Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation   总被引：2，自引：0，他引：2  

Nomura DK  Morrison BE  Blankman JL  Long JZ  Kinsey SG  Marcondes MC  Ward AM  Hahn YK  Lichtman AH  Conti B  Cravatt BF 《Science (New York, N.Y.)》2011,334(6057):809-813

Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA(2). These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.  相似文献   

Statement on scientific publication and security     

Atlas R  Campbell P  Cozzarelli NR  Curfman G  Enquist L  Fink G  Flanagin A  Fletcher J  George E  Hammes G  Heyman D  Inglesby T  Kaplan S  Kennedy D  Krug J  Levinson R  Marcus E  Metzger H  Morse SS  O'Brien A  Onderdonk A  Poste G  Renault B  Rich R  Rosengard A  Salzburg S  Scanlan M  Shenk T  Tabor H  Varmus H  Wimmer E  Yamamoto K;Journal Editors  Authors Group 《Science (New York, N.Y.)》2003,299(5610):1149

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The FERONIA receptor-like kinase mediates male-female interactions during pollen tube reception     

Escobar-Restrepo JM  Huck N  Kessler S  Gagliardini V  Gheyselinck J  Yang WC  Grossniklaus U 《Science (New York, N.Y.)》2007,317(5838):656-660

In flowering plants, signaling between the male pollen tube and the synergid cells of the female gametophyte is required for fertilization. In the Arabidopsis thaliana mutant feronia (fer), fertilization is impaired; the pollen tube fails to arrest and thus continues to grow inside the female gametophyte. FER encodes a synergid-expressed, plasma membrane-localized receptor-like kinase. We found that the FER protein accumulates asymmetrically in the synergid membrane at the filiform apparatus. Interspecific crosses using pollen from Arabidopsis lyrata and Cardamine flexuosa on A. thaliana stigmas resulted in a fer-like phenotype that correlates with sequence divergence in the extracellular domain of FER. Our findings show that the female control of pollen tube reception is based on a FER-dependent signaling pathway, which may play a role in reproductive isolation barriers.  相似文献   

Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast     

Roguev A  Bandyopadhyay S  Zofall M  Zhang K  Fischer T  Collins SR  Qu H  Shales M  Park HO  Hayles J  Hoe KL  Kim DU  Ideker T  Grewal SI  Weissman JS  Krogan NJ 《Science (New York, N.Y.)》2008,322(5900):405-410

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Condensation of semiconductor microcavity exciton polaritons     

Deng H  Weihs G  Santori C  Bloch J  Yamamoto Y 《Science (New York, N.Y.)》2002,298(5591):199-202

A phase transition from a classical thermal mixed state to a quantum-mechanical pure state of exciton polaritons is observed in a GaAs multiple quantum-well microcavity from the decrease of the second-order coherence function. Supporting evidence is obtained from the observation of a nonlinear threshold behavior in the pump-intensity dependence of the emission, a polariton-like dispersion relation above threshold, and a decrease of the relaxation time into the lower polariton state. The condensation of microcavity exciton polaritons is confirmed.  相似文献   

Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis   总被引：1，自引：0，他引：1  

Mallucci G  Dickinson A  Linehan J  Klöhn PC  Brandner S  Collinge J 《Science (New York, N.Y.)》2003,302(5646):871-874

The mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of PrPSc, the disease-associated form of prion protein (PrP), do not significantly prolong survival in mice with central nervous system prion infection. We found that depleting endogenous neuronal PrPc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. This occurred despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity.  相似文献   

TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis   总被引：1，自引：0，他引：1  

Sreedharan J  Blair IP  Tripathi VB  Hu X  Vance C  Rogelj B  Ackerley S  Durnall JC  Williams KL  Buratti E  Baralle F  de Belleroche J  Mitchell JD  Leigh PN  Al-Chalabi A  Miller CC  Nicholson G  Shaw CE 《Science (New York, N.Y.)》2008,319(5870):1668-1672

