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At least 937 records · Page 52

Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

60 APPLIED LIFE SCIENCES↗

Perinatal exposure to organohalogen pollutants decreases vasopressin content and its mRNA expression in magnocellular neuroendocrine cells activated by osmotic stress in adult rats

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported that rats perinatally exposed to Aroclor-1254 (A1254) and DE-71 (commercial mixtures of PCBs and PBDEs) decrease somatodendritic vasopressin (AVP) release while increasing plasma AVP responses to osmotic activation, potentially emptying AVP reserves required for body-water balance. The aim of this research was to evaluate the effects of perinatal exposure to A1254 or DE-71 (30 mg kg/day) on AVP transcription and protein content in the paraventricular and supraoptic hypothalamic nuclei, of male and female rats, by in situ hybridization and immunohistochemistry. cFOS mRNA expression was evaluated in order to determine neuroendocrine cells activation due to osmotic stimulation. Animal groups were: vehicle (control); exposed to either A1254 or DE-71; both, control and exposed, subjected to osmotic challenge. The results confirmed a physiological increase in AVP-immunoreactivity (AVP-IR) and gene expression in response to osmotic challenge as reported elsewhere. In contrast, the exposed groups did not show this response to osmotic activation, they showed significant reduction in AVP-IR neurons, and AVP mRNA expression as compared to the hyperosmotic controls. cFOS mRNA expression increased in A1254 dehydrated groups, suggesting that the AVP-IR decrease was not due to a lack of the response to the osmotic activation. Therefore, A1254 may interfere with the activation of AVP mRNA transcript levels and protein, causing a central dysfunction of vasopressinergic system. - Highlights: • Perinatal exposure to A1254 and DE-71 disrupts the vasopressin system of adult rats. • Exposure to organohalogens reduces AVP responses to osmotic stress in PVN and SON. • Perinatal exposure to A1254 fails to increase AVP mRNA in the hyperosmotic challenge. • Hyperosmotic stress and A1254 exposure activate cFOS gene in PVN and SON neurons. • Perinatal exposure to A1254 disrupts the AVP system similarly in Wistar and SD rats.

60 APPLIED LIFE SCIENCES↗

NdFeB content in ancillary motors of U.S. conventional passenger cars and light trucks: Results from the field

Research into secondary recovery of rare earth elements (REE) has focused mostly on hard disk drives and automotive applications. While REE content in Japanese and European vehicles is relatively well-known, understanding of U.S. vehicles is mostly based on database analysis. An attempt to pinpoint which components contain the most REEs was conducted on four different vehicle models including the Ford F-150, Chevrolet Silverado, Toyota Corolla and Honda Accord. The disassembly data were combined with 2017 vehicles in operation to estimate stocks and flows of Neodymium-Iron-Boron (NdFeB). Results showed that U.S. vehicles had major differences compared to Japanese and European vehicles. NdFeB magnets were only found in speakers ranging from 16 to 114 g/vehicle. An estimated 3.0 – 14 tonnes of NdFeB could be available from end-of-life vehicles in 2018 from different cohorts of the four aforementioned models. Furthermore, while opportunities for recycling NdFeB in vehicles exist, challenges are also present.

36 MATERIALS SCIENCE↗

Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.

60 APPLIED LIFE SCIENCES↗

Delineating the Roles of Mn, Al, and Co by Comparing Three Layered Oxide Cathodes with the Same Nickel Content of 70% for Lithium-Ion Batteries

High-nickel layered oxides continue to prevail in the energy storage market as the frontmost cathode candidates for next-generation lithium-ion batteries. Demand and development of LiNi 1–x–y Mn x Co y O 2 (NMC) and LiNi 1–x–y Co x Al y O 2 (NCA) cathodes are rampantly increasing, particularly for the electric vehicle (EV) industry. However, the continued presence of cobalt in NMC and NCA cathodes raises global concerns due to geopolitical and ethical issues attributed to Co sourcing. We herein introduce a novel cobalt-free, high-nickel cathode LiNi 0.7 Mn 0.25 Al 0.05 O 2 (NMA70) and benchmark it against Co-containing LiNi 0.7 Mn 0.15 Co 0.15 O 2 (NMC70) as well as Co- and Al-free LiNi 0.7 Mn 0.3 O 2 (NM70) cathodes with equivalent 70% Ni contents that are all synthesized in-house. NMA70 displays a high initial C/10 capacity of 210 mA h g –1 , matching that of NMC70 in half cells with a cutoff voltage of 4.5 V. NMA70 also exhibits an impressive high-voltage full cell cycling performance with a cutoff voltage of 4.4 V with a nearly identical capacity retention of 83% compared to that of 82% for NMC70 after 300 cycles. Postmortem X-ray photoelectron spectroscopy (XPS), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), and electron energy loss spectroscopy (EELS) analyses indicate a thinner cathode–electrolyte interface (CEI) developed in NMA70 compared to that in NM70 and unveil a more robust solid-electrolyte interface (SEI) passivation on the graphite anode among all samples. The benefits of Al doping are additionally highlighted with enhanced high-voltage CEI and thermal stabilities in NMA70. Furthermore, this work assesses the roles of Mn, Al, and Co to demonstrate both the practicality and feasibility of synthesizing cobalt-free, high-nickel cathodes that are promising alternatives to current NMC- and NCA-based cathodes.

25 ENERGY STORAGE↗

Role of Fe(II) Content in Olivine Carbonation in Wet Supercritical CO2

Basalt geologic reservoirs are targeted for carbon storage because they are abundant in divalent silicates such as olivine ((Mg,Fe)2SiO4) that can carbonate to permanently trap CO2. At reservoir conditions, CO2 is a supercritical fluid that contains dissolved H2O, which adsorbs to minerals as nanometer-thin films. In this study, the role of Fe(II) in the thin H2O film carbonation of olivine was investigated using in situ high pressure infrared spectroscopy and ab initio thermodynamic calculations. Experiments were performed at 50 °C and 90 bar in both scCO2 and scCO2 with 1% H2 at a relative humidity of 79% on synthetic forsterite, fayalite, and two Mg-Fe mixture olivines (MgxFe1-x)2SiO4 (x = 0.33 and 0.66). Carbonation rates and extents are lower with increasing concentrations of Fe(II) in the olivine, but the addition of 1% H2 increases carbonation in Fe(II)-rich olivines. These trends are explained according to the dependencies of olivine acidic solubilities, carbonate precipitation equilibria, and dissolution/growth kinetics on Fe(II) content, and by considering that Fe(II)-rich olivines can undergo competing oxidation reactions by O2 and H2O and Fe(III)-containing oxides. Given that CO2 injected into the subsurface will be relatively oxic, the oxidation of Fe(II)-rich olivines could impact their carbonation potential.

Wood, Cecelia E.↗

Effect of Nanoscale Ce 0.8 Gd 0.2 O 2–δ Infiltrant and Steam Content on Ni–(Y 2 O 3 ) 0.08 (ZrO 2 ) 0.92 Fuel Electrode Degradation during High-Temperature Electrolysis

Studies of Ni–yttria-stabilized zirconia (YSZ) fuel electrode degradation mechanisms in solid oxide electrolysis cells (SOECs) are complicated by the different possible Ni–YSZ microstructures and compositions, and the variations in the H 2 /H 2 O ratio encountered in an electrolysis stack. Here, in this study, we describe a life testing scheme aimed at providing survey results on degradation as a function of the H 2 O–H 2 composition, with life tests carried out at five different steam contents from 90% to 10%. A Ni–YSZ-supported symmetric cell geometry is employed both with and without infiltrated nanoscale gadolinia-doped ceria (GDC). Impedance spectroscopy is utilized to observe changes in electrochemical characteristics during the life test, and a transmission-line-based equivalent circuit is used to model the data. Post-test electrode microstructures were observed. The results suggest that the GDC infiltrant reduces the electrode polarization resistance and provides more stable electrode polarization over a range of conditions.

