Thyroid hormone controls carnitine status through modifications of γ-butyrobetaine hydroxylase activity and gene expression

The carnitine system plays a key role in β-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on γ-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability. Received 23 October 2001; received after revision 11 January 2002; accepted 15 January 2002     

The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP^C). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP^C. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP^C-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrP^C signaling.     

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

Study of the mechanism of inhibition produced by hexoses on histamine release activity of dextran

Zusammenfassung Die Hemmung der Histaminfreisetzung durch Hexosen wurde untersucht. Es gelang, nachzuweisen bzw. graphisch darzustellen, dass ein Zusammenhang zwischen dem Prozentgehalt der Histaminfreisetzung und der Dextrankonzentration besteht, wenn nachLineweaver undBurk analysiert wurde.     

企业研发团队知识共享影响因素的实证研究

基于知识共享理论和研发团队知识共享特征和影响因素,提出企业研发团队知识共享影响因素概念模型及理论假设,并运用调查问卷和结构方程模型对研发团队知识共享影响因素进行实证研究.结果表明,知识提供者、接受者、共享手段和共享双方关系4因素对研发团队知识共享水平有显著影响,而知识共享文化对知识共享水平影响作用不显著.提出了提高企业研发团队知识共享水平的对策与建议.     

基于Simulink的动态电路分析

介绍了Simulink应用于动态电路仿真分析的方法,以一个实例详述了图形输入式建模、参数设置、仿真配置、Matlab绘图分析等步骤．指出了联合运用To File、To Workspace和Scope模块,实现不同参数情况下仿真分析的优越性．     

数学分析在高等代数中的某些应用

高等代数中的某些问题,若用代数学的方法解决起来可能相当繁琐,但若结合数学分析的方法,则问题往往会迎刃而解．该文使用数学分析中的函数连续性和无穷区间的广义积分知识解决某些矩阵问题和二次型问题．     

Adenosine-3,5-phosphate levels in brain structures of rats submitted to four different behavioral procedures

Shuttle avoidance training decreased the cAMP content of rat brain (excluding hippocampus and caudate nucleus), amygdala and hypothalamus. Stimulation by tones alone had a similar effect, but only in the brain fraction. Pseudoconditioning or footshocks alone had no effect.