AKTIP/Ft1, a new shelterin-interacting factor required for telomere maintenance

Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes from incomplete replication, degradation and detection as DNA breaks. Mammalian telomeres are protected by shelterin, a multiprotein complex that binds the TTAGGG telomeric repeats and recruits a series of additional factors that are essential for telomere function. Although many shelterin-associated proteins have been so far identified, the inventory of shelterin-interacting factors required for telomere maintenance is still largely incomplete. Here, we characterize AKTIP/Ft1 (humanAKTIP and mouse Ft1 are orthologous), a novel mammalian shelterin-bound factoridentified on the basis of its homology with the Drosophila telomere protein Pendolino. AKTIP/Ft1 shares homology with the E2 variant ubiquitin-conjugating (UEV) enzymes and has been previously implicated in the control of apoptosis and in vesicle trafficking. RNAi-mediated depletion of AKTIP results in formation of telomere disfunction foci (TIFs). Consistent with these results, AKTIP interacts with telomeric DNA and binds the shelterin components TRF1 and TRF2 both in vivo and in vitro. Analysis of AKTIP- depleted human primary fibroblasts showed that they are defective in PCNA recruiting and arrest in the S phase due to the activation of the intra S checkpoint. Accordingly, AKTIP physically interacts with PCNA and the RPA70 DNA replication factor. Ft1-depleted p53-/- MEFs did not arrest in the S phase but displayed significant increases in multiple telomeric signals (MTS) and sister telomere associations (STAs), two hallmarks of defective telomere replication. In addition, we found an epistatic relation for MST formation between Ft1 and TRF1, which has been previously shown to be required for replication fork progression through telomeric DNA. Ch-IP experiments further suggested that in AKTIP-depleted cells undergoing the S phase, TRF1 is less tightly bound to telomeric DNA than in controls. Thus, our results collectively suggest that AKTIP/Ft1 works in concert with TRF1 to facilitate telomeric DNA replication

DFT Calculations as a Tool to Analyse Quadrupole Splittings of Spin Crossover Fe(II) complexes

Density functional methods have been applied to calculate the quadrupole splitting of a series of iron(II) spin crossover complexes. Experimental and calculated values are in reasonable agreement. In one case spin-orbit coupling is necessary to explain the very small quadrupole splitting value of 0.77 mm/s at 293 K for a high-spin isomer

Angular Forces Around Transition Metals in Biomolecules

Quantum-mechanical analysis based on an exact sum rule is used to extract an semiclassical angle-dependent energy function for transition metal ions in biomolecules. The angular dependence is simple but different from existing classical potentials. Comparison of predicted energies with a computer-generated database shows that the semiclassical energy function is remarkably accurate, and that its angular dependence is optimal.Comment: Tex file plus 4 postscript figure

Electronic transport, structure, and energetics of endohedral Gd@C82 metallofullerenes

Electronic structure and transport properties of the fullerene C$_{82}$ and the metallofullerene Gd@C$_{82}$ are investigated with density functional theory and the Landauer-Buttiker formalism. The ground state structure of Gd@C$_{82}$ is found to have the Gd atom below the C-C bond on the C$_2$ molecular axis of C$_{82}$. Insertion of Gd into C$_{82}$ deforms the carbon chain in the vicinity of the Gd atoms. Significant overlap of the electron distribution is found between Gd and the C$_{82}$ cage, with the transferred Gd electron density localized mainly on the nearest carbon atoms. This charge localization reduces some of the conducting channels for the transport, causing a reduction in the conductivity of the Gd@C$_{82}$ species relative to the empty C$_{82}$ molecule. The electron transport across the metallofullerene is found to be insensitive to the spin state of the Gd atom.Comment: 13 pages, 7 figures, submitted Nano Let

Selectivity and Mechanism of Hydrogen Atom Transfer by an Isolable Imidoiron (III) Complex

This article discusses a mechanistic study of hydrogen atom transfer by an isolable iron (III) imido complex, LᴹᵉFeNAd (Lᴹᵉ = bulky β-diketiminate ligand, 2,4-bis(2,6-diisopropylphenylimido)pentyl; Ad = 1-adamantyl)

Second-order grey-scale texture analysis of pleural ultrasound images to differentiate acute respiratory distress syndrome and cardiogenic pulmonary edema

Discriminating acute respiratory distress syndrome (ARDS) from acute cardiogenic pulmonary edema (CPE) may be challenging in critically ill patients. Aim of this study was to investigate if gray-level co-occurrence matrix (GLCM) analysis of lung ultrasound (LUS) images can differentiate ARDS from CPE. The study population consisted of critically ill patients admitted to intensive care unit (ICU) with acute respiratory failure and submitted to LUS and extravascular lung water monitoring, and of a healthy control group (HCG). A digital analysis of pleural line and subpleural space, based on the GLCM with second order statistical texture analysis, was tested. We prospectively evaluated 47 subjects: 16 with a clinical diagnosis of CPE, 8 of ARDS, and 23 healthy subjects. By comparing ARDS and CPE patients’ subgroups with HCG, the one-way ANOVA models found a statistical significance in 9 out of 11 GLCM textural features. Post-hoc pairwise comparisons found statistical significance within each matrix feature for ARDS vs. CPE and CPE vs. HCG (P ≤ 0.001 for all). For ARDS vs. HCG a statistical significance occurred only in two matrix features (correlation: P = 0.005; homogeneity: P = 0.048). The quantitative method proposed has shown high diagnostic accuracy in differentiating normal lung from ARDS or CPE, and good diagnostic accuracy in differentiating CPE and ARDS. Gray-level co-occurrence matrix analysis of LUS images has the potential to aid pulmonary edemas differential diagnosis

Three-Coordinate Terminal Imidoiron(III) Complexes: Structure, Spectroscopy, and Mechanism of Formation

Article discussing three-coordinate terminal imidoiron(III) complexes and the structure, spectroscopy, and the mechanism of formation

Molybdenum and Tungsten Structural Differences are Dependent on ndz2/(n + 1)ѕ Mixing: Comparisons of (silox)3MX/R (M = Mo, W; silox = tBu3SiO)

Article discussing molybdenum and tungsten structural differences being dependent on ndz2/(n + 1)s mixing and a comparison of (silox)3MX/R (M = Mo, W; silox - tBu3SiO)

Cobalt-Dinitrogen Complexes with Weakened N-N Bonds

Article discussing research on cobalt-dinitrogen complexes with weakened N-N bonds