Profilin1 biology and its mutation,actin(g) in disease

Profilins were discovered in the 1970s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to amyotrophic lateral sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we will discuss the implications of mutant profilin1 in various diseases with an emphasis on its contribution to the pathogenesis of ALS.     

基于土性相关蒙特卡罗法的争岗滑坡堆积体可靠性分析

针对澜沧江古水水电站争岗滑坡堆积体工程地质务件,在室内剪切试验、工程类比、参数反演基础上综合确定了岩土体力学参数及其统计分布规律.采用基于黏聚力c与内摩擦角φ相关抽样下的蒙特卡罗法对堆积体典型剖面进行了多种工况下的可靠性分析,预测了其未来的变形失稳特征.研究结果表明:当前堆积体B-B'剖面在正常运行工况下的破坏概率为2...     

Modelling the long QT syndrome with induced pluripotent stem cells

The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.     

核能谱与两类转动惯量的精确表达式

用最小二乘拟合法,将稀土区的能谱实验数据,拟合不同的能谱公式,从而证明E=a〔(1+bI(I+1))~(1/2)-1〕是符合得较好的,本文还推导了与上述能谱相应的两类转动惯量,并以此与实验计算值进行比较,结果仍很满意.     

Accelerated carbonation and leaching behavior of the slag from iron and steel making industry

Ground granulated blast furnace slag(GGBFS)and steelmaking slag have been used as a raw material for cement production or as an aggregate to make concrete,which contribute aluminum,calcium,iron,and silicon oxides.The suitability of the slag for a particular application depends on its reactivity,cost,availability,and its influence on the properties of the resulting concrete.For the interest of durability studying of concrete in the presence of slag,the accelerated carbonation products and leaching behavior of the slag and Portland cement(PC)were studied.The experimental results confirmed that the slag was more resistant to carbonation compared to PC.The carbonation degree of GGBFS reduced by 17.74%;and the carbonation degrees of steelmaking slags reduced by 9.51%-11.94%.Carbonation neutralized the alkaline nature of the hydrated pastes and gave rise to the redox potential of the leachate slightly(30-77 mV).The carbonation also increased the release of most of the elements presented,except for calcium,to the aqueous environment.It is concluded that blend cements(PC plus slag)have economical advantages and better durability compared to PC.     

Effect of polyalkyl polyphosphonates on bone development in young rats

Zusammenfassung Es wird gezeigt, dass Knochenentwicklung junger Ratten durch Behandlung mit Polyethylen-Polyphosphonat ohne toxische Wirkung verhindert wird. Die Polyphosphonate wirken direkt auf den Knochen und können eventuell verschiedene klinische Anwendungen finden.

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Supported by Public Health Grant No. GM 17367-01.     

Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors

One of the central aims of ecology is to identify mechanisms that maintain biodiversity. Numerous theoretical models have shown that competing species can coexist if ecological processes such as dispersal, movement, and interaction occur over small spatial scales. In particular, this may be the case for non-transitive communities, that is, those without strict competitive hierarchies. The classic non-transitive system involves a community of three competing species satisfying a relationship similar to the children's game rock-paper-scissors, where rock crushes scissors, scissors cuts paper, and paper covers rock. Such relationships have been demonstrated in several natural systems. Some models predict that local interaction and dispersal are sufficient to ensure coexistence of all three species in such a community, whereas diversity is lost when ecological processes occur over larger scales. Here, we test these predictions empirically using a non-transitive model community containing three populations of Escherichia coli. We find that diversity is rapidly lost in our experimental community when dispersal and interaction occur over relatively large spatial scales, whereas all populations coexist when ecological processes are localized.     

'Inverse' melting of a vortex lattice

Inverse melting is the process in which a crystal reversibly transforms into a liquid or amorphous phase when its temperature is decreased. Such a process is considered to be very rare, and the search for it is often hampered by the formation of non-equilibrium states or intermediate phases. Here we report the discovery of first-order inverse melting of the lattice formed by magnetic flux lines in a high-temperature superconductor. At low temperatures, disorder in the material pins the vortices, preventing the observation of their equilibrium properties and therefore the determination of whether a phase transition occurs. But by using a technique to 'dither' the vortices, we were able to equilibrate the lattice, which enabled us to obtain direct thermodynamic evidence of inverse melting of the ordered lattice into a disordered vortex phase as the temperature is decreased. The ordered lattice has larger entropy than the low-temperature disordered phase. The mechanism of the first-order phase transition changes gradually from thermally induced melting at high temperatures to a disorder-induced transition at low temperatures.     

Decreased serum responsiveness by primary monolayer cultures of preneoplastic and neoplastic mammary epithelial cells

Monolayer cultures of normal, preneoplastic and neoplastic murine mammary epithelial cells were exposed to various types of mammalian serum. A progressive decline in levels of thymidine incorporation together with a change in the ordering of sera which stimulates optimal incorporation was observed in the transformed cells.