Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

The CatWISE Preliminary Catalog: Motions from WISE and NEOWISE Data

CatWISE is a program to catalog sources selected from combined WISE and NEOWISE all-sky survey data at 3.4 and 4.6 μm (W1 and W2). The CatWISE Preliminary Catalog consists of 900,849,014 sources measured in data collected from 2010 to 2016. This data set represents four times as many exposures and spans over 10 times as large a time baseline as that used for the AllWISE Catalog. CatWISE adapts AllWISE software to measure the sources in coadded images created from six-month subsets of these data, each representing one coverage of the inertial sky, or epoch. The catalog includes the measured motion of sources in eight epochs over the 6.5 yr span of the data. From comparison to Spitzer, signal-to-noise ratio = 5 limits in magnitudes in the Vega system are W1 = 17.67 and W2 = 16.47, compared to W1 = 16.96 and W2 = 16.02 for AllWISE. From comparison to Gaia, CatWISE positions have typical accuracies of 50 mas for stars at W1 = 10 mag and 275 mas for stars at W1 = 15.5 mag. Proper motions have typical accuracies of 10 mas yr⁻¹ and 30 mas yr⁻¹ for stars with these brightnesses, an order of magnitude better than from AllWISE. The catalog is available in the WISE/NEOWISE Enhanced and Contributed Products area of the NASA/IPAC Infrared Science Archive

Dynamic Energy Landscapes of Riboswitches Help Interpret Conformational Rearrangements and Function

Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant “downhill” pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the “new view” of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design

CWISEP J193518.59-154620.3: An Extremely Cold Brown Dwarf in the Solar Neighborhood Discovered with CatWISE

We present the discovery of an extremely cold, nearby brown dwarf in the solar neighborhood, found in the CatWISE catalog. Photometric follow-up with Spitzer reveals that the object, CWISEP J193518.59-154620.3, has ch1-ch2 = 3.24 ±0.31 mag, making it one of the reddest brown dwarfs known. Using the Spitzer photometry and the polynomial relations from Kirkpatrick et al. we estimate an effective temperature in the ∼270-360 K range, and a distance estimate in the 5.6-10.9 pc range. We combined the WISE, NEOWISE, and Spitzer data to measure a proper motion of mas yr-1, μ δ = -50 ±97 mas yr-1, which implies a relatively low tangential velocity in the range 7-22 km s-1

Redder than Red: Discovery of an Exceptionally Red L/T Transition Dwarf

We present the discovery of CWISE J050626.96+073842.4 (CWISE J0506+0738), an L/T transition dwarf with extremely red near-infrared colors discovered through the Backyard Worlds: Planet 9 citizen science project. Photometry from UKIRT and CatWISE give a (J − K)MKO color of 2.97 ± 0.03 mag and a J MKO − W2 color of 4.93 ± 0.02 mag, making CWISE J0506+0738 the reddest known free-floating L/T dwarf in both colors. We confirm the extremely red nature of CWISE J0506+0738 using Keck/NIRES near-infrared spectroscopy and establish that it is a low-gravity, late-type L/T transition dwarf. The spectrum of CWISE J0506+0738 shows possible signatures of CH4 absorption in its atmosphere, suggesting a colder effective temperature than other known, young, red L dwarfs. We assign a preliminary spectral type for this source of L8γ-T0γ. We tentatively find that CWISE J0506+0738 is variable at 3-5 μm based on multiepoch WISE photometry. Proper motions derived from follow-up UKIRT observations combined with a radial velocity from our Keck/NIRES spectrum and a photometric distance estimate indicate a strong membership probability in the β Pic moving group. A future parallax measurement will help to establish a more definitive moving group membership for this unusual object

Redder than Red: Discovery of an Exceptionally Red L/T Transition Dwarf

We present the discovery of CWISE J050626.96+073842.4 (CWISE J0506+0738), an L/T transition dwarf with extremely red near-infrared colors discovered through the Backyard Worlds: Planet 9 citizen science project. Photometry from UKIRT and CatWISE give a (J − K)MKO color of 2.97 ± 0.03 mag and a J MKO − W2 color of 4.93 ± 0.02 mag, making CWISE J0506+0738 the reddest known free-floating L/T dwarf in both colors. We confirm the extremely red nature of CWISE J0506+0738 using Keck/NIRES near-infrared spectroscopy and establish that it is a low-gravity, late-type L/T transition dwarf. The spectrum of CWISE J0506+0738 shows possible signatures of CH4 absorption in its atmosphere, suggesting a colder effective temperature than other known, young, red L dwarfs. We assign a preliminary spectral type for this source of L8γ-T0γ. We tentatively find that CWISE J0506+0738 is variable at 3-5 μm based on multiepoch WISE photometry. Proper motions derived from follow-up UKIRT observations combined with a radial velocity from our Keck/NIRES spectrum and a photometric distance estimate indicate a strong membership probability in the β Pic moving group. A future parallax measurement will help to establish a more definitive moving group membership for this unusual object