Identification of Protein Networks Involved in the Disease Course of Experimental Autoimmune Encephalomyelitis, an Animal Model of Multiple Sclerosis

A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE), a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE) followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4), a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1), involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and networks that warrant further research to study their actual contribution to disease pathology

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

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Understanding soft tissue behavior for microlaparoscopic surface scan

This paper presents an approach for understanding the soft-tissue behavior in surface contact with a probe scanning the tissue. The application domain is confocal microlaparoscopy, mostly used for imaging the outer surface of the organs in the abdominal cavity. The probe is swept over the tissue to collect sequential images to obtain a large field of view with mosaicking. The problem we address is that the tissue also moves with the probe due to its softness; therefore, the resulting mosaic is not in the same shape and dimension as traversed by the probe. Our approach is inspired by the finger slip studies and adapts the idea of load-slip phenomenon that explains the movement of the soft part of the finger when dragged on a hard surface. We propose the concept of loading-distance and perform measurements on beef liver and chicken breast tissues. We propose a protocol to determine the loading-distance prior to an automated scan and introduce an approach to compensate the tissue movement in raster scans. Our implementation and experiments show that we can have an image mosaic of the tissue surface in a desired rectangular shape with this approach

Thermal and hydrodynamic modelling of active catheters for interventional radiology.

Interventional radiologists desire to improve their operating tools such as catheters. Active catheters in which the tip is moved using shape memory alloy actuators activated using the Joule effect present a promising approach for easier navigation in the small vessels. However, the increase in temperature caused by this Joule effect must be controlled in order to prevent damage to blood cells and tissues. This paper is devoted to the simulation and experimental validation of a fluid-thermal model of an active catheter prototype. Comparisons between computer-predicted and experimentally measured temperatures are presented for both experiments in air and water at 37°C. Good agreement between the computational and experimental results is found, demonstrating the validity of the developed computer model. These comparisons enable us to highlight some important issues in the modelling process and to determine the optimal current for the activation of the catheter

Robotic Hand-Held Surgical Device: Evaluation of End-Effector's Kinematics and Development of Proof-of-Concept Prototypes

We are working towards the development of a robotic hand-held surgical device for laparoscopic interventions that enhances the surgeons' dexterity. In this paper, the kinematics of the end effector is studied. Different choices of kinematics are compared during an evaluation campaign using a virtual reality simulator to find the optimal one: the Yaw-Roll (YR) kinematics. A proof of concept prototype is made based on the results

Toward the Development of a Hand-Held Surgical Robot for Laparoscopy

Minimally invasive surgery (MIS), which typically involves endoscopic camera and laparoscopic instruments may seem to be the ideal surgical procedure for its apparent benefits. However, in comparison to open surgeries, the spatial and mechanical tool limitations posed on surgeons are so high that often MIS is foregone for complex cases and even when it is possible, the procedure requires a high dexterity, caliber, and experience from the surgeon. Particularly, suturing procedure through MIS is known to be extremely challenging. We are working toward the development of a robotic hand-held surgical device for laparoscopic interventions that enhances the surgeons' dexterity. The instrument produces two independent DOFs, which is sufficient for enabling MIS suturing procedure in vivo. The end-effector's orientation is controlled by an intuitive and ergonomic controller and its position is controlled directly by the surgeon. Different control modes, handles, and end-effector kinematics are primarily evaluated using a virtual reality simulator before choosing the best combination. A proof-of-concept prototype of the device has been developed