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.     

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。     

Community Work Research through Co-Operative Inquiry in Timor-Leste,Australia and Peru: Insights into Process

Co-operative inquiry is an under-explored method in community-based research. Its democratic approach involves a group of “co-researchers” collaboratively inquiring into a mutually-agreed research topic through systematic cycles of reflection and action. This article shares the process, outcomes, and methodological reflections of three co-operative inquiries that were conducted as part of an international study regarding love in community work. Groups of up to 10 community workers in rural villages in Timor-Leste, Australia, and Peru engaged in co-operative inquiry to collaboratively develop new knowledge to inform practice. The article analyses data regarding co-inquirer experiences of the methodology, and identifies the strengths and challenges of the co-operative inquiry method to support the collective generation of new knowledge. The article concludes that co-operative inquiry involves shared power, participation, action, and contextual reflexivity, and is a useful method for community workers to collaboratively develop innovative approaches to community work practice through cycles of reflection and action.     

Friction-stir-welded overaged 7020-T6 alloy joint: an investigation on the effect of rotational speed on the microstructure and mechanical properties

Commercial A7020-T6 plates in the overaged state were subjected to friction stir welding with four different tool rotational speeds of 500, 710, 1000, and 1400 r/min and a single traverse feed rate of 40 mm/min. The resultant changes in the welding heat input, microstructure, and the mechanical properties of the joints were investigated. The changes were related to the processes of growth, dissolution, and re-formation of precipitates. The precipitate evolution was examined by differential scanning calorimetry, and the microstructural analysis was conducted using optical, scanning, and transmission electron microscopes. The results showed that the grain size in the stirred zone(SZ) decreased substantially compared with the base metal, but increased with tool rotational speed because of the rise in temperature. We found that the width of the heat-affected zone increased with tool rotational speed. The hardness and the tensile strength in the SZ increased with increasing heat input compared with the base metal in the overaged condition. This recovery in mechanical properties of the joints can be attributed to the dissolution and re-formation of precipitates in the SZ and the thermomechanically affected zone. This process is referred to as an "auto-aging treatment."     

(In)consistency of airsea heat flux estimates; ocean heat uptake anomalies and top of atmosphere radiation budgets

This paper introduces the consistency between top of atmosphere （TOA） imbalances and ocean heat uptake, and the inconsistency between ocean heat uptake estimates and flux climatologies, and then gives some recommendations and outlook.