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At least 1,693 records · Page 94

DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells

DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1. These DDX1-targeted alternative splicing genes are mainly associated with calcium ion binding, high voltage-gated calcium channel, and transmembrane transporter. Functionally, silencing DDX1 impairs calcium influx and insulin secretion in the pancreatic β cells. These results reveal an important role for DDX1 in the regulation of gene alternative splicing and insulin secretion in pancreatic β cells.

60 APPLIED LIFE SCIENCES↗

Extreme Fast Charge Challenges for Lithium-Ion Battery: Variability and Positive Electrode Issues

Enabling a 10 min fast charge for electric vehicles is a possible route to reduce range anxiety and increase the utility of electric vehicles. While lithium plating during fast charging is a known challenge, the full suite of limitations which occur in full cells during a 10 min fast charge are unknown. In the present work the central constraints of extreme fast charging are explored through extensive experiments and analysis in single layer graphite/NMC532 pouch cells. Methods of developing fast-charging protocols considering the impedance and transport limitations are presented and the relative benefits of altering the charging rate, profile, relaxation, etc., are investigated. Analysis during and at the end of cycling identified both known and unexpected aging pathways. The most distinct outcomes from the work are a significant increase in cell-to-cell variability as the number of fast charge cycles increase [up to 11% (1σ)] and the identification of distinct aging of the NMC532 positive electrode including cracking of the secondary particles and a trend toward under-lithiation of the positive electrode. Here, while significant aging of the positive electrode was observed, only a few conditions had discernible Li plating and no distinct reversible Li signature was seen during periodic reference performance tests.

25 ENERGY STORAGE↗

Cell migration and organization in three-dimensional in vitro culture driven by stiffness gradient: Cell Migration Driven by Stiffness Gradient

Durotaxis, a phenomenon that cells move according to changes in stiffness of the extra cellular matrix, has emerged as a crucial parameter controlling cell migration behavior. The current study provides a simple method to generate three-dimensional continuous stiffness variations without changing other physical characteristics of the extra cellular environment. Using Finite Element simulations, the stiffness and the stiffness gradient variations are evaluated quantitatively, leading to an analysis of the dependence of cell migration behavior on the substrate stiffness parameters. We tested various cell lines on several 3-D environments. In this work, the durotaxis results show that the cell migration velocity does not have any consistency with the stiffness of the substrate, rather it is more related to the stiffness gradient of the substrate. This finding suggests a new mechanism underlying the durotaxis phenomenon, highlighting the importance of the substrate stiffness gradient, rather than the stiffness itself.

36 MATERIALS SCIENCE↗

MiR-361 targets Yes-associated protein (YAP) mRNA to suppress cell proliferation in lung cancer

Yes-associated protein (YAP) contributes to the development of multiple tumors, but the post-transcription modulation of YAP remains unexplored. Here, we present a new regulatory microRNA of YAP, miR-361, which directly targets YAP to inhibit cell proliferation in lung cancer. We used bioinformatics to predict that miR-361 could target 3′-untranslated region (3′UTR) of YAP mRNA. Luciferase reporter gene assays demonstrated that miR-361 could decrease the luciferase activities of 3′UTR vector of YAP. Furthermore, YAP expression was obviously abated by miR-361 using RT-PCR and immunoblotting in lung cancer A549 cells. In terms of function, MTT and colony formation analysis showed that ectopic miR-361 expression significantly suppressed cell proliferation in lung cancer. Notably, overexpressed YAP accelerated miR-361-bated proliferation of lung cancer cells. MiR-361 inhibitor promoted cell proliferation in lung cancer, but YAP RNA interference reversed miR-361 inhibitor-driven cell proliferation. Interestingly, miR-361 was capable of affecting the cell cycle in lung cancer progression. Finally, the negative correlation of miR-361 with YAP was found in clinical human lung cancer tissues. In conclusion, miR-361 targets 3′UTR of YAP mRNA to depress the proliferation of lung cancer cells. - Highlights: • MiR-361 is able to target 3′UTR of YAP mRNA. • MiR-361 suppresses the proliferation of lung cancer by inhibiting YAP. • YAP is negatively correlated with miR-361 in lung cancer tissues. • YAP is up-regulated in clinical lung cancer tissues.

60 APPLIED LIFE SCIENCES↗

The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts

The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed in many cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression of individual pre-miRs-182, -96 and -183 in prostate cells decreased zinc import, which is a characteristic feature of PCa tumours. Zinc is concentrated in healthy prostate 10-fold higher than any other tissue, and an >80% decrease in zinc is observed in PCa specimens. Here, we studied the effect of overexpression of the entire 4.8 kb miR-183 family cluster, including the intergenic region which contains highly conserved genomic regions, in prostate cells. This resulted in overexpression of mature miR-183 family miRs at levels that mimic cancer-related changes. Overexpression of the miR-183 cluster reduced zinc transporter and intracellular zinc levels in benign prostate cells, PCa xenografts and fresh prostate epithelial organoids. Microarray analysis of miR-183 family cluster overexpression in prostate cells showed an enrichment for cancer-related pathways including adhesion, migration and wound healing. An active secondary transcription start site was identified within the intergenic region of the miR-183 cluster, which may regulate expression of miR-182. Taken together, this study shows that physiologically relevant expression of the miR-183 family regulates zinc levels and carcinogenic pathways in prostate cells.

Science & Technology - Other Topics↗

Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung

Systems biology uses computational approaches to integrate diverse data types to understand cell and organ behavior. Data derived from complementary technologies, for example transcriptomic and proteomic analyses, are providing new insights into development and disease. We compared mRNA and protein profiles from purified endothelial, epithelial, immune, and mesenchymal cells from normal human lung tissue. Signatures for each cell type were identified and compared at both mRNA and protein levels. Cell specific biological processes and pathways were predicted by analysis of concordant and discordant RNA-protein pairs. Cell clustering and gene set enrichment comparisons identified shared versus unique processes associated with transcriptomic and/or proteomic data. Clear cell-cell correlations between mRNA and protein data were obtained from each cell type. Approximately 40% of RNA-protein pairs were coherently expressed. While the correlation between RNA and their protein products was relatively low (approximately 0.4), cell specific signature genes involved in functional processes characteristic of each cell type, were more highly correlated with their protein products. Consistency of cell specific RNA-protein signatures indicated an essential framework for the function of each cell type. Visualization and reutilization of the protein and RNA profiles are supported by a new web application, "LungProteomics," which is incorporated into the LGEA web portal and freely accessible at (https://research.cchmc.org/pbge/lunggens/lungProteomics/human_sorted_profiles.html).

human lung, sorted cells, integrated omics, Transc↗

Fuel Cell Electric Vehicles: Drivers and Impacts of Adoption.

We present scenario and parametric analyses of the US light duty vehicle (LDV) stock, sim- ulating the evolution of the stock in order to assess the potential role and impacts of fuel cell electric vehicles (FCEVs). The analysis probes the competition of FCEVs with other LDVs and the effects of FCEV adoption on LDV fuel use and emissions. We parameterize commodity and technology prices in order to explore the sensitivities of FCEV sales and emissions to oil, natural gas, battery technology, fuel cell technology, and hydrogen produc- tion prices. We additionally explore the effects of vehicle purchasing incentives for FCEVs, identifying potential impacts and tipping points. Our analyses lead to the following conclu- sions: (1) In the business as usual scenario, FCEVs comprise 7% of all new LDV sales by 2050. (2) FCEV adoption will not substantially impact green house gas emissions without either policy intervention, significant increases in natural gas prices, or technology improve- ments that motivate low carbon hydrogen production. (3) FCEV technology cost reductions have a much greater potential for impact on FCEV sales than hydrogen fuel cost reductions. (4) FCEV purchasing incentives must be both substantial and sustained in order to motivate lasting changes to FCEV adoption.

33 ADVANCED PROPULSION SYSTEMS↗

A non-invasive measure of minerals and electrolytes in tissue

A system for collecting epithelial cells from the oral mucosa for the determination of ion concentration is discussed with application to the study of man's adaptation to microgravity. A number of characteristics of these cells influenced the choice for clinical testing. They are non-cornified epithelial cells located on the inferior aspect of the tongue; therefore, they are well protected from trauma. They have the capability of reflecting relatively recent physiologic changes since they are renewed every three days and have aerobic metabolism. Most importantly, they are easily accessible and can be removed by a wooden applicator stick with minimum discomfort. Smears of cells removed in this manner show predominantly individual cells rather than sheets of contiuous cells. This facilitates the visual isolation of single cells with the electron microscope for analysis. NASA's principle effort in the development of a test to measure the ion concentration in sublingual cells has been research by the biomedical program carried out by scientists with expertise in skeletal metabolism. These efforts were directed toward determining the biological meaning and deviations in interacellular ions in nonhuman primates and in male volunteers for experiments in a model for weightlessness. A brief one page summary of the experiments and results are presented.

Arnaud, Sara B.↗

Structural and Functional Analysis of the Spermatogenic Epithelium in Rats Exposed to Titanium Dioxide Nanoparticles

We studied immunohistochemical and morphometric characteristics of the spermatogenic epithelium in rats against the background of peroral administration of nanoparticles containing titanium dioxide. Substantial degenerative changes in the spermatogenic epithelium were revealed: thinning, disorganization of layers, and detachment of sperm cells from the basement membrane. Immunohistochemical analysis revealed reduced proliferative activity and differentiation potential of epithelial cells, which was confirmed by changes in the expression of Ki-67 and c-kit markers. Our data attest to unfavorable effects of titanium dioxide nanoparticles on the structural and functional characteristics of the reproductive system in male rats leading to spermatogenesis disturbances.

60 APPLIED LIFE SCIENCES↗

Effects of thermal annealing on the deep-level defects and I-V characteristics of 200 keV proton irradiated AlGaAs-GaAs solar cells

Detailed characterization of deep-level defects and analysis of dark I-V data in 200 keV proton irradiated AlGaAs-GaAs solar cells have been carried out for several proton fluences (5 x 10 to the 11th, 10 to the 12th, and 10 to the 13th P/sq cm), using DLTS, C-V, and I-V measurement techniques. To study the effect of low temperature thermal annealing on the deep-level defect properties, these irradiated samples were annealed in vacuum at 300 C for one hour. Comparison was then made on the measured defect parameters (i.e., defect energy levels and densities) and the dark I-V characteristics for both the annealed and unannealed samples.

Li, S. S.↗

A Review and Perspective on Cathodoluminescence Analysis of Halide Perovskites

Halide perovskite solar cells have achieved a certified efficiency of 25.2%, surpassing CdTe and CuInGaSe 2 , which have long been regarded as the most-efficient thin-film photovoltaic materials. As this exciting class of materials continues to mature, researchers will require characterization techniques capable of exposing the interplay among structure, chemistry, and optoelectronic properties to inform processing strategies and increase both device efficiencies and long-term stability. Cathodoluminescence microscopy is an ideal technique to provide such information due to the high spatial resolution and robust optical information acquired. Here, the current body of work related to cathodoluminescence analysis of halide perovskite materials for optoelectronic applications is surveyed. This review demonstrates how cathodoluminescence can monitor degradation due to environmental stressors, phase segregation resulting from material processing, and other halide perovskite-centric material issues. A persistent concern associated with e-beam-based analysis of halide perovskites is what effect the electron beam has on the material properties being probed. Addressing this, a detailed discussion is provided on the origin of the cathodoluminescence signal and a review of studies focused on revealing changes in the properties of halide perovskites resulting from e-beam excitation. Finally, a perspective on future opportunities to expand the role of cathodoluminescence analysis for halide perovskites is provided.

14 SOLAR ENERGY↗

Hypergravity Loading the Cultured Osteoblasts: Modeling and Experimental Analysis of Cellular Morphology and the Cytoskeleton

Bone forming cells, osteoblasts, respond to various mechanical forces, including mechanical strain and fluid-induced shear stress. This study examined whether osteoblasts detect changes in gravity as a mechanical force, as assessed by cellular morphology and dimensions of the cytoskeletal network. We used modeling to evaluate how gravity influences cell morphology given theoretical differences in densities between the surrounding medium, cytoplasm, and nucleus. A mechanical model was built based on analysis of axisymmetric shell structures (Fast4 software) to study the effects of 10 times gravity (10G) on cell height. The model indicated 0.02% decrease in overall cell height when the medium was 10% denser than the nucleus or cytoplasm, 5.9 x 10(exp-5)% decrease when the nucleus was 10% denser than the cytoplasm or medium, and 1.3 x 10(exp-5)% decrease when the cell cytoplasm was 10% denser than the nucleus or medium. To experimentally evaluate the influence of gravity, cultured primary fetal rat osteoblasts were grown to near confluence and centrifuged at 10G for 3 hours. Actin, microtubules, and nuclei were fluorescently labeled and analyzed by confocal microscopy to determine overall microtubule and actin network height. Centrifugation led to an apparent reduction in height of both the microtubule (-16%) and the actin (-20%) networks relative to stationary controls. Thus, both modeling and experiments indicate that hypergravity reduces the height of the osteoblast cell layer and their microtubule and actin networks. This combination of modeling and experimental analyses will help us to better understand the mechanical loading of osteoblasts.

Searby, N. D.↗

Analysis and Simulation of One-Dimensional Transport Models for Lithium Symmetric Cells

The main objective of this paper is to analyze transport models for lithium symmetric cells and arrive at an efficient model and code to simulate the same. Two one-dimensional models are considered. The first model uses the dilute solution Nernst–Planck equations in conjunction with the electroneutrality assumption (EN-NP model). For binary electrolytes, an analytical solution for electrolyte concentration is derived and compared with numerical solutions by an approximate finite volume method. The second approach relaxes the electroneutrality assumption by way of Poisson’s equation for the electrostatic potential (PNP model). The computational difficulties of the PNP model are tackled using the approximate finite volume method, with demonstrated convergence characteristics even with bulk dimensions several orders of magnitude larger than the characteristic double layer size. A robust code is developed for the PNP model. The computationally efficient transport models can facilitate simulations, physical understanding, and analysis. This is illustrated by a case study in which these models are coupled with modified kinetic models, which are then parameterized with experimental voltage response data using a systems-level approach. The estimated parameters provide further insight into the electrochemical phenomena underpinning voltage transitions in symmetric cells.

25 ENERGY STORAGE↗

Chemical imaging of molecular changes in a hydrated single cell by dynamic secondary ion mass spectrometry and super-resolution microscopy

Chemical imaging of single cells is important in capturing biological dynamics. Single cell correlative imaging is realized between structured illumination microscopy (SIM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) using System for Analysis at the Liquid Vacuum Interface (SALVI), a multimodal microreactor. SIM characterized cells and guided subsequent ToF-SIMS analysis. Dynamic ToF-SIMS provided time- and space-resolved cell molecular mapping. Lipid fragments were identified in the hydrated cell membrane. Principal component analysis was used to elucidate chemical component differences among mouse lung cells that uptake zinc oxide nanoparticles. Our results provided submicron chemical spatial mapping for investigations of cell dynamics at the molecular level.

correlative chemical imaging • microfluidic • surf↗

Laser-zone growth in a Ribbon-To-Ribbon, RTR, process silicon sheet growth development for the large area silicon sheet task of the low cost silicon solar array project

A ribbon-to-ribbon process was used for routine growth of samples for analysis and fabrication into solar cells. One lot of solar cells was completely evaluated: ribbon solar cell efficiencies averaged 9.23% with a highest efficiency of 11.7%. Spherical reflectors have demonstrated significant improvements in laser silicon coupling efficiencies. Material analyses were performed including silicon photovoltage and open circuit photovoltage diffusion length measurements, crystal morphology studies, modulus of rupture measurements, and annealing/gettering studies. An initial economic analysis was performed indicating that ribbon-to-ribbon add-on costs of $.10/watt might be expected in the early 1980's.

Gurtler, R. W.↗

GLOBAL HELIOSEISMIC EVIDENCE FOR A DEEPLY PENETRATING SOLAR MERIDIONAL FLOW CONSISTING OF MULTIPLE FLOW CELLS

We use a novel global helioseismic analysis method to infer the meridional flow in the deep Solar interior. The method is based on the perturbation of eigenfunctions of Solar p modes due to meridional flow. We apply this method to time series obtained from Dopplergrams measured by the Michelson Doppler Imager aboard the Solar and Heliospheric Observatory covering the observation period 2004-2010. Our results show evidence that the meridional flow reaches down to the base of the convection zone. The flow profile has a complex spatial structure consisting of multiple flow cells distributed in depth and latitude. Toward the Solar surface, our results are in good agreement with flow measurements from local helioseismology.

79 ASTRONOMY AND ASTROPHYSICS↗

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

60 APPLIED LIFE SCIENCES↗