Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats

The arginyltransferase Ate1 is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. At least six isoforms of mouse Ate1 are produced through alternative splicing of Ate1 pre-mRNA. We identified a previously uncharacterized mouse protein, termed Liat1 (ligand of Ate1), that interacts with Ate1 but does not appear to be its arginylation substrate. Liat1 has a higher affinity for the isoforms Ate1^(1A7A) and Ate1^(1B7A). Liat1 stimulated the in vitro N-terminal arginylation of a model substrate by Ate1. All examined vertebrate and some invertebrate genomes encode proteins sequelogous (similar in sequence) to mouse Liat1. Sequelogs of Liat1 share a highly conserved ∼30-residue region that is shown here to be required for the binding of Liat1 to Ate1. We also identified non-Ate1 proteins that interact with Liat1. In contrast to Liat1 genes of nonprimate mammals, Liat1 genes of primates are subtelomeric, a location that tends to confer evolutionary instability on a gene. Remarkably, Liat1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas Liat1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in Liat1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human Liat1, respectively, suggesting that repeat number changes in this previously uncharacterized protein may contribute to evolution of primates

Advanced seismic characterization of a geothermal carbonate reservoir – insight into the structure and diagenesis of a reservoir in the German Molasse Basin

The quality of geothermal carbonate reservoirs is controlled by, for instance, depositional environment, lithology, diagenesis, karstification, fracture networks, and tectonic deformation. Carbonatic rock formations are thus often extremely heterogeneous, and reservoir parameters and their spatial distribution difficult to predict. Using a 3D seismic dataset combined with well data from Munich, Germany, we demonstrate how a comprehensive seismic attribute analysis can significantly improve the understanding of a complex carbonate reservoir. We deliver an improved reservoir model concept and identify possible exploitation targets within the Upper Jurassic carbonates. We use seismic attributes and different carbonate lithologies from well logs to identify parameter correlations. From this, we obtain a supervised neural-network-based 3D lithology model of the geothermal reservoir. Furthermore, we compare fracture orientations measured in seismic (ant-tracking analysis) and well scale (image log analysis) to address scalability. Our results show that, for example, acoustic impedance is suitable to identify reefs and karst-related dolines, and sweetness proves useful to analyse the internal reef architecture, whereas frequency- and phase-related attributes allow the detection of karst. In addition, reef edges, dolines, and fractures, associated with high permeabilities, are characterized by strong phase changes. Fractures are also identified using variance and ant tracking. Morphological characteristics, like dolines, are captured using the shape index. Regarding the diagenetic evolution of the reservoir and the corresponding lithology distribution, we show that the Upper Jurassic carbonate reservoir experienced a complex evolution, consisting of at least three dolomitization phases, two karstification phases, and a phase of tectonic deformation. We observe spatial trends in the degree of dolomitization and show that it is mainly facies-controlled and that karstification is facies- and fault-controlled. Karstification improves porosity and permeability, whereas dolomitization can either increase or decrease porosity. Therefore, reservoir zones should be exploited that experienced only weak diagenetic alteration, i.e. the dolomitic limestone in the upper part of the Upper Jurassic carbonates. Regarding the fracture scalability across seismic and well scales, we note that a general scalability is, due to a combination of methodological limitations and geological reasons, not possible. Nevertheless, both methods provide an improved understanding of the fracture system and possible fluid pathways. By integrating all the results, we are able to improve and adapt recent reservoir concepts, to outline the different phases of the reservoir's structural and diagenetic evolution, and to identify high-quality reservoir zones in the Munich area. These are located southeast at the Ottobrunn Fault and north of the Munich Fault close to the Nymphenburg Fault.</p

Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA

Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of 64Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of 64Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that 64Cu-NOTA-TRC105 exhibited better stability than 64Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with 64Cu-labeled TRC105

