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Zinc Deficiency Leads to Lipofuscin Accumulation in the Retinal Pigment Epithelium of Pigmented Rats
Sylvie Julien, Antje Biesemeier, Despina Kokkinou, Oliver Eibl, Ulrich Schraermeyer
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029245
Abstract: Background Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. Methodology/Principal Findings Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (?>3 μm) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 μm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4–3 μm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. Conclusions/Significance In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.
Cyclical Appearance of African Trypanosomes in the Cerebrospinal Fluid: New Insights in How Trypanosomes Enter the CNS
Stefan Mogk, Andreas Meiwes, Swetlana Shtopel, Ulrich Schraermeyer, Michael Lazarus, Bruno Kubata, Hartwig Wolburg, Michael Duszenko
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091372
Abstract: It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense) or months (gambiense) in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG), loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.
Towards a Quantitative OCT Image Analysis
Marina Garcia Garrido, Susanne C. Beck, Regine Mühlfriedel, Sylvie Julien, Ulrich Schraermeyer, Mathias W. Seeliger
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100080
Abstract: Background Optical coherence tomography (OCT) is an invaluable diagnostic tool for the detection and follow-up of retinal pathology in patients and experimental disease models. However, as morphological structures and layering in health as well as their alterations in disease are complex, segmentation procedures have not yet reached a satisfactory level of performance. Therefore, raw images and qualitative data are commonly used in clinical and scientific reports. Here, we assess the value of OCT reflectivity profiles as a basis for a quantitative characterization of the retinal status in a cross-species comparative study. Methods Spectral-Domain Optical Coherence Tomography (OCT), confocal Scanning-La-ser Ophthalmoscopy (SLO), and Fluorescein Angiography (FA) were performed in mice (Mus musculus), gerbils (Gerbillus perpadillus), and cynomolgus monkeys (Macaca fascicularis) using the Heidelberg Engineering Spectralis system, and additional SLOs and FAs were obtained with the HRA I (same manufacturer). Reflectivity profiles were extracted from 8-bit greyscale OCT images using the ImageJ software package (http://rsb.info.nih.gov/ij/). Results Reflectivity profiles obtained from OCT scans of all three animal species correlated well with ex vivo histomorphometric data. Each of the retinal layers showed a typical pattern that varied in relative size and degree of reflectivity across species. In general, plexiform layers showed a higher level of reflectivity than nuclear layers. A comparison of reflectivity profiles from specialized retinal regions (e.g. visual streak in gerbils, fovea in non-human primates) with respective regions of human retina revealed multiple similarities. In a model of Retinitis Pigmentosa (RP), the value of reflectivity profiles for the follow-up of therapeutic interventions was demonstrated. Conclusions OCT reflectivity profiles provide a detailed, quantitative description of retinal layers and structures including specialized retinal regions. Our results highlight the potential of this approach in the long-term follow-up of therapeutic strategies.
