Search

High hyperopia is a common and severe form of refractive error. Genetic factors play important roles in the development of high hyperopia but the exact gene responsible for this condition is mostly unknown. We identified a large Chinese family with autosomal dominant high hyperopia. A genome-wide linkage scan mapped the high hyperopia to chromosome 11p12-q13.3, with maximum log of the odds scores of 4.68 at theta = 0 for D11S987. Parallel whole-exome sequencing detected a novel c.3377delG (p.Gly1126Valfs*31) heterozygous mutation in the MYRF gene within the linkage interval. Whole-exome sequencing in other 121 probands with high hyperopia identified additional novel mutations in MYRF within two other families: a de novo c.3274_3275delAG (p.Leu1093Profs*22) heterozygous mutation and a c.3194+2T>C heterozygous mutation. All three mutations are located in the C-terminal region of MYRF and are predicted to result in truncation of that portion. Two patients from two of the three families developed angle-closure glaucoma. These three mutations were present in neither the ExAC database nor our in-house whole-exome sequencing data from 3280 individuals. No other truncation mutations in MYRF were detected in the 3280 individuals. Knockdown of myrf resulted in small eye size in zebrafish. These evidence all support that truncation mutations in the C-terminal region of MYRF are responsible for autosomal dominant high hyperopia in these families. Our results may provide useful clues for further understanding the functional role of the C-terminal region of this critical myelin regulatory factor, as well as the molecular pathogenesis of high hyperopia and its associated angle-closure glaucoma.

A 360° video offers a more immersive experience, gaining increasing popularity among users. However, enhancing the transmission efficiency of 360° videos under limited bandwidth conditions remains a significant challenge. This paper segments the video into three areas: the attention area, the edge area, and the viewpoint-switching transition area. Based on the segmentation of these three distinct video areas, a novel non-uniform coding transmission method for 360° videos is presented, along with mathematical modeling to define the optimization problem. A heuristic algorithm is subsequently introduced, which adaptively determines the optimal number of tiles and allocates the bitrate for each tile in real time to enhance the user's quality of experience (QoE). Finally, a simulation platform has been developed to validate the efficacy of the proposed algorithm by conducting comparative analyses with existing algorithms. [ABSTRACT FROM AUTHOR]

Purpose: Heterozygous variants of IMPDH1 are associated with autosomal dominant retinitis pigmentosa (adRP). The current study aims to investigate the characteristics of the adRP-associated variants. Methods: IMPDH1 variants from our exome sequencing dataset were retrieved and systemically evaluated through multiple online prediction tools, comparative genomics (in-house dataset, HGMD, and gnomAD), and phenotypic association. Potential pathogenic variants (PPVs) were further confirmed by Sanger sequencing and segregation analysis. Results: In total, seven heterozygous PPVs (six missenses and one inframe) were identified in 10 families with RP, in which six of the seven might be classified as pathogenic or likely pathogenic while one others as variants of uncertain significance. IMPDH1 variants contributed to 0.7% (10/1519) of RP families in our cohort, ranking the top four genes implicated in adRP. These adRP-associated variants were located in exons 8–10, a region within or downstream of the CBS domain. All these variants were predicted to be damaged by at least three of the six online prediction tools. Two truncation variants were considered non-pathogenic. Hitherto, 41 heterozygous variants of IMPDH1 were detected in 110 families in published literature, including 33 missenses, two inframes, and six truncations (including a synonymous variant affecting splicing). Of the 35 missense and inframe variants, most were clustered in exons 8–10 (77.1%, 27/35), including 18 (51.4%, 18/35) in exon 10 accounting for 70.9% (78/110) of the families. However, truncation variants were enriched in the general population with a pLI value of 0 (tolerated), and the reported variants in patients with RP did not cluster in specific region. Conclusions: Our data together with comprehensive analysis of existing datasets suggest that causative variants of IMPDH1 are usually missense and mostly clustered in exons 8–10. Conversely, most missense variants outside this region and truncation variants should be interpreted with great care in clinical gene test. [ABSTRACT FROM AUTHOR]

Based on research into how static pressure piles sink in saturated cohesive soil, alterations caused by a rise in pore stress during the load process between the pile and the earth as well as the effects of a variation in valid radial thrust on the project are thoroughly studied. These changes are of great importance for the application and practice of practical projects. Microtest components are embedded on the surfaces of open and closed piles, and test research is conducted using a large-scale system and double-deck open and closed pipe piles. Finally, complete consideration is given to how variations in effective radial stress. Through this test, it was determined that as the pile’s buried depth gradually grows, so do the valid radial thrust and excess pore pressure. However, the quantity of the superfluous pore water stress for a closed pile is higher than for an open pile. And the higher half has substantially lower effective radial thrust and overall surplus pore stress than the lower part does. The pile penetration depth is constant, and the value of h/L of the pile shaft is also rising, the occurrence of “lateral pressure degradation” of earth load between pile and earth is becoming increasingly prominent. The maximum ratio of the excess pore stress to the valid soil pressure between the pile and earth contact is 62.1% for an exposed pile and 52.1% for a sealed pile. At the interface, the effective radial stress is about 3.76∼5.46 times that of the remaining pore water stress. Therefore, under changing pile penetration depths, the value of h/L will have an impact on the pile’s and the soil’s additional pore water pressure or excellent soil pressure. The test results have a significant impact on how static pressure piles are built and how bearing capacity is designed in real-world applications.