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.  相似文献   

The ecoresponsive genome of Daphnia pulex     

Colbourne JK  Pfrender ME  Gilbert D  Thomas WK  Tucker A  Oakley TH  Tokishita S  Aerts A  Arnold GJ  Basu MK  Bauer DJ  Cáceres CE  Carmel L  Casola C  Choi JH  Detter JC  Dong Q  Dusheyko S  Eads BD  Fröhlich T  Geiler-Samerotte KA  Gerlach D  Hatcher P  Jogdeo S  Krijgsveld J  Kriventseva EV  Kültz D  Laforsch C  Lindquist E  Lopez J  Manak JR  Muller J  Pangilinan J  Patwardhan RP  Pitluck S  Pritham EJ  Rechtsteiner A  Rho M  Rogozin IB  Sakarya O  Salamov A  Schaack S  Shapiro H  Shiga Y  Skalitzky C  Smith Z  Souvorov A  Sung W 《Science (New York, N.Y.)》2011,331(6017):555-561

We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.  相似文献   

Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases     

Gunn-Moore DA  McFarland SE  Schock A  Brewer JI  Crawshaw TR  Clifton-Hadley RS  Shaw DJ 《Journal of Feline Medicine and Surgery》2011,13(12):945-952

This study investigated 339 cases of feline mycobacterial infection, with histopathology findings from 225 cases, and treatment and outcome information from 184 cases. Tissue samples from cats with cutaneous lesions or suspicious masses at exploratory laparotomy were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study reviewed the files for information about histopathology, treatment and outcome, and blindly reviewed histopathological changes (including staining for acid-fast bacteria [AFB]) in a sub-set of 45 cases. When a cat is suspected of having a mycobacterial infection, accurate identification of the species involved helps to determine possible treatment options and prognosis. The study confirmed that histopathology and the presence of AFB are useful tools in the recognition of mycobacterial infection. Unfortunately, they did little to help determine the species of mycobacteria involved. The study identified a group of cats that were negative for AFB at the primary laboratory, but from which mycobacteria could be cultured; commonly Mycobacterium bovis or Mycobacterium microti. The study also identified a group of cats which where culture negative, despite typical signs of mycobacterial infection and positive AFB staining. Many cases responded favourably to treatment (56% of the cases where information was available), and many cats gained complete remission (42%). However, relapses were common (64%) and often followed by pulmonary and/or systemic spread that may have resulted from treatment with short courses of single drugs. This study shows that the diagnosis and treatment of feline mycobacteriosis is complex and challenging.  相似文献   

Resveratrol in raw and baked blueberries and bilberries     

Lyons MM  Yu C  Toma RB  Cho SY  Reiboldt W  Lee J  van Breemen RB 《Journal of agricultural and food chemistry》2003,51(20):5867-5870

Resveratrol in the fruits of bilberry (Vaccinium myrtillus L.), the lowbush "wild" blueberry (Vaccinium angustifolium Aiton), the rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry (Vaccinium corymbosum L.) were measured using a new assay based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS assay provided lower limits of detection than previous methods for resveratrol measurement, 90 fmol of trans-resveratrol injected on-column, and a linear standard curve spanning >3 orders of magnitude. The recoveries of resveratrol from blueberries spiked with 1.8, 3.6, or 36 ng/g were 91.5 +/- 4.5, 95.6 +/- 6.5, and 88.0 +/- 3.6%, respectively. trans-Resveratrol but not cis-resveratrol was detected in both blueberry and bilberry samples. The highest levels of trans-resvertatrol in these specimens were 140.0 +/- 29.9 pmol/g in highbush blueberries from Michigan and 71.0 +/- 15.0 pmol/g in bilberries from Poland. However, considerable regional variation was observed; highbush blueberries from British Columbia contained no detectable resveratrol. Because blueberries and bilberries are often consumed after cooking, the effect of baking on resveratrol content was investigated. After 18 min of heating at 190 degrees C, between 17 and 46% of the resveratrol had degraded in the various Vaccinium species. Therefore, the resveratrol content of baked or heat-processed blueberries or bilberries should be expected to be lower than in the raw fruit. Although blueberries and bilberries were found to contain resveratrol, the level of this chemoprotective compound in these fruits was <10% that reported for grapes. Furthermore, cooking or heat processing of these berries will contribute to the degradation of resveratrol.  相似文献