Molecular function of the novel α7β2 nicotinic receptor

The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.     

Inhibition of protein misfolding and aggregation by natural phenolic compounds

Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases.     

Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property

Mesenchymal stem cells (MSCs) are heterogeneous likely consisting of subpopulations with various therapeutic potentials. Here we attempted to acquire a subset of MSCs with enhanced effect in wound healing. We found that human placental MSCs expressing platelet-derived growth factor (PDGF) receptor (PDGFR)-β exhibited greater proliferation rates and generated more colony-forming unit-fibroblast (CFU-F), compared to PDGFR-β^? MSCs. Notably, PDGFR-β⁺ MSCs expressed higher levels of pro-angiogenic factors such as Ang1, Ang2, VEGF, bFGF and PDGF. When 10⁶ GFP-expressing MSCs were topically applied into excisional wounds in mice, PDGFR-β⁺ MSCs actively incorporated into the wound tissue, resulting in enhanced engraftment (3.92 ± 0.31 × 10⁵ remained in wound by 7 days) and accelerated wound closure; meanwhile, PDGFR-β^? MSCs tended to remain on the top of the wound bed with significantly fewer cells (2.46 ± 0.26 × 10⁵) engrafted into the wound, suggesting enhanced chemotactic migration and engraftment of PDGFR-β⁺ MSCs into the wound. Real-Time PCR and immunostain analyses revealed that the expression of PDGF-B was upregulated after wounding; transwell migration assay showed that PDGFR-β⁺ MSCs migrated eightfold more than PDGFR-β^? MSCs toward PDGF-BB. Intriguingly, PDGFR-β⁺ MSC-treated wounds showed significantly enhanced angiogenesis compared to PDGFR-β^? MSC- or vehicle-treated wounds. Thus, our results indicate that PDGFR-β identifies a subset of MSCs with enhanced chemotactic migration to wound injury and effect in promoting angiogenesis and wound healing, implying a greater therapeutic potential for certain diseases.     

Feeding ecology of the common sun skink,Eutropis multifasciata (Reptilia: Squamata: Scincidae), in the plains of central Vietnam

We studied the feeding ecology of Eutropis multifasciata in the tropical plains of central Vietnam to understand better the foraging mode, spatiotemporal and sexual variation in dietary composition, and rarefaction curves of prey-taxon richness for males and females. Stomach contents (n = 161) were collected from October 2013 to May 2014 using a nonlethal stomach-flushing technique. A total of 680 food items (624 animal items and 56 plant items) was found in 161 stomachs of skinks, representing 19 unique animal categories. We found that the diet of E. multifasciata is composed mainly of small, sedentary and clumped prey and that this skink specialises on spiders, insect larvae, snails, grasshoppers and crickets (with a combined importance index of 60%). Dietary composition, prey size and total prey volume in E. multifasciata changed between dry and rainy seasons and among regions. The total volume of food items consumed by males was larger than that of females, and the diversity and evenness index of prey categories were larger in males than in females. However, using rarefaction curves revealed that females have the higher prey-taxon richness after points between 130 and 140 prey items for frequency, and between 160 and 170 prey items for number of items, and the differences were not statistically significant. The foraging behaviour of E. multifasciata best fits a ‘widely foraging’ model.     

The material theory of induction and the epistemology of thought experiments

John D. Norton is responsible for a number of influential views in contemporary philosophy of science. This paper will discuss two of them. The material theory of induction claims that inductive arguments are ultimately justified by their material features, not their formal features. Thus, while a deductive argument can be valid irrespective of the content of the propositions that make up the argument, an inductive argument about, say, apples, will be justified (or not) depending on facts about apples. The argument view of thought experiments claims that thought experiments are arguments, and that they function epistemically however arguments do. These two views have generated a great deal of discussion, although there hasn't been much written about their combination. I argue that despite some interesting harmonies, there is a serious tension between them. I consider several options for easing this tension, before suggesting a set of changes to the argument view that I take to be consistent with Norton's fundamental philosophical commitments, and which retain what seems intuitively correct about the argument view. These changes require that we move away from a unitary epistemology of thought experiments and towards a more pluralist position.     

On the Difficulty of Measuring Forecasting Skill in Financial Markets

The use of correlation between forecasts and actual returns is commonplace in the literature, often used as a measurement of investors' skill. A prominent application of this is the concept of the information coefficient (IC). Not only can the IC be used as a tool to rate analysts and fund managers but it also represents an important parameter in the asset allocation and portfolio construction process. Nevertheless, a theoretical understanding of it has typically been limited to the partial equilibrium context where the investing activities of each agent have no effect on other market participants. In this paper we show that this can be an undesirable oversimplification and we demonstrate plausible circumstances in which conventional empirical measurements of IC can be highly misleading. We suggest that improved understanding of IC in a general equilibrium setting can lead to refined portfolio decision making ex ante and more informative analysis of performance ex post. Copyright © 2015 John Wiley & Sons, Ltd.     

地方工科院校大学物理实验开放教学对策

内蒙古科技大学是位于中西部地区的一所以冶金、采矿、煤炭、稀土为特色的院校。做好大学期间的基础课教育是培养"上手快、留得住、后劲足"的毕业生的关键环节。以内蒙古科技大学大学物理实验示范中心为研究对象,探讨了大学物理实验课程开放教学目前存在的困难,并从选排课、物理仿真实验与考试系统、实验报告的评阅、开设实验选修课和创新性实验四个方面对实现地方工科院校的大学物理实验开放教学提出了对策。