Crystal structure of quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni - Structural basis for substrate oxidation and electron transfer

Quinoprotein alcohol dehydrogenases are redox enzymes that participate in distinctive catabolic pathways that enable bacteria to grow on various alcohols as the sole source of carbon and energy. The x-ray structure of the quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni has been determined at 1.44 Angstrom resolution. It comprises two domains. The N-terminal domain has a beta-propeller fold and binds one pyrrolo-quinoliue quinone cofactor and one calcium ion in the active site. A tetrahydrofuran-2-carboxylic acid molecule is present in the substrate-binding cleft. The position of this oxidation product provides valuable information on the amino acid residues involved in the reaction mechanism and their function. The C-terminal domain is an a-helical type I cytochrome c with His(608) and Met(647) as heme-iron ligands. This is the first reported structure of an electron transfer system between a quinoprotein alcohol dehydrogenase and cytochrome c. The shortest distance between pyrroloquinoline quinone and heme c is 12.9 Angstrom, one of the longest physiological edge-to-edge distances yet determined between two redox centers. A highly unusual disulfide bond between two adjacent cysteines bridges the redox centers. It appears essential for electron transfer. A water channel delineates a possible pathway for proton transfer from the active site to the solvent.</p

Advanced Image Analysis for Modeling the Aging Brain

Both normal aging and neurodegenerative diseases such as Alzheimer’s disease (AD) cause morphological changes of the brain due to neurodegeneration. As neurodegeneration due to disease may be difficult to distinguish from that of normal aging, interpretation of magnetic resonance (MR) brain images in the context of diagnosis of neurodegenerative diseases is challenging, especially in the early stages of the disease. This thesis presented comprehensive models of the aging brain and novel computer-aided diagnosis methods, based on advanced, quantitative analysis of brain MR images, facilitating the differentiation between normal and abnormal neurodegeneration. I aimed to evaluate and develop methods for clinical decision support using features derived from MR brain images: I evaluated a classification method to predict global cognitive decline in the general population, evaluated five brain segmentation methods and developed a spatio-temporal model of morphological differences in the brain due to normal aging. To create this model I developed two novel techniques that allow performing non-rigid groupwise image registration on large imaging datasets. The novel aging brain models and computer-aided diagnosis methods facilitate the differentiation between normal and abnormal neurodegeneration. This will help in establishing more accurate diagnoses of patients, and in identifying patients at risk of developing neurodegenerative disease before symptoms emerge. In the future, the method’s performance and efficacy should be evaluated in clinical practice

Prevention of wound sepsis in amputations by peri-operative antibiotic cover with an amoxycillin-clavulanic acid combination

In a series of 44 patients with lower limb ischaemia requiring amputation for major limb sepsis, the performance of a new antibiotic combination with Blactamase- inhibiting properties, amoxycillin plus . clavulanic acid (A-CA) (Augmentin; Beecham), was compared with that of penicillin in the prevention of wound infection. The sepsis rate of ·12,9% in the group of patients receiving peri-operative A-CA was significantly lower than the 76,9% in the penicillin control group (x2 = 14,48; P&lt;O,OO1).lt is concluded that there is a need for peri-operative antibiotic cover in this situation and that A-CA appears to be highly effective. No statistical difference was found as regards development of sepsis in wounds closed primarily or left open while under A-CA cover

395 OSTEOPHYTES AND JOINT SPACE NARROWING ARE INDEPENDENTLY ASSOCIATED WITH PAIN IN FINGER JOINTS IN HAND OSTEOARTHRITIS

Objective To study the associations between structural abnormalities on ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis (HOA). Methods In 55 consecutive patients with HOA (mean age 61 years, 86% women) fulfilling the American College of Rheumatology criteria, pain in 30 separate hand joints was assessed upon palpation; osteophytes were assessed by US and CR and joint space narrowing (JSN) by CR. Associations between structural abnormalities and pain per joint were analysed using generalised estimated equations to account for patient effects and adjusted for age, sex, body mass index, US inflammatory features and other remaining structural abnormalities. Results In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively and 47% had JSN. Osteophytes and JSN showed independent associations with pain per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1 (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0). Conclusions Osteophytes and JSN are independently associated with pain in individual HOA joints, taking into account patient effects

Two lectures on the historical development of Dutch agriculture, 1600 - 1985

Twee lezingen, de een over het tijdvak 1600-1880 en de ander over 1880-1985, met historische achtergrondinformatie bedoeld voor buitenlander

Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis

PMCID: PMC3856490This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PMCID: PMC385649

Intrasubject multimodal groupwise registration with the conditional template entropy

Image registration is an important task in medical image analysis. Whereas most methods are designed for the registration of two images (pairwise registration), there is an increasing interest in simultaneously aligning more than two images using groupwise registration. Multimodal registration in a groupwise setting remains difficult, due to the lack of generally applicable similarity metrics. In this work, a novel similarity metric for such groupwise registration problems is proposed. The metric calculates the sum of the conditional entropy between each image in the group and a representative template image constructed iteratively using principal component analysis. The proposed metric is validated in extensive experiments on synthetic and intrasubject clinical image data. These experiments showed equivalent or improved registration accuracy compared to other state-of-the-art (dis)similarity metrics and improved transformation consistency compared to pairwise mutual information