Pluripotency of mesenchymal stem cells derived from adult marrow

We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.     

Nanoscale double emulsions stabilized by single-component block copolypeptides

Water-in-oil-in-water emulsions are examples of double emulsions, in which dispersions of small water droplets within larger oil droplets are themselves dispersed in a continuous aqueous phase. Emulsions occur in many forms of processing and are used extensively by the foods, cosmetics and coatings industries. Because of their compartmentalized internal structure, double emulsions can provide advantages over simple oil-in-water emulsions for encapsulation, such as the ability to carry both polar and non-polar cargos, and improved control over release of therapeutic molecules. The preparation of double emulsions typically requires mixtures of surfactants for stability; the formation of double nanoemulsions, where both inner and outer droplets are under 100 nm, has not yet been achieved. Here we show that water-in-oil-in-water double emulsions can be prepared in a simple process and stabilized over many months using single-component, synthetic amphiphilic diblock copolypeptide surfactants. These surfactants even stabilize droplets subjected to extreme flow, leading to direct, mass production of robust double nanoemulsions that are amenable to nanostructured encapsulation applications in foods, cosmetics and drug delivery.     

First Line Steps in Requirements Identification for Guidelines Development in Responsible Research and Innovation (RRI)

Responsible research and innovation (RRI) considers the impact of research and development on those who are likely to be directly or indirectly impacted by those activities, and provides a direction for the future of research practices in science and technology for the greater good. In the practical world of the lab or research group therefore, guidelines to assist researchers and scientists in the application of those RRI principles are needed. However, this paper is not concerned with the creation of guidelines themselves, but presents an RRI approach to identifying the requirements for guidelines. This is a first step that is often overlooked or presented as a fait accompli and yet it provides an essential factor in the eventual success or failure of guidelines, created for any purpose. What is required in a set of guidelines however, is not only dictated by the preferred outcome, but is also reflected in the process of its creation. Therefore, an RRI approach to identifying those requirements should also practice what the resulting RRI guidelines preach. Whilst initially developed for the production of guidelines for researchers in an EU RRI project, these approaches and principles can be applied across all disciplines when a set of guidelines need to be developed. The approach taken here, utilized several steps in its implementation. Firstly, through a review of the literature and an examination of guideline development in several research projects, a set of indicative requirements were created. A workshop/focus group with researchers from a range of disciplines, career stages and institutions led to the production of the second iteration, which then received further input from both experts in the field of RRI, philosophy and ethics. This led to the creation of the table of requirements for guidelines. By utilizing the core principles of RRI and through a critical and reflexive approach, this work presents a new technique for identifying first line steps in the creation of guidelines. The practical and flexible nature of this approach means that researchers and policy-makers are invited to use this method in their own guideline development.     

The hottest planet

Of the over 200 known extrasolar planets, just 14 pass in front of and behind their parent stars as seen from Earth. This fortuitous geometry allows direct determination of many planetary properties. Previous reports of planetary thermal emission give fluxes that are roughly consistent with predictions based on thermal equilibrium with the planets' received radiation, assuming a Bond albedo of approximately 0.3. Here we report direct detection of thermal emission from the smallest known transiting planet, HD 149026b, that indicates a brightness temperature (an expression of flux) of 2,300 +/- 200 K at 8 microm. The planet's predicted temperature for uniform, spherical, blackbody emission and zero albedo (unprecedented for planets) is 1,741 K. As models with non-zero albedo are cooler, this essentially eliminates uniform blackbody models, and may also require an albedo lower than any measured for a planet, very strong 8 microm emission, strong temporal variability, or a heat source other than stellar radiation. On the other hand, an instantaneous re-emission blackbody model, in which each patch of surface area instantly re-emits all received light, matches the data. This planet is known to be enriched in heavy elements, which may give rise to novel atmospheric properties yet to be investigated.     

柠檬酸纳米金与丙烯酸纳米金修饰的金-海藻酸钙-几丁聚糖微胶囊渗透性比较

 分别用柠檬酸钠和丙烯酸钠做还原剂制备金纳米微粒,并分别用它们对几丁聚糖微胶囊进行化学修饰,提出了新的修饰方法,制备出新的金-海藻酸钙-几丁聚糖微胶囊(GACM).运用分光光度法对2个体系下制得的GACM的渗透性进行了测定,结果表明柠檬酸体系下制得的GACM的渗透性比丙烯酸钠体系下制得的GACM的渗透性要大.     

Fluorescence spectroscopy and molecular dynamics simulations in studies on the mechanism of membrane destabilization by antimicrobial peptides

Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism of membrane destabilization by AMPs.     

Detectable clonal mosaicism from birth to old age and its relationship to cancer

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).     

Overexpression of Fto leads to increased food intake and results in obesity

Genome-wide association studies have identified SNPs within FTO, the human fat mass and obesity-associated gene, that are strongly associated with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh, on average, ~3 kg more than individuals with the low-risk T allele. Mice that lack FTO function and/or Fto expression display increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or a high-fat diet. Our results suggest that increased body mass results primarily from increased food intake. Mice with increased Fto expression on a high-fat diet develop glucose intolerance. This study provides the first direct evidence that increased Fto expression causes obesity in mice.     

Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy

Guanylate cyclase activating protein 1 (GCAP1) is a neuronal Ca²⁺ sensor (NCS) that regulates the activation of rod outer segment guanylate cyclases (ROS-GCs) in photoreceptors. In this study, we investigated the Ca²⁺-induced effects on the conformation and the thermal stability of four GCAP1 variants associated with hereditary human cone dystrophies. Ca²⁺ binding stabilized the conformation of all the GCAP1 variants independent of myristoylation. The myristoylated wild-type GCAP1 was found to have the highest Ca²⁺ affinity and thermal stability, whereas all the mutants showed decreased Ca²⁺ affinity and significantly lower thermal stability in both apo and Ca²⁺-loaded forms. No apparent cooperativity of Ca²⁺ binding was detected for any variant. Finally, the nonmyristoylated mutants were still capable of activating ROS-GC1, but the measured cyclase activity was shifted toward high, nonphysiological Ca²⁺ concentrations. Thus, we conclude that distorted Ca²⁺-sensor properties could lead to cone dysfunction.