Retinal ganglion cells lose response to laminin with maturation

The decisive role played by adhesive interactions between neuronal processes and the culture substrate in determining the form and extent of neurite outgrowth in vitro has greatly influenced ideas about the mechanisms of axonal growth and guidance in the vertebrate nervous system. These studies have also helped to identify adhesive molecules that might be involved in guiding axonal growth in vivo. One candidate molecule is laminin, a major glycoprotein of basal laminae which has been shown to induce a wide variety of embryonic neurones to extend neurites in culture. Moreover, laminin is found in large amounts in injured nerves that can successfully regenerate but is absent from nerves where regeneration fails. However, it is unclear to what extent the mechanisms that regulate axonal regeneration also operate in the embryo when axon outgrowth is initiated. Here we have examined the substrate requirements for neurite outgrowth in vitro by chick embryo retinal ganglion cells, the only cells in the retina to send axons to the brain. We show that while retinal ganglion cells from embryonic day 6 (E6) chicks extend profuse neurites on laminin, those from E11 do not, although they retain the ability to extend neurites on astrocytes via a laminin-independent mechanism. This represents the first evidence that central nervous system neurones may undergo a change in their substrate requirements for neurite outgrowth as they mature.     

Offset rate of action of muscarinic antagonists depends on their structural flexibility

Summary Time course measurements of the action of muscarinic antagonists were performed in the spontaneously beating carp atrium. Several high affinity drugs, which embody the quinuclidine structure were examined. The structural flexibility of these molecules was reflected in the dissociation of the drugs from the muscarinic receptor. The dissociation of rigid drugs was very much prolonged as compared to flexible drugs of the same affinity.We thank Prof. S. Lifson for helpful discussion and Mrs M. Bendikovsky for technical assistance. This work was supported by a USA-Israel Binational Science Foundation (BSF-Jerusalem) grant to Y. Lass.     

Fluorescein staining of guinea-pig lymphocytes induced byEchis colorata venom

Résumé Les lymphocytes de cobayes inoculés avec du venin de serpentEchis colorata, additionné de fluorescéinc, acquièrent une forte fluorescence. Le même effet du venin est observé avec des lymphocytes traités in vitro. Les fractions protéolytiques du venin sont responsables de ce phénomène, alors que la phospholipasc est sans effet.     

The generation of the superoxide radical by 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine (DMPH4)

Zusammenfassung Es werden neue Befunde beigebracht, die für die Bildung von Superoxyd-Radikal durch DMPH₄, ein biologisch wichtiges Pterinderivat, sprechen.

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This work was supported by the Clinical Research Center for Parkinsons and Allied Diseases and USPHS Grant No. NS-05184.     

Base stacking controls excited-state dynamics in A.T DNA

Solar ultraviolet light creates excited electronic states in DNA that can decay to mutagenic photoproducts. This vulnerability is compensated for in all organisms by enzymatic repair of photodamaged DNA. As repair is energetically costly, DNA is intrinsically photostable. Single bases eliminate electronic energy non-radiatively on a subpicosecond timescale, but base stacking and base pairing mediate the decay of excess electronic energy in the double helix in poorly understood ways. In the past, considerable attention has been paid to excited base pairs. Recent reports have suggested that light-triggered motion of a proton in one of the hydrogen bonds of an isolated base pair initiates non-radiative decay to the electronic ground state. Here we show that vertical base stacking, and not base pairing, determines the fate of excited singlet electronic states in single- and double-stranded oligonucleotides composed of adenine (A) and thymine (T) bases. Intrastrand excimer states with lifetimes of 50-150 ps are formed in high yields whenever A is stacked with itself or with T. Excimers limit excitation energy to one strand at a time in the B-form double helix, enabling repair using the undamaged strand as a template.     

Detachment fronts and the onset of dynamic friction

The dynamics of friction have been studied for hundreds of years, yet many aspects of these everyday processes are not understood. One such aspect is the onset of frictional motion (slip). First described more than 200 years ago as the transition from static to dynamic friction, the onset of slip is central to fields as diverse as physics, tribology, mechanics of earthquakes and fracture. Here we show that the onset of frictional slip is governed by three different types of coherent crack-like fronts: these are observed by real-time visualization of the net contact area that forms the interface separating two blocks of like material. Two of these fronts, which propagate at subsonic and intersonic velocities, have been the subject of intensive recent interest. We show that a third type of front, which propagates an order of magnitude more slowly, is the dominant mechanism for the rupture of the interface. No overall motion (sliding) of the blocks occurs until either of the slower two fronts traverses the entire interface.