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Lipophagy is a central cellular process for providing the cell with a readily utilized, high energy source of neutral lipids. Since its discovery over a decade ago, we are just starting to understand the molecular components that drive lipophagy, how it is activated in response to nutrient availability, and its potential as a therapeutic target in disease. In this Cell Science at a Glance article and the accompanying poster, we first provide a brief overview of the different structural and enzymatic proteins that comprise the lipid droplet (LD) proteome and reside within the limiting phospholipid monolayer of this complex organelle. We then highlight key players in the catabolic breakdown of LDs during the functionally linked lipolysis and lipophagy processes. Finally, we discuss what is currently known about macro- and micro-lipophagy based on findings in yeast, mammalian and other model systems, and how impairment of these important functions can lead to disease states. [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM) acts on the airway epithelium to induce airway inflammation in asthma. We previously showed that the ability of HDM to induce allergic sensitization in mice is related to airway epithelial CCL20 secretion. Objective: As a disintegrin and metalloprotease (ADAM)s have been implicated in chemokine shedding, we sought to determine their involvement in HDMinduced release of chemokines, including CCL20, by airway epithelial cells. Methods: We studied the effects of pharmacological ADAM inhibitors as well as ADAM10 and ADAM17 siRNA downregulation on chemokine release using (multiplex) ELISA in supernatants from HDM-exposed human bronchial epithelial 16HBE cells and primary normal human bronchial epithelial cells (NHBE) at 4-24 h. Results: House dust) mite markedly increased CCL20 levels in both 16HBE and NHBE cells (16-24 h). In 16HBE cells, the HDM-induced increase was observed as early as 4 h upon exposure and the use of specific inhibitors indicated the involvement of ADAM10/17-mediated shedding. siRNA knockdown of ADAM10, but not of ADAM17, significantly reduced the HDM-induced release of CCL20 in both 16HBE and NHBE cells. A similar effect was observed for HDM-induced CCL2, CCL5, and CXCL8 release in NHBE cells. The HDMinduced increase in CCL20 levels was not affected by protein synthesis inhibitor cycloheximide nor protein transport inhibitor monensin, indicating that HDM induces surface shedding of chemokines. Conclusion: Our data show for the first time that ADAM10 activity contributes to HDM-induced shedding of chemokines, including CCL20. The ADAM10/ CCL20 axis may be a target for novel therapeutic strategies in asthma. [ABSTRACT FROM AUTHOR]

R3458 --> 481.3 --> Introduction and Objective: Alcohol consumption has increased dramatically in recent years, representing a significant challenge to human health in metabolic disease. The leading cause of alcohol‐related death is alcohol‐associated liver disease (AALD), which is present at early stages (i.e. steatosis) in 90% of heavy drinkers. During early AALD, liver hepatocytes accumulate large stores of triglycerides in the form of lipid droplets (LDs). Under normal conditions, degradative lysosomes form direct contacts with LDs and catabolize lipid via microlipophagy, a specialized autophagic pathway utilizing the lipid‐degrading enzyme lysosomal acid lipase (LAL). However, the trafficking mechanisms that govern LD‐lysosome contacts during microlipophagy are poorly understood. Several promising candidates exist within the Rab family of small GTPases, which are well‐known to direct the trafficking of intracellular vesicles and LDs. Moreover, previous studies suggest that Rab proteins play central roles in LD catabolism. Thus, the OBJECTIVE of this study was to investigate novel Rab proteins that might be impaired by EtOH leading to altered LD dynamics and microautophagy. Materials and Methods: To this end, we utilized RNAi gene silencing, subcellular fractionation, Western blot analysis, and high‐resolution microscopy to define Rabs that might target LDs to lysosomes during microlipophagy. To mimic alcoholic fatty liver, cellular and animal models of alcohol consumption were also used. Changes in LD‐lysosome interaction were measured by quantitative confocal microscopy following pharmacological inhibition of LAL by LAListat. Results: First, confocal microscopy revealed that GFP‐Rab5, an early endosomal Rab GTPase, localizes to hepatocellular LDs consistent with proteomic and Western blot analyses showing abundant levels of Rab5 in biochemically isolated LDs. Importantly, siRNA knockdown of Rab5 in cultured hepatocytes showed substantial increases in total LD area (2‐fold) and LD number (1.6‐fold), and also blocked the catabolism of LDs in lipid‐loaded cells. Finally, Rab5 knockdown nearly completely abolished microlipophagy as measured by fluorescent LD accumulation in lysosomes following LAListat treatment. The dissociation of LDs from lysosomes in Rab5 knockdown cells was strikingly similar to the defect observed in EtOH‐fed hepatocytes. Together, these findings suggest that Rab5 is a key mediator of targeting LDs to the lysosome compartment for catabolism and may be a target of EtOH insult. Significance/Implication: This study sheds light on new molecular mechanisms of microlipophagy that are affected by chronic alcohol consumption. These mechanisms may represent promising avenues for future therapeutic development toward mitigating hepatic steatosis and slowing the progression of AALD. [ABSTRACT FROM AUTHOR]

Focuses on the used of focused ion beam for transmission electron microscopy (TEM) analysis of semiconductor materials. Provision of compositional information; Preparation of TEM samples located on device's smallest features; Improvement in dual-beam capabilities and sample-handling solutions.

Ultra‐low‐dose electron diffraction is performed with a double metal cyanide catalyst (DMC) to understand how electron irradiation stimulates structural alterations in functional materials. The commonly fading diffraction patterns with dose accumulation depend on the irradiated area and the beam current even when below 50 femto Amperes. Heat generation is observed and modeled by statistical, inelastic scattering events to describe how phonon excitations modulate radiation hardness. Specifically, the characteristic 1/e‐decay of Bragg intensities from DMC is delayed from 6 to 30 eÅ−2 at room temperature, which is comparable to the effect of embedding radiation soft matter in ice. DMC's radiation hardness is enhanced by a latency dose that forms during a phase transformation. This unifying model predicts that a critical dose rate exists for any material that varies between 0.1 and 104 eÅ−2s−1 because of a material dependent competition of heat generation and spread. It shows that Brillouin scattering causes time dependent perturbations in electron irradiated solids that trigger time‐temperature‐transformations on a time scale of nanoseconds to microseconds at room temperature, which is not included in traditional models describing the decay of Bragg intensities by radiolysis. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are the main proteolytic enzymes involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). A radiolabeled MMP inhibitor, [(18)F]FB-ML5, was prepared, and its in vivo kinetics were tested in a mouse model of pulmonary inflammation. BALB/c mice were exposed for 4 days to cigarette smoke (CS) or air. On the fifth day, a dynamic microPET scan was made with [(18)F]FB-ML5. Standardized uptake values (PET-SUVmean) were 0.19 ± 0.06 in the lungs of CS-exposed mice (n = 6) compared to 0.11 ± 0.03 (n = 5) in air-exposed controls (p < 0.05), 90 min post-injection MMP-9 levels in bronchoalveolar lavage fluid (BALF) were increased from undetectable level to 4615 ± 1963 pg/ml by CS exposure. Increased MMP expression in a COPD mouse model was shown to lead to increased retention of [(18)F]FB-ML5. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proximate metal and Brønsted acid sites reduce esters to ethers. • Kinetically relevant C = O bond hydrogenation on metal nanoparticles form hemiacetals. • Increasing the metal to acid ratio increases rates for ester reduction pathways. • Increasing Pt weight loading blocks access to the Brønsted acid site. Ethers are highly desirable commodities in food, cosmetics, rubber, and coatings due to their low chemical reactivity, stability, and miscibility with other organic solvents. The direct reduction of esters to ethers by reactions with H 2 provides a pathway to create nonsymmetrical ethers from biomass-derived esters. Propyl acetate (PA) and H 2 react over platinum nanoparticles supported on Brønsted acidic faujasite zeolite (Pt-FAU) by two primary pathways: hydrogenation to form ethyl propyl ether and water and hydrogenolysis to form acetaldehyde and propanol. Here, we evaluate how rates and selectivities for these pathways depend on the ratios of the metal to Brønsted acid sites and the densities of Brønsted acid sites within Pt-FAU. X-ray absorption spectroscopy and infrared spectroscopy of adsorbed CO show that Pt species exist in a metallic state in the presence of H 2 at elevated temperatures. The vibrational frequencies of chemisorbed CO on surface Pt atoms (Pt s) do not vary significantly with differences in Pt contents or Brønsted acid site (H+) density. Temperature programmed reactions of amines protonated upon Brønsted acid sites demonstrate that the fractions of Brønsted acid sites accessible to organic reactants decrease with increasing Pt content, which implies intimate contact between Pt nanoparticles and acid sites. Comparisons between electron microscopy and rate measurements indicate that the proximity between Pt and H+ matters even when Pt nanoparticles appear to be within pores. Even though rates for reactions between PA and H 2 over Pt-FAU decrease significantly during the initial use of the catalysts, analysis of initial rates provides mechanistic insight into elementary steps that determine rates. Initial hydrogenation rates increase by 13-fold, and hydrogenolysis rates increase by 33-fold when the atomic ratio of Pt s to H+ increases from 0.08 to 0.6. Hydrogenation and hydrogenolysis rates increase with Pt s density but do not correlate with H+ densities, which indicates kinetically relevant steps occur on Pt sites. These elementary steps likely involve the formation of hydrogenated intermediates (i.e., hemiacetal) that diffuse and react rapidly upon Brønsted acid sites, which generates intraparticle hemiacetal gradients. These correlations confirm that ester reduction rates and selectivities depend sensitively on the metal to acid ratio and proximity between these functions in a manner reminiscent of bifunctional catalysts used for hydroisomerization and hydrocracking catalysis. Consequently, increasing the number of stable Pt sites close to H+ sites should increase rates per mass catalyst by increasing the concentration of hemiacetals at Brønsted acid sites. [ABSTRACT FROM AUTHOR]

