A FACED lift for cerebral blood flow imaging

ISSN:0027-8424ISSN:1091-649

Localised edge states nucleate turbulence in extended plane Couette cells

We study the turbulence transition of plane Couette flow in large domains where localised perturbations are observed to generate growing turbulent spots. Extending previous studies on the boundary between laminar and turbulent dynamics we determine invariant structures intermediate between laminar and turbulent flow. In wide but short domains we find states that are localised in spanwise direction, and in wide and long domains the states are also localised in downstream direction. These localised states act as critical nuclei for the transition to turbulence in spatially extended domains.Comment: 15 pages, 5 figure

Phosphorylation of CREB affects its binding to high and low affinity sites

Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation

Der Entfremdungsbegriff in der Gegenwart und seine ethische Relevanz

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Metabolic network capacity of Escherichia coli for Krebs cycle-dependent proline hydroxylation

Figure S1. Physiology of recombinant E. coli BL21(DE3)(pLysS) strains bearing pET-24a. Panel A and B show biomass formation (circles), glucose consumption (squares), acetate formation (triangles), and proline consumption (diamonds) during batch cultivation of wildtype (closed symbols) and ΔputA (open symbols) strains at 30°C in M9 medium supplemented with 5 g L−1 glucose in the absence (A) or presence (B) of 5 mM proline, respectively. Figure S2. SDS-PAGE analysis of recombinant E. coli BL21(DE3)(pLysS) (pET_p4h1of) and E. coli BL21 ΔputA (DE3) (pLysS) (pET_p4h1of) at different time points during growth in M9 medium with 5 g L−1 glucose (glc) only or with addition of 5 mM proline (pro) at 30°C. M: protein size marker. Figure S3. Physiology of recombinant E. coli BL21(DE3)(pLysS) strains bearing pET_p4h1of. Biomass formation (circles), glucose consumption (squares), acetate formation (triangles), hyp formation (stars), and proline consumption (diamonds) during batch cultivation of wildtype (closed symbols) and ΔputA (open symbols) strains are shown. Cultivation was performed at 30°C in M9 medium supplemented with 5 g L−1 glucose in the absence (panel A) or presence of 5 mM proline (panels B and C). Table S4. Mass isotopomer distribution of alanine for the wt_pET strain at 30°C in M9 medium supplemented with 5 g L−1 U-13C labeled glucose in the absence or presence of 5 mM proline. Table S5. Reactions of the central carbon metabolism generating or consuming NTP and/or redox equivalents. Table S6. Bacterial strains and plasmids used in this study. Table S7. Correlation factors between OD600 1 and cell dry weight concentration (gCDW L−1) of the strains used in this study

Towards carbon nanotube growth into superconducting microwave resonator geometries

The in-place growth of suspended carbon nanotubes facilitates the observation of both unperturbed electronic transport spectra and high-Q vibrational modes. For complex structures integrating, e.g., superconducting rf elements on-chip, selection of a chemically and physically resistant material that survives the chemical vapor deposition (CVD) process provides a challenge. We demonstrate the implementation of molybdenum-rhenium coplanar waveguide resonators that exhibit clear resonant behaviour at cryogenic temperatures even after having been exposed to nanotube growth conditions. The properties of the MoRe devices before and after CVD are compared to a reference niobium device.Comment: 6 pages, 4 figures, IWEPNM conference proceedin

Magma Plumbing During the 2014-2015 Eruption of Fogo (Cape Verde Islands)

