Effects of Acute Ethanol Intoxication on Local Field Potentials in the Rat Lateral Septum

Neurophysiology - The lateral septum (LS) is an important part of the limbic and reward brain systems; its activity has been associated with the development of different aspects of addiction. Using...     

多通道局部场电位时变频谱的同步模式及其对行为事件的编码

用时变相干（time-varying coherence）频谱方法分析多通道局部场电位（local field potentials, LFPs）随时间变化的同步模式及其对行为事件的编码。实验数据为行为事件前后3秒的28通道LFPs。分别计算每个通道LFP的功率谱密度（power spectral density, PSD）及多通道LFPs各个特征频段的PSD,选取PSD分布集中的?兹频段为LFPs的特征频段;应用离散二进小波变换获取LFPs的?兹频段分量;从28通道LFPs中选取PSD最大的通道作为参考通道。选取计算窗口为50 ms,从初始点开始计算每个窗口中每个通道LFP及其?兹分量对参考通道的频谱相干分析。移动窗口步长为25 ms,获取多通道LFPs及其?兹分量的时变频谱相干动态分布。研究结果显示,?兹频段分量的PSD占LFPs总功率的71.95%,表明?兹分量是实验中多通道LFPs同步的特征频段;多通道LFPs的?兹分量频谱相干值随时间变化,行为事件点前后1 s的相干值具有显著差别（P＜0.05）,表明多通道LFPs的?兹频段时变频谱相干有效地编码了这一行为事件。     

Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception

The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral recordings, we investigated whether the human insula exhibits local field potentials (LFPs) specific for pain. Forty-seven insular sites were investigated. Participants received brief stimuli belonging to four different modalities (nociceptive, vibrotactile, auditory, and visual). Both nociceptive stimuli and non-nociceptive vibrotactile, auditory, and visual stimuli elicited consistent LFPs in the posterior and anterior insula, with matching spatial distributions. Furthermore, a blind source separation procedure showed that nociceptive LFPs are largely explained by multimodal neural activity also contributing to non-nociceptive LFPs. By revealing that LFPs elicited by nociceptive stimuli reflect activity unrelated to nociception and pain, our results confute the widespread assumption that these brain responses are a signature for pain perception and its modulation.     

Macroscopic Models of Local Field Potentials and the Apparent 1/f Noise in Brain Activity

The power spectrum of local field potentials (LFPs) has been reported to scale as the inverse of the frequency, but the origin of this 1/f noise is at present unclear. Macroscopic measurements in cortical tissue demonstrated that electric conductivity (as well as permittivity) is frequency-dependent, while other measurements failed to evidence any dependence on frequency. In this article, we propose a model of the genesis of LFPs that accounts for the above data and contradictions. Starting from first principles (Maxwell equations), we introduce a macroscopic formalism in which macroscopic measurements are naturally incorporated, and also examine different physical causes for the frequency dependence. We suggest that ionic diffusion primes over electric field effects, and is responsible for the frequency dependence. This explains the contradictory observations, and also reproduces the 1/f power spectral structure of LFPs, as well as more complex frequency scaling. Finally, we suggest a measurement method to reveal the frequency dependence of current propagation in biological tissue, and which could be used to directly test the predictions of this formalism.     

Local Anesthetics Affect Gramicidin A Channels via Membrane Electrostatic Potentials

The effects of local anesthetics (LAs), including aminoamides and aminoesters, on the characteristics of single gramicidin A (GA) channels in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers were studied. Aminoamides, namely lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), and bupivacaine (BPV), reduced the conductance of GA channels. Aminoesters influenced the current fluctuations induced by GA differently; procaine (PC) did not affect the fluctuations, whereas tetracaine (TTC) distinctly reduced the conductance of single GA channels. Using electrophysiological technique, we estimated the changes in the membrane boundary potential at the adsorption of LAs; LDC, PLC, MPV, BPV, and TTC substantially increased, while PC did not affect it. To elucidate which component of the membrane boundary potential, the surface or dipole potential, is responsible for the observed effects of LAs, we employed a fluorescence assay. We found that TTC led to a significant increase in the membrane dipole potential, whereas the adsorption of LDC, PLC, MPV, BPV, and PC did not produce any changes in the membrane dipole potential. We concluded that aminoamides affected the surface potential of lipid bilayers. Together, these data suggest that the effects of LAs on the conductance of single GA channels are caused by their influence on membrane electrostatic potentials; the regulation of GA pores by aminoamides is associated with the surface potential of membranes, whereas TTC modulation of channel properties is predominantly due to changes in dipole potential of lipid bilayers. These data might provide some significant implications for voltage-gated ion channels of cell membranes.     

An Analysis of Field Potentials During Different Tailflip Behaviours in Crayfish

Crayfish tailflips have been intensively studied to reveal the decision-making processes and neural organisation underlying a stereotyped escape behaviour. Three behaviours mediated by different neural pathways have been well described: medial giant, lateral giant and non-giant tailflips. It has proved difficult to distinguish between the three without invasive or restrictive experimental manipulation. We report unambiguous differences between the signals generated by the crayfish Cherax destructor during the three types of tailflip when recorded by bath electrodes placed in the holding aquarium. Using our ability to distinguish between the different behaviours in freely moving animals we examined the relationship between the type of tailflip evoked by stimulation to different parts of the body. The transition zone between medial and lateral giant tailflips is the thoracic-abdominal border but it is not absolute and some stimuli produce responses that cannot be unambiguously assigned to either behavioural category. We examined the latency between stimulation at different points down the length of the body and the appearance of the electrical signal accompanying escape for both medial and lateral tailflips. We used two methods to estimate the proportion of the latency accounted for by giant fibre conduction velocity. The results support current views of the differences between the activation sites of the two giant fibre systems and suggest why stimulation in the transition zone results in ambiguous outcomes.     

Uncovering the human methyltransferasome

We present a comprehensive analysis of the human methyltransferasome. Primary sequences, predicted secondary structures, and solved crystal structures of known methyltransferases were analyzed by hidden Markov models, Fisher-based statistical matrices, and fold recognition prediction-based threading algorithms to create a model, or profile, of each methyltransferase superfamily. These profiles were used to scan the human proteome database and detect novel methyltransferases. 208 proteins in the human genome are now identified as known or putative methyltransferases, including 38 proteins that were not annotated previously. To date, 30% of these proteins have been linked to disease states. Possible substrates of methylation for all of the SET domain and SPOUT methyltransferases as well as 100 of the 131 seven-β-strand methyltransferases were surmised from sequence similarity clusters based on alignments of the substrate-specific domains.     

On the Origins of Signal Variance in FMRI of the Human Midbrain at High Field

Functional Magnetic Resonance Imaging (fMRI) in the midbrain at 7 Tesla suffers from unexpectedly low temporal signal to noise ratio (TSNR) compared to other brain regions. Various methodologies were used in this study to quantitatively identify causes of the noise and signal differences in midbrain fMRI data. The influence of physiological noise sources was examined using RETROICOR, phase regression analysis, and power spectral analyses of contributions in the respiratory and cardiac frequency ranges. The impact of between-shot phase shifts in 3-D multi-shot sequences was tested using a one-dimensional (1-D) phase navigator approach. Additionally, the effects of shared noise influences between regions that were temporally, but not functionally, correlated with the midbrain (adjacent white matter and anterior cerebellum) were investigated via analyses with regressors of ‘no interest’. These attempts to reduce noise did not improve the overall TSNR in the midbrain. In addition, the steady state signal and noise were measured in the midbrain and the visual cortex for resting state data. We observed comparable steady state signals from both the midbrain and the cortex. However, the noise was 2–3 times higher in the midbrain relative to the cortex, confirming that the low TSNR in the midbrain was not due to low signal but rather a result of large signal variance. These temporal variations did not behave as known physiological or other noise sources, and were not mitigated by conventional strategies. Upon further investigation, resting state functional connectivity analysis in the midbrain showed strong intrinsic fluctuations between homologous midbrain regions. These data suggest that the low TSNR in the midbrain may originate from larger signal fluctuations arising from functional connectivity compared to cortex, rather than simply reflecting physiological noise.     

Uncovering the Laurasian roots ofEubranchipus

The species of the anostracan genusEubranchipus Verrill, 1870 can be recognized as belonging to the same taxon and unambiguously distinguished from all other taxa in the family Chirocephalidae Daday, 1910 by the common morphology of their eversible penes. These reproductive structures are short, fat, and cylindrical with a single long, thin spine on the lateral margin at the tip of each penis. This ends the erroneous perception ofEubranchipus as a New World genus and recognizes it as an old taxon with members distributed accross the modern continents that once comprised Laurasia.     

Uncovering the Nutritional Landscape of Food

Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food’s frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition.     

Water Stress and Leaf Growth of Field Beans (Vicia faba L.) in the Field: Water Potentials and Laminar Expansion

Field beans were grown in three different irrigation treatments.The growth of each leaf was followed and estimates made of plantwater potential at dawn and of plant water potential, solutepotential, and pressure potential in the afternoon. The growthin area of the leaves against time was fitted with a logisticcurve from which the parameters of leaf growth were defined.The parameters were the area at which a leaf unfolds, the meangrowth rate, and the duration of growth, which combine to givethe final leaf size. Water stress reduced the final leaf sizeby reducing both the area at unfolding and the mean growth rate.The duration of growth was not consistently altered. Final leafsize was closely correlated with the plant water potential inthe afternoon and apparently more with pressure than solutepotential. Vicia faba, field bean, water stress, leaf area, leaf growth, water potential     

基于节点-模块置信度及局部模块度双重约束挖掘前列腺癌候选疾病模块

前列腺癌病因及发病机理研究有助于前列腺癌预防和治疗.目前,前列腺癌生化试验研究方法成本高、耗时,而基于网络计算方法容易受基因表达谱数据不完整、噪声高及实验样本数量少等约束.为此,本文提出一种基于节点-模块置信度及局部模块度的双重约束算法(命名为NMCOM),挖掘前列腺癌候选疾病模块.NMCOM算法不依赖基因表达谱数据,采用候选基因与致病表型之间一致性得分,候选基因与致病基因之间语义相似性得分融合排序策略,选取起始节点,并基于节点-模块置信度及局部模块度双重约束挖掘前列腺癌候选疾病模块.通过对挖掘出的模块进行富集分析,最终得到18个有显著意义的候选疾病基因模块.与单一打分排序方法及随机游走重开始方法相比,NMCOM融合排序策略的平均排名比小、AUC值大,且挖掘出结果明显优于其他模块挖掘算法,模块生物学意义显著.NMCOM算法不仅能准确有效地挖掘前列腺癌候选疾病模块,且可扩展挖掘其他疾病候选模块.     

Uncovering the secretes of mesenchymal stem cells

Mesenchymal stem cells (MSC) show great promise in a wide array of therapeutic applications due mainly to their capacity to suppress immune and inflammatory reactions and instigate normal tissue repair processes. The secretion of bioactive factors is thought to play a predominant role in the mechanisms of action for these clinically relevant functions. As such, a large body of MSC research has focussed on characterization of the MSC secretome; including both soluble factors and factors released in extracellular vesicles (e.g., exosomes and microvesicles). This review provides an overview of our current knowledge of the MSC secretome in the context of determining the clinical relevance of these cells. In addition, the review summarizes various approaches that have been utilized to identify proteins secreted by MSC and discusses the advantages and limitations of different proteomic methods. Finally, we discuss issues that must be addressed before the clinical relevance of research into the MSC secretome can be realized.