Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production

Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.     

The temporal response of the brain after eating revealed by functional MRI

After eating, the human brain senses a biochemical change and then signals satiation, but precisely when this occurs is unknown. Even for well-established physiological systems like glucose-insulin regulation, the timing of interaction between hormonal processes and neural events is inferred mostly from blood sampling. Recently, neuroimaging studies have provided in vivo information about the neuroanatomical correlates of the regulation of energy intake. Temporal orchestration of such systems, however, is crucial to the integration of neuronal and hormonal signals that control eating behaviour. The challenge of this functional magnetic resonance imaging study is to map not only where but also when the brain will respond after food ingestion. Here we use a temporal clustering analysis technique to demonstrate that eating-related neural activity peaks at two different times with distinct localization. Importantly, the differentiated responses are interacting with an internal signal, the plasma insulin. These results support the concept of temporal parcellation of brain activity, which reflects the different natures of stimuli and responses. Moreover, this study provides a neuroimaging basis for detecting dynamic processes without prior knowledge of their timing, such as the acute effects of medication and nutrition in the brain.     

Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells

Antagonistic activities of glucagon and insulin control metabolism in mammals, and disruption of this balance underlies diabetes pathogenesis. Insulin-producing cells (IPCs) in the brain of insects such as Drosophila also regulate serum glucose, but it remains unclear whether insulin is the sole hormonal regulator of glucose homeostasis and whether mechanisms of glucose-sensing and response in IPCs resemble those in pancreatic islets. Here we show, by targeted cell ablation, that Drosophila corpora cardiaca (CC) cells of the ring gland are also essential for larval glucose homeostasis. Unlike IPCs, CC cells express Drosophila cognates of sulphonylurea receptor (Sur) and potassium channel (Ir), proteins that comprise ATP-sensitive potassium channels regulating hormone secretion by islets and other mammalian glucose-sensing cells. They also produce adipokinetic hormone, a polypeptide with glucagon-like functions. Glucose regulation by CC cells is impaired by exposure to sulphonylureas, drugs that target the Sur subunit. Furthermore, ubiquitous expression of an akh transgene reverses the effect of CC ablation on serum glucose. Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells.     

Central nervous system control of food intake

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.     

Microenvironmental regulation of stem cells in intestinal homeostasis and cancer

The identification of intestinal stem cells as well as their malignant counterparts, colon cancer stem cells, has undergone rapid development in recent years. Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and the microenvironment. These interactions regulate the astonishingly rapid renewal of the intestinal epithelial layer, which consequently puts us at serious risk of developing cancer. Here we highlight the microenvironment-derived signals that regulate stem-cell fate and epithelial differentiation. As our understanding of normal intestinal crypt homeostasis grows, these developments may point towards new insights into the origin of cancer and the maintenance and regulation of cancer stem cells.     

脑机接口的伦理问题及对策

 随着神经科学对人脑信息编码和加工机制的深入揭示以及脑机接口技术的日益革新，脑机接口的范围和精度得到了快速扩大和提升，应用场景也越来越广泛。伴随着技术与应用的发展，潜在的伦理问题逐渐暴露。本文结合脑机接口研究进展，分析其可能存在的安全、隐私、公平及自由意志等问题，提出降低伦理风险、让脑机接口更好地服务人类的建议。     

基于ANN与ES混合系统的银行贷款风险预警研究

鉴于银行贷款风险预警信号通常包括有关财务状况信号与非财务状况因素信号，即既具有可量化也有非量化信号的特点，这里尝试运用人工智能技术，基于人工神经网络（ANN）和专家系统（亦称基于知识系统KBS）的混合系统进行贷款风险预警研究。对于有关财务状况预警信号采用前向三层BP神经网络建立财务预警模式。对于BP网络的输出，把它同非财务因素信号一起直接输入专家系统。最后将由专家系统作出风险预警的最终建议。文中在对财务预警BP神经网络进行实验设计基础上再整合到经过结构化的KBS原型系统。     

激光水下目标探测中混沌背景信号重构的研究

对激光水下目标探测中混沌背景信号的重构问题进行了研究．讨论了混沌时间序列的动态特性，并实际计算了激光水下目标探测中混沌背景信号的时延、混沌维数等有关特征参量．在阐述神经网络重构时间序列模型机理的基础上，提出用神经网络局部预测法重构水下目标探测中混沌背景信号，最后在成功地重构出混沌背景信号的条件下，利用预测误差检测到水下目标探测中的有用弱信号．实验结果表明这种方法是比较有效的．     

高等植物铁元素的吸收、转位和调控

铁(Fe)是大多数生物体必需的微量营养元素.虽然铁在许多土壤中是丰富的,但铁在土壤中的可溶性非常低,常常限制植物生长.此外,铁自身存在高度的氧化还原特性,对细胞具有潜在的毒性.因此,细胞内铁的动态平衡需要严格调控.植物细胞中形成了一个复杂的信号网络来调节对铁的摄取、分配、运输及其代谢等过程.非禾本科和禾本科植物物种分别通过基于铁还原和铁螯合的两种不同策略从土壤中获得铁.植物对铁的吸收受到局部和全身信号的调控.系统信号通路似乎整合了激素信号、一氧化氮(NO)信号和植物营养需求等多种因素.综述了两种策略所依赖的分子机制和在铁缺乏条件下负责诱导这些策略的因素.     

A Self-Adaptive Control Method for Uncertainty Systems Based on ANN with AEP

A self-adaptive control method is proposed basedon an artificial neural network(ANN) with acceleratedevolutionary programming(AEP.) algorithm. The neuralnetwork is used to model the uncertainty process, fromwhich the teacher signals are produced online to regulate theparameters of the controller. The accelerated evolutionaryprogramming is used to train the neural network. Theexperiment results show that the method can obviouslyimprove the dynamic performance of uncertainty systems.     

基于BP神经网络的癫痫脑电信号识别研究

为了有效识别癫痫脑电信号,建立了基于误差反向传播（BP）神经网络的癫痫脑电信号识别模型,并提出了一种适合于非平稳脑电信号的特征提取方法。本文以临床采集的包含癫痫发作期的五组500个EEG公共数据为样本,选择了具有任意多分辨分解特性的小波包．对信号进行多尺度分解,提取了各级节点的小波包系数。将小波包系数能量作为特征值,构建了特征向量并输入到BP神经网络分类器中进行自动识别。实验结果表明,该算法的识别率达到了92．5％。     

PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans

The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.     

负重深蹲过程中下肢冗余肌肉力分析

人体负重深蹲过程中下肢肌力协调机理分析是康复工程和体育科学的重要课题。该文建立了4刚体10组肌肉的肌骨生物力学模型,引入约束最优化方法和最优控制理论求解了冗余肌肉力分布和神经控制信号。理论计算与实验测量结果表明:在人体负重深蹲运动过程中,神经系统将肌肉结成不同的协同肌群,并将最小疲劳作为目标函数,来控制不同的协调肌群按照特定的时序结构执行运动的加速和姿态的控制。     

Local sleep and learning

Human sleep is a global state whose functions remain unclear. During much of sleep, cortical neurons undergo slow oscillations in membrane potential, which appear in electroencephalograms as slow wave activity (SWA) of <4 Hz. The amount of SWA is homeostatically regulated, increasing after wakefulness and returning to baseline during sleep. It has been suggested that SWA homeostasis may reflect synaptic changes underlying a cellular need for sleep. If this were so, inducing local synaptic changes should induce local SWA changes, and these should benefit neural function. Here we show that sleep homeostasis indeed has a local component, which can be triggered by a learning task involving specific brain regions. Furthermore, we show that the local increase in SWA after learning correlates with improved performance of the task after sleep. Thus, sleep homeostasis can be induced on a local level and can benefit performance.     

Temporal patterns of human cortical activity reflect tone sequence structure

Despite growing interest in temporal aspects of auditory neural processing, little is known about large-scale timing patterns of brain activity during the perception of auditory sequences. This is partly because it has not been possible to distinguish stimulus-related activity from other, endogenous brain signals recorded by electrical or magnetic sensors. Here we use amplitude modulation of unfamiliar, approximately 1-minute-long tone sequences to label stimulus-related magnetoencephalographic neural activity in human subjects. We show that temporal patterns of activity recorded over particular brain regions track the pitch contour of tone sequences, with the accuracy of tracking increasing as tone sequences become more predictable in structure. In contrast, temporal synchronization between recording locations, particularly between sites over the left posterior hemisphere and the rest of the brain, is greatest when sequences have melody-like statistical properties, which may reflect the perceptual integration of local and global pitch patterns in melody-like sequences. This method is particularly well suited to studying temporal neural correlates of complex auditory sequences (such as speech or music) which engage multiple brain areas as perception unfolds in time.     

Intrinsic transition of embryonic stem-cell differentiation into neural progenitors

The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.