Binge drinking during adolescence increases the risk for neuropsychiatric disorders including alcoholism in adulthood. DNA methylation in post-mitotic neurons is an important epigenetic modification ...that plays a crucial role in neurodevelopment. We examined the effects of intermittent ethanol exposure during adolescence on adult behavior and whether DNA methylation changes provide a plausible explanation for the lasting effects of this developmental insult. One hour after last adolescent intermittent ethanol (AIE), growth arrest and DNA damage inducible protein 45 (Gadd45a, Gadd45b, and Gadd45g) mRNA expression was increased and DNA methyltransferase (DNMT) activity and Dnmt3b expression was decreased in the amygdala as compared to adolescent intermittent saline (AIS) rats. However, AIE rats 24 h after last exposure displayed increased DNMT activity but normalized Gadd45 and Dnmt3b mRNA expression compared to AIS rats. In adulthood, rats exposed to AIE show increased Dnmt3b mRNA expression and DNMT activity, along with decreased Gadd45g mRNA expression in the amygdala. DNA methylation of neuropeptide Y (Npy) and brain-derived neurotrophic factor (Bdnf) exon IV is increased in the AIE adult amygdala compared to AIS adult rats. Treatment with the DNMT inhibitor 5-azacytidine (5-azaC) at adulthood normalizes the AIE-induced DNA hypermethylation of Npy and Bdnf exon IV with concomitant reversal of AIE-induced anxiety-like and alcohol-drinking behaviors. These results suggest that binge-like ethanol exposure during adolescence leads to dysregulation in DNA methylation mechanisms in the amygdala which may contribute to behavioral phenotypes of anxiety and alcohol use in adulthood.
•Adolescent intermittent ethanol (AIE) increases adult anxiety and alcohol drinking.•AIE increased DMNT function in the amygdala in adulthood.•AIE increased DNA methylation at Npy and Bdnf exon IV in the adult amygdala.•5-azacytidine treatment normalizes AIE-induced anxiety and alcohol consumption.•5-azacytidine treatment restores AIE-induced DNA hypermethylation at Npy and Bdnf.
We present a novel and fully automated fundus image processing technique for glaucoma prescreening based on the rim-to-disc ratio (RDR). The technique accurately segments the optic disc and optic cup ...and then computes the RDR based on which it is possible to differentiate a normal fundus from a glaucomatous one. The technique performs a further categorization into normal, moderate, or severely glaucomatous classes following the disc-damage-likelihood scale (DDLS). To the best of our knowledge, this is the first engineering attempt at using RDR and DDLS to perform glaucoma severity assessment. The segmentation of the optic disc and cup is based on the active disc, whose parameters are optimized to maximize the local contrast. The optimization is performed efficiently by means of a multiscale representation, accelerated gradient-descent, and Green's theorem. Validations are performed on several publicly available databases as well as data provided by manufacturers of some commercially available fundus imaging devices. The segmentation and classification performance is assessed against expert clinician annotations in terms of sensitivity, specificity, accuracy, Jaccard, and Dice similarity indices. The results show that RDR based automated glaucoma assessment is about 8% to 10% more accurate than a cup-to-disc ratio (CDR) based system. An ablation study carried out considering the ground-truth expert outlines alone for classification showed that RDR is superior to CDR by 5.28% in a two-stage classification and about 3.21% in a three-stage severity grading.
Sugarcane (Saccharum spp.) is one of the most valuable food and industrial crops. Its production is constrained due to major biotic (fungi, bacteria, viruses and insect pests) and abiotic (drought, ...salt, cold/heat, water logging and heavy metals) stresses. The ever-increasing demand for sugar and biofuel and the rise of new pest and disease variants call for the use of innovative technologies to speed up the sugarcane genetic improvement process. Developing new cultivars through conventional breeding techniques requires much time and resources. The advent of CRISPR/Cas genome editing technology enables the creation of new cultivars with improved resistance/tolerance to various biotic and abiotic stresses. The presence of genome editing cassette inside the genome of genome-edited plants hinders commercial exploitation due to regulatory issues. However, this limitation can be overcome by using transgene-free genome editing techniques. Transgene-free genome editing approaches, such as delivery of the RNPs through biolistics or protoplast fusion, virus-induced genome editing (VIGE), transient expression of CRISPR/Cas reagents through Agrobacterium-mediated transformation and other approaches, are discussed. A well-established PCR-based assay and advanced screening systems such as visual marker system and Transgene killer CRISPR system (TKC) rapidly identify transgene-free genome edits. These advancements in CRISPR/Cas technology speed up the creation of genome-edited climate-smart cultivars that combat various biotic and abiotic stresses and produce good yields under ever-changing conditions.
