Fabrication of Functionalized Double-Lamellar Multifunctional Envelope-Type Nanodevices Using a Microfluidic Chip with a Chaotic Mixer Array

Multifunctional envelope-type nanodevices (MENDs) are very promising non-viral gene delivery vectors because they are biocompatible and enable programmed packaging of various functional elements into an individual nanostructured liposome. Conventionally MENDs have been fabricated by complicated, labor-intensive, time-consuming bulk batch methods. To avoid these problems in MEND fabrication, we adopted a microfluidic chip with a chaotic mixer array on the floor of its reaction channel. The array was composed of 69 cycles of the staggered chaotic mixer with bas-relief structures. Although the reaction channel had very large Péclet numbers (>105) favorable for laminar flows, its chaotic mixer array led to very small mixing lengths (<1.5 cm) and that allowed homogeneous mixing of MEND precursors in a short time. Using the microfluidic chip, we fabricated a double-lamellar MEND (D-MEND) composed of a condensed plasmid DNA core and a lipid bilayer membrane envelope as well as the D-MEND modified with trans-membrane peptide octaarginine. Our lab-on-a-chip approach was much simpler, faster, and more convenient for fabricating the MENDs, as compared with the conventional bulk batch approaches. Further, the physical properties of the on-chip-fabricated MENDs were comparable to or better than those of the bulk batch-fabricated MENDs. Our fabrication strategy using microfluidic chips with short mixing length reaction channels may provide practical ways for constructing more elegant liposome-based non-viral vectors that can effectively penetrate all membranes in cells and lead to high gene transfection efficiency

Adiponectin Upregulates Prolyl-4-Hydroxylase α1 Expression in Interleukin 6-Stimulated Human Aortic Smooth Muscle Cells by Regulating ERK 1/2 and Sp1

Adiponectin is an anti-atherogenic adipokine that inhibits the development of plaque by mechanisms that are not completely understood. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis. We explored the effect and mechanisms of adiponectin on the synthesis of prolyl-4-hydroxylase (P4H) in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs). P4Hα1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Hα1 were quantified by western blot analysis, and activation of specific protein 1 (Sp1) was determined by electrophoretic mobility shift assay and subcellular localization of Sp1 by immunofluorescence analysis. Adiponectin significantly increased P4Hα1 mRNA and protein levels in IL-6-stimulated HASMCs in a dose- and time-dependent manner. As well, ERK1/2 and Sp1 played a crucial role in the effect of adiponectin upregulating P4Hα1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Hα1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6–inhibited P4Hα1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Hα1-dependent pathway

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Leaf Trait-Environment Relationships in a Subtropical Broadleaved Forest in South-East China

Although trait analyses have become more important in community ecology, trait-environment correlations have rarely been studied along successional gradients. We asked which environmental variables had the strongest impact on intraspecific and interspecific trait variation in the community and which traits were most responsive to the environment. We established a series of plots in a secondary forest in the Chinese subtropics, stratified by successional stages that were defined by the time elapsed since the last logging activities. On a total of 27 plots all woody plants were recorded and a set of individuals of every species was analysed for leaf traits, resulting in a trait matrix of 26 leaf traits for 122 species. A Fourth Corner Analysis revealed that the mean values of many leaf traits were tightly related to the successional gradient. Most shifts in traits followed the leaf economics spectrum with decreasing specific leaf area and leaf nutrient contents with successional time. Beside succession, few additional environmental variables resulted in significant trait relationships, such as soil moisture and soil C and N content as well as topographical variables. Not all traits were related to the leaf economics spectrum, and thus, to the successional gradient, such as stomata size and density. By comparing different permutation models in the Fourth Corner Analysis, we found that the trait-environment link was based more on the association of species with the environment than of the communities with species traits. The strong species-environment association was brought about by a clear gradient in species composition along the succession series, while communities were not well differentiated in mean trait composition. In contrast, intraspecific trait variation did not show close environmental relationships. The study confirmed the role of environmental trait filtering in subtropical forests, with traits associated with the leaf economics spectrum being the most responsive ones

New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc

The molecular determinants of Alzheimer's (AD) disease are still not completely known; however, in the past two decades, a large body of evidence has indicated that an important contributing factor for the disease is the development of an unbalanced homeostasis of two signaling cations: calcium (Ca2+) and zinc (Zn2+). Both ions serve a critical role in the physiological functioning of the central nervous system, but their brain deregulation promotes amyloid-β dysmetabolism as well as tau phosphorylation. AD is also characterized by an altered glutamatergic activation, and glutamate can promote both Ca2+ and Zn2+ dyshomeostasis. The two cations can operate synergistically to promote the generation of free radicals that further intracellular Ca2+ and Zn2+ rises and set the stage for a self-perpetuating harmful loop. These phenomena can be the initial steps in the pathogenic cascade leading to AD, therefore, therapeutic interventions aiming at preventing Ca2+ and Zn2+ dyshomeostasis may offer a great opportunity for disease-modifying strategies

Measurement of the polar-angle distribution of leptons from W boson decay as a function of the W transverse momentum in proton-antiproton collisions at sqrt{s}=1.8 TeV

We present a measurement of the coefficient alpha_2 of the leptonic polar-angle distribution from W boson decays, as a function of the W transverse momentum. The measurement uses an 80+/-4 pb^{-1} sample of proton-antiproton collisions at sqrt{s}=1.8 TeV collected by the CDF detector and includes data from both the W->e+nu and W->mu+nu decay channels. We fit the W boson transverse mass distribution to a set of templates from a Monte Carlo event generator and detector simulation in several ranges of the W transverse momentum. The measurement agrees with the Standard Model expectation, whereby the ratio of longitudinally to transversely polarized W bosons, in the Collins-Soper W rest frame, increases with the W transverse momentum at a rate of approximately 15% per 10 GeV/c.Comment: 47 pages, 16 figures, submitted to Physical Review

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved