CRVO tortuosity Data English

CRVO tortuosity Data Englis

Structural and mechanistic insights into nuclear transport and delivery of the critical pluripotency factor Oct4 to DNA

<p>Oct4 is a master regulator of the induction and maintenance of cellular pluripotency, and has crucial roles in early stages of differentiation. It is the only factor that cannot be substituted by other members of the same protein family to induce pluripotency. However, although Oct4 nuclear transport and delivery to target DNA are critical events for reprogramming to pluripotency, little is known about the molecular mechanism. Oct4 is imported to the nucleus by the classical nuclear transport mechanism, which requires importin α as an adaptor to bind the nuclear localization signal (NLS). Although there are structures of complexes of the NLS of transcription factors (TFs) in complex with importin α, there are no structures available for complexes involving intact TFs. We have therefore modeled the structure of the complex of the whole Oct4 POU domain and importin α2 using protein-protein docking and molecular dynamics. The model explains how the Ebola virus VP24 protein has a negative effect on the nuclear import of STAT1 by importin α but not on Oct4, and how Nup 50 facilitates cargo release from importin α. The model demonstrates the structural differences between the Oct4 importin α bound and DNA bound crystal states. We propose that the ‘expanded linker’ between the two DNA-binding domains of Oct4 is an intrinsically disordered region and that its conformational changes have a key role in the recognition/binding to both DNA and importin α. Moreover, we propose that this structural change enables efficient delivery to DNA after release from importin α.</p

Correlation between venous tortuosity and concentration of VEGF in the aqueous humor.

<p>The degree of venous tortuosity is significantly correlated with the VEGF concentration in the aqueous. (r = 0.49, <i>P</i> = 0.004)</p

Correlation between venous tortuosity index and foveal thickness.

<p>The degree of venous tortuosity is significantly correlated with the foveal thickness. (r = 0.40, <i>P</i> = 0.02)</p

Calculation of venous tortuosity index.

<p>Measurements of superior and inferior venous arcades were obtained starting from the optic disc margin to the crossing point of a circle (A) whose diameter is the distance from the center of optic disc to the fovea. The course of the veins were traced using Photoshop (Adobe Systems, Inc. Ca, USA). NIH ImageJ software was used to measure the lengths of the vein (A) and chord (B and C) of the vessels. The venous tortuosity index was calculated by dividing the length of the retinal veins by the chord length of the same segment (B/ A and C/A). The average of the venous tortuosity ((B/A + C/A)/2) was calculated to obtain the venous tortuosity index.</p

Characteristics of patients with CRVO.

<p>*Data are expressed as mean ± SD (range)</p><p>Characteristics of patients with CRVO.</p

Comparison between 1-year outcomes of aflibercept with and without photodynamic therapy for polypoidal choroidal vasculopathy: Retrospective observation study

<div><p>Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like choroidal neovascularization and a branching vascular network. Intravitreal aflibercept injection (IAI) or photodynamic therapy (PDT) is used for treatment. We retrospectively compared the 1-year outcomes of IAI monotherapy and its combination with initial PDT for PCV. Twelve eyes with naïve PCV received three IAIs and a single PDT after the first IAI and as needed injection (combination group); 11 eyes with naïve PCV received three IAIs and as needed injections (IAI group). Significant improvements in visual acuity after 2 months and in CRT after 1 month were maintained at 12 months in both groups (both <i>P</i> < 0.05); groups did not differ significantly at any time point. CCT significantly reduced after 3 and 12 months in the combination group (both <i>P</i> < 0.05) but not in the IAI group. A mean of 3.7 ± 0.9 and 5.6 ± 2.0 injections was administered to the combination and IAI groups, respectively (<i>P</i> = 0.013). Within a 1-year period, combination therapy was found to yield similar visual acuity and retinal structure improvements and maintenance as IAI monotherapy while requiring fewer IAIs.</p></div

Numbers of intravitreal aflibercept injections (IAI) administered to the two study groups.

<p><b>(A)</b> Significantly fewer IAIs were administered to the combination group than to the IAI group. <b>(B)</b> The groups had no significant difference in terms of the percentage of cases over 12 months. * <i>P</i> < 0.05 by Mann–Whitney <i>U</i> test.</p

Central retinal thickness (CRT) and central choroidal thickness (CCT) outcomes in the two study groups.

<p><b>(A)</b> Reductions in CRT were maintained at 12 months after both treatments, and no significant differences were observed between the groups at any time point during the 12-month study period. <b>(B)</b> A significant reduction in CCT from baseline to 3 and 12 months was observed in the combination group. No significant differences were observed between the two groups at any time point. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 by Repeated measures ANOVA.</p

Patient characteristics.

<p>Patient characteristics.</p