Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy

Voltage-gated ion channels are transmembrane proteins that are essential for nerve impulses and regulate ion flow across cell membranes in response to changes in membrane potential. They are made up of four homologous domains or subunits, each of which contains six transmembrane segments. Studies of potassium channels have shown that the second (S2) and fourth (S4) segments contain several charged residues, which sense changes in voltage and form part of the voltage sensor. Although these regions clearly undergo conformational changes in response to voltage, little is known about the nature of these changes because voltage-dependent distance changes have not been measured. Here we use lanthanide-based resonance energy transfer to measure distances between Shaker potassium channel subunits at specific residues. Voltage-dependent distance changes of up to 3.2 A were measured at several sites near the S4 segment. These movements directly correlated with electrical measurements of the voltage sensor, establishing the link between physical changes and electrical charge movement. Measured distance changes suggest that the region associated with the S4 segment undergoes a rotation and possible tilt, rather than a large transmembrane movement, in response to voltage. These results demonstrate the first in situ measurement of atomic scale movement in a trans-membrane protein.     

Exponential smoothing of seasonal data: a comparison

A parsimonious method of exponential smoothing is introduced for time series generated from a combination of local trends and local seasonal effects. It is compared with the additive version of the Holt–Winters method of forecasting on a standard collection of real time series. Copyright © 2001 John Wiley & Sons, Ltd.     

Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons

The physiological state of the cell is controlled by signal transduction mechanisms which regulate the balance between protein kinase and protein phosphatase activities. Here we report that a single protein can, depending on which particular amino-acid residue is phosphorylated, function either as a kinase or phosphatase inhibitor. DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34. We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism. Decreasing phospho-Thr 75 DARPP-32 in striatal slices, either by a Cdk5-specific inhibitor or by using genetically altered mice, results in increased dopamine-induced phosphorylation of PKA substrates and augmented peak voltage-gated calcium currents. Thus DARPP-32 is a bifunctional signal transduction molecule which, by distinct mechanisms, controls a serine/threonine kinase and a serine/threonine phosphatase.     

Intrinsic functional architecture in the anaesthetized monkey brain

The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.     

Experimental manipulations of precipitation seasonality: effects on oak ( Quercus ) seedling demography and physiology

Predicted changes in regional precipitation patterns and soil moisture caused by anthropogenic trace gas emissions may affect the distribution and abundance of woody plants in arid and semiarid regions. To test the response of woody plants to potential changes in precipitation regimes, we manipulated summer and winter precipitation on plots that contained seedlings of Quercus emoryi Torr. (Emory oak), the dominant tree in oak savannas of the southwestern United States. Throughout the growing season, we monitored seedling survival and physiology (predawn leaf water potential, midday instantaneous gas exchange, and leaf carbon isotope discrimination). Seedling survival and physiological performance differed little between treatments, which embodied 50% changes to quantities of summer and winter precipitation, and encompassed a continuum of precipitation from 359 mm · year -1 to 846 mm · year -1 . However, survival and physiological performance of seedlings were negatively impacted by seasonal environmental conditions common to all treatments, especially during the annual pre-'monsoon' drought. Seedling predawn leaf water potentials, net CO 2 assimilation, and stomatal conductance indicate that growing conditions for Q. emoryi seedlings at this site are generally restricted to periods with adequate soil moisture (i.e., April and August). Results contrast with an assumption implicit to the ""two-layer"" soil water resource partitioning hypothesis that woody plants in all life history stages are more dependent upon winter than summer precipitation. In fact, summer precipitation appears more important than winter precipitation for Q. emoryi seedling recruitment and growth.     

Introduction

The question of the existence of intelligent life on other worlds has never been a purely scientific one. Philosophical, religious and literary issues have been intertwined with scientific ones throughout the history of the “plurality of worlds” debate. This collection of papers in –Studies in History and Philosophy of Science– explores the interrelation of science, philosophy, religion and literature in debates about extraterrestrial life.     

Inhibition ofNeisseria catarrhalis NE-11 transformation

Zusammenfassung Nachweis, dass die Transformation vonNeisseria catarrhalis sich mit Antibiotika und Chemikalien hemmen lässt, die ihrerseits die Eiweiss-und Zellwandsynthese hemmen. Daraus wird geschlossen, dass Eiweiss- und Zellwandsynthese zur Transformation nötig sind.

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Eastern Kentucky University Grant No. 05-03-422-41 was the sole support of this project and was given to the last author.     

Catecholamines in adult iron deficiency patients.

Patients with iron deficiency whether uncomplicated or associated with other types of anemias, had plasma catecholamine levels which were significantly increased above normal controls. Patients with a variety of other anemias had no significant increase in catecholamine levels. Plasma catecholamine levels in uncomplicated iron deficient patients approached normal values as early as 3 h following oral FeSO4.