A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications
Abstract not provided
Flynn, E. Megan↗
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Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification
Abstract not provided
Eisemann, Travis↗
Human CEACAM1 N-domain dimerization is independent from glycan modifications
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Dufrisne, Meagan Belcher↗
Tuning the Product Selectivity of Single-Atom Alloys by Active Site Modification
There is widespread interest in developing catalysts with uniform active sites that consist of single atoms, thereby simplifying the reaction mechanism and improving product selectivity. Here, we examine experimentally how CO can be used to modify the active sites on a strong binding single-atom alloy and examine how this in turn impacts product selectivity for a reaction that has two different pathways. Specifically, we find that CO can be used to selectively block isolated Rh atom active sites in a RhCu(111) model single-atom alloy catalyst surface and promote the dehydrogenation pathway for adsorbed ethyl groups by suppressing the hydrogenation pathway.
36 MATERIALS SCIENCE↗
Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1
Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site of myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (∼ 2-fold) to the myogenin promoter at the transcription start site (− 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (− 40 to + 42). -- Highlights: ► Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ► Arsenic exposure alters histone remodeling on the myogenin promoter. ► Glp expression, a H3–K9 methyltransferase, was increased in arsenic-exposed cells. ► Ezh2 and Dnmt3a localization to the myogenin promoter is induced by arsenic.
60 APPLIED LIFE SCIENCES↗
Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide
Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were unchanged. • The amplitude and conductance of Nav1.9 were increased 8 weeks following exposure. • Nociceptors exhibit increased action potential duration and afterhyperpolarization. • Acute permethrin altered activation physiology and increased the amplitude of Nav1.9.
60 APPLIED LIFE SCIENCES↗
Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis
Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a DNA methylation, histones, and transcription factors.
60 APPLIED LIFE SCIENCES↗
Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus
Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35 mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as a target of miR-10a in vitro and in vivo. CREB1 and its downstream fibronectin (FN, extracellular matrix) were increased in HFD/STZ-treated mice, which was reversed by kidney miR-10a overexpression. The content of CREB1 and FN was increased by miR-10a knockdown in kidney of naïve mice. Furthermore, histone deacetylase 3 (HDAC3) was revealed to be increased in kidney of HFD/STZ mice, accompanied with the augmentation of ACR ratio and FN level. Knockdown of HDAC3 with siRNA significantly caused the increase of miR-10a, resulting in the decrease in CREB1 and FN expression in kidney of HFD/STZ mice. Contrarily, HDAC3 overexpression mediated by lentivirus decreased miR-10a content, and enhanced ACR value, CREB1 and FN formation in naïve mice. Collectively, these results elucidate that HDAC3/miR-10a/CREB1 serves as a new mechanism underlying kidney injury, providing potential therapeutic targets in type 2 diabetes. - Highlights: • Diabetes induces the decrease of miR-10a level in the kidney. • MiR-10a overexpression improves kidney damage of diabetes. • MiR-10a targeting CREB1/FN implicates in kidney impairment. • HDAC3 regulates kidney damage by epigenetically modulating miR-10a.
60 APPLIED LIFE SCIENCES↗
Insights into pectin O-acetylation in the plant cell wall: structure, synthesis, and modification
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Controlling electron beam-induced structure modifications and cation exchange in cadmium sulfide–copper sulfide heterostructured nanorods
The atomic structure and interfaces of CdS/Cu 2 S heterostructured nanorods are explored with the aberration-corrected TEAM 0.5 electron microscope operated at 80 kV and 300 kV applying in-line holography and complementary techniques. Cu 2 S exhibits a low-chalcocite structure in pristine CdS/Cu 2 S nanorods. Under electron beam irradiation the Cu 2 S phase transforms into a high-chalcocite phase while the CdS phase maintains its wurtzite structure. Time-resolved experiments reveal that Cu + -Cd 2+ cation exchange at the CdS/Cu 2 S interfaces is stimulated by the electron beam and proceeds within an undisturbed and coherent sulfur sub-lattice. A variation of the electron beam current provides an efficient way to control and exploit such irreversible solid-state chemical processes that provide unique information about system dynamics at the atomic scale. Particularly, we show that the electron beam-induced copper-cadmium exchange is site specific and anisotropic. A resulting displacement of the CdS/Cu 2 S interfaces caused by beam-induced cation interdiffusion equals within a factor of 3-10 previously reported Cu diffusion length measurements in heterostructured CdS/Cu 2 S thin film solar cells with an activation energy of 0.96 eV.
36 MATERIALS SCIENCE↗
Translation, modification and cellular distribution of two AC4 variants of African cassava mosaic virus in yeast and their pathogenic potential in plants
Plant infecting geminiviruses encode a small (A)C4 protein within the open reading frame of the replication-initiator protein. In African cassava mosaic virus, two in-frame start codons may be used for the translation of a longer and a shorter AC4 variant. Both were fused to green fluorescent protein or glutathione-S-transferase genes and expressed in fission yeast. The longer variant accumulated in discrete spots in the cytoplasm, whereas the shorter variant localized to the plasma membrane. A similar expression pattern was found in plants. A myristoylation motif may promote a targeting of the shorter variant to the plasma membrane. Mass spectrometry analysis of the yeast-expressed shorter variant detected the corresponding myristoylation. The biological relevance of the second start codon was confirmed using mutated infectious clones. Whereas mutating the first start codon had no effect on the infectivity in Nicotiana benthamiana plants, the second start codon proved to be essential. -- Highlights: •The ACMV AC4 may be translated from one or the other in-frame start codon. •Both AC4 variants are translated in fission yeast. •The long AC4 protein localizes to the cytoplasm, the short to the plasma membrane. •The short variant is myristoylated in yeast and may promote membrane localization. •Only the shorter AC4 variant has an impact on viral infections in plants.
60 APPLIED LIFE SCIENCES↗
Improved methodology to assess modification and completion of landfill gas management in the aftercare period
Highlights: Black-Right-Pointing-Pointer Performance-based evaluation of landfill gas control system. Black-Right-Pointing-Pointer Analytical framework to evaluate transition from active to passive gas control. Black-Right-Pointing-Pointer Focus on cover oxidation as an alternative means of passive gas control. Black-Right-Pointing-Pointer Integrates research on long-term landfill behavior with practical guidance. - Abstract: Municipal solid waste landfills represent the dominant option for waste disposal in many parts of the world. While some countries have greatly reduced their reliance on landfills, there remain thousands of landfills that require aftercare. The development of cost-effective strategies for landfill aftercare is in society's interest to protect human health and the environment and to prevent the emergence of landfills with exhausted aftercare funding. The Evaluation of Post-Closure Care (EPCC) methodology is a performance-based approach in which landfill performance is assessed in four modules including leachate, gas, groundwater, and final cover. In the methodology, the objective is to evaluate landfill performance to determine when aftercare monitoring and maintenance can be reduced or possibly eliminated. This study presents an improved gas module for the methodology. While the original version of the module focused narrowly on regulatory requirements for control of methane migration, the improved gas module also considers best available control technology for landfill gas in terms of greenhouse gas emissions, air quality, and emissions of odoriferous compounds. The improved module emphasizes the reduction or elimination of fugitive methane by considering the methane oxidation capacity of the cover system. The module also allows for the installation of biologically active covers or other features designed to enhance methane oxidation. A methane emissions model, CALMIM, was used to assist with an assessment of the methane oxidation capacity of landfill covers.
12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
Energy-efficient modification of reduction-melting for lead recovery from cathode ray tube funnel glass
Highlights: • We recovered Pb from cathode ray tube funnel glass using reduction melting process. • We modified the melting process to achieve Pb recovery with low energy consumption. • Pb in the funnel glass is efficiently recovered at 1000 °C by adding Na{sub 2}CO{sub 3}. • Pb remaining in the glass after reduction melting is extracted with 1 M HCl. • 98% of Pb in the funnel glass was recovered by reduction melting and HCl leaching. - Abstract: Lead can be recovered from funnel glass of waste cathode ray tubes via reduction melting. While low-temperature melting is necessary for reduced energy consumption, previously proposed methods required high melting temperatures (1400 °C) for the reduction melting. In this study, the reduction melting of the funnel glass was performed at 900–1000 °C using a lab-scale reactor with varying concentrations of Na{sub 2}CO{sub 3} at different melting temperatures and melting times. The optimum Na{sub 2}CO{sub 3} dosage and melting temperature for efficient lead recovery was 0.5 g per 1 g of the funnel glass and 1000 °C respectively. By the reduction melting with the mentioned conditions, 92% of the lead in the funnel glass was recovered in 60 min. However, further lead recovery was difficult because the rate of the lead recovery decreased as with the recovery of increasing quantity of the lead from the glass. Thus, the lead remaining in the glass after the reduction melting was extracted with 1 M HCl, and the lead recovery improved to 98%.
12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
Simple device modification simultaneously enhances indoor passive evaporative cooling power and duration
Passive evaporative cooling from a damp cloth or vessel can be used for localized cooling of perishables such as food and medicine, drinking water, and even people. Such applications have two key objectives, which are normally in tension with each other: minimizing the water consumption rate and maximizing the cooling (steady-state temperature swing between the cool cloth and the warm surroundings). Here, we present a simple device that delivers higher performance in both metrics simultaneously by adding a perforated aluminum foil sheet suspended over a stagnant air layer to thermally shield the evaporating surface while also facilitating mass transfer. Experimental results demonstrate a simultaneous 10%–25% increase in temperature swing and 2–3× reduction in water consumption rate as compared to conventional evaporative cooling. This improvement is achieved through careful modeling to optimize the coupled heat and mass transfer through the airgap (thermally insulating and vapor permeable) and perforated foil (infrared reflective and vapor permeable).
Chen, Sarah Mizuno↗
Protein phosphorylation and oxidative protein modification promote plant photosystem II disassembly for repair
Not Available
McKenzie, Steven D.↗
Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions
Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.
60 APPLIED LIFE SCIENCES↗
Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status
Glioblastoma cells exhibit highly invasive behavior whose mechanisms are not yet fully understood. The present study explores the relationship between the invasion capacity of 5 glioblastoma cell lines differing in p53 and PTEN status, expression of mTOR and several other marker proteins involved in cell invasion, actin cytoskeleton organization and cell morphology. We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix. In DK-MG (p53wt/PTENwt) and GaMG (p53mut/PTENwt) cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG (p53wt/PTENmut), U373-MG and SNB19 (both p53mut/PTENmut) cells preferentially expressed F-actin in filopodia and lamellipodia. Scanning electron microscopy confirmed the abundant filopodia and lamellipodia in the PTEN mutated cell lines. Interestingly, the gene profiling analysis revealed two clusters of cell lines, corresponding to the most (U373-MG and SNB19, i.e. p53 and PTEN mutated cells) and less invasive phenotypes. The results of this study might shed new light on the mechanisms of glioblastoma invasion. - Highlights: • We examine 5 glioblastoma lines on the invasion capacity and actin cytoskeleton. • Glioblastoma cell lines mutated in both p53 and PTEN were the most invasive. • Less invasive cells showed much less lamellipodia, but more actin stress fibers. • A mechanism for the differences in tumor cell invasion is proposed.
60 APPLIED LIFE SCIENCES↗