Developmental Defects Mediated by the P1/HC-Pro Potyviral Silencing Suppressor Are Not Due to Misregulation of AUXIN RESPONSE FACTOR 8

Plant viral suppressors of RNA silencing induce developmental defects similar to those caused by mutations in genes involved in the microRNA pathway. A recent report has attributed viral suppressor-mediated developmental defects to up-regulation of AUXIN RESPONSE FACTOR 8 (ARF8), a target of miR167. The key piece of evidence was that the developmental defects in transgenic Arabidopsis (Arabidopsis thaliana) expressing viral suppressors were greatly alleviated in the F1 progeny of a cross with plants carrying the arf8-6 mutation. Arf8-6 is a SALK line T-DNA insertion mutant, a class of mutations prone to inducing transcriptional silencing of transgenes expressed from the 35S promoter. We have reinvestigated the role of ARF8 in viral suppressor-mediated developmental defects, using two independent arf8 mutations and the P1/HC-Pro potyviral suppressor of silencing. Progeny of a cross between P1/HC-Pro transgenic Arabidopsis and the arf8-6 T-DNA insertion mutant showed little effect on the P1/HC-Pro phenotype in the F1 generation, but almost all arf8-6/P1/HC-Pro progeny had lost the phenotype in the F2 generation. However, the loss of phenotype in the F2 generation was not correlated with the number of functional copies of the ARF8 gene. Instead, it reflected transcriptional silencing of the P1/HC-Pro transgene, as evidenced by a pronounced decrease in P1/HC-Pro mRNA and the appearance of 35S promoter small interfering RNAs. Furthermore, an independent loss-of-function point mutation, Arf8-8, had no detectable effects on P1/HC-Pro phenotype in either the F1 or F2 generations. Together, these data argue against the previously reported role of increased ARF8 expression in developmental defects caused by P1/HC-Pro

Factors Influencing Bike Share Among Underserved Populations: Evidence from Three US Cities

There is evidence that lower-income and people of color (POC) in the U.S. do not use bike share as much as higher-income and white people. Using data from residents living near stations in New York, Chicago, and Philadelphia, our analysis examines reasons for these disparities. While smaller shares of POC are members (vs higher-income white people), large shares of POC are interested in bike share. Among POC, having positive attitudes about bicycling and having family and friends that use bike share are strong predictors of interest in bike share. POC are also motivated to use bike share for recreational reasons. Receiving information from interactive sources may be effective at increasing bike share use and interest, though it is not clear whether these efforts have affected POC. Cost is a barrier for people who have tried bike share and are interested in using it in the future but are not members

The Next Generation Virgo Cluster Survey. XII. Stellar Populations and Kinematics of Compact, Low-Mass Early-Type Galaxies from Gemini GMOS-IFU Spectroscopy

We present Gemini GMOS-IFU data of eight compact low-mass early-type galaxies (ETGs) in the Virgo cluster. We analyse their stellar kinematics, stellar population, and present two-dimensional maps of these properties covering the central 5"x 7" region. We find a large variety of kinematics: from non- to highly-rotating objects, often associated with underlying disky isophotes revealed by deep images from the Next Generation Virgo Cluster Survey. In half of our objects, we find a centrally-concentrated younger and more metal-rich stellar population. We analyze the specific stellar angular momentum through the lambdaR parameter and find six fast-rotators and two slow-rotators, one having a thin counter-rotating disk. We compare the local galaxy density and stellar populations of our objects with those of 39 more extended low-mass Virgo ETGs from the SMAKCED survey and 260 massive ($M>10^{10}$\Msun) ETGs from the A3D sample. The compact low-mass ETGs in our sample are located in high density regions, often close to a massive galaxy and have, on average, older and more metal-rich stellar populations than less compact low-mass galaxies. We find that the stellar population parameters follow lines of constant velocity dispersion in the mass-size plane, smoothly extending the comparable trends found for massive ETGs. Our study supports a scenario where low-mass compact ETGs have experienced long-lived interactions with their environment, including ram-pressure stripping and gravitational tidal forces, that may be responsible for their compact nature.Comment: Accepted in ApJ, 19 pages, 10 figure

The Next Generation Virgo Cluster Survey. X. Properties of Ultra-Compact Dwarfs in the M87, M49 and M60 Regions

