Ultra-remote stereocontrol by conformational communication of information along a carbon chain

Many receptors and allosteric proteins function through binding of a molecule to induce a conformational change, which then influences a remote active site. In synthetic systems, comparable intramolecular information transfer can be effected by using the shape of one part of a molecule to control the stereoselectivity of reactions occurring some distance away. However, the need for direct communication with the reaction site usually limits such remote stereocontrol to distances of not more than about five bond lengths. Cyclic structures overcome this problem by allowing the controlling centre and the reaction site to approach each other, but the information transfer spans only short absolute distances. Truly remote stereocontrol can, however, be achieved with rigid compounds containing amide groups: the conformation of the amides can be controlled by stereogenic centres and responds to that of neighbouring amide groups and in turn influences stereoselective reactions. This strategy has allowed remote stereocontrol spanning 8 (ref. 11) or 9 (ref. 12) bonds. Here we demonstrate stereocontrol over a reaction taking place more than 20 bond lengths from the controlling centre, corresponding to a linear distance of over 2.5 nm. This transmission of information, achieved by conformational changes relayed through the molecule, provides a chemical model of allostery and might serve as a molecular mechanism for communicating and processing information.     

Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene

The fibrinolytic potential of the vasculature is modulated primarily by the availability and activity of plasminogen activators, which convert the zymogen plasminogen into the active fibrin-degrading enzyme plasmin. The activities of these key regulatory enzymes are directly neutralized by their primary endogenous inhibitor, plasminogen activator inhibitor-1 (PAI-1). Although some individuals with a tendency to develop thrombotic disorders exhibit elevated levels of PAI-1 in their plasma, the cause-and-effect relationship between increased PAI-1 and thrombosis is still unclear. Specifically, it is not known whether chronic depression of fibrinolytic activity results in the development of thrombosis. To address this question we developed transgenic mice in which the contribution of PAI-1 to thrombus formation could be evaluated. The results presented in this report indicate that elevated levels of PAI-1 contribute to the development of venous but not arterial occlusions.     

A descending pathway with monosynaptic action on flexor motoneurones

Zusammenfassung Erregung eines dorsomedialen Stammhirngebietes verursacht ein monosynaptisches EPSP in Motoneuronen der Beugemuskeln.     

Postural effects of neck muscle vibration in man

Summary Vibration of the dorsal neck muscles in man induces falling reactions, walking and marche en étoile, probably by muscle afferent activation. It can be used as a reproducible error signal in analyzing the interaction between neck muscle proprioception and vestibular as well as ocular motor systems. These interactions are important for posture and coordinated head-eye movements.     

Compact sources as the origin of the soft gamma-ray emission of the Milky Way

The Milky Way is known to be an abundant source of gamma-ray photons, now determined to be mainly diffuse in nature and resulting from interstellar processes. In the soft gamma-ray domain, point sources are expected to dominate, but the lack of sensitive high-resolution observations did not allow for a clear estimate of the contribution from such sources. Even the best imaging experiment revealed only a few point sources, accounting for about 50% of the total Galactic flux. Theoretical studies were unable to explain the remaining intense diffuse emission. Investigating the origin of the soft gamma-rays is therefore necessary to determine the dominant particle acceleration processes and to gain insights into the physical and chemical equilibrium of the interstellar medium. Here we report observations in the soft gamma-ray domain that reveal numerous compact sources. We show that these sources account for the entirety of the Milky Way's emission in soft gamma-rays, leaving at most a minor role for diffuse processes.     

Decline of surface temperature and salinity in the western tropical Pacific Ocean in the Holocene epoch

In the present-day climate, surface water salinities are low in the western tropical Pacific Ocean and increase towards the eastern part of the basin. The salinity of surface waters in the tropical Pacific Ocean is thought to be controlled by a combination of atmospheric convection, precipitation, evaporation and ocean dynamics, and on interannual timescales significant variability is associated with the El Ni?o/Southern Oscillation cycles. However, little is known about the variability of the coupled ocean-atmosphere system on timescales of centuries to millennia. Here we combine oxygen isotope and Mg/Ca data from foraminifers retrieved from three sediment cores in the western tropical Pacific Ocean to reconstruct Holocene sea surface temperatures and salinities in the region. We find a decrease in sea surface temperatures of approximately 0.5 degrees C over the past 10,000 yr, whereas sea surface salinities decreased by approximately 1.5 practical salinity units. Our data imply either that the Pacific basin as a whole has become progressively less salty or that the present salinity gradient along the Equator has developed relatively recently.     

Localization of the receptor-binding protein adhesin at the tip of the bacterial pilus

Strains of the bacterium Escherichia coli that cause infections of the human urinary tract produce so-called Pap-pili, which are hair-like appendages consisting of about 10(3) helically arranged subunits of the protein PapA. These pili mediate binding to digalactoside-containing glycolipids present on the epithelial cells which line the urinary tract. Recently, it has been suggested that three proteins, PapE, PapF and PapG, are responsible for this binding. In the absence of PapA, non-piliated bacteria are formed which nonetheless exhibit binding, showing that the bulk of the pilus is not essential for binding. Although pili can form without PapF and PapG, such pili are unable to bind to the digalactoside. The protein PapG mediates binding specificity in trans-complementation experiments, so this protein is the digalactoside-specific adhesin. Using immuno-electron microscopy we have found that Pap-pili are heteropolymers composed of the major pilin, PapA, the minor pilins, PapE and PapF, and the adhesin, PapG. The last three proteins are located at the tip of the pilus.