Abstract Background The antianxiety effects of ethanol appear to be a crucial factor in promoting alcohol intake. Regulation of gene expression by microRNA (miRNA) is an important epigenetic ...mechanism that affects neuronal pathways and behaviors. We investigated the role of miRNAs underlying the mechanisms of ethanol-induced anxiolysis. Methods Acute ethanol-induced anxiolysis was measured in adult rats, and amygdaloid tissues were used for miRNA profiling by microarray analysis. The expression of miR-494 and its target genes in the amygdala was measured using real-time quantitative polymerase chain reaction. The direct role of miR-494 in the anxiety phenotype was also investigated via infusion of a miR-494 antagomir into the central nucleus of amygdala. Results Microarray profiling of miRNAs in the amygdala showed significant alteration of several miRNA expression levels by acute ethanol exposure. Expression of miR-494 was significantly decreased, whereas expression of the binding protein of cyclic adenosine monophosphate response element binding protein ( CBP ), p300 , and Cbp/p300-interacting transactivator 2 ( Cited2 ) was increased in the amygdala during ethanol-induced anxiolysis. Inhibition of miR-494 in the central nucleus of amygdala, through infusion of a specific antagomir, provoked anxiolysis, mimicking the action of ethanol. Also, expression of Cited2 , CBP , and p300 as well as histone H3-lysine 9 acetylation was significantly increased by miR-494 antagomir infusion, indicating their regulation by miR-494 in the amygdala. Conclusions These novel results suggest that acute ethanol-induced reduction in miR-494 expression in the amygdala can serve as a key regulatory mechanism for chromatin remodeling possibly leading to anxiolysis.
Antioxidant activity and hepatoprotective potential of
Phyllanthus niruri, a widely used medicinal plant, were investigated. Methanolic and aqueous extract of leaves and fruits of
P. niruri showed ...inhibition of membrane lipid peroxidation (LPO), scavenging of 1,1-diphenyl-2picrylhydrazyl (DPPH) radical and inhibition of reactive oxygen species (ROS) in vitro. Antioxidant activity of the extracts were also demonstrable in vivo by the inhibition of the carbon tetrachloride (CCl
4) – induced formation of lipid peroxides in the liver of rats by pretreatment with the extracts. CCl
4 – induced hepatotoxicity in rats, as judged by the raised serum enzymes, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), was prevented by pretreatment with the extracts, demonstrating the hepatoprotective action of
P. niruri.
Numerical investigations are conducted to investigate the impact of the magnetic field on the molten phase formation and thermal performance of phase change material (PCM) incorporated with hybrid ...nanoparticles within a three-dimensional vertical channel subjected to differential heating. The PCM, lauric acid, is dispersed using nanoparticle pairings consisting of iron oxide combined with aluminum oxide, titanium dioxide, and single-wall carbon nanotubes. This study focuses on examining the melting characteristics under turbulent conditions, specifically at high Rayleigh (Ra) and Hartmann number (Ha) within the specified range of 106≤Ra≤1010 and 0≤Ha≤1500. The enthalpy-porosity method is being considered for evaluating the phase change characteristics with an in-house code. For Ha of 1500, the melting process influenced by thermal convection was effectively suppressed, leading to significant delays in the melting rates. The melting time and molten fraction of the PCM exhibit a decreasing trend in response to the applied magnetic field, which results in an 82.14% reduction in the heat transfer rate. The SWCNT-Fe3O4 nanoparticle pairs demonstrated superior thermal performance, as the melting fraction and convective heat transfer were increased by 84.03% and 43.83%, respectively. The thermal performance exhibits a decreasing relationship with the Hartmann number, resulting in a 23.87% reduction in the heat transfer of nanoenhanced lauric acid. The accuracy of the present mathematical model is confirmed through validation against experimental benchmark data.
Air flow is a major characteristic in the tunnel ventilation design, to avoid severe disasters like smoke suffocation problems in tunnel and fire accidents. Tunnels are best ways to reduce distance ...between two adjacent places. It may be underground or above ground, depending upon the usage of it. There are different types of tunnel ventilation, e.g. roof vents, side vents, mechanical ventilation, naturally ventilated etc. This paper majorly focuses on roof vents mass extraction with different sizes of the heat sources and it also records the horizontal and normal velocity for different sizes of heat sources. The Reynolds Number is low but still turbulence occurs when we deal with buoyant smoke keeping density as incompressible ideal gas. Ratio of height by width is taken into account and the transient air flow is simulated for 10 seconds, and mass flow is recorded at each time step of 0.1 seconds using Large Eddy turbulence Model to capture the flow physics. It is observed that with changing the heat source size, mass flow rate from each vent changes significantly and it drastically affects the air flow patterns and heat transfer characteristics inside the tunnel.
In the current industry, coolants are widely used in numerous operations for the purpose of cooling and heat transfer. These operations include all kinds of heat sinks for electronic devices and ...manufacturing processes such as milling, drilling, turning, and CNC machining. The thermophysical properties of coolants play a vital role in determining the effectiveness of heat transfer and help prevent the components from wear and tear caused by extremely high temperatures. The computational domain consists of a drill bit and rectangular workpiece, and hybrid nanocoolants are sprayed from duplex nozzles. The nanocoolant heat transfer and flow characteristics of the drill bit–workpiece interface were analysed using the large eddy simulation (LES) turbulence model. The workpiece is made of Ti-6Al-4V alloy maintained at a temperature of 1073.15 K. The coolant used is a mineral oil into which different nanoparticles of Al2O3, TiO2, Cu, MWCNT, and SWCNT are dispersed by varying the volume concentration. The variations in temperature, Nusselt number, and wall heat transfer coefficient, with respect to the volume fraction of nanoparticles and the Reynolds number, were investigated. It was concluded that Cu–Al2O3 nanoparticles dispersed in mineral oil depicted the most favourable heat transfer.
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