抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

On the basis of data from brain network science, Bullmore and Sporns propose that brain organization is shaped by an economical trade-off between minimizing wiring cost and maximizing the efficiency of information transfer between neuronal populations and discuss this idea in the context of psychiatric and neurological disorders. The brain is expensive, incurring high material and metabolic costs for its size — relative to the size of the body — and many aspects of brain network organization can be mostly explained by a parsimonious drive to minimize these costs. However, brain networks or connectomes also have high topological efficiency, robustness, modularity and a 'rich club' of connector hubs. Many of these and other advantageous topological properties will probably entail a wiring-cost premium. We propose that brain organization is shaped by an economic trade-off between minimizing costs and allowing the emergence of adaptively valuable topological patterns of anatomical or functional connectivity between multiple neuronal populations. This process of negotiating, and re-negotiating, trade-offs between wiring cost and topological value continues over long (decades) and short (millisecond) timescales as brain networks evolve, grow and adapt to changing cognitive demands. An economical analysis of neuropsychiatric disorders highlights the vulnerability of the more costly elements of brain networks to pathological attack or abnormal development.

The economy of brain network organization

Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.

Several brain regions and physiological processes have been proposed to constitute the neural correlates of consciousness. In this Review, Koch and colleagues discuss studies that distinguish the neural correlates of consciousness from other neural processes that precede, accompany or follow it, and suggest that the neural correlates of consciousness are localized to posterior cortical regions.

Neural correlates of consciousness: progress and problems

Spontaneous neuronal activity is a ubiquitous feature of cortex. Its spatiotemporal organization reflects past input and modulates future network output. Here we study whether a particular type of spontaneous activity is generated by a network that is optimized for input processing. Neuronal avalanches are a type of spontaneous activity observed in superficial cortical layers in vitro and in vivo with statistical properties expected from a network operating at “criticality.” Theory predicts that criticality and, therefore, neuronal avalanches are optimal for input processing, but until now, this has not been tested in experiments. Here, we use cortex slice cultures grown on planar microelectrode arrays to demonstrate that cortical networks that generate neuronal avalanches benefit from a maximized dynamic range, i.e., the ability to respond to the greatest range of stimuli. By changing the ratio of excitation and inhibition in the cultures, we derive a network tuning curve for stimulus processing as a function of distance from criticality in agreement with predictions from our simulations. Our findings suggest that in the cortex, (1) balanced excitation and inhibition establishes criticality, which maximizes the range of inputs that can be processed, and (2) spontaneous activity and input processing are unified in the context of critical phenomena.

https://www.jneurosci.org/content/jneuro/29/49/15595.full.pdf

Neuronal avalanches imply maximum dynamic range in cortical networks at criticality

Rapidly growing empirical evidence supports the hypothesis that the cortex operates near criticality. Although the confirmation of this hypothesis would mark a significant advance in fundamental understanding of cortical physiology, a natural question arises: What functional benefits are endowed to cortical circuits that operate at criticality? In this review, we first describe an introductory-level thought experiment to provide the reader with an intuitive understanding of criticality. Second, we discuss some practical approaches for investigating criticality. Finally, we review quantitative evidence that three functional properties of the cortex are optimized at criticality: 1) dynamic range, 2) information transmission, and 3) information capacity. We focus on recently reported experimental evidence and briefly discuss the theory and history of these ideas.

http://journals.sagepub.com/doi/pdf/10.1177/1073858412445487

The Functional Benefits of Criticality in the Cortex

The repertoire of neural activity patterns that a cortical network can produce constrains the ability of the network to transfer and process information. Here, we measured activity patterns obtained from multisite local field potential recordings in cortex cultures, urethane-anesthetized rats, and awake macaque monkeys. First, we quantified the information capacity of the pattern repertoire of ongoing and stimulus-evoked activity using Shannon entropy. Next, we quantified the efficacy of information transmission between stimulus and response using mutual information. By systematically changing the ratio of excitation/inhibition (E/I) in vitro and in a network model, we discovered that both information capacity and information transmission are maximized at a particular intermediate E/I, at which ongoing activity emerges as neuronal avalanches. Next, we used our in vitro and model results to correctly predict in vivo information capacity and interactions between neuronal groups during ongoing activity. Close agreement between our experiments and model suggest that neuronal avalanches and peak information capacity arise because of criticality and are general properties of cortical networks with balanced E/I.

https://www.jneurosci.org/content/jneuro/31/1/55.full.pdf

Information capacity and transmission are maximized in balanced cortical networks with neuronal avalanches.

The repertoire of neural activity patterns that a cortical network can produce constrains the network's ability to transfer and process information. Here, we measured activity patterns obtained from multi-site local field potential (LFP) recordings in cortex cultures, urethane anesthetized rats, and awake macaque monkeys. First, we quantified the information capacity of the pattern repertoire of ongoing and stimulus-evoked activity using Shannon entropy. Next, we quantified the efficacy of information transmission between stimulus and response using mutual information. By systematically changing the ratio of excitation/inhibition (E/I) in vitro and in a network model, we discovered that both information capacity and information transmission are maximized at a particular intermediate E/I, at which ongoing activity emerges as neuronal avalanches. Next, we used our in vitro and model results to correctly predict in vivo information capacity and interactions between neuronal groups during ongoing activity. Close agreement between our experiments and model suggest that neuronal avalanches and peak information capacity arise due to criticality and are general properties of cortical networks with balanced E/I.

Information capacity and transmission are maximized in balanced cortical networks with neuronal avalanches

The collective dynamics of a network of coupled excitable systems in response to an external stimulus depends on the topology of the connections in the network. Here we develop a general theoretical approach to study the effects of network topology on dynamic range, which quantifies the range of stimulus intensities resulting in distinguishable network responses. We find that the largest eigenvalue of the weighted network adjacency matrix governs the network dynamic range. When the largest eigenvalue is exactly one, the system is in a critical state and its dynamic range is maximized. Further, we examine higher order behavior of the steady state system, which predicts that networks with more homogeneous degree distributions should have higher dynamic range. Our analysis, confirmed by numerical simulations, generalizes previous studies in terms of the largest eigenvalue of the adjacency matrix.

Woodrow L. Shew

Papers

Neuronal avalanches imply maximum dynamic range in cortical networks at criticality

The Functional Benefits of Criticality in the Cortex

Information capacity and transmission are maximized in balanced cortical networks with neuronal avalanches.

Information capacity and transmission are maximized in balanced cortical networks with neuronal avalanches

Predicting criticality and dynamic range in complex networks: effects of topology.