Glucose metabolism in patients with psoriasis.

BACKGROUND: Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. OBJECTIVES: Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. METHODS: We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. RESULTS: Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. CONCLUSIONS: The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.

The static local field correction of the warm dense electron gas: An ab initio path integral Monte Carlo study and machine learning representation.

The study of matter at extreme densities and temperatures as they occur in astrophysical objects and state-of-the-art experiments with high-intensity lasers is of high current interest for many applications. While no overarching theory for this regime exists, accurate data for the density response of correlated electrons to an external perturbation are of paramount importance. In this context, the key quantity is given by the local field correction (LFC), which provides a wave-vector resolved description of exchange-correlation effects. In this work, we present extensive new path integral Monte Carlo (PIMC) results for the static LFC of the uniform electron gas, which are subsequently used to train a fully connected deep neural network. This allows us to present a representation of the LFC with respect to continuous wave-vectors, densities, and temperatures covering the entire warm dense matter regime. Both the PIMC data and neural-net results are available online. Moreover, we expect the presented combination of ab initio calculations with machine-learning methods to be a promising strategy for many applications.

Phase Domain Walls in Weakly Nonlinear Deep Water Surface Gravity Waves.

We report a theoretical derivation, an experimental observation and a numerical validation of nonlinear phase domain walls in weakly nonlinear deep water surface gravity waves. The domain walls presented are connecting homogeneous zones of weakly nonlinear plane Stokes waves of identical amplitude and wave vector but differences in phase. By exploiting symmetry transformations within the framework of the nonlinear Schrödinger equation we demonstrate the existence of exact analytical solutions representing such domain walls in the weakly nonlinear limit. The walls are in general oblique to the direction of the wave vector and stationary in moving reference frames. Experimental and numerical studies confirm and visualize the findings. Our present results demonstrate that nonlinear domain walls do exist in the weakly nonlinear regime of general systems exhibiting dispersive waves.

Detection of unstable periodic orbits in mineralising geological systems.

Worldwide, mineral exploration is suffering from rising capital costs, due to the depletion of readily recoverable reserves and the need to discover and assess more inaccessible or geologically complex deposits. For gold exploration, this problem is particularly acute. We propose an innovative approach to mineral exploration and orebody characterisation, based on the analysis of geological core data as a spatial dynamical system, using the mathematical tools of dynamical system analysis. This approach is highly relevant for orogenic gold deposits, which-in contrast to systems formed at chemical equilibrium-exhibit many features of nonlinear dynamical systems, including episodic fluctuations on various length and time scales. Feedback relationships between thermo-chemical and deformation processes produce recurrent fluid temperatures and pressures and the deposition of vein-filling minerals such as pyrite and gold. We therefore relax the typical assumption of chemical equilibrium and analyse the underlying processes as aseismic, non-adiabatic, and inherent to a hydrothermal, nonlinear dynamical open-flow chemical reactor. These processes are approximated using the Gray-Scott model of reaction-diffusion as a complex toy system, which captures some of the features of the underlying mineralisation processes, including the spatiotemporal Turing patterns of unsteady chemical reactions. By use of this analysis, we demonstrate the capability of recurrence plots, recurrence power spectra, and recurrence time probabilities to detect underlying unstable periodic orbits as one sign of deterministic dynamics and their robustness for the analysis of data contaminated by noise. Recurrence plot based quantification is then applied to three mineral concentrations in the core data from the Sunrise Dam gold deposit in the Yilgarn region of Western Australia. Using a moving window, we reveal the episodic recurring low-dimensional dynamic structures and the period doubling route to instability with depth, embedded in and originating from higher-dimensional processes of the complex mineralisation system.

In situ starch and crude protein degradation in the rumen and in vitro gas production kinetics of wheat genotypes.

The objective of this study was to determine the variation of in situ ruminal degradation characteristics of dry matter (DM), crude protein (CP) and starch (ST), and to determine the effective degradation (ED) of wheat genotypes. Further, multivariate associations of these in situ values with their corresponding in vitro gas production (GP) kinetics and laboratory measurements were evaluated using correlation and multiple linear regression analyses. Grains of 20 genotypes of wheat were characterized by proximate constituents, amino acid (AA) composition and physical characteristics. Ruminal degradation kinetics were determined by in situ degradation of DM, CP and ST, and subsequent evaluation of in vitro GP relative to time courses. In situ and GP measurements were fitted to an exponential equation, and ED was calculated using passage rates in the rumen of 5%/h (ED5) and 8%/h (ED8). To predict ED8 of CP (EDCP8) and ST (EDST8), correlations were evaluated and stepwise multiple linear regression analyses were applied. Estimated degradation parameters varied considerably between wheat genotypes irrespective of the nutrient tested. Variance in a, b and c was not reflected in the variation of the ED, due to high degradation rates (c). The assumed passage rate also impacted estimation of the ED minimally. Estimated GP parameters varied only slightly among wheat genotypes. Nevertheless, regression models explained up to 80 and 99% of the variance in EDCP8 and EDST8, respectively, and associations between EDST8 and EDCP8 and chemical and physical characteristics of grains were detected. As ST is the primary nutrient in wheat grains and can comprise substantial portions of dairy rations, the total amount of ST as well as its ED in the rumen should be taken into account when wheat is incorporated into dairy rations. Conversely, variance in wheat grain CP degradation was very low and can largely be neglected in practical ration formulation for ruminants.

Hydrodynamic supercontinuum.

We report the experimental observation of multi-bound-soliton solutions of the nonlinear Schrödinger equation (NLS) in the context of hydrodynamic surface gravity waves. Higher-order N-soliton solutions with N=2, 3 are studied in detail and shown to be associated with self-focusing in the wave group dynamics and the generation of a steep localized carrier wave underneath the group envelope. We also show that for larger input soliton numbers, the wave group experiences irreversible spectral broadening, which we refer to as a hydrodynamic supercontinuum by analogy with optics. This process is shown to be associated with the fission of the initial multisoliton into individual fundamental solitons due to higher-order nonlinear perturbations to the NLS. Numerical simulations using an extended NLS model described by the modified nonlinear Schrödinger equation, show excellent agreement with experiment and highlight the universal role that higher-order nonlinear perturbations to the NLS play in supercontinuum generation.

Experimental observation of dark solitons on the surface of water.

We present the first ever observation of dark solitons on the surface of water. It takes the form of an amplitude drop of the carrier wave which does not change shape in propagation. The shape and width of the soliton depend on the water depth, carrier frequency, and the amplitude of the background wave. The experimental data taken in a water tank show an excellent agreement with the theory. These results may improve our understanding of the nonlinear dynamics of water waves at finite depths.

Streptomyces genus as a source of probiotics and its potential for its use in health.

The effect of a probiotic on gut microbiota depends not only on the species of microorganism but specifically on the strain. In human beings, as in other animals, specific probiotics have been associated with numerous beneficial properties, which include weight modulation (gain or loss), immune modulation, and prevention of many disorders such as lactose intolerance, cardiovascular diseases, and antibiotic-associated diarrhoea. Streptomyces are an essential group of soil bacteria in the Actinomycetes family. They are related to producing a wide range of secondary metabolites known for their beneficial effects on human health. However, according to the human microbiome analysis, a lower prevalence of Streptomyces genus exists than in other non-human microbiomes. This difference can be associated with current lifestyles. In this article, we review the benefits associated with different compounds produced by Streptomyces, with a particular focus on the production of exopolysaccharides, antibiotics, and other secondary metabolites and the potential innovative use of Streptomyces spp. as probiotics.

Enhanced gene delivery to the neonatal retina through systemic administration of tyrosine-mutated AAV9.

Delivery of therapeutic genes to a large region of the retina with minimal damage from intraocular surgery is a central goal of treatment for retinal degenerations. Recent studies have shown that AAV9 can reach the central nervous system (CNS) and retina when administered systemically to neonates, which is a promising strategy for some retinal diseases. We investigated whether the retinal transduction efficiency of systemically delivered AAV9 could be improved by mutating capsid surface tyrosines, previously shown to increase the infectivity of several AAV vectors. Specifically, we evaluated retinal transduction following neonatal intravascular administration of AAV9 vectors containing tyrosine to phenylalanine mutations at two highly conserved sites. Our results show that a novel, double tyrosine mutant of AAV9 significantly enhanced gene delivery to the CNS and retina, and that gene expression can be restricted to rod photoreceptor cells by incorporating a rhodopsin promoter. This approach provides a new methodology for the development of retinal gene therapies or creation of animal models of neurodegenerative disease.

[Undergraduate teaching of anaesthesiology : a nationwide survey in Germany]. / Universitäre Lehre der Anästhesiologie : Bestandsaufnahme in Deutschland.

BACKGROUND: In 2003 anaesthesiology was implemented as a compulsory speciality of undergraduate teaching in Germany due to the revised regulations of medical education. Besides the preexisting subject of emergency medicine an obligatory course in anaesthesiology was introduced. Thus anaesthesiology has gained considerable importance in all medical faculties. To gain insight into the current status of undergraduate medical education in the university departments of anaesthesiology a nationwide survey at all university departments in Germany was initiated. METHODS: In cooperation with the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) a standardized questionnaire was developed and sent to 36 departments of anaesthesiology of all German medical faculties. Questions concerned the structure of the respective curriculum, learning goals, teaching, assessment and evaluation methods as well as facultative courses. RESULTS: Of the 36 university departments of anaesthesiology, 35 returned the questionnaire. In 66% undergraduate education in anaesthesiology is part of the fourth or fifth year of medical training. In 91% of the faculties lectures were accompanied by teaching in small student groups. A simulator-based training is integrated either in anaesthesiology and/or in emergency medicine in 91% of the departments of anaesthesiology. In 69% of the departments contents of anaesthesia, critical care medicine, emergency medicine and pain management are an integral part of undergraduate teaching in anaesthesiology. The primary learning goals are directed towards general anaesthesia and there is less focus on topics of preoperative or postoperative care, such as preoperative risk evaluation, postoperative pain management and regional anaesthesia. Besides a multiple choice test (91%) oral (63%) and/or practical examinations (71%) are used as assessment tools. In 71% of the medical faculties the respective departments of anaesthesiology are leading and organising skills laboratories. In student evaluations anaesthesiology achieved best ranking in 66% of the medical faculties compared to other specialties. The possibility to take an elective course in anaesthesiology exists in 74% of the faculties. Half of these faculties organize this elective as a longitudinal course for one complete semester, the other half as a full time course over mostly 1 or 2 weeks. At present E-learning plays a minor role. CONCLUSIONS: This survey provides detailed information about the current status of undergraduate teaching of the university departments of anaesthesiology in Germany. The study shows a remarkable consistency of structure, contents and methods of education in anaesthesiology throughout all university departments of anaesthesiology. This information is the basis for triggering synergistic effects, for improving educational standards in anaesthesiology and for introducing a platform for developing modern learning media, e.g. through the scientific society DGAI.

Extreme wave excitation from localized phase-shift perturbations.

The modulation instability is a focusing mechanism responsible for the formation of strong wave localizations not only on the water surface, but also in a variety of nonlinear dispersive media. Such dynamics is initiated from the injection of sidebands, which translate into an amplitude modulation of the wave field. The nonlinear stage of unstable wave evolution can be described by exact solutions of the nonlinear Schrödinger equation (NLSE). In that case, the amplitude modulation of such coherent extreme wave structures is connected to a particular phase-shift seed in the carrier wave. In this Letter, we show that phase-shift localization applied to the background, excluding any amplitude modulation excitation, can indeed trigger extreme events. Such rogue waves can be for instance generated by considering the parametrization of fundamental breathers, and thus by seeding only the local phase-shift information to the regular carrier wave. Our wave tank experiments show an excellent agreement with the expected NLSE hydrodynamics and confirm that even though delayed in their evolution, breather-type extreme waves can be generated from a purely regular wave train. Such a focusing mechanism awaits experimental confirmation in other nonlinear media, such optics, plasma, and Bose-Einstein condensates.

Rogue wave observation in a water wave tank.

The conventional definition of rogue waves in the ocean is that their heights, from crest to trough, are more than about twice the significant wave height, which is the average wave height of the largest one-third of nearby waves. When modeling deep water waves using the nonlinear Schrödinger equation, the most likely candidate satisfying this criterion is the so-called Peregrine solution. It is localized in both space and time, thus describing a unique wave event. Until now, experiments specifically designed for observation of breather states in the evolution of deep water waves have never been made in this double limit. In the present work, we present the first experimental results with observations of the Peregrine soliton in a water wave tank.

Inheritance of functional foreign genes in plants.

Morphologically normal plants were regenerated from Nicotiana plumbaginifolia cells transformed with an Agrobacterium tumefaciens strain containing a tumor-inducing plasmid with a chimeric gene for kanamycin resistance. The presence of the chimeric gene in regenerated plants was demonstrated by Southern hybridization analysis, and its expression in plant tissues was confirmed by the ability of leaf segments to form callus on media containing kanamycin at concentrations that were normally inhibitory. Progeny derived from several transformed plants inherited the foreign gene in a Mendelian manner.

Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene.

A chimeric gene containing a cloned cDNA of the coat protein (CP) gene of tobacco mosaic virus (TMV) was introduced into tobacco cells on a Ti plasmid of Agrobacterium tumefaciens from which tumor inducing genes had been removed. Plants regenerated from transformed cells expressed TMV mRNA and CP as a nuclear trait. Seedlings from self-fertilized transgenic plants were inoculated with TMV and observed for development of disease symptoms. The seedlings that expressed the CP gene were delayed in symptom development and 10 to 60 percent of the transgenic plants failed to develop symptoms for the duration of the experiments. Increasing the concentration of TMV in the inoculum shortened the delay in appearance of symptoms. The results of these experiments indicate that plants can be genetically transformed for resistance to virus disease development.

Area at risk and viability after myocardial ischemia and reperfusion can be determined by contrast-enhanced cardiac magnetic resonance imaging.

BACKGROUND/AIMS: Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. METHODS: Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining. RESULTS: The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14-15%) while good agreement was present in group B. CONCLUSION: The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.

Lipidomics informatics for life-science.

Lipidomics encompasses analytical approaches that aim to identify and quantify the complete set of lipids, defined as lipidome in a given cell, tissue or organism as well as their interactions with other molecules. The majority of lipidomics workflows is based on mass spectrometry and has been proven as a powerful tool in system biology in concert with other Omics disciplines. Unfortunately, bioinformatics infrastructures for this relatively young discipline are limited only to some specialists. Search engines, quantification algorithms, visualization tools and databases developed by the 'Lipidomics Informatics for Life-Science' (LIFS) partners will be restructured and standardized to provide broad access to these specialized bioinformatics pipelines. There are many medical challenges related to lipid metabolic alterations that will be fostered by capacity building suggested by LIFS. LIFS as member of the 'German Network for Bioinformatics' (de.NBI) node for 'Bioinformatics for Proteomics' (BioInfra.Prot) and will provide access to the described software as well as to tutorials and consulting services via a unified web-portal.

CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells.

Tumor surveillance of natural killer (NK) cells is mediated by the cytotoxicity receptor natural-killer group 2 member D (NKG2D). Ligands for NKG2D are generally not expressed on healthy cells, but induced on the surface of malignant cells. To date, NKG2D ligand (NKG2D-L) induction was mainly described to depend on the activation of the DNA damage response, although the molecular mechanisms that regulate NKG2D-L expression remain largely unknown. Here, we show that the acetyltransferases CBP (CREB-binding protein) and p300 play a crucial role in the regulation of NKG2D-L on tumor cells. Loss of CBP/p300 decreased the basal cell surface expression of human ligands and reduced the upregulation of MICA/B and ULBP2 in response to histone deacetylase inhibitors or DNA damage. Furthermore, CBP/P300 deficiency abrogated the sensitivity of stressed cells to NK cell-mediated killing. CBP/p300 were also identified as major regulators of mouse NKG2D ligand RAE-1 in vitro and in vivo using the Eµ-Myc lymphoma model. Mechanistically, we observed an enhanced activation of the CBP/p300 binding transcription factor CREB (cAMP response element-binding protein) correlating to the NKG2D-L upregulation. Moreover, increased binding of CREB and CBP/p300 to NKG2D-L promoters and elevated histone acetylation were detectable. This study provides strong evidence for a major role of CBP and p300 in orchestrating NKG2D-L induction and consequently immunosurveillance of tumors in mice and humans. These findings might help to develop novel immunotherapeutic approaches against cancer.

Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction.

Studies with cGMP-dependent protein kinase I (cGK-I)-deficient human cells and mice demonstrated that cGK-I ablation completely disrupts the NO/cGMP pathway in vascular tissue, which indicates a key role of this protein kinase as a mediator of the NO/cGMP action. Analysis of the vasodilator-stimulated phosphoprotein phosphorylated at serine 239 (P-VASP) is a useful tool to monitor cGK-I activation in platelets and cultured endothelial and smooth muscle cells. Therefore, we investigated whether endothelial dysfunction and/or vascular NO bioavailability is reflected by decreased vessel wall P-VASP and whether improvement of endothelial dysfunction restores this P-VASP. Incubation of aortic tissue from New Zealand White Rabbits with the NOS inhibitor N:(G)-nitro-Ld-arginine and endothelial removal strikingly reduced P-VASP. Oxidative stress induced by inhibition of CuZn superoxide dismutase increased superoxide and decreased P-VASP. Endothelial dysfunction in hyperlipidemic Watanabe rabbits (WHHL) was associated with increased vascular superoxide and with decreased P-VASP. Treatment of WHHL with AT(1) receptor blockade improved endothelial dysfunction, reduced vascular superoxide, increased vascular NO bioavailability, and increased P-VASP. Therefore, the level of vessel P-VASP closely follows changes in endothelial function and vascular oxidative stress. P-VASP is suggested to represent a novel biochemical marker for monitoring the NO-stimulated sGC/cGK-I pathway and endothelial integrity in vascular tissue.

Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture.

OBJECTIVES: This study sought to 1) assess in vivo release of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary circulation after vascular injury in human subjects; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs). BACKGROUND: Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointimal response to vascular injury. To date, no study has shown biologically active growth factors within the coronary circulation after vascular injury in human subjects. METHODS: In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min after angioplasty. In five patients undergoing atherectomy, coronary sinus serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributable to PDGF and bFGF was determined using neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized within the atherectomy tissue using immunocytochemical analysis. RESULTS: Before angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients scheduled for angioplasty compared with those in control patients (p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue. CONCLUSIONS: The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.