Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

高阶统计量地震子波估计建模

本文在反射系数序列为非高斯、平稳和统计独立的随机过程,地震子波为非因果、混合相位的假设条件下,分别应用滑动平均(MA)和自回归滑动平均(ARMA)模型对地震记录进行建模,并采用运算代价较小的基于高阶累积量的线性化求解方法——累积量矩阵方程法进行了子波提取和模型适应性的研究。数值模拟结果和实际地震数据处理结果表明:自回归滑动平均(ARMA)模型比滑动平均(MA)模型具有参数节省、模型更为高效的特点;累积量矩阵方程法可以有效地压制加性高斯噪声,但对累积量样本估计的准确性要求较高;如果累积量样本估计的误差和方差适度,结合自回归滑动平均(ARMA)模型描述的累积量矩阵方程法可以高效、准确地估计出地震子波。     

Behavioral depression during cocaine withdrawal is associated with decreased spontaneous activity of ventral tegmental area dopamine neurons.

Withdrawal from an escalating-dose, bingelike regimen of cocaine administration in rats produced significantly depressed levels of locomotor activity during the nocturnal portion of the day-night cycle. This effect was observed during the first 48 hrs of testing. Extracellular single-unit recordings of ventral tegmental area (VTA) dopamine (DA) neurons revealed no differences between saline- and cocaine-treated rats with respect to basal firing rates. However, significantly fewer spontaneously active VTA DA neurons were encountered in rats withdrawn from binge cocaine. As with the nocturnal hypoactivity, this effect was observed only during the first 48 hrs of withdrawal. These findings suggest that short-term DA neuron dysfunction during cocaine withdrawal temporally corresponds to behavioral disruptions that are similar to those described in human addicts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

'PURIFYING' NOISY SIGNALS

Abstract. A method is presented for obtaining the set of all possible pure origins of a given noisy ARMA(2,2) signal. By a transformation to a new set of variables the locus of this set becomes a straight line.     

ARMA噪声中的正弦波检测

本文提出一种ＡＲＭＡ噪声中正弦波检测的方法，本方法先用改进的Ｐｒｏｎｙ法估计可能存在的正弦波，然后利用一种综合考虑衰减因子以及ＭＵＳＩＣ值的准则从估计结果中区分正统率波的真伪。数值例子表明，本文方法比Ｐｒｏｎｇ方法及ＭＵＳＩＣ方法具有更高的分辨力。     

一种有效的振动信号分离算法

振动信号包含随机成分与周期成分 ,其中的随机成分占据了很宽的频域 ,其能量极易引起其它设备特别是电子设备的共振 ,从而导致设备失效。为评估随机成分对设备的影响 ,需要将周期成分从振动信号中去除。为此 ,首先使用ARMA建模法对振动信号中周期成分出现的频率位置进行估计 ,然后设计阻带带宽极窄 (小于 0 .5Hz)的V型滤波器来完成相应的滤波。实验表明本文中的方法能有效地去除振动信号中的周期成分 ,而完整地保留随机成分     

Bullwhip reduction for ARMA demand: The proportional order-up-to policy versus the full-state-feedback policy

A ‘proportional’ order-up-to policy reacting to ARMA demand is analyzed using stochastic optimal control theory. This policy is compared with a full-state-feedback order-up-to policy. Necessary conditions for an optimum of a weighted sum of the inventory and the ordering variances for both policies are formulated. Based on this a relatively simple expression for the ‘full-state’ policy is derived. The comparison between the two policies demonstrates that the ‘intuitively’ designed proportional policy does not fulfill the objective of controlling both the inventory and ordering variance for all parameter values of the demand model as well as the full-state-feedback policy. The full-state-feedback policy outperforms the proportional policy in several aspects.     

SPECTRAL RADIUS,KRONECKER PRODUCTS AND STATIONARITY

Abstract. We provide a stochastic proof of the inequality ρ(A?A+B?B) ≥ρ(A?A), where ρ(M) denotes the spectral radius of any square matrix M, i.e. max{|eigenvalues| of M}, and M?N denotes the Kronecker product of any two matrices M and N. The inequality is then used to show that stationarity of the bilinear model will imply stationarity of the linear part, i.e. the linear ARMA model for r= 1 and q= 1. Furthermore, it is shown that stationarity of the subdiagonal model, i.e. the bilinear model with b_ij=0 for i< j, again implies stationarity of its linear part, provided that the stationarity condition given by Bhaskara Rao and his colleagues is met. Interestingly, the conclusion that stationarity of the subdiagonal models, implies that the linear component models cannot be extended to the general non-subdiagonal bilinear models. The last observation is demonstrated via a simple example with p=m= 1, r= 0 and q= 2.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.