Phenocrysts in volcanic rocks are recorders of magmatic processes that have occurred at depth before and during a volcanic eruption. Our petrological investigations of stratigraphically controlled tephrite and phonotephrite samples from the latest eruption of Fogo (Cape Verde Islands) aimed to reconstructing magma storage and transport. The dates of sample emplacement have been determined using satellite instrument - derived high resolution thermal infrared maps. All samples are strongly phyric and commonly contain complexly zoned clinopyroxene crystals and cumulate fragments. Clinopyroxenes from all samples exhibit 10-50 mu m wide rim zones, inferred to have grown in a few days to weeks during the ongoing eruption as a consequence of H2O loss from the melt. Clinopyroxene-melt thermobarometry using tephrite groundmass compositions suggests that the rims formed at upper mantle pressures of around 600 MPa (21 km depth). This level is interpreted to reflect temporary reduction in magma ascent velocity by near-isobaric movement through a complex storage system. Previously, the tephrite magma had accumulated at a deeper level, possibly between 700 and 900 MPa as indicated by clinopyroxene cores (Mata et al., 2017). The cause for H2O loss initiating rim growth could be degassing after rise of the magma from the deeper level, or CO(2)flushing by a carbonic fluid phase released at depth. Corresponding data from phonotephrites indicate last equilibration at around 440 MPa (16 km);the phonotephrite magma is inferred to be a residuum from an earlier magmatic event that was entrained by advancing tephrite. Microthermometry of CO2-dominated fluid inclusions in tephrite clinopyroxenes results in pressures of around 330 MPa (12 km), indicating another short pause in magma ascent in the lowermost crust. Rim zonations of olivine phenocrysts indicate that after leaving this final stalling zone, the magma ascended to the surface in less than half a day. In strong contrast to these petrological equilibration depths, seismic events precursory to the eruption were located at < 5 km below sea level, with only two exceptions at 17 and 21 km depth consistent with our barometry. Our results enhance the understanding of this potentially dangerous volcano, which helps to interpret future pre-eruptive unrest

CCL5 Neutralization Restricts Cancer Growth and Potentiates the Targeting of PDGFRβ in Colorectal Carcinoma

Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorectal carcinoma clinical specimens and found CCL5 and its receptors over-expressed within primary as well as liver and pulmonary metastases of patients compared to healthy tissues. In vitro, CCL5 increased the growth and migratory responses of colon cancer cells from both human and mouse origins. In addition, systemic treatment of mice with CCL5-directed antibodies reduced the extent of development of subcutaneous colon tumors, of liver metastases and of peritoneal carcinosis. Consistently, we found increased numbers of CD45-immunoreactive cells within the stroma of the remaining lesions as well as at the interface with the healthy tissue. In contrast, selective targeting of CCR5 through administration of TAK-779, a CCR5 antagonist, only partially compromised colon cancer progression. Furthermore, CCL5 neutralization rendered the tumors more sensitive to a PDGFRβ-directed strategy in mice, this combination regimen offering the greatest protection against liver metastases and suppressing macroscopic peritoneal carcinosis. Collectively, our data demonstrate the involvement of CCL5 in the pathogenesis of colorectal carcinoma and point to its potential value as a therapeutic target

Steroid biotransformations in biphasic systems with Yarrowia lipolytica expressing human liver cytochrome P450 genes

BACKGROUND: Yarrowia lipolytica efficiently metabolizes and assimilates hydrophobic compounds such as n-alkanes and fatty acids. Efficient substrate uptake is enabled by naturally secreted emulsifiers and a modified cell surface hydrophobicity and protrusions formed by this yeast. We were examining the potential of recombinant Y. lipolytica as a biocatalyst for the oxidation of hardly soluble hydrophobic steroids. Furthermore, two-liquid biphasic culture systems were evaluated to increase substrate availability. While cells, together with water soluble nutrients, are maintained in the aqueous phase, substrates and most of the products are contained in a second water-immiscible organic solvent phase. RESULTS: For the first time we have co-expressed the human cytochromes P450 2D6 and 3A4 genes in Y. lipolytica together with human cytochrome P450 reductase (hCPR) or Y. lipolytica cytochrome P450 reductase (YlCPR). These whole-cell biocatalysts were used for the conversion of poorly soluble steroids in biphasic systems. Employing a biphasic system with the organic solvent and Y. lipolytica carbon source ethyl oleate for the whole-cell bioconversion of progesterone, the initial specific hydroxylation rate in a 1.5 L stirred tank bioreactor was further increased 2-fold. Furthermore, the product formation was significantly prolonged as compared to the aqueous system. Co-expression of the human CPR gene led to a 4-10-fold higher specific activity, compared to the co-overexpression of the native Y. lipolytica CPR gene. Multicopy transformants showed a 50-70-fold increase of activity as compared to single copy strains. CONCLUSIONS: Alkane-assimilating yeast Y. lipolytica, coupled with the described expression strategies, demonstrated its high potential for biotransformations of hydrophobic substrates in two-liquid biphasic systems. Especially organic solvents which can be efficiently taken up and/or metabolized by the cell might enable more efficient bioconversion as compared to aqueous systems and even enable simple, continuous or at least high yield long time processes