<Emphasis Type="Italic">Ginkgo biloba</Emphasis> extract EGb<Superscript>®</Superscript> 761 increases endothelial nitric oxide production <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Beneficial effects of Ginkgo biloba on peripheral arterial occlusive disease have been repeatedly shown in clinical trials, especially after use of EGb 761, a standardized special extract. Since the underlying mechanisms are widely unknown, we aimed to elucidate the molecular basis on which EGb 761 protects against endothelial dysfunction in vitro and in vivo. Application of therapeutically feasible doses of EGb 761 for 48 h caused endothelial nitric oxide (NO) production by increasing endothelial nitric oxide synthase (eNOS) promoter activity and eNOS expression in vitro. Phosphorylation of eNOS at a site typical for Akt (Ser 1177) was acutely enhanced by treatment with EGb 761, as was Akt phosphorylation at Ser 478. Furthermore, the extract caused acute relaxation of isolated aortic rings and NO-dependent reduction of blood pressure in vivo in rats. These influences on eNOS represent a putative molecular basis for the protective cardiovascular properties of EGb 761.     

<Emphasis Type="Italic">Cis</Emphasis>–<Emphasis Type="Italic">trans</Emphasis> interactions of cell surface receptors: biological roles and structural basis

Cell surface receptors bind ligands expressed on other cells (in trans) in order to communicate with neighboring cells. However, an increasing number of cell surface receptors are found to also interact with ligands expressed on the same cell (in cis). These observations raise questions regarding the biological role of such cis interactions. Specifically, it is important to know whether cis and trans binding have distinct functional effects and, if so, how a single cell discriminates between interactions in cis versus trans. Further, what are the structural features that allow certain cell surface receptors to engage ligand both on the same as well as on an apposed cell membrane? Here, we summarize known examples of receptors that display cis–trans binding and discuss the emerging diversity of biological roles played by these unconventional two-way interactions, along with their structural basis.     

Is Newton a ‘radical empiricist’ about method?

Recently, some Newton scholars have argued that Newton is an empiricist about metaphysics—that ideally, he wants to let advances in physical theory resolve either some or all metaphysical issues. But while proponents of this interpretation are using ‘metaphysics’ in a very broad sense, to include the ‘principles that enable our knowledge of natural phenomena’, attention has thus far been focused on Newton’s approach to ontological, not epistemological or methodological, issues. In this essay, I therefore consider whether Newton wants to let physical theory bear on the very ‘principles that enable our knowledge’. By examining two kinds of argument in the Principia, I contend that Newton can be considered a methodological empiricist in a substantial respect. I also argue, however, that he cannot be a ‘radical empiricist’—that he does not and cannot convert all methodological issues into empirical issues.     

What leads from <Emphasis Type="Italic">dead-end?</Emphasis>

The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified. The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development due to Dnd1 inactivation. Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007     

"Add-on" domains of<Emphasis Type="Italic"> Drosophila</Emphasis> β1,4-<Emphasis Type="Italic">N</Emphasis>-acetylgalactosaminyltransferase B in the stem region and its pilot protein

The glycolipid specific Drosophila melanogaster β1,4-N-acetylgalactosaminyltransferase B (β4GalNAcTB) depends on a zinc finger DHHC protein family member named GalNAcTB pilot (GABPI) for activity and translocation to the Golgi. The six-membrane spanning protein actually lacks the cysteine in the cytoplasmic DHHC motif, displaying DHHS instead. Here we show that the whole conserved region around the DHHS sequence, which is essential for palmitoylation in DHHC proteins, is not required for GABPI to interact with β4GalNAcTB. In contrast, the two luminal loops between transmembrane domain 3–4 and 5–6 contain conserved amino acids, which are crucial for activity. Besides the dependence on GABPI, β4GalNAcTB requires its exceptional short stem region for activity. A few hydrophobic amino acids positioned close to the transmembrane domain are essential for the interaction with GABPI. Along with its catalytic domain, β4GalNAcTB, thus, requires an area in its own stem region and two small luminal loops of GABPI as "add-on" domains. Moreover, some inactive GABPI mutants could be rescued by fusion with β4GalNAcTB, indicating their importance in direct GABPI-β4GalNAcTB interaction.     

回复“对‘辐射热力学的新进展——辐射有效能 光量子等效温度光量子熵常数’一文的讨论”

本文关于“对‘辐射热力学的新进展——辐射有效能 光量子等效温度 光量子熵常数’一文的讨论”中所举例证进行了分析, 指明其例证中对相关概念的理解和使用有误. 同时进一步阐述了光量子等效温度、光谱辐射有效能和光子熵常数与宏观态温度、热能有效能和宏观态熵的异同点, 指出辐射能具有微观态的量子作用特性和宏观态的平均热能作用特性的双重性.     

Elemental sulphur (S<Subscript>8</Subscript>) in higher plants — biogenic or anthropogenic origin

In the course of investigating lipophilic air pollutants in the epicuticular wax ofPinus sylvestris L. needles, elemental sulphur, S₈, was found in all samples. An investigation was conducted to determined the origin of this substance. No correlation between the level of S₈ in the needles and human activities in the sampling area could be found, contrary to what would have been expected of an anthropogenic compound. The internal lipids ofP. sylvestris as well as the epicuticular wax of historical herbarium material and seedlings grown in clean, filtered air, and the epicuticular wax of several other species, both gymnosperms and angiosperms, also contained S₈. Quantitation of S₈ inP. sylvestris gave levels of 7.2±2.9 μg/g wax, 3.8±1.9 μg/g internal lipid and 0.43±0.17 μg/g total needle dry weight. Almost 0.1% of the total sulphur in pine needles is S₈, and approximately half of the total S₈ is found in the wax. The results suggest that S₈ is endogenous in many higher plants. A function for S₈ as part of an antifungal defence system is possible.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

国家自然科学基金重大研究计划“重大工程的动力灾变”研究进展

重大研究计划“重大工程的动力灾变”瞄准强地震动场和强/台风场及其动力作用下重大工程的损伤演化破坏过程的国际研究前沿, 重点解决两大关键科学问题, 即: (1) 强地震动场和强/台风场的特性与规律; (2) 重大工程动力灾变的过程与机理. 为此重点开展4个方面的研究工作, 包括: (1) 强地震动场和强/台风场的建模与预测; (2) 重大工程动力灾变的关键效应; (3) 重大工程动力灾变的全过程分析; (4) 重大工程动力灾变模拟系统的集成与验证.     

Proposition II (Book I) of Newton’s <Emphasis Type="Italic">Principia</Emphasis>

After preparing the way with comments on evanescent quantities and then Newton’s interpretation of his second law, this study of Proposition II (Book I)— Proposition II Every body that moves in some curved line described in a plane and, by a radius drawn to a point, either unmoving or moving uniformly forward with a rectilinear motion, describes areas around that point proportional to the times, is urged by a centripetal force tending toward that same point. —asks and answers the following questions: When does a version of Proposition II first appear in Newton’s work? What revisions bring that initial version to the final form in the 1726 Principia? What, exactly, does this proposition assert? In particular, what does Newton mean by the motion of a body “urged by a centripetal force”? Does it assert a true mathematical claim? If not, what revision makes it true? Does the demonstration of Proposition II persuade? Is it as convincing, for example, as the most convincing arguments of the Principia? If not, what revisions would make the demonstration more persuasive? What is the importance of Proposition II, to the physics of Book III and the mathematics of Book I?     

<Emphasis Type="Italic">Legionella pneumophila</Emphasis> — a human pathogen that co-evolved with fresh water protozoa

The bacterial pathogen Legionella pneumophila is found ubiquitously in fresh water environments where it replicates within protozoan hosts. When inhaled by humans it can replicate within alveolar macrophages and cause a severe pneumonia, Legionnaires disease. Yet much needs to be learned regarding the mechanisms that allow Legionella to modulate host functions to its advantage and the regulatory network governing its intracellular life cycle. The establishment and publication of the complete genome sequences of three clinical L. pneumophila isolates paved the way for major breakthroughs in understanding the biology of L. pneumophila. Based on sequence analysis many new putative virulence factors have been identified foremost among them eukaryotic-like proteins that may be implicated in many different steps of the Legionella life cycle. This review summarizes what is currently known about regulation of the Legionella life cycle and gives insight in the Legionella-specific features as deduced from genome analysis. Received 1 September 2006; received after revision 10 October 2006; accepted 22 November 2006     

Intracellular organelles in the saga of Ca<Superscript>2+</Superscript> homeostasis: different molecules for different purposes?

An increase in the concentration of cytosolic free Ca²⁺ is a key component regulating different cellular processes ranging from egg fertilization, active secretion and movement, to cell differentiation and death. The multitude of phenomena modulated by Ca²⁺, however, do not simply rely on increases/decreases in its concentration, but also on specific timing, shape and sub-cellular localization of its signals that, combined together, provide a huge versatility in Ca²⁺ signaling. Intracellular organelles and their Ca²⁺ handling machineries exert key roles in this complex and precise mechanism, and this review will try to depict a map of Ca²⁺ routes inside cells, highlighting the uniqueness of the different Ca²⁺ toolkit components and the complexity of the interactions between them.     

RIPK4 activity in keratinocytes is controlled by the SCF<Superscript>β-TrCP</Superscript> ubiquitin ligase to maintain cortical actin organization

RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state. Interestingly, we identified the SCF^β-TrCP ubiquitin E3 ligase complex responsible for regulating the active RIPK4 protein level. The SCF^β-TrCP complex binds to a conserved phosphodegron motif in the intermediate domain of RIPK4, subsequently leading to K48-linked ubiquitinylation and degradation. The recruitment of β-TrCP is dependent on RIPK4 activation and trans-autophosphorylation. β-TrCP knock-down resulted in RIPK4-dependent formation of actin stress fibers, cell scattering and increased cell motility, suggesting that tight control of RIPK4 activity levels is crucial to maintain cell shape and behavior in keratinocytes.