Human RGR Gene and Associated Features of Age-Related Macular Degeneration in Models of Retina-Choriocapillaris Atrophy.

Age-related macular degeneration (AMD) is a progressive eye disease and the most common cause of blindness among the elderly. AMD is characterized by early atrophy of the choriocapillaris and retinal pigment epithelium (RPE). Although AMD is a multifactorial disease with many environmental and genetic risk factors, a hallmark of the disease is the origination of extracellular deposits, or drusen, between the RPE and Bruch membrane. Human retinal G-protein-coupled receptor (RGR) gene generates an exon-skipping splice variant of RGR-opsin (RGR-d; NP_001012740) that is a persistent component of small and large drusen. Herein, the findings show that abnormal RGR proteins, including RGR-d, are pathogenic in an animal retina with degeneration of the choriocapillaris, RPE, and photoreceptors. A frameshift truncating mutation resulted in severe retinal degeneration with a continuous band of basal deposits along the Bruch membrane. RGR-d produced less severe disease with choriocapillaris and RPE atrophy, including focal accumulation of abnormal RGR-d protein at the basal boundary of the RPE. Degeneration of the choriocapillaris was marked by a decrease in endothelial CD31 protein and choriocapillaris breakdown at the ultrastructural level. Fundus lesions with patchy depigmentation were characteristic of old RGR-d mice. RGR-d was mislocalized in cultured cells and caused a strong cell growth defect. These results uphold the notion of a potential hidden link between AMD and a high-frequency RGR allele.

Analysis of pupil size by repeat dilation at shrinkage stage.

PURPOSE: To compare the pupil size of the original mydriasis and repeat mydriasis at the pupil shrinkage stage. METHODS: Randomized prospective study. In total, 60 eyes of 30 patients aged 50-70 with age-related cataracts were included. Pupil sizes were measured by the Sirius system before mydriasis, after the first batch of mydriasis, and after the second batch of mydriasis which was 5 h later. Statistical analysis was performed using MedCalc statistical software version 20.0.3 RESULTS: The pupil size of the second batch of mydriasis 5 h later was smaller than the first batch of mydriasis (3.94 ± 0.88 mm vs 5.12 ± 0.96 mm, P < 0.0001). CONCLUSIONS: Less efficiency repeat mydriasis several hours later compared with original mydriasis in our study suggests that preparation of mydriasis at an appropriate time is necessary for ophthalmological operations. The effect of repeat mydriasis again by tropicamide at the shrinkage stage still needs to be explored.

Generation and characterization of pathogenic Mab21l2(R51C) mouse model.

MAB21L2(R51C) is one of the five documented MAB21L2 mutations in human patients with bilateral eye malformations identified via whole exome sequencing. In addition to the eye abnormality, patients with MAB21L2 R51C/+ mutation also have skeletal dysplasia and intellectual disability. To evaluate the pathology of this mutant allele systematically in understanding the functional role of MAB21L2 in human development, we introduce the R51C mutation into the mouse genome by CRISPR/Cas9 system to generate a mouse model for detailed characterization. The Mab21l2 R51C/+ mice have eyeless phenotype and skeletal abnormalities. Micro-computed tomography (micro-CT) analysis showed the Mab21l2 R51C/+ mice have no eye balls but with two abnormal tissues underneath the brain. Histological analysis revealed that the early eye development in the mutant embryos is interrupted. In addition, Mab21l2 R51C/+ mice also have joint fusion phenotype; the humerus is fused with radius, whereas femur is fused with tibia. Limbs in the mutant animals are distinctly shorter than the wild type; and deltoid tuberosities in humeri are absent in these Mab21l2 R51C/+ mice. In summary, we showed that our Mab21l2 R51C/+ mutant mice have recapitulated the pathological features in eye and bone of human patients. Further analyses of the mutant phenotype with molecular markers will provide insight on how MAB21L2 guides the optic differentiation and skeletogenesis, revealing specific underlying pathogenic mechanism of the MAB21L2(R51C) mutation.

Energy diffusion in two-dimensional momentum-conserving nonlinear lattices: Lévy walk and renormalized phonon.

The energy diffusion process in a few two-dimensional Fermi-Pasta-Ulam-type lattices is numerically simulated via the equilibrium local energy spatiotemporal correlation. Just as the nonlinear fluctuating hydrodynamic theory suggested, the diffusion propagator consists of a bell-shaped central heat mode and a sound mode extending with a constant speed. The profiles of the heat and sound modes satisfy the scaling properties from a random-walk-with-velocity-fluctuation process very well. An effective phonon approach is proposed, which expects the frequencies of renormalized phonons as well as the sound speed with quite good accuracy. Since many existing analytical and numerical studies indicate that heat conduction in such two-dimensional momentum-conserving lattices is divergent and the thermal conductivity κ increases logarithmically with lattice length, it is expected that the mean-square displacement of energy diffusion grows as tlnt. Discrepancies, however, are noticeably observed.

Thermalization process in a one-dimensional lattice with two-dimensional motions: The role of angular momentum conservation.

We study the thermalization process in a one-dimensional lattice with two-dimensional motions. The phonon modes in such a lattice consist of two branches. Unlike in general nonlinear Hamiltonian systems, for which the only conserved quantity is the total energy, the total angular momentum J is also conserved in this system. Consequently, the intra- and interbranch energy transports behave significantly differently. For the intrabranch transport, all the existing rules for the one-dimensional systems including the Chirikov overlap criterion apply. As for the interbranch transport, some trivial processes in one-dimensional lattices become nontrivial. During these processes, all the conservation laws can be satisfied exactly; thus the Chirikov criterion does not apply. These processes provide some fast channels for the interbranch transport, although the thermalization cannot be reached through them alone. A system with nonzero-J initial state, however, can never be thermalized to an equipartition state having zero J. Quite counterintuitively, the corresponding asymptotic mode energy distribution greatly concentrates to a few lowest-frequency modes in one branch.

Projective-truncation-approximation study of the one-dimensional ϕ

In this paper, we first develop the projective truncation approximation (PTA) in the Green's function equation of motion (EOM) formalism for classical statistical models. To implement PTA for a given Hamiltonian, we choose a set of basis variables and projectively truncate the hierarchical EOM. We apply PTA to the one-dimensional ϕ^{4} lattice model. Phonon dispersion and static correlation functions are studied in detail. Using one- and two-dimensional bases, we obtain results identical to and beyond the quadratic variational approximation, respectively. In particular, we analyze the power-law temperature dependence of the static averages in the low- and high-temperature limits, and we give exact exponents.

Heat current flows across an interface in two-dimensional lattices.

Heat current J that flows through a few typical two-dimensional nonlinear lattices is systematically studied. Each lattice consists of two identical segments that are coupled by an interface with strength k_{int}. It is found that the two-universality-class scenario that is revealed in one-dimensional systems is still valid in the two-dimensional systems. Namely, J may follow k_{int} in two entirely different ways, depending on whether or not the interface potential energy decays to zero. We also study the dependence of J on lattice width N_{Y} and transverse interaction strength k_{Y}. Universal power-law decay or divergence is observed. Finally, we check the equipartition theorem in the systems since it is the basis of all our theoretical analyses. Surprisingly, it holds perfectly even at the interface where there is a finite temperature jump, which makes the system far from equilibrium. However, the equipartition of potential energy, which is observed in one-dimensional systems, is no longer satisfied due to the interaction between different dimensions.