The LGN:Insc tetramer stabilises the apical site in asymmetric cell divisions

Asymmetric cell divisions regulate the position and the fate choice of daughter cells, with impact on developmental programs and tissue homeostasis. The asymmetric outcome of a stem cell division relies on the coordination between cortical polarity and the orientation of the mitotic spindle. To date the adaptor Inscuteable (Insc) is considered the molecular bridge between cortical polarity proteins and the spindle tethering machinery assembled on NuMA:LGN:Gαi. Insc interacts with the polarity protein Par3, and competes with NuMA for the binding to LGN [1]. I will present the crystallographic structure of Drosophila LGN in complex with the asymmetric domain of Insc. The structure reveals a tetrameric arrangement of intertwined molecules, and is compatible with the concomitant binding of Insc to LGN and Par3. Binding assays indicate that Insc interacts directly with the PDZ region of Par3. The finding that LGN enters a stable tetrameric complex with Insc and Par3 suggests a novel function for LGN in stabilizing the apical site, where polarity proteins enrich during asymmetric cell divisions. I will propose a revised model for mitotic spindle coupling to polarity cues based on the dual role of LGN in organizing microtubule motors when in complex with NuMA and Dynein, and securing their cortical attachment when bound to Insc and Par3.

[6,6′-Bis(1,1-dimethylethyl)-4,4′-dimethyl-2,2′-methylenediphenolato-κ2O,O′]dichlorido(9H-fluoren-9-ol-κO)titanium(IV)–fluorene–diethyl ether (1/0.5/1)

The title adduct, [TiCl2(C23H30O2)(C13H10O]·0.5C13H10·C4H10O, is a monomer with a trigonal–bypyramidal coordination sphere of the TiIVatom in which the ligand O atoms of the bidentate diphenolate anion are located in both apical and equatorial positions. Chloride ligands occupy the remaining two equatorial sites of the trigonal bypyramid with the fluoren-9-ol O atom occupying the other apical site. The hydroxy group H atom of this latter group is hydrogen bonded to an O atom of a non-coordinating diethyl ether molecule. The title compound also contains a further fluorene solvent molecule, which lies across a centre of symmetry and which is equally disordered over an inversion centre.

Oxido[2-{(E)-[((1E)-{(E)-2-[1-(2-oxidophenyl)ethylidene]hydrazin-1-ylidene}(prop-2-en-1-ylsulfanyl)methyl)imino]methyl}phenolato]vanadium(IV)

The VIVatom in the title complex, [V(C19H17N3O2S)O], is coordinated by two N and two O atoms of the dianionic tetradentate Schiff base ligand and the terminal oxide O atom. The N2O3donor set defines a square-pyramidal coordination geometry with the oxide O atom in the apical site. Some buckling in the tetradentate ligand is indicated by the dihedral angle of 17.92 (19)° between the six-membered chelate rings. Supramolecular chains are formed along thebaxisviaC—H...O contacts in the crystal. The chains are connected into a layer in theabplaneviaC—H...π interactions. The atoms comprising the –SCH2—CH=CH2and methyl substituents were found to be disordered in a 0.916 (2):0.088 (2) ratio. The crystal studied was found to be twinned by nonmerohedry with a 28.1 (4)% minor twin component.

Di-μ-methanolato-κ4O:O-bis[bis(3-methyl-5-phenyl-1H-pyrazole-κN2)(nitrato-κO)copper(II)]

Copper nitrate in methanol solution cleaves the N—Cmethanolbond when reacted with 3-methyl-5-phenylpyrazole-1-methanol to yield the centrosymmetric dinuclear title compound, [Cu2(CH3O)2(NO3)2(C10H10N2)4], in which the CuIIatom is linked to a nitrate ion, two methanolate ions and two pyrazole ligands in a distorted square-pyramidal environment. The O atom of the nitrate anion occupies the apical site. The crystal structure features intramolecular N—H...O hydrogen bonds.

Photoelastic Comparison of Single Tooth Implant-Abutment-Bone of Platform Switching vs Conventional Implant Designs

ABSTRACT Objectives The maintenance and stability of peri-implantar soft tissue seem to be related to the crestal bone around the implant platform and different implant designs connections might affect this phenomenon. The aim of this study was to evaluate by photoelastic analysis the stress distribution in the cervical and apical site of implant-abutment interface of conventional implant joints (external hex, internal hex and cone morse) and compare to the novel platform switching design. Materials and methods It was fabricated photoelastic models using five different implant-abutment connection, one set of external hex (Alvim Ti, Neodent, Curitiba, Brazil), one set of internal hex (Full Osseotite, Biomet 3i, Florida, USA), one cone morse set (Alvim CM, Neodent, Curitiba, Brazil), and two sets of internal hex plus platform switching concept (Alvim II Plus, Neodent, Curitiba, Brazil) (Certain Prevail, Biomet 3i, Florida, USA). These models were submitted to two compressive loads, axial from 20 kgf (load I) and another (load II), inclined 45° from 10 kgf. During the qualitative analysis, digital pictures were taken from a polariscope, for each load situation. For the quantitative analyses in both situations of load, the medium, minimum and maximum in MPa values of shear strain were determined in the cervical and apical site. The Kruskal-Wallis test was used to compare the results between the different systems and between cervical and apical site were compared using Mann-Whitney U test. Conclusion The minor stress concentration strongly suggest the use of platform switching design as a manner to prevent bone loss around the implant-abutment platform. Clinical Significance From the result of this study its possible to make clinical decision for implant system which provides implant components with platform switching characteristics. How to cite this article Rossi F, Zavanelli AC, Zavanelli RA. Photoelastic Comparison of Single Tooth Implant-abutment- Bone of Platform Switching vs Conventional Implant Designs. J Contemp Dent Pract 2011;12(2):124-130.

Inhibitory Effect of Flavonoids on the Efflux of -Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells

-acetyl 5-aminosalicylic acid (5-AcASA) that was intracellularly formed from 5-aminosalicylic acid (5-ASA) at 200 M was discharged 5.3, 7.1, and 8.1-fold higher into the apical site than into the basolateral site during 1, 2, and 4-hour incubations, respectively, in Caco-2 cells grown in Transwells. The addition of flavonols (100 M) such as fisetin and quercetin with 5-ASA remarkably decreased the apically directed efflux of 5-AcASA. When 5-ASA (200 M) was added to Caco-2 cells grown in tissue culture dishes, the formation of 5-AcASA decreased, and, in addition, the formed 5-AcASA was found to be accumulated within the cells in the presence of such flavonols. Thus, the decrease in 5-AcASA efflux by such flavonols was attributed not only to the inhibition of -acetyl-conjugation of 5-ASA but to the predominant cellular accumulation of 5-AcASA. Various flavonoids also had both of the effects with potencies that depend on their specific structures. The essential structure of flavonoids was an absence of a hydroxyl substitution at the C5 position on the A-ring of flavone structure for the inhibitory effect on the -acetyl-conjugation of 5-ASA, and a presence of hydroxyl substitutions at the C or C position on the B-ring of flavone structure for the promoting effect on the cellular accumulation of 5-AcASA. Both the decrease in 5-AcASA apical efflux and the increase in 5-AcASA cellular accumulation were also caused by MK571 and indomethacin, inhibitors of MRPs, but not by quinidine, cyclosporin A, P-glycoprotein inhibitors, and mitoxantrone, a BCRP substrate. These results suggest that certain flavonoids suppress the apical efflux of 5-AcASA possibly by inhibiting MRPs pumps located on apical membranes in Caco-2 cells.

Dibromo[N,N-dimethyl-N′-(2-pyridylmethylidene)propane-1,3-diamine]zinc(II)

In the title mononuclear zinc(II) compound, [ZnBr2(C11H17N3)], the ZnII ion is five-coordinated by three N atoms of a Schiff base ligand and by two Br− anions, forming a distorted square-pyramidal geometry with a Br atom in the apical site.

Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 ± 2 wk (means ± SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 ± 0.030; P < 0.05), whereas the apical site did not [ P = not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 ± 0.003 at 2 wk and 0.054 ± 0.021 at final; both P < 0.05), which contributed to a significant increase in wall thickness at the final study (0.181 ± 0.047; P < 0.05), whereas the apical site did not ( P = NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.