Molecular characterization of geminivirus-derived small RNAs in different plant species

DNA geminiviruses are thought to be targets of RNA silencing. Here, we characterize small interfering (si) RNAs—the hallmarks of silencing—associated with Cabbage leaf curl begomovirus in Arabidopsis and African cassava mosaic begomovirus in Nicotiana benthamiana and cassava. We detected 21, 22 and 24 nt siRNAs of both polarities, derived from both the coding and the intergenic regions of these geminiviruses. Genetic evidence showed that all the 24 nt and a substantial fraction of the 22 nt viral siRNAs are generated by the dicer-like proteins DCL3 and DCL2, respectively. The viral siRNAs were 5′ end phosphorylated, as shown by phosphatase treatments, and methylated at the 3′-nucleotide, as shown by HEN1 miRNA methylase-dependent resistance to β-elimination. Similar modifications were found in all types of endogenous and transgene-derived siRNAs tested, but not in a major fraction of siRNAs from a cytoplasmic RNA tobamovirus. We conclude that several distinct silencing pathways are involved in DNA virus-plant interaction

Molecular characterization of geminivirus-derived small RNAs in different plant species

DNA geminiviruses are thought to be targets of RNA silencing. Here, we characterize small interfering (si) RNAs—the hallmarks of silencing—associated with Cabbage leaf curl begomovirus in Arabidopsis and African cassava mosaic begomovirus in Nicotiana benthamiana and cassava. We detected 21, 22 and 24 nt siRNAs of both polarities, derived from both the coding and the intergenic regions of these geminiviruses. Genetic evidence showed that all the 24 nt and a substantial fraction of the 22 nt viral siRNAs are generated by the dicer-like proteins DCL3 and DCL2, respectively. The viral siRNAs were 5′ end phosphorylated, as shown by phosphatase treatments, and methylated at the 3′-nucleotide, as shown by HEN1 miRNA methylase-dependent resistance to β-elimination. Similar modifications were found in all types of endogenous and transgene-derived siRNAs tested, but not in a major fraction of siRNAs from a cytoplasmic RNA tobamovirus. We conclude that several distinct silencing pathways are involved in DNA virus-plant interactions

The break up of heavy electrons at a quantum critical point

The point at absolute zero where matter becomes unstable to new forms of order is called a quantum critical point (QCP). The quantum fluctuations between order and disorder that develop at this point induce profound transformations in the finite temperature electronic properties of the material. Magnetic fields are ideal for tuning a material as close as possible to a QCP, where the most intense effects of criticality can be studied. A previous study on theheavy-electron material $YbRh_2Si_2$ found that near a field-induced quantum critical point electrons move ever more slowly and scatter off one-another with ever increasing probability, as indicated by a divergence to infinity of the electron effective mass and cross-section. These studies could not shed light on whether these properties were an artifact of the applied field, or a more general feature of field-free QCPs. Here we report that when Germanium-doped $YbRh_2Si_2$ is tuned away from a chemically induced quantum critical point by magnetic fields there is a universal behavior in the temperature dependence of the specific heat and resistivity: the characteristic kinetic energy of electrons is directly proportional to the strength of the applied field. We infer that all ballistic motion of electrons vanishes at a QCP, forming a new class of conductor in which individual electrons decay into collective current carrying motions of the electron fluid.Comment: Pdf files of article available at http://www.physics.rutgers.edu/~coleman/online/breakup.pdf, pdf file of news and views article available at http://www.physics.rutgers.edu/~coleman/online/nvbreakup.pd

Local fluctuations in quantum critical metals

We show that spatially local, yet low-energy, fluctuations can play an essential role in the physics of strongly correlated electron systems tuned to a quantum critical point. A detailed microscopic analysis of the Kondo lattice model is carried out within an extended dynamical mean-field approach. The correlation functions for the lattice model are calculated through a self-consistent Bose-Fermi Kondo problem, in which a local moment is coupled both to a fermionic bath and to a bosonic bath (a fluctuating magnetic field). A renormalization-group treatment of this impurity problem--perturbative in $\epsilon=1-\gamma$, where $\gamma$ is an exponent characterizing the spectrum of the bosonic bath--shows that competition between the two couplings can drive the local-moment fluctuations critical. As a result, two distinct types of quantum critical point emerge in the Kondo lattice, one being of the usual spin-density-wave type, the other ``locally critical.'' Near the locally critical point, the dynamical spin susceptibility exhibits $\omega/T$ scaling with a fractional exponent. While the spin-density-wave critical point is Gaussian, the locally critical point is an interacting fixed point at which long-wavelength and spatially local critical modes coexist. A Ginzburg-Landau description for the locally critical point is discussed. It is argued that these results are robust, that local criticality provides a natural description of the quantum critical behavior seen in a number of heavy-fermion metals, and that this picture may also be relevant to other strongly correlated metals.Comment: 20 pages, 12 figures; typos in figure 3 and in the main text corrected, version as publishe

