c-Src/Cav1-dependent activation of the EGFR by Dsg2.

The desmosomal cadherin, desmoglein 2 (Dsg2), is deregulated in a variety of human cancers including those of the skin. When ectopically expressed in the epidermis of transgenic mice, Dsg2 activates multiple mitogenic signaling pathways and increases susceptibility to tumorigenesis. However, the molecular mechanism responsible for Dsg2-mediated cellular signaling is poorly understood. Here we show overexpression as well as co-localization of Dsg2 and EGFR in cutaneous SCCs in vivo. Using HaCaT keratinocytes, knockdown of Dsg2 decreases EGFR expression and abrogates the activation of EGFR, c-Src and Stat3, but not Erk1/2 or Akt, in response to EGF ligand stimulation. To determine whether Dsg2 mediates signaling through lipid microdomains, sucrose density fractionation illustrated that Dsg2 is recruited to and displaces Cav1, EGFR and c-Src from light density lipid raft fractions. STED imaging confirmed that the presence of Dsg2 disperses Cav1 from the cell-cell borders. Perturbation of lipid rafts with the cholesterol-chelating agent MβCD also shifts Cav1, c-Src and EGFR out of the rafts and activates signaling pathways. Functionally, overexpression of Dsg2 in human SCC A431 cells enhances EGFR activation and increases cell proliferation and migration through a c-Src and EGFR dependent manner. In summary, our data suggest that Dsg2 stimulates cell growth and migration by positively regulating EGFR level and signaling through a c-Src and Cav1-dependent mechanism using lipid rafts as signal modulatory platforms

Isolation of a Highly Thermal Stable Lama Single Domain Antibody Specific for Staphylococcus aureus Enterotoxin B

<p>Abstract</p> <p>Background</p> <p>Camelids and sharks possess a unique subclass of antibodies comprised of only heavy chains. The antigen binding fragments of these unique antibodies can be cloned and expressed as single domain antibodies (sdAbs). The ability of these small antigen-binding molecules to refold after heating to achieve their original structure, as well as their diminutive size, makes them attractive candidates for diagnostic assays.</p> <p>Results</p> <p>Here we describe the isolation of an sdAb against <it>Staphyloccocus aureus </it>enterotoxin B (SEB). The clone, A3, was found to have high affinity (Kd = 75 pM) and good specificity for SEB, showing no cross reactivity to related molecules such as Staphylococcal enterotoxin A (SEA), Staphylococcal enterotoxin D (SED), and Shiga toxin. Most remarkably, this anti-SEB sdAb had an extremely high Tm of 85°C and an ability to refold after heating to 95°C. The sharp Tm determined by circular dichroism, was found to contrast with the gradual decrease observed in intrinsic fluorescence. We demonstrated the utility of this sdAb as a capture and detector molecule in Luminex based assays providing limits of detection (LODs) of at least 64 pg/mL.</p> <p>Conclusion</p> <p>The anti-SEB sdAb A3 was found to have a high affinity and an extraordinarily high Tm and could still refold to recover activity after heat denaturation. This combination of heat resilience and strong, specific binding make this sdAb a good candidate for use in antibody-based toxin detection technologies.</p

Productivity change in Nigerian seaports after reform: a Malmquist productivity index decomposition approach

During the 1990s, Nigerian seaports were considered inefficient, unsafe due to massive cargo theft (wharf rat phenomenon) and one of the most expensive port systems in the world. This resulted in long turnaround times for ships and increased container dwell times. As a result, port operations were transferred to the private sector through concession contracts. This paper employs a Malmquist productivity index (MPI) technique to benchmark pre-and post-reform total factor productivity growth of the six major Nigeria seaports (Apapa, Calabar, Onne, Port Harcourt, TinCan Island and Warri) for the period 2000–2011 which represents six years before (2000–2005) and six years after (2006–2011) the reform. The results indicate progress in technical efficiency of the ports after reform but deterioration in technological progress. Overall productivity growth was higher in the pre-concession period compared to the post-concession period. The source of pre-concession period productivity growth was technological progress while the change in productivity of the post-concession period is generated by an increase in scale efficiency. This suggests that concessionaires have not brought in the much anticipated investment in modern technology to drive port efficiency. The ports of Calabar and Apapa experienced the highest productivity growth while lowest result was Onne

The lack of star formation gradients in galaxy groups up to z~1.6

In the local Universe, galaxy properties show a strong dependence on environment. In cluster cores, early type galaxies dominate, whereas star-forming galaxies are more and more common in the outskirts. At higher redshifts and in somewhat less dense environments (e.g. galaxy groups), the situation is less clear. One open issue is that of whether and how the star formation rate (SFR) of galaxies in groups depends on the distance from the centre of mass. To shed light on this topic, we have built a sample of X-ray selected galaxy groups at 0<z<1.6 in various blank fields (ECDFS, COSMOS, GOODS). We use a sample of spectroscopically confirmed group members with stellar mass M >10^10.3 M_sun in order to have a high spectroscopic completeness. As we use only spectroscopic redshifts, our results are not affected by uncertainties due to projection effects. We use several SFR indicators to link the star formation (SF) activity to the galaxy environment. Taking advantage of the extremely deep mid-infrared Spitzer MIPS and far-infrared Herschel PACS observations, we have an accurate, broad-band measure of the SFR for the bulk of the star-forming galaxies. We use multi-wavelength SED fitting techniques to estimate the stellar masses of all objects and the SFR of the MIPS and PACS undetected galaxies. We analyse the dependence of the SF activity, stellar mass and specific SFR on the group-centric distance, up to z~1.6, for the first time. We do not find any correlation between the mean SFR and group-centric distance at any redshift. We do not observe any strong mass segregation either, in agreement with predictions from simulations. Our results suggest that either groups have a much smaller spread in accretion times with respect to the clusters and that the relaxation time is longer than the group crossing time.Comment: Accepted for publication in MNRA

2012-2013 Concert Panino and Friendship Tea

https://spiral.lynn.edu/foc-events/1016/thumbnail.jp