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

Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.

https://rupress.org/jcb/article-pdf/200/4/373/1262520/jcb_201211138.pdf

Extracellular vesicles: exosomes, microvesicles, and friends.

▪ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca2+]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases...

/pdf/short-term-synaptic-plasticity-5d4dx79319.pdf

Short-Term Synaptic Plasticity

Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

Neurotrophins: roles in neuronal development and function.

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

Modulation of neuronal firing: What role can nanotechnology play?

Organic semiconducting polymers display several beneficial properties to interface with biological substrates. These materials have been employed successfully for cellular interfaces such as neural probes, biosensors, and actuators for drug release. Recent experiments demonstrate that they can also be used to optically modulate the membrane potential of cultured neurons and astrocytes. Moreover, application of an organic light-sensitive semiconductor has been shown to restore light sensitivity in degenerated retinas, suggesting the use of conjugated polymers as active materials in retinal prosthesis.

The Use of Light-Sensitive Organic Semiconductors to Manipulate Neuronal Activity

The introduction of fluorescent probes and light-sensitive molecules and the recent development of 8 optogenetics are tremendously contributing to our understanding of neuronal circuit function. In parallel 9 with the development of these optical tools, new technologies for the illumination of neural tissue with 10 complex spatiotemporal patterns have been introduced. Here, we describe a method for generating 11 spatially modulated illumination by using liquid crystal on silicon spatial light modulators (LCOS12 SLMs). The theoretical background and the description of working principles of LCOS-SLMs are 13 presented together with a detailed experimental procedure to install LCOS-SLMs on conventional two14 photon laser scanning microscopes and perform experiments on neuronal cells. In combination with the 15 development of light-sensitive proteins with cell-specific and subcellularly localized expression, this 16 technical approach has the potential to open new horizons for the optical investigation of neuronal 17 circuits. 18 tion, Uncaging

Illumination of Neuronal Networks

We report on the isomerization dynamics of an amphiphilic azobenzene that dwells within the plasma membrane. We found that in aggregates formed in water, the isomerization reaction is hindered, while radiative deactivation is favoured. However, once in the membrane, the molecule reacquires its isomerisation capacity. These data fully account for the recently reported experiments in neurons, showing that the amphiphilic azobenzenes are effective light actuators for the modification of the electrical state of the membrane.

/pdf/membrane-environment-enables-ultrafast-isomerization-of-2kxrwf3sol.pdf

Membrane Environment Enables Ultrafast Isomerization of Amphiphilic Azobenzene -INVITED

Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response to the gold standard ADHD medication, methylphenidate (MPH), a monoamine transporter inhibitor whose efficacy appears related with the stimulation of brain-derived neurotrophic factor (BDNF). Interestingly, we previously showed that MPH can bind Syn III, which can regulate neuronal development. These observations suggest that Syn III polymorphism may impinge on ADHD onset and response to therapy by affecting BDNF-dependent dopaminergic neuron development. Here, by studying zebrafish embryos exposed to Syn III gene knock-down (KD), Syn III knock-out (ko) mice and human induced pluripotent stem cells (iPSCs)-derived neurons subjected to Syn III RNA interference, we found that Syn III governs the earliest stages of dopaminergic neurons development and that this function is conserved in vertebrates. We also observed that in mammals Syn III exerts this function acting upstream of brain-derived neurotrophic factor (BDNF)- and cAMP-dependent protein kinase 5 (Cdk5)-stimulated dendrite development. Collectively, these findings own significant implications for deciphering the biological basis of ADHD.

/pdf/synapsin-iii-regulates-dopaminergic-neuron-development-in-1r6zqgfm.pdf

Fabio Benfenati

Papers

Modulation of neuronal firing: What role can nanotechnology play?

The Use of Light-Sensitive Organic Semiconductors to Manipulate Neuronal Activity

Illumination of Neuronal Networks

Membrane Environment Enables Ultrafast Isomerization of Amphiphilic Azobenzene -INVITED

Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates