Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing

Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound healing; however, the mechanisms involved are barely understood. In this study, we examined paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing compared to those released by dermal fibroblasts. Analyses of BM-MSCs with Real-Time PCR and of BM-MSC-conditioned medium by antibody-based protein array and ELISA indicated that BM-MSCs secreted distinctively different cytokines and chemokines, such as greater amounts of VEGF-α, IGF-1, EGF, keratinocyte growth factor, angiopoietin-1, stromal derived factor-1, macrophage inflammatory protein-1alpha and beta and erythropoietin, compared to dermal fibroblasts. These molecules are known to be important in normal wound healing. BM-MSC-conditioned medium significantly enhanced migration of macrophages, keratinocytes and endothelial cells and proliferation of keratinocytes and endothelial cells compared to fibroblast-conditioned medium. Moreover, in a mouse model of excisional wound healing, where concentrated BM-MSC-conditioned medium was applied, accelerated wound healing occurred compared to administration of pre-conditioned or fibroblast-conditioned medium. Analysis of cell suspensions derived from the wound by FACS showed that wounds treated with BM-MSC-conditioned medium had increased proportions of CD4/80-postive macrophages and Flk-1-, CD34- or c-kit-positive endothelial (progenitor) cells compared to wounds treated with pre-conditioned medium or fibroblast-conditioned medium. Consistent with the above findings, immunohistochemical analysis of wound sections showed that wounds treated with BM-MSC-conditioned medium had increased abundance of macrophages. Our results suggest that factors released by BM-MSCs recruit macrophages and endothelial lineage cells into the wound thus enhancing wound healing

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis

Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis. Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected. Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage. Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis

Nonlinear r-Modes in Neutron Stars: Instability of an unstable mode

We study the dynamical evolution of a large amplitude r-mode by numerical simulations. R-modes in neutron stars are unstable growing modes, driven by gravitational radiation reaction. In these simulations, r-modes of amplitude unity or above are destroyed by a catastrophic decay: A large amplitude r-mode gradually leaks energy into other fluid modes, which in turn act nonlinearly with the r-mode, leading to the onset of the rapid decay. As a result the r-mode suddenly breaks down into a differentially rotating configuration. The catastrophic decay does not appear to be related to shock waves at the star's surface. The limit it imposes on the r-mode amplitude is significantly smaller than that suggested by previous fully nonlinear numerical simulations.Comment: Published in Phys. Rev. D Rapid Comm. 66, 041303(R) (2002

Quantum Electronics

Contains report on ten research projects split into three sections.Joint Services Electronics Program (Contract DAAG29-78-C-0020)National Science Foundation (Grant PHY77-07156)U. S. Air Force-Office of Scientific Research (Grant AFOSR-3042)National Science Foundation (Grant ENG77-24981

Quantum Electronics

Contains reports on eight research projects divided into three sections.National Science Foundation (Grant PHY79-09739)Joint Services Electronics Program (Contract DAAG29-78-C-0020)U.S. Air Force Geophysics Laboratory (AFSC) (Contract F19628-79-C-0082)National Science Foundation (Grant ENG79-09980

Structure and Property of Microinjection Molded Poly(lactic acid) with High Degree of Long Chain Branching

YesLong chain branches (LCB) are successfully grafted to linear poly(lactic acid) (PLA) using functional group reactions with pentaerythritol triacrylate (PETA) and tetraethylthiuram disulfide (TETDS). Results show a high branching degree of PLA (∼49.5%) can be effectively obtained with adding only 1 wt % PETA, contributing remarkably to enhancing strain hardening. The density of the nuclei formed during nonisothermal crystallization for LCB-PLA samples is markedly increased contrasted with PLA, resulting in significantly enhancing crystallinity from 13.3% to 41%, the onset crystallization temperature (∼20 °C), and the crystallization rate. Interestingly, compared with mini-injection molding, the elevated wall shear rates (and corresponding shear stresses) prove to be beneficial to the creation of special crystalline morphologies (β-crystal form) and oriented structures under microinjection molding conditions, resulting in the improvement of tensile strength by ∼45 MPa.Chinese Scholarship Counci

Quantum Electronics

Contains reports on three research projects.National Science Foundation (Grant PHY77-07156)Joint Services Electronics Program (Contract DAABO7-76-C-1400)U. S. Air Force - Office of Scientific Research (Grant AFOSR-76-3042)U. S. Air Force - Office of Scientific Research (Contract F-44620-76-C-0079)M.I.T. Sloan Fund for Basic Researc

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Joint pricing and ordering policies for deteriorating item with retail price-dependent demand in response to announced supply price increase

[[abstract]]Recently, due to rapid economic development in emerging nations, the world's raw material prices have been rising. In today's unrestricted information environment, suppliers typically announce impending supply price increases at specific times. This allows retailers to replenish their stock at the present price, before the price increase takes effect. The supplier, however, will generally offer only limited quantities prior to the price increase, so as to avoid excessive orders. The retail price will usually reflect any supply price increases, as market demand is dependent on retail price. This paper considers deteriorating items and investigates (1) the possible effects of a supply price increase on retail pricing, and (2) ordering policies under the conditions that special order quantities are limited and demand is dependent on retail price. The purpose of this paper is to determine the optimal special order quantity and retail price to maximize profit. Our theoretical analysis examines the necessary and sufficient conditions for an optimal solution, and an algorithm is established to obtain the optimal solution. Furthermore, several numerical examples are given to illustrate the developed model and the solution procedure. Finally, a sensitivity analysis is conducted on the optimal solutions with respect to major parameters.[[incitationindex]]SCI[[booktype]]紙

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure