Transmission of new CRF07_BC Strains with 7 amino acid deletion in Gag p6

A 7 amino acid deletion in Gag p6 (P6delta7) emerged in Chinese prevalent HIV-1 strain CRF07_BC from different epidemic regions. It is important to determine whether this mutation could be transmitted and spread. In this study, HIV-1 Gag sequences from 5 different epidemic regions in China were collected to trace the transmission linkage and to analyze genetic evolution of P6delta7 strains. The sequence analysis demonstrated that P6delta7 is a CRF07_BC specific deletion, different P6delta7 strains could be originated from different parental CRF07_BC recombinants in different epidemic regions, and the transmission of P6delta7 strain has occurred in IDU populations. This is for the first time to identify the transmission linkage for P6delta7 strains and serves as a wake-up call for further monitoring in the future; In addition, P6delta7 deletion may represent an evolutionary feature which might exert influence on the fitness of CRF07_BC strain

Direct conversion of astrocytes into neuronal cells by drug cocktail

Direct conversion of astrocytes into neuronal cells by drug cocktail Cell Research advance online publication 2 October 2015; doi:10.1038/cr.2015.120 Dear Editor, Neurological disorder is one of the greatest threats to public health according to the World Health Organization. Because neurons have little or no regenerative capacity, conventional therapies for neurological disorders yielded poor outcomes. While the introduction of exogenous neural stem cells or neurons holds promise, many challenges still need to be tackled, including cell resource, delivery strategy, cell integration and cell maturation. Reprogramming of fibroblasts into induced pluripotent stem cells or directly into desirable neuronal cells by transcription factors (TFs) or small molecules can solve some problems, but other issues remain to be addressed, including safety, conversion efficiency and epigenetic memory [1, 2]. Astrocytes are considered to be the ideal starting candidate cell type for generating new neurons, due to their proximity in lineage distance to neurons and ability to proliferate after brain damage. Many studies have already revealed that astrocytes of the central nervous system can be reprogrammed into induced neuronal cells by virus-mediated overexpression of specific TFs in vitro and in vivo [3-6]. However, application of this virus-mediated direct conversion is still limited due to concerns on clinical safety. We have previously reported direct conversion of somatic cells into neural progenitor cells (NPCs) in vitro by cocktail of small molecules under hypoxia [7]. Here we set out to explore whether astrocytes can be induced into neuronal cells by the chemical cocktail in vitro

Generation and Bioenergetic Profiles of Cybrids with East Asian mtDNA Haplogroups

Human mitochondrial DNA (mtDNA) variants and haplogroups may contribute to susceptibility to various diseases and pathological conditions, but the underlying mechanisms are not well understood. To address this issue, we established a cytoplasmic hybrid (cybrid) system to investigate the role of mtDNA haplogroups in human disease; specifically, we examined the effects of East Asian mtDNA genetic backgrounds on oxidative phosphorylation (OxPhos). We found that mtDNA single nucleotide polymorphisms such as m.489T>C, m.10398A>G, m.10400C>T, m.C16223T, and m.T16362C affected mitochondrial function at the level of mtDNA, mtRNA, or the OxPhos complex. Macrohaplogroup M exhibited higher respiratory activity than haplogroup N owing to its higher mtDNA content, mtRNA transcript levels, and complex III abundance. Additionally, haplogroup M had higher reactive oxygen species levels and NAD+/NADH ratios than haplogroup N, suggesting difference in mitonuclear interactions. Notably, subhaplogroups G2, B4, and F1 appeared to contribute significantly to the differences between haplogroups M and N. Thus, our cybrid-based system can provide insight into the mechanistic basis for the role of mtDNA haplogroups in human diseases and the effect of mtDNA variants on mitochondrial OxPhos function. In addition, studies of mitonuclear interaction using this system can reveal predisposition to certain diseases conferred by variations in mtDNA

Hot isostatic pressing of in-situ TiB/Ti-6Al-4V composites with novel reinforcement architecture, enhanced hardness and elevated tribological properties

In this study, titanium borides reinforced Ti-6Al-4V composites have been successfully prepared by hot isostatic pressing (HIPing). The microstructure of the as-fabricated samples was investigated using X-ray diffraction technique, secondary electron microscopy and electron backscatter diffraction and the mechanical properties evaluated through micro-hardness and wear resistance measurements together with nano-indentation. It was found that during HIPing the additive particles TiB2 have transformed into TiB needles which tend to decorate at prior particle boundaries of the consolidated powder particles to form a network structure. Under the same HIPing condition, the needles became increasingly coarser and agglomerated with increased addition of TiB2. The micro-hardness of the synthesized materials increased with increased volume fraction of TiB. Nano-indentation measurement demonstrates that the TiB network structure shows much higher nanohardness than the surrounding matrix regions. The friction coefficient of the synthesized composites decreased continuously with increased volume fraction of TiB, indicating improved wear resistance. High resolution transmission electron microscopy analysis on wear debris revealed the formation of a series of oxides suggesting that chemical reaction between alloy elements and oxygen in air may have happened. It is thus believed that the wearing of the current samples is a result of both friction and chemical reaction

Chaos Suppression of an Electrically Actuated Microresonator Based on Fractional-Order Nonsingular Fast Terminal Sliding Mode Control

