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CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-alpha transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-a emission has been a long-standing goal of observational astrophysics(1-3), but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-alpha emission from hydrogen around high-redshift galaxies(4,5). Such measurements were previously limited to especially favourable systems(6-8) or to the use of massive statistical averaging(9,10) because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-alpha emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-alpha emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars(11-14). This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.
Context. We map the interstellar medium (ISM) including the diffuse interstellar bands (DIBs) in absorption toward the globular cluster NGC6397 using VLT/MUSE. Assuming the absorbers are located at the rim of the Local Bubble we trace structures on the order of mpc (milliparsec, a few thousand AU). Aims. We aimed to demonstrate the feasibility to map variations of DIBs on small scales with MUSE. The sightlines defined by binned stellar spectra are separated by only a few arcseconds and we probe the absorption within a physically connected region. Methods. This analysis utilized the fitting residuals of individual stellar spectra of NGC6397 member stars and analyzed lines from neutral species and several DIBs in Voronoi-binned composite spectra with high signal-to-noise ratio (S/N). Results. This pilot study demonstrates the power of MUSE for mapping the local ISM on very small scales which provides a new window for ISM observations. We detect small scale variations in Na-I and K-I as well as in several DIBs within few arcseconds, or mpc with regard to the Local Bubble. We verify the suitability of the MUSE 3D spectrograph for such measurements and gain new insights by probing a single physical absorber with multiple sight lines.
Three small stalagmites from Zoolithencave (southern Germany) show visible laminae, which consist of a clear and a brownish, pigmented layer pair. This potentially provides the opportunity to construct precise chronologies by counting annual laminae. The growth period of the three stalagmites was constrained by the C-14 bomb peak in the youngest part of all three stalagmites and C-14-dating of a piece of charcoal in the consolidated base part of stalagmite Zoo-rez-2. These data suggest an age of AD 1970 for the top laminae and a lower age limit of AD 1973-1682 or AD 1735-1778. Laminae were counted and their thickness determined on scanned thin sections of all stalagmites. On stalagmites Zoo-rez-1 and -2, three tracks were measured near the growth axes, each separated into three sections at prominent anchor laminae (I, II, III). Each section was replicated three times (a, b, c). For Zoo-rez-3, only one track was measured. The total number of laminae counted for Zoo-rez-1 ranges from 138 to 177, for Zoo-rez-2 from 119 to 145, and for Zoo-rez-3 from 159 to 166. The numbers agree well with the range constrained by the bomb peak and the age of the charcoal, which supports the annual origin of the laminae. The replicated measurements of the different tracks as well as the three different tracks on the stalagmites Zoo-rez-1 and-2 were cross-dated using the TSAP-Win (R) tree-ring software. This software is very useful for cross-dating because it enables to insert or delete missing or false laminae as well as identifying common pattern by shifting the series back and forth in time. However, visual inspection of the thin sections was necessary to confirm detection of missing or false laminae by TSAP-Win (R). For all three Zoo-rez speleothems, crossdating of the mean lamina thickness series was not possible due to a missing common pattern. The cross-dating procedure results in three refined chronologies for the three Zoo-rez stalagmites of ranging from AD 1821-1970 (Zoo-rez-1), AD 1835-1970 (Zoo-rez-2), and AD 1808-1970 (Zoo-rez-3).
Aims. Doubly ionized silicon (Si III) is a powerful tracer of diffuse ionized gas inside and outside of galaxies. It can be observed in the local Universe in ultraviolet (UV) absorption against bright extragalactic background sources. We here present an extensive study of intervening Si III-selected absorbers and study the properties of the warm circumgalactic medium (CGM) around low-redshift (z <= 0.1) galaxies. Methods. We analyzed the UV absorption spectra of 303 extragalactic background sources, as obtained with the Cosmic Origins Spectrograph (COS) on-board the Hubble Space Telescope (HST). We developed a geometrical model for the absorption-cross section of the CGM around the local galaxy population and compared the observed Si III absorption statistics with predictions provided by the model. We also compared redshifts and positions of the absorbers with those of similar to 64 000 galaxies using archival galaxy-survey data to investigate the relation between intervening Si III absorbers and the CGM. Results. Along a total redshift path of Delta z approximate to 24, we identify 69 intervening Si III systems that all show associated absorption from other low and high ions (e.g., H I, Si II, Si IV, C II, C IV). We derive a bias-corrected number density of dN/dz(Si III) = 2.5 +/- 0.4 for absorbers with column densities log N(Si III) > 12.2, which is similar to 3 times the number density of strong Mg II systems at z = 0. This number density matches the expected cross section of a Si III absorbing CGM around the local galaxy population with a mean covering fraction of < f(c)> = 0.69. For the majority (similar to 60 percent) of the absorbers, we identify possible host galaxies within 300 km s(-1) of the absorbers and derive impact parameters rho < 200 kpc, demonstrating that the spatial distributions of Si III absorbers and galaxies are highly correlated. Conclusions. Our study indicates that the majority of Si III-selected absorbers in our sample trace the CGM of nearby galaxies within their virial radii at a typical covering fraction of similar to 70 percent. We estimate that diffuse gas in the CGM around galaxies, as traced by Si III, contains substantially more (more than twice as much) baryonic mass than their neutral interstellar medium.
Ausgehend von der These, dass kommunale Unternehmen gerade in strukturschwachen Regionen eine besondere politische und wirtschaftliche Bedeutung besitzen, wird die Entwicklung der kommunalen Wirtschaft im Land Brandenburg untersucht. Die Autoren bereiten dazu in einer Längsschnittanalyse nicht unmittelbar dazu abrufbare Daten der öffentlichen Statistik auf und untersetzen die statistische Analyse durch eine Einzelfallstudie. Im Ergebnis wird deutlich, dass Entscheidungen über Privatisierungen oder Kommunalisierungen keinen „Sachgesetzlichkeiten“ folgen, sondern politisch in Abhängigkeit von Situationsinterpretationen, Denkstilen, Macht- und Interessenkonstellationen getroffen werden. Die Offenheit der Entscheidung über die Zukunft der kommunalen Wirtschaft verweist damit auf politischen Handlungsspielraum und die politische Verantwortung für Ausbau, Erhalt oder Privatisierung kommunaler Unternehmen.