Genetic Fingerprint of Immunosuppression Following Half-marathon Running in Microarray Study

ABSTRACT Introduction: An acute bout of exhaustive exercise such as marathon or half-marathon running can interfere with immunity, reflected by transient immunosuppression and inflammation like reaction following the event. To gain more insights into these mechanisms, the capacity of whole blood cultures in profiling gene expression in response to endotoxin (LPS) was studied in athletes before, 30min after, 3h after and 24h after a half-marathon run. Methods: Four well trained men and 4 well trained women participated and gene expression patterns were assessed in LPS-stimulated (1h) and unstimulated whole blood using Affymetrix GeneChip microarrays. Results: exercise significantly altered several genes in LPS-stimualted and unstimulated blood cultures of male and female athletes. A row of genes with prominent anti-inflammatory function were strongly up-regulated in unstimulated cultures in both sexes (ARG-1, SOCS3, DUSP-1, BMX, GOS2, CD177, and GJB6). In the same cultures a row of highly inflammatory and apoptotic genes were down-regulated (Granzymes A-M-B-K-H, PRF1, SPON2, Granulysin, KLRF1, PLEKHF1). Some of these genes which were significantly up-or down-regulated in unstimulated cultures were also strongly regulated in LPS-stimulated cultures (GJB6, ARG-1, ORM2, KLRF1, TRA@///TRD@, Granzymes, SPON2). In addition, there were some strongly regulated genes which could only be detected in LPS-stimulated cultures but not in unstimulated cultures. Among these, TNIP3, PLAU, HIVEP1, and SLED were up-regulated and IFN-β, IFN-γ, L-12B, CXCL4. CXCL10 and TRAF1 were significantly down-regulated. Conclusion: there is a row of genes which are strongly regulated through exercise but can only be detected in (endotoxin) stimulated cultures. This is direct evidence showing that the response to pathogens is strongly down-regulated following prolonged exhaustive exercise through different ways

Beating the confusion limit: The necessity of high angular resolution for probing the physics of Sagittarius A* and its environment: Opportunities for LINC-NIRVANA (LBT), GRAVITY (VLTI) and and METIS (E-ELT)

The super-massive 4 million solar mass black hole (SMBH) SgrA* shows variable emission from the millimeter to the X-ray domain. A detailed analysis of the infrared light curves allows us to address the accretion phenomenon in a statistical way. The analysis shows that the near-infrared flux density excursions are dominated by a single state power law, with the low states of SgrA* limited by confusion through the unresolved stellar background. We show that for 8-10m class telescopes blending effects along the line of sight will result in artificial compact star-like objects of 0.5-1 mJy that last for about 3-4 years. We discuss how the imaging capabilities of GRAVITY at the VLTI, LINC-NIRVANA at the LBT and METIS at the E-ELT will contribute to the investigation of the low variability states of SgrA*.Comment: 19 pages, 5 figure, Conf. Proc. SPIE Astronomical Telescopes + Instrumentation 1 - 6 July 2012. Amsterdam No. 8445-

First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&

Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Pancreatic secretion can be influenced by cholecystokinin (CCK) either directly via actions on acinar cells or indirectly via actions on nerves. The presence and functional roles of CCK receptors on human pancreatic acinar cells remains unclear. In the current study human pancreatic acini were isolated and then treated with CCK-8, gastrin and/or carbachol. Functional parameters were measured including intracellular [Ca2+] and amylase secretion. It was observed that human acini did not respond to CCK agonists but did respond to carbachol with robust increases in functional parameters. Adenoviral-mediated gene transfer of CCK1 or CCK2 receptors to the human cells resulted in cell responses to CCK agonists. In order to determine the reason for the lack of responsiveness of the human acini, expression of receptor mRNAs was determined using quantitative RT-PCR and localized by in situ hybridization. mRNA levels for CCK1 receptors were ∼30 times lower than those of CCK2 receptors, which were ∼10 times lower than those of m3 Ach receptors as measured by quantitative PCR. Neither CCK1 nor CCK2 receptors were localized in adult human pancreas by i n situ hybridization. These results indicate that human pancreatic acinar cells do not respond directly to CCK receptor activation and this is likely due to an insufficient level of receptor expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73903/1/j.1600-0773.2002.910610.x.pd

Radiolabeled CCK/gastrin peptides for imaging and therapy of CCK2 receptor-expressing tumors

Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, like medullary thyroid carcinomas, small cell lung cancers and stromal ovarian cancers. The specific receptor-binding property of the endogenous ligands for these receptors can be exploited by labeling peptides with a radionuclide and using these as carriers to guide the radioactivity to the tissues that express the receptors. In this way, tumors can be visualized using positron emission tomography and single photon emission computed tomography imaging. A variety of radiolabeled CCK/gastrin-related peptides has been synthesized and characterized for imaging. All peptides have the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-Phe-NH2 in common or derivatives thereof. This review focuses on the development and application of radiolabeled CCK/gastrin peptides for radionuclide imaging and radionuclide therapy of tumors expressing CCK receptors. We discuss both preclinical studies as well as clinical studies with CCK and gastrin peptides

Constructing a new understanding of the environment under postsocialism

This paper introduces a special grouping of papers on the theme of the environment and postsocialism. After the collapse of state socialism in Europe between 1989 and 1991, many immediate approaches to environmental reconstruction assumed that economic liberalisation and democratisation would alleviate problems. Since then, critics have argued that these proposed solutions were themselves problematic, and too closely reflected Western European and North American conceptions of environmental quality and democracy. The result has been a counterreaction focusing on detail and specificity at national levels and below. In this paper, we summarise debates about the environment and postsocialism since the period 1989 - 91. In particular, we examine whether an essentialistic link can be made between state socialism and environmental problems, and how far civil society -- or environmentalism -- may result in an improvement in perceived environmental quality. Finally, we consider the possibility for developing an approach to the environment and postsocialism that lies between crude generalisation and microscale studies

Accretion-ejection morphology of the microquasar SS 433 resolved at sub-au scale

This is the author accepted manuscript. the final version is available from EDP Sciences via the DOI in this recordWe present the first optical observation of the microquasar SS 433 at sub-milliarcsecond (mas) scale obtained with the GRAVITY instrument on the Very Large Telescope interferometer (VLTI). The 3.5-h exposure reveals a rich K-band spectrum dominated by hydrogen Brγand He i lines, as well as (red-shifted)emission lines coming from the jets. The K-band-continuum-emitting region is dominated by a marginally resolved point source (<1 mas) embedded inside a diffuse background accounting for 10% of the total flux. The jet line positions agree well with the ones expected from the jet kinematic model, an interpretation also supported by the consistent sign (i.e., negative/positive for the receding/approaching jet component) of the phase shifts observed in the lines. The significant visibility drop across the jet lines, together with the small and nearly identical phases for all baselines, point toward a jet that is offset by less than 0.5 mas from the continuum source and resolved in the direction of propagation, with a typical size of 2 mas. The jet position angle of ~80° is consistent with the expected one at the observation date. Jet emission so close to the central binary system would suggest that line locking, if relevant to explain the amplitude and stability of the 0.26c jet velocity, operates on elements heavier than hydrogen. The Brγprofile is broad and double peaked. It is better resolved than the continuum and the change of the phase signal sign across the line on all baselines suggests an East-West-oriented geometry similar to the jet direction and supporting a (polar) disk wind origin.Centre National d’Etudes Spatiales (CNES)Programme National Hautes Energies (PNHE)Humboldt FoundationNAS

The group II intron ribonucleoprotein precursor is a large, loosely packed structure

Group II self-splicing introns are phylogenetically diverse retroelements that are widely held to be the ancestors of spliceosomal introns and retrotransposons that insert into DNA. Folding of group II intron RNA is often guided by an intron-encoded protein to form a catalytically active ribonucleoprotein (RNP) complex that plays a key role in the activity of the intron. To date, possible structural differences between the intron RNP in its precursor and spliced forms remain unexplored. In this work, we have trapped the native Lactococcus lactis group II intron RNP complex in its precursor form, by deleting the adenosine nucleophile that initiates splicing. Sedimentation velocity, size-exclusion chromatography and cryo-electron microscopy provide the first glimpse of the intron RNP precursor as a large, loosely packed structure. The dimensions contrast with those of compact spliced introns, implying that the RNP undergoes a dramatic conformational change to achieve the catalytically active state