Two dimensional soliton in tumor induced angiogenesis

Ensemble averages of a stochastic model show that, after a formation stage, the tips of active blood vessels in an angiogenic network form a moving two dimensional stable diffusive soliton, which advances toward sources of growth factor. Here we use methods of multiple scales to find the diffusive soliton as a solution of a deterministic equation for the mean density of active endothelial cells tips. We characterize the diffusive soliton shape in a general geometry, and find that its vector velocity and the trajectory of its center of mass along curvilinear coordinates solve appropriate collective coordinate equations. The vessel tip density predicted by the soliton compares well with that obtained by ensemble averages of simulations of the stochastic model.Comment: 35 pages, 10 figures, to appear in JSTA

Soliton approximation in continuum models of leader-follower behavior

Complex biological processes involve collective behavior of entities (bacteria, cells, animals) over many length and time scales and can be described by discrete models that track individuals or by continuum models involving densities and fields. We consider hybrid stochastic agent-based models of branching morphogenesis and angiogenesis (new blood vessel creation from pre-existing vasculature), which treat cells as individuals that are guided by underlying continuous chemical and/or mechanical fields. In these descriptions, leader (tip) cells emerge from existing branches and follower (stalk) cells build the new sprout in their wake. Vessel branching and fusion (anastomosis) occur as a result of tip and stalk cell dynamics. Coarse-graining these hybrid models in appropriate limits produces continuum partial differential equations (PDEs) for endothelial cell densities that are more analytically tractable. While these models differ in nonlinearity, they produce similar equations at leading order when chemotaxis is dominant. We analyze this leading order system in a simple quasi-one-dimensional geometry and show that the numerical solution of the leading order PDE is well described by a soliton wave that evolves from vessel to source. This wave is an attractor for intermediate times until it arrives at the hypoxic region releasing the growth factor. The mathematical techniques used here thus identify common features of discrete and continuum approaches and provide insight into general biological mechanisms governing their collective dynamics.Comment: 13 pages, 9 figure

Systematic mapping review of the factors influencing dietary behaviour in ethnic minority groups living in Europe: A DEDIPAC study

.Background: Europe has a growing population of ethnic minority groups whose dietary behaviours are potentially of public health concern. To promote healthier diets, the factors driving dietary behaviours need to be understood. This review mapped the broad range of factors influencing dietary behaviour among ethnic minority groups living in Europe, in order to identify research gaps in the literature to guide future research. Methods: A systematic mapping review was conducted (protocol registered with PROSPERO 2014: CRD42014013549). Nine databases were searched for quantitative and qualitative primary research published between 1999 and 2014. Ethnic minority groups were defined as immigrants/populations of immigrant background from low and middle income countries, population groups from former Eastern Bloc countries and minority indigenous populations. In synthesizing the findings, all factors were sorted and structured into emerging clusters according to how they were seen to relate to each other. Results: Thirty-seven of 2965 studies met the inclusion criteria (n = 18 quantitative; n = 19 qualitative). Most studies were conducted in Northern Europe and were limited to specific European countries, and focused on a selected number of ethnic minority groups, predominantly among populations of South Asian origin. The 63 factors influencing dietary behaviour that emerged were sorted into seven clusters: social and cultural environment (16 factors), food beliefs and perceptions (11 factors), psychosocial (9 factors), social and material resources (5 factors), accessibility of food (10 factors), migration context (7 factors), and the body (5 factors). Conclusion: This review identified a broad range of factors and clusters influencing dietary behaviour among ethnic minority groups. Gaps in the literature identified a need for researchers to explore the underlying mechanisms that shape dietary behaviours, which can be gleaned from more holistic, systems-based studies exploring relationships between factors and clusters. The dominance of studies exploring 'differences' between ethnic minority groups and the majority population in terms of the socio-cultural environment and food beliefs suggests a need for research exploring 'similarities'. The evidence from this review will feed into developing a framework for the study of factors influencing dietary behaviours in ethnic minority groups in Europe

A convergent numerical scheme for integrodifferential kinetic models of angiogenesis

We study a robust finite difference scheme for integrodifferential kinetic systems of Fokker-Planck type modeling tumor driven blood vessel growth. The scheme is of order one and enjoys positivity features. We analyze stability and convergence properties, and show that soliton-like asymptotic solutions are correctly captured. We also find good agreement with the solution of the original stochastic model from which the deterministic kinetic equations are derived working with ensemble averages. A numerical study clarifies the influence of velocity cut-offs on the solutions for exponentially decaying data

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits

DNMT1-interacting RNAs block gene specific DNA methylation

Summary DNA methylation was described almost a century ago. However, the rules governing its establishment and maintenance remain elusive. Here, we present data demonstrating that active transcription regulates levels of genomic methylation. We identified a novel RNA arising from the CEBPA gene locus critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extended the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene selective demethylation of therapeutic targets in disease

iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability

Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder characterized by distinctive facial features, growth retardation, broad thumbs and toes and mild to severe intellectual disability, caused by heterozygous mutations in either CREBBP or EP300 genes, encoding the homologous CBP and p300 lysine-acetyltransferases and transcriptional coactivators. No RSTS in vitro induced Pluripotent Stem Cell (iPSC)-neuronal model is available yet to achieve mechanistic insights on cognitive impairment of RSTS patients. We established iPSC-derived neurons (i-neurons) from peripheral blood cells of three CREBBP- and two EP300-mutated patients displaying different levels of intellectual disability, and four unaffected controls. Pan neuronal and cortical-specific markers were expressed by all patients' i-neurons. Altered morphology of patients' differentiating neurons, showing reduced branch length and increased branch number, and hypoexcitability of differentiated neurons emerged as potential disease biomarkers. Anomalous neuronal morphology and reduced excitability varied across different RSTS patients' i-neurons. Further studies are needed to validate these markers and assess whether they reflect cognitive and behavioural impairment of the donor patients