Search Results (12)

Background/Objectives: We aimed to investigate the genetic loci related to disc hemorrhage (DH) and the relationship of causation between DH and primary open-angle glaucoma (POAG) using a genome-wide association study (GWAS) in East Asian individuals. Methods: The GWAS included 8488 Koreans who underwent ocular examination including fundus photography to determine the presence of DH and POAG. We performed a GWAS to identify significant single-nucleotide polymorphisms (SNPs) associated with DH and analyzed the heritability of DH and genetic correlation between DH and POAG. The identified SNPs were utilized as instrumental variables (IVs) for two-sample Mendelian randomization (MR) analysis. The POAG outcome dataset was adopted from Biobank Japan data (n = 179,351). Results: We found that the rs62463744 (TMEM270;ELN), rs11658281 (CCDC42), and rs77127203 (PDE10A;LINC00473) SNPs were associated with DH. The SNP heritability of DH was estimated to be 6.7%, with an absence of a genetic correlation with POAG. MR analysis did not reveal a causal association between DH and POAG for East Asian individuals. Conclusions: The novel loci underlying DH in the Korean cohort revealed SNPs in the ELN, CCDC41, and LINC00473 genes. The absence of a causal association between DH and POAG implies that DH is a shared risk factor, rather than an independent culprit factor, and warrants further investigation. Full article

Our aim was to compare the stroke outcomes of a direct transfer (DT) to a thrombectomy-capable center vs. initial care at two local stroke centers: a nearby hospital (NH, 36 km) and a distant hospital (DH, 113 km). Patients who underwent a mechanical thrombectomy were analyzed (February 2017–October 2021), and the outcome was considered favorable if the modified Rankin scale (mRS) score was ≤ 2 at three months. A total of 300 patients were included, 55 of which were transferred from the NH and 58 from the DH. There was a difference in the median (IQR) transfer time of 39 min between the hospitals (149 min for the NH vs. 188 min for the DH, p = 0.003). After adjusting for confounding variables, a secondary transfer from the DH, compared to a DT, was associated with a lower functional independence: mRS score ≤ 2 (OR = 0.37, 95% CI = 0.14–0.97, p = 0.043), without significant differences in the mortality between the groups. These differences were not observed in patients from the NH. Conclusions: A secondary transfer from a distant hospital was associated with a poorer functional outcome at 3 months. This unfavorable outcome was not observed among patients transferred from a nearby hospital. These findings highlight the importance of categorizing the suitability of one transfer model over another based on the proximity of hospitals to the thrombectomy center, but also in accordance with organizational and geographic characteristics that vary within each health region. Full article

Effects of modulation of glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) on acute neuroinflammatory response were studied in the dorsal (DH) and ventral (VH) parts of the hippocampus of male Wistar rats. Local neuroinflammatory response was induced by administration of bacterial lipopolysaccharide (LPS) to the DH. The modulation of GR and MR was performed by dexamethasone (GR activation), mifepristone, and spironolactone (GR and MR inhibition, respectively). Experimental drugs were delivered to the dentate gyrus of the DH bilaterally by stereotaxic injections. Dexamethasone, mifepristone, and spironolactone were administered either alone (basal conditions) or in combination with LPS (neuroinflammatory conditions). Changes in expression levels of neuroinflammation-related genes and morphology of microglia 3 days after intrahippocampal administration of above substances were assessed. Dexamethasone alone induced a weak proinflammatory response in the hippocampal tissue, while neither mifepristone nor spironolactone showed significant effects. During LPS-induced neuroinflammation, GR activation suppressed expression of selected inflammatory genes, though it did not prevent appearance of activated forms of microglia. In contrast to GR activation, GR or MR inhibition had virtually no influence on LPS-induced inflammatory response. The results suggest glucocorticosteroids ambiguously modulate specific aspects of neuroinflammatory response in the hippocampus of rats at molecular and cellular levels. Full article

Precision object handling and manipulation require the accurate positioning of industrial robots. A common practice for performing end effector positioning is to read joint angles and use industrial robot forward kinematics (FKs). However, industrial robot FKs rely on the robot Denavit–Hartenberg (DH) parameter values, which include uncertainties. Sources of uncertainty associated with industrial robot FKs include mechanical wear, manufacturing and assembly tolerances, and robot calibration errors. It is therefore necessary to increase the accuracy of DH parameter values to reduce the impact of uncertainties on industrial robot FKs. In this paper, we use differential evolution, particle swarm optimization, an artificial bee colony, and a gravitational search algorithm to calibrate industrial robot DH parameters. A laser tracker system, Leica AT960-MR, is utilized to register accurate positional measurements. The nominal accuracy of this non-contact metrology equipment is less than 3 μm/m. Metaheuristic optimization approaches such as differential evolution, particle swarm optimization, an artificial bee colony and a gravitational search algorithm are used as optimization methods to perform the calibration using laser tracker position data. It is observed that, using the proposed approach with an artificial bee colony optimization algorithm, the accuracy of industrial robot FKs in terms of mean absolute errors of static and near-static motion over all three dimensions for the test data decreases from its measured value of 75.4 μm to 60.1 μm (a 20.3% improvement). Full article

