Distribution of inulin space in the rabbit thoracic aorta

Zusammenfassung Die ganze Länge und Dicke des extrazellulären Raumes der thorakalen Kaninchenaorta wurde gemessen. Der Raum ist unverändert die ganze Länge des Blutgefässes hindurch und entspricht 0,59 ml/g 0,39 ml/g für die Adventitia und die Media. In jeder dieser Tunicae ist der Raum durch ihre ganze Dicke gleichmässig verteilt.

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Supported by grants from The American Medical Association Education and Research Foundation, U.S. Public Health Service (HE-08359) and the Los Angeles County Heart Association (408 IG).     

On the synthesis of poliovirus RNA at supraoptimal temperatures

Riassunto La scarsa incorporazione di precursori dello ARN in cellule infette da poliovirus ed incubate a 41,5°C è dovuta ad una inibizione della sintesi dello ARN virale più che non ad una sua digestione ad opera di nucleasi.

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Work supported by a Grant of Consiglio Nazionale delle Ricerche, Rome.     

Axonal transport of neurofilaments in normal and disease states

Neurofilaments are among the most abundant organelles in neurones. They are synthesised in cell bodies and then transported into and through axons by a process termed 'slow axonal transport' at a rate that is distinct from that driven by conventional fast motors. Several recent studies have now demonstrated that this slow rate of transport is actually the consequence of conventional fast rates of movement that are interrupted by extended pausing. At any one time, most neurofilaments are thus stationary. Accumulations of neurofilaments are a pathological feature of several human neurodegenerative diseases suggesting that neurofilament transport is disrupted in disease states. Here, we review recent advances in our understanding of neurofilament transport in both normal and disease states. Increasing evidence suggests that phosphorylation of neurofilaments is a mechanism for regulating their transport properties, possibly by promoting their detachment from the motor(s). In some neurodegenerative diseases, signal transduction mechanisms involving neurofilament kinases and phosphatases may be perturbed leading to disruption of transport. Received 11 July 2001; received after revision 30 August 2001; accepted 31 August 2001     

The coagulation of insect hemolymph

In contrast to both vertebrates and non-insect arthropods, little is known about the coagulation of hemolymph (hemostasis) in insects. We discuss the integration of the hemostatic response with other branches of the insect immune system. We also describe the present stage in the characterization of both soluble and cellular factors that contribute to hemostasis in insects. The factors of the well-characterized clotting cascades of vertebrates, primitive chelicerates and crustaceans are used to assess the implications of sequencing the whole Drosophila genome for searching candidate genes involved in hemostasis. Some striking similarities between blood clotting in vertebrates and the reaction of insect cells involved in hemolymph coagulation have implications for a phylogenetic comparison of hemostasis between divergent animal classes.     

Transmitter-evoked local calcium release stabilizes developing dendrites

In the central nervous system, dendritic arborizations of neurons undergo dynamic structural remodelling during development. Processes are elaborated, maintained or eliminated to attain the adult pattern of synaptic connections. Although neuronal activity influences this remodelling, it is not known how activity exerts its effects. Here we show that neurotransmission-evoked calcium (Ca(2+)) release from intracellular stores stabilizes dendrites during the period of synapse formation. Using a ballistic labelling method to load cells with Ca(2+) indicator dyes, we simultaneously monitored dendritic activity and structure in the intact retina. Two distinct patterns of spontaneous Ca(2+) increases occurred in developing retinal ganglion cells--global increases throughout the arborization, and local 'flashes' of activity restricted to small dendritic segments. Blockade of local, but not global, activity caused rapid retraction of dendrites. This retraction was prevented locally by focal uncaging of caged Ca(2+) that triggered Ca(2+) release from internal stores. Thus, local Ca(2+) release is a mechanism by which afferent activity can selectively and differentially regulate dendritic structure across the developing arborization.     

Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms

Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling. In the heart, NO inhibits L-type Ca2+ channels but stimulates sarcoplasmic reticulum (SR) Ca2+ release, leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae, where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels allows NO to inhibit beta-adrenergic-induced inotropy. Neuronal NO synthase (NOS1), however, is targeted to cardiac SR. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro, suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1-/- and NOS3-/- mice develop age-related hypertrophy, although only NOS3-/- mice are hypertensive. NOS1/3-/- double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function.