Mitochondria: Sovereign of inflammation?

NLRP3 inflammasome-dependent inflammatory responses are triggered by a variety of signals of host danger, including infection, tissue damage and metabolic dysregulation. How these diverse activators cause inflammasome activation is poorly understood. Recent data suggest that the mitochondria integrate these distinct signals and relay this information to the NLRP3 inflammasome. Dysfunctional mitochondria generate ROS, which is required for inflammasome activation. On the contrary, the NLRP3 inflammasome is negatively regulated by autophagy, which is a catabolic process that removes damaged or otherwise dysfunctional organelles, including mitochondria. In addition to the processing and secretion of pro-inflammatory cytokines such as IL-1β, NLRP3 inflammasome activation also influences cellular metabolic pathways such as glycolysis and lipogenesis. Mapping the connections between mitochondria, metabolism and inflammation is of great interest, as malfunctioning of this network is associated with many chronic inflammatory diseases.

Pore space analysis of beech wood: The vessel network

Water transport in wood is vital for the survival of trees. With synchrotron radiation X-ray tomographic microscopy (SRXTM), it has become possible to characterize and quantify the three-dimensional (3D) network formed by vessels that are responsible for longitudinal transport. In the present study, the spatial size dependence of vessels and the organization inside single growth rings in terms of vessel-induced porosity was studied by SRXTM. Network characteristics, such as connectivity, were deduced by digital image analysis from the processed tomographic data and related to known complex network topologies.

Debris flow susceptibility mapping at a regional scale

Debris flow susceptibility mapping at a regional scale has been the subject of various studies. The complexity of the phenomenon and the variability of local controlling factors limit the use of process-based models for a first assessment. GISbased approaches associating an automatic detection of the source areas and a simple assessment of the debris flow spreading may provide a substantial basis for a preliminary susceptibility assessment at the regional scale. The use of a digital elevation model, with a 10 m resolution, for the Canton de Vaud territory (Switzerland), a lithological map and a land use map, has allowed automatic identification of the potential source areas. The spreading estimates are based on basic probabilistic and energy calculations that allow to define the maximal runout distance of a debris flow.

A Modulated Closed Form solution for Quantitative Susceptibility Mapping - A thorough evaluation and comparison to iterative methods based on edge prior knowledge.

The aim of this study is to perform a thorough comparison of quantitative susceptibility mapping (QSM) techniques and their dependence on the assumptions made. The compared methodologies were: two iterative single orientation methodologies minimizing the l2, l1TV norm of the prior knowledge of the edges of the object, one over-determined multiple orientation method (COSMOS) and anewly proposed modulated closed-form solution (MCF). The performance of these methods was compared using a numerical phantom and in-vivo high resolution (0.65mm isotropic) brain data acquired at 7T using a new coil combination method. For all QSM methods, the relevant regularization and prior-knowledge parameters were systematically changed in order to evaluate the optimal reconstruction in the presence and absence of a ground truth. Additionally, the QSM contrast was compared to conventional gradient recalled echo (GRE) magnitude and R2* maps obtained from the same dataset. The QSM reconstruction results of the single orientation methods show comparable performance. The MCF method has the highest correlation (corrMCF=0.95, r(2)MCF =0.97) with the state of the art method (COSMOS) with additional advantage of extreme fast computation time. The l-curve method gave the visually most satisfactory balance between reduction of streaking artifacts and over-regularization with the latter being overemphasized when the using the COSMOS susceptibility maps as ground-truth. R2* and susceptibility maps, when calculated from the same datasets, although based on distinct features of the data, have a comparable ability to distinguish deep gray matter structures.

SYSGENET: a meeting report from a new European network for systems genetics.

The first scientific meeting of the newly established European SYSGENET network took place at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, April 7-9, 2010. About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. In addition, the future of GRP resources and phenotyping in Europe was discussed.