The Flux-Line Lattice in Superconductors

Magnetic flux can penetrate a type-II superconductor in form of Abrikosov vortices. These tend to arrange in a triangular flux-line lattice (FLL) which is more or less perturbed by material inhomogeneities that pin the flux lines, and in high-$T_c$ supercon- ductors (HTSC's) also by thermal fluctuations. Many properties of the FLL are well described by the phenomenological Ginzburg-Landau theory or by the electromagnetic London theory, which treats the vortex core as a singularity. In Nb alloys and HTSC's the FLL is very soft mainly because of the large magnetic penetration depth: The shear modulus of the FLL is thus small and the tilt modulus is dispersive and becomes very small for short distortion wavelength. This softness of the FLL is enhanced further by the pronounced anisotropy and layered structure of HTSC's, which strongly increases the penetration depth for currents along the c-axis of these uniaxial crystals and may even cause a decoupling of two-dimensional vortex lattices in the Cu-O layers. Thermal fluctuations and softening may melt the FLL and cause thermally activated depinning of the flux lines or of the 2D pancake vortices in the layers. Various phase transitions are predicted for the FLL in layered HTSC's. The linear and nonlinear magnetic response of HTSC's gives rise to interesting effects which strongly depend on the geometry of the experiment.Comment: Review paper for Rep.Prog.Phys., 124 narrow pages. The 30 figures do not exist as postscript file

High-resolution shear-wave seismic reflection as a tool to image near-surface subrosion structures – a case study in Bad Frankenhausen, Germany

Subrosion is the subsurface leaching of soluble rocks that results in the formation of depression and collapse structures. This global phenomenon is a geohazard in urban areas. To study near-surface subrosion structures, four shear-wave seismic reflection profiles, with a total length of ca. 332 m, were carried out around the famous leaning church tower of Bad Frankenhausen in northern Thuringia, Germany, which shows an inclination of 4.93° from the vertical. Most of the geological underground of Thuringia is characterized by soluble Permian deposits, and the Kyffhäuser Southern Margin Fault is assumed to be a main pathway for water to leach the evaporite. The seismic profiles were acquired with the horizontal micro-vibrator ELVIS, developed at Leibniz Institute for Applied Geophysics (LIAG), and a 72 m long landstreamer equipped with 72 horizontal geophones. The high-resolution seismic sections show subrosion-induced structures to a depth of ca. 100 m and reveal five features associated with the leaching of Permian deposits: (1) lateral and vertical varying reflection patterns caused by strongly heterogeneous strata, (2) discontinuous reflectors, small offsets, and faults, which show the underground is heavily fractured, (3) formation of depression structures in the near-surface, (4) diffractions in the unmigrated seismic sections that indicate increased scattering of the seismic waves, and (5) varying seismic velocities and low-velocity zones that are presumably caused by fractures and upward-migrating cavities. A previously undiscovered southward-dipping listric normal fault was also found, to the north of the church. It probably serves as a pathway for water to leach the Permian formations below the church and causes the tilting of the church tower. This case study shows the potential of horizontal shear-wave seismic reflection to image near-surface subrosion structures in an urban environment with a horizontal resolution of less than 1 m in the uppermost 10–15 m

Structural analysis of S-wave seismics around an urban sinkhole: evidence of enhanced dissolution in a strike-slip fault zone

In November 2010, a large sinkhole opened up in the urban area of Schmalkalden, Germany. To determine the key factors which benefited the development of this collapse structure and therefore the dissolution, we carried out several shear-wave reflection-seismic profiles around the sinkhole. In the seismic sections we see evidence of the Mesozoic tectonic movement in the form of a NW–SE striking, dextral strike-slip fault, known as the Heßleser Fault, which faulted and fractured the subsurface below the town. The strike-slip faulting created a zone of small blocks ( &lt; 100 m in size), around which steep-dipping normal faults, reverse faults and a dense fracture network serve as fluid pathways for the artesian-confined groundwater. The faults also acted as barriers for horizontal groundwater flow perpendicular to the fault planes. Instead groundwater flows along the faults which serve as conduits and forms cavities in the Permian deposits below ca. 60 m depth. Mass movements and the resulting cavities lead to the formation of sinkholes and dissolution-induced depressions. Since the processes are still ongoing, the occurrence of a new sinkhole cannot be ruled out. This case study demonstrates how S-wave seismics can characterize a sinkhole and, together with geological information, can be used to study the processes that result in sinkhole formation, such as a near-surface fault zone located in soluble rocks. The more complex the fault geometry and interaction between faults, the more prone an area is to sinkhole occurrence