We use imaging from the Next Generation Virgo cluster Survey (NGVS) to present a comparative study of ultra-compact dwarf (UCD) galaxies associated with three prominent Virgo sub-clusters: those centered on the massive, red-sequence galaxies M87, M49 and M60. We show how UCDs can be selected with high completeness using a combination of half-light radius and location in color-color diagrams ($u^*iK_s$ or $u^*gz$). Although the central galaxies in each of these sub-clusters have nearly identical luminosities and stellar masses, we find large differences in the sizes of their UCD populations, with M87 containing ~3.5 and 7.8 times more UCDs than M49 and M60, respectively. The relative abundance of UCDs in the three regions scales in proportion to sub-cluster mass, as traced by X-ray gas mass, total gravitating mass, number of globular clusters, and number of nearby galaxies. We find that the UCDs are predominantly blue in color, with ~85% of the UCDs having colors similar to blue GCs and stellar nuclei of dwarf galaxies. We present evidence that UCDs surrounding M87 and M49 may follow a morphological sequence ordered by the prominence of their outer, low surface brightness envelope, ultimately merging with the sequence of nucleated low-mass galaxies, and that envelope prominence correlates with distance from either galaxy. Our analysis provides evidence that tidal stripping of nucleated galaxies is an important process in the formation of UCDs.Comment: 37 pages, 40 figures. To appear in The Astrophysical Journa

The Next Generation Virgo Cluster Survey - Infrared (NGVS-IR): I. A new Near-UV/Optical/Near-IR Globular Cluster selection tool

The NGVS-IR project (Next Generation Virgo Survey - Infrared) is a contiguous near-infrared imaging survey of the Virgo cluster of galaxies. It complements the optical wide-field survey of Virgo (NGVS). The current state of NGVS-IR consists of Ks-band imaging of 4 deg^2 centered on M87, and J and Ks-band imaging of 16 deg^2 covering the region between M49 and M87. In this paper, we present the observations of the central 4 deg^2 centered on Virgo's core region. The data were acquired with WIRCam on the Canada-France-Hawaii Telescope and the total integration time was 41 hours distributed in 34 contiguous tiles. A survey-specific strategy was designed to account for extended galaxies while still measuring accurate sky brightness within the survey area. The average 5\sigma limiting magnitude is Ks=24.4 AB mag and the 50% completeness limit is Ks=23.75 AB mag for point source detections, when using only images with better than 0.7" seeing (median seeing 0.54"). Star clusters are marginally resolved in these image stacks, and Virgo galaxies with \mu_Ks=24.4 AB mag arcsec^-2 are detected. Combining the Ks data with optical and ultraviolet data, we build the uiK color-color diagram which allows a very clean color-based selection of globular clusters in Virgo. This diagnostic plot will provide reliable globular cluster candidates for spectroscopic follow-up campaigns needed to continue the exploration of Virgo's photometric and kinematic sub-structures, and will help the design of future searches for globular clusters in extragalactic systems. Equipped with this powerful new tool, future NGVS-IR investigations based on the uiK diagram will address the mapping and analysis of extended structures and compact stellar systems in and around Virgo galaxies.Comment: 23 pages, 18 figures. Accepted for publication in ApJ

Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy

Natural history of coexistent tricuspid regurgitation in patients with degenerative mitral valve disease: Implications for future guidelines

ObjectiveThe management of coexistent tricuspid regurgitation in patients with mitral regurgitation remains controversial. We sought to define the incidence and natural history of coexistent tricuspid regurgitation in patients undergoing isolated mitral surgery for degenerative mitral regurgitation, as well as the effect of late secondary tricuspid regurgitation on cardiovascular symptom burden and survival.MethodsTo minimize confounding, analysis was limited to 495 consecutive patients who underwent isolated mitral surgery for degenerative mitral valve disease between 2002 and 2011. Patients with coexistent severe tricuspid regurgitation were excluded because such patients typically undergo concomitant tricuspid intervention.ResultsGrade 1 to 3 coexistent tricuspid regurgitation was present in 215 patients (43%) preoperatively. Actuarial freedom from grade 3 to 4 tricuspid regurgitation 1, 5, and 9 years after surgery was 100% ± 0%, 90% ± 2%, and 64% ± 7%, respectively. Older age (P < .001) and grade of preoperative tricuspid regurgitation (P = .006) independently predicted postoperative progression of tricuspid regurgitation on multivariable analysis. However, when limited to patients with mild or absent tricuspid regurgitation, indexed tricuspid annular diameter was the only significant risk factor for late tricuspid regurgitation (P = .04). New York Heart Association functional class and long-term survival did not worsen with development of late secondary tricuspid regurgitation (P = .4 and P = .6, respectively). However, right ventricular dysfunction was significantly more common in patients with more severe late tricuspid regurgitation (P = .007).ConclusionsDespite durable correction of degenerative mitral regurgitation, less than severe tricuspid regurgitation is likely to progress after surgery if uncorrected. Given the low incremental risk of tricuspid annuloplasty, a more aggressive strategy of concomitant tricuspid repair may be warranted

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer

Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II–IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet