The significance of bioelectricity on all levels of organization of an organism. Part 1: From the subcellular level to cells

Bioelectricity plays an essential role in the structural and functional organization of biological organisms. In this first part of our multi-part series of articles, we summarise the importance of bioelectricity for the basic structural level of biological organization, i.e. from the subcellular level (charges, ion channels, molecules and cell organelles) to cells

An investigation of the loads on the vertical tail of a jet-bomber airplane resulting from flight through rough air

Vertical-tail loads were measured in turbulent air on a four-engine jet bomber. Results showed large load oscillations which were lightly damped. Comparison of experimental results with discrete-load calculations indicated that discrete-gust calculations underestimated the loads by 30 to 40 percent and gave no indication of the low damping. Power spectral analysis, on the other hand, indicated the general frequency characteristics and gave a somewhat better estimate of the peak-load distributions. The present results strongly suggest that discrete-gust calculation for gust loads on vertical tails may seriously underestimate the gust loads for airplanes having lightly damped lateral oscillations

Wirkung von Oberflächenladungen auf Zellen - Beobachtungen in der Nanodimension

Living organisms and in particular cells actively structure their inner world in the nano-dimension. Not only organelles are formed by the cells, but also their direct environment, the extracellular matrix. Recent studies show that electrical potentials are similarly important in the process of adhesion and directed migration. Nanostructured charge patterns may also influence the interactions between cells, tissues and implants used in therapy. Even small differences in the structure of charged molecules can already change the behaviour of cells drastically. Inside the cell, furthermore, very small topographic features are decisive: In ion channels, dimensions of 1/100 nm are essential for their function. Such precise structures are nowadays still a technical challenge. When modelling such cellular “electronics” using chip technology, we can learn a lot from nature’s tricks in cell physiology.Lebende Organismen und insbesondere die einzelnen Zellen selbst sind Meister in der aktiven Strukturierung auf Nanoebene. So bilden die Zellen nicht nur ihr reichhaltiges „Innenleben“ in dieser Dimension, sondern strukturieren auch ihre direkte Umgebung, den extrazellulären Bereich. Bei der Haftung und gerichteten Bewegung der Zellen scheinen nach neueren Befunden auch elektrische Potenziale und Oberflächenladungen mit Mustern bis „hinab“ auf die Nanoebene eine Rolle zu spielen. Nanostrukturierte Muster von Ladungen können so auch die Wechselwirkung von Zellen und Geweben mit Implantaten beeinflussen. Diese Beobachtungen führen wieder zurück zu den Zellen selbst, die zum Beispiel im Falle von Ionenkanälen mit hundertstel Nanometer Genauigkeit Topographie und Potenziale kontrollieren. Solche Strukturen könnten zukünftig auch über Chiptechnologie modelliert werden – eine Chance, von der Natur zu lernen und dies technisch umzusetzen

A target enrichment method for gathering phylogenetic information from hundreds of loci: An example from the Compositae.

UnlabelledPremise of the studyThe Compositae (Asteraceae) are a large and diverse family of plants, and the most comprehensive phylogeny to date is a meta-tree based on 10 chloroplast loci that has several major unresolved nodes. We describe the development of an approach that enables the rapid sequencing of large numbers of orthologous nuclear loci to facilitate efficient phylogenomic analyses. •Methods and resultsWe designed a set of sequence capture probes that target conserved orthologous sequences in the Compositae. We also developed a bioinformatic and phylogenetic workflow for processing and analyzing the resulting data. Application of our approach to 15 species from across the Compositae resulted in the production of phylogenetically informative sequence data from 763 loci and the successful reconstruction of known phylogenetic relationships across the family. •ConclusionsThese methods should be of great use to members of the broader Compositae community, and the general approach should also be of use to researchers studying other families

Local Calcium Elevation and Cell Elongation Initiate Guided Motility in Electrically Stimulated Osteoblast-Like Cells

BACKGROUND: Investigation of the mechanisms of guided cell migration can contribute to our understanding of many crucial biological processes, such as development and regeneration. Endogenous and exogenous direct current electric fields (dcEF) are known to induce directional cell migration, however the initial cellular responses to electrical stimulation are poorly understood. Ion fluxes, besides regulating intracellular homeostasis, have been implicated in many biological events, including regeneration. Therefore understanding intracellular ion kinetics during EF-directed cell migration can provide useful information for development and regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the initial events during migration of two osteogenic cell types, rat calvarial and human SaOS-2 cells, exposed to strong (10-15 V/cm) and weak (< or = 5 V/cm) dcEFs. Cell elongation and perpendicular orientation to the EF vector occurred in a time- and voltage-dependent manner. Calvarial osteoblasts migrated to the cathode as they formed new filopodia or lamellipodia and reorganized their cytoskeleton on the cathodal side. SaOS-2 cells showed similar responses except towards the anode. Strong dcEFs triggered a rapid increase in intracellular calcium levels, whereas a steady state level of intracellular calcium was observed in weaker fields. Interestingly, we found that dcEF-induced intracellular calcium elevation was initiated with a local rise on opposite sides in calvarial and SaOS-2 cells, which may explain their preferred directionality. In calcium-free conditions, dcEFs induced neither intracellular calcium elevation nor directed migration, indicating an important role for calcium ions. Blocking studies using cadmium chloride revealed that voltage-gated calcium channels (VGCCs) are involved in dcEF-induced intracellular calcium elevation. CONCLUSION/SIGNIFICANCE: Taken together, these data form a time scale of the morphological and physiological rearrangements underlying EF-guided migration of osteoblast-like cell types and reveal a requirement for calcium in these reactions. We show for the first time here that dcEFs trigger different patterns of intracellular calcium elevation and positional shifting in osteogenic cell types that migrate in opposite directions

