BACKGROUND & AIMS: AIM:During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury. MATERIALS & METHODS:Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing. RESULTS:hNPs and bNCSCs form similar gaps in the glial scar, but unlike hNPs, bNCSCs contribute Mts1/S100A4 (calcium-binding protein) expression to the scar and do not assist sensory axon regeneration. CONCLUSION:bNCSC transplants contribute nonpermissive Mts1/S100A4-expressing cells to the glial scar after dorsal root avulsion.

背景与目标：

BACKGROUND & AIMS: :Social interaction is a fundamental part of our daily lives; however, exactly how our brains use social cues to determine whether to cooperate without being exploited remains unclear. In this study, we used an electroencephalography (EEG) hyperscanning approach to investigate the effect of face-to-face contact on the brain mechanisms underlying the decision to cooperate or defect in an iterated version of the Prisoner's Dilemma Game. Participants played the game either in face-to-face or face-blocked conditions. The face-to-face interaction led players to cooperate more often, providing behavioral evidence for the use of these nonverbal cues in their social decision-making. In addition, the EEG hyperscanning identified temporal dynamics and inter-brain synchronization across the cortex, providing evidence for involvement of these regions in the processing of face-to-face cues to read each other's intent to cooperate. Most notably, the power of the alpha frequency band (8-13Hz) in the right temporoparietal region immediately after seeing a round outcome significantly differed between face-to-face and face-blocked conditions and predicted whether an individual would adopt a 'cooperation' or 'defection' strategy. Moreover, inter-brain synchronies within this time and frequency range reflected the use of these strategies. This study provides evidence for how the cortex uses nonverbal social cues to determine other's intentions, and highlights the significance of power in the alpha band and inter-brain phase synchronizations in high-level socio-cognitive processing.

背景与目标： : 社交互动是我们日常生活的基本组成部分; 但是，我们的大脑究竟如何利用社交线索来确定是否在不被利用的情况下进行合作尚不清楚。在这项研究中，我们使用了脑电图 (EEG) 超扫描方法来研究面对面接触对决定在囚徒困境游戏的迭代版本中合作或缺陷的大脑机制的影响。参与者在面对面或面对面的情况下玩游戏。面对面的互动导致玩家更频繁地合作，为在社会决策中使用这些非语言提示提供了行为证据。此外，EEG的超扫描识别了整个皮层的时间动态和大脑间同步，为这些区域参与面对面提示的处理提供了证据，以读取彼此的合作意图。最值得注意的是，在看到一轮结果后立即在右侧颞顶区域的alpha频带 (8-13hz) 的功率在面对面和面对面的情况下显着不同，并预测了个人是否会采取 “合作” 或 “缺陷” 策略。此外，在此时间和频率范围内的大脑间同步反映了这些策略的使用。这项研究为大脑皮层如何使用非语言社交线索来确定他人的意图提供了证据，并强调了在高级社会认知处理中alpha带和脑间阶段同步的力量的重要性。

BACKGROUND & AIMS: :This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

背景与目标： : 本文介绍了右美托咪定 (DEX) -美托咪定的有效成分，美托咪定是啮齿动物功能磁共振成像 (fMRI) 的最新流行镇静剂-对多单位活动，局部场电位 (LFP)，脑血流 (CBF)，血管直径 [指示脑血容量 (CBV)] 和血氧水平依赖性 (BOLD) fMRI。这些测量值是在前爪刺激10 s期间从大鼠体感皮层获得的。我们发现，连续血管内全身输注DEX (50 μ g/kg/h，通常用于fMRI研究的剂量) 引起癫痫活动，并且〜0.3% 的补充异氟烷 (ISO) 给药有助于抑制癫痫活动的发展，并在长达3小时的时间内保持强大的神经元和血液动力学反应。除DEX外，补充施用N(2)O几乎消除了血液动力学反应，即使神经元活性仍然存在。在DEX ISO麻醉下，与仅ISO麻醉相比，尖峰放电速率和LFP的 δ 功率增加，而 β 和 γ 功率降低。DEX给药导致腰肌动脉和静脉几乎相等地收缩，导致基线CBF和CBV降低。诱发的LFP和CBF对前爪刺激的反应在8-10Hz的频率下最大，并且观察到非线性关系。类似地，在9.4 T处测量的BOLD fMRI响应在10 hz的频率下最大。腰肌动脉和静脉均迅速扩张 (动脉，32.2%; 静脉，5.8%)，并且静脉直径恢复到基线的速度比动脉直径慢。这些结果将有助于在DEX镇静下设计，进行和解释fMRI实验。

BACKGROUND & AIMS: OBJECTIVE:The study sought to quantify coordination of epilepsy care, over time, between neurologists and other health care providers using social network analysis (SNA). METHODS:The Veterans Health Administration (VA) instituted an Epilepsy Center of Excellence (ECOE) model in 2008 to enhance care coordination between neurologists and other health care providers. Provider networks in the 16 VA ECOE facilities (hub sites) were compared to a subset of 33 VA facilities formally affiliated (consortium sites) and 14 unaffiliated VA facilities. The number of connections between neurologists and each provider (node degree) was measured by shared epilepsy patients and tallied to generate estimates at the facility level separately within and across facilities. Mixed models were used to compare change of facility-level node degree over time across the three facility types, adjusted for number of providers per facility. RESULTS:Over the time period 2000-2013, epilepsy care coordination both within and across facilities significantly increased. These increases were seen in all three types of facilities namely hub, consortium, and unaffiliated site, relatively equally. The increase in connectivity was more dramatic with providers across facilities compared to providers within the same facilities. CONCLUSION:Establishment of the ECOE hub and spoke model contributed to an increase in epilepsy care coordination both within and across facilities from 2000 to 2013, but there was substantial variation across different facilities. SNA is a tool that may help measure coordination of specialty care.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments. RESULTS:We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. CONCLUSION:Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.

背景与目标：

BACKGROUND & AIMS: :Only a few methods permit researchers to study selected regions of the central and peripheral nervous systems with a spatial and time resolution sufficient to image the function of neural structures. Usually, these methods cannot analyse deep-brain regions and a high-resolution method, which could repeatedly probe dynamic processes in any region of the central and peripheral nervous systems, is much needed. Here, we show that fibred fluorescence microscopy-which uses a small-diameter fibre-optic probe to provide real-time images-has the spatial resolution to image various neural structures in the living animal, the consistency needed for a sequential, quantitative evaluation of axonal degeneration/regeneration of a peripheral nerve, and the sensitivity to detect calcium transients on a sub-second timescale. These unique features should prove useful in many physiological studies requiring the in situ functional imaging of tissues in a living animal.

背景与目标： : 只有少数方法允许研究人员以足以成像神经结构功能的空间和时间分辨率研究中枢和外周神经系统的选定区域。通常，这些方法无法分析脑深部区域，因此非常需要一种高分辨率的方法，该方法可以反复探测中枢和周围神经系统任何区域的动态过程。在这里，我们显示了fibred荧光显微镜-使用小直径的光纤探针提供实时图像-具有空间分辨率来成像活体动物中的各种神经结构，这是连续定量评估所需的一致性周围神经的轴突变性/再生，以及在亚秒级时间尺度上检测钙瞬变的灵敏度。这些独特的功能应在许多需要对活体动物的组织进行原位功能成像的生理研究中证明是有用的。

BACKGROUND & AIMS: :Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on alpha-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.

背景与目标： : 人们普遍认为干细胞能够替代许多疾病中丢失或受损的细胞，包括帕金森氏病 (PD)，其中黑质 (SN) 的神经元死亡，无法向纹状体提供神经递质多巴胺 (DA)。我们报告了植入1-甲基-4-苯基-1,4，2,3-四氢吡啶处理的帕金森氏灵长类动物中的未分化人类神经干细胞 (hNSCs) 存活，迁移并通过行为改善定量评估具有功能影响在这个DA-缺陷模型中，其中帕金森氏征与DA水平降低直接相关。少数hNSC后代分化为酪氨酸羟化酶 (TH) 和/或多巴胺转运蛋白 (DAT) 免疫阳性细胞，这表明受损的成年宿主SN内部和周围的微环境仍允许通过反应性祖细胞发展DA表型。发现大量不表达神经元或DA标记的hNSC衍生细胞沿持续的黑质纹状体路径排列，与宿主细胞并列。因此，这些表达DA保护因子的hNSCs可以很好地影响宿主TH细胞并介导其他稳态调节，这反映在恢复到基线内源性神经元数量与大小之比，保留现存的宿主黑质纹状体回路以及对 α-突触核蛋白聚集的正常化作用。我们建议外源性hNSCs与病理性宿主环境之间相互作用的多种模式是该PD模型中观察到的功能改善的基础。

BACKGROUND & AIMS: :Despite a growing number of splicing mutations found in hereditary diseases, utilization of aberrant splice sites and their effects on gene expression remain challenging to predict. We compiled sequences of 346 aberrant 5'splice sites (5'ss) that were activated by mutations in 166 human disease genes. Mutations within the 5'ss consensus accounted for 254 cryptic 5'ss and mutations elsewhere activated 92 de novo 5'ss. Point mutations leading to cryptic 5'ss activation were most common in the first intron nucleotide, followed by the fifth nucleotide. Substitutions at position +5 were exclusively G>A transitions, which was largely attributable to high mutability rates of C/G>T/A. However, the frequency of point mutations at position +5 was significantly higher than that observed in the Human Gene Mutation Database, suggesting that alterations of this position are particularly prone to aberrant splicing, possibly due to a requirement for sequential interactions with U1 and U6 snRNAs. Cryptic 5'ss were best predicted by computational algorithms that accommodate nucleotide dependencies and not by weight-matrix models. Discrimination of intronic 5'ss from their authentic counterparts was less effective than for exonic sites, as the former were intrinsically stronger than the latter. Computational prediction of exonic de novo 5'ss was poor, suggesting that their activation critically depends on exonic splicing enhancers or silencers. The authentic counterparts of aberrant 5'ss were significantly weaker than the average human 5'ss. The development of an online database of aberrant 5'ss will be useful for studying basic mechanisms of splice-site selection, identifying splicing mutations and optimizing splice-site prediction algorithms.

背景与目标： : 尽管遗传性疾病中发现了越来越多的剪接突变，但异常剪接位点的利用及其对基因表达的影响仍难以预测。我们汇编了346个异常5' 剪接位点 (5'ss) 的序列，这些位点被166人类疾病基因的突变激活。5'ss共识内的突变占254个隐秘的5'ss，而其他地方的突变从头激活92个5'ss。导致隐式5'ss激活的点突变最常见于第一个内含子核苷酸，其次是第五个核苷酸。位置5的取代仅是G>A跃迁，这在很大程度上归因于C/G>T/A的高变异性。然而，5位点突变的频率明显高于人类基因突变数据库中观察到的频率，这表明该位置的改变特别容易产生异常剪接，这可能是由于需要与U1和U6 snrna的顺序相互作用。最好通过适应核苷酸依赖性的计算算法而不是通过权重矩阵模型来预测隐式5'ss。将内含子5'ss与真实的对应物区分的效果不如外显子位点，因为前者本质上比后者强。外显子从头5'ss的计算预测很差，表明它们的激活主要取决于外显子剪接增强剂或消音器。异常5'ss的真实对应物明显弱于人类的平均5'ss。异常5'ss在线数据库的开发将有助于研究剪接位点选择的基本机制，识别剪接突变和优化剪接位点预测算法。

