An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis

Approaches to developing the capacity of health policy analysis institutes: a comparative case study

<p>Abstract</p> <p>Objectives</p> <p>To review and assess (i) the factors that facilitate the development of sustainable health policy analysis institutes in low and middle income countries and (ii) the nature of external support for capacity development provided to such institutes.</p> <p>Methods</p> <p>Comparative case studies of six health policy analysis institutes (3 from Asia and 3 from Africa) were conducted. In each region an NGO institute, an institute linked to government and a university based institute were included. Data collection comprised document review, semi-structured interviews with stakeholders and discussion of preliminary findings with institute staff.</p> <p>Findings</p> <p>The findings are organized around four key themes: (i) Financial resources: three of the institutes had received substantial external grants at start-up, however two of these institutes subsequently collapsed. At all but one institute, reliance upon short term, donor funding, created high administrative costs and unpredictability. (ii) Human resources: the retention of skilled human resources was perceived to be key to institute success but was problematic at all but one institute. In particular staff often moved to better paid positions elsewhere once having acquired necessary skills and experience, leaving remaining senior staff with heavy workloads. (iii) Governance and management: board structures and roles varied according to the nature of institute ownership. Boards made important contributions to organizational capacity through promoting continuity, independence and fund raising. Routine management systems were typically perceived to be strong. (iv) Networks: linkages to policy makers helped promote policy influences. External networks with other research organizations, particularly where these were longer term institutional collaborations helped promote capacity.</p> <p>Conclusions</p> <p>The development of strong in-country analytical and research capacity to guide health policy development is critical, yet many health policy analysis institutes remain very fragile. A combination of more strategic planning, active recruitment and retention strategies, and longer term, flexible funding, for example through endowments, needs to be promoted. Specific recommendations to funders and institutes are provided.</p

Reversine treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle

Stem cells hold a great potential for the regeneration of damaged tissues in cardiovascular or musculoskeletal diseases. Unfortunately, problems such as limited availability, control of cell fate, and allograft rejection need to be addressed before therapeutic applications may become feasible. Generation of multipotent progenitors from adult differentiated cells could be a very attractive alternative to the limited in vitro self renewal of several types of stem cells. In this direction, a recently synthesized unnatural purine, named reversine, has been proposed to induce reversion of adult cells to a multipotent state, which could be then converted into other cell types under appropriate stimuli. Our study suggests that reversine treatment transforms primary murine and human dermal fibroblasts into myogenic competent cells both in vitro and in vivo. Moreover, this is the first study to demonstrate that plasticity changes arise in primary mouse and human cells following reversine exposure