Abstract:揭示脑的奥秘是人类面临的最大挑战之一。神经元是构成神经系统结构与功能的基本单位。神经元与神经元之间通过突触实现信息交互，并构成神经环路或神经网络。神经环路有局部的，也有跨脑区或长程的，甚至全脑尺度的。神经环路则是脑实现神经信息处理的基本单元。若干神经环路构成脑网络。脑网络研究已经成为脑功能与脑疾病研究领域的热点。
在国家自然科学基金委员会和科技部“973计划”等项目的支持下，我国科学家在这一领域已经开展了卓有成效的工作。2011年第393次香山科学会议“脑网络组及其临床应用的前沿科学问题”曾对此进行过比较深入的研讨。为促进对该领域现状及发展的了解，本期汇集了2篇述评和2篇研究论文，作为脑成像与脑网络专题发表，以飨读者。
利用9.4T功能磁共振成像(fMRI)获得轻度麻醉状态下大鼠静息状态及刺激激活的数据，通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数，赖永秀等人报道了大鼠感觉运动系统静息态脑网络的研究成果，发现感觉运动系统在静息态时的脑网络具有小世界属性。
扩散磁共振成像(dMRI)的出现为大脑结构与功能研究提供了全新的检测手段，雷皓等报道了小动物高分辨扩散磁共振成像数据分析方法，为小动物脑dMRI研究提供了统一图像模板与完善的计算方法，对于检测神经纤维微观结构的变化，以及临床诊断，将具有极其重要的意义。
神经环路功能变化的实时在体监测是研究脑网络不可或缺的手段，曾绍群等评述了基于声光偏转器的快速无惯性随机扫描双光子显微成像技术的研究进展及发展趋势，指出该技术的进一步发展将为神经活动观测提供一种全新的方法，从而极大地推动脑科学研究的发展。
针对哺乳动物全脑的神经元网络成像，龚辉等从空间分辨率、探测范围、数据配准和成像速度等方面评述了光学显微水平全脑成像方法的研究进展，并讨论所面临的挑战。他们指出，要在全脑尺度获取突起水平分辨率的结构与功能数据，光学成像方法最为成熟。华中科技大学研制的MOST系统，率先获得了一系列高分辨率的完整大脑解剖数据集，该成果将在神经元网络的构建和脑功能与疾病研究中发挥重要作用。
我们期待更多、更好的有关脑成像与脑网络的论文发表，以更广泛和深入地促进我国脑科学研究领域的学术交流。

Abstract:One of the basic goals of modern neuroscience is to study the brain-wide complex neural network of mammals' brain. Because of the technological limitations, the traditional tools can only study the local circuits of the higher animals or the small brain network of the lower animals. Here we review recent efforts to resolve the contradiction between large specimen and high-resolution, and some of them have been applied to image the neural network in mammals' whole brain. We focus on some technology index includes spatial resolution, detection range, data registration and throughput, and also discuss the challenges of the emerging methods.

Abstract:Two-photon microscope has become an important instrument in neuroscience research. However, the current commercial instruments can hardly meet the need for the detection of neural signal in millisecond scale due to their low imaging rates. Fast random-access two-photon microscopy based on acousto-optic deflector (AOD) has the potential for increasing the observation speed while maintaining adequate signal to noise ratio (SNR). We summarize the latest related research progress. It is demonstrated from four parts, including the spatio-temporal evolution theory of the femtosecond laser after passing the angular dispersion devices, dispersion compensation method for AOD, random-access two-photon microscopy instrument, and calcium signal identification method in the instrument applications. In the end, the future development trends for random-access two-photon microscopy are discussed. The systematic and in-deep research on this technology will provide a new tool for the neural activity observation and boost the development of brain science.

Abstract:Diffusion magnetic resonance imaging (dMRI) is a non-invasive imaging technique capable of characterizing the diffusion properties of water molecules in vivo and detecting microstructural changes in brain tissue. It provides new tools to investigate the integrity of brain white matter. Although dMRI is widely used in clinical studies, and has become a common method in clinical radiology, it is infrequently used in preclinical brain imaging studies on small animal models. In this paper, we implemented computational methods for small animal dMRI. First, a high-resolution dMRI template for rat was constructed. Secondly, voxel-based analysis and tract-based spatial statistics methods for small animal dMRI were implemented. Last but not least, the deterministic and probabilistic tractography methods for small animal imaging were implemented. The implementation of these methods will facilitate the applications of dMRI in preclincal small animal imaging.

