Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases

This study aimed to identify what information triggered social media users' responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.published_or_final_versio

Biological impact of nanodiamond particles – label free, high-resolution methods for nanotoxicity assessment

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assays that offer high sensitivity and are label-free. Here we developed ‘mini-liver’ models using scaffold-free bioprinting and used these models together with label-free nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticle-cell interactions, thus could be considered as a complementary approach to currently used methods

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Tracing Functional Antigen-Specific CCR6+ Th17 Cells after Vaccination

BACKGROUND: The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6(+) Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6(+) Th cells indicate their activated status. Vaccination induces antigen-specific CCR6(+) Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6(+) Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice. CONCLUSIONS/SIGNIFICANCE: In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections

Superconductivity at 44 K in K intercalated FeSe system with excess Fe

We report here that a new superconducting phase with much higher Tc has been found in K intercalated FeSe compound with excess Fe. We successfully grew crystals by precisely controlling the starting amount of Fe. Besides the superconducting (SC) transition at ~30 K, we observed a sharp drop in resistivity and a kink in susceptibility at 44 K. By combining thermodynamic measurements with electron spin resonance (ESR), we demonstrate that this is a new SC transition. Structural analysis unambiguously reveals two phases coexisting in the crystals, which are responsible respectively for the SC transitions at 30 and 44 K. The structural experiments and first-principles calculations consistently indicate that the 44 K SC phase is close to a 122 structure, but with an unexpectedly large c-axis of 18.10 {\AA}. We further find a novel monotonic dependence of the maximum Tc on the separation of neighbouring FeSe layers.Comment: 15 pages, 5 figure

Validity and reliability of the semi-quantitative self-report Home Food Availability Inventory Checklist (HFAI-C) in White and South Asian populations.

Despite interest in the importance of the home food environment and its potential influence on children's diets and social norms, there remain few self-report checklist methods that have been validated against the gold standard of researcher-conducted inventories. This study aimed to assess the criterion validity and reliability of the 'Home Food Availability Inventory Checklist' (HFAI-C), a 39-item checklist including categories of fruit, vegetables, snacks and drinks.The HFAI-C was completed by 97 participants of White and Pakistani origin in the UK. Validity was determined by comparing participant-reported HFAI-C responses to data from researcher observations of home food availability using PABAK and weighted kappa statistics. The validity of measuring the amount of items (in addition to presence/absence) available was also determined. Test-retest reliability compared repeated administrations of the HFAI-C using intra-class correlation coefficients.Validity and reliability was fair to moderate overall. For validity, the average category-level PABAK ranged from 0.31 (95 % CI: 0.25, 0.37) for vegetables to 0.44 (95 % CI: 0.40, 0.49) for fruits. Assessment of the presence/absence of items demonstrated higher validity compared to quantity measurements. Reliability was increased when the HFAI-C was repeated close to the time of the first administration. For example, ICCs for reliability of the measurement of fruits were 0.52 (95 %CI: 0.47, 0.56) if re-administered within 5 months, 0.58 (95 % CI: 0.51, 0.64) within 30 days and 0.97 (95 %CI: 0.94, 1.00) if re-administered on the same day.Overall, the HFAI-C demonstrated fair to moderate validity and reliability in a population of White and South Asian participants. This evaluation is consistent with previous work on other checklists in less diverse, more affluent populations. Our research supports the use of the HFAI-C as a useful, albeit imperfect, representation of researcher-conducted inventories. The feasibility of collecting information using the HFAI-C in large, multi-ethnic samples can facilitate examination of home food availability in relation to exposures such as ethnicity and outcomes including behavioural, social and health outcomes. Future work using the HFAI-C could provide important insights into a modifiable influence with potential to impact health

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation