Complex refractive index, single scattering albedo, and mass absorption coefficient of secondary organic aerosols generated from oxidation of biogenic and anthropogenic precursors

Refractive index and optical properties of biogenic and anthropogenic secondary organic aerosol (SOA) particles were investigated. Aerosol precursors, namely longifolene, α-pinene, 1-methylnaphthalene, phenol, and toluene were oxidized in a Teflon chamber to produce SOA particles under different initial hydrocarbon concentrations and hydroxyl radical sources, reflecting exposures to different levels of nitrogen oxides (NOx). The real and imaginary components (n and k, respectively) of the refractive index at 375 nm and 632 nm were determined by Mie theory calculations through an iterative process, using the χ2 function to evaluate the fitness of the predicted optical parameters with the measured scattering, absorption, and extinction coefficients from a Photoacoustic Extinctiometer and Cavity Attenuated Phase Shift Spectrometer. Single scattering albedo (SSA) and bulk mass absorption coefficient (MAC) at 375 nm were calculated. SSA values of SOA particles from biogenic precursors (longifolene and α-pinene) were ∼0.98–0.99 (∼6.3% uncertainty), reflecting purely scattering aerosols regardless of the NOx regime. However, SOA particles from aromatic precursors were more absorbing and displayed NOx-dependent SSA values. For 1-methylnaphthalene SOA particles, SSA values of 0.92–0.95 and ∼0.75–0.90 (∼6.1% uncertainty) were observed under intermediate- and high-NOx conditions, respectively, reflecting the absorbing effects of SOA particles and NOx chemistry for this aromatic system. In mixtures of longifolene and phenol or longifolene and toluene SOA under intermediate- and high-NOx conditions, k values of the aromatic-related component of the SOA mixture were higher than that of 1-methylnaphthalene SOA particles. With the increase in OH exposure, kphenol decreased from 0.10 to 0.02 and 0.22 to 0.05 for intermediate- and high-NOx conditions, respectively. A simple relative radiative forcing calculation for urban environments at λ = 375 nm suggests the influence of absorbing SOA particles on relative radiative forcing at this wavelength is most significant for aerosol sizes greater than 0.4 µm. Copyright © 2019 American Association for Aerosol Research</p

Tackling MARCKS-PIP3 circuit attenuates fibroblast activation and fibrosis progression.

Targeting activated fibroblasts, including myofibroblast differentiation, has emerged as a key therapeutic strategy in patients with idiopathic pulmonary fibrosis (IPF). However, there is no available therapy capable of selectively eradicating myofibroblasts or limiting their genesis. Through an integrative analysis of the regulator genes that are responsible for the activation of IPF fibroblasts, we noticed the phosphatidylinositol 4,5-bisphosphate (PIP2)-binding protein, myristoylated alanine-rich C-kinase substrate (MARCKS), as a potential target molecule for IPF. Herein, we have employed a 25-mer novel peptide, MARCKS phosphorylation site domain sequence (MPS), to determine if MARCKS inhibition reduces pulmonary fibrosis through the inactivation of PI3K/protein kinase B (AKT) signaling in fibroblast cells. We first observed that higher levels of MARCKS phosphorylation and the myofibroblast marker α-smooth muscle actin (α-SMA) were notably overexpressed in all tested IPF lung tissues and fibroblast cells. Treatment with the MPS peptide suppressed levels of MARCKS phosphorylation in primary IPF fibroblasts. A kinetic assay confirmed that this peptide binds to phospholipids, particularly PIP2, with a dissociation constant of 17.64 nM. As expected, a decrease of phosphatidylinositol (3,4,5)-trisphosphate pools and AKT activity occurred in MPS-treated IPF fibroblast cells. MPS peptide was demonstrated to impair cell proliferation, invasion, and migration in multiple IPF fibroblast cells in vitro as well as to reduce pulmonary fibrosis in bleomycin-treated mice in vivo. Surprisingly, we found that MPS peptide decreases α-SMA expression and synergistically interacts with nintedanib treatment in IPF fibroblasts. Our data suggest MARCKS as a druggable target in pulmonary fibrosis and also provide a promising antifibrotic agent that may lead to effective IPF treatments.-Yang, D. C., Li, J.-M., Xu, J., Oldham, J., Phan, S. H., Last, J. A., Wu, R., Chen, C.-H. Tackling MARCKS-PIP3 circuit attenuates fibroblast activation and fibrosis progression

Ribosomal proteins produced in excess are degraded by the ubiquitin-proteasome system

Ribosome assembly is an essential process that consumes prodigious quantities of cellular resources. Ribosomal proteins cannot be overproduced in Saccharomyces cerevisiae because the excess proteins are rapidly degraded. However, the responsible quality-control (QC) mechanisms remain poorly characterized. Here, we demonstrate that overexpression of multiple proteins of the small and large yeast ribosomal subunits is suppressed. Rpl26 overexpressed from a plasmid can be detected in the nucleolus and nucleoplasm, but it largely fails to assemble into ribosomes and is rapidly degraded. However, if the endogenous RPL26 loci are deleted, plasmid-encoded Rpl26 assembles into ribosomes and localizes to the cytosol. Chemical and genetic perturbation studies indicate that overexpressed ribosomal proteins are degraded by the ubiquitin-proteasome system, and not by autophagy. Inhibition of the proteasome led to accumulation of multiple endogenous ribosomal proteins in insoluble aggregates, consistent with the operation of this QC mechanism in the absence of ribosomal protein overexpression. Our studies reveal that ribosomal proteins that fail to assemble into ribosomes are rapidly distinguished from their assembled counterparts and are ubiquitinated and degraded within the nuclear compartment

Welcome to Molecular Brain

We are delighted to announce the arrival of a brand new journal dedicated to the ever-expanding field of neuroscience. Molecular Brain is a peer-reviewed, open-access online journal that aims at publishing high quality articles as rapidly as possible. The journal will cover a broad spectrum of neuroscience ranging from molecular/cellular to behavioral/cognitive neuroscience and from basic to clinical research. Molecular Brain will publish not only research articles, but also methodology articles, editorials, reviews, and short reports. It will be a premier platform for neuroscientists to exchange their ideas with researchers from around the world to help improve our understanding of the molecular mechanisms of the brain and mind

Language Embedded Radiance Fields for Zero-Shot Task-Oriented Grasping

Grasping objects by a specific part is often crucial for safety and for executing downstream tasks. Yet, learning-based grasp planners lack this behavior unless they are trained on specific object part data, making it a significant challenge to scale object diversity. Instead, we propose LERF-TOGO, Language Embedded Radiance Fields for Task-Oriented Grasping of Objects, which uses vision-language models zero-shot to output a grasp distribution over an object given a natural language query. To accomplish this, we first reconstruct a LERF of the scene, which distills CLIP embeddings into a multi-scale 3D language field queryable with text. However, LERF has no sense of objectness, meaning its relevancy outputs often return incomplete activations over an object which are insufficient for subsequent part queries. LERF-TOGO mitigates this lack of spatial grouping by extracting a 3D object mask via DINO features and then conditionally querying LERF on this mask to obtain a semantic distribution over the object with which to rank grasps from an off-the-shelf grasp planner. We evaluate LERF-TOGO's ability to grasp task-oriented object parts on 31 different physical objects, and find it selects grasps on the correct part in 81% of all trials and grasps successfully in 69%. See the project website at: lerftogo.github.ioComment: See the project website at: lerftogo.github.i

Measuring the velocity field of a shear-coaxial, cryogenic flame in a high-pressure rocket thrust chamber

High-speed imaging was used to visualize one of the transcritical flames in a multi-injector, sub-scale rocket thrust chamber at pressures up to 80 bar. Image correlation velocimetry (ICV) was applied to the imaging to obtain quantitative information on the flow field from the shear-coaxial injectors. ICV was used to track surface irregularities on the liquid oxygen (LOX) jet in imaging filtered to blue wavelengths. By choosing the interrogation area carefully, only the LOX jet was effectively tracked, excluding the coaxial H2 flow, and the time-averaged velocity field was reconstructed. Due to the transient nature of the tracked features, which frequently change shape or disappear, the averaged ICV result underestimates the absolute values of velocity. Therefore, the averaged values were scaled by the mean of the instantaneous velocity maxima. A second, reference measurement of LOX jet propagation speed was calculated using dynamic mode decomposition (DMD). The results were consistent following the aforementioned correction of the ICV values. Comparing the ICV fields for two different operating conditions showed a marked difference in the axial velocity distribution and lateral expansion of the LOX jet, demonstrating the potential of the method in studying injection in rocket combustion chambers

Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K2P) and voltage-gated (Kv1.1 and Kv1.2) potassium channels

<p>Abstract</p> <p>Background</p> <p>Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons.</p> <p>Findings</p> <p>When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K⁺channels, K_v1.1 and K_v1.2 (voltage-gated K⁺channels) and TREK1 and TRAAK (K_2Pchannels). IQ effectively reduced the currents mediated by both K⁺channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K_v1.1 and K_v1.2.</p> <p>Conclusions</p> <p>Our results demonstrate that IQ blocks the voltage-gated K⁺channels to increase AP duration and K_2Pchannels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.</p

Role of ALDH1A1 and HTRA2 expression in CCL2/CCR2-mediated breast cancer cell growth and invasion

This work is licensed under a Creative Commons Attribution 4.0 International License.Chemokines mediate immune cell trafficking during tissue development, wound healing and infection. The chemokine CCL2 is best known to regulate macrophage recruitment during wound healing, infection and inflammatory diseases. While the importance of CCL2/CCR2 signaling in macrophages during cancer progression is well documented, we recently showed that CCL2-mediated breast cancer progression depends on CCR2 expression in carcinoma cells. Using 3D Matrigel: Collagen cultures of SUM225 and DCIS.com breast cancer cells, this study characterized the mechanisms of CCL2/CCR2 signaling in cell growth and invasion. SUM225 cells, which expressed lower levels of CCR2 than DCIS.com cells, formed symmetrical spheroids in Matrigel: Collagen, and were not responsive to CCL2 treatment. DCIS.com cells formed asymmetric cell clusters in Matrigel: Collagen. CCL2 treatment increased growth, decreased expression of E-cadherin and increased TWIST1 expression. CCR2 overexpression in SUM225 cells increased responsiveness to CCL2 treatment, enhancing growth and invasion. These phenotypes corresponded to increased expression of Aldehyde Dehydrogenase 1A1 (ALDH1A1) and decreased expression of the mitochondrial serine protease HTRA2. CCR2 deficiency in DCIS.com cells inhibited CCL2-mediated growth and invasion, corresponding to decreased ALDH1A1 expression and increased HTRA2 expression. ALDH1A1 and HTRA2 expression were modulated in CCR2-deficient and CCR2-overexpressing cell lines. We found that ALDH1A1 and HTRA2 regulates CCR2-mediated breast cancer cell growth and cellular invasion in a CCL2/CCR2 context-dependent manner. These data provide novel insight on the mechanisms of chemokine signaling in breast cancer cell growth and invasion, with important implications on targeted therapeutics for anti-cancer treatment.Susan G. Komen Foundation (CCR13261859)NIH CA17276

Development, Characterization, and Application of Two Reporter-Expressing Recombinant Zika Viruses

Zika virus (ZIKV), a mosquito-borne transplacentally transmissible flavivirus, is an enveloped virus with an ~10.8 kb plus-strand RNA genome that can cause neurological disease. To facilitate the identification of potential antivirals, we developed two reporter-expressing ZIKVs, each capable of expressing an enhanced green fluorescent protein or an improved luminescent NanoLuc luciferase. First, a full-length functional ZIKV cDNA clone was engineered as a bacterial artificial chromosome, with each reporter gene under the cap-independent translational control of a cardiovirus-derived internal ribosome entry site inserted downstream of the single open reading frame of the viral genome. Two reporter-expressing ZIKVs were then generated by transfection of ZIKV-susceptible BHK-21 cells with infectious RNAs derived by in vitro run-off transcription from the respective cDNAs. As compared to the parental virus, the two reporter-expressing ZIKVs grew to lower titers with slower growth kinetics and formed smaller foci; however, they displayed a genome-wide viral protein expression profile identical to that of the parental virus, except for two previously unrecognized larger forms of the C and NS1 proteins. We then used the NanoLuc-expressing ZIKV to assess the in vitro antiviral activity of three inhibitors (T-705, NITD-008, and ribavirin). Altogether, our reporter-expressing ZIKVs represent an excellent molecular tool for the discovery of novel antivirals