367 research outputs found
The role of the mitochondria profission protein DRP1 in T cell development and function
No full textT cells rely on cell proliferation and migration both during their development inside the thymus and in the periphery to perform immunoprotective functions. Mitochondrial dynamics and in particular Drp1dependent mitochondrial fragmentation deeply affect both these processes in several other different cellular contexts. Moreover, mature polarized T cell relies on mitochondrial accumulation at the back-located uropod to correctly migrate. Therefore, in this work, we decided to investigate whether Drp1 could have a role in development and different physiological functions of the adaptive immune system. Here we show that conditional removal of Drp1 in T lymphocyte lineage, starting from the stage of developing thymocyte, results in a reduction of proliferation capability of both developing and activated T cells due to a longer mitosis length. Furthermore, impairment of T lymphocytes to accumulate mitochondria at the uropode in absence of Drp1 causes a reduction in migration of thymocytes inside thymus, with a consequent increase in cell death sensitivity in cortical areas and a reduced accumulation of medullary thymocytes. Similarly, also mature T cells show an impairment in transmigration across endothelial barriers. This gives rise to an in vivo defective recirculation of T cells inside secondary lymphoid organs and inflamed sites. Together these findings suggest that Drp1 conditional KO mice could develop an immunodeficient phenotype when the immune system is challenged. Indeed, injection of subcutaneous tumours into Drp1 conditional KO mice results in a faster tumour growth due to a reduced capability of T cells to infiltrate the tumoural mass
Radiative corrections to decay amplitudes in lattice QCD
No full textThe precision of lattice QCD computations of many quantities has reached such a precision that isospin-breaking corrections, including electromagnetism, must be included if further progress is to be made in extracting fundamental information, such as the values of Cabibbo-Kobayashi-Maskawa matrix elements, from experimental measurements. We discuss the framework for including radiative corrections in leptonic and semileptonic decays of hadrons, including the treatment of infrared divergences. We briefly review isospin breaking in leptonic decays and present the first numerical results for the ratio Gamma(Kmu2)=Gamma(pimu2) in which these corrections have been included. We also discuss the additional theoretical issues which arise when including electromagnetic corrections to semileptonic decays, such as Kl3 decays. The separate definition of strong isospin-breaking effects and those due to electromagnetism requires a convention. We define and advocate conventions based on hadronic schemes, in which a chosen set of hadronic quantities, hadronic masses for example, are set equal in QCD and in QCD+QED. This is in contrast with schemes which have been largely used to date, in which the renormalised alphas(mu) and quark masses are set equal in QCD and in QCD+QED in some renormalisation scheme and at some scale mu
HVP contribution of the light quarks to the muon including isospin-breaking corrections with Twisted-Mass fermions
No full textWe present a preliminary lattice calculation of the leading-order electromagnetic and strong isospin-breaking corrections to the Hadronic Vacuum Polarization (HVP) contribution of the light quarks to the anomalous magnetic moment of the muon. The results are obtained in the quenched- approximation using the gauge configurations generated by the European Twisted Mass Collaboration (ETMC) with dynamical quarks, at three values of the lattice spacing varying from to 0.062 ~ \mbox{fm}, at several lattice volumes and with pion masses in the range M_\pi \simeq 220 \div 490 ~ \mbox{MeV}
AN APPROACH TO DISCRETE EVENT MODELLING PART 1: SIMULA
No full textThis paper covers the design and implementation of the
latest Simula based package for discrete event simulation modelling.
Demos inherits Simula's process approach and provides additional features
for handling process synchronisations and interrupts, (unobtrusive) data collection,
automatic tracing and reporting, and for the automatic generation of
well-separated seeds in the random number routines. This paper outlines
the implementation of these facilities and gives examples of how they
can be used.
