Concerted Transport and Phosphorylation of Diacylglycerol at ER-PM Contacts Sites Regulates Phospholipid Dynamics During Stress

A universal response of plants to environmental stresses is the activation of plasma membrane (PM) phospholipase C (PLC) that hydrolyzes phosphatidylinositol phosphate (PIP) to produce soluble inositol phosphate (IP) and diacylglycerol (DAG). DAG produced in this way can be either phosphorylated by PM diacylglycerol kinases (DGKs) to produce the second messenger phosphatidic acid (PA) or transferred to the endoplasmic reticulum (ER) by the Synaptotagmin 1 (SYT1) protein at ER-PM Contact Sites (CS). In Arabidopsis, the clearance of DAG at the PM (avoiding deleterious accumulation) by the transfer activity of SYT is essential to maintain PM stability after stress. In this study we identify that DGK1 and DGK2 form a module with SYT1 at ER-PM CS through interaction of their C1 and C2 domains respectively. Global transcriptomic and metabolomic analyses confirms that SYT1 and DGK1/DGK2 are functionally related and lipidomic analysis supports the hypothesis that DGK1 and DGK2 function at the ER by phosphorylating DAG transferred by SYT1 from the PM. DGK1 and DGK2 show structural similarity to human DGKε, the DGK isoform that function at ER-PM CS in the phosphoinositide (PI) cycle. Our data indicate that components of the PI cycle are conserved between animals and plants and provide a novel mechanism leading to an increase in the efficiency of the PI cycle by channeling the transport and hydrolysis of DAG at the ER-PM CS

Short-Wave Excitations in Non-Local Gross-Pitaevskii Model

It is shown, that a non-local form of the Gross-Pitaevskii equation allows to describe not only the long-wave excitations, but also the short-wave ones in the systems with Bose-condensate. At given parameter values, the excitation spectrum mimics the Landau spectrum of quasi-particle excitations in superfluid Helium with roton minimum. The excitation wavelength, at which the roton minimum exists, is close to the inter-particle interaction range. It is shown, that the existence domain of the spectrum with a roton minimum is reduced, if one accounts for an inter-particle attraction.Comment: 5 pages, 5 figures, UJP style; presented at Bogolyubov Kyiv Conference "Modern Problems of Theoretical and Mathematical Physics", September 15-18, 200

Point of care diagnostics for tuberculosis

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the ‘‘missed TB cases’’

Topological Color Codes and Two-Body Quantum Lattice Hamiltonians

Topological color codes are among the stabilizer codes with remarkable properties from quantum information perspective. In this paper we construct a four-valent lattice, the so called ruby lattice, governed by a 2-body Hamiltonian. In a particular regime of coupling constants, degenerate perturbation theory implies that the low energy spectrum of the model can be described by a many-body effective Hamiltonian, which encodes the color code as its ground state subspace. The gauge symmetry $\mathbf{Z}_{2}\times\mathbf{Z}_{2}$ of color code could already be realized by identifying three distinct plaquette operators on the lattice. Plaquettes are extended to closed strings or string-net structures. Non-contractible closed strings winding the space commute with Hamiltonian but not always with each other giving rise to exact topological degeneracy of the model. Connection to 2-colexes can be established at the non-perturbative level. The particular structure of the 2-body Hamiltonian provides a fruitful interpretation in terms of mapping to bosons coupled to effective spins. We show that high energy excitations of the model have fermionic statistics. They form three families of high energy excitations each of one color. Furthermore, we show that they belong to a particular family of topological charges. Also, we use Jordan-Wigner transformation in order to test the integrability of the model via introducing of Majorana fermions. The four-valent structure of the lattice prevents to reduce the fermionized Hamiltonian into a quadratic form due to interacting gauge fields. We also propose another construction for 2-body Hamiltonian based on the connection between color codes and cluster states. We discuss this latter approach along the construction based on the ruby lattice.Comment: 56 pages, 16 figures, published version

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a measurement of the top quark pair production cross section in ppbar collisions at sqrt(s)=1.96 TeV using 318 pb^{-1} of data collected with the Collider Detector at Fermilab. We select ttbar decays into the final states e nu + jets and mu nu + jets, in which at least one b quark from the t-quark decays is identified using a secondary vertex-finding algorithm. Assuming a top quark mass of 178 GeV/c^2, we measure a cross section of 8.7 +-0.9 (stat) +1.1-0.9 (syst) pb. We also report the first observation of ttbar with significance greater than 5 sigma in the subsample in which both b quarks are identified, corresponding to a cross section of 10.1 +1.6-1.4(stat)+2.0-1.3 (syst) pb.Comment: Accepted for publication in Physics Review Letters, 7 page

Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson

We report first evidence for a fully reconstructed decay mode of the B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability of a peak of this magnitude occurring by random fluctuation in the search region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR

Top quark mass measurement using the template method at CDF

We present a measurement of the top quark mass in the lepton+jets and dilepton channels of $t\bar{t}$ decays using the template method. The data sample corresponds to an integrated luminosity of 5.6 fb$^{-1}$ of $p\bar{p}$ collisions at Tevatron with $\sqrt{s}=1.96$ TeV, collected with the CDF II detector. The measurement is performed by constructing templates of three kinematic variables in the lepton+jets and two kinematic variables in the dilepton channel. The variables are two reconstructed top quark masses from different jets-to-quarks combinations and the invariant mass of two jets from the $W$ decay in the lepton+jets channel, and a reconstructed top quark mass and $m_{T2}$, a variable related to the transverse mass in events with two missing particles, in the dilepton channel. The simultaneous fit of the templates from signal and background events in the lepton+jets and dilepton channels to the data yields a measured top quark mass of $M_{top} = 172.1 \pm 1.1(stat) \pm 0.9(syst).$Comment: submitted to Phys. Rev.

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracellular disposal of protein aggregates

Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species