Power asymmetry in CMB polarization maps from PLANCK : a local variance analysis

A persistent signal of power asymmetry on opposite hemispheres of CMB sky was seen in full-sky temperature measurements made so far. This asymmetry was seen in microwave sky from WMAP as well as PLANCK satellites, and calls for attention the larger question of \emph{statistical isotropy}, one of the foundational principles of modern cosmology. In this work we present an analysis of polarized CMB maps from PLANCK 2015 full mission data. We apply the local variance estimator on low resolution $E-$mode maps from PLANCK 2015 polarization \texttt{Commander} solution. We find a significant hemispherical power asymmetry in polarization data on large angular scales, at the level of $\sim 2.6-3.9\%$ depending on the galactic mask, and the circular disc radius used for computing local variance maps. However the direction is found to be pointing broadly towards CMB kinetic dipole direction. Precise measurements of CMB polarization in future will shed light on this apparent discrepancy in the anisotropy axis seen in temperature and polarized CMB sky, and likely influence of systematics on our findings.Comment: 21 pages, 10 figures, 3 table

Anticancer Therapy Targeting Cancer-Derived Extracellular Vesicles

Extracellular vesicles (EVs) are natural lipid nanoparticles secreted by most types of cells. In malignant cancer, EVs derived from cancer cells contribute to its progression and metastasis by facilitating tumor growth and invasion, interfering with anticancer immunity, and establishing premetastasis niches in distant organs. In recent years, multiple strategies targeting cancer-derived EVs have been proposed to improve cancer patient outcomes, including inhibiting EV generation, disrupting EVs during trafficking, and blocking EV uptake by recipient cells. Developments in EV engineering also show promising results in harnessing cancer-derived EVs as anticancer agents. Here, we summarize the current understanding of the origin and functions of cancer-derived EVs and review the recent progress in anticancer therapy targeting these EVs

Microarray gene analysis results.

<p>Whole genome analysis was performed for SCG cells in 2D and 3D after 5 days in culture or in freshly dissected SCG tissue. Gene expression levels of L-type VGCC alpha 1 subunits (a) and other common subunits in VGCC (b) are presented here. The final gene expression levels were averaged from analysis of four biological replicates in each experimental condition (2D, 3D and tissue) (n = 4). Error bars represent the standard deviation. # Indicates the mean of expression level from tissue sample was significantly different from that of 2D or 3D cultures (in PS scaffolds) with p<0.05 by Student’s t-test.</p

Polymer (PLLA) scaffolds seeded with SCG cells.

<p>(a) Confocal image with calcein stained SCG cells cultured on flat surfaces. (b) Confocal depth projection micrograph of a 20∶1 PLLA polymer scaffold with 60–100 µm sized pores, seeded with SCG cells. Cells were stained with calcein and thirty Confocal images were taken in row along the z-axis after 7 days in culture. Maximum projected images were generated with different color corresponding to different depth from the polymer surface. As shown in the color bar, pink is closest to the surface and red is at 150 µm from the surface. (c) SEM image of polymer (PLLA) scaffold without cells. (c) SEM image of a SCG cell cluster (indicated by arrow) inside a pore on day 2 after plating. (e): SEM image showing a neurite (indicated by arrow) from one cell to another on day 7 after plating. Bars represent 50 µm in (a), 100 µm (b), 50 µm in (c), 10 µm in (d) and 5 µm in (e).</p

Cell morphology and high K⁺ depolarization induced intracellular calcium changes.

<p>Cell morphology was observed with a live cell indicator and cytoplasmic marker Calcein AM (a–e). Fluorescent images were captured by laser scanning confocal microscopy. (a) and (b) are confocal images of cells on 2D substrates on day 2 and day 7 after plating, respectively. (c) and (d) are volume rendered confocal depth projection images of cells on 3D PS scaffolds on day 2 and day 7 after plating, respectively. (e) is a volume rendered confocal image of the cells in a intact SCG tissue. (e*) is a blow-up of the insert in (e) to easily compare the morphology to that in (d). Bars represent 50 µm in all these 5 images. High K⁺ depolarization induced intracellular calcium changes were studied by Calcium Green, a calcium indicator (f–k). Intracellular calcium were reflected by Calcium Green’s fluorescent intensities and recorded by Confocal microscopy every 3 seconds. Shown in (f) and (h) are the typical calcium time course in responses to high K⁺ (50 mM) depolarization on 2D substrates and 3D PS scaffolds, respectively for day 2 cultures. (j) shows calcium time course from a typical responsive cell in an intact SCG tissue after dissection. (g), (i) and (k) are the typical calcium time course when calcium transient was suppressed by L-type calcium blocker from 2D, 3D and tissue samples, respectively. Arrows show the times points when high K⁺ buffer was added. The general decreasing trend of fluorescence intensity was resulting from photo-bleaching during recording.</p

Cell morphology on 2D substrates.

*<p>value was significantly different from that for Day 2 (p<0.05).</p

L-type VGCC and caveolin-1 colocalization.

<p>(a)–(c) Confocal images of L-type calcium channel staining of SCG cells cultured on 2D surface (a), 3D scaffolds (b) and in freshly dissected SCG tissue (c). Arrows point to one cell. (d)–(f) Confocal images of caveolin-1 (caveolar protein) from SCG cells cultured on 2D surface (d), 3D scaffolds (e) and in freshly dissected SCG tissue (f). (g)–(i) are the super-imposed image of VGCC and caveolin-1 staining, yellow indicates that VGCC protein and caveolin-1 are colocalized. Scale bars are 20 µm.</p

Cellular VGCC functionality.

<p>“NS” indicates that the means of the two samples compared are not significantly different with a level of p>0.8 by Student’s t-test. “n” is the number of responsive cells. The percentage of responsive cells from the total cell pool is indicated in parenthesis. 3D cells were cultured in PLLA scaffolds. Error bars are the 95% confidence intervals.</p

Cell morphology on 3D PLLA substrates.

*<p>value was significantly different from that for Day 2 (p<0.05).</p>#<p>value was significantly different from that for 2D in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045074#pone-0045074-t001" target="_blank">Table 1</a>.</p

Detachable Microneedle Patches Deliver Mesenchymal Stromal Cell Factor-Loaded Nanoparticles for Cardiac Repair

Intramyocardial injection is a direct and efficient approach to deliver therapeutics to the heart. However, the injected volume must be very limited, and there is injury to the injection site and leakage issues during heart beating. Herein, we developed a detachable therapeutic microneedle (MN) patch, which is comprised of mesenchymal stromal cell-secreted factors (MSCF)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) in MN tips made of elastin-like polypeptide gel, with a resolvable non-cross-linked hyaluronic acid (HA) gel as the MN base. The tips can be firmly inserted into the infarcted myocardium after base removal, and no suture is needed. In isolated neonatal rat cardiac cells, we found that the cellular uptake of MSCF-NP in the cardiomyocytes was higher than in cardiac fibroblasts. MSCF-NP promoted the proliferation of injured cardiomyocytes. In a rat model of myocardial infarction, MN-MSCF-NP treatment reduced cardiomyocyte apoptosis, restored myocardium volume, and reduced fibrosis during the cardiac remodeling process. Our work demonstrated the therapeutic potential of MN to deliver MSCF directly into the myocardium and provides a promising treatment approach for cardiac diseases