0383 : In vitro 3D model of in vitro angiogenesis using human endothelial cells and pericytes

Human tissue is three-dimensional, and requires convective transport of nutrients and waste through capillary networks to meet metabolic demands Angiogenesis is the formation of new blood vessels from the existing vasculature. It is a multi-step process that include: degradation of the basement membrane, proliferation and migration (sprouting) of endothelial cells (EC) into the extracellular matrix, alignment of EC into cords, branching, lumen formation, anastomosis, and formation of a new basement membrane. The literatture in 3D in vitro models using endothelial cells is wide, using various types of EC (essentially Human Umbilical Vein Endothelial Cells), but blood vessels are composed of two interacting cells types: endothelial cells form the inner of the vessel wall, and mural cells that wrap the first ones. Pericytes are the mural cells of microvessels. They serve as scaffolding, and they communicate with endothelial cells by direct physical contacts and paracrine signaling pathways. Presently, there are no three-dimensional in vitro models of 3D Matrices which contain human pericyte-coated capillaries. Therefore, we aim at including pericytes in a 3D vascular morphogenesis assay in order to create a 3D in vitro model more close to physiologic conditions. We’ll show and discuss our first analyzes and results, the goal of which is to provide new in vitro tools in order to better understand vascular biology, for later studies of endothelial cells-pericytes interactions, extracellular matrix-pericytes interactions, and eventually, further elucidate the role of pericytes in the microvasculature

Doublet identification in single-cell sequencing data using scDblFinder

Doublets are prevalent in single-cell sequencing data and can lead to artifactual findings. A number of strategies have therefore been proposed to detect them. Building on the strengths of existing approaches, we developed scDblFinder, a fast, flexible and accurate Bioconductor-based doublet detection method. Here we present the method, justify its design choices, demonstrate its performance on both single-cell RNA and accessibility (ATAC) sequencing data, and provide some observations on doublet formation, detection, and enrichment analysis. Even in complex datasets, scDblFinder can accurately identify most heterotypic doublets, and was already found by an independent benchmark to outcompete alternatives

Advancing sexual and reproductive health and rights in low- and middle-income countries : implications for the post-2015 global development agenda

The post-2015 global agenda must prioritize equality, quality and accountability in sexual and reproductive health and rights (SRHR). While the last two decades have seen a patchwork of health sector reforms that have had mixed effects on equality of access and on the quality of Sexual and Reproductive Health (SRH) services, significant national efforts demonstrate the possibility of alternative approaches that promote both equality and quality. Early investments in the poorest girls from the poorest communities can have important pay-offs. The next priority actions to close the quality gap in SRH services are delineated

El interes superior del niño a la filiacion extramatrimonial por medio de la prueba de ADN, Distrito Ate Vitarte, 2021

La presente investigación se llevó a cabo con el objetivo de determinar la relación que existe entre el interés superior del niño y la filiación extramatrimonial por medio de la prueba de ADN, distrito Ate Vitarte, 2021, para lo cual se realizó un estudio bajo el enfoque cuantitativo del tipo aplicado, mediante la aplicación de una encuesta entre 40 personas del distrito de Ate Vitarte. Los resultados mostraron que existe una relación significativa entre el interés superior del niño y la filiación extramatrimonial por medio de la prueba de ADN, distrito Ate Vitarte, 2021 (p<0.05; r=0.782)

Finite Time Stabilization of the Four Tanks System: Extensions to the Uncertain Systems

We consider the finite time stability and stabilization of linear systems described in continuous time. First, we provide a condition for the stability over time using the state transition matrix standard. Then we give conditions to design a state feedback control that stabilizes the system over time. In some cases where there is uncertainty in the system model, the previous conditions are extended to a certain class of uncertain systems. The considered uncertainties are the polytopic and norm bounded ones. To reveal the proposed approach, an application to the four tanks system was made

Coordination over a unique medium of exchange under information scarcity

International audienceSeveral micro-founded macroeconomic models with rational expectations address the issue of money emergence, by characterizing it as a coordination game. ese models have in common the use of agents who dispose of perfect or near-perfect information on the global state of the economy and who display full-edged computational abilities. Several experimental studies have shown that a simple trial-and-error learning process could constitute an explanation for how agents coordinate on a single mean of exchange (Brown, 1996; Du y, 2001; Kindler et al., 2017; Lefebvre et al., 2018). However, these studies provide subjects with full information regarding the state of the economy while restricting the number of goods in circulation to three. In this study, by the mean of multi-agent simulations and human experiments, we test the hypothesis according to which coordination over a unique medium of exchange is possible in the context of information scarcity. In our experimental design, subjects and arti cial agents are only aware of the outcome of their own decisions. We provide results for economies with 3 and 4 goods to evaluate to which extent it is possible to generalize results obtained with 3 goods to n goods. Our ndings show that in an economyà la Iwai (1996), commodity money can emerge under drastic information restrictions with 3 goods in circulation, but generalization to 4 or more goods is not guaranteed

Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK Responses

T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide–major histocompatibility complex (pMHC) ligand engagement of clonally distributed antigen receptors (T cell receptors or TCRs). Even a few foreign pMHCs on the surface of an antigen-presenting cell trigger effective signaling within seconds, whereas 1 × 10(5)–1 × 10(6) self-pMHC ligands that may differ from the foreign stimulus by only a single amino acid fail to elicit this response. No existing model accounts for this nearly absolute distinction between closely related TCR ligands while also preserving the other canonical features of T-cell responses. Here we document the unexpected highly amplified and digital nature of extracellular signal-regulated kinase (ERK) activation in T cells. Based on this observation and evidence that competing positive- and negative-feedback loops contribute to TCR ligand discrimination, we constructed a new mathematical model of proximal TCR-dependent signaling. The model made clear that competition between a digital positive feedback based on ERK activity and an analog negative feedback involving SH2 domain-containing tyrosine phosphatase (SHP-1) was critical for defining a sharp ligand-discrimination threshold while preserving a rapid and sensitive response. Several nontrivial predictions of this model, including the notion that this threshold is highly sensitive to small changes in SHP-1 expression levels during cellular differentiation, were confirmed by experiment. These results combining computation and experiment reveal that ligand discrimination by T cells is controlled by the dynamics of competing feedback loops that regulate a high-gain digital amplifier, which is itself modulated during differentiation by alterations in the intracellular concentrations of key enzymes. The organization of the signaling network that we model here may be a prototypic solution to the problem of achieving ligand selectivity, low noise, and high sensitivity in biological responses

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition

A multi-voiced account of family entrepreneuring research: expanding the agenda of family entrepreneurship

Purpose This conceptual, multi-voiced paper aims to collectively explore and theorize family entrepreneuring, which is a research stream dedicated to investigating the emergence and becoming of entrepreneurial phenomena in business families and family firms. Design/methodology/approach Because of the novelty of this research stream, the authors asked 20 scholars in entrepreneurship and family business to reflect on topics, methods and issues that should be addressed to move this field forward. Findings Authors highlight key challenges and point to new research directions for understanding family entrepreneuring in relation to issues such as agency, processualism and context. Originality/value This study offers a compilation of multiple perspectives and leverage recent developments in the fields of entrepreneurship and family business to advance research on family entrepreneuring