Further analysis of the quantum critical point of Ce1−x_{1-x}Lax_{x}Ru2_{2}Si2_{2}

New data on the spin dynamics and the magnetic order of Ce$_{1-x}$La$_{x}$Ru$_{2}$Si$_{2}$ are presented. The importance of the Kondo effect at the quantum critical point of this system is emphasized from the behaviour of the relaxation rate at high temperature and from the variation of the ordered moment with respect to the one of the N\'eel temperature for various $x$.Comment: Contribution for the Festschrift on the occasion of Hilbert von Loehneysen 60 th birthday. To be published as a special issue in the Journal of Low Temperature Physic

Orbital-selective Mott transitions: Heavy fermions and beyond

Quantum phase transitions in metals are often accompanied by violations of Fermi liquid behavior in the quantum critical regime. Particularly fascinating are transitions beyond the Landau-Ginzburg-Wilson concept of a local order parameter. The breakdown of the Kondo effect in heavy-fermion metals constitutes a prime example of such a transition. Here, the strongly correlated f electrons become localized and disappear from the Fermi surface, implying that the transition is equivalent to an orbital-selective Mott transition, as has been discussed for multi-band transition-metal oxides. In this article, available theoretical descriptions for orbital-selective Mott transitions will be reviewed, with an emphasis on conceptual aspects like the distinction between different low-temperature phases and the structure of the global phase diagram. Selected results for quantum critical properties will be listed as well. Finally, a brief overview is given on experiments which have been interpreted in terms of orbital-selective Mott physics.Comment: 29 pages, 4 figs, mini-review prepared for a special issue of JLT

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm

K-Ras Mediated Murine Epidermal Tumorigenesis Is Dependent upon and Associated with Elevated Rac1 Activity

A common goal for potential cancer therapies is the identification of differences in protein expression or activity that would allow for the selective targeting of tumor vs. normal cells. The Ras proto-oncogene family (K-Ras, H-Ras and N-Ras) are amongst the most frequently mutated genes in human cancers. As a result, there has been substantial effort dedicated to determining which pathways are activated by Ras signaling and, more importantly, which of these contribute to cancer. Although the most widely studied Ras-regulated signaling pathway is the Raf/mitogen-activated protein kinase cascade, previous research in model systems has revealed that the Rac1 GTP-binding protein is also required for Ras-induced biological responses. However, what have been lacking are rigorous in vivo Rac1 target validation data and a clear demonstration that in Ras-driven hyperplastic lesions, Rac1 activity is increased. Using a combination of genetically-modified mouse models that allow for the tissue-selective activation or deletion of signaling molecules and an activation-state sensitive Rac1 antibody that detects GTP-bound Rac1, we found that Rac1 contributes to K-Ras induced epidermal papilloma initiation and growth and that Rac1 activity is elevated by oncogenic K-Ras in vivo. Previously, it was not practical to assess Rac1 activation status in the most commonly used format for clinical tumor specimens, formalin-fixed paraffin embedded (FFPE) tissues samples. However, this study clearly demonstrates that Rac1 is essential for K-Ras driven epithelial cell hyperproliferation and that Rac1 activity is elevated in tissues expressing mutant oncogenic K-Ras, while also characterizing the activation-state specific Rac1-GTP antibody as a probe to examine Rac1 activation status in FFPE samples. Our findings will facilitate further research on the status of Rac1 activity in human tumors and will help to define the tumor types of the patient population that could potentially benefit from therapies targeting Rac activation or downstream effector signaling pathways

Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging

Labeling of cells with nanoparticles for living detection is of interest to various biomedical applications. In this study, novel fluorescent/magnetic nanoparticles were prepared and used in high-efficient cellular imaging. The nanoparticles coated with the modified chitosan possessed a magnetic oxide core and a covalently attached fluorescent dye. We evaluated the feasibility and efficiency in labeling cancer cells (SMMC-7721) with the nanoparticles. The nanoparticles exhibited a high affinity to cells, which was demonstrated by flow cytometry and magnetic resonance imaging. The results showed that cell-labeling efficiency of the nanoparticles was dependent on the incubation time and nanoparticles’ concentration. The minimum detected number of labeled cells was around 104by using a clinical 1.5-T MRI imager. Fluorescence and transmission electron microscopy instruments were used to monitor the localization patterns of the magnetic nanoparticles in cells. These new magneto-fluorescent nanoagents have demonstrated the potential for future medical use

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal