell Publishing Ltd  (4)
  • The American Physiological Society (APS)  (3)
  • Institute of Physics Publishing (IOP)  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Ferritin in Parkinsonian and control brains (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ferritin, the main iron storage protein, may be involved in triggering oxidative stress injury in Parkinson's disease. Aim: To determine the ratio of H and L chains of ferritin and the size of its iron-core in brain areas with high amounts of iron: substantia nigra (SN), globus pallidus (GP) and hippocampus (Hip). Methods: H/L ratio was determined by ELISA and iron size of ferritin by direct measurements of isolated ferritin with the use of electron microscopy (EM). Material: ELISA was made on 11 control and four Parkinsonian GP, Hip and SN. EM data were obtained from measurements of 50 iron-cores of ferritin in control GP, SN and Hip. Results: H/L ratios in control brains vs. PD brains were 5.92 ± 1.65 vs. 9.45 ± 1.93 for GP, 5.05 ± 1.67 vs. 11.41 ± 3.47 for SN, 16.01 ± 9.86 vs. 24.85 ± 5.88 for Hip. The sizes of iron-cores in control brains were 3.3 ± 0.5 nm for GP, 3.7 ± 0.5 nm for SN and 3.1 ± 0.5 nm for Hip. These results may suggest different iron metabolism both in different brain areas and between PD and control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.19_8.x
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Sequestration and Release of Basic Fibroblast Growth Factor (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 638 (1991), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1991.tb49032.x
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Intracellular Calcium and Control of Burst Generation in Neurons of Guinea-Pig Neocortex in Vitro (1989)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 1 (1989), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Response properties of neurons in brain slices of guinea pig parietal neocortex were examined following intracellular injection of the Ca2+ chelators, EGTA and BAPTA. Although chelator injection did not cause any consistent change in passive membrane properties, it did induce 81% of neurons encountered at all sub-pial depths to become ‘bursters’, in that just-threshold depolarizing current pulses triggered all-or-none bursts of 2–5 fast action potentials. Transition to ‘burstiness’ was associated with disappearance of an AHP and appearance of a DAP. Although chelator caused a slight increase in steady-state firing rate, marked accommodation persisted. Extracellular Co2+ or Mn2+ had an effect on steady-state firing rate similar to that of the intracellular chelators; however, exposure to these Ca2+ channel blockers also caused steady state depolarization, increased resting input resistance and time constant, and profound spike broadening. This treatment never induced transition to ‘burstiness’. Chelator-injected neurons ceased to generate bursts when Ca2+ was replaced by Mn2+ in the Ringer's solution. During exposure to 10−6 M TTX and 20 mM TEA, 50–200 msec Ca2+ spikes followed brief depolarizing pulses. As chelator was injected into the cell, there was progressive prolongation of the Ca2+ plateaus, which was associated with slowing of the rate at which membrane resistance gradually recovered following the initial increase in conductance.These findings indicate that under normal conditions, activity-related increases in intracellular Ca2+ activate processes which prevent most neocortical neurons from being bursters. These processes probably include Ca2+ -dependent K+ currents, and Ca2+ -dependent Ca2+ channel inactivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1989.tb00802.x
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    CHRONOPHARMACOLOGY OF STRYCHNINE AND ALLYLGLYCINE IN THE MOUSE (1977)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 4 (1977), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The response of individually caged mice to the lethal actions of allylglycine and strychnine was evaluated in animals previously conditioned on an LD 12:12 (12 h light-12 h darkness) schedule in a controlled environment.2. These convulsant agents were most toxic at 18.00 hours (during the light phase), and least toxic in the dark phase of the programmed lighting schedule. The relationship is considered of the circadian fluctuations in levels of inhibitory transmitter substances to the time-linked action of convulsant agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1977.tb02623.x
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    Paper (German National Licenses)
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  • 5
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    Neutron measurements with Time-Resolved Event-Counting Optical Radiation (TRECOR) detector (2012)
    Institute of Physics Publishing (IOP)
    Details
    Publication Date: 2012-04-04
    Description: Results are presented from the latest experiment with a new neutron/gamma detector, a Time-Resolved, Event-Counting Optical Radiation (TRECOR) detector. It is composed of a scintillating fiber-screen converter, bending mirror, lens and Event-Counting Image Intensifier (ECII), capable of specifying the position and time-of-flight of each event. TRECOR is designated for a multipurpose integrated system that will detect Special Nuclear Materials (SNM) and explosives in cargo. Explosives are detected by Fast-Neutron Resonance Radiography, and SNM by Dual Discrete-Energy gamma-Radiography. Neutrons and gamma-rays are both produced in the 11 B(d,n+γ) 12 C reaction. The two detection modes can be implemented simultaneously in TRECOR, using two adjacent radiation converters that share a common optical readout. In the present experiment the neutron detection mode was studied, using a plastic scintillator converter. The measurements were performed at the PTB cyclotron, usi...
    Electronic ISSN: 1748-0221
    Topics: Physics
    Published by Institute of Physics Publishing (IOP)
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  • 6
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    Mechanistic modeling of the effects of myoferlin on tumor cell invasion [Applied Mathematics] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-14
    Description: Myoferlin (MYOF) is a member of the evolutionarily conserved ferlin family of proteins, noted for their role in a variety of membrane processes, including endocytosis, repair, and vesicular transport. Notably, ferlins are implicated in Caenorhabditis elegans sperm motility (Fer-1), mammalian skeletal muscle development and repair (MYOF and dysferlin), and presynaptic transmission in the auditory system (otoferlin). In this paper, we demonstrate that MYOF plays a previously unrecognized role in cancer cell invasion, using a combination of mathematical modeling and in vitro experiments. Using a real-time impedance-based invasion assay (xCELLigence), we have shown that lentiviral-based knockdown of MYOF significantly reduced invasion of MDA-MB-231 breast cancer cells in Matrigel bioassays. Based on these experimental data, we developed a partial differential equation model of MYOF effects on cancer cell invasion, which we used to generate mechanistic hypotheses. The mathematical model predictions revealed that matrix metalloproteinases (MMPs) may play a key role in modulating this invasive property, which was supported by experimental data using quantitative RT-PCR screens. These results suggest that MYOF may be a promising target for biomarkers or drug target for metastatic cancer diagnosis and therapy, perhaps mediated through MMPs.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Mathematical modeling of prostate cancer progression in response to androgen ablation therapy [Applied Mathematics] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-07
    Description: Prostate cancer progression depends in part on the complex interactions between testosterone, its active metabolite DHT, and androgen receptors. In a metastatic setting, the first line of treatment is the elimination of testosterone. However, such interventions are not curative because cancer cells evolve via multiple mechanisms to a castrate-resistant state, allowing progression to a lethal outcome. It is hypothesized that administration of antiandrogen therapy in an intermittent, as opposed to continuous, manner may bestow improved disease control with fewer treatment-related toxicities. The present study develops a biochemically motivated mathematical model of antiandrogen therapy that can be tested prospectively as a predictive tool. The model includes “personalized” parameters, which address the heterogeneity in the predicted course of the disease under various androgen-deprivation schedules. Model simulations are able to capture a variety of clinically observed outcomes for “average” patient data under different intermittent schedules. The model predicts that in the absence of a competitive advantage of androgen-dependent cancer cells over castration-resistant cancer cells, intermittent scheduling can lead to more rapid treatment failure as compared to continuous treatment. However, increasing a competitive advantage for hormone-sensitive cells swings the balance in favor of intermittent scheduling, delaying the acquisition of genetic or epigenetic alterations empowering androgen resistance. Given the near universal prevalence of antiandrogen treatment failure in the absence of competing mortality, such modeling has the potential of developing into a useful tool for incorporation into clinical research trials and ultimately as a prognostic tool for individual patients.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Unsupervised multipass spike-sorting algorithm [Neuroscience] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-04-08
    Description: A critical problem faced in many scientific fields is the adequate separation of data derived from individual sources. Often, such datasets require analysis of multiple features in a highly multidimensional space, with overlap of features and sources. The datasets generated by simultaneous recording from hundreds of neurons emitting phasic action...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Renal interstitial fibrosis [Applied Mathematics] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-10-01
    Description: Lupus nephritis (LN) is an autoimmune disease that occurs when autoantibodies complex with self-antigen and form immune complexes that accumulate in the glomeruli. These immune complexes initiate an inflammatory response resulting in glomerular injury. LN often concomitantly affects the tubulointerstitial compartment of the kidney, leading first to interstitial inflammation and...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney (2016)
    The American Physiological Society (APS)
    Details
    Publication Date: 2016-04-28
    Description: The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2- 18 fluoro-2-deoxyglucose ( 18 F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18 F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[ N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.
    Print ISSN: 1931-857X
    Electronic ISSN: 1522-1466
    Topics: Medicine
    Published by The American Physiological Society (APS)
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