Cloning and function of the rat colonic epithelial K+ channel K(V)LQT1

K(V)LQT1 (K(V)LQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential that is defective in cardiac arrhythmia. The channel is inhibited by the chromanol 293B, a compound that blocks cAMP-dependent electrolyte secretion in rat and human colon, therefore suggesting expression of a similar type of K+ channel in the colonic epithelium. We now report cloning and expression of K(V)LQT1 from rat colon. Overlapping clones identified by cDNA-library screening were combined to a full length cDNA that shares high sequence homology to K(V)LQT1 cloned from other species. RT-PCR analysis of rat colonic musoca demonstrated expression of K(V)LQT1 in crypt cells and surface epithelium. Expression of rK(V)LQT1 in Xenopus oocytes induced a typical delayed activated K+ current. that was further activated by increase of intracellular cAMP but not Ca2+ and that was blocked by the chromanol 293B. The same compound blocked a basolateral cAMP-activated K+ conductance in the colonic mucosal epithelium and inhibited whole cell K+ currents in patch-clamp experiments on isolated colonic crypts. We conclude that K(V)QT1 is forming an important component of the basolateral cAMP-activated K+ conductance in the colonic epithelium and plays a crucial role in diseases like secretory diarrhea and cystic fibrosis.

Expression and function of colonic epithelial K(v)LQT1 K+ channels

1. K(V)LQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential Defects in ion channels have been demonstrated in cardiac arrhythmia. This channel is inhibited potently by the chromanol 293B, The same compound has been shown to block cAMP-dependent electrolyte secretion in rat and human colon, Therefore, it was suggested that a K+ channel similar to K(V)LQT1 is expressed in the colonic epithelium. 2, In the present paper, expression of K(V)LQT1 and its function in colonic epithelial cells is described. Reverse transcription-polymerase chain reaction analysis of rat colonic mucosa demonstrated expression of K(V)LQT1 in both crypt cells and surface epithelium. When expressed in Xenopus oocytes, K(V)LQT1 induced a typical delayed activated K+ current. 3, As demonstrated, the channel activity could be further activated by increases in intracellular cAMP. These and other data support the concept that K(V)LQT1 is forming a component of the basolateral cAMP-activated Kf conductance in the colonic epithelium.

The dorsomedial visual areas in New World and Old World monkeys: homology and function

The extrastriate cortex near the dorsal midline has been described as part of an 'express' pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self-motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.

Step size control for efficient discrete element simulation

The step size determines the accuracy of a discrete element simulation. The position and velocity updating calculation uses a pre-calculated table and hence the control of step size can not use the integration formulas for step size control. A step size control scheme for use with the table driven velocity and position calculation uses the difference between the calculation result from one big step and that from two small steps. This variable time step size method chooses the suitable time step size for each particle at each step automatically according to the conditions. Simulation using fixed time step method is compared with that of using variable time step method. The difference in computation time for the same accuracy using a variable step size (compared to the fixed step) depends on the particular problem. For a simple test case the times are roughly similar. However, the variable step size gives the required accuracy on the first run. A fixed step size may require several runs to check the simulation accuracy or a conservative step size that results in longer run times. (C) 2001 Elsevier Science Ltd. All rights reserved.

Derivation of the probability distribution function for the local density of states of a disordered quantum wire via the replica trick and supersymmetry

We consider the statistical properties of the local density of states of a one-dimensional Dirac equation in the presence of various types of disorder with Gaussian white-noise distribution. It is shown how either the replica trick or supersymmetry can be used to calculate exactly all the moments of the local density of states.' Careful attention is paid to how the results change if the local density of states is averaged over atomic length scales. For both the replica trick and supersymmetry the problem is reduced to finding the ground state of a zero-dimensional Hamiltonian which is written solely in terms of a pair of coupled spins which are elements of u(1, 1). This ground state is explicitly found for the particular case of the Dirac equation corresponding to an infinite metallic quantum wire with a single conduction channel. The calculated moments of the local density of states agree with those found previously by Al'tshuler and Prigodin [Sov. Phys. JETP 68 (1989) 198] using a technique based on recursion relations for Feynman diagrams. (C) 2001 Elsevier Science B.V. All rights reserved.

Noninvasive tests of vascular function and structure: Why and how to perform them

Background Early atherosclerosis involves the endothelium of many arteries. Information about peripheral arterial anatomy and function derived from vascular imaging studies such as brachial artery reactivity (BAR) and carotid intima media thickness (IMT) may be pertinent to the coronary circulation. The prevention and early treatment of atherosclerosis is gaining more attention, and these tests might be used as indications or perhaps guides to the effectiveness of therapy, but their application in clinical practice has been limited. This review seeks to define the anatomy and pathophysiology underlying these investigations, their methodology, the significance of their Findings, and the issues that must be resolved before their application. Methods The literature on BAR and IMT is extensively reviewed, especially in relation to clinical use. Results Abnormal flow-mediated dilation is present in atherosclerotic vessels, is associated with cardiovascular risk factors, and may be a marker of preclinical disease. Treatment of known atherosclerotic risk Factors has been shown to improve flow-mediated dilation, and some data suggest that vascular responsiveness is related to outcome. Carotid IMT is associated with cardiovascular risk factors, and increased levels can predict myocardial infarction and stroke. Aggressive risk factor management can decrease IMT. Conclusions BAR and IMT ate functional and structural markers of the atherosclerotic process. The clinical use of BAR has been limited by varying reproducibility and the influence by exogenous factors, but IMT exhibits less variability. A desirable next step in the development of BAR and IMT as useful clinical tools would be to show an association of improvement in response to treatment with improvement in prognosis.

Assessment of regional long-axis function during dobutamine echocardiography

Echocardiographic analysis of regional left ventricular function is based upon the assessment of radial motion. Long-axis motion is an important contributor to overall function. but has been difficult to evaluate clinically until the recent development of tissue Doppler techniques. We sought to compare the standard visual assessment of radial motion with quantitative tissue Doppler measurement of peak systolic velocity. timing and strain rate (SRI) in 104 patients with known or suspected coronary artery disease undergoing dobutamine stress echocardiography (DbE). A standard DbE protocol was used with colour tissue Doppler images acquired in digital cine-loop format. peak systolic velocity (PSV), time to peak velocity (TPV) and SRI were assessed off-line by an independent operator. Wall motion was assessed by an experienced reader. Mean PSV, TPV and SRI values were compared with wall motion and the presence of coronary artery disease by angiography. A further analysis included assessing the extent of jeopardized myocardium by comparing average values of PSV, TPV and SRI against the previously validated angiographic score. Segments identified as having normal and abnormal radial wall motion showed significant differences in mean PSV (7.9 +/- 3.8 and 5.9 +/- 3.3 cm/s respectively; P < 0.001), TPV (84 40 and 95 +/- 48 ms respectively; P = 0.005) and SRI (- 1.45 +/- 0.5 and - 1.1 +/- 0.9 s(-1) respectively; P < 0.001). The presence of a stenosed subtending coronary artery was also associated with significant differences from normally perfused segments for mean PSV (8.1 3.4 compared with 5.7 +/- 3.7 cm/s; P < 0.001), TPV (78 50 compared with 92 +/- 45 ms; P < 0.001) and SRI (- 1.35 0.5 compared with - 1.20 +/- 0.4 s(-1); P = 0.05). PSV, TPV and SRI also varied significantly according to the extent of jeopardized myocardium within a vascular territory. These results suggest that peak systolic velocity, timing of contraction and SRI reflect the underlying physiological characteristics of the regional myocardium during DbE, and may potentially allow objective analysis of wall motion.

