Clues on black hole feedback from simulated and observed X-ray properties of elliptical galaxies

The centers of elliptical galaxies host supermassive black holes that significantly affect the surrounding interstellar medium through feedback resulting from the accretion process. The evolution of this gas and of the nuclear emission during the galaxies' lifetime has been studied recently with high-resolution hydrodynamical simulations. These included gas cooling and heating specific for an average AGN spectral energy distribution, a radiative efficiency declining at low mass accretion rates, and mechanical coupling between the hot gas and AGN winds. Here we present a short summary of the observational properties resulting from the simulations, focussing on 1) the nuclear luminosity; 2) the global luminosity and temperature of the hot gas; 3) its temperature profile and X-ray brightness profile. These properties are compared with those of galaxies of the local universe, pointing out the successes of the adopted feedback and the needs for new input in the simulations.Comment: 15 pages, 6 figures, accepted for publication in Advances in Space Researc

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

The first IRAM/PdBI polarimetric millimeter survey of active galactic nuclei. II. Activity and properties of individual sources

We present an analysis of the linear polarization of six active galactic nuclei - 0415+379 (3C~111), 0507+179, 0528+134 (OG+134), 0954+658, 1418+546 (OQ+530), and 1637+574 (OS+562). Our targets were monitored from 2007 to 2011 in the observatory-frame frequency range 80-253 GHz, corresponding to a rest-frame frequency range 88-705 GHz. We find average degrees of polarization m_L ~ 2-7%; this indicates that the polarization signals are effectively averaged out by the emitter geometries. We see indication for fairly strong shocks and/or complex, variable emission region geometries in our sources, with compression factors 10 deg. An analysis of correlations between source fluxes and polarization parameter points out special cases: the presence of (at least) two distinct emission regions with different levels of polarization (for 0415+379) as well as emission from a single, predominant component (for 0507+179 and 1418+546). Regarding the evolution of flux and polarization, we find good agreement between observations and the signal predicted by "oblique shock in jet" scenarios in one source (1418+546). We attempt to derive rotation measures for all sources, leading to actual measurements for two AGN and upper limits for three sources. We derive values of RM = -39,000 +/- 1,000 (stat) +/- 13,000 (sys) rad/m^2 and RM = 420,000 +/- 10,000 (stat) +/- 110,000 (sys) rad/m^2 for 1418+546 and 1637+574, respectively; these are the highest values reported to date for AGN. These values indicate magnetic field strengths of the order ~0.0001 G. For 0415+379, 0507+179, and 0954+658 we derive upper limits |RM| < 17,000 rad/m^2. From the relation |RM| ~ nu^a we find a = 1.9 +/- 0.3 for 1418+546, in good agreement with a = 2 as expected for a spherical or conical outflow.Comment: 23 pages, 8 figures, 4 tables. Accepted by Astronomy and Astrophysics. Minor language editing, one missing reference (Macquart et al. 2006) adde

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD

KLF15 Is a Molecular Link between Endoplasmic Reticulum Stress and Insulin Resistance

Obesity places major demands on the protein folding capacity of the endoplasmic reticulum (ER), resulting in ER stress, a condition that promotes hepatic insulin resistance and steatosis. Here we identify the transcription factor, Kruppel-like factor 15 (KLF15), as an essential mediator of ER stress-induced insulin resistance in the liver. Mice with a targeted deletion of KLF15 exhibit increased hepatic ER stress, inflammation, and JNK activation compared to WT mice; however, KLF15-/- mice are protected against hepatic insulin resistance and fatty liver under high-fat feeding conditions and in response to pharmacological induction of ER stress. The mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cellular energy homeostasis, has been shown to cooperate with ER stress signaling pathways to promote hepatic insulin resistance and lipid accumulation. We find that the uncoupling of ER stress and insulin resistance in KLF15-/- liver is associated with the maintenance of a low energy state characterized by decreased mTORC1 activity, increased AMPK phosphorylation and PGC-1α expression and activation of autophagy, an intracellular degradation process that enhances hepatic insulin sensitivity. Furthermore, in primary hepatocytes, KLF15 deficiency markedly inhibits activation of mTORC1 by amino acids and insulin, suggesting a mechanism by which KLF15 controls mTORC1-mediated insulin resistance. This study establishes KLF15 as an important molecular link between ER stress and insulin action

Target gene analyses of 39 amelogenesis imperfecta kindreds

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90297/1/EOS_857_sm_FigsS1-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90297/2/j.1600-0722.2011.00857.x.pd

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

The Micro-Pillar Shear-Stress Sensor MPS3 for Turbulent Flow

Wall-shear stress results from the relative motion of a fluid over a body surface as a consequence of the no-slip condition of the fluid in the vicinity of the wall. To determine the two-dimensional wall-shear stress distribution is of utter importance in theoretical and applied turbulence research. In this article, characteristics of the Micro-Pillar Shear-Stress Sensor MPS3, which has been shown to offer the potential to measure the two-directional dynamic wall-shear stress distribution in turbulent flows, will be summarized. After a brief general description of the sensor concept, material characteristics, possible sensor-structure related error sources, various sensitivity and distinct sensor performance aspects will be addressed. Especially, pressure-sensitivity related aspects will be discussed. This discussion will serve as ‘design rules’ for possible new fields of applications of the sensor technology

Development of a Quartz Crystal Microbalance Biosensor with Aptamers as Bio-recognition Element

The ultimate goal in any biosensor development project is its use for actual sample detection. Recently, there has been an interest in biosensors with aptamers as bio-recognition elements, but reported examples all deal with standards, not human serum. In order to verify the differences of aptamer-based biosensor and antibody-based biosensor in clinical detection, a comparison of the performance of aptamer-based and antibody-based quartz crystal microbalance (QCM) biosensors for the detection of immunoglobulin E (IgE) in human serum was carried out. Aptamers (or antibodies) specific to IgE were immobilized on the gold surface of a quartz crystal. The frequency shifts of the QCM were measured. The linear range with the antibody (10–240 μg/L) compared to that of the aptamer (2.5–200 μg/L), but a lower detection limit could be observed in the aptamer-based biosensor. The reproducibility of the two biosensors was comparable. The aptamers were equivalent or superior to antibodies in terms of specificity and sensitivity. In addition, the aptamer receptors could tolerate repeated affine layer regeneration after ligand binding and recycling of the biosensor with little loss of sensitivity. When stored for three weeks, the frequency shifts of the aptamer-coated crystals were all greater than 90% of those on the response at the first day