It is written in five parts: part 1 introduces Simula; part 2 describes
the process approach to discrete event modelling; part 3 compares that
approach with the transaction, event and activity styles and gives
implementation outlines of GPSS, Simscript, and ECSL in Simula; part 4
goes through the facilities contained in Demos and motivates them via
examples; and part 5 is concerned with the implementation techniques
involved.We are currently acquiring citations for the work deposited into this collection. We recognize the distribution rights of this item may have been assigned to another entity, other than the author(s) of the work.If you can provide the citation for this work or you think you own the distribution rights to this work please contact the Institutional Repository Administrator at [email protected]
Electromagnetic corrections to leptonic decay rates of charged pseudoscalar mesons: finite-volume effects
No full textIn Carrasco et al. we have recently proposed a method to calculate O(e^2) electromagnetic corrections to leptonic decay widths of pseudoscalar mesons. The method is based on the observation that the infrared divergent contributions (that appear at intermediate stages of the calculation and that cancel in physical quantities thanks to the Bloch-Nordsieck mechanism) are
universal, i.e. depend on the charge and the mass of the meson but not on its internal structure. In this talk we perform a detailed analysis of the finite-volume effects associated with our method. In particular we show that also the leading 1/L finite-volume effects are universal and perform an analytical calculation of the finite-volume leptonic decay rate for a
point-like meson
Semileptonic D-decays with twisted mass QCD on the lattice
No full textWe study matrix elements of the "chromomagnetic" operator on the lattice. This operator is contained in the strangeness-changing effective Hamiltonian which describes electroweak effects in the Standard Model and beyond. Having dimension 5, the chromomagnetic operator is characterized by a rich pattern of mixing with other operators of equal and lower dimensionality, including also non gauge invariant quantities; it is thus quite a challenge to extract from lattice simulations a clear signal for the hadronic matrix elements of this operator. We compute all relevant mixing coefficients to one loop in lattice perturbation theory; this necessitates calculating both 2-point (quark-antiquark) and 3-point (gluon-quark-antiquark) Green's functions at nonzero quark masses. We use the twisted mass lattice formulation, with Symanzik improved gluon action. For a comprehensive presentation of our results, along with detailed explanations and a more complete list of references, we refer to our forthcoming publication [1]
Mn-peptides complexes involved in γ-radiation resistance in Deinococcus radiodurans
No full textDeinococcus Radiodurans (Dr) is a bacterium which has drawn a lot of attention on its
extraordinary radioprotective properties since its discovery in 1956. Different authors
have reported that Mn-peptide complexes, isolated from Dr cell-free extract, could act as
scavenging agents by neutralizing ROS molecules induced through radiation exposure [1].
In this study we have investigated the interaction between Mn(II) and two different
peptides, DP1(DEHGTAVMLK) and DP2 (THMVLAKGED), as a model of the
antioxidative mechanism in Dr. The amino acid composition of these peptides was chosen
randomly on the basis of their natural abundance in the Dr protein-free cell extract
(ultrafiltrate). We have focused our attention on the coordination of Mn(II) with DP1 and
DP2 peptides by using NMR, EPR and ESI-MS techniques. Additionally, competition
experiments have been done to study the equilibrium between Mn-peptides and Mnphosphate
complexes, which, according to recent findings, could be a key point to explain
the radiation resistance of Dr [2]
Metal interactions with peptide fragments from Parkinson’s disease genes
No full textRecently, a connection between the genetic and environmental causes of Parkinson’s disease (PD) has been reported1-3.
Among transition metals, manganese is an important metal that is both an essential and a toxic element at high doses. Cells have therefore to carefully control uptake and trafficking of this ion.
It has been reported that a human PD gene, PARK9 and its homologue in yeast, YPK9, can prevent manganese-induced PD symptoms and protect neurons and cells from manganese poisoning. These genes encode a protein which, considering its richness in coordinating residues, looks like a metal transporter protein3, 4.
We studied the possibility of metal binding to some portions of PARK9 and YPK9. In fact, from the inspection within the protein amino acid sequence, we detected very promising sites for metal interaction, excluding the membrane-spanning and the alpha-helical rich segments, probably not easily accessible to metals.
They contain histidine and cysteine residues, known for being good metal anchoring sites, which are surrounded by residues bearing coordinating side chains, especially aspartate and glutamate, amino acids usually relevant in the homeostasis, transport or detoxification of manganese ions.
Mono- and bi-dimensional NMR spectroscopy has been used to study the metal binding sites at different ligand to metal molar ratios and pH values.
Among others, Mn(II) coordination with peptide involves imidazole Nδ or Nε of His and carboxyl γ-O of Asp and Glu residues. Six donor atoms participate in Mn(II) binding resulting in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl group. When cysteines are present in the sequence, Mn(II) coordination involves sulphur donor atoms from cysteine residues; additional oxygen donors from Glu or Asp complete the coordination sphere
The coordination properties of a small peptide fragment from Human TLR4 sequence are relevant in Nickel Allergy mechanism
No full textNickel Allergy (NA) is a contact allergy which could occur in sensitised persons exposed
for long periods of time to objects containing Nickel. In recent years, the human TLR4
(hTLR4) has been recognized as a key target in the Nickel-induced inflammation that
eventually lead to allergy symptoms [1]. A peptide of 32 amino acids from 429-460
sequence of hTLR4 receptor has been selected as a simplified model to study the
molecular mechanism of NA. The fragment contains three histidines, the non-conserved
H431, and the conserved H456 and H458 in human (Fig. 1) which could be important for
Ni(II) activation hTLR4 and to trigger an inflammatory response. The aim of our study
was to confirm the coordination ability of a peptide fragment toward the H456 and H458
histidines potentially involved in hTLR4 activation. Spectroscopic (NMR, UV-Vis, CD,
MS) and potentiometric techniques confirm the important role of the histidine-rich 429-
460 hTLR4 fragment in Ni(II) coordination and its relevance in NA mechanism [2]
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