Water quality is directly linked to drinking water safety for millions of people receiving the water. The Danjiangkou Reservoir is the main water source for the Middle Route of the South-to-North Water Diversion Project (MR-SNWDP), located in the vicinity of Henan and Hubei provinces in China. Aquatic microorganisms are key indicators of biologically assessing and monitoring the water quality of the reservoir as they are sensitive to environmental and water quality changes. This study aimed to investigate the spatiotemporal variations in bacterioplankton communities during wet (April) and dry (October) seasons at eight monitoring points in Hanku reservoir and five monitoring points in Danku reservoir. Each time point had three replicates, labeled as wet season Hanku (WH), wet season Danku (WD), dry season Hanku (DH), and dry season Danku (DD) of Danjiangkou Reservoir in 2021. High-throughput sequencing (Illumina PE250) of the 16S rRNA gene was performed, and alpha (ACE and Shannon) and beta (PCoA and NDMS) diversity indices were analyzed. The results showed that the dry season (DH and DD) had more diverse bacterioplankton communities compared to the wet season (WH and WD). Proteobacteria, Actinobacteria, and Firmicutes were the most abundant phyla, and Acinetobacter, Exiguobacterium, and Planomicrobium were abundant in the wet season, while polynucleobacter was abundant in the dry season. The functional prediction of metabolic pathways revealed six major functions including carbohydrate metabolism, membrane transport, amino acid metabolism, signal transduction, and energy metabolism. Redundancy analysis showed that environmental parameters greatly affected bacterioplankton diversity during the dry season compared to the wet season. The findings suggest that seasonality has a significant impact on bacterioplankton communities, and the dry season has more diverse communities influenced by environmental parameters. Further, the relatively high abundance of certain bacteria such as Acinetobacter deteriorated the water quality during the wet season compared to the dry season. Our findings have significant implications for water resource management in China, and other countries facing similar challenges. However, further investigations are required to elucidate the role of environmental parameters in influencing bacterioplankton diversity in order to devise potential strategies for improving water quality management in the reservoir. Full article

Profiling of 5-hydroxymethylcytosine (5hmC) in the brain regions of rhesus monkey at different ages reveals accumulation and tissue-specific patterns of 5hmC with aging. Region-specific differentially hydroxymethylated regions (DhMRs) are involved in neuronal functions and signal transduction. These data suggest that 5hmC may be a key regulator of gene transcription in neurodevelopment and thus a potential candidate for the epigenetic clock. Importantly, non-human primates are the ideal animal models for investigation of human aging and diseases not only because they are more genetically similar to humans but also epigenetically. Full article

An imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remains elusive. In this study, we describe the landscape of 5-mC and 5-hmC and their association with breast cancer development. We found a distinguishable global loss of 5-hmC in the localized and invasive types of breast cancer that strongly correlate with TET expression. Genome-wide analysis revealed a unique 5-mC and 5-hmC signature in breast cancer. The differentially methylated regions (DMRs) were primarily concentrated in the proximal regulatory regions such as the promoters and UTRs, while the differentially hydroxymethylated regions (DhMRs) were densely packed in the distal regulatory regions, such as the intergenic regions (>−5 kb from TSSs). Our results indicate 4809 DMRs and 4841 DhMRs associated with breast cancer. Validation of nine 5-hmC enriched loci in a distinct set of breast cancer and normal samples positively correlated with their corresponding gene expression. The novel 5-hmC candidates such as TXNL1, and CNIH3 implicate a pro-oncogenic role in breast cancer. Overall, these results provide new insights into the loci-specific accumulation of 5-mC and 5-hmC, which are aberrantly methylated and demethylated in breast cancer. Full article

Epigenetics is a mechanism underlying cardiovascular disease. It is unknown whether DNA hydroxymethylation is prospectively associated with the risk for cardiovascular death independent of germline and common environment. Male twin pairs middle-aged in 1969–1973 and discordant for cardiovascular death through December 31, 2014, were included. Hydroxymethylation was quantified in buffy coat DNA collected in 1986–1987. The 1893 differentially hydroxymethylated regions (DhMRs) were identified after controlling for blood leukocyte subtypes and age among 12 monozygotic (MZ) pairs (Benjamini–Hochberg False Discovery Rate < 0.01), of which the 102 DhMRs were confirmed with directionally consistent log₂-fold changes and p < 0.01 among additional 7 MZ pairs. These signature 102 DhMRs, independent of the germline, were located on all chromosomes except for chromosome 21 and the Y chromosome, mainly within/overlapped with intergenic regions and introns, and predominantly hyper-hydroxymethylated. A binary linear classifier predicting cardiovascular death among 19 dizygotic pairs was identified and equivalent to that generated from MZ via the 2D transformation. Computational bioinformatics discovered pathways, phenotypes, and DNA motifs for these DhMRs or their subtypes, suggesting that hydroxymethylation was a pathophysiological mechanism underlying cardiovascular death that might be influenced by genetic factors and warranted further investigations of mechanisms of these signature regions in vivo and in vitro. Full article

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer. Full article

5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22–35 years and 74–94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes. Full article

We describe a versatile simulation chamber that operates under representative space conditions (pressures from < 10⁻⁵ mbar to ambient and temperatures from 163 to 423 K), the SpaceQ chamber. This chamber allows to test instrumentation, procedures, and materials and evaluate their performance when exposed to outgassing, thermal vacuum, low temperatures, baking, dry heat microbial reduction (DHMR) sterilization protocols, and water. The SpaceQ is a cubical stainless-steel chamber of 27,000 cm³ with a door of aluminum. The chamber has a table which can be cooled using liquid nitrogen. The chamber walls can be heated (for outgassing, thermal vacuum, or dry heat applications) using an outer jacket. The chamber walls include two viewports and 12 utility ports (KF, CF, and Swagelok connectors). It has sensors for temperature, relative humidity, and pressure, a UV–VIS–NIR spectrometer, a UV irradiation lamp that operates within the chamber as well as a stainless-steel syringe for water vapor injection, and USB, DB-25 ports to read the data from the instruments while being tested inside. This facility has been specifically designed for investigating the effect of water on the Martian surface. The core novelties of this chamber are: (1) its ability to simulate the Martian near-surface water cycle by injecting water multiple times into the chamber through a syringe which allows to control and monitor precisely the initial relative humidity inside with a sensor that can operate from vacuum to Martian pressures and (2) the availability of a high-intensity UV lamp, operating from vacuum to Martian pressures, within the chamber, which can be used to test material curation, the role of the production of atmospheric radicals, and the degradation of certain products like polymers and organics. For illustration, here we present some applications of the SpaceQ chamber at simulated Martian conditions with and without atmospheric water to (i) calibrate the ground temperature sensor of the Engineering Qualification Model of HABIT (HabitAbility: Brines, Irradiation and Temperature) instrument, which is a part of ExoMars 2022 mission. These tests demonstrate that the overall accuracy of the temperature retrieval at a temperature between −50 and 10 °C is within 1.3 °C and (ii) investigate the curation of composite materials of Martian soil simulant and binders, with added water, under Martian surface conditions under dry and humid conditions. Our studies have demonstrated that the regolith, when mixed with super absorbent polymer (SAP), water, and binders exposed to Martian conditions, can form a solid block and retain more than 80% of the added water, which may be of interest to screen radiation while maintaining a low weight. Full article

Allometric models to estimate biomass components such as stem mass M_s, foliage mass M_l, root mass M_r and aboveground mass M_a, were developed for the palm species Euterpe precatoria Mart., which is the most abundant tree species in the Amazon. We harvested twenty palms including above- and below-ground parts in an old growth Amazonian forest in Brazil. The diameter at breast height D ranged from 3.9–12.7 cm, and the stem height H ranged from 2.3–16.4 m. The D, diameter at ground basis D₀, crown diameter CD, H, stem specific gravity ρ, and number of fronds N_f were considered as independent variables and incorporated into a power function model. The best predictors were D²Hρ for M_s and M_a, D²HN_f for M_l, and D for M_r. Slender index (H/D) ranged from 0.56–1.46 m·cm⁻¹, and the D-H relationship suggested that the stem shape becomes more slender with increasing D. On the other hand, ρ increased with D implying a stiffening of stem tissue. The average root/shoot ratio was estimated as 0.29 which was higher than that reported for the non-palm tree species in the Amazon. Comparisons of several models to estimate M_a of different palm species, suggested that the variations of the D-H relationship and ρ should be considered to develop allometric models for estimating biomass in palm species. In particular the ρ largely varied depending on individual size, which should be important to consider, when developing the allometric models for palms. Full article