Ceacam1 deficiency causes endothelial dysfunction and atherosclerosis

Die in dieser Arbeit präsentierten Ergebnisse führen zu der Annahme, dass der endothelialen Expression des Carcinoembryonic antigen-related Cell Adhesion Molecule 1 (Ceacam1) auf aortalen atherosklerotischen Plaques Apolipoprotein-E-defizienter Mäuse eine duale pathogenetische Bedeutung zugeschrieben werden kann. Ceacam1 vermag Signaltransduktionswege, wie z.B. die Aktivität der Proteinkinase B (PKB/Akt), zu modu­lieren und die Transkription bedeutsamer Endothelzellfunktionsmarker, wie z.B. des vas­kulären endothelialen Wachstumsfaktor-Rezeptor-2 (VEGFR-2), der endothelialen Stick­stoffmonoxidsynthase (e-NOS) und des vaskulären endothelialen Cadherins (VE-Cadherin) zu regulieren. Dadurch erhält Ceacam1 Einfluss auf den Zellzyklus und die Apoptose, den Redoxstatus, das Entzündungsgeschehen, die endotheliale Per­meabilität und die Immunantwort. Somit kann Ceacam1 einerseits zum zeitweiligen Erhalt der En­dothelzellfunktion beitragen und somit der Progression der Atherosklero­se entgegenwir­ken. Andererseits kann das proangiogenetische Ceacam1 unter der fortwährenden Ein­wirkung atherosklerotischer Risikofaktoren durch die Bildung unreifer und durchlässiger Gefäße das Plaquewachstum und die Plaqueinstabilität provozieren und somit nachteilige Auswirkungen auf die Pathogenese der Gefäßerkrankung haben. Im Ceacam1-Knockout-Modell bestand hintergründig ein ätiologischer Zusammenhang zur Athersklerose. Der leberspezifische Ausfall von Ceacam1 führte zur Entstehung einer Hyperinsulinämie, Leberverfettung, vizeraler Adipositas und zu einem Anstieg von freien Fettsäuren und proinflammatorischen Zytokinen im Blut. Das Fehlen von Ceacam1 in der Niere hatte zudem die Entwicklung einer arteriellen Hypertonie zur Folge. Obgleich es in den Aorten der Ceacam1-Knockout-Mäuse im Vergleich zur Wildtypgruppe zur Entwick­lung kleiner atherosklerotischer Läsionen kam, konnte die hierfür zugrunde liegende en­dothelialen Dysfunktion nicht alleinig mit den hier auftretenden atherosklerotischen Risiko­faktoren, wie z.B. dem Anstieg des oxidativen Stresses und des Tumornekrosefaktors-α, erklärt werden. Die deutlich verminderte Expression der drei endothelialen Funktionsmar­ker VEGFR-2, e-NOS und VE-Cadherin in den Aorten der Ceacam1-Knockout-Mäuse im Vergleich zur Wildtypkontrollgruppe, die eine endotheliale Dysfunktion hinreichend cha­rakterisiert, musste auf die potentielle Abwesenheit des regulatorischen Ceacam1 zurück­geführt werden. Das Fehlen von Ceacam1 geht einher mit einer Modulation von Signal­transduktionswegen, wie z.B. einer reduzierten Aktivität der PKB/Akt, die in kritischem Ausmass Einfluss auf die Expression jener Marker und die Kompensation der Endothel­zellfunktion ausübt. Welche protektive Rolle Ceacam1 darüberhinaus im Endothel großer Blutgefäße bei der Entstehung der Atherosklerose spielt, muss in zukünftigen Analysen geklärt werden

The new national energy concept 2015-The future of brown coal in the Czech Republic

Reserves of brown coal in the Czech Republic are, in the long term view, still recognized as the main domestic fuel and energy resource. The biggest issues, concerning the use of these domestic resources, are, according to the authors, the existence of the “Resolution of the Government of the Czech Republic No. 444” of 30 October, 1991 together with the new State Energy Concept, which was approved in May this year, and which states that the CR will export three out of four key fuels and energy resources, namely oil, gas and nuclear fuel. Brown coal is, therefore, the only domestic energy resource that allows a long-term guarantee leading towards reducing the energy dependence.Web of Science20431029

What is the biological basis of pattern formation of skin lesions?