Advanced mapping of environmental data: Geostatistics, Machine Learning and Bayesian Maximum Entropy

This book combines geostatistics and global mapping systems to present an up-to-the-minute study of environmental data. Featuring numerous case studies, the reference covers model dependent (geostatistics) and data driven (machine learning algorithms) analysis techniques such as risk mapping, conditional stochastic simulations, descriptions of spatial uncertainty and variability, artificial neural networks (ANN) for spatial data, Bayesian maximum entropy (BME), and more.

Functional mapping of the human visual cortex with intravoxel incoherent motion MRI.

Functional imaging with intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is demonstrated. Images were acquired at 3 Tesla using a standard Stejskal-Tanner diffusion-weighted echo-planar imaging sequence with multiple b-values. Cerebro-spinal fluid signal, which is highly incoherent, was suppressed with an inversion recovery preparation pulse. IVIM microvascular perfusion parameters were calculated according to a two-compartment (vascular and non-vascular) diffusion model. The results obtained in 8 healthy human volunteers during visual stimulation are presented. The IVIM blood flow related parameter fD* increased 170% during stimulation in the visual cortex, and 70% in the underlying white matter.

Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network.

Postnatal glucocorticoid treatment of preterm infants was mimicked by treating newborn rats with dexamethasone (0.1-0.01 microg/g, days 1-4). This regimen has been shown to cause delayed alveolarization. Knowing that microvascular maturation (transformation of double- to single-layered capillary networks in alveolar septa) and septal thinning prevent further alveolarization, we measured septal maturation on electron photomicrographs in treated and control animals. In treated rats and before day 10, we observed a premature nonreversing microvascular maturation and a transient septal thinning, which both appeared focally. In vascular casts of both groups, we observed contacts between the two capillary layers of immature alveolar septa, which were predictive for capillary fusions. Studying serial electron microscopic sections of human lungs, we were able to confirm the postulated fusion process for the first time. We conclude that alveolar microvascular maturation indeed occurs by capillary fusion and that the dexamethasone-induced impairment of alveolarization is associated with focal premature capillary fusion.

The Swiss Early Psychosis Project SWEPP: a national network.

Aim: The study aims to describe the activities of the Swiss Early Psychosis Project (SWEPP) which was founded in 1999 as a national network to further and disseminate knowledge on early psychosis (EP) and to enhance collaboration between healthcare groups. Methods: The present paper is a detailed account of the initiation and the development of the Swiss network. We describe all activities such as the several educational campaigns that were addressed to primary and secondary care groups since the early days. We also provide an overview of the current status of EP services throughout the country. Results: Today, most regions in Switzerland provide specialized EP inpatient and/or outpatient services with a clinical or combined clinical research approach that targets at-risk and/or first-episode populations. Some more recently initiated EP services have been launched as collaborative models between several local or regional psychiatric services. Conclusions: The increasing number of EP services and experts in Switzerland may mirror the catalyzing contribution of the Swiss Early Psychosis Project in this important field of health care. The country's small size and the increasing density of specialized services provide excellent bases for larger-scale networking activities in the future, both in clinical and research areas.

Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance.

Accumulating evidence suggests that changes in the metabolic signature of astrocytes underlie their response to neuroinflammation, but how proinflammatory stimuli induce these changes is poorly understood. By monitoring astrocytes following acute cortical injury, we identified a differential and region-specific remodeling of their mitochondrial network: while astrocytes within the penumbra of the lesion undergo mitochondrial elongation, those located in the core-the area invaded by proinflammatory cells-experience transient mitochondrial fragmentation. In brain slices, proinflammatory stimuli reproduced localized changes in mitochondrial dynamics, favoring fission over fusion. This effect was triggered by Drp1 phosphorylation and ultimately resulted in reduced respiratory capacity. Furthermore, maintenance of the mitochondrial architecture critically depended on the induction of autophagy. Deletion of Atg7, required for autophagosome formation, prevented the reestablishment of tubular mitochondria, leading to marked reactive oxygen species accumulation and cell death. Thus, our data reveal autophagy to be essential for regenerating astrocyte mitochondrial networks during inflammation.

Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans.

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2 weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3.9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p<0.001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17.0, 13.8, 24.9 L/min respectively) vs. control (8.4 L/min) and was associated with significant (p<0.05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem.