Costimulatory Effect of Fas in Mouse T Lymphocytes

To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28-engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation.     

A melanosome-associated monoclonal antibody J1 recognizes luminal membrane of prelysosomes common to biogenesis of melanosomes and lysosomes

Melanogenesis cascade may be directly or indirectly linked to the dynamics of endosome-lysosome biogenesis. This study aims to identify how and to what extent the endosome-lysosome system is involved in melanosome biogenesis, by utilizing a novel melanogenesis marker, J1, which we identified in the process of developing monoclonal antibodies (MoAbs) against human melanosomes. The antigenic epitope of MoAb J1 was expressed by all of the melanotic and nonmelanotic cells examined. It was expressed primarily by granular structures located in regions proximal to the Golgi complex. Most of MoAb J1 positive granules were co-stained with melanogenic markers, tyrosinase or tyrosinase-related protein (TRP-1). The epitope of MoAb J1 was also coexpressed by most, but not all, of LGP85 (a lysosomal marker) positive granules in both melanoma and non-melanoma cells, indicating that MoAb J1 recognizes a subset of lysosomal vesicles. MoAb J1 did not, however, react with vesicles with late/early (syntaxin 8/ EEA1) endosomal markers. Further examination using fluorophore-labeled pepstatin, a marker of lysosomal luminal content, confirmed that MoAb J1 specifically recognizes the luminal surface of lysosomes. These results indicate that MoAb J1 possesses an antigen epitope that is expressed in the luminal component of prelysosomal granules which are involved in the biogenesis cascade common to both melanosomes and lysosomes. We suggest that tyrosinase family protein, tyrosinase and TRP-1 are transported to melanosomes from TGN via these prelysosomal granules after being transiently transported to late endosomes.     

长白山地区产18种根类药材对四氯化碳肝损伤的影响

目的 研究18种药材水提物对小鼠SGPT和SGOT的影响。方法 在四氯化碳所致小鼠急性肝损伤的血清中检测SGTP和SGOT值。结果 东当归、党参、莪术、北龙胆、茜草、黄芪、川芎和北柴胡水提物显著抑制四氯化碳所致小鼠SGTP和SGOT值升高。结论 东当归等8药材水提取对四氯化碳损伤具有保护作用。     

Peony Glycosides Protect Against Corticosterone-Induced Neurotoxicity in PC12 Cells

Preclinical and clinical investigations have shown the involvement of dysregulation of hypothalamic–pituitary–adrenal (HPA) axis in the pathogenesis of depression. Hypercortisolemia and the associated hippocampal atrophy were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Previous studies in our laboratory have demonstrated the antidepressant-like activity of total glycosides of peony (TGP) in mice. This study aimed to examine the effect of TGP treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Treating the cells with corticosterone at 200 μM for 48 h caused apoptotic cell death. The cytotoxicity was associated with the activation of caspase-3 activity and the decrease in the mRNA ratio of bcl-2 to bax. TPG treatment at increasing doses (1–10 mg/l) protected against the corticosterone-induced toxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with the inhibition of caspase-3 activity and the up-regulation of bcl-2/bax mRNA ratio. The anti-apoptotic effect of TGP is therefore likely mediated by the suppression of the mitochondrial pathway leading to apoptosis.     

Reducing stem bending increases the height growth of tall pines

The hypothesis was tested that upper limits to height growth in trees are the result of the increasing bending moment of trees as they grow in height. The increasing bending moment of tall trees demands increased radial growth at the expense of height growth to maintain mechanical stability. In this study, the bending moment of large lodgepole pine (Pinus contorta Dougl. Ex Loud. var. latifolia Engelm.) was reduced by tethering trees at 10 m height to counter the wind load. Average bending moment of tethered trees was reduced to 38% of control trees. Six years of tethering resulted in a 40% increase in height growth relative to the period before tethering. By contrast, control trees showed decreased height growth in the period after tethering treatment. Average radial growth along the bole, relative to height growth, was reduced in tethered trees. This strongly suggests that mechanical constraints play a crucial role in limiting the height growth of tall trees. Analysis of bending moment and basal area increment at both 10 m and 1.3 m showed that the amount of wood added to the stem was closely related to the bending moment produced at these heights, in both control and tethered trees. The tethering treatment also resulted in an increase in the proportion of latewood at the tethering height, relative to 1.3 m height. For untethered control trees, the ratio of bending stresses at 10 m versus 1.3 m height was close to 1 in both 1998 and 2003, suggesting a uniform stress distribution along the outer surface of the bole.     

Ketoprofen resolution by enzymatic estirification and hydrolysis of the ester product

ImmobilizedCandida antarctica lipase was used to catalyze the separation of ketoprofen into its components by means of esterification followed by the enzymatic hydrolysis of the ester product. In this study, ketoprofen underwent esterification to ethanol in the presence of isooctane. When the reaction was complete, 58.3% of the ketoprofen had been transformed into an ester. The ketoprofen remaining in solution after the reation was complete consisted primarily of itsS-enantiomer (83.0%), while the 59.4% of the ketoprofen component of the ester consisted of itsR-enantiomer. We then subjected the ester product to enzymatic hydrolysis in the presence of the same enzyme and produced a ketoprofen product rich in theR-enantiomer; 77% of this product consisted of theR-enantiomer when 50% of the ester had been hydrolyzed, and 90% of it consisted of theR-enantiomer when 30% of the ester had been hydrolyzed. By contrast, theR-enantiomer levels only reached approximately 42 and 65%, respectively, when 50 and 30% of the racemic ester was hydrolyzed under the same conditions.     

High prevalence of serum folate receptor autoantibodies in children with autism spectrum disorders

Abstract

Background: Supplementation of folic acid by pregnant mothers is thought to lower the risk of autism spectrum disorders (ASDs) in the offspring. Folic acid is taken up by cells via receptors with high affinity for folate and reduced folic acid derivatives. However, this is blocked by the presence of folate receptor autoantibodies (FRAA). Cerebral FRAA have been detected with high frequency in children with ASDs, suggesting the existence of a link between folic acid uptake and disease aetiology.

Methods: We investigated the frequency of FRAA in serum samples from 40 children with ASDs and 42 gender- and age-matched children with typical development (TD). Serum FRAA concentrations were measured by enzyme-linked immunosorbent assay.

Results: We found a significant difference in the frequency of serum FRAA in the two study cohorts. Serum FRAA were present in 77.5% (31/40) of children with ASDs compared with 54.8% (23/42) of TD children (p?=?0.03746, Fischer’s exact test). Thus, serum FRAA are more prevalent in children with ASDs than in TD children.

Conclusions: Our data suggest that children with ASDs may have defects in folic acid absorption that play a role in the onset of ASDs.     

ICAM-1与脑梗死关系的研究进展

炎症在脑梗死的发病机制中扮演着非常重要的角色,动脉粥样硬化是脑梗死的病理基础,动脉粥样硬化被认为是一种慢性炎症过程,这种炎症过程与黏附分子的表达有关,如细胞间黏附分子-1(ICAM-1),它能黏附循环中的白细胞,促进内皮细胞表面粥样斑块的形成,许多研究表明,ICAM-1与脑梗死密切相关,本文就二者的关系做一综述.