The structure of human Procathepsin S: crystallographic investigations on the functional role of the propeptide

In dieser Arbeit wird die Struktur einer kristallisierten menschlichen Procathepsin S Mutante (Cys25->Ala), in der das Cystein im aktiven Zentrum zur Herstellung einer inaktiven Mutante ausgetauscht wurde, vorgestellt. Als Vorläufermolekül der lysosomalen Cystein-Proteinase Cathepsin S gewährt die aufgeklärte Struktur Einblicke in die Wechselwirkungen zwischen Enzymdomänen und der N-terminalen Prodomäne (Propeptid), die die katalytische Aktivität des Enzyms blockiert und darüberhinaus als Faltungskatalysator für die Enzymdomänen agiert. Trotz einer hohen strukturellen Übereinstimmung zwischen Procathepsin S und anderen Procathepsinen der gleichen Unterfamilie (L-Cathepsine) konnten Cathepsin S spezifische Interaktionen zwischen Propeptid und Enzym nachgewiesen werden, die die Gruppenspezifität des Cathepsin S Propeptids als Inhibitor einerseits, und die mehr selektive Hemmung verwandter Enzym Propeptide gegenüber ihrer Mutterenzyme andererseits, erklärt. Darüberhinaus wird eine neuartige Methode zur Kristallisation des Cathepsin S Propeptids vorgestellt. Aufgrund der Beteiligung des Cathepsin S an der Immunantwort, Tumorausbreitung und an Autoimmunerkrankungen liegt das Interesse in der Entwicklung von pharmakologisch wirksamen Inhibitoren, die sich möglicherweise von Propeptiden ableiten lassen, wobei die Procathepsin S Struktur weitere wichtige Informationen dazu liefert

Model Reduction for Multiscale Lithium-Ion Battery Simulation

In this contribution we are concerned with efficient model reduction for multiscale problems arising in lithium-ion battery modeling with spatially resolved porous electrodes. We present new results on the application of the reduced basis method to the resulting instationary 3D battery model that involves strong non-linearities due to Buttler-Volmer kinetics. Empirical operator interpolation is used to efficiently deal with this issue. Furthermore, we present the localized reduced basis multiscale method for parabolic problems applied to a thermal model of batteries with resolved porous electrodes. Numerical experiments are given that demonstrate the reduction capabilities of the presented approaches for these real world applications

Consolidation of the postural set during voluntary intermittent light finger contact as a function of hand dominance

Light fingertip contact with an earth-fixed referent decreases body sway. In a previous study Johannsen et al. (2014) demonstrated longer return-to-baseline of body sway for intermittent contacts of more than 2 seconds duration. This indicates that sway reduction with light tactile contact involves postural control strategies independent of the availability of tactile feedback and may depend on the intention to control body sway with light touch feedback. In the present study, we investigated the effect of hand dominance on post-contact return-to-baseline to probe for potential inter-hemispheric differences in the utilization of light finger contact for sway control. Twelve healthy, right-handed young adults stood in normal bipedal stance with eyes closed on a force plate with an earth-fixed referent directly in front. Acoustic signals instructed onset and removal of intermittent light touch. We found that return-to-baseline of sway following longer contact durations is affected by hand dominance with the dominant hand resulting in a slower return to No-contact levels of sway. Our results indicate that the light touch postural set is more persistent and might need longer to disengage when established with the dominant hand or takes longer to consolidate when established with the non-dominant hand

Ressourceneffiziente Realisierung pulscodierter neuronaler Netze

Tim KaulmannPaderborn, Univ., Diss., 200

Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls

Inflammatory bowel diseases (IBDs) are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis) and additional parts of the digestive tract (Crohn’s disease). Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α), and boosting the bodies’ own antioxidant status (HO-1, SOD, and GPx). Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia), short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD

Serving performance in a suprapostural visual signal detection task: context-dependent and direction-specific control of body sway with fingertip light touch

Keeping gaze fixed on a target during visual smooth pursuit or touch light during fingertip contact while standing may resemble the goals of a suprapostural task with the implicit demands to minimize self-imposed sensorimotor variability. To test whether the principle of a suprapostural task generalizes to more complex sensorimotor stimulus-response mappings, we investigated how the control of body sway is influenced by an implicit feedback coupling (IFC) between the variability of touch forces at the contact point and perceptual difficulty, that is vertical jitter of a horizontally oscillating Landolt-C, in a visual signal detection task (VSDT). Mediolateral (ML) body sway of ten young healthy adults was assessed in four IFC conditions: (1) LT with independent jitter (LT-IJ), (2) LT with jitter depending on LT contact force (LT-CF), (3) LT with jitter depending on body sway (LT-BS), and (4) no contact with jitter depending on body sway (NT-BS). We assumed that the postural control system would be responsive to IFC and therefore reduce body sway in both IFC conditions. Resulting mediolateral body sway differed between the IFC conditions. Reduced sway was found in LT-CF and LT-BS compared to LT-IJ and in LT-BS compared to NT-BS. Our results demonstrate that processes controlling body sway can reduce postural variability below a variability level achieved by LT augmentation of body sway-related feedback alone. Both direct (LT-CF) and indirect (LT-BS) IFC involvement of fingertip contact minimized sway, which implies that no hierarchy existed for whole body sway or precision of fingertip contact (integration of both control processes) or that they can be reversed flexibly (one facilitating the other) if it serves the implicit goal of reduced perceptual noise and enhanced performance within the context of our suprapostural VSDT