Abstract In this paper, we report the effect of growth conditions on the properties of sputtered precursor thin films for CuIn 1-x Ga x Se 2 (CIGS) absorber layers. Specifically, precursor films containing Cu, In, Ga, and Se were deposited via co-sputtering on flexible Mo-coated stainless steel substrates over a wide range of compositions and deposition conditions. The impact on precursor film phase, morphology, and elemental distribution was investigated as a function of precursor Se content, substrate temperature, target type (CIG/CIG vs. In/Cu 3 Ga), and Na content. Precursor films selenized at high temperature (>500 °C) to form stoichiometric CIGS and completed using a CdS n-type buffer layer and transparent conducting oxide window layers exhibited full-cell efficiencies as high as 11.5%. Highlights • Microstructure of sputtered precursor for CuIn1-xGaxSe2 (CIGS) absorber is studied. • Polycrystalline CIGS thin films are obtained on Mo-coated steel substrates. • Full cells with efficiencies upto 11.48% have been fabricated. [ABSTRACT FROM AUTHOR]

Particulate bis[1-(hydroxy-κO)-2(1H)-pyridinethionato-κS2]-(T-4)-zinc (zinc pyrithione; ZPT) in the diameter range 0.5–0.7 µm is a US FDA-approved anti-dandruff active widely used in anti-dandruff shampoos. A nanoparticulate form of ZPT is expected to exhibit a higher activity, be distributed more effectively on the scalp, require less thickening agent in the shampoo formulation to ensure its stability against settling than the standard form of ZPT, and would enable clear anti-dandruff shampoo formulations. We demonstrate, for the first time, that a green, mechanochemical nanoparticle synthesis process can be used to prepare nanoparticulate ZPT from zinc chloride and sodium pyrithione monohydrate. Both a Reeves attrition mill and a Retsch MixerMill were found to be effective tools for delivering the mechanical energy needed for the conversion. The infrared spectra and X-ray powder diffraction patterns for the products correspond to those for the known desired material. Transmission electron microscopic analysis indicates that ZPT nanoparticles with primary particle diameters in the range of 20–200 nm (mean diameters of 65–100 nm) can be obtained via this method. [ABSTRACT FROM PUBLISHER]

Polycrystalline, tetragonal ( P42 / nmc ) zinc phosphide (Zn 3 P 2 ) thin films were deposited on borosilicate glass substrates by reactive radio frequency (r.f.) sputtering of zinc (Zn) in the presence of phosphine gas (PH 3 ). Various sputtering parameters, including substrate temperature ( T sub ), gun power, gas flow rates of PH 3 and argon (Ar), and total sputtering pressure ( P Tot ) were varied to optimize crystalline growth. Under optimal growth conditions [ T sub ~ 200–230 °C, PH 3 :(PH 3 + Ar) < 0.1, and P Tot : 1.30–2 Pa], films were polycrystalline in nature, with crystallite sizes up to 100–150 nm and orientation along the (004) direction. Lowering the T sub or increasing the PH 3 content resulted in amorphous growth. The stoichiometry of the films was measured by top-down energy dispersive X-ray spectroscopy (EDS), and cross-sectional EDS mapping indicated compositional homogeneity throughout the film depth. The average surface roughness under optimal growth conditions was less than 10 nm. As-grown films were p-type, with high carrier concentrations (~ 10 16 cm − 3 ) but low mobilities (< 1 cm 2 /V·s). Ex situ annealing of films in nitrogen or argon/hydrogen (Ar/H 2 ) led to an order of magnitude decrease in the film's resistivity. Films exhibited a direct and an indirect optical bandgap of 1.58 and 1.44 eV, respectively, as measured by ellipsometry. Equipment limitations defined the reactive sputtering conditions explored here, but the data suggest that film properties may be further improved with deposition at higher substrate temperatures (> 250 °C) and higher sputtering pressures (> 2 Pa). [ABSTRACT FROM AUTHOR]

This work validates the appropriateapplication of chemical reactionengineering principles in the successful design of a full-scale industrialtrickle bed reactor for a proprietary hydrogenation reaction overa palladium catalyst. After identifying an effective catalyst formulationin a continuous laboratory scale trickle bed reactor, the projectteam used the same small-scale reactor to generate kinetic data forscale-up. The scale factor from the laboratory to the final designwas about 3 × 106. The development effort identifiedand resolved three important problems: (1) incomplete catalyst wettingof the small catalyst bed, even though the catalyst was diluted withinert fines; (2) lower than economically attractive catalyst productivity;and (3) catalyst deactivation. [ABSTRACT FROM AUTHOR]

Highlights: [•] The way K is added to MoS2 influences the catalyst performance. [•] The addition method has an effect on the final structure of the MoS2 slabs. [•] A MoSK catalyst that shows TEM images with short slabs is more selective. [Copyright &y& Elsevier]

Aberration-corrected electron microscopy opens new ways for material characterization. In catalyst research it will enable the observation of single atom arrangements, such as the location of promoter atoms on catalyst particles. However, quantitative procedures must be developed to account for dynamic contrast changes resulting from beam-sample interactions and incoherent instrument aberrations. We demonstrate that at low acceleration voltage (80 kV), for which knock-on damage is suppressed, the residual intensity fluctuations can be attributed to the presence of phonons resulting in 3D low frequency atom displacements. For rhodium [110] oriented particles it was found that the catalysts are platelets with an aspect ratio of about 0.2 and a surface roughness of ±1 atom. Observation of single surface atoms requires minimization of phonon-induced motion. The figure shows a high-resolution image of a [110] Rh nanoparticle on alumina recorded with sub-Ångstrom resolution at 80 kV (peak width at full width half maximum=75 pm). After performing a quantitative contrast interpretation and various calculations, it becomes possible to count the number of atoms in each column. The recorded [110] Rh particle is a platelet with an aspect ratio of about 0.2, an average column height of 4 atoms, and a surface roughness of ±1 atom. [ABSTRACT FROM AUTHOR]

Abstract: Nickel oxide (NiO) nanoparticles were synthesized via a solvothermal reaction with nickel(II) acetylacetonate as the metal containing precursor and 2-butanone (methyl ethyl ketone, MEK) as the solvent. The particles were characterized using X-ray diffraction, electron microscopy, Brunauer–Emmett–Teller (BET) surface area measurements and thermal gravimetric analysis (TGA) to determine that the crystal structure, particle size, and the presence of residual organic material upon completion of the reaction. The effect of varying the reaction temperature, time and metal precursor concentration were investigated. A range of optimal reaction conditions; defined here as a high yield, low residual organic content; were determined. A particle size in the range of 5.5–6.5nm was observed for the optimal reaction conditions. The formation of metallic Ni was also observed for reactions carried out at 225°C and time durations longer than 24h. The reaction mechanism for the formation of NiO nanoparticles was investigated using mass spectrometry and a proposed pathway based on a keto-enol tautamerization is presented. [Copyright &y& Elsevier]

PURPOSE: Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. CXCR4 is the most widely expressed chemokine receptor in many different types of cancer and has been linked to tumor dissemination and poor prognosis. Several CXCR4 antagonists have been synthesized. A totally novel approach to discover chemokine receptor antagonists is the use of bacteria. Bacteria produce chemokine receptor inhibitors to prevent neutrophil extravasation and migration toward the infection site to escape clearance by innate immune cells. The aim of the current study was to find and identify the mechanism of a bacterial protein that specifically targets CXCR4, a chemokine receptor shared by neutrophils and cancer cells. EXPERIMENTAL DESIGN: Several staphylococcal proteins were screened for their capacity to prevent binding of a function-blocking antibody against CXCR4. RESULTS: Staphylococcal superantigen-like 10 was found to bind CXCR4 expressed on human T acute lymphoblastic leukemia, lymphoma, and cervical carcinoma cell lines. It potently inhibited CXCL12-induced calcium mobilization and cell migration. CONCLUSIONS: Staphylococcal superantigen-like 10 is a potential lead in the development of new anticancer compounds preventing metastasis by targeting CXCR4. [ABSTRACT FROM AUTHOR]

The C 1s, Si 2p, Si 2s, and O 1s inner-shell excitation spectra of vinyltriethoxysilane, trimethylethoxysilane, and vinyltriacetoxysilane have been recorded by electron energy loss spectroscopy under scattering conditions dominated by electric dipole transitions. The spectra are converted to absolute optical oscillator strength scales and interpreted with the aid of ab initio calculations of the inner-shell excitation spectra of model compounds. Electron energy loss spectra recorded in a transmission electron microscope on partly cured adhesion promoter, atomic force micrographs, and images and X-ray absorption spectra from X-ray photoemission electron microscopy of as-spun and cured vinyltriacetoxysilane-based adhesion promoter films on silicon are presented. The use of these measurements in assisting chemistry studies of adhesion promoters for electronics applications is discussed. [ABSTRACT FROM AUTHOR]

The use of hybrid integration schemes is investigated using a combination of a SiOC film at the via level and a porous SiLK Y film at the trench level. Sequential finite element analysis is used to determine the mechanics and, subsequently, a hybrid damascene interconnect is built to demonstrate the approach. [Copyright &y& Elsevier]

Barrier integrity of Ta-films deposited using the enhanced coverage by re-sputtering (EnCoRe11EnCoRe is a trademark of Applied Materials.) barrier was investigated on untreated surfaces of blanket porous SiLK22SiLK is a trademark of The Dow Chemical Company. semiconductor dielectric (developmental version 7, hereinafter v7). Barrier integrity of a bi-layer EnCoRe Ta(N)/Ta film was studied on single damascene lines using v7 and porous SiLK semiconductor dielectric (developmental version 9, hereinafter v9). On blanket wafers more than 30 nm barrier thickness is necessary to achieve complete pore sealing. Analysis of the sheet resistance showed that when tantalum is deposited, a low resistivity α-phase is nucleated on the low-k surface. When deposited onto single damascene structures, EnCoRe Ta(N)/Ta is successful in providing a continuous metallic barrier layer over v7 and v9 semiconductor dielectric lines. [Copyright &y& Elsevier]

A combination of atomic resolution phase contrast electron microscopy and pulsed electron beams reveals pristine properties of MgCl2 at 1.7 Å resolution that were previously masked by air and beam damage. Both the inter‐ and intra‐layer bonding in pristine MgCl2 are weak, which leads to uncommonly large local orientation variations that characterize this Ziegler–Natta catalyst support. By delivering electrons with 1–10 ps pulses and ≈160 ps delay times, phonons induced by the electron irradiation in the material are allowed to dissipate before the subsequent delivery of the next electron packet, thus mitigating phonon accumulations. As a result, the total electron dose can be extended by a factor of 80–100 to study genuine material properties at atomic resolution without causing object alterations, which is more effective than reducing the sample temperature. In conditions of minimal damage, beam currents approach femtoamperes with dose rates around 1 eÅ−2 s−1. Generally, the utilization of pulsed electron beams is introduced herein to access genuine material properties while minimizing beam damage. Ultrafast atomic resolution electron microscopy is developed and applied to reveal the pristine material properties of MgCl2. The emerging tool is generally applicable and allows minimizing electron beam–induced damage processes by modulating phonon excitations in the time domain. The resulting damage retardation can be more efficient than temperature reduction. [ABSTRACT FROM AUTHOR]