Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions

© 2019, The Author(s), under exclusive licence to Springer Nature Limited. The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells

A comparison of earthwork designs for railway transition zones

Railway track transitions are zones where there is an abrupt change in the track-ground structure. They are often the location of rapid track deterioration, which means more frequent track maintenance is needed compared to plain line tracks. With the aim of reducing maintenance, modern transition zone designs use tapered stiffness earthwork profiles to minimise train-track dynamics. However, there has been limited comparison regarding the effect of different tapered profiles on dynamic behaviour. Therefore, this paper's novelty is the investigation of the performance of different earthwork designs in smoothing stiffness transition's considering different types of improvement and also train speed. To do so, first a 3D finite element track model is developed, with support conditions transitioning from an earth embankment onto a concrete bridge. A dynamic moving train load is simulated using a rigid multi-body approach capable of accounting for train-track interaction. The model is used to study the effect of four earthwork solutions with differing stiffness tapers. For each scenario, two different track structure types (ballast and concrete slab) are considered, along with different magnitudes of ground improvement. Lastly, the effects of train speed are explored. It is found tapered earthwork solutions for ballasted tracks show greater dynamic improvement compared to slabs due to their reduced bending stiffness. Further, the more complex improvement geometries such as double trapezoid shapes offer some additional improvement at locations within 3 m of the bridge. However, when considering such tapered stiffness-based earthwork solutions, additional factors such as constructability must also be considered.Railway Engineerin

Microwave Susceptibility Observation of Interacting Many-Body Andreev States

Electrostatic charging affects the many-body spectrum of Andreev states, yet its influence on their microwave properties has not been elucidated. We developed a circuit quantum electrodynamics probe that, in addition to transition spectroscopy, measures the microwave susceptibility of different states of a semiconductor nanowire weak link with a single dominant (spin-degenerate) Andreev level. We found that the microwave susceptibility does not exhibit a particle-hole symmetry, which we qualitatively explain as an influence of Coulomb interaction. Moreover, our state-selective measurement reveals a large, ?-phase shifted contribution to the response common to all many-body states which can be interpreted as arising from a phase-dependent continuum in the superconducting density of states.BUS/Quantum DelftQRD/Geresdi La

Correction: Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions (Oncogene, (2019), 38, 30, (5839-5859), 10.1038/s41388-019-0844-0)

© 2019, The Author(s), under exclusive licence to Springer Nature Limited. The original version of this Article contained an error in the author affiliations. Vladislav V. Verkhusha was incorrectly associated with the School of Mathematics, Statistics & Applied Mathematics, National University of Ireland Galway, Galway, Ireland. The correct affiliation is Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA