Models of Human Vascular Disease: Is There an Animal of La Mancha?

Cervantes understood that models–be they physical or moral lessons–are valid only in as much as they mirror that which they seek to mimic. This is the essential issue presented by Diego et al. in the article published in Revista Española de Cardiología. Drug-eluting stents have changed the practice of medicine and are perhaps the most common intervention used today. Millions of stents are placed each year and yet critical questions remain as to whether one design is better than another. The challenge in major part is that, though device designs may be significantly different one from another, detection of a clinical difference is difficult given the rarity of side effects. Human clinical trials are too small and too short to detect differences even in fatal events that occur in 1 in 100 patients per year. The natural fallback is to rely on animal model systems and yet it is unclear how best to use them. Diego et al. describe a study that compares the proliferative response elicited after deployment of paclitaxel-eluting and bare metal stents in porcine coronary arteries. They suggest that the ability of a stent platform to significantly impact late vascular healing depends upon the degree of injury that is created at the time of implantation. Such a result has profound impact on how we consider animal model systems for critical technologies, our view of vascular biology and vascular repair, and our appreciation of the history of work in this field. Moreover, the study shows how a difficult parameter rarely controlled in human interventions–the extent of injury–is such a powerful regulator of clinical effect and restenotic side effect.National Institutes of Health (U.S.) (Grant RO1/GM049039)National Institute of General Medical Sciences (U.S.) (Grant RO1/GM049039

A human plasma derived supplement preserves function of human vascular cells in absence of fetal bovine serum

Current techniques for cell culture routinely use animal-derived components. Fetal bovine serum (FBS) is the most widely applied supplement, but it often displays significant batch-to-batch variations and is generally not suitable for clinical applications in humans. A robust and xeno-free alternative to FBS is of high interest for cellular therapies, from early in vitro testing to clinical trials in human subjects. In the current work, a highly consistent human plasma derived supplement (SCC) has been tested, as a potential substitute of FBS in primary human vascular cells culture. Our results show that SCC is able to support proliferation, preserve cellular morphology and potentiate functionality analogously to FBS. We conclude that SCC is a viable substitute of FBS for culture and expansion of cells in advanced therapies using human vascular cells and fibroblasts

Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment

Objective: Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. Design: Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. Results: Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. Conclusions: Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation

Evolution along the sequence of S0 Hubble types induced by dry minor mergers. II - Bulge-disk coupling in the photometric relations through merger-induced internal secular evolution

Galaxy mergers are considered as questionable mechanisms for the evolution of lenticular galaxies (S0's), on the basis that even minor ones induce structural changes that are difficult to reconcile with the strong bulge-disk coupling observed in the photometric scaling relations of S0's. We check if the evolution induced onto S0's by dry intermediate and minor mergers can reproduce their photometric scaling relations, analysing the bulge-disk decompositions of the merger simulations presented in Eliche-Moral et al. (2012). The mergers induce an evolution in the photometric planes compatible with the data of S0's, even in those ones indicating a strong bulge-disk coupling. The mergers drive the formation of the observed photometric relation in some cases, whereas they induce a slight dispersion compatible with data in others. Therefore, this evolutionary mechanism tends to preserve these scaling relations. In those photometric planes where the morphological types segregate, the mergers always induce evolution towards the region populated by S0's. The structural coupling of the bulge and the disk is preserved or reinforced because the mergers trigger internal secular processes in the primary disk that induce significant bulge growth, even although these models do not induce bars. Intermediate and minor mergers can thus be considered as plausible mechanisms for the evolution of S0's attending to their photometric scaling relations, as they can preserve and even strengthen any pre-existing structural bulge-disk coupling, triggering significant internal secular evolution (even in the absence of bars or dissipational effects). This means that it may be difficult to isolate the effects of pure internal secular evolution from those of the merger-driven one in present-day early-type disks (abridged).Comment: Accepted for publication in Astronomy & Astrophysics, 13 pages, 8 figures. Definitive version after proofs. Added references and corrected typo

Evolution induced by dry minor mergers onto fast-rotator S0 galaxies

We analysed collisionless N-body simulations of intermediate and minor dry mergers onto S0s to test whether these mergers can generate S0 galaxies with kinematics intermediate between fast and slow rotators. We find that minor mergers induce a lower decrease of the global rotational support than encounters of lower mass ratios, which results in S0s with properties intermediate between fast and slow rotators. The resulting remnants are intrinsically more triaxial, less flattened, and span the whole range of apparent ellipticities up to $\epsilon_\mathrm{e} \sim 0.8$. They do not show lower apparent ellipticities in random projections than initially; on the contrary, the formation of oval distortions and the disc thickening increase the percentage of projections at $0.4 < \epsilon_\mathrm{e} < 0.7$. In the experiments with S0b progenitor galaxies, minor mergers tend to spin up the bulge and to decrease slightly its intrinsic ellipticity, whereas in the cases of primary S0c galaxies they keep the rotational support of the bulge nearly constant and decrease significantly its intrinsic ellipticity. The remnant bulges remain nearly spherical ($B/A \sim C/A > 0.9$), but exhibit a wide range of triaxialities ($0.20 < T < 1.00$). In the plane of global anisotropy of velocities ($\delta$) vs. intrinsic ellipticity ($\epsilon_\mathrm{e,intr}$), some of our models extend the linear trend found in previous major merger simulations towards higher $\epsilon_\mathrm{e,intr}$ values, while others depart from it. This is consistent with the wide dispersion exhibited by real S0s in this diagram compared with ellipticals, which follow the linear trend drawn by major merger simulations. The different trends exhibited by ellipticals and S0 galaxies in the $\delta$ - $\epsilon_\mathrm{e}$ diagram may be pointing to the different role played by major mergers in the build-up of each morphological type.Comment: Corrected typos. 20 pages, 14 figures. Accepted for publishing in A&

Монацит как источник стратегических металлов

Объектом исследования являются минерал монацит и его разновидность куларит. Цель работы – Изучение минералого-геохимических особенностей монацитов и рассмотрение их как потенциальных источников редкоземельных элементов. В процессе исследования проводились исследования элементного состава, электронно-микроскопические исследования, определялось пространственное распределение редкоземельных элементов в кристаллах монацитов. В результате исследования показан элементный состав монацитов, сопоставлены содержания тех или иных элементов в минералах. Степень применения: настоящая работа находится на стадии научного исследования. Область применения: полученные данные могут быть использованы при дальнейшем изучении монацита и его разновидности куларита, а также при анализе минерально-сырьевой базы.The object of research is the mineral monazite and its variety of kularit (dark monazite). The aim of the work was mineralogical and geochemical features of monazites and their consideration as potential sources of rare-earth elements. During the study, conducted the study of the elemental composition, electron microscopic studies determined the spatial distribution of rare earth elements in crystals of monazite. In the result shows the elemental composition of monazites associated content or other elements in minerals. The extent of the use: this work is under research. Applications: the data obtained can be used for further study of monazite and its variants kularit (dark monazite), as well as in the analysis of mineral resources base

Smooth muscle cells orchestrate the endothelial cell response to flow and injury

available in PMC 2011 May 25Background— Local modulation of vascular mammalian target of rapamycin (mTOR) signaling reduces smooth muscle cell (SMC) proliferation after endovascular interventions but may be associated with endothelial cell (EC) toxicity. The trilaminate vascular architecture juxtaposes ECs and SMCs to enable complex paracrine coregulation but shields SMCs from flow. We hypothesized that flow differentially affects mTOR signaling in ECs and SMCs and that SMCs regulate mTOR in ECs. Methods and Results— SMCs and/or ECs were exposed to coronary artery flow in a perfusion bioreactor. We demonstrated by flow cytometry, immunofluorescence, and immunoblotting that EC expression of phospho-S6 ribosomal protein (p-S6RP), a downstream target of mTOR, was doubled by flow. Conversely, S6RP in SMCs was growth factor but not flow responsive, and SMCs eliminated the flow sensitivity of ECs. Temsirolimus, a sirolimus analog, eliminated the effect of growth factor on SMCs and of flow on ECs, reducing p-S6RP below basal levels and inhibiting endothelial recovery. EC p-S6RP expression in stented porcine arteries confirmed our in vitro findings: Phosphorylation was greatest in ECs farthest from intact SMCs in metal stented arteries and altogether absent after sirolimus stent elution. Conclusions— The mTOR pathway is activated in ECs in response to luminal flow. SMCs inhibit this flow-induced stimulation of endothelial mTOR pathway. Thus, we now define a novel external stimulus regulating phosphorylation of S6RP and another level of EC-SMC crosstalk. These interactions may explain the impact of local antiproliferative delivery that targets SMC proliferation and suggest that future stents integrate design influences on flow and drug effects on their molecular targets.National Institutes of Health (U.S.) (NIH/NIGMS RO1/GM049039)National Institutes of Health (U.S.) (NIH-NIDDK (1K08DK080946))Fundación Empresas IQSBarcelona Chamber of Commerc

K_(s) number counts in the Groth and Coppi fields

We have used William Herschel Telescope/INGRID K_(s) images on two high-latitude fields, the Coppi and Groth strips, to obtain galaxy number counts over similar to 180 arcmin^(2), to a depth of K_(s) similar to 21.0. Detection efficiency corrections as a function of object size have been calculated on each pointing. We have used a signal-to-noise threshold in two complementary half-exposure images to remove spurious detections. Our data cover the range from K_(s) = 14.5 to K_(s) = 21.0, so they are useful for investigating a previously reported change in the number count slope (d log N/dm) at K similar to 17. We find a slope gamma(b) = 0.54 0.63 for K 17.5. A total contribution from galaxies to the extragalactic background light (EBL) in the K band of nuI(nu) = 10.5 nW m^(-2) sr^(-1) has been calculated. This K-band EBL coming from galaxies accounts for only similar to 50% of the recent measurements of the diffuse EBL. Standard number count models fail to reproduce the observed slope change at K similar to 17.5 unless elliptical and spiral formation is pushed to z less than or similar to 2

K-s number counts in the Groth and Coppi fields

We have used William Herschel Telescope/INGRID K_(s) images on two high-latitude fields, the Coppi and Groth strips, to obtain galaxy number counts over ~ 180 arcmin^(2), to a depth of K_(s) ~ 21:0. Detection efficiency corrections as a function of object size have been calculated on each pointing. We have used a signalto-noise threshold in two complementary half-exposure images to remove spurious detections. Our data cover the range from K_(s) = 14.5 to K_(s) = 21.0, so they are useful for investigating a previously reported change in the number count slope (d log N/dm) at K ~ 17. We find a slope ϒ_(b)= 0:54- 0:63 for K 17.5. A total contribution from galaxies to the extragalactic background light (EBL) in the K band of νI_(ν)=10.5 nW m^(-2) sr^(-1) has been calculated. This K-band EBL coming from galaxies accounts for only ~50% of the recent measurements of the diffuse EBL. Standard number count models fail to reproduce the observed slope change at K ~ 17.5 unless elliptical and spiral formation is pushed to z<̱̱̰2