Abstract:In order to better understand functional connectivity of rodent brain, we analyzed the functional magnetic resonance imaging (fMRI) data of the resting-state and forepaw electrical stimulation from lightly anesthetized rat at 9.4 T using cross-correlation analysis. The results showed that the primary somatosensory cortex (S1) and thalamus(Tha) were significantly positively activated, the caudate putamen nucleus(CPu) was significantly negatively activated during forepaw stimulation. The higher connectivity bilateral intra-sensory/motor cortices and bilateral intra- thalamus, but lower connectivity between sensory/motor cortex and thalamus were found during the resting state. Synchronized low frequency fluctuation (LFF) was observed between functionally related brain regions. In addition, the brain network of sensorimotor system showed small-world feature during resting-state. These results suggested that rodents have some similar properties with human in functional separation and integration during brain information processing, and strongly support the view that the underlying physiology of CNS is conserved across mammalian species.

Abstract:Myxobacteira are noted for their capabilities of synthesizing series of natural products with diverse structures and novel functions. Modular polyketide synthase (PKS) and non ribosomal peptide synthetase (NRPS) are the major natural products of myxobacteria. Compared to classical modular PKS/NRPS, myxobacteria modular PKSs/NRPSs usually show novel assembly features, exhibiting diverse genetic assembly potential and abundant product structure varieties. This review classified novel characters of Myxobacterial PKSs/NRPSs assembly lines and further illustrated their corresponding structure features, revealed their vital and potential in genetics, biochemistry, combination biosynthesis, evolution and drug research areas, and also forecasted their opportunities coming with genome era.

Abstract:Injury of peripheral nerve is very common in trauma, which easily causes partial or whole damage to peripheral nerves and will further result in function loss or other neurological diseases. With the development of technology, the treatment efficacy of peripheral nerve injury has been improved significantly. However, it is still very difficult to obtain the morpgologic and functional regeneration. Slow rates of nerve regeneration and functional recovery are still the difficulty in clinics. Electrical stimulation is convenient, non-invasive and with few side effects. More and more researchers have paid attention to using stem cells combined with electrical stimulation to repair injured peripheral nerve. In this study, the applications and advancement of using stem cells combined with electrical stimulation in injured peripheral nerve regeneration were comprehensively reviewed. The possible mechanisms of them were further discussed. Particularly, the difficulties of using stem cells combined with electrical stimulation to repair injured peripheral nerve were analyzed. Prospect along this direction was also discussed.

Abstract:Sialyl-Tn (sTn) is a tumor-associated carbohydrate antigen overexpressed in many carcinomas. But whether it is expressed in neoplastic human endometrium is controversial. Here we screened 111 clinical samples including 82 endometrial cancers, 16 atypical hyperplastic and 13 normal endometria, by immunohistochemistry using a novel anti-sTn antibody, namely 3P9. Our results showed that the expression of sTn in the endometrial carcinoma was significantly higher (76%) than that in normal tissues (31%) (P < 0.01) and in atypical hyperplasia (44%) (P < 0.05). Importantly, we found that sTn expression in typeⅠ carcinoma (80%) was obviously higher than that in typeⅡ(45%) (P < 0.05). These results suggested that sTn may be a biomarker for endometrial carcinoma, especially for typeⅠcarcinoma. Moreover, we observed that sTn expression was increased with the decline of tumor histological grade (P < 0.05), indicating that sTn was associated with a favorable prognosis in endometrial carcinoma.

Abstract:Rim is an active zone protein which is suggested to be involved in the regulation of vesicle exocytosis and synaptic plasticity. The C. elegans genome encodes only one Rim gene, unc-10. In this study, we demonstrate that UNC-10 is involved in the dense core vesicle (DCV) exocytosis in C. elegans neurons. We find that unc-10 mutants exhibit reduced peptide release in vivo. In IDA-1::GFP labelled ALA neurons, which serve as a good model for studying DCV exocytosis, mutations of UNC-10 lead to a visible reduction of the readily released pool (RRP) size. The analysis of vesicular docking by total internal reflection fluorescence microscopy (TIRFM) reveals that the loss of function of unc-10 hinders the docking of DCVs in neurons. The above results provide evidence that UNC-10 is required for the exocytosis of DCVs and may be involved in the docking step of DCV release.

