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

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway1–8. The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .

The L-Arginine-Nitric Oxide Pathway

Parkinson's disease (PD) is one of the commonest neurodegenerative diseases of old age but its causes remain unclear. It is known that a cardinal feature of the disease is loss of dopamine neurons in the substantia nigra of the brain with concomitant loss of motor control. Several genes that are mutated in the rare inherited form of the disease have been discovered. Now, as [Dawson][1] outlines, two recent papers report the first animal models of PD in flies and mice, fueling optimism that there will be rapid further progress in working out the pathogenesis of this disease and in designing more effective treatments.

 [1]: http://www.sciencemag.org/cgi/content/full/288/5466/631

Of Flies and Mice

Stroke,is the third leading cause of death and disability in the Western world.Stroke refers to set of ischemic conditions resulting from the occlusion or hemorrhage of blood vessels supplying the brain.Loss of blood flow to the brain results in neuronal injury due to both oxygen and nutrient deprivation and the activation of injurious signal cascades.Ultimately cerebral ischemia results in death and dysfunction of brain cells,and neurological deficits that reflect the location and size of the compromised brain area.Injury due to ischemic stroke occurs by a highly choreographed series of complex spatial and temporal events that evolve over hours to days.These events involve complex interactions between fundamental cell injury mechanisms including excitotoxicity and ionic imbalance, oxidative and nitrosative stress,apoptotic-like cell death and inflammatory responses.Genetically engineered mice have been valuable tools to probe putative mechanisms of neuronal death and uncover potential strategies that might render neurons resistant to ischemic injury.Findings from experimental stroke studies in genetically engineered animals are discussed.

What have genetically engineered mice taught us about ischemic injury

PAAN/MIF nuclease inhibition prevents neurodegeneration in Parkinson’s disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. Although many of the causes of PD remain unclear, a consistent finding is the abnormal accumulation of the protein α-synuclein. In a recent issue of Cell, Mazzuli et al. provide a molecular explanation for the unexpected link between PD and Gaucher's disease, a glycolipid lysosomal storage disorder caused by loss of the enzyme glucocerebrosidase (GBA). They report a reciprocal connection between loss of GBA activity and the accumulation of α-synuclein in lysosomes that establishes a bidirectional positive feedback loop with pathogenic consequences. Understanding how lysosomes are implicated in PD may reveal new therapeutic targets for treating this disease.

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A Lysosomal Lair for a Pathogenic Protein Pair

Parkinson's disease is caused by the preferential loss of substantia nigra dopamine neurons A Parkin Interacting Substrate, PARIS (ZNF746) is identified The levels of PARIS are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human brain Parkinson's disease patients PARIS represses the expression of the transcriptional co-activator, PGC-1α and the PGC-1α target gene, NRF-1 by binding to insulin response sequences in the PGC-1α promoter Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons that is PARIS dependent Overexpression of PARIS causes selective loss of DA neurons in the substantia nigra, which is reversed by either parkin or PGC-1α co-expression The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation

Valina L. Dawson

Papers

Of Flies and Mice

What have genetically engineered mice taught us about ischemic injury

PAAN/MIF nuclease inhibition prevents neurodegeneration in Parkinson’s disease

A Lysosomal Lair for a Pathogenic Protein Pair

Transcriptional repression leading to parkinson's disease