Lens Injury Has a Protective Effect on Photoreceptors in the RCS Rat
Peter Heiduschka,Daniel Renninger,Dietmar Fischer,Adrienne Müller,Sabine Hofmeister,Ulrich Schraermeyer
ISRN Ophthalmology , 2013, DOI: 10.1155/2013/814814
Abstract: Lens injury induced activation of retinal glia, and subsequent release of ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) potently protect axotomised retinal ganglion cells from apoptosis and promotes axon regeneration in the injured optic nerve. The goal of the current study was to investigate if similar effects may also be applicable to rescue photoreceptors from degeneration in a model of retinitis pigmentosa. Lens injury was performed in the Royal College of Surgeons (RCS) rats at the age of one month. The survival of photoreceptors was evaluated histologically, and retinal function was analysed by electroretinography (ERG). Expression of CNTF was also analysed. Lens injury significantly enhanced the survival of photoreceptors 1 month after surgery compared to untreated controls, which was associated with an enhanced ERG response. In addition, lens injury significantly protected photoreceptors from degeneration in the contralateral eye, although to a much lesser extent. We could show that lens injury is sufficient to transiently delay the degeneration of photoreceptors in the RCS rat. The observed neuroprotective effects may be at least partially mediated by an upregulation of CNTF expression seen after lens injury. 1. Introduction It has recently been shown that lens injury or intravitreal applications of lens-derived β/γ-crystallins potently protect axotomised retinal ganglion cells (RGCs) from cell death and stimulate axon regeneration in the injured optic nerve [1–5]. All treatments induce an activation of retinal astrocytes and Müller cells, which subsequently upregulate and release the cytokines ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) [6–10]. The strong neuroprotective effects of lens injury are completely absent in CNTF/LIF double knockout mice, demonstrating that both cytokines act as essential key mediators [9, 11]. Similar to these factors, interleukin 6 also promotes neuroprotection [12]. The purpose of the current study was to investigate whether lens injury is also sufficient to protect photoreceptors from degeneration. As a model, we chose the Royal College of Surgeons (RCS) rat, which is a commonly used model of retinal degeneration, in particular retinitis pigmentosa. The cells of the retinal pigment epithelium (RPE) are not capable of phagocytosing photoreceptor outer segments due to a mutation in the Mertk gene. This leads to a gradual degeneration of the photoreceptors starting at the time point of eye opening (i.e., approximately at P20) and being completed at the age of 3
Mathematical Rotordynamic Model Regarding Excitation Due to Elliptical Shaft Journals in Electrical Motors Considering the Gyroscopic Effect  [PDF]
Ulrich Werner
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.48A009

The paper presents a mathematical rotordynamic model regarding excitation due to elliptical shaft journals in sleeve bearings of electrical motors also considering the gyroscopic effect. For this kind of excitation, a mathematical rotordynamic model was developed considering the influence of the oil film stiffness and damping of the sleeve bearings, the stiffness of the end-shields and bearing housings, the stiffness of the rotor, the electromagnetic stiffness in the air gap of the electrical motor and the mass moment of inertia of the rotor and therefore also considering the gyroscopic effect. The solution of the linear differential equation system leads to the mathematical description of the absolute orbits of the shaft centre, the shaft journals and the bearing housings and to the relative orbits between the shaft journals and the bearing housings. Additionally, the bearing housing velocities can also be derived with this mathematical rotordynamic model.

Mathematical Multibody Model of a Soft Mounted Induction Motor Regarding Forced Vibrations Due to Dynamic Rotor Eccentricities Considering Electromagnetic Field Damping  [PDF]
Ulrich Werner
Journal of Applied Mathematics and Physics (JAMP) , 2017, DOI: 10.4236/jamp.2017.52032
Abstract: The paper presents a mathematical multibody model of a soft mounted induction motor with sleeve bearings regarding forced vibrations caused by dynamic rotor eccentricities considering electromagnetic field damping. The multibody model contains the mass of the stator, rotor, shaft journals and bearing housings, the electromagnetic forces with respect of electromagnetic field damping, stiffness and internal (rotating) damping of the rotor, different kinds of dynamic rotor eccentricity, stiffness and damping of the bearing housings and end shields, stiffness and damping of the oil film of the sleeve bearings and stiffness and damping of the foundation. With this multibody model, the bearing housing vibrations and the relative shaft vibrations in the sleeve bearings can be derived.
Influence of the Foundation on the Threshold of Stability for Rotating Machines with Roller Bearings—A Theoretical Analysis  [PDF]
Ulrich Werner
Journal of Applied Mathematics and Physics (JAMP) , 2017, DOI: 10.4236/jamp.2017.56114
Abstract: The paper presents a mathematical model for analyzing the threshold of stability for rotating machines, where the rotor is linked to the stator by roller bearings, bearing housings and end-shields and where the stator feet are mounted on a soft foundation. The internal (rotating) damping of the rotor is the only source of instability, which is considered in the paper. After the mathematical coherences of the multibody model are described, a procedure is presented for deriving the threshold of stability. Additionally, a numerical example is shown, where the threshold of stability is calculated for different boundary conditions. It could be demonstrated, that the stiffness of the foundation—even if the foundation stiffness is isotropic—can help stabilizing this kind of vibration system in the same way as orthotropic bearing stiffness or orthotropic bearing housing and end-shield stiffness for a rigid foundation.
Analysis of Different Vibration Control Strategies for Soft Mounted Induction Motors with Sleeve Bearings Using Active Motor Foot Mounts  [PDF]
Ulrich Werner
Journal of Applied Mathematics and Physics (JAMP) , 2019, DOI: 10.4236/jamp.2019.73045
Abstract: The paper presents a theoretical analysis of different vibration control strategies of soft mounted induction motors with sleeve bearings, using active motor foot mounts. After the vibration model is presented, different controllers in combination with different feedback strategies are mathematically investigated. The focus is here on the forced vibrations, caused by dynamic rotor eccentricityrotor mass eccentricity, magnetic eccentricity and bent rotor deflection. After the mathematically coherences are described, a numerical example is shown, where the forced vibrations caused by bent rotor deflection are investigated, for different control strategies, where the mass matrix, the stiffness matrix and the damping matrix are influenced by different control parameters. The aim of the paper is to show the mathematically coherences and the possibility to influence the vibration behaviour, by different control strategies to optimize the vibration behaviour of soft mounted induction motors.
Dirac Hamiltonian with Imaginary Mass and Induced Helicity—Dependence by Indefinite Metric  [PDF]
Ulrich D. Jentschura
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.39116
Abstract: It is of general theoretical interest to investigate the properties of superluminal matter wave equations for spin one-half particles. One can either enforce superluminal propagation by an explicit substitution of the real mass term for an imaginary mass, or one can use a matrix representation of the imaginary unit that multiplies the mass term. The latter leads to the tachyonic Dirac equation, while the equation obtained by the substitution m im in the Dirac equation is naturally referred to as the imaginary-mass Dirac equation. Both the tachyonic as well as the imaginary-mass Dirac Hamiltonians commute with the helicity operator. Both Hamiltonians are pseudo-Hermitian and also possess additional modified pseudo-Hermitian properties, leading to constraints on the resonance eigenvalues. Here, by an explicit calculation, we show that specific sum rules over the The spectrum is found to consist of well-defined real energy eigenvalues and complex resonance and anti-resonance energies. In the quantized imaginary-mass Dirac field, one-particle states of right-handed helicity acquire a negative norm (“indefinite metric”) and can be excluded from the physical spectrum by a Gupta-Bleuler type condition.
Non-peptide ligands in the characterization of peptide receptors at the interface between neuroendocrine and mental diseases  [PDF]
Margit Pissarek, Ulrich Disko
World Journal of Neuroscience (WJNS) , 2013, DOI: 10.4236/wjns.2013.32014

Hypothalamic receptors for neuropeptide Y, melaninconcentrating hormone, melanocortins and orexins/ hypocretins as well as for the downstream signaling corticotrophic factor have been discussed broadly for their influence on food intake and reward but also on several psychiatric disorders. For the development of non-peptide ligands for the in vivo detection of alterations in density and affinity of such G-protein coupled (GPCRs) peptide receptors the requirements to affinity and pharmacokinetics have been shifted to thresholds markedly distict from classical GPCRs to dissociation constants < 0.5 nM, partition coefficients log P < 3.5 and transcellular transport ratios, e.g. for the permeability glycoprotein transporter, below 3. Nevertheless, a multitude of compounds has been reported originally as potential therapeutics in the treatment of obesity among which some are suitable candidates for labeling as PET or SPECT-tracers providing receptor affinities even below 0.1 nM. These could be unique tools not only for better understanding of the mechanism of obesity but also for investigations of extrahypothalamic role of “feeding receptors” at the interface between neuroendocrine and mental diseases.

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