Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A₂-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation.     

非小细胞肺癌术后并发乳糜胸对患者生活质量影响的研究

目的:探讨非小细胞肺癌术后并发乳糜胸对患者生活质量的影响。方法:采用生活质量测定量表(QLQ-C30)回顾性分析第四军医大学唐都医院胸外科自2013年至2016年中收治的1015例肺癌手术患者的生活质量,发生乳糜胸组记为A组,未发生乳糜胸组记为B组。对比术前和术后1、3、6和12个月的生活质量有无统计学差异。结果:(1)术后1月时,除了社会功能、便秘、腹泻以外,两组生活质量指标评分均显著低于术前,且B组均显著低于A组,有统计学差异(表3,P0.05)。在手术后3月及以后逐渐恢复,至12月时,各组指标与术前基本相同(表3,P0.05);(2)两组术后生活质量相比较,术后1、3月,除社会功能、便秘、腹泻以外,其余生活质量功能指标B组均显著优于A组,有统计学差异(表3,P0.05)。在手术后6月及以后,B组所有指标与A组无统计学差异(表3,P0.05)。结论:肺癌根治术后发生乳糜胸患者生活质量显著低于未发生乳糜胸患者,因此应合理选择手术方式,注意术中操作,降低乳糜胸发生率,提高肺癌患者术后的生活质量。     

Evaluating the role of livelihood assets in suitable livelihood strategies: Protocol for anti-poverty policy in the Eastern Tibetan Plateau,China

Although numerous studies have been conducted on the relationship between livelihood assets and strategies, only a few quantitative studies exist on the topic for anti-poverty policies with regard to the Tibetan Plateau. This study investigated 357 households in the upper reaches of the Dadu River watershed in the Eastern Tibetan Plateau, China, using the participatory rural appraisal method. Then, applying a multinomial logistic regression model, we quantitatively analyzed the relationship between livelihood assets and livelihood strategies, the findings of which have implications for local agricultural policy interventions. The preliminary results indicate that of the four classifications of livelihood strategies used in this study, the main livelihood strategy is that of the non-farming-dependent household type (i.e., Type III in our study) that combines agricultural and non-farm activities or practices self-employment for wages. There are significant differences in the livelihood assets owned by households with different livelihood strategies. Human, natural, and financial assets have significant influences on livelihood strategies, and the choice of livelihood strategy varies by livelihood assets. Further, with improvements in household labor capacity and cash income per capita, the livelihood strategies of non-agricultural and non-farming households may shift away from agriculture, while an increase in farmland cultivated per capita, cash income per capita, and household labor capacity may encourage households to adopt agriculture-dependent livelihood strategies. These findings contribute to research on livelihood and related development strategies and anti-poverty policies in not only the Eastern Tibetan Plateau but also other regions with similar livelihood strategies.     

The evolution of intermediate castration virulence and ant coexistence in a spatially structured environment

Theory suggests that spatial structuring should select for intermediate levels of virulence in parasites, but empirical tests are rare and have never been conducted with castration (sterilizing) parasites. To test this theory in a natural landscape, we construct a spatially explicit model of the symbiosis between the ant-plant Cordia nodosa and its two, protecting ant symbionts, Allomerus and Azteca . Allomerus is also a castration parasite, preventing fruiting to increase colony fecundity. Limiting the dispersal of Allomerus and host plant selects for intermediate castration virulence. Increasing the frequency of the mutualist, Azteca , selects for higher castration virulence in Allomerus , because seeds from Azteca -inhabited plants are a public good that Allomerus exploits. These results are consistent with field observations and, to our knowledge, provide the first empirical evidence supporting the hypothesis that spatial structure can reduce castration virulence and the first such evidence in a natural landscape for either mortality or castration virulence.     

The tRNA A76 Hydroxyl Groups Control Partitioning of the tRNA-dependent Pre- and Post-transfer Editing Pathways in Class I tRNA Synthetase

Aminoacyl-tRNA synthetases catalyze ATP-dependent covalent coupling of cognate amino acids and tRNAs for ribosomal protein synthesis. Escherichia coli isoleucyl-tRNA synthetase (IleRS) exploits both the tRNA-dependent pre- and post-transfer editing pathways to minimize errors in translation. However, the molecular mechanisms by which tRNA^Ile organizes the synthetic site to enhance pre-transfer editing, an idiosyncratic feature of IleRS, remains elusive. Here we show that tRNA^Ile affects both the synthetic and editing reactions localized within the IleRS synthetic site. In a complex with cognate tRNA, IleRS exhibits a 10-fold faster aminoacyl-AMP hydrolysis and a 10-fold drop in amino acid affinity relative to the free enzyme. Remarkably, the specificity against non-cognate valine was not improved by the presence of tRNA in either of these processes. Instead, amino acid specificity is determined by the protein component per se, whereas the tRNA promotes catalytic performance of the synthetic site, bringing about less error-prone and kinetically optimized isoleucyl-tRNA^Ile synthesis under cellular conditions. Finally, the extent to which tRNA^Ile modulates activation and pre-transfer editing is independent of the intactness of its 3′-end. This finding decouples aminoacylation and pre-transfer editing within the IleRS synthetic site and further demonstrates that the A76 hydroxyl groups participate in post-transfer editing only. The data are consistent with a model whereby the 3′-end of the tRNA remains free to sample different positions within the IleRS·tRNA complex, whereas the fine-tuning of the synthetic site is attained via conformational rearrangement of the enzyme through the interactions with the remaining parts of the tRNA body.     

Identification of cardiac stem cells within mature cardiac myocytes

Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit⁺, Sca⁺, and Isl1⁺ stem cells were revealed to be located inside the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40-day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes.     

Effects of acupuncture on declined cerebral blood flow,impaired mitochondrial respiratory function and oxidative stress in multi-infarct dementia rats

Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain.     

1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase

A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.     

4-phenylylboronic acid: A new type of enhancer for the horseradish peroxidase catalysed chemiluminescent oxidation of luminol

4-Phenylylboronic acid enhances the light emission from the horseradish peroxidase catalysed oxidation of luminol by hydrogen peroxide. Optimization studies showed that the greatest enhancement was obtained using micromolar concentrations of the new enhancer. The largest degree of enhancement was found with the basic isoenzyme of horseradish peroxidase (Type VIA), and lesser degrees of enhancement were obtained with Type VII and Type IX horseradish peroxidase. The enhancer was also effective in the peroxidase catalysed oxidation of isoluminol by peroxide.