MiR-206-mediated dynamic mechanism of the mammalian circadian clock

<p>Abstract</p> <p>Background</p> <p>As a group of highly conserved small non-coding RNAs with a length of 21~23 nucleotides, microRNAs (miRNAs) regulate the gene expression post-transcriptionally by base pairing with the partial or full complementary sequences in target mRNAs, thus resulting in the repression of mRNA translation and the acceleration of mRNA degradation. Recent work has revealed that miRNAs are essential for the development and functioning of the skeletal muscles where they are. In particular, miR-206 has not only been identified as the only miRNA expressed in skeletal muscles, but also exhibited crucial roles in regulation of the muscle development. Although miRNAs are known to regulate various biological processes ranging from development to cancer, much less is known about their role in the dynamic regulation of the mammalian circadian clock.</p> <p>Results</p> <p>A detailed dynamic model of miR-206-mediated mammalian circadian clock system was developed presently by using Hill-type terms, Michaelis-Menten type and mass action kinetics. Based on a system-theoretic approach, the model accurately predicts both the periodicity and the entrainment of the circadian clock. It also explores the dynamics properties of the oscillations mediated by miR-206 by means of sensitivity analysis and alterations of parameters. Our results show that miR-206 is an important regulator of the circadian clock in skeletal muscle, and thus by study of miR-206 the main features of its mediation on the clock may be captured. Simulations of these processes display that the amplitude and frequency of the oscillation can be significantly altered through the miR-206-mediated control.</p> <p>Conclusions</p> <p>MiR-206 has a profound effect on the dynamic mechanism of the mammalian circadian clock, both by control of the amplitude and control or alteration of the frequency to affect the level of the gene expression and to interfere with the temporal sequence of the gene production or delivery. This undoubtedly uncovers a new mechanism for regulation of the circadian clock at a post-transcriptional level and provides important insights into the normal development as well as the pathological conditions of skeletal muscles, such as the aging, chronic disease and cancer.</p

Thermal expansion and impurity effects on lattice thermal conductivity of solid argon

Thermal expansion and impurity effects on the lattice thermal conductivity of solid argon have been investigated with equilibrium molecular dynamics simulation. Thermal conductivity is simulated over the temperature range of 20 – 80 K. Thermal expansion effects, which strongly reduce thermal conductivity, are incorporated into the simulations using experimentally measured lattice constants of solid argon at different temperatures. It is found that the experimentally measured deviations from a T-1 high-temperature dependence in thermal conductivity can be quantitatively attributed to thermal expansion effects. Phonon scattering on defects also contributes to the deviations. Comparison of simulation results on argon lattices with vacancy and impurity defects to those predicted from the theoretical models of Klemens and Ashegi et al. demonstrates that phonon scattering on impurities due to lattice strain is stronger than that due to differences in mass between the defect and the surrounding matrix. In addition, the results indicate the utility of molecular dynamics simulation for determining parameters in theoretical impurity scattering models under a wide range of conditions. It is also confirmed from the simulation results that thermal conductivity is not sensitive to the impurity concentration at high temperatures

Molecular Dynamics Study of the Lattice Thermal Conductivity of Kr/Ar Superlattice Nanowires

The nonequilibrium molecular dynamics (NEMD) method has been used to calculate the lattice thermal conductivities of Ar and Kr/Ar nanostructures in order to study the effects of interface scattering, boundary scattering, and elastic strain on lattice thermal conductivity. Results show that interface scattering poses significant resistance to phonon transport in superlattices and superlattice nanowires. The thermal conductivity of the Kr/Ar superlattice nanowire is only about 1/3 of that for pure Ar nanowires with the same cross sectional area and total length due to the additional interfacial thermal resistance. It is found that nanowire boundary scattering provides significant resistance to phonon transport. As the cross sectional area increases, the nanowire boundary scattering decreases, which leads to increased nanowire thermal conductivity. The ratio of the interfacial thermal resistance to the total effective thermal resistance increases from 30% for the superlattice nanowire to 42% for the superlattice film. Period length is another important factor affecting the effective thermal conductivity of the nanostructures. Increasing the period length will lead to increased acoustic mismatch between the adjacent layers, and hence increased interfacial thermal resistance. However, if the total length of the superlattice nanowire is fixed, reducing the period length will lead to decreased effective thermal conductivity due to the increased number of interfaces. Finally, it is found that the interfacial thermal resistance decreases as the reference temperature increases, which might be due to the inelastic interface scattering

Equipo simulador de agua de lluvia para experimentos a campo en ecosistemas áridos y semiáridos

The predicted changes in precipitation patterns because of global change have profound effects on terrestrial ecosystems. In the present study, the principle and design details of a rainfall enrichment system (RAINES) for open field experiments in semi-arid and arid ecosystems are presented. The rainfall intensity, validity and uniformity of this experimental facility were also tested. During the period from 2008 to 2010, our data showed that the RAINES was able to simulate rainfall events with different rainfall sizes, frequencies and timing. The greatest advantage of the RAINES was its high uniformity in rainfall distribution over a relatively large experimental surface area (>65 m2), which was important for experimental studies of semi-arid and arid ecosystems where vegetation distribution is sparse. The rainfall validity of RAINES was steadily at 66% or higher as long as the hydraulic pressure exceeded 1.4 KPa and the wind speed was below 2.5 m s-1. Since the RAINES is light-weight, inexpensive and versatile enough to be used to simulate various rainfall events with needed properties in remote fields, it is able to provide reliable simulated rainfall in the field for studying possible responses of soil and vegetation processes to rainfall change in arid and semi-arid ecosystems. The application of the RAINES will improve our understanding on the relationship between water availability and ecosystem processes in arid and semi-arid ecosystems, which will provide useful knowledge for the protection, restoration and sustainable management of semi-arid and arid desert ecosystems worldwide.Los cambios predichos en los modelos de precipitación como resultado del cambio global tienen efectos profundos en los ecosistemas terrestres. Un equipo que simule la lluvia es una herramienta de investigación efectiva para explorar los efectos de los cambios en los modelos de lluvia sin varias restricciones naturales. En el presente estudio, se presentan los principios y detalles de diseño de un equipo simulador de lluvia (RAINES) para estudios a campo en ecosistemas áridos y semiaridos. También se determinaron la intensidad de lluvia, validez y uniformidad del RAINES. Durante el período 2008 al 2010, nuestros datos mostraron que el RAINES fue capaz de simular eventos de lluvia con diferentes cantidades, frecuencias y momentos de lluvia. La mayor ventaja del RAINES fue su gran uniformidad en la distribución de la lluvia sobre una superficie experimental relativamente grande (>65 m2 ). Esto es importante para estudios experimentales en ecosistemas áridos y semiáridos donde la distribución de la vegetación es dispersa. La validez de la lluvia provista por el RAINES fue al menos de 66% siempre y cuando la presión hidráulica excedió los 1.4 KPa y la velocidad del viento fue menor que 2.5 m s-1. El RAINES es de bajo peso, no costoso y lo suficientemente versátil como para ser usado para simular varios eventos de lluvia bajo condiciones de campo distantes. Es capaz de proveer lluvia simulada en forma confiable en el campo para estudiar la respuesta de procesos en el suelo y la vegetación a cambios en la cantidad de lluvia en ecosistemas áridos y semiáridos. El uso del RAINES mejorará nuestro entendimiento en la relación entre la disponibilidad de agua y los procesos en ecosistemas áridos y semiáridos. También proveerá conocimiento útil para la protección, restauración y menejo sustentable de ecosistemas de desierto áridos y semiáridos a escala mundial.Fil: Xin, Zhiming. Chinese Academy of Forestry; ChinaFil: Qian, Jianqiang. Henan Agricultural University; ChinaFil: Busso, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Wu, Bo. Chinese Academy of Forestry; ChinaFil: Zhu, Yajuan. Chinese Academy of Forestry; ChinaFil: Zhang, Jinxin. Chinese Academy of Forestry; ChinaFil: Li, Yonghua. Chinese Academy of Forestry; China. State Forestry Administration; ChinaFil: Lu, Qi. Chinese Academy of Forestry; China. State Forestry Administration; Chin

β-MSCs: Successful fusion of MSCs with β-cells results in a β-cell like phenotype

Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, antiapoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes. Human eGFP+ puromycin+ MSCs were co-cultured with either stably mCherryexpressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion. MSCs and fused cells were selected by puromycin treatment. With an improved fusion protocol, 29.8 ± 2.9% of all MSCs were β-MSC heterokaryons based on double positivity for mCherry and eGFP. After fusion and puromycin selection, human NKX6.1 and insulin as well as rat Neurod1, Nkx2.2, MafA, Pdx1 and Ins1 mRNA were highly elevated in fused human MSC/INS-1E cells, compared to the mixed control population. Such induction of betacell markers was confirmed in fused human MSC/human dispersed islet cells, which showed elevated NEUROD1, NKX2.2, MAFA, PDX1 and insulin mRNA compared to the mixed control. Fused cells had higher insulin content and improved insulin secretion compared to the mixed control and insulin positive beta-MSCs also expressed nuclear PDX1. We established a protocol for fusion of human MSCs and beta cells, which resulted in a beta cell like phenotype. This could be a novel tool for cell-based therapies of diabetes

Study of PBLH and Its Correlation with Particulate Matter from One-Year Observation over Nanjing, Southeast China

The Planetary Boundary Layer Height (PBLH) plays an important role in the formation and development of air pollution events. Particulate Matter is one of major pollutants in China. Here, we present the characteristics of PBLH through three-methods of Lidar data inversion and show the correlation between the PBLH and the PM2.5 (PM2.5 with the diameter 75 μg/m3 and the PM2.5 \u3c 35 μg/m3 in daytime, respectively. The low PBLH often occurs with condition of the low wind speed and high relative humidity, which will lead to high PM2.5 concentration and the low visibility. On the other hand, the stability of PBL is enhanced by high PM concentration and low visibility

Two-Phase Iteration for Value Function Approximation and Hyperparameter Optimization in Gaussian-Kernel-Based Adaptive Critic Design

Adaptive Dynamic Programming (ADP) with critic-actor architecture is an effective way to perform online learning control. To avoid the subjectivity in the design of a neural network that serves as a critic network, kernel-based adaptive critic design (ACD) was developed recently. There are two essential issues for a static kernel-based model: how to determine proper hyperparameters in advance and how to select right samples to describe the value function. They all rely on the assessment of sample values. Based on the theoretical analysis, this paper presents a two-phase simultaneous learning method for a Gaussian-kernel-based critic network. It is able to estimate the values of samples without infinitively revisiting them. And the hyperparameters of the kernel model are optimized simultaneously. Based on the estimated sample values, the sample set can be refined by adding alternatives or deleting redundances. Combining this critic design with actor network, we present a Gaussian-kernel-based Adaptive Dynamic Programming (GK-ADP) approach. Simulations are used to verify its feasibility, particularly the necessity of two-phase learning, the convergence characteristics, and the improvement of the system performance by using a varying sample set