Structure,biosynthesis and functions of glycoprotein glycans

Since the pioneering work on structure and function of heteroglycans compiled in the classical books edited by A. Gottschalk in 1972¹, there have been several promising developments in glycoconjugate research, as reviewed in this article.In Part 1, contributed by A. Kobata, current knowledge on heteroglycan structures is presented and representative examples taken from higher organisms are given. Part 2, written by J. F. G. Vliegenthart and J. P. Kamerling, covers the most important achievements in methodology: procedures to obtain pure glycans and to analyze their structures. Part 3, contributed by J. Paulson, is devoted to biosynthesis of glycans now describable as pathways since several of the glycosyltransferases have been isolated and analyzed for specificity. In Part 4, contributed by E. Buddecke, current knowledge on functional roles of glycans is presented. It will become apparent that the prerequisite for valid work either in biosynthetic or functional context depends on solid structural information. This is particularly true whenever glycosyltransferase reaction products are being analyzed, or glycans involved in biological functions are investigated. Although in past years, a great deal of important knowledge has been gathered by use of crude glycosidase or glycosyltransferase activities (a notable example is found in reference 2), one may now postulate that glycans implicated in biological reactions should be thoroughly analyzed.This review may familiarize newcomers with the field of glycoconjugate research with special emphasis on glycoprotein glycans. Glycolipids are not included in this article as they have recently been reviewed by S. I. Hakomori³. The reader is also referred to several excellent monographs^4,5 and the Proceedings of the Glycoconjugate Symposia held biannually^6–8.     

Influence of the Gulf Stream on the troposphere

The Gulf Stream transports large amounts of heat from the tropics to middle and high latitudes, and thereby affects weather phenomena such as cyclogenesis and low cloud formation. But its climatic influence, on monthly and longer timescales, remains poorly understood. In particular, it is unclear how the warm current affects the free atmosphere above the marine atmospheric boundary layer. Here we consider the Gulf Stream's influence on the troposphere, using a combination of operational weather analyses, satellite observations and an atmospheric general circulation model. Our results reveal that the Gulf Stream affects the entire troposphere. In the marine boundary layer, atmospheric pressure adjustments to sharp sea surface temperature gradients lead to surface wind convergence, which anchors a narrow band of precipitation along the Gulf Stream. In this rain band, upward motion and cloud formation extend into the upper troposphere, as corroborated by the frequent occurrence of very low cloud-top temperatures. These mechanisms provide a pathway by which the Gulf Stream can affect the atmosphere locally, and possibly also in remote regions by forcing planetary waves. The identification of this pathway may have implications for our understanding of the processes involved in climate change, because the Gulf Stream is the upper limb of the Atlantic meridional overturning circulation, which has varied in strength in the past and is predicted to weaken in response to human-induced global warming in the future.     

Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells

Immunoglobulin-A has an irreplaceable role in the mucosal defence against infectious microbes. In human and mouse, IgA-producing plasma cells comprise approximately 20% of total plasma cells of peripheral lymphoid tissues, whereas more than 80% of plasma cells produce IgA in mucosa-associated lymphoid tissues (MALT). One of the most biologically important and long-standing questions in immunology is why this 'biased' IgA synthesis takes place in the MALT but not other lymphoid organs. Here we show that IgA class-switch recombination (CSR) is impaired in inducible-nitric-oxide-synthase-deficient (iNOS-/-; gene also called Nos2) mice. iNOS regulates the T-cell-dependent IgA CSR through expression of transforming growth factor-beta receptor, and the T-cell-independent IgA CSR through production of a proliferation-inducing ligand (APRIL, also called Tnfsf13) and a B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF, also called Tnfsf13b). Notably, iNOS is preferentially expressed in MALT dendritic cells in response to the recognition of commensal bacteria by toll-like receptor. Furthermore, adoptive transfer of iNOS+ dendritic cells rescues IgA production in iNOS-/- mice. Further analysis revealed that the MALT dendritic cells are a TNF-alpha/iNOS-producing dendritic-cell subset, originally identified in mice infected with Listeria monocytogenes. The presence of a naturally occurring TNF-alpha/iNOS-producing dendritic-cell subset may explain the predominance of IgA production in the MALT, critical for gut homeostasis.     

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

陶瓷热喷涂层的化学强化

采用化学后处理的方法，即把热喷涂试样在特制的化学溶液中浸渍、干燥、脱水缩合后，使在涂层缺隐处析出某种陶瓷，从而对涂层产生显著的强化作用，这种强化既有界面的强化，又有涂层积层粒子间的强化，可使涂层的结合强度提高约２倍。     

Emergence of cooperation and evolutionary stability in finite populations

To explain the evolution of cooperation by natural selection has been a major goal of biologists since Darwin. Cooperators help others at a cost to themselves, while defectors receive the benefits of altruism without providing any help in return. The standard game dynamical formulation is the 'Prisoner's Dilemma', in which two players have a choice between cooperation and defection. In the repeated game, cooperators using direct reciprocity cannot be exploited by defectors, but it is unclear how such cooperators can arise in the first place. In general, defectors are stable against invasion by cooperators. This understanding is based on traditional concepts of evolutionary stability and dynamics in infinite populations. Here we study evolutionary game dynamics in finite populations. We show that a single cooperator using a strategy like 'tit-for-tat' can invade a population of defectors with a probability that corresponds to a net selective advantage. We specify the conditions required for natural selection to favour the emergence of cooperation and define evolutionary stability in finite populations.     

Mechanically driven ATP synthesis by F1-ATPase

ATP, the main biological energy currency, is synthesized from ADP and inorganic phosphate by ATP synthase in an energy-requiring reaction. The F1 portion of ATP synthase, also known as F1-ATPase, functions as a rotary molecular motor: in vitro its gamma-subunit rotates against the surrounding alpha3beta3 subunits, hydrolysing ATP in three separate catalytic sites on the beta-subunits. It is widely believed that reverse rotation of the gamma-subunit, driven by proton flow through the associated F(o) portion of ATP synthase, leads to ATP synthesis in biological systems. Here we present direct evidence for the chemical synthesis of ATP driven by mechanical energy. We attached a magnetic bead to the gamma-subunit of isolated F1 on a glass surface, and rotated the bead using electrical magnets. Rotation in the appropriate direction resulted in the appearance of ATP in the medium as detected by the luciferase-luciferin reaction. This shows that a vectorial force (torque) working at one particular point on a protein machine can influence a chemical reaction occurring in physically remote catalytic sites, driving the reaction far from equilibrium.