Sutureless fixation of amniotic membrane for therapy of ocular surface disorders

Amniotic membrane is applied to the diseased ocular surface to stimulate wound healing and tissue repair, because it releases supportive growth factors and cytokines. These effects fade within about a week after application, necessitating repeated application. Generally, amniotic membrane is fixed with sutures to the ocular surface, but surgical intervention at the inflamed or diseased site can be detrimental. Therefore, we have developed a system for the mounting of amniotic membrane between two rings for application to a diseased ocular surface without surgical intervention (sutureless amniotic membrane transplantation). With this system, AmnioClip, amniotic membrane can be applied like a large contact lens. First prototypes were tested in an experiment on oneself for wearing comfort. The final system was tested on 7 patients in a pilot study. A possible influence of the ring system on the biological effects of amniotic membrane was analyzed by histochemistry and by analyzing the expression of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF) from amniotic membranes before and after therapeutic application. The final product, AmnioClip, showed good tolerance and did not impair the biological effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic membrane after storage and mounting before transplantation, but was undetectable after a 7-day application period. Consequently, transplantation of amniotic membranes with AmnioClip provides a sutureless and hence improved therapeutic strategy for corneal surface disorders

Potent Stimulation of Blood Flow in Fingers of Volunteers after Local Short-Term Treatment with Low-Frequency Magnetic Fields from a Novel Device

A novel hand-held low-frequency magnetic stimulator (MagCell-SR) was tested for its ability to stimulate microcirculation in fingers of healthy volunteers. Blood flow during and after 5 minutes exposure was quantified using Laser Doppler Perfusion Imaging Technique. The device was positioned between the wrist and the dorsal part of the backhand. Because the increase in blood flow could be caused by a release of nitric oxide (NO) from the vascular endothelial cells we tested NO production with a fluorescence marker and quantified the measurements in cell cultures of human umbilical endothelial cells (HUVEC). Exposure increased blood flow significantly, persisted several minutes, and then disappeared gradually. In order to assess the effect of a static magnetic field, the measurements were also carried out with the device shutoff. Here, only a small increase in blood flow was noted. The application of the rotating MagCell-SR to the HUVEC cultures leads to a rapid onset and a significant increase of NO release after 15 minutes. Thus, frequencies between 4 and 12 Hz supplied by the device improve microcirculation significantly. Therefore, this device can be used in all clinical situations where an improvement of the microcirculation is useful like in chronic wound healing deficits

Potent Stimulation of Blood Flow in Fingers of Volunteers after Local Short-Term Treatment with Low-Frequency Magnetic Fields from a Novel Device

A novel hand-held low-frequency magnetic stimulator (MagCell-SR) was tested for its ability to stimulate microcirculation in fingers of healthy volunteers. Blood flow during and after 5 minutes exposure was quantified using Laser Doppler Perfusion Imaging Technique. The device was positioned between the wrist and the dorsal part of the backhand. Because the increase in blood flow could be caused by a release of nitric oxide (NO) from the vascular endothelial cells we tested NO production with a fluorescence marker and quantified the measurements in cell cultures of human umbilical endothelial cells (HUVEC). Exposure increased blood flow significantly, persisted several minutes, and then disappeared gradually. In order to assess the effect of a static magnetic field, the measurements were also carried out with the device shutoff. Here, only a small increase in blood flow was noted. The application of the rotating MagCell-SR to the HUVEC cultures leads to a rapid onset and a significant increase of NO release after 15 minutes. Thus, frequencies between 4 and 12 Hz supplied by the device improve microcirculation significantly. Therefore, this device can be used in all clinical situations where an improvement of the microcirculation is useful like in chronic wound healing deficits

Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice

In patients with Parkinson's disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system

Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice

Pathological studies on Parkinson’s disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PDThis work was supported by the Fritz-Thyssen Foundation, theGerman Parkinson’s disease Society and by Amelia Jimenez Gomez as private dono