University of Groningen

About: University of Groningen is a education organization based out in Groningen, Groningen, Netherlands. It is known for research contribution in the topics: Population & Poison control. The organization has 36346 authors who have published 69116 publications receiving 2940370 citations. The organization is also known as: Rijksuniversiteit Groningen & RUG.

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Abstract: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

Systematic analysis of domain motions in proteins from conformational change: new results on citrate synthase and T4 lysozyme.

Abstract: Methods developed originally to analyze domain motions from simulation (Proteins 27:425-437, 1997) are adapted and extended for the analysis of X-ray conformers and for proteins with more than two domains. The method can be applied as an automatic procedure to any case where more than one conformation is available. The basis of the methodology is that domains can be recog- nized from the difference in the parameters governing their quasi-rigid body motion, and in particular their rotation vectors. A cluster- ing algorithm is used to determine clusters of rotation vectors corresponding to main-chain segments that form possible dynamic domains. Domains are accepted for further analysis on the basis of a ratio of interdomain to intrado- main fluctuation, and Chasles' theorem is used to determine interdomain screw axes. Finally residues involved in the interdomain motion are identified. The methodology is tested on citrate synthase and the M6I mutant of T4 lysozyme. In both cases new aspects to their conformational change are revealed, as are individual residues intimately involved in their dynamics. For citrate synthase the beta sheet is identified to be part of the hinging mecha- nism. In the case of T4 lysozyme, one of the four transitions in the pathway from the closed to the open conformation, furnished four dy- namic domains rather than the expected two. This result indicates that the number of dy- namic domains a protein possesses may not be a constant of the motion. Proteins 30:144-154,

Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative.

Abstract: A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.

Assessment of baroreceptor reflex sensitivity by means of spectral analysis.

Abstract: A method of determining baroreceptor reflex sensitivity is proposed that is based on spectral analysis of systolic pressure values and RR interval times, namely, the modulus (or gain) in the mid frequency band (0.07-0.14 Hz) between these two signals. Results using this method were highly correlated (0.94; n = 8) with results of the phenylephrine method. In addition, compared with the values for the preceding rest period, the modulus decreased during mental challenge, as might be expected from the literature.

Computational Lipidomics with insane: A Versatile Tool for Generating Custom Membranes for Molecular Simulations

Abstract: For simulations of membranes and membrane proteins, the generation of the lipid bilayer is a critical step in the setup of the system. Membranes comprising multiple components pose a particular challenge, because the relative abundances need to be controlled and the equilibration of the system may take several microseconds. Here we present a comprehensive method for building membrane containing systems, characterized by simplicity and versatility. The program uses preset, coarse-grain lipid templates to build the membrane, and also allows on-the-fly generation of simple lipid types by specifying the headgroup, linker, and lipid tails on the command line. The resulting models can be equilibrated, after which a relaxed atomistic model can be obtained by reverse transformation. For multicomponent membranes, this provides an efficient means for generating equilibrated atomistic models. The method is called insane, an acronym for INSert membrANE. The program has been made available, together with the complemen...