Purinergic signalling in neuron-glia interactions

Activity-dependent release of ATP from synapses, axons and glia activates purinergic membrane receptors that modulate intracellular calcium and cyclic AMP. This enables glia to detect neural activity and communicate among other glial cells by releasing ATP through membrane channels and vesicles. Through purinergic signalling, impulse activity regulates glial proliferation, motility, survival, differentiation and myelination, and facilitates interactions between neurons, and vascular and immune system cells. Interactions among purinergic, growth factor and cytokine signalling regulate synaptic strength, development and responses to injury. We review the involvement of ATP and adenosine receptors in neuron-glia signalling, including the release and hydrolysis of ATP, how the receptors signal, the pharmacological tools used to study them, and their functional significance.     

Advances in understanding archaea-virus interactions in controlled and natural environments

Our understanding of host-virus interactions in archaeal systems generally lags behind our knowledge of host-virus interactions in bacterial and eukaryotic systems. This is due to the limited number of archaeal host-virus systems available for study under laboratory conditions, as well as the absence of diseases known to be caused by archaea. However, in recent years there has been a rapid expansion of our understanding of archaeal host-virus interactions combining traditional genetic and biochemical approaches with 'omics' based approaches in both laboratory and natural environmental studies. We highlight here the emerging features of host-virus interactions in archaea with a particular emphasis on host-virus interactions gathered from the study of archaeal viruses from high temperature acidic thermal environments.     

Computer simulations of neuron-glia interactions mediated by ion flux

Extracellular potassium concentration, [K⁺]_o, and intracellular calcium, [Ca²⁺]_i, rise during neuron excitation, seizures and spreading depression. Astrocytes probably restrain the rise of K⁺ in a way that is only partly understood. To examine the effect of glial K⁺ uptake, we used a model neuron equipped with Na⁺, K⁺, Ca²⁺ and Cl⁻ conductances, ion pumps and ion exchangers, surrounded by interstitial space and glia. The glial membrane was either “passive”, incorporating only leak channels and an ion exchange pump, or it had rectifying K⁺ channels. We computed ion fluxes, concentration changes and osmotic volume changes. Increase of [K⁺]_o stimulated the glial uptake by the glial 3Na/2K ion pump. The [K⁺]_o flux through glial leak and rectifier channels was outward as long as the driving potential was outwardly directed, but it turned inward when rising [K⁺]_o/[K⁺]_i ratio reversed the driving potential. Adjustments of glial membrane parameters influenced the neuronal firing patterns, the length of paroxysmal afterdischarge and the ignition point of spreading depression. We conclude that voltage gated K⁺ currents can boost the effectiveness of the glial “potassium buffer” and that this buffer function is important even at moderate or low levels of excitation, but especially so in pathological states.     

Cerebellar Bergmann glia: an important model to study neuron-glia interactions

The biochemical effects triggered by the action of glutamate, the main excitatory amino acid, on a specialized type of glia cells, Bergmann glial cells of the cerebellum, are a model system with which to study glia-neuronal interactions. Neuron to Bergmann glia signaling is involved in early stages of development, mainly in cell migration and synaptogenesis. Later, in adulthood, these cells have an important role in the maintenance and proper function of the synapses that they surround. Major molecular targets of this cellular interplay are glial glutamate receptors and transporters, both of which sense synaptic activity. Glutamate receptors trigger a complex network of signaling cascades that involve Ca(2+) influx and lead to a differential gene-expression pattern. In contrast, Bergmann glia glutamate transporters participate in the removal of the neurotransmitter from the synaptic cleft and act also as signal transducers that regulate, in the short term, their own activity. These exciting findings strengthen the concept of active participation of glial cells in synaptic transmission and the involvement of neuron-glia circuits in the processing of brain information.     

Advances in understanding genome maintenance

A report from the Abcam genome stability conference 'Maintenance of Genome Stability', Jolly Beach Resort, Antigua, 8-11 March 2010.     

Advances in understanding L-DOPA-induced dyskinesia

The crucial role of dopamine (DA) in movement control is illustrated by the spectrum of motor disorders caused by either a deficiency or a hyperactivity of dopaminergic transmission in the basal ganglia. The degeneration of nigrostriatal DA neurons in Parkinson's disease causes poverty and slowness of movement. These symptoms are greatly improved by pharmacological DA replacement with L-3,4-dihydroxy-phenylalanine (L-DOPA), which however causes excessive involuntary movements in a majority of patients. L-DOPA-induced dyskinesia (abnormal involuntary movements) provides a topic of investigation at the interface between clinical and basic neuroscience. In this article, we review recent studies in rodent models, which have uncovered two principal alterations at the basis of the movement disorder, namely, an abnormal pre-synaptic handling of exogenous L-DOPA, and a hyper-reactive post-synaptic response to DA. Dysregulated nigrostriatal DA transmission causes secondary alterations in a variety of non-dopaminergic transmitter systems, the manipulation of which modulates dyskinesia through mechanisms that are presently unclear. Further research on L-DOPA-induced dyskinesia will contribute to a deeper understanding of the functional interplay between neurotransmitters and neuromodulators in the motor circuits of the basal ganglia.     

Advances in understanding bacterial outer-membrane biogenesis

The outer membrane of gram-negative bacteria such as Escherichia coli serves as a protective barrier that controls the influx and efflux of solutes. This allows the bacteria to inhabit several different, and often hostile, environments. The assembly of the E. coli outer membrane has been difficult to study using traditional genetic and biochemical methods, and how all its components reach the outer membrane after being synthesized in the cytoplasm and cytoplasmic membrane, how they are assembled in an environment that is devoid of an obvious energy source, and how assembly proceeds without disrupting the integrity of this essential cellular structure are all fundamental questions that remain unanswered. Here, we review the new approaches that have led to the recent discovery of components of the machinery involved in the biogenesis of this distinctive cellular organelle.     

Advances in understanding bone cancer pain

Experimental animal models of bone cancer pain have emerged and findings have provided a unique glimpse into unraveling the mechanism that drives this debilitating condition. Key contributors to the generation and maintenance of bone cancer pain are tumor-induced osteolysis, tumor itself, and production of nociceptive mediators in the bone-tumor microenvironment.     

Advances in understanding neuronal somatostatin receptors

It has long been considered that somatostatin acts as a neuromodulator in the mammalian central nervous system but its precise physiological roles remain elusive. Early studies to identify somatostatin-binding sites revealed a widespread heterogeneous pattern, especially in the CNS. More recently, a family of somatostatin receptors have been identified, of which five genes (sst_1–5) have been cloned. In this review, we discuss current data describing the localisation of the five receptor types. Recent progress in understanding their function has been made using high-affinity, selective receptor ligands and transgenic animal technology. Finally, the therapeutic potential for somatostatin receptor-selective compounds as analgesics is considered.     

肠道微生物群与药物相互作用的研究进展

药物的代谢是机体对药物处置过程的关键步骤,而肠道作为机体中重要的微生态系统,其在药物代谢方面的作用至关重要。肠道微生物群能够对各种药物等外源化合物进行生物转化、积累,并改变这些物质的活性和毒性,从而影响宿主机体对它们的反应。肠道微生物群与药物之间的相互作用相当复杂,亟待更多更加深入、全面的发掘和研究。近年来,随着人们对肠道微生物群代谢及其与药物互作关系,肠道菌-宿主共代谢认知的不断深化,越来越多的研究表明肠道微生物在药代动力学中扮演重要角色。本文通过调研、整理、归纳和总结国内外相关文献资料,对机体肠道微生物的分类、功能,几种常用药物对肠道微生物的影响以及肠道菌群对药物的代谢作用效果与几个主要的机制进行了梳理和综述,并讨论了微生物和药物之间的双向互作。有利于增进对微生物群影响药物疗效及其代谢途径和机制的了解,提高调控肠道微生物改善治疗的可能性,为指导临床合理用药、精准用药、个体化治疗、药物的评价和新药研发等提供科学参考。     

Advances in our understanding of vitamin E

Vitamin E is an essential nutrient for animals and man since it is not synthesized in the body. The level of vitamin E in the lipoproteins of plasma and in the phospholipids of vital mitochondria, microsomes, and plasma membranes in humans depends (as in experimental animals) on the amount of biologically active vitamin E being consumed, the levels of dietary prooxidants and antioxidants, and the adequacy of dietary selenium. Studies with chicks have demonstrated an important mode of action of both vitamin E and selenium in metabolism, and provide a solution to the long-term enigma of the true role of vitamin E in the diet of all animals, including man. The biochemical actions of vitamin E and selenium are concerned with prevention of peroxidative damage to cells and subcellular elements, thereby aiding the body in maintaining its normal defense mechanisms against disease and environmental insult.     

Hormonal induction of glutamine synthetase in cultures of embryonic retina cells: requirement for neuron-glia contact interactions

Cortisol induces glutamine synthetase (GS) in gliocytes of chick embryo neural retina. Using adherent cultures of retina cells we have demonstrated that responsiveness of the gliocytes to GS induction by the hormone requires contact with neurons. GS is not inducible in high-density cultures depleted of neurons and consisting only of gliocytes. In neuron-containing cultures, induced GS was detected immunohistochemically only in those gliocytes that were closely juxtaposed with clusters of neurons. Unlike the induction of GS, the expression of carbonic anhydrase-C (which does not require cortisol) persisted in these glia cells also in the absence of neurons. The nature and role of glia-neuron interactions in the hormonal induction of GS are briefly discussed.     

Development of functional units within trigeminal ganglia correlates with increased expression of proteins involved in neuron-glia interactions

Cell bodies of trigeminal nerves, which are located in the trigeminal ganglion, are completely surrounded by satellite glial cells and together form a functional unit that regulates neuronal excitability. The goals of this study were to investigate the cellular organization of the rat trigeminal ganglia during postnatal development and correlate those findings with expression of proteins implicated in neuron-glia interactions. During postnatal development there was an increase in the volume of the neuronal cell body, which correlated with a steady increase in the number of glial cells associated with an individual neuron from an average of 2.16 at birth to 7.35 on day 56 in young adults. Interestingly, while the levels of the inwardly rectifying K+ channel Kir4.1 were barely detectable during the first week, its expression in satellite glial cells increased by day 9 and correlated with initial formation of functional units. Similarly, expression of the vesicle docking protein SNAP-25 and neuropeptide calcitonin gene-related peptide was readily detected beginning on day 9 and remained elevated throughout postnatal development. Based on our findings, we propose that the expression of proteins involved in facilitating neuron-glia interactions temporally correlates with the formation of mature functional units during postnatal development of trigeminal ganglion.     

生物间高阶相互作用研究进展

生物间的相互作用是物种共存和生物多样性维持的关键。传统的物种共存研究主要关注配对物种之间的直接相互作用, 而忽略了更为复杂的间接相互作用。本文首先介绍了两种间接相互作用: 链式相互作用(本质上仍是两两物种之间的相互作用)和高阶相互作用。在此基础上, 我们回顾了高阶相互作用定义的演变历史(包括狭义的高阶相互作用和广义的高阶相互作用)及其检验方法, 并介绍了高阶相互作用在多营养级之间和同一营养级内的研究概况。目前, 生态学家主要对多营养级之间(如食物网)的高阶相互作用的特征、发生机制、作用途径及实验证据等方面进行了详尽的研究。近年来, 同一营养级内的高阶相互作用也开始受到关注, 因此我们进一步介绍了同一营养级内个体水平高阶相互作用的重要意义和度量方法。从个体水平上研究高阶相互作用, 既能统一狭义和广义高阶相互作用在定义上的争议, 又可以将个体间的差异(如个体大小、个体的空间分布等信息)考虑进来。最后, 本文对高阶相互作用一些可能的重要研究方向进行了展望: 在自然群落中(尤其同一营养级内)检验高阶相互作用的普遍性与相对重要性, 探讨高阶相互作用的发生机制以及如何将高阶相互作用整合到现有的理论体系中等。高阶相互作用的研究有助于我们全面深刻地理解物种共存和生物多样性的维持机制, 丰富和完善群落生态学的理论框架, 为人类世背景下的生物多样性保护和生态系统功能维持与提升提供基础。     

Advances in understanding E. coli cell fission

Much of what we know about cytokinesis in bacteria has come from studies with Escherichia coli, and efforts to comprehensively understand this fundamental process in this organism continue to intensify. Major recent advances include in vitro assembly of a membrane-tethered version of FtsZ into contractile rings in lipid tubules, in vitro dynamic patterning of the Min proteins and a deeper understanding of how they direct assembly of the FtsZ-ring to midcell, the elucidation of structures, biochemical activities and interactions of other key components of the cell fission machinery, and the uncovering of additional components of this machinery with often redundant but important roles in invagination of the three cell envelope layers.     

Advances and challenges in understanding histone demethylase biology

1. Download : Download high-res image (189KB)
2. Download : Download full-size image