08 HYDROGEN↗

Effect of Diphenyl Content on Viscoelasticity of Poly(dimethyl- co -diphenyl)siloxane Melt and Network

Polydimethylsiloxane (PDMS) is one of the most widely used polymeric materials for sealants, adhesives, lubricants, and thermal as well as electrical insulation. At low temperatures, however, PDMS is subject to crystallization that can cause deterioration in mechanical function. A common way to suppress such crystallization is through the incorporation of phenylsiloxane into the backbone of polysiloxane. Nevertheless, the introduction of phenyl components, even in small quantities, could potentially change the properties of the siloxane in a significant way. In this work, a series of mechanical tests and finite element simulations were performed to study the macroscale viscoelasticity of two poly(dimethyl-co-diphenyl)siloxane formulations in order to understand the effects of a few percent diphenyl contents on the viscoelasticity of the polysiloxane material. Here, we utilized the small-angle X-ray scattering to investigate the microscopic structures of the copolymers and broadband dielectric spectroscopy and rheology to probe the chain dynamics at the microscale. The results of these characterizations were used to inform the finite element simulations. We found that the degree of cross-linking does not significantly alter the microstructure but can profoundly affect the viscoelastic response of the copolymer networks. The corresponding hysteretic behavior is interpreted in terms of reptation-like motion and relaxation of the effective free chains in the cured polymer network. The relaxation of the copolymer chains is slowed significantly by even a small increase in the molar ratio of the diphenyl component.

36 MATERIALS SCIENCE↗

Determination of Arsenic Content in Water Using a Silver Coordination Polymer

In this report, we describe a practical method for the colorimetric determination of dissolved inorganic arsenic content in water samples, using a silver coordination polymer as the sensing material. We demonstrate that a crystalline polymer framework can be used to stabilize silver(I) ions, greatly reducing both photosensitivity and water solubility, while still affording sufficient reactivity to detect arsenic in water samples at low parts-per-billion (ppb) levels. Test strips fabricated with the silver-based polymer are shown to be effective for field tests of groundwater under real-world operating conditions and display performance that is competitive with commercially available mercury-based test strips. Spectroscopic methods are also used to probe the reaction products formed, in order to better understand the sensing mechanism. Thus, our work provides the foundation for an improved field test that could be deployed to help manage groundwater usage in regions where arsenic contamination is problematic but sophisticated lab testing is not readily available.

36 MATERIALS SCIENCE↗

Identifying the Role of Magnesium Content in Assessing the Electrochemical Performance of (CoCuMgNiZn)O

High-entropy oxides (HEOs) featuring 5 or more metals in approximately equimolar ratios, such as the prototypical rock-salt-structured (CoCuMgNiZn)O, have attracted interest for their potential to display material properties superior to oxides with combinations of 4 or fewer of the component metals. In particular, (CoCuMgNiZn)O has shown promise as an anode for lithium-ion batteries with a high specific capacity retention over extended cycling. Previous studies have suggested that magnesium, despite being electrochemically inert, provides a crucial contribution to the favorable performance of this HEO by stabilizing the crystal structure through repeated charge–discharge cycles. This paper probes the extent and mechanism of the magnesium effect by using a facile microwave-assisted hydrothermal synthesis method to vary the level of Mg content. Moreover, we extensively characterized the product with techniques such as 4D-STEM and ICP-OES, which have not previously been applied in combination with this material, in order to elucidate the relationships among chemical composition, nanostructure, and performance. Here, we show that the level of Mg incorporation is positively correlated with long-term stability and negatively correlated with rate capacity, and that the latter effect yields a stronger influence upon the overall performance, with the best-performing sample possessing a Mg quantity equivalent to ∼1/5 that of an equimolar concentration. This finding demonstrates not only that the variation of individual elemental levels offers a promising and relatively unexplored avenue to optimize the electrochemical performance of HEO materials but also that it should not be assumed that equimolar compositions of constituent elements are necessarily the best.

36 MATERIALS SCIENCE↗

Derivations of the Total Radiation Belt Electron Content

Abstract We present multiple derivations of the Total Radiation Belt Electron Content (TRBEC), an indicator of the global number of electrons that instantaneously occupy the radiation belts. Derived from electron flux measurements, the TRBEC reduces the spatial information into a scalar quantity that concisely describes global aspects of the system. This index provides a simple, global, and long‐term assessment of the radiation belts that enables systematic analysis. In this work, we examine the TRBEC using the adiabatic invariants of which has been used in previous articles as this coordinate system removes reversible adiabatic effects. We then introduce a new expression to compute the TRBEC using the non‐adiabatic coordinates of , relevant in the contexts of energetic electron precipitation, chorus, and hiss scattering where adiabatic invariant quantities are no longer conserved. From both expressions of the TRBEC we demonstrate that an erroneous factor of that appeared in previous works using the adiabatic derivation led to an overestimate of the reported electron populations. In addition, we quantify electron loss in the outer radiation belt via a case study using the Van Allen Probes data over a 20‐day period from March 2013 specifying particle populations both in terms of the aforementioned adiabatic and non‐adiabatic variables. The total number of electrons in the outer radiation belt reached upwards of electrons at the peak of the storm, a rest mass of roughly 10 g.

Astronomy & Astrophysics↗

Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content

Transcription Factor 4 ( TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4 . We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

59 BASIC BIOLOGICAL SCIENCES↗

Resolving complex intralayer transition motifs in high-Ni-content layered cathode materials for lithium-ion batteries

High-Ni-content layered materials are promising cathodes for next-generation lithium-ion batteries. However, investigating the atomic configurations of the delithiation-induced complex phase boundaries and their transitions remains challenging. Here, in this study, by using deep-learning-aided super-resolution electron microscopy, we resolve the intralayer transition motifs at complex phase boundaries in high-Ni cathodes. We reveal that an O3 → O1 transformation driven by delithiation leads to the formation of two types of O1–O3 interface, the continuous- and abrupt-transition interfaces. The interfacial misfit is accommodated by a continuous shear-transition zone and an abrupt structural unit, respectively. Atomic-scale simulations show that uneven in-plane Li+ distribution contributes to the formation of both types of interface, and the abrupt transition is energetically more favourable in a delithiated state where O1 is dominant, or when there is an uneven in-plane Li + distribution in a delithiated O3 lattice. Moreover, a twin-like motif that introduces structural units analogous to the abrupt-type O1–O3 interface is also uncovered. The structural transition motifs resolved in this study provide further understanding of shear-induced phase transformations and phase boundaries in high-Ni layered cathodes.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Ultra-low binder content 3D printed calcium phosphate graphene scaffolds as resorbable, osteoinductive matrices that support bone formation in vivo

Bone regenerative engineering could replace autografts; however, no synthetic material fulfills all design criteria. Nanocarbons incorporated into three-dimensional printed (3DP) matrices can improve properties, but incorporation is constrained to low wt%. Further, unmodified nanocarbons have limited osteogenic potential. Functionalization to calcium phosphate graphene (CaPG) imparts osteoinductivity and osteoconductivity, but loading into matrices remained limited. This work presents ultra-high content (90%), 3DP-CaPG matrices. 3DP-CaPG matrices are highly porous (95%), moderately stiff (3 MPa), and mechanically robust. In vitro, they are cytocompatible and induce osteogenic differentiation of human mesenchymal stem cells (hMSCs), indicated by alkaline phosphatase, mineralization, and COL1α1 expression. In vivo, bone regeneration was studied using a transgenic fluorescent-reporter mouse non-union calvarial defect model. 3DP-CaPG stimulates cellular ingrowth, retains donor cells, and induces osteogenic differentiation. Histology shows TRAP staining around struts, suggesting potential osteoclast activity. Apparent resorption of 3DP-CaPG was observed and presented no toxicity. 3DP-CaPG represents an advancement towards a synthetic bone regeneration matrix.

60 APPLIED LIFE SCIENCES↗

Improved robustness of sequentially deposited potassium cesium antimonide photocathodes achieved by increasing the potassium content towards theoretical stoichiometry

Alkali antimonide semiconductor photocathodes are promising candidates for high-brightness electron sources for advanced accelerators, including free-electron lasers (FEL), due to their high quantum efficiency (QE), low emittance, and high temporal resolution. Two challenges with these photocathodes are (1) the lack of a universal deposition recipe to achieve crystal stoichiometries and (2) their high susceptibility to vacuum contamination, which restricts their operation pressure to ultrahigh vacuums and leads to a short lifetime and low extraction charge. To resolve these issues, it is essential to understand the elemental compositions of deposited photocathodes and correlate them to robustness. Here, we report depth profiles for potassium cesium antimonide photocathodes, which were investigated using synchrotron radiation x-ray photoelectron spectroscopy, and the robustness of those photocathodes. We prepared two types of photocathodes with different potassium contents via sequential thermal evaporation. Depth profiles revealed that the photocathodes with a potassium deficit had excess cesium at the surface, while the ratio of potassium and cesium to antimony decreased rapidly within the film. In contrast, the photocathodes with sufficient potassium had close to the theoretical stoichiometry of K 2 CsSb at the surface and maintained that stoichiometry for over half the entire film thickness. Both photocathode types had a similar maximum QE at 532 nm; however, exposure to oxygen revealed that the photocathode with a crystalline stoichiometry of K 2 CsSb maintained QE at one order of magnitude higher pressure compared to its potassium-deficit counterpart. These results highlight the importance of synthesizing potassium cesium antimonide photocathodes with sufficient potassium to achieve the theoretical crystalline stoichiometry for both high QE and improved robustness.

47 OTHER INSTRUMENTATION↗

Enhancing glass-forming ability via frustration of nano-clustering in alloys with a high solvent content

The glass-forming ability (GFA) of alloys with a high-solvent content such as soft magnetic Fe-based and Al-based alloys is usually limited due to strong formation of the solvent-based solid solution phase. Herein, we report that the GFA of soft magnetic Fe-based alloys (with .70 at.% Fe to ensure large saturation magnetization) could be dramatically improved by doping with only 0.3 at.% Cu which has a positive enthalpy of mixing with Fe. It was found that an appropriate Cu addition could enhance the liquid phase stability and crystallization resistance by destabilizing the a-Fe nano-clusters due to the necessity to redistribute the Cu atoms. However, excessive Cu doping would stimulate nucleation of the a-Fe nano-clusters due to the repulsive nature between the Fe and Cu atoms, thus deteriorating the GFA. Our findings provide new insights into understanding of glass formation in general.

36 MATERIALS SCIENCE↗

Low Pt-content ternary PdCuPt nanodendrites: an efficient electrocatalyst for oxygen reduction reaction

Dendritic nanostructures are capturing increasing attentions in electrocatalysis owing to their unique structural features and low density. Herein, we report for the first time bromide ions mediated synthesis of low-Pt-content PdCuPt ternary nanodendrites via galvanic replacement reaction between Pt precursor and PdCu template in aqueous solution. The experimental results show that the ternary PdCuPt nanodendrites present enhanced electrocatalytic performance for oxygen reduction reaction in acid solution compared with commercial Pt/C as well as some state-of-the-art catalysts. In details, the mass activity of the PdCuPt catalyst with optimized composition is 1.73 A/mgPt at 0.85 V vs RHE, which is 14 times higher than that of commercial Pt/C catalyst. Moreover, the long-term stability test demonstrates its better durability in acid solution. After 5k cycles, there is still 70% electrochemical surface area maintained. This method provides an efficient way to synthesize trimetallic alloys with controllable composition and specific structure for oxygen reduction reaction.

Environmental Molecular Sciences Laboratory↗