This paper focuses on chaos suppression strategy of a microresonator actuated by two symmetrical electrodes. Dynamic behavior of this system under the case where the origin is the only stable equilibrium is investigated first. Numerical simulations reveal that system may exhibit chaotic motion under certain excitation conditions. Then, bifurcation diagrams versus amplitude or frequency of AC excitation are drawn to grasp system dynamics nearby its natural frequency. Results show that the vibration is complex and may exhibit period-doubling bifurcation, chaotic motion, or dynamic pull-in instability. For the suppression of chaos, a novel control algorithm, based on an integer-order nonsingular fast terminal sliding mode and a fractional-order switching law, is proposed. Fractional Lyapunov Stability Theorem is used to guarantee the asymptotic stability of the system. Finally, numerical results with both fractional-order and integer-order control laws show that our proposed control law is effective in controlling chaos with system uncertainties and external disturbances

Comparative proteomic analysis reveals alterations in development and photosynthesis-related proteins in diploid and triploid rice

Six pairs of primers were designed for gene-specific transcript amplification. (DOC 25 kb

Audio-Visual Spatiotemporal Perceptual Training Enhances the P300 Component in Healthy Older Adults

In older adults, cognitive abilities, such as those associated with vision and hearing, generally decrease with age. According to several studies, audio-visual perceptual training can improve perceived competence regarding visual and auditory stimuli, suggesting that perceptual training is effective and beneficial. However, whether audio-visual perceptual training can induce far-transfer effects in other forms of untrained cognitive processing that are not directly trained in older adults remains unclear. In this study, the classic P300 component, a neurophysiological indicator of cognitive processing of a stimulus, was selected as an evaluation index of the training effect. We trained both young and older adults on the ability to judge the temporal and spatial consistency of visual and auditory stimuli. P300 amplitudes were significantly greater in the posttraining session than in the pretraining session in older adults (P = 0.001). However, perceptual training had no significant effect (P = 0.949) on the P300 component in young adults. Our results illustrate that audio-visual perceptual training can lead to far-transfer effects in healthy older adults. These findings highlight the robust malleability of the aging brain, and further provide evidence to motivate exploration to improve cognitive abilities in older adults

Hot isostatic pressing of in-situ TiB/Ti-6Al-4V composites with novel reinforcement architecture, enhanced hardness and elevated tribological properties

In this study, titanium borides reinforced Ti-6Al-4V composites have been successfully prepared by hot isostatic pressing (HIPing). The microstructure of the as-fabricated samples was investigated using X-ray diffraction technique, secondary electron microscopy and electron backscatter diffraction and the mechanical properties evaluated through micro-hardness and wear resistance measurements together with nano-indentation. It was found that during HIPing the additive particles TiB2 have transformed into TiB needles which tend to decorate at prior particle boundaries of the consolidated powder particles to form a network structure. Under the same HIPing condition, the needles became increasingly coarser and agglomerated with increased addition of TiB2. The micro-hardness of the synthesized materials increased with increased volume fraction of TiB. Nano-indentation measurement demonstrates that the TiB network structure shows much higher nanohardness than the surrounding matrix regions. The friction coefficient of the synthesized composites decreased continuously with increased volume fraction of TiB, indicating improved wear resistance. High resolution transmission electron microscopy analysis on wear debris revealed the formation of a series of oxides suggesting that chemical reaction between alloy elements and oxygen in air may have happened. It is thus believed that the wearing of the current samples is a result of both friction and chemical reaction

Dynamic modeling and structural optimization of a bistable electromagnetic vibration energy harvester

A novel bistable electromagnetic vibration energy harvester (BEMH) is constructed and optimized in this study, based on a nonlinear system consisting mainly of a flexible membrane and a magnetic spring. A large-amplitude transverse vibration equation of the system is established with the general nonlinear geometry and magnetic force. Firstly, the mathematical model, considering the higher-order nonlinearities given by nonlinear Galerkin method, is applied to a membrane with a co-axial magnet mass and magnetic spring. Secondly, the steady vibration response of the membrane subjected to a harmonic base motion is obtained, and then the output power considering electromagnetic effect is analytically derived. On this basis, a parametric study in a broad frequency domain has been achieved for the BEMH with different radius ratios and membrane thicknesses. It is demonstrated that model predictions are both in close agreement with results from the finite element simulation and experiment data. Finally, the proposed efficient solution method is used to obtain an optimizing strategy for the design of multi-stable energy harvesters with the similar flexible structure

High-Throughput Functional MicroRNAs Profiling by Recombinant AAV-Based MicroRNA Sensor Arrays

BACKGROUND: microRNAs (miRNAs) are small and non-coding RNAs which play critical roles in physiological and pathological processes. A number of methods have been established to detect and quantify miRNA expression. However, method for high-throughput miRNA function detection is still lacking. PRINCIPAL FINDINGS: We describe an adeno-associated virus (AAV) vector-based microRNA (miRNA) sensor (Asensor) array for high-throughput functional miRNA profiling. Each Asensor contains a Gaussia luciferase (Gluc) and a firefly luciferase (Fluc) expression cassette to sense functional miRNA and to serve as an internal control respectively. Using this array, we acquired functional profiles of 115 miRNAs for 12 cell lines and found "functional miRNA signatures" for several specific cell lines. The activities of specific miRNAs including the let-7 family, miR-17-92 cluster, miR-221, and miR-222 in HEK 293 cells were compared with their expression levels determined by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). We also demonstrate two other practical applications of the array, including a comparison of the miRNA activity between HEK293 and HEK293T cells and the ability to monitor miRNA activity changes in K562 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). CONCLUSIONS/SIGNIFICANCE: Our approach has potential applications in the identification of cell types, the characterization of biological and pathological processes, and the evaluation of responses to interventions