Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

Background: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and Methods: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture. ASC proliferation, collagen production, and gene expression were examined. As comparison, the effect of macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNγ) [M(LPS/IFNγ)] or interleukin (IL) 4 [M(IL-4)] on ASCs was examined. Results: Macrophage-CM increased collagen deposition, proliferation, and gene expression of MMP1, PLOD2, and PTGS2 in ASCs, irrespective of the material. Culturing ASCs and macrophages in coculture when only macrophages were on the materials induced the same effects on gene expression. When both ASCs and macrophages were cultured on biomaterials, PP induced COL1A1 and MMP1 more than PET/Col. M(LPS/IFNγ) CM increased PLOD2, MMP1, and PTGS2 and decreased TGFB in ASCs more than the M(IL-4) CM. Conclusion: Biomaterials influence wound healing by influencing the interaction between macrophages and ASCs. We provided more insight into the behavior of different cell types during wound healing. This behavior appears to be biomaterial specific depending on which cell type interacts with the biomaterial. As such, the biomaterial will influence tissue regeneration

Geometry of entangled states

Geometric properties of the set of quantum entangled states are investigated. We propose an explicit method to compute the dimension of local orbits for any mixed state of the general K x M problem and characterize the set of effectively different states (which cannot be related by local transformations). Thus we generalize earlier results obtained for the simplest 2 x 2 system, which lead to a stratification of the 6D set of N=4 pure states. We define the concept of absolutely separable states, for which all globally equivalent states are separable.Comment: 16 latex pages, 4 figures in epsf, minor corrections, references updated, to appear in Phys. Rev.

A Geometric Picture of Entanglement and Bell Inequalities

We work in the real Hilbert space H_s of hermitian Hilbert-Schmid operators and show that the entanglement witness which shows the maximal violation of a generalized Bell inequality (GBI) is a tangent functional to the convex set S subset H_s of separable states. This violation equals the euclidean distance in H_s of the entangled state to S and thus entanglement, GBI and tangent functional are only different aspects of the same geometric picture. This is explicitly illustrated in the example of two spins, where also a comparison with familiar Bell inequalities is presented.Comment: 17 pages, 5 figures, 4 references adde

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of LINC00261 diminishes insulin(+) cells, in a manner independent of the nearby TF FOXA2. One-by-one deletion of each of LINC00261's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles

Single-neutron orbits near Ni-78: Spectroscopy of the N=49 isotope Zn-79

5 pags., 6 figs.Single-neutron states in the , isotope 79Zn have been populated using the 78Zn(d, p)79Zn transfer reaction at REX-ISOLDE, CERN. The experimental setup allowed the combined detection of protons ejected in the reaction, and of γ rays emitted by 79Zn. The analysis reveals that the lowest excited states populated in the reaction lie at approximately 1 MeV of excitation, and involve neutron orbits above the shell gap. From the analysis of γ-ray data and of proton angular distributions, characteristic of the amount of angular momentum transferred, a configuration was assigned to a state at 983 keV. Comparison with large-scale-shell-model calculations supports a robust neutron shell-closure for 78Ni. These data constitute an important step towards the understanding of the magicity of 78Ni and of the structure of nuclei in the region.This work was supported by the European Commission through the Marie Curie Actions Contracts Nos. PIEFGA-2011-30096 (R.O.) and PIEFGA-2008-219175 (J.P.), by the Spanish Ministerio de Ciencia e Innovación under contracts FPA2009-13377-C02 and FPA2011-29854-C04, by the Spanish MEC Consolider – Ingenio 2010, Project No. CDS2007-00042 (CPAN), by FWO-Vlaanderen (Belgium), by GOA/2010/010 (BOF KU Leuven), by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12), by the European Union Seventh Framework Programme through ENSAR, contract no. RII3-CT-2010-262010, and by the German BMBF under contracts 05P09PKCI5, 05P12PKFNE, 05P12RDCIA and 06DA9036I. R.O., R.C., J.F.W.L., V.L. and J.F.S. also acknowledge support from STFC, Grant Nos. PP/F000944/1, ST/F007590/1, and ST/J000183/2

Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele