Mesenchymal Stem Cell Spheroids Retain Osteogenic Phenotype Through α2β1 Signaling.

Unlabelled: The induction of mesenchymal stem cells (MSCs) toward the osteoblastic lineage using osteogenic supplements prior to implantation is one approach under examination to enhance their bone-forming potential. MSCs rapidly lose their induced phenotype upon removal of the soluble stimuli; however, their bone-forming potential can be sustained when provided with continued instruction via extracellular matrix (ECM) cues. In comparison with dissociated cells, MSC spheroids exhibit improved survival and secretion of trophic factors while maintaining their osteogenic potential. We hypothesized that entrapment of MSC spheroids formed from osteogenically induced cells would exhibit better preservation of their bone-forming potential than would dissociated cells from monolayer culture. Spheroids exhibited comparable osteogenic potential and increased proangiogenic potential with or without osteogenic preconditioning versus monolayer-cultured MSCs. Spheroids were then entrapped in collagen hydrogels, and the osteogenic stimulus was removed. In comparison with entrapped dissociated MSCs, spheroids exhibited significantly increased markers of osteogenic differentiation. The capacity of MSC spheroids to retain their osteogenic phenotype upon withdrawal of inductive cues was mediated by α2β1 integrin binding to cell-secreted ECM. These results demonstrate the capacity of spheroidal culture to sustain the mineral-producing phenotype of MSCs, thus enhancing their contribution toward bone formation and repair.SignificanceDespite the promise of mesenchymal stem cells (MSCs) for cell-based therapies for tissue repair and regeneration, there is little evidence that transplanted MSCs directly contribute to new bone formation, suggesting that induced cells rapidly lose their osteogenic phenotype or undergo apoptosis. In comparison with dissociated cells, MSC spheroids exhibit increased trophic factor secretion and improved cell survival. The loss of phenotype represents a significant clinical challenge for cell therapies, yet there is no evidence for whether MSC spheroids retain their osteogenic phenotype upon entrapment in a clinically relevant biomaterial. These findings demonstrate that MSC spheroids retain their osteogenic phenotype better than do dissociated MSCs, and this is due to integrin engagement with the cell-secreted extracellular matrix. These data provide evidence for a novel approach for potentiating the use of MSCs in bone repair

A Systems Approach to the Physiology of Weightlessness

A systems approach to the unraveling of the complex response pattern of the human subjected to weightlessness is presented. The major goal of this research is to obtain an understanding of the role that each of the major components of the human system plays following the transition to and from space. The cornerstone of this approach is the utilization of a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. An integrated hypothesis for the human physiological response to weightlessness is developed

Gender violence in schools: taking the ‘girls-as-victims’ discourse forward

This paper draws attention to the gendered nature of violence in schools. Recent recognition that schools can be violent places has tended to ignore the fact that many such acts originate in unequal and antagonistic gender relations, which are tolerated and ‘normalised’ by everyday school structures and processes. After examining some key concepts and definitions, we provide a brief overview of the scope and various manifestations of gender violence in schools, noting that most research to date has focused on girls as victims of gender violence within a heterosexual context and ignores other forms such as homophobic and girl violence. We then move on to look at a few interventions designed to address gender violence in schools in the developing world and end by highlighting the need for more research and improved understanding of the problem and how it can be addressed

Computing the Effective Hamiltonian of Low-Energy Vacuum Gauge Fields

A standard approach to investigate the non-perturbative QCD dynamics is through vacuum models which emphasize the role played by specific gauge field fluctuations, such as instantons, monopoles or vortexes. The effective Hamiltonian describing the dynamics of the low-energy degrees of freedom in such approaches is usually postulated phenomenologically, or obtained through uncontrolled approximations. In a recent paper, we have shown how lattice field theory simulations can be used to rigorously compute the effective Hamiltonian of arbitrary vacuum models by stochastically performing the path integral over all the vacuum field fluctuations which are not explicitly taken into account. In this work, we present the first illustrative application of such an approach to a gauge theory and we use it to compute the instanton size distribution in SU(2) gluon-dynamics in a fully model independent and parameter-free way.Comment: 10 pages, 4 figure

IgG anti-apolipoprotein A-1 antibodies in patients with systemic lupus erythematosus are associated with disease activity and corticosteroid therapy: an observational study.

IgG anti-apolipoprotein A-1 (IgG anti-apoA-1) antibodies are present in patients with systemic lupus erythematosus (SLE) and may link inflammatory disease activity and the increased risk of developing atherosclerosis and cardiovascular disease (CVD) in these patients. We carried out a rigorous analysis of the associations between IgG anti-apoA-1 levels and disease activity, drug therapy, serology, damage, mortality and CVD events in a large British SLE cohort

Cyclic AMP-vepenvent protein kinase phosphorylates residues in the C-terminal domain of the cardiac L-type calcium channel α1 subunit

AbstractThe molecular basis of the regulation of cardiac L-type calcium channel activity by cAMP-vepenvent protein kinase (cA-PK) remains unclear. Direct cA-PK-vepenvent phosphorylation of the bovine ventricular α1 subunit in vitro has been vemonstrated in microsomal membranes, vetergent extracts and partially purified (+)-[3H]PN 200-100 receptor preparations. Two 32P-labelled phosphopeptives, herived from cyanogen bromive cleavage, of 4.7 and 9.5 kDa were immunoprecipitated specifically by site-directed antibodies against the rabbit cardiac α1 subunit amino acid sequences 1602–1616 and 1681–1694, respectively, consistent with phosphorylation at the cA-PK consensus sites at Ser1627 and Ser1700. No phosphopeptive products consistent with phosphorylation at three other C-terminal cA-PK consensus phosphorylation sites (Ser1575, Ser1848 and Ser1928) were iventified using similar procedures suggesting that these sites are poor substrates for this kinase. Ser1627 and Ser1700 may represent sites of cA-PK phosphorylation involved in the physiological regulation of cardiac L-type calcium channel function

Constraining slow-roll inflation with WMAP and 2dF

We constrain slow-roll inflationary models using the recent WMAP data combined with data from the VSA, CBI, ACBAR and 2dF experiments. We find the slow-roll parameters to be $0 < \epsilon_1 < 0.032$ and $\epsilon_2 + 5.0 \epsilon_1 = 0.036 \pm 0.025$. For inflation models $V \propto \phi^{\alpha}$ we find that $\alpha< 3.9, 4.3$ at the 2$\sigma$ and $3\sigma$ levels, indicating that the $\lambda\phi^4$ model is under very strong pressure from observations. We define a convergence criterion to judge the necessity of introducing further power spectrum parameters such as the spectral index and running of the spectral index. This criterion is typically violated by models with large negative running that fit the data, indicating that the running cannot be reliably measured with present data.Comment: 8 pages RevTeX4 file with six figures incorporate

Vocabulario ocaina

PM6682.Z5, ISO 639-3 : oca , ISO 639-3 : spa , Ocaina language--Dictionaries--Spanish, Spanish language--Dictionaries--Ocain