Pattern recognition is at the heart of clinical dermatology and dermatopathology. Yet, while every practitioner of the art of dermatological diagnosis recognizes the supreme value of diagnostic cues provided by defined patterns of 'efflorescences', few contemplate on the biological basis of pattern formation in and of skin lesions. Vice versa, developmental and theoretical biologists, who would be best prepared to study skin lesion patterns, are lamentably slow to discover this field as a uniquely instructive testing ground for probing theoretical concepts on pattern generation in the human system. As a result, we have at best scraped the surface of understanding the biological basis of pattern formation of skin lesions, and widely open questions dominate over definitive answer. As a symmetry-breaking force, pattern formation represents one of the most fundamental principles that nature enlists for system organization. Thus, the peculiar and often characteristic arrangements that skin lesions display provide a unique opportunity to reflect upon – and to experimentally dissect – the powerful organizing principles at the crossroads of developmental, skin and theoretical biology, genetics, and clinical dermatology that underlie these – increasingly less enigmatic – phenomena. The current 'Controversies' feature offers a range of different perspectives on how pattern formation of skin lesions can be approached. With this, we hope to encourage more systematic interdisciplinary research efforts geared at unraveling the many unsolved, yet utterly fascinating mysteries of dermatological pattern formation. In short: never a dull pattern

The Superoanterior Fasciculus (SAF): A Novel White Matter Pathway in the Human Brain?

Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain’s circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that—to the best of our knowledge—has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe

Circadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling

Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK–regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes

Search for physics beyond the standard model in events with two leptons, jets, and missing transverse momentum in pp collisions at √s = 8 TeV

A search is presented for physics beyond the standard model in final states with two opposite-sign same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 19.4 fb[superscript −1] of proton-proton collisions at √s = 8 TeV collected with the CMS detector at the CERN LHC in 2012. The analysis focuses on searches for a kinematic edge in the invariant mass distribution of the oppositesign same-flavor lepton pair and for final states with an on-shell Z boson. The observations are consistent with expectations from standard model processes and are interpreted in terms of upper limits on the production of supersymmetric particles.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

Two basic neuroimaging-based characterizations of white matter tracts are the magnitude of water diffusion along the principal tract orientation (axial diffusivity, AD) and water diffusion perpendicular to the principal orientation (radial diffusivity, RD). It is generally accepted that decreases in AD reflect disorganization, damage, or loss of axons, whereas increases in RD are indicative of disruptions to the myelin sheath. Previous reports have detailed the heritability of individual AD and RD measures, but have not examined the extent to which the same or different genetic or environmental factors influence these two phenotypes (except for corpus callosum). We implemented bivariate twin analyses to examine the shared and independent genetic influences on AD and RD. In the Vietnam Era Twin Study of Aging, 393 men (mean age = 61.8 years, SD = 2.6) underwent diffusion-weighted magnetic resonance imaging. We derived fractional anisotropy (FA), mean diffusivity (MD), AD, and RD estimates for 11 major bilateral white matter tracts and the mid-hemispheric corpus callosum, forceps major, and forceps minor. Separately, AD and RD were each highly heritable. In about three-quarters of the tracts, genetic correlations between AD and RD were >.50 (median = .67) and showed both unique and common variance. Genetic variance of FA and MD were predominately explained by RD over AD. These findings are important for informing genetic association studies of axonal coherence/damage and myelination/demyelination. Thus, genetic studies would benefit from examining the shared and unique contributions of AD and RD.Peer reviewe

Measurement of Exclusive rho+rho- Production in Mid-Virtuality Two-Photon Interactions and Study of the gamma gamma* -> rho rho Process at LEP

Exclusive rho+rho- production in two-photon collisions between a quasi-real photon, gamma, and a mid-virtuality photon, gamma*, is studied with data collected at LEP at centre-of-mass energies root(s)=183-209GeV with a total integrated luminosity of 684.8pb^-1. The cross section of the gamma gamma* -> rho+ rho- process is determined as a function of the photon virtuality, Q^2, and the two-photon centre-of-mass energy, W_gg, in the kinematic region: 0.2GeV^2 < Q^2 <0.85GeV^2 and 1.1GeV < W_gg < 3GeV. These results, together with previous L3 measurements of rho0 rho0 and rho+ rho- production, allow a study of the gamma gamma* -> rho rho process over the Q^2-region 0.2GeV^2 < Q^2 < 30 GeV^2

Bose-Einstein Correlations of Neutral and Charged Pions in Hadronic Z Decays

Bose-Einstein correlations of both neutral and like-sign charged pion pairs are measured in a sample of 2 million hadronic Z decays collected with the L3 detector at LEP. The analysis is performed in the four-momentum difference range 300 MeV < Q < 2 GeV. The radius of the neutral pion source is found to be smaller than that of charged pions. This result is in qualitative agreement with the string fragmentation model

Measurement of Exclusive rho^0 rho^0 Production in Mid-Virtuality Two-Photon Interactions at LEP

Exclusive rho^0 rho^0 production in two-photon collisions between a quasi-real and a mid-virtuality photon is studied with data collected at LEP at centre-of-mass energies 183GeV < sqrt{s} < 209GeV with a total integrated luminosity of 684.8/pb. The cross section of the process gamma gamma* -> rho^0 rho^0 is determined as a function of the photon virtuality, q^2, and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 0.2GeV^2 < q^2 < 0.85GeV^2 and 1.1GeV < Wgg < 3GeV