Oligodendrocytes, BK channels and the preservation of myelin

Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2+-activated K+ channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies

Oligodendrocytes, BK channels and remyelination [version 1; peer review: awaiting peer review]

Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2+-activated K+ channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies

Oligodendrocytes, BK channels and the preservation of myelin.

Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2 +-activated K + channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies

LANDSLIDE EVOLUTION PATTERN REVEALED BY MULTI-TEMPORAL DSMS OBTAINED FROM HISTORICAL AERIAL IMAGES

Abstract. Landslides are a widespread natural hazard that cause damages to people and to the built up environment. Accurate knowledge of landslide distribution is crucial to develop planning strategies, prevention and resilient communities worldwide. One of the most diffuse way of reporting landslides distribution in a territory is by preparing landslide inventory maps. Such a task is mostly accomplished by expert photo-interpretation of historical aerial photographs, which are an invaluable source of information because they portray the landscape when the anthropic pressure was lower than the present day, providing an observation of the landscape closer to the natural conditions. Despite such a common use of aerial photographs, they are poorly exploited to obtain quantitative measures to support landslide mapping activities. In this paper we present a comparison of two photogrammetric approaches to measure elevation changes in a 50-years period for an area densely affected by landslides in Southern Italy. The obtained results allowed to revisit the original expert mapping proving that such a method is a useful tool to support geomorphological mapping and to improve the overall accuracy of landslide inventories

EVALUATION OF PHOTOGRAMMETRIC BLOCK ORIENTATION USING QUALITY DESCRIPTORS FROM STATISTICALLY FILTERED TIE POINTS

Due to the increasing number of low-cost sensors, widely accessible on the market, and because of the supposed granted correctness of the semi-automatic workflow for 3D reconstruction, highly implemented in the recent commercial software, more and more users operate nowadays without following the rigorousness of classical photogrammetric methods. This behaviour often naively leads to 3D products that lacks metric quality assessment. This paper proposes and analyses an approach that gives the users the possibility to preserve the trustworthiness of the metric information inherent in the 3D model, without sacrificing the automation offered by modern photogrammetry software. At the beginning, the importance of Data Quality Assessment is outlined, together with some recall of photogrammetry best practices. With the purpose of guiding the user through a correct pipeline for a certified 3D model reconstruction, an operative workflow is proposed, focusing on the first part of the object reconstruction steps (tie-points extraction, camera calibration, and relative orientation). A new GUI (Graphical User Interface) developed for the open source MicMac suite is then presented, and a sample dataset is used for the evaluation of the photogrammetric block orientation using statistically obtained quality descriptors. The results and the future directions are then presented and discussed

The results of a non-destructive site exploration and a rescue excavation at the site of Pusztaszabolcs-Dohányos völgy északi part

It is only possible in rare cases to compare aerial photographs, fieldwork data, surveys of two types of magnetometer measurements, and metal detector surveys of a site with the results of a previous rescue excavation. The cooperation of the Castle Headquaters Integrated Developement Centre, the Szent István Király Museum of Székesfehérvár, and the Institute of Archaeological Sciences at the Eötvös Loránd University made the discovery of the multi-period site on the outskirts of Pusztaszabolcs possible

SIMULATION AND ANALYSIS OF PHOTOGRAMMETRIC UAV IMAGE BLOCKS: INFLUENCE OF CAMERA CALIBRATION ERROR

Unmanned aerial vehicles (UAV) are increasingly used for topographic mapping. The camera calibration for UAV image blocks can be performed a priori or during the bundle block adjustment (self-calibration). For an area of interest with flat, corridor configuration, the focal length of camera is highly correlated with the height of camera. Furthermore, systematic errors of camera calibration accumulate on the longer dimension and cause deformation. Therefore, special precautions must be taken when estimating camera calibration parameters. In this paper, a simulated, error-free aerial image block is generated. error is then added on camera calibration and given as initial solution to bundle block adjustment. Depending on the nature of the error and the investigation purpose, camera calibration parameters are either fixed or re-estimated during the bundle block adjustment. The objective is to investigate how certain errors in the camera calibration impact the accuracy of 3D measurement without the influence of other errors. All experiments are carried out with Fraser camera calibration model being employed. When adopting a proper flight configuration, an error on focal length for the initial camera calibration can be corrected almost entirely during bundle block adjustment. For the case where an erroneous focal length is given for pre-calibration and not re-estimated, the presence of oblique images limits the drift on camera height hence gives better camera pose estimation. Other than that, the error on focal length when neglecting its variation during the acquisition (e.g., due to camera temperature increase) is also investigated; a bowl effect is observed when one focal length is given in camera pre-calibration to the whole image block. At last, a local error is added in image space to simulate camera flaws; this type of error is more difficult to be corrected with the Fraser camera model and the accuracy of 3D measurement degrades substantially

Infection of hamsters with the UK Clostridium difficile ribotype 027 outbreak strain R20291

Clostridium difficile is the main cause of antibiotic-associated disease, a disease of high socio-economical importance that has recently been compounded by the global spread of the 027 (BI/NAP1/027) ribotype. C. difficile cases attributed to ribotype 027 strains have high recurrence rates (up to 36 %) and increased disease severity. The hamster model of infection is widely accepted as an appropriate model for studying aspects of C. difficile host–pathogen interactions. Using this model we characterized the infection kinetics of the UK 2006 outbreak strain, R20291. Hamsters were orally given a dose of clindamycin, followed 5 days later with 10 000 C. difficile spores. All 100 % of the hamsters succumbed to infection with a mean time to the clinical end point of 46.7 h. Colonization of the caecum and colon were observed 12 h post-infection reaching a maximum of approximately 3×104 c.f.u. per organ, but spores were not detected until 24 h post-infection. At 36 h post-infection C. difficile numbers increased significantly to approximately 6×107 c.f.u. per organ where numbers remained high until the clinical end point. Increasing levels of in vivo toxin production coincided with increases in C. difficile numbers in organs reaching a maximum at 36 h post-infection in the caecum. Epithelial destruction and polymorphonuclear leukocyte (PMN) recruitment occurred early on during infection (24 h) accumulating as gross microvilli damage, luminal PMN influx, and blood associated with mucosal muscle and microvilli. These data describe the fatal infection kinetics of the clinical UK epidemic C. difficile strain R20291 in the hamster infection model