Two-electron lateral quantum-dot molecules in a magnetic field

Laterally coupled quantum dot molecules are studied using exact diagonalization techniques. We examine the two-electron singlet-triplet energy difference as a function of magnetic field strength and investigate the magnetization and vortex formation of two- and four-minima lateral quantum dot molecules. Special attention is paid to the analysis of how the distorted symmetry affects the properties of quantum-dot molecules.Comment: 18 pages, 26 figure

Magnetoplasmon excitations in an array of periodically modulated quantum wires

Motivated by the recent experiment of Hochgraefe et al., we have investigated the magnetoplasmon excitations in a periodic array of quantum wires with a periodic modulation along the wire direction. The equilibrium and dynamic properties of the system are treated self-consistently within the Thomas-Fermi-Dirac-von Weizsaecker approximation. A calculation of the dynamical response of the system to a far-infrared radiation field reveals a resonant anticrossing between the Kohn mode and a finite-wavevector longitudinal excitation which is induced by the density modulation along the wires. Our theoretical calculations are found to be in excellent agreement with experiment.Comment: 9 pages, 8 figure

Real-time imaging of the bacillithiol redox potential in the human pathogen Staphylococcus aureus using a genetically encoded bacilliredoxin-fused redox biosensor

Aims: Bacillithiol (BSH) is utilized as major thiol-redox buffer in the human pathogen Staphylococcus aureus. Under oxidative stress, BSH forms mixed disulfides with proteins, termed as S-bacillithiolation which can be reversed by bacilliredoxins (Brx). In eukaryotes, glutaredoxin-fused roGFP2 biosensors have been applied for dynamic live-imaging of the glutathione redox potential. Here, we have constructed a genetically encoded bacilliredoxin-fused redox biosensor (Brx-roGFP2) to monitor dynamic changes in the BSH redox potential in S. aureus. Results: The Brx-roGFP2 biosensor showed a specific and rapid response to low levels bacillithiol disulphide (BSSB) in vitro which required the active-site Cys of Brx. Dynamic live-imaging in two methicillin-resistant S. aureus (MRSA) USA300 and COL strains revealed fast and dynamic responses of the Brx-roGFP2 biosensor under hypochlorite and H2O2 stress and constitutive oxidation of the probe in different BSH-deficient mutants. Furthermore, we found that the Brx-roGFP2 expression level and the dynamic range is higher in S. aureus COL compared to the USA300 strain. In phagocytosis assays with THP-1 macrophages, the biosensor was 87 % oxidized in S. aureus COL. However, no changes in the BSH redox potential were measured after treatment with different antibiotics classes indicating that antibiotics do not cause oxidative stress in S. aureus. Conclusion and Innovation: This Brx-roGFP2 biosensor catalyzes specific equilibration between the BSH and roGFP2 redox couples and can be applied for dynamic live imaging of redox changes in S. aureus and other BSH-producing Firmicutes

Neuronal activity regulates extracellular tau in vivo

Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it is also found in the extracellular space of the brain at appreciable concentrations. Although its presence there may be relevant to the intercellular spread of tau pathology, the cellular mechanisms regulating tau release into the extracellular space are not well understood. To test this in the context of neuronal networks in vivo, we used in vivo microdialysis. Increasing neuronal activity rapidly increased the steady-state levels of extracellular tau in vivo. Importantly, presynaptic glutamate release is sufficient to drive tau release. Although tau release occurred within hours in response to neuronal activity, the elimination rate of tau from the extracellular compartment and the brain is slow (half-life of ∼11 d). The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself

Quasiclassical magnetotransport in a random array of antidots

We study theoretically the magnetoresistance $\rho_{xx}(B)$ of a two-dimensional electron gas scattered by a random ensemble of impenetrable discs in the presence of a long-range correlated random potential. We believe that this model describes a high-mobility semiconductor heterostructure with a random array of antidots. We show that the interplay of scattering by the two types of disorder generates new behavior of $\rho_{xx}(B)$ which is absent for only one kind of disorder. We demonstrate that even a weak long-range disorder becomes important with increasing $B$. In particular, although $\rho_{xx}(B)$ vanishes in the limit of large $B$ when only one type of disorder is present, we show that it keeps growing with increasing $B$ in the antidot array in the presence of smooth disorder. The reversal of the behavior of $\rho_{xx}(B)$ is due to a mutual destruction of the quasiclassical localization induced by a strong magnetic field: specifically, the adiabatic localization in the long-range Gaussian disorder is washed out by the scattering on hard discs, whereas the adiabatic drift and related percolation of cyclotron orbits destroys the localization in the dilute system of hard discs. For intermediate magnetic fields in a dilute antidot array, we show the existence of a strong negative magnetoresistance, which leads to a nonmonotonic dependence of $\rho_{xx}(B)$.Comment: 21 pages, 13 figure

Profiling the tyrosine phosphoproteome of different mouse mammary tumour models reveals distinct, model-specific signalling networks and conserved oncogenic pathways

Introduction Although aberrant tyrosine kinase signalling characterises particular breast cancer subtypes, a global analysis of tyrosine phosphorylation in mouse models of breast cancer has not been undertaken to date. This may identify conserved oncogenic pathways and potential therapeutic targets. Methods We applied an immunoaffinity/mass spectrometry workflow to three mouse models: murine stem cell virus-Neu, expressing truncated Neu, the rat orthologue of human epidermal growth factor receptor 2, Her2 (HER2); mouse mammary tumour virus-polyoma virus middle T antigen (PyMT); and the p53?/? transplant model (p53). Pathways and protein¿protein interaction networks were identified by bioinformatics analysis. Molecular mechanisms underpinning differences in tyrosine phosphorylation were characterised by Western blot analysis and array comparative genomic hybridisation. The functional role of mesenchymal¿epithelial transition factor (Met) in a subset of p53-null tumours was interrogated using a selective tyrosine kinase inhibitor (TKI), small interfering RNA (siRNA)¿mediated knockdown and cell proliferation assays. Results The three models could be distinguished on the basis of tyrosine phosphorylation signatures and signalling networks. HER2 tumours exhibited a protein¿protein interaction network centred on avian erythroblastic leukaemia viral oncogene homologue 2 (Erbb2), epidermal growth factor receptor and platelet-derived growth factor receptor ?, and they displayed enhanced tyrosine phosphorylation of ERBB receptor feedback inhibitor 1. In contrast, the PyMT network displayed significant enrichment for components of the phosphatidylinositol 3-kinase signalling pathway, whereas p53 tumours exhibited increased tyrosine phosphorylation of Met and components or regulators of the cytoskeleton and shared signalling network characteristics with basal and claudin-low breast cancer cells. A subset of p53 tumours displayed markedly elevated cellular tyrosine phosphorylation and Met expression, as well as Met gene amplification. Treatment of cultured p53-null cells exhibiting Met amplification with a selective Met TKI abrogated aberrant tyrosine phosphorylation and blocked cell proliferation. The effects on proliferation were recapitulated when Met was knocked down using siRNA. Additional subtypes of p53 tumours exhibited increased tyrosine phosphorylation of other oncogenes, including Peak1/SgK269 and Prex2. Conclusion This study provides network-level insights into signalling in the breast cancer models utilised and demonstrates that comparative phosphoproteomics can identify conserved oncogenic signalling pathways. The Met-amplified, p53-null tumours provide a new preclinical model for a subset of triple-negative breast cancers

The state of the art in the analysis of two-dimensional gel electrophoresis images

Software-based image analysis is a crucial step in the biological interpretation of two-dimensional gel electrophoresis experiments. Recent significant advances in image processing methods combined with powerful computing hardware have enabled the routine analysis of large experiments. We cover the process starting with the imaging of 2-D gels, quantitation of spots, creation of expression profiles to statistical expression analysis followed by the presentation of results. Challenges for analysis software as well as good practices are highlighted. We emphasize image warping and related methods that are able to overcome the difficulties that are due to varying migration positions of spots between gels. Spot detection, quantitation, normalization, and the creation of expression profiles are described in detail. The recent development of consensus spot patterns and complete expression profiles enables one to take full advantage of statistical methods for expression analysis that are well established for the analysis of DNA microarray experiments. We close with an overview of visualization and presentation methods (proteome maps) and current challenges in the field

The clinical and functional significance of c-Met in breast cancer: a review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.CMH-Y is funded by a Cancer Research UK Clinical Research Fellowship. JLJ is funded by the Breast Cancer Campaign Tissue Bank

Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD