Phosphoinositide kinase signaling controls ER-PM cross-talk

Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in lipid homeostasis are linked to the progression of several diseases. However, little is known about the sensory mechanisms for detecting membrane composition and how lipid metabolism is regulated in response to membrane stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the endoplasmic reticulum (ER) to modulate essential responses, including Ca(2+)-regulated lipid biogenesis, upon plasma membrane (PM) stress. Furthermore, loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Thus PI kinase-mediated ER-PM cross-talk comprises a regulatory system that ensures cellular integrity under membrane stress conditions

Bilayer manganites: polarons in the midst of a metallic breakdown

The exact nature of the low temperature electronic phase of the manganite materials family, and hence the origin of their colossal magnetoresistant (CMR) effect, is still under heavy debate. By combining new photoemission and tunneling data, we show that in La{2-2x}Sr{1+2x}Mn2O7 the polaronic degrees of freedom win out across the CMR region of the phase diagram. This means that the generic ground state is that of a system in which strong electron-lattice interactions result in vanishing coherent quasi-particle spectral weight at the Fermi level for all locations in k-space. The incoherence of the charge carriers offers a unifying explanation for the anomalous charge-carrier dynamics seen in transport, optics and electron spectroscopic data. The stacking number N is the key factor for true metallic behavior, as an intergrowth-driven breakdown of the polaronic domination to give a metal possessing a traditional Fermi surface is seen in the bilayer system.Comment: 7 pages, 2 figures, includes supplementary informatio

Transition-metal dimers and physical limits on magnetic anisotropy

Recent advances in nanoscience have raised interest in the minimum bit size required for classical information storage, i.e. for bistability with suppressed quantum tunnelling and energy barriers that exceed ambient temperatures. In the case of magnetic information storage much attention has centred on molecular magnets[1] with bits consisting of ~ 100 atoms, magnetic uniaxial anisotropy energy barriers ~ 50 K, and very slow relaxation at low temperatures. In this article we draw attention to the remarkable magnetic properties of some transition metal dimers which have energy barriers approaching ~ 500 K with only two atoms. The spin dynamics of these ultra small nanomagnets is strongly affected by a Berry phase which arises from quasi-degeneracies at the electronic Highest Occupied Molecular Orbital (HOMO) energy. In a giant spin-approximation, this Berry phase makes the effective reversal barrier thicker. [1] Gatteschi, D., Sessoli, R. & Villain, J. Molecular Nanomagnets. (Oxford, New York 2006).Comment: 14 pages, 1 figur

Myosin VI in PC12 cells plays important roles in cell migration and proliferation but not in catecholamine secretion

Myosin VI (MVI) is the only known myosin walking towards minus end of actin filaments and is believed to play distinct role(s) than other myosins. We addressed a role of this unique motor in secretory PC12 cells, derived from rat adrenal medulla pheochromocytoma using cell lines with reduced MVI synthesis (produced by means of siRNA). Decrease of MVI expression caused severe changes in cell size and morphology, and profound defects in actin cytoskeleton organization and Golgi structure. Also, significant inhibition of cell migration as well as cell proliferation was observed. Flow cytometric analysis revealed that MVI-deficient cells were arrested in G0/G1 phase of the cell cycle but did not undergo increased senescence as compared with control cells. Also, neither polyploidy nor aneuploidy were detected. Surprisingly, no significant effect on noradrenaline secretion was observed. These data indicate that in PC12 cells MVI is involved in cell migration and proliferation but is not crucial for stimulation-dependent catecholamine release

Effect of Crystallographic Texture on Magnetic Characteristics of Cobalt Nanowires

Cobalt nanowires with controlled diameters have been synthesized using electrochemical deposition in etched ion-track polycarbonate membranes. Structural characterization of these nanowires with diameter 70, 90, 120 nm and length 30 μm was performed by scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray diffraction techniques. The as-prepared wires show uniform diameter along the whole length and X-ray diffraction analysis reveals that [002] texture of these wires become more pronounced as diameter is reduced. Magnetic characterization of the nanowires shows a clear difference of squareness and coercivity between parallel and perpendicular orientations of the wires with respect to the applied field direction. In case of parallel applied field, the coercivity has been found to be decreasing with increasing diameter of the wires while in perpendicular case; the coercivity observes lower values for larger diameter. The results are explained by taking into account the magnetocrystalline and shape anisotropies with respect to the applied field and domain transformation mechanism when single domain limit is surpassed

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair

DroID: the Drosophila Interactions Database, a comprehensive resource for annotated gene and protein interactions

<p>Abstract</p> <p>Background</p> <p>Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, <it>Drosophila melanogaster</it>.</p> <p>Description</p> <p>DroID, the <it>Drosophila </it>Interactions Database, is a comprehensive interactions database designed specifically for <it>Drosophila</it>. DroID houses published physical protein interactions, genetic interactions, and computationally predicted interactions, including interologs based on data for other model organisms and humans. All interactions are annotated with original experimental data and source information. DroID can be searched and filtered based on interaction information or a comprehensive set of gene attributes from Flybase. DroID also contains gene expression and expression correlation data that can be searched and used to filter datasets, for example, to focus a study on sub-networks of co-expressed genes. To address the inherent noise in interaction data, DroID employs an updatable confidence scoring system that assigns a score to each physical interaction based on the likelihood that it represents a biologically significant link.</p> <p>Conclusion</p> <p>DroID is the most comprehensive interactions database available for <it>Drosophila</it>. To facilitate downstream analyses, interactions are annotated with original experimental information, gene expression data, and confidence scores. All data in DroID are freely available and can be searched, explored, and downloaded through three different interfaces, including a text based web site, a Java applet with dynamic graphing capabilities (IM Browser), and a Cytoscape plug-in. DroID is available at <url>http://www.droidb.org</url>.</p

Automatic Annotation of Spatial Expression Patterns via Sparse Bayesian Factor Models

Advances in reporters for gene expression have made it possible to document and quantify expression patterns in 2D–4D. In contrast to microarrays, which provide data for many genes but averaged and/or at low resolution, images reveal the high spatial dynamics of gene expression. Developing computational methods to compare, annotate, and model gene expression based on images is imperative, considering that available data are rapidly increasing. We have developed a sparse Bayesian factor analysis model in which the observed expression diversity of among a large set of high-dimensional images is modeled by a small number of hidden common factors. We apply this approach on embryonic expression patterns from a Drosophila RNA in situ image database, and show that the automatically inferred factors provide for a meaningful decomposition and represent common co-regulation or biological functions. The low-dimensional set of factor mixing weights is further used as features by a classifier to annotate expression patterns with functional categories. On human-curated annotations, our sparse approach reaches similar or better classification of expression patterns at different developmental stages, when compared to other automatic image annotation methods using thousands of hard-to-interpret features. Our study therefore outlines a general framework for large microscopy data sets, in which both the generative model itself, as well as its application for analysis tasks such as automated annotation, can provide insight into biological questions

Reduced Neutrophil Apoptosis in Diabetic Mice during Staphylococcal Infection Leads to Prolonged Tnfα Production and Reduced Neutrophil Clearance

Diabetes is a frequent underlying medical condition among individuals with Staphylococcus aureus infections, and diabetic patients often suffer from chronic inflammation and prolonged infections. Neutrophils are the most abundant inflammatory cells during the early stages of bacterial diseases, and previous studies have reported deficiencies in neutrophil function in diabetic hosts. We challenged age-matched hyperglycemic and normoglycemic NOD mice intraperitoneally with S. aureus and evaluated the fate of neutrophils recruited to the peritoneal cavity. Neutrophils were more abundant in the peritoneal fluids of infected diabetic mice by 48 h after bacterial inoculation, and they showed prolonged viability ex vivo compared to neutrophils from infected nondiabetic mice. These differences correlated with reduced apoptosis of neutrophils from diabetic mice and were dependent upon the presence of S. aureus and a functional neutrophil respiratory burst. Decreased apoptosis correlated with impaired clearance of neutrophils by macrophages both in vitro and in vivo and prolonged production of proinflammatory tumor necrosis factor alpha by neutrophils from diabetic mice. Our results suggest that defects in neutrophil apoptosis may contribute to the chronic inflammation and the inability to clear staphylococcal infections observed in diabetic patients