Melatonin transport into mitochondria

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.     

System optimization model of adoption of a new infrastructure with multi-resource and multi-demand sites

This study develops a conceptual system optimization model of adoption of a new infrastructure technology with multiple resource sites and multiple demand sites. With the model, this paper analyzes how the distance, spillover effect, demand, initial investment cost, and learning rate influence the adoption of the new infrastructure technology and presents optimization results of the model in different scenarios. The main findings of the study are: from the perspective of system optimization, (1) different distances among different resource-demand pairs will result in different adoption time of a new infrastructure; (2) technological spillover among different resource-demand pairs will accelerate the adoption of a new infrastructure; (3) it is hard to say that higher demand will pull faster adoption of a new infrastructure, and the optimal time of adopting of a new infrastructure is very sensitive to its technological learning rate.     

Social Media as a Mean for Improved Technical Communication

Technical communication (TC) is an important activity in order to provide the users of technical artifacts with necessary information concerning the operation and maintenance of the products they are using. In the current working procedures of TC, however, the users become too passive. They are just receivers of information. Further, there is no effective feedback from the users to the producers of the information. In order to overcome those problems we here propose an application of social media (SM) in future TC. By using SM as a complementary channel for TC it becomes possible for technology firms to boost their competitive advantage and to improve the quality and completeness of their TC. This technique, however, is still more of a potential and less of a reality. Several problems, mostly concerning security and confidentiality remain to be solved. The empirical base for this work comes from TIC, an EU-funded development project involving several Swedish technology companies. Published research results are somewhat scattered but several sources coherently indicate both the need and potential for SM as a vehicle in TC. By scanning the net it is further possible to identify a number of seemingly successful applications of SM in such applications.     

系统功能语言学的《荷塘月色》对比语篇分析

基于韩礼德系统功能语言学的理论框架,从概念功能和语篇功能的视角出发,对朱自清先生的《荷塘月色》和四个英译本(朱纯深译本、杨宪益、戴乃迭译本、王椒升译本和李明译本)的及物性过程和主位进行了对比分析,用统计数字来说明哪个译本和原文的概念功能和语篇功能最接近,为四个英译本的对比语篇分析提供了一种较为客观的视角,在一定程度弥补了从各个译文中人为地挑选出几个句子来进行分析时存在的主观性与随意性的不足。     

Mechanical and corrosion properties of low-carbon steel prepared by friction stir processing

Low-carbon steel plates were successfully subjected to normal friction stir processing(NFSP) in air and submerged friction stir processing(SFSP) under water, and the microstructure, mechanical properties, and corrosion behavior of the NFSP and SFSP samples were investigated. Phase transformation and dynamic recrystallization resulted in fine-grained ferrite and martensite in the processed zone. The SFSP samples had smaller ferrites(5.1 μm), finer martensite laths(557 nm), and more uniform distribution of martensite compared to the NFSP samples. Compared to the base material(BM), the microhardness of the NFSP and SFSP samples increased by 19.8% and 27.1%, respectively because of the combined strengthening effects of grain refinement, phase transformation, and dislocation. The ultimate tensile strengths(UTSs) of the NFSP and SFSP samples increased by 27.1% and 38.7%, respectively. Grain refinement and martensite transformation also improved the electrochemical corrosion properties of the low-carbon steel. Overall, the SFSP samples had better mechanical properties and electrochemical corrosion resistance than the NFSP samples.     

BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β

Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis.     

Viral journeys on the intracellular highways

Viruses are obligate intracellular pathogens that are dependent on cellular machineries for their replication. Recent technological breakthroughs have facilitated reliable identification of host factors required for viral infections and better characterization of the virus–host interplay. While these studies have revealed cellular machineries that are uniquely required by individual viruses, accumulating data also indicate the presence of broadly required mechanisms. Among these overlapping cellular functions are components of intracellular membrane trafficking pathways. Here, we review recent discoveries focused on how viruses exploit intracellular membrane trafficking pathways to promote various stages of their life cycle, with an emphasis on cellular factors that are usurped by a broad range of viruses. We describe broadly required components of the endocytic and secretory pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Identification of such overlapping host functions offers new opportunities to develop broad-spectrum host-targeted antiviral strategies.     

PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization

Polarity is a fundamental feature of cells. Protein complexes, including the PAR3–PAR6–aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3–PAR6–aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity.     

Including the mitochondrial metabolism of <Emphasis Type="SmallCaps">l</Emphasis>-lactate in cancer metabolic reprogramming

Glucose avidity, high glycolysis and l-lactate production, regardless of oxygen availability, are the main traits of cancer metabolic reprogramming. The idea that mitochondria are dysfunctional in cancer, thus causing a glycolysis increase for ATP production and l-lactate accumulation as a dead-end product of glucose catabolism, has oriented cancer research for many years. However, it was shown that mitochondrial metabolism is essential for cancer cell proliferation and tumorigenesis and that l-lactate is a fundamental energy substrate with tumor growth-promoting and signaling capabilities. Nevertheless, the known ability of mitochondria to take up and oxidize l-lactate has remained ignored by cancer research. Beginning with a brief overview of the metabolic changes occurring in cancer, we review the present knowledge of l-lactate formation, transport, and intracellular oxidation and underline the possible role of l-lactate metabolism as energetic, signaling and anabolic support for cancer cell proliferation. These unexplored aspects of cancer biochemistry might be exploited for therapeutic benefit.     

铝合金表面ZSM-5型分子筛涂层耐蚀性研究

【目的】探究分子筛作为填料添加到水性涂料中对涂层防腐性能的影响。【方法】利用光学显微镜、XRD及SEM对涂层的中分子筛填料分散效果和涂层微观形貌进行表征,利用极化曲线分析分子筛水性涂层的电化学性能。【结果】分子筛粉末在水性漆中的最大添加比例为15%,超过此比例会出现大块团聚现象。其中10%的分子筛粉末对涂料耐蚀性提升最大。【结论】分子筛良好的高温水热稳定性有助于提高涂料的耐蚀性,但由于水性树脂不能够将分子筛颗粒紧密粘结,其添加量过大时会导致涂层耐蚀性能下降。