Ultraviolet irradiation represses TGF ‐β type II receptor transcription through a 38‐bp sequence in the proximal promoter in human skin fibroblasts

Transforming growth factor‐β ( TGF ‐β) is a major regulator of collagen gene expression in human skin fibroblasts. Cellular responses to TGF ‐β are mediated primarily through its cell surface type I (TβRI) and type II (TβRII) receptors. Ultraviolet ( UV ) irradiation impairs TGF ‐β signalling largely due to reduced TβRII gene expression, thereby decreasing type I procollagen synthesis, in human skin fibroblasts. UV irradiation does not alter either TβRII m RNA or protein stability, indicating that UV reduction in TβRII expression likely results from transcriptional or translational repression. To understand how UV irradiation regulates TβRII transcription, we used a series of TβRII promoter‐luciferase 5′‐deletion constructs (covering 2 kb of the TβRII proximal promoter) to determine transcriptional rate in response to UV irradiation. We identified a 137‐bp region upstream of the transcriptional start site that exhibited high promoter activity and was repressed 60% by UV irradiation, whereas all other TβRII promoter reporter constructs exhibited either low promoter activities or no regulation by UV irradiation. Mutation of potential transcription factor binding sites within the promoter region revealed that an inverted CCAAT box (−81 bp from transcription start site) is required for promoter activity. Mutation of the CCAAT box completely abolished UV irradiation regulation of the TβRII promoter. Protein‐binding assay, as determined by electrophoretic mobility‐shift assays (EMSAs) using the inverted CCAAT box as probe (−100/−62), demonstrated significantly enhanced protein binding in response to UV irradiation. Super shift experiments indicated that nuclear factor Y ( NFY ) is able to binding to this sequence, but NFY binding was not altered in response to UV irradiation, indicating additional protein(s) are capable of binding this sequence in response to UV irradiation. Taken together, these data indicate that UV irradiation reduces TβRII expression, at least partially, through transcriptional repression. This repression is mediated by a 38‐bp sequence in TβRII promoter, in human skin fibroblasts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108702/1/exd12389.pd

Impaction of spray droplets on leaves: influence of formulation and leaf character on shatter, bounce and adhesion

This paper combines experimental data with simple mathematical models to investigate the influence of spray formulation type and leaf character (wettability) on shatter, bounce and adhesion of droplets impacting with cotton, rice and wheat leaves. Impaction criteria that allow for different angles of the leaf surface and the droplet impact trajectory are presented; their predictions are based on whether combinations of droplet size and velocity lie above or below bounce and shatter boundaries. In the experimental component, real leaves are used, with all their inherent natural variability. Further, commercial agricultural spray nozzles are employed, resulting in a range of droplet characteristics. Given this natural variability, there is broad agreement between the data and predictions. As predicted, the shatter of droplets was found to increase as droplet size and velocity increased, and the surface became harder to wet. Bouncing of droplets occurred most frequently on hard to wet surfaces with high surface tension mixtures. On the other hand, a number of small droplets with low impact velocity were observed to bounce when predicted to lie well within the adhering regime. We believe this discrepancy between the predictions and experimental data could be due to air layer effects that were not taken into account in the current bounce equations. Other discrepancies between experiment and theory are thought to be due to the current assumption of a dry impact surface, whereas, in practice, the leaf surfaces became increasingly covered with fluid throughout the spray test runs.Comment: 19 pages, 6 figures, accepted for publication by Experiments in Fluid

Dendritic GluN2A Synthesis Mediates Activity-Induced NMDA Receptor Insertion

Long-term synaptic plasticity involves changes in the expression and membrane insertion of cell-surface proteins. Interestingly, the mRNAs encoding many cell-surface proteins are localized to dendrites, but whether dendritic protein synthesis is required for activity-induced surface expression of specific proteins is unknown. Herein, we used microfluidic devices to demonstrate that dendritic protein synthesis is necessary for activity-induced insertion of GluN2A-containing NMDA receptors in rat hippocampal neurons. Furthermore, visualization of activity-induced local translation of GluN2A mRNA and membrane insertion of GluN2A protein in dendrites was directly observed and shown to depend on a 3\u27 untranslated region cytoplasmic polyadenylation element and its associated translation complex. These findings uncover a novel mechanism for cytoplasmic polyadenylation element-mediated posttranscriptional regulation of GluN2A mRNA to control NMDA receptor surface expression during synaptic plasticity

Expression of catalytically active matrix metalloproteinase‐1 in dermal fibroblasts induces collagen fragmentation and functional alterations that resemble aged human skin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99047/1/acel12089.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99047/2/acel12089-sup-0001-FigS1-S4.pd

Hydrodynamics of thermal granular convection

A hydrodynamic theory is formulated for buoyancy-driven ("thermal") granular convection, recently predicted in molecular dynamic simulations and observed in experiment. The limit of a dilute flow is considered. The problem is fully described by three scaled parameters. The convection occurs via a supercritical bifurcation, the inelasticity of the collisions being the control parameter. The theory is expected to be valid for small Knudsen numbers and nearly elastic grain collisions.Comment: 4 pages, 4 EPS figures, some details adde

Roles of Fast-Cyclotron and Alfven-Cyclotron Waves for the Multi-Ion Solar Wind

Using linear Vlasov theory of plasma waves and quasi-linear theory of resonant wave-particle interaction, the dispersion relations and the electromagnetic field fluctuations of fast and Alfven waves are studied for a low-beta multi-ion plasma in the inner corona. Their probable roles in heating and accelerating the solar wind via Landau and cyclotron resonances are quantified. We assume that (1) low-frequency Alfven and fast waves have the same spectral shape and the same amplitude of power spectral density; (2) these waves eventually reach ion cyclotron frequencies due to a turbulence cascade; (3) kinetic wave-particle interaction powers the solar wind. The existence of alpha particles in a dominant proton/electron plasma can trigger linear mode conversion between oblique fast-whistler and hybrid alpha-proton cyclotron waves. The fast-cyclotron waves undergo both alpha and proton cyclotron resonances. The alpha cyclotron resonance in fast-cyclotron waves is much stronger than that in Alfven-cyclotron waves. For alpha cyclotron resonance, an oblique fast-cyclotron wave has a larger left-handed electric field fluctuation, a smaller wave number, a larger local wave amplitude, and a greater energization capability than a corresponding Alfven-cyclotron wave at the same wave propagation angle \theta, particularly at $80^\circ$ < \theta < $90^\circ$. When Alfven-cyclotron or fast-cyclotron waves are present, alpha particles are the chief energy recipient. The transition of preferential energization from alpha particles to protons may be self-modulated by differential speed and temperature anisotropy of alpha particles via the self-consistently evolving wave-particle interaction. Therefore, fast-cyclotron waves as a result of linear mode coupling is a potentially important mechanism for preferential energization of minor ions in the main acceleration region of the solar wind.Comment: 29 pages, 10 figures, 3 tables. Accepted for publication in Solar Physic

A Statistical Study on Force-Freeness of Solar Magnetic Fields in the Photosphere

It is an indisputable fact that solar magnetic fields are force-free in the corona, where force free fields means that current and magnetic fields are parallel and there is no Lorentz force in the fields. While the force-free extent of photospheric magnetic fields remains open. In this paper, the statistical results about it is given. The vector magnetograms (namely, $B_{x}$, $B_{y}$ and $B_{z}$ in heliocentric coordinates) are employed, which are deduced and calibrated from Stokes spectra, observed by Solar Magnetic Field Telescope (SMFT) at Huairou Solar Observing Station (HSOS) are used. We study and calibrated 925 magnetograms calibrated by two sets of calibration coefficients, that indicate the relations between magnetic fields and the strength of Stokes spectrum and can be calculated either theoretically or empirically. The statistical results show that the majority of active region magnetic fields are not consistent with the force-free model.Comment: 10 pages, 5 figures, has been accepted by PAS

A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas

Schwannomas are common, highly morbid and medically untreatable tumors that can arise in patients with germ line as well as somatic mutations in neurofibromatosis type 2 (NF2). These mutations most commonly result in the loss of function of the NF2-encoded protein, Merlin. Little is known about how Merlin functions endogenously as a tumor suppressor and how its loss leads to oncogenic transformation in Schwann cells (SCs). Here, we identify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-inducing kinase (NIK) as a potential drug target driving NF-κB signaling and Merlin-deficient schwannoma genesis. Using a genomic approach to profile aberrant tumor signaling pathways, we describe multiple upregulated NF-κB signaling elements in human and murine schwannomas, leading us to identify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-κB signaling. Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, survival, and adhesion while inducing schwannoma formation in a novel in vivo orthotopic transplant model. Furthermore, we describe an NF-κB-potentiated hepatocyte growth factor (HGF) to MET proto-oncogene receptor tyrosine kinase (c-Met) autocrine feed-forward loop promoting SC proliferation. These innovative studies identify a novel signaling axis underlying schwannoma formation, revealing new and potentially druggable schwannoma vulnerabilities with future therapeutic potential

Probing spin-phonon interactions in silicon carbide with Gaussian acoustics

Hybrid spin-mechanical systems provide a platform for integrating quantum registers and transducers. Efficient creation and control of such systems require a comprehensive understanding of the individual spin and mechanical components as well as their mutual interactions. Point defects in silicon carbide (SiC) offer long-lived, optically addressable spin registers in a wafer-scale material with low acoustic losses, making them natural candidates for integration with high quality factor mechanical resonators. Here, we show Gaussian focusing of a surface acoustic wave in SiC, characterized by a novel stroboscopic X-ray diffraction imaging technique, which delivers direct, strain amplitude information at nanoscale spatial resolution. Using ab initio calculations, we provide a more complete picture of spin-strain coupling for various defects in SiC with C3v symmetry. This reveals the importance of shear for future device engineering and enhanced spin-mechanical coupling. We demonstrate all-optical detection of acoustic paramagnetic resonance without microwave magnetic fields, relevant to sensing applications. Finally, we show mechanically driven Autler-Townes splittings and magnetically forbidden Rabi oscillations. These results offer a basis for full strain control of three-level spin systems.Comment: 17 pages, 4 figure

Mechanical properties of freely suspended atomically thin dielectric layers of mica

We have studied the elastic deformation of freely suspended atomically thin sheets of muscovite mica, a widely used electrical insulator in its bulk form. Using an atomic force microscope, we carried out bending test experiments to determine the Young's modulus and the initial pre-tension of mica nanosheets with thicknesses ranging from 14 layers down to just one bilayer. We found that their Young's modulus is high (190 GPa), in agreement with the bulk value, which indicates that the exfoliation procedure employed to fabricate these nanolayers does not introduce a noticeable amount of defects. Additionally, ultrathin mica shows low pre-strain and can withstand reversible deformations up to tens of nanometers without breaking. The low pre-tension and high Young's modulus and breaking force found in these ultrathin mica layers demonstrates their prospective use as a complement for graphene in applications requiring flexible insulating materials or as reinforcement in nanocomposites.Comment: 9 pages, 5 figures, selected as cover of Nano Research, Volume 5, Number 8 (2012