Proton Transfer via Arginine with Suppressed pKa Mediates Catalysis by Gentisate and Salicylate Dioxygenase.

Gentisate and salicylate 1,2-dioxygenases (GDO and SDO) facilitate aerobic degradation of aromatic rings by inserting both atoms of dioxygen into their substrates, thereby participating in global carbon cycling. The role of acid-base catalysts in the reaction cycles of these enzymes is debatable. We present evidence of the participation of a proton shuffler during catalysis by GDO and SDO. The pH dependence of Michaelis-Menten parameters demonstrates that a single proton transfer is mandatory for the catalysis. Measurements at variable temperatures and pHs were used to determine the standard enthalpy of ionization (ΔHion°) of 51 kJ/mol for the proton transfer event. Although the observed apparent pKa in the range of 6.0-7.0 for substrates of both enzymes is highly suggestive of a histidine residue, ΔHion° establishes an arginine residue as the likely proton source, providing phylogenetic relevance for this strictly conserved residue in the GDO family. We propose that the atypical 3-histidine ferrous binding scaffold of GDOs contributes to the suppression of arginine pKa and provides support for this argument by employing a 2-histidine-1-carboxylate variant of the enzyme that exhibits elevated pKa. A reaction mechanism considering the role of the proton source in stabilizing key reaction intermediates is proposed.

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

Association between sleep and myopia in children and adolescents: a systematic review and meta-analysis.

PURPOSE: There is a scarcity of literature focusing on sleep's impact on myopia in children despite an epidemic rise of myopia among the age group and the importance of early prevention. As such, this systematic review-meta-analysis aims to evaluate the association between various aspects of sleep and myopia in children and adolescents aged 0-19 years. METHODS: We searched PubMed, EMBASE, and Cochrane Library on 08/12/2022 for studies reporting sleep in relation to myopia among children and adolescents. Myopia was defined as spherical equivalent refraction < -0.5 diopter. The primary outcome was the relationship between sleep duration and myopia prevalence. Secondary outcomes include the effect of sleep quality, bedtime, and waketime on myopia prevalence, incidence, and progression. Odds ratio (OR) was estimated with a 95% confidence interval (95% CI). RESULTS: Eighteen studies (49,277 participants) were included in the review, and six studies (14,116 participants) were included in the meta-analysis for the primary outcome. There was no significant correlation between sleep and myopia prevalence (OR = 0.905, 95% CI = 0.782 to 1.047). Some studies suggested that better sleep quality (2 of 6 studies), earlier bedtime (3 of 5 studies), and later waketimes (2 of 3 studies) had protective effects on myopia. CONCLUSION: Sleep duration did not affect myopia prevalence in children, while other aspects of sleep had plausible but inconclusive impacts on myopia development and progression. More research with diverse populations and standardized methods of reporting is needed.

DepLink: an R Shiny app to systematically link genetic and pharmacologic dependencies of cancer.

Motivation: Large-scale genetic and pharmacologic dependency maps are generated to reveal genetic vulnerabilities and drug sensitivities of cancer. However, user-friendly software is needed to systematically link such maps. Results: Here, we present DepLink, a web server to identify genetic and pharmacologic perturbations that induce similar effects on cell viability or molecular changes. DepLink integrates heterogeneous datasets of genome-wide CRISPR loss-of-function screens, high-throughput pharmacologic screens and gene expression signatures of perturbations. The datasets are systematically connected by four complementary modules tailored for different query scenarios. It allows users to search for potential inhibitors that target a gene (Module 1) or multiple genes (Module 2), mechanisms of action of a known drug (Module 3) and drugs with similar biochemical features to an investigational compound (Module 4). We performed a validation analysis to confirm the capability of our tool to link the effects of drug treatments to knockouts of the drug's annotated target genes. By querying with a demonstrating example of CDK6, the tool identified well-studied inhibitor drugs, novel synergistic gene and drug partners and insights into an investigational drug. In summary, DepLink enables easy navigation, visualization and linkage of rapidly evolving cancer dependency maps. Availability and implementation: The DepLink web server, demonstrating examples and detailed user manual are available at https://shiny.crc.pitt.edu/deplink/. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Band Alignment of ScxAl1-xN/GaN Heterojunctions.

ScAlN is an emergent ultrawide-band-gap material with both a high piezoresponse and demonstrated ferroelectric polarization switching. Recent demonstration of epitaxial growth of ScAlN on GaN has unlocked prospects for new high-power transistors and nonvolatile memory technologies fabricated from these materials. An understanding of the band alignments between ScAlN and GaN is crucial in order to control the electronic and optical properties of engineered devices. To date, there have been no experimental studies of the band offsets between ScAlN and GaN. This work presents optical characterization of the band gap of molecular beam epitaxy grown ScxAl1-xN using spectroscopic ellipsometry and measurements of the band offsets of ScxAl1-xN with GaN using X-ray photoemission spectroscopy, along with a comparison to first-principles calculations. The band gap is shown to continuously decrease as a function of increasing ScN alloy fraction with a negative bowing parameter. Furthermore, a crossover from straddling (type-I) to staggered (type-II) band offsets is demonstrated as Sc composition increases beyond approximately x = 0.11. These results show that the ScAlN/GaN valence band alignment can be tuned by changing the Sc alloy fraction, which can help guide the design of heterostructures in future ScAlN/GaN-based devices.

Cutoff wavelength of ridge waveguide near field transducer for disk data storage.

The electromagnetic eigenmodes of and light transmission through a C-aperture to the far field, and to a storage medium, have been studied based on the full vectorial finite difference method. It is found that the cutoff wavelength of C-aperture waveguides in a gold film is much longer than that in a perfect electric conductor, and the fundamental mode is confined in the gap and polarized with the electric field along the gap. The light transmission resonance through C-apertures to far field and to a storage medium occurs at wavelengths below the waveguide cutoff wavelength. Measurements on the fabricated C-apertures confirm the mode confinement and transmission resonance.

Nanolithography using high transmission nanoscale bowtie apertures.

We demonstrate that bowtie apertures can be used for contact lithography to achieve nanometer scale resolution. The bowtie apertures with a 30 nm gap size are fabricated in aluminum thin films coated on quartz substrates. Lithography results show that holes of sub-50-nm dimensions can be produced in photoresist by illuminating the apertures with a 355 nm laser beam polarized in the direction across the gap. Experimental results show enhanced transmission and light concentration of bowtie apertures compared to square and rectangular apertures of the same opening area. Finite different time domain simulations are used to explain the experimental results.

Contact optical nanolithography using nanoscale C-shaped apertures.

C-shaped ridge apertures are used in contact nanolithography to achieve nanometer scale resolution. Lithography results demonstrated that holes as small as 60 nm can be produced in the photoresist by illuminating the apertures with a 355 nm laser beam. Experiments are also performed using comparable square and rectangular apertures. Results show enhanced transmission and light concentration of C apertures compared to the apertures with regular shapes. Finite difference time domain simulations are used to design the apertures and explain the experimental results.