Paleoenvironments from robust loess stratigraphy using high-resolution color and grain-size data of the last glacial Krems-Wachtberg record (NE Austria)

The complex interplay of dust sedimentation, pedogenesis, and erosion/reworking in the formation of loess-paleosol sequences (LPS) challenges paleoenvironmental proxies. Here we show that color and grain size are essential parameters characterizing loess profiles and support robust stratigraphies as a basis for reconstructions in the context of local geo-ecological and large-scale paleoclimatic evolution. Detailed paleoenvironmental records from the period since the arrival of anatomically modern humans to the last glacial maximum are scarce in the Alpine surroundings. The c. 7.5 m thick LPS Krems-Wachtberg, NE Austria, known for its well-preserved Upper Paleolithic context at a depth of 5.5 m, formed between 40 and 20 ka BP by quasi-continuous dust-sedimentation, interrupted by phases of incipient pedogenesis and local reworking. The new KW2015 composite is based on three sections studied and sampled at 2.5 cm resolution. Color and grain size data support a robust stratigraphy for reconstructions of the pedosedimentary evolution. The marked transition from oxidized to reduced paleosols of KW2015 around 34–35 ka corresponds to the Middle-to Upper Pleniglacial transition as part of a general cooling trend from marine isotope stage (MIS) 3 to 2, intensely modulated by millennial-scale climatic fluctuations as recorded in the Greenland ice core data. The distinct response of KW2015 to these trends highlights that reconstructing LPS evolution based on a robust stratigraphy is a prerequisite to paleoenvironmental proxy interpretation

Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells

Signaling through the primary cilium

© 2018 Wheway, Nazlamova and Hancock. The presence of single, non-motile "primary" cilia on the surface of epithelial cells has been well described since the 1960s. However, for decades these organelles were believed to be vestigial, with no remaining function, having lost their motility. It wasn't until 2003, with the discovery that proteins responsible for transport along the primary cilium are essential for hedgehog signaling in mice, that the fundamental importance of primary cilia in signal transduction was realized. Little more than a decade later, it is now clear that the vast majority of signaling pathways in vertebrates function through the primary cilium. This has led to the adoption of the term "the cells's antenna" as a description for the primary cilium. Primary cilia are particularly important during development, playing fundamental roles in embryonic patterning and organogenesis, with a suite of inherited developmental disorders known as the "ciliopathies" resulting from mutations in genes encoding cilia proteins. This review summarizes our current understanding of the role of these fascinating organelles in a wide range of signaling pathways

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Einfluss von Legierungselementen auf die Phasenbildung im System Co-Si

Im Rahmen dieser Diplomarbeit erfolgte die Charakterisierung von dünnen Co-Al-Si-Schichten durch elektrische Messungen, RBS, REM, TEM, AES, MOKE sowie temperaturabhängige Messungen des spezifischen elektrischen Widerstandes. Es wurde die Phasenbildung in diesem ternären System und die Beeinträchtigung der Phasenbildung im System Co-Si in Abhängigkeit des Al-Gehaltes betrachtet. Die Co-Al-Schichten wurden duch Magnetronsputtern auf Si(001)-Substraten abgeschieden und im Temperaturbereich von 500°C bis 900°C getempert (30s)

Einfluss von Legierungselementen auf die Phasenbildung im System Co-Si

Im Rahmen dieser Diplomarbeit erfolgte die Charakterisierung von dünnen Co-Al-Si-Schichten durch elektrische Messungen, RBS, REM, TEM, AES, MOKE sowie temperaturabhängige Messungen des spezifischen elektrischen Widerstandes. Es wurde die Phasenbildung in diesem ternären System und die Beeinträchtigung der Phasenbildung im System Co-Si in Abhängigkeit des Al-Gehaltes betrachtet. Die Co-Al-Schichten wurden duch Magnetronsputtern auf Si(001)-Substraten abgeschieden und im Temperaturbereich von 500°C bis 900°C getempert (30s)

Extracting near-surface Q(L) between 1-4 Hz from higher-order noise correlations in the Euroseistest area, Greece

Knowledge of the quality factor of near-surface materials is of fundamental interest in various applications. Attenuation can be very strong close to the surface and thus needs to be properly assessed. In recent years, several researchers have studied the retrieval of attenuation coefficients from the cross correlation of ambient seismic noise. Yet, the determination of exact amplitude information from noise-correlation functions is, in contrast to the extraction of traveltimes, not trivial. Most of the studies estimated attenuation coefficients on the regional scale and within the microseism band. In this paper, we investigate the possibility to derive attenuation coefficients from seismic noise at much shallower depths and higher frequencies (> 1 Hz). The Euroseistest area in northern Greece offers ideal conditions to study quality factor retrieval from ambient noise for different rock types. Correlations are computed between the stations of a small scale array experiment (station spacings < 2 km) that was carried out in the Euroseistest area in 2011. We employ the correlation of the coda of the correlation (C-3) method instead of simple cross correlations to mitigate the effect of uneven noise source distributions on the correlation amplitude. Transient removal and temporal flattening are applied instead of 1-bit normalization in order to retain relative amplitudes. The C-3 method leads to improved correlation results (higher signal-to-noise ratio and improved time symmetry) compared to simple cross correlations. The C-3 functions are rotated from the ZNE to the ZRT system and we focus on Love wave arrivals on the transverse component and on Love wave quality factors Q(L). The analysis is performed for selected stations being either situated on soft soil or on weathered rock. Phase slowness is extracted using a slant-stack method. Attenuation parameters are inferred by inspecting the relative amplitude decay of Love waves with increasing interstation distance. We observe that the attenuation coefficient gamma and Q(L) can be reliably extracted for stations situated on soft soil whereas the derivation of attenuation parameters is more problematic for stations that are located on weathered rock. The results are in acceptable conformance with theoretical Love wave attenuation curves that were computed using 1-D shear wave velocity and quality factor profiles from the Euroseistest area