Faculty Bibliography

Monitoring Editor: Guido Guidotti KCa3.1 is an intermediate conductance Ca(2+)-activated K channels that is expressed predominantly in hematopoietic cells, smooth muscle cells, and epithelia where it functions to regulate membrane potential, Ca2+ influx, cell volume and chloride secretion. We recently found that the KCa3.1 channel also specifically requires PI(3)P for channel activity and is inhibited by myotubularin related protein 6 (MTMR6), a PI(3)P phosphatase. We now show that PI(3)P indirectly activates KCa3.1. Unlike KCa3.1 channels, the related KCa2.1, KCa2.2 or KCa2.3 channels do not require PI(3)P for activity, suggesting that the KCa3.1 channel has evolved a unique means of regulation that is critical for their biological function. By making chimeric channels between KCa3.1 and KCa2.3, we identified a stretch of 14 amino acids in the carboxyterminal calmodulin binding domain of KCa3.1 that is sufficient to confer regulation of KCa2.3 by PI(3)P. However, mutation of a single potential phosphorylation site in these 14 amino acids did not affect channel activity. These data when taken together suggest that PI(3)P and these 14 amino acids regulate KCa3.1 channel activity by recruiting an as yet to be defined regulatory subunit that is required for Ca2+ gating of KCa3.1

PURPOSE: To develop a multislice, first-pass perfusion imaging sequence for increasing the effective dynamic range of the contrast-enhanced blood signal and the contrast-to-noise ratio (CNR) of myocardial wall enhancement. MATERIALS AND METHODS: A hybrid echo-planar imaging (EPI) pulse sequence was modified to acquire data for both the arterial input function (AIF) and the myocardium, using two different saturation-recovery time delays (TDs) and spatial resolutions, after a single saturation pulse. Five healthy subjects were scanned at 3T in three short-axis levels of the heart per heartbeat during passage of a high-dose bolus of contrast agent. The T(1)-weighted signal-time curve of the blood was converted to AIF using empirical conversion tables derived from phantom experiments. RESULTS: In all subjects the calculated AIF was consistently less distorted and higher for the short-TD protocol than for the long-TD protocol (peak concentration: 5.0 +/- 1.0 mM vs. 3.0 +/- 0.6 mM; P < 0.01). A combination of EPI, long TD, high-dose bolus of contrast agent, and 3T imaging yielded relatively strong peak enhancement in the myocardium (CNR = 11.9 +/- 3.3). CONCLUSION: Our dual-imaging approach at 3T seems promising for acquiring both a relatively accurate AIF and a high CNR of myocardial wall enhancement in multiple slices per heartbeat

Image compression systems commonly operate by transforming the input signal into a new representation whose elements are independently quantized. The success of such a system depends on two properties of the representation. First, the coding rate is minimized only if the elements of the representation are statistically independent. Second, the perceived coding distortion is minimized only if the errors in a reconstructed image arising from quantization of the different elements of the representation are perceptually independent. We argue that linear transforms cannot achieve either of these goals and propose, instead, an adaptive nonlinear image representation in which each coefficient of a linear transform is divided by a weighted sum of coefficient amplitudes in a generalized neighborhood. We then show that the divisive operation greatly reduces both the statistical and the perceptual redundancy amongst representation elements. We develop an efficient method of inverting this transformation, and we demonstrate through simulations that the dual reduction in dependency can greatly improve the visual quality of compressed images

EHD1 is a member of the EHD family that contains four mammalian homologs. Among the invertebrate orthologs are a single Drosophila and Caenorhabditis elegans proteins and two plant members. They all contain three modules, a N-terminal domain that contains nucleotide-binding motifs, a central coiled-coil domain involved in oligomerization and a C-terminal region that harbors the EH domain. Studies in C. elegans and EHD1 depletion by RNA interference in human cells have demonstrated that it regulates recycling of membrane proteins. We addressed the physiological role of EHD1 through its inactivation in the mouse. Ehd1 knockout mice were indistinguishable from normal mice, had a normal life span and showed no histological abnormalities. Analysis of transferrin uptake in Ehd1(-/-) embryonic fibroblasts demonstrated delayed recycling to the plasma membrane with accumulation of transferrin in the endocytic recycling compartment. Our results corroborate the established role of EHD1 in the exit of membrane proteins from recycling endosomes in vivo in a mouse model

Most words in natural language are polysemous, that is, they can be used in more than one way. For example, paper can be used to refer to a substance made out of wood pulp or to a daily publication printed on that substance. Although virtually every sentence contains polysemy, there is little agreement as to how polysemy is represented in the mental lexicon. Do different uses of polysemous words involve access to a single representation or do our minds store distinct representations for each different sense? Here we investigated priming between senses with a combination of behavioral and