Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins

The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 localisation and its interacting partners may greatly impact its function and need to be defined more clearly. In this study we used mass spectrometry to determine the interactomes of SIRT2 in whole cells and in specific cellular fractions; cytoplasm, nucleus and chromatin. Using this approach, we identified novel interacting partners of SIRT2. These included a number of proteins that function in nuclear import. We show that multiple importins interact with and contribute to the basal nuclear shuttling of SIRT2 and that one of these, IPO7 is required for SIRT2 mediated H3K18 deacetylation in response to bacterial infection. Furthermore, we reveal that the unstructured C-terminus of SIRT2 negatively regulates importin-binding and nuclear transport. This study demonstrates that SIRT2 is actively transported into the nucleus via a process regulated by its C-terminus and provides a resource of SIRT2 interacting partners

Silent cerebral infarct after cardiac catheterization as detected by diffusion weighted Magnetic Resonance Imaging: a randomized comparison of radial and femoral arterial approaches

Background and objective: Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site, comparing radial and femoral access, on this phenomenon. Study design: This prospective study will be performed in patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24 hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test performance and number of microembolism signals observed in the two groups. Implications: Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization and its potential relationship to cognitive decline needs to be assessed. Study registration: The SCIPION study is registered through National Institutes of Health-sponsored clinical trials registry and has been assigned the Identifier: NCT 00329979

Root exudates of the hyperaccumulator Thlaspi caerulescens do not enhance metal mobilization

To examine whether root exudates of the Zn/Cd hyperaccumulator Thlaspi caerulescens play a role in metal hyperaccumulation, we compared the metal mobilization capacity of root exudates collected from two ecotypes of T. caerulescens, and from the nonaccumulators wheat (Triticum aestivum) and canola (Brassica napus). Plants were grown hydroponically and three treatments (control, -Fe and -Zn) were later imposed for 2 wk before collection of root exudates. On a basis of root d. wt, the total soluble organic C in the root exudates of T. caerulescens was similar to that of wheat, and significantly higher than that of canola. In all treatment, the root exudates of T. caerulescens and canola mobilized little Cu and Zn from Cu- or Zn-loaded resins, and little Zn, Cd, Cu or Fe from a contaminated calcareous soil. By contrast, the root exudates of wheat generally mobilized more metals from both resin and soil. In particular, the -Fe treatment, and to a lesser extent the -Zn treatment, elicited large increases in the metal mobilization capacity of the root exudates from wheat. We conclude that root exudates from T. caerulescens do not significantly enhance mobilization of Zn and Cd, and therefore are not involved in Zn and Cd hyperaccumulation. (C) New Phytologist (2001)

Toxic gas removal – metal–organic frameworks for the capture and degradation of toxic gases and vapours

The release of anthropogenic toxic pollutants into the atmosphere is a worldwide threat of growing concern. In this regard, it is possible to take advantage of the high versatility of MOFs materials in order to develop new technologies for environmental remediation purposes. Consequently, one of the main scientific challenges to be achieved in the field of MOF research should be to maximize the performance of these solids towards the sensing, capture and catalytic degradation of harmful gases and vapors by means of a rational control of size and reactivity of the pore walls that are directly accessible to guest molecules.The authors are grateful for the generous support by the Spanish Ministries of Economy (project: CTQ2011-22787) and Defense (COINCIDENTE Program) as well as Junta de Andalucia (P09-FQM-4981)

Epigenetic Silencing of Host Cell Defense Genes Enhances Intracellular Survival of the Rickettsial Pathogen Anaplasma phagocytophilum

Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum–infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease

Towards a generalized vision of oxides: disclosing the role of cations and anions in determining unit-cell dimensions

Theoretical calculations of the electron-localization function show that, at the volumes of the two CaO phases (rocksalt and CsCl type), the parent Ca structures (fcc: face-centred cubic; sc: simple cubic) exhibit charge-concentration zones which coincide with the positions occupied by the O atoms in their oxides. For the first time, the structure type, dimension and topology of CaO and BaSnO3 are explained in univocal physical terms

A versatile, solvent-free methodology for the functionalisation of carbon nanotubes

High temperature activation of carbon nanotubes (CNTs) provides a new and highly versatile functionalisation strategy. The reaction allows the attachment of a wide variety of functional species onto the nanotube surface at grafting ratios between 1-8 wt%, whilst maintaining the intrinsic properties of the untreated materials. The underlying, radical-based, reaction mechanism has been established by quenching experiments and EPR studies. The distribution of the functionalised sites has been investigated at. the microscopic scale using tagging reactions. The grafted products have been characterized by electron microscopy, thermal analysis (TGA), Raman spectroscopy, and inverse gas chromatography (IGC). The change in the CNT surface properties after grafting has been quantified in terms of dispersive and specific surface energies, and altered dispersibilities in a broad range of solvents. It is possible to carry out the reaction using gas phase reagents, providing a clean, efficient, and scalable methodology, relevant to a diverse range of applications

Cooperation between Engulfment Receptors: The Case of ABCA1 and MEGF10

The engulfment of dying cells is a specialized form of phagocytosis that is extremely conserved across evolution. In the worm, it is genetically controlled by two parallel pathways, which are only partially reconstituted in mammals. We focused on the recapitulation of the CED-1 defined pathway in mammalian systems. We first explored and validated MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals and hence progressed toward the analysis of molecular interactions along the corresponding pathway. We ascertained that, in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a functional or a mutant ABCA1 exerted a transdominant positive or negative modulation on the MEGF10-dependent engulfment. The combined use of biochemical and biophysical approaches indicated that this functional cooperation relies on the alternate association of these receptors with a common partner, endogenously expressed in our cell system. We provide the first working model structuring in mammals the CED-1 dependent pathway

Glyburide inhibits the Cryopyrin/Nalp3 inflammasome

Glyburide, a sulfonylurea drug commonly used to treat type 2 diabetes, shuts down IL-1β secretion by preventing Cyropyrin activation