Adaptation of the pupil light reflex

The consensual photopupil responses to light flashes presented in uniform illumination to the entire visual field were recorded in full dark adaptation, over a gamut of intensities of ganzfeld backgrounds and in the dark after full bleach of all visual pigment in the retina. The equivalent background of such bleaching was found to be valid not only at the photopupillomotor threshold but also for flashes several log units suprathreshold (as judged by matching of the waveform of the pupillomotor response). The pupillomotor equivalent background is in reasonable agreement with its psychophysical counterpart, suggesting that the neural pathways for vision and photopupillary motion are common, at least to the level that retinal sensitivity adjustment in dark and light adaptation has been achieved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34117/1/0000401.pd

The effect of bleaching and backgrounds on pupil size

Measurements of pupil size and retinal rhodopsin in the dark after a full bleach confirm the suggestion of Alpern and Campbell that pupil dia. is linearly related to the fraction of unregenerated rhodopsin. This provides a transform [equation (1)] which can be used in conjunction with current ideas of visual adaptation to infer the pupil diameter at any luminance level (log I <= 5.0 scotopic td) in equilibrium viewing in a uniformly illuminated ganzfeld. Experimental determinations of such values on three normal subjects are in reasonable accord with expectation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34116/1/0000400.pd

The kinetics of cone visual pigments in man

Rushton's general kinetic equation for human cone pigments is tested by estimating the photolysis rate at equilibrium from the initial photolysis rate and comparing it to the equilibrium rate of regeneration measured immediately after the bleaching light is turned off. Thirty-seven experiments carried out at a variety of intermediate bleaches confirm the validity of this equation. The hypothesis that the regeneration rate depends upon the store of 11-cis retinal leads to the expectation that recovery from a prolonged weak bleach will proceed with a shorter time constant than recovery from a long intense bleach, and this is not found. This could happen if even the prolonged weak bleach depleted the 11-cis store but this possibility is excluded by an experiment in which recovery is measured following 5 sec full bleaching which follows straight on a prolonged weak one. Why recovery from short full bleaches proceed twice as fast as recovery from long full ones remains unexplained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33643/1/0000152.pd

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Isolation and characterization of galectins in the mammalian retina. Invest Ophthalmol Vis Sci.

PURPOSE. Previous studies have suggested that galectins may be involved in retinal adhesion and photoreceptor cell survival. To elucidate the underlying mechanisms, the authors isolated retinal galectins, determined their types and distributions, and investigated the validity of the hypothesis, using rat models. METHODS. An antibody was prepared against a bovine retinal lectin that was isolated by use of a lactose-agarose column. cDNA of the lectin was isolated by screening of a bovine retinal cDNA library, using the antibody, and then was sequenced. The cDNAs of rat retinal galectins were also isolated by means of polymerase chain reaction and used to produce an antibody against recombinant galectin-3. Using the described antibodies, the authors examined the distributions of galectins in bovine and rat retinas, morphologic changes of rat retinas induced by the antibodies, and distributional changes of galectins in constant-light-exposed rat retinas. RESULTS. The cDNAs of bovine galectin-1, rat galectin-1, and rat galectin-3 were isolated. Galectin-1 was found in various regions, including the retinal pigment epithelium, outer limiting membrane, and outer plexiform layer in bovine and rat retinas. Galectin-3 was increasingly detected in the cytoplasm of Müller cells after constant light exposure after an increase in its transcript. Retinal detachment and vacuolation of the outer plexiform layer were induced in rat eyes by intravitreous injection of the anti-galectin-1 antibody. CONCLUSIONS. Galectin-1 may be involved in adhesion of the photoreceptor and outer plexiform layers by interacting with glycoconjugates with ␤-galactoside residues in the interphotoreceptor matrix and synaptic cleft matrix. Galectin-3 may increase in Müller cells of a degenerative rat retina, probably through endogenous anti-apoptosis. (Invest Ophthalmol Vis Sci. 2001;42:2164 -217

Review of Bumpless Build Cube (BBCube) Using Wafer-on-Wafer (WOW) and Chip-on-Wafer (COW) for Tera-Scale Three-Dimensional Integration (3DI)

Bumpless Build Cube (BBCube) using Wafer-on-Wafer (WOW) and Chip-on-Wafer (COW) for Tera-Scale Three-Dimensional Integration (3DI) is discussed. Bumpless interconnects between wafers and between chips and wafers are a second-generation alternative to the use of micro-bumps for WOW and COW technologies. WOW and COW technologies for BBCube can be used for homogeneous and heterogeneous 3DI, respectively. Ultra-thinning of wafers down to 4 μm offers the advantage of a small form factor, not only in terms of the total volume of 3D ICs, but also the aspect ratio of Through-Silicon-Vias (TSVs). Bumpless interconnect technology can increase the number of TSVs per chip due to the finer TSV pitch and the lower impedance of bumpless TSV interconnects. In addition, high-density TSV interconnects with a short length provide the highest thermal dissipation from high-temperature devices such as CPUs and GPUs. This paper describes the process platform for BBCube WOW and COW technologies and BBCube DRAMs with high speed and low IO buffer power by enhancing parallelism and increasing yield by using a vertically replaceable memory block architecture, and also presents a comparison of thermal characteristics in 3D structures constructed with micro-bumps and BBCube