Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation

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.     

A yeast gene that is essential for release from glucose repression encodes a protein kinase

The SNF1 gene plays a central role in carbon catabolite repression in the yeast Saccharomyces cerevisiae, namely that SNF1 function is required for expression of glucose-repressible genes. The nucleotide sequence of the cloned SNF1 gene was determined, and the predicted amino acid sequence shows that SNF1 encodes a 72,040-dalton polypeptide that has significant homology to the conserved catalytic domain of mammalian protein kinases. Specific antisera were prepared and used to identify the SNF1 protein. The protein was shown to transfer phosphate from adenosine triphosphate to serine and threonine residues in an in vitro autophosphorylation reaction. These findings indicate that SNF1 encodes a protein kinase and suggest that protein phosphorylation plays a critical role in regulation by carbon catabolite repression in eukaryotic cells.     

Class II-independent generation of CD4 memory T cells from effectors

The factors required for the generation of memory CD4 T cells remain unclear, and whether there is a continuing requirement for antigen stimulation is critical to design of vaccine strategies. CD4 effectors generated in vitro from na?ve CD4 T cells of mice efficiently gave rise to small resting memory cells after transfer to class II-deficient hosts, indicating no requirement for further antigen or class II recognition.     

植原体分类研究进展

目的明确云南元谋地区发生的萝卜花变叶病病原以及赤霉素合成途径中关键酶基因表达量的变化。方法对自然表现花变叶、丛枝和节间缩短的萝卜感病植株总DNA进行植原体16S rRNA基因扩增、克隆、测序及系统进化树构建,并采用实时荧光定量PCR技术分析赤霉素合成及代谢途径中关键酶基因(GA20ox1、GA3ox1和GA2ox1)表达量的变化。结果该植原体株系与16SrII-A亚组相似性最高(0.98),并与16SrII-A亚组中的其他植原体株系明显形成一个进化支。结论萝卜花变叶植原体(Raphanus sativus phyllody,RsPh-YNym)为植原体16SrII-A亚组成员,且与候选种Candidatus Phytoplasma aurantifolia相关,明确了该株系的分类地位;感病植株茎中3种关键酶基因GA20ox1、GA3ox1和GA2ox1表达水平发生了变化,表达量均下调,说明植原体的侵染造成了植株赤霉素稳态被破坏,从而导致植株表型改变。     

Phase modifiers promote efficient production of hydroxymethylfurfural from fructose

Furan derivatives obtained from renewable biomass resources have the potential to serve as substitutes for the petroleum-based building blocks that are currently used in the production of plastics and fine chemicals. We developed a process for the selective dehydration of fructose to 5-hydroxymethylfurfural (HMF) that operates at high fructose concentrations (10 to 50 weight %), achieves high yields (80% HMF selectivity at 90% fructose conversion), and delivers HMF in a separation-friendly solvent. In a two-phase reactor system, fructose is dehydrated in the aqueous phase with the use of an acid catalyst (hydrochloric acid or an acidic ion-exchange resin) with dimethylsulfoxide and/or poly(1-vinyl-2-pyrrolidinone) added to suppress undesired side reactions. The HMF product is continuously extracted into an organic phase (methylisobutylketone) modified with 2-butanol to enhance partitioning from the reactive aqueous solution.     

Channel-mediated tonic GABA release from glia

Synaptic inhibition is based on both tonic and phasic release of the inhibitory transmitter γ-aminobutyric acid (GABA). Although phasic GABA release arises from Ca(2+)-dependent exocytosis from neurons, the mechanism of tonic GABA release is unclear. Here we report that tonic inhibition in the cerebellum is due to GABA being released from glial cells by permeation through the Bestrophin 1 (Best1) anion channel. We demonstrate that GABA directly permeates through Best1 to yield GABA release and that tonic inhibition is eliminated by silencing of Best1. Glial cells express both GABA and Best1, and selective expression of Best1 in glial cells, after preventing general expression of Best1, fully rescues tonic inhibition. Our results identify a molecular mechanism for tonic inhibition and establish a role for interactions between glia and neurons in mediating tonic inhibition.     

Selective release of enzymes from bacteria

A group of hydrolytic enzymes, including phosphatases and nucleases, is selectively released from E. coli and certain other Gram-negative bacteria by a process designated as osmotic shock. This procedure involves exposure of the cells to ethylenediaminetetraacetate (EDTA) in 0.5 molar sucrose followed by a sudden osmotic transition to cold, dilute MgCl(2). Osmotic shock also results in an alteration of the permeability barrier of the bacterial cell and a depletion of the pool of acid-soluble nucleotides, but there is no loss of viability. On being restored to growth medium, the shocked cells recover after a lag period. Formation of spheroplasts by treatment with EDTA and lysozyme leads to selective release of the same group of enzymes. We believe that the selectively released enzymes are confined in a region between the bacterial cell wall and the cytoplasmic membrane. Histochemical studies indicate such a localization. Further, the enzyme activities are measurable with intact cells, even when the substrate is a nucleotide, to which whole cells are impermeable. Another piece of evidence concerns a mutant E. coli with a defective cell wall. In contrast to normal bacteria, this organism loses one of these enzymes into the medium in the course of growth. After osmotic shock, the bacteria show reduced uptake of sulfate,betagalactosides, galactose, and certain amino acids. Furthermore, the shock treatment causes the release of nondialyzable factors able to bind sulfate, galactose, and the same amino acids. A possible interpretation of these observations is the following: the binding proteins occupy sites near the bacterial surface, and they may be components of active transport systems responsible for the concentrative uptake of these nutrients.     

Thiamine release from nerve membranes by tetrodotoxin

Tetrodotoxin (3 x 10(-8) molar) promoted the release of thiamine from perfused rat and frog nerve preparations in a manner similar to other neuroactive drugs. When the rats were injected with thiamine labeled with sulfur-35, analyses of brain, spinal cord, and sciatic nerve homogenates revealed labeled thiamine in membrane, synaptosomes, and mitochondrial subfractions. However, on incubation of these fractions with tetrodotoxin, thiamine was released only from the membrane fragments.     

Glucose-dependent insulin release from genetically engineered K cells

Genetic engineering of non-beta cells to release insulin upon feeding could be a therapeutic modality for patients with diabetes. A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP). Mice expressing this transgene produced human insulin specifically in gut K cells. This insulin protected the mice from developing diabetes and maintained glucose tolerance after destruction of the native insulin-producing beta cells.     

Insulin release from isolated human fetal pancreatic islets

Pancreases were obtained from five human fetuses 12 to 16 weeks old. The islets of Langerhans were isolated with collagenase, and then incubated with buffer, glucose, tolbutamide, or glucagon added to the medium. The insulin released into the medium was measured by immunoassay. Glucagon produced the only significant increase above base line; glucose and tolbutamide failed to enhance secretion of insulin. The data suggest that isolated human fetal islets of this gestational age develop responsiveness to glucagon earlier than to glucose or tolbutamide.     

Evidence that glucose "marks" beta cells resulting in preferential release of newly synthesized insulin

Studies of isolated islets labeled with radioactive leucine show that glucose at a critical time "marks" islets in such a way as to cause preferential release of newly synthesized insulin. The preferential release of insulin from marked islets is relatively independent of subsequent secretagogues or rates of insulin secretion. Previous kinetic studies have indicated that the critical time at which marking occurs is after proinsulin biosynthesis but before the secretory event. Thus, secretory cells may regulate the diversion of newly synthesized material for immediate release as it is approaching or transiting the Golgi apparatus.     

Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum

The role of sodium-calcium exchange at the sarcolemma in the release of calcium from cardiac sarcoplasmic reticulum was investigated in voltage-clamped, isolated cardiac myocytes. In the absence of calcium entry through voltage-dependent calcium channels, membrane depolarization elicited release of calcium from ryanodine-sensitive internal stores. This process was dependent on sodium entry through tetrodotoxin-sensitive sodium channels. Calcium release under these conditions was also dependent on extracellular calcium concentration, suggesting a calcium-induced trigger release mechanism that involves calcium entry into the cell by sodium-calcium exchange. This sodium current-induced calcium release mechanism may explain, in part, the positive inotropic effects of cardiac glycosides and the negative inotropic effects of a variety of antiarrhythmic drugs that interact with cardiac sodium channels. In response to a transient rise of intracellular sodium, sodium-calcium exchange may promote calcium entry into cardiac cells and trigger sarcoplasmic calcium release during physiologic action potentials.     

Norepinephrine: release from brain by d-amphetamine in vivo

After injection of H(3)-norepinephrine into the left lateral cerebral ventricle of cats, the lateral and third cerebral ventricles were perfused with an artificial cerebrospinal fluid. Addition of d-amphetamine to the perfusion fluid caused a significant increase in the concentration of H(3)-norepinephrine in the effluent.     

Superconductivity--the state that came in from the cold

The exploration of high transition temperature copper-oxide-based superconductors has proceeded vigorously and internationally during the first year following the initial publication of the work of Bednorz and Müller. Progress in understanding the physics that underlies the phenomena has been slowed by difficulties resulting from the delicate and complex crystal chemistry of the material. Reports of superconducting behavior well above 100 kelvin have not been confirmed to date, although there is some suggestive evidence. A survey of the present state of the science and the possibilities for electronic and electrical power technologies is given.     

A compound from smoke that promotes seed germination

Exposure of seeds to aerosol smoke or crude smoke extracts stimulates the germination of a number of fire-dependent and fire-independent plant species. We now report the identity of a germination-promoting compound present in plant- and cellulose-derived smoke. The structure of this compound, deduced from spectroscopic analysis and confirmed by synthesis, was shown to be that of the butenolide 3-methyl-2H-furo[2,3-c]pyran-2-one (1). Here we show that 1 promotes germination of a number of plant species at a level similar to that observed with plant-derived smoke water.     

海峡两岸水产品对东盟市场出口增长的影响因素及合作对策

利用1996—2014年中国大陆与中国台湾地区水产品出口贸易数据,采用恒定市场份额模型对海峡两岸水产品对东盟市场出口增长的影响因素进行分析。结果表明:1)两岸水产品对东盟市场出口增长受到国际市场贸易政策变化的影响。2)东盟市场需求增长是两岸对东盟市场出口增长的主要原因。3)中国大陆对东盟市场总体竞争效应不断增强,但在需求量较大的市场其竞争力提升较慢;中国台湾水产品在东盟市场的竞争力不断增强,但受困于自身渔业发展瓶颈,近年来竞争效应的比重有所下降。4)随着市场的融合,两岸水产品出口与东盟水产品进口需求的匹配度越来越高。针对两岸在东盟市场出口增长的影响因素,本研究提出二者在东盟市场渔业合作的对策建议:力求出口与需求相匹配,加强两岸渔业领域的深层次合作,两岸合作共同投资开发东盟市场,开展差异性的营销策略。     

有机肥氮素释放动态模型的初步研究

在大田填埋试验资料的基础上,假定有机肥C／N随分解时间而变,其变化规律遵循一阶动力学方程,根据作物残体分解过程中C／N的变化及业已建成的作物残体有机碳分解动态模型,建立了有机肥氮素释放动态模型。分析结果表明,模型对于有机物料初始C／N和木质素含量有较强的敏感性。利用文献资料对所建模型进行了验证,结果表明,模型对大部分数据有较好的模拟效果。本模型可以为指导有机肥的合理施用提供依据。     

Proportional release of norepinephrine and dopamine- -hydroxylase from sympathetic nerves

Dopamine-beta-hydroxylase(DBH), the enzyme that catalyzes the conversion of dopamine to norepinephrine, is localized in the vesicles containing catecholamine in sympathetic nerves. This enzyme is released with norepinephrine when the nerves to the guinea pig vas deferens are stimulated in vitro, and the amount of enzyme discharged increases as the length of stimulation periods increases. The amount of DBH released is proportional to the amount of norepinephrine released, and the ratio of norepinephrine to DBH discharged into the incubation medium is similar to that in the soluble portion of the contents of the synaptic vesicles from the vas deferens. These data are compatible with the release of the neurotransmitter norepinephrine and DBH from symnpathetic nerves by a process of exocytosis.