Theory of pseudomodes in quantum optical processes

This paper deals with non-Markovian behavior in atomic systems coupled to a structured reservoir of quantum electromagnetic field modes, with particular relevance to atoms interacting with the field in high-Q cavities or photonic band-gap materials. In cases such as the former, we show that the pseudomode theory for single-quantum reservoir excitations can be obtained by applying the Fano diagonalization method to a system in which the atomic transitions are coupled to a discrete set of (cavity) quasimodes, which in turn are coupled to a continuum set of (external) quasimodes with slowly varying coupling constants and continuum mode density. Each pseudomode can be identified with a discrete quasimode, which gives structure to the actual reservoir of true modes via the expressions for the equivalent atom-true mode coupling constants. The quasimode theory enables cases of multiple excitation of the reservoir to now be treated via Markovian master equations for the atom-discrete quasimode system. Applications of the theory to one, two, and many discrete quasimodes are made. For a simple photonic band-gap model, where the reservoir structure is associated with the true mode density rather than the coupling constants, the single quantum excitation case appears to be equivalent to a case with two discrete quasimodes.

A comparison of low-storage strategies for spectral analysis in dissipative systems: filter diagonalisation in the Lanczos representation and harmonic inversion of the Chebychev-order-domain autocorrelation function

We compare the performance of two different low-storage filter diagonalisation (LSFD) strategies in the calculation of complex resonance energies of the HO2, radical. The first is carried out within a complex-symmetric Lanczos subspace representation [H. Zhang, S.C. Smith, Phys. Chem. Chem. Phys. 3 (2001) 2281]. The second involves harmonic inversion of a real autocorrelation function obtained via a damped Chebychev recursion [V.A. Mandelshtam, H.S. Taylor, J. Chem. Phys. 107 (1997) 6756]. We find that while the Chebychev approach has the advantage of utilizing real algebra in the time-consuming process of generating the vector recursion, the Lanczos, method (using complex vectors) requires fewer iterations, especially for low-energy part of the spectrum. The overall efficiency in calculating resonances for these two methods is comparable for this challenging system. (C) 2001 Elsevier Science B.V. All rights reserved.

Calculation of product state distributions from resonance decay via Lanczos subspace filter diagonalization: Application to HO2

Resonance phenomena associated with the unimolecular dissociation of HO2 have been investigated quantum-mechanically by the Lanczos homogeneous filter diagonalization (LHFD) method. The calculated resonance energies, rates (widths), and product state distributions are compared to results from an autocorrelation function-based filter diagonalization (ACFFD) method. For calculating resonance wave functions via ACFFD, an analytical expression for the expansion coefficients of the modified Chebyshev polynomials is introduced. Both dissociation rates and product state distributions of O-2 show strong fluctuations, indicating the dissociation of HO2 is essentially irregular. (C) 2001 American Institute of Physics.

Genetics of brain function and cognition

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscience This special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the ldquoblack boxrdquo between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.

Cavity QED analog of the harmonic-oscillator probability distribution function and quantum collapses

We establish a connection between the simple harmonic oscillator and a two-level atom interacting with resonant, quantized cavity and strong driving fields, which suggests an experiment to measure the harmonic-oscillator's probability distribution function. To achieve this, we calculate the Autler-Townes spectrum by coupling the system to a third level. We find that there are two different regions of the atomic dynamics depending on the ratio of the: Rabi frequency Omega (c) of the cavity field to that of the Rabi frequency Omega of the driving field. For Omega (c)

Non-Markovian quantum optical processes and pseudomodes

Non-Markovian behaviour in atomic systems coupled to a structured reservoir of quantum EM field modes, such as in high Q cavities, is treated using a quasimode description, and the pseudo mode theory for single quantum reservoir excitations is obtained via Fano diagonalisation. The atomic transitions are coupled to a discrete set of (cavity) quasimodes, which are also coupled to a continuum set of (external) quasimodes with slowly varying coupling constants. Each pseudomode corresponds to a cavity quasimode, and the original reservoir structure is obtained in expressions for the equivalent atom-true mode coupling constants. Cases of multiple excitation of the reservoir are now treatable via Markovian master equations for the atom-discrete quasimode system.