An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma

The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer

Stress effect on magnetoimpedance (MI) in amorphous wires at GHz frequencies and application to stress-tunable microwave composite materials

The effect of tensile stress on magnetoimpedance (MI) in CoMnSiB amorphous wires at microwave frequencies (0.5-3 GHz) is investigated both experimentally and theoretically. In the presence of the dc bias magnetic field of the order of the anisotropy field, the impedance shows very large and sensitive change when the wire is subjected to a tensile stress: 100% and 60% per 180 MPa for frequencies 500 MHz and 2.5 GHz, respectively. It is demonstrated that this behavior owes mainly to the directional change in the equilibrium magnetization caused by the applied stress and field, which agrees well with the theoretical results for the surface impedance. This stress effect on MI is proposed to use for creating microwave stress-tunable composite materials containing short magnetic wires. The analysis of the dielectric response from such materials shows that depending on the stress level in the material, the dispersion of the effective permittivity can be of a resonant or relaxation type with a considerable change in its values (up to 100% at 600 MPa). This media can be used for structural stress monitoring by microwave contrast imaging

Broadband multi-wavelength campaign on PKS 2005-489

The spectral energy distribution (SED) of high-frequency peaked BL Lac objects (HBL) is characterized by two peaks: one in the UV-X-ray and one in the GeV-TeV regime. An interesting object for analyzing these broadband characteristics is PKS 2005-489, which in 2004 showed the softest TeV spectrum ever measured. In 2009, a multi-wavelength campaign has been conducted with, for the first time, simultaneous observations by H.E.S.S. (TeV), Fermi/LAT (GeV), RXTE (keV), Swift (keV, UV, optical) and ATOM (optical) to cover the two peaks of the SED. During this campaign PKS 2005-489 underwent a high state in all wavebands which gives the opportunity to study in detail the emission processes of a high state of this interesting HBL.Comment: 2009 Fermi Symposium; eConf Proceedings C09112

Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy

Water footprints of cities indicators for sustainable consumption and production

Water footprints have been proposed as sustainabilityindicators, relating the consumption of goods likefood to the amount of water necessary for their productionand the impacts of that water use in the source regions. Wefurther developed the existing water footprint methodology,by globally resolving virtual water flows from production toconsumption regions for major food crops at 5 arcmin spatialresolution. We distinguished domestic and internationalflows, and assessed local impacts of export production. Applyingthis method to three exemplary cities, Berlin, Delhiand Lagos, we find major differences in amounts, composition,and origin of green and blue virtual water imports,due to differences in diets, trade integration and crop waterproductivities in the source regions. While almost all ofDelhi’s and Lagos’ virtual water imports are of domestic origin,Berlin on average imports from more than 4000 km distance,in particular soy (livestock feed), coffee and cocoa.While 42% of Delhi’s virtual water imports are blue waterbased, the fractions for Berlin and Lagos are 2 and 0.5 %, respectively,roughly equal to the water volumes abstracted inthese two cities for domestic water use. Some of the externalsource regions of Berlin’s virtual water imports appear tobe critically water scarce and/or food insecure. However, forderiving recommendations on sustainable consumption andtrade, further analysis of context-specific costs and benefitsassociated with export production will be required