Abstract:Many studies have demonstrated that Sirtuin 1, an NAD⁺-dependent deacetylase, reduces apoptosis in several different cells. However, the role of Sirtuin 1 in apoptosis of disc nucleus pulposus (NP) cells remains unclear. The present study was performed to determine whether degenerative human NP would express Sirtuin 1, and to investigate the role of Sirtuin 1 in NP cells apoptosis. Here we show that Sirtuin 1 mRNA and protein levels in disc NP from patients (< 25 years) with lumbar vertebra fracture (LVF) are greater than those in degenerative disc NP from patients (> 55 years) with lumbar disc herniation (LDH). The rate of apoptosis was far fewer in resveratrol-treated NP cells than that in siRNA transfected or nicotinamide-treated NP cells. We also tried to explore the signaling molecules that mediate the protective property of Sirtuin 1 by Western blot and inhibitor analysis. After Sirtuin 1 siRNA transfected, NP cells decreased phosphorylation of Akt, while resveratrol phosphorylated Akt. Treatment with LY294002 or Akt siRNA increased the rate of apoptosis. Our results indicate that Sirtuin 1 plays a critical role in survival of degenerative human NP cells through the Akt anti-apoptotic signaling pathway.

Abstract:Rosiglitazone, a PPARγ thiazolidinediones (TZDs) agonist, has been proposed to have neuroprotective effects in the central nervous system (CNS). However, the mechanisms underlying the beneficial effects of rosiglitazone are unclear. In the present study, primary cultured hippocampal neurons of 1-day-old wistar rats were transfected with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on day 5 in vitro (DIV5) to display the morphological details of the dendrites and dendritic protrusions. Different doses of rosiglitazone (5, 10 and 20 μmol/L) or 20 μmol/L rosiglitazone with the presence of 5 μmol/L GW9662, an antagonist of PPARγ, were applied to neurons for 24 h at DIV6. Live-cell imaging technology was used to investigate the effects of rosiglitazone on the development of dendritic filopodia and dendritic tree in hippocampal neurons at DIV7. Our results have shown that rosiglitazone increased the density of dendritic filopodia in a dose-dependent manner. The filopodia density of cultured neurons in 10 μmol/L ((34.27 ± 2.12)/100 μm, n = 21) and 20 μmol/L ((37.75 ± 2.09)/100 μm, n=21) rosiglitazone treated group was significantly increased compared with those of control group((26.45±1.47)/100 μm, n=21), but the filopodia density of cultured neurons in 5 μmol/L rosiglitazone treated group ((27.66 ± 1.84)/100 μm, n=20) was not significantly altered compared with those of control group. Rosiglitazone treatment of 5, 10 and 20 μmol/L concentrations has no effect on the length and motility of dendritic filopodia. In addition, neither the length nor the number of dendritic branches was altered by treatment of 5, 10 and 20 μmol/L rosiglitazone. 5 μmol/L GW9662 attenuated the increased filopodia density induced by 20 μmol/L rosiglitazone. These results suggest that rosiglitazone may affect the initial stage of hippocampal neuron development through the PPARγ pathway. This may be a possible mechanism of the neuroprotective effects of rosiglitazone.

Abstract:In this paper, a novel scale-free network construction algorithm based on reconnection method was proposed. The regulatory node of the new node will be reselected according to the reconnection method. The probability of reconnection depends on the gamma in the power-law distribution model parameters. The constructed network with our algorithm was used for simulating gene expression profiles using differential equation model with two heuristic search algorithms, GA and PSO, and new algorithm GFA to optimize the criterion. The candidate old node can be selected as regulatory node based on the number of links the old node already has. The network in the experiment was testified using log-log graph. And the simulated gene expression profiles were also tested with three different well developed algorithms' software available free from internet by reconstructing the network. PPV and Se of the links were calculated and visualized. A part of the results and the full version program written by java could be downloaded from our website: http://ccst.jlu.edu.cn/CSBG/ourown/.