BACKGROUND & AIMS: This paper reports on the application of an artificial neural network to the clinical analysis of ophthalmological data. In particular a 2-dimensional Kohonen self-organising feature map (SOM) is used to analyse visual field data from glaucoma patients. Importantly, the paper addresses the problem of how the SOM can be utilised to accommodate the noise within the data. This is a particularly important problem within longitudinal assessment, where detecting significant change is the crux of the problem in clinical diagnosis. Data from 737 glaucomatous visual field records (Humphrey Visual Field Analyzer, program 24-2) are used to train a SOM with 25 nodes organised on a square grid. The SOM clusters the data organising the output map such that fields with early and advanced loss are at extreme positions, with a continuum of change in place and extent of loss represented by the intervening nodes. For each SOM node 100 variants, generated by a computer simulation modelling the variability that might be expected in a glaucomatous eye, are also classified by the network to establish the extent of noise upon classification. Field change is then measured with respect to classification of a subsequent field, outside the area defined by the original field and its variants. The significant contribution of this paper is that the spatial analysis of the field data, which is provided by the SOM, has been augmented with noise analysis enhancing the visual representation of longitudinal data and enabling quantification of significant class change.

背景与目标： 本文报告了人工神经网络在眼科数据临床分析中的应用。特别是二维Kohonen自组织特征图 (SOM) 用于分析青光眼患者的视野数据。重要的是，本文解决了如何利用SOM来容纳数据中的噪声的问题。在纵向评估中，这是一个特别重要的问题，在纵向评估中，检测显着变化是临床诊断问题的关键。来自737青光眼视野记录 (Humphrey视野分析仪，程序24-2) 的数据用于训练具有25个节点的SOM在方形网格上。SOM对组织输出图的数据进行聚类，以使具有早期和高级损失的字段处于极端位置，并且由中间节点表示连续的变化和损失程度。对于每个SOM节点100变体，由对青光眼眼中可能预期的可变性建模的计算机模拟生成，也由网络分类以建立分类时的噪声程度。然后，针对原始字段及其变体定义的区域之外的后续字段的分类来测量字段变化。本文的重要贡献在于，由SOM提供的现场数据的空间分析已通过噪声分析得到了增强，从而增强了纵向数据的视觉表示并能够量化重大的类别变化。

BACKGROUND & AIMS: :Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

背景与目标： : 阿托莫西汀改善健康志愿者和患有注意力缺陷/多动障碍 (ADHD) 的成年人的抑制控制和视觉处理。然而，对于长期使用阿托莫西汀治疗后这两种功能的神经相关性知之甚少。这项研究旨在使用功能磁共振成像 (fMRI) 和剑桥神经心理测试自动电池 (CANTAB) 的计数Stroop任务来研究ADHD成人与抑制性控制和视觉处理相关的变化。这项研究是一项为期8周，安慰剂对照，双盲，随机临床试验的阿托莫西汀在24名未用药的ADHD成人中进行的试验。我们使用Stroop fMRI计数和两种CANTAB测试研究了与安慰剂治疗的对应物相比，托莫西汀治疗的变化: 用于抑制控制的快速视觉信息处理 (RVP) 和用于视觉处理的延迟匹配 (DMS)。阿托莫西汀降低了右下额回和前扣带回皮层的激活，这与RVP评估的抑制性控制的改善有关。此外，阿托莫西汀增加了左前肌的激活，这与DMS评估的正确反应的平均潜伏期的改善有关。此外，治疗前的扣带回激活能够预测临床症状的改善。用阿托莫西汀治疗可以改善抑制控制以抑制干扰，并可以增强视觉处理以处理数字。此外，前扣带回皮层可能是阿托莫西汀治疗效果的生物学标记。Hum Brain Mapp 38:4850-4864，2017。©2017威利期刊公司

BACKGROUND & AIMS: :Suramin is a polyanionic compound currently used under evaluation for antineoplastic activity. One of the main problems encountered during clinical trials was an adverse neurotoxic effect, probably due to a direct cytotoxic effect on neural cells. Suramin is also known to trigger differentiation of human colon cancer cells, yet a chronic treatment induces a lysosomal storage disorder. The aim of this study was to evaluate suramin analogs for their effect: (i) on the lysosomal system of the human colon cancer cell clone HT29-D4; and (ii) on C6 glioma cell growth and morphology. One of the derivatives tested, NF036, induced terminal differentiation of HT29-D4 cells without any impairment of the lysosomal system. Furthermore, in contrast to suramin, NF036 did not alter C6 cell growth and morphology. We conclude that there is a relationship between the ability of a suramin derivative to induce a lysosomal storage disorder in human colon cancer cells and its neurotoxic effect. A double screening of suramin analogs on HT29-D4 and C6 cells allowed us to identify a new candidate antineoplastic drug: NF036.

背景与目标： : 苏拉明是目前用于抗肿瘤活性评估的聚阴离子化合物。在临床试验中遇到的主要问题之一是不良的神经毒性作用，可能是由于对神经细胞的直接细胞毒性作用所致。苏拉明还已知会触发人结肠癌细胞的分化，但长期治疗会导致溶酶体贮积障碍。这项研究的目的是评估苏拉明类似物的作用 :( i) 对人结肠癌细胞克隆HT29-D4的溶酶体系统; (ii) 对C6神经胶质瘤细胞的生长和形态。测试的衍生物之一NF036诱导了HT29-D4细胞的终末分化，而溶酶体系统没有任何损伤。此外，与苏拉明相反，NF036没有改变C6细胞的生长和形态。我们得出的结论是，苏拉明衍生物在人结肠癌细胞中诱导溶酶体贮积障碍的能力与其神经毒性作用之间存在关系。苏拉明类似物在HT29-D4和C6细胞上的双重筛选使我们能够鉴定一种新的候选抗肿瘤药物: nf036。

BACKGROUND & AIMS: :Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies might be gleaned using publicly available databases. A web-based microarray gene expression data-mining platform, Oncomine, was selected and used to determine whether QR2 may serve as a mechanistic and functional biotarget within the various CRC etiologies. We found that QR2 messenger RNA (mRNA) is overexpressed in CRC characterized by CIN, particularly in cells showing a positive KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation, as well as by the MSI but not the CIMP phenotype. Mining of Oncomine revealed an excellent correlation between QR2 mRNA expression and certain CRC etiologies. Two resveratrol-associated genes, adenomatous polyposis coli (APC) and TP53, found in CRC were further mined, using cBio portal and Colorectal Cancer Atlas which predicted a mechanistic link to exist between resveratrol→QR2/TP53→CIN. Multiple web-based data mining can provide valuable insights which may lead to hypotheses serving to guide clinical trials and design of therapies for enhanced disease prognosis and patient survival. This approach resembles a BioGPS, a capability for mining web-based databases that can elucidate the potential links between compounds to provide correlations of these interactions with specific diseases.

背景与目标： : 结直肠癌 (CRC) 是全球癌症相关死亡的主要原因。最近，据报道口服白藜芦醇 (trans-3，5,4 '-三羟基二苯乙烯) 可显着降低结直肠癌患者的肿瘤增殖，然而，关于功能连接的具体信息很少。大肠癌的发病机理和发展是一个多步骤的过程，可以使用三种表型途径进行分类，分别是染色体不稳定性 (CIN)，微卫星不稳定性 (MSI) 和CpG岛甲基化因子 (CIMP)。白藜芦醇的靶标，包括高亲和力结合蛋白醌还原酶2 (QR2)，已被确定，但有关疾病关联的信息很少。我们假设白藜芦醇与不同CRC病因之间的关系可能是使用公开可用的数据库收集的。选择了基于web的微阵列基因表达数据挖掘平台Oncomine，并将其用于确定QR2是否可以作为各种CRC病因中的机械和功能性生物目标。我们发现QR2信使RNA (mRNA) 在以CIN为特征的CRC中过表达，特别是在显示KRAS (Kirsten大鼠肉瘤病毒癌基因同源物) 突变阳性的细胞中，以及MSI但不是CIMP表型。对Oncomine的挖掘显示QR2 mRNA表达与某些CRC病因之间具有极好的相关性。使用cBio portal和结直肠癌图谱，进一步挖掘了在CRC中发现的两个与白藜芦醇相关的基因，即腺瘤性息肉病大肠杆菌 (APC) 和TP53，这预测了白藜芦醇 → QR2/TP53 → cin之间存在机械联系。基于web的多个数据挖掘可以提供有价值的见解，这些观点可能会导致指导临床试验和治疗方法设计的假设，以提高疾病的预后和患者的生存率。这种方法类似于BioGPS，这是一种挖掘基于web的数据库的功能，可以阐明化合物之间的潜在联系，以提供这些相互作用与特定疾病的相关性。

BACKGROUND & AIMS: :Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRYON) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRYON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

背景与目标： : 性二态性在人类的发育，生理和疾病中普遍存在。目前，在这些过程中，基因在Y染色体的男性特定区域 (MSY) 上的贡献尚不确定。使用转基因激活系统，人类决定性别的基因hSRY在小鼠的单细胞胚胎中被激活。hSRY激活的幼崽 (hSRYON) 的大小与未激活的对照组相似。但是，它们在出生后的生长和发育方面显着延迟，并且在两周大之前都死于多器官衰竭。病理和分子分析表明，hSRYON幼崽缺乏先天的哺乳活动，并发展为脂肪肝疾病，阻止了肺泡发育，损害了大脑的神经发生，偶尔出现了心肌纤维化，并使胸腺发育最小化。转录组分析表明，除了各自器官特有的细胞外，转基因小鼠的各种细胞生长和存活途径和功能也受到不同的影响。这些观察结果表明，位于Y位的SRY基因的异位激活可以在多个器官的发育和生理中发挥男性特异性作用，从而在受影响的个体的正常生物学功能和疾病过程中促进性二态性。

BACKGROUND & AIMS: :Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

背景与目标： : 假设记忆形成涉及学习过程中事件特定的神经活动模式的产生以及这些模式随后的自发重新激活。在这里，我们提供的证据表明，这些过程也可以在氨基甲酸酯麻醉的大鼠中观察到，并且通过尾巴捏合，皮质下卡巴胆碱输注或全身苯丙胺给药引起的不同步的大脑状态而增强。在去同步化过程中，我们发现反复的触觉或听觉刺激诱发了体感和听觉皮层中神经放电的独特顺序模式，并且这些模式随后在随后的自发活动中再次发生，类似于我们在清醒动物中观察到的情况。此外，这些模式的形成被NMDA受体拮抗剂阻断，表明该现象取决于突触可塑性。这些结果表明，大脑状态不同步的麻醉动物可以作为研究刺激诱导的可塑性的方便模型，以提高我们对大脑中记忆形成和重放的理解。

BACKGROUND & AIMS: :Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice. The microglia exhibited an activated M1 phenotype consistent with their potential to inhibit differentiation of FIP200-null NSCs. Blocking either microglia infiltration or activation rescued the deficient differentiation of FIP200-null NSCs from FIP200;p53hGFAP 2cKO mice. Lastly, we showed that increased chemokine expression in FIP200-null NSCs was induced by abnormal p62 aggregate formation and activation of NF-κB signaling. Our results suggest that autophagy plays a crucial role in regulating neurogenesis and restricting local immune response in postnatal NSCs through non-cell autonomous mechanisms.

背景与目标： : 最近的研究表明，自噬基因在调节不同组织干细胞 (包括神经干/祖细胞 (NSCs)) 中的重要作用。然而，对于自噬是否可以通过细胞外源性机制调节NSCs知之甚少。在这里，我们显示nsc中必需的自噬基因FIP200的缺失以p53-independent的方式增加了Ccl5和Cxcl10的表达，介导了小胶质细胞向FIP200hGFAP条件性敲除 (cKO) 和FIP200的脑室下区的浸润增加; p53hGFAP 2cKO小鼠。小胶质细胞表现出与它们抑制FIP200-null NSCs分化的潜力一致的活化M1表型。阻断小胶质细胞的浸润或激活挽救了FIP200;p53hGFAP 2cKO小鼠中FIP200-null NSCs的分化不足。最后，我们发现FIP200-null NSCs中趋化因子表达增加是由异常p62聚集形成和NF-κ b信号激活诱导的。我们的结果表明，自噬通过非细胞自主机制在调节神经发生和限制出生后NSCs局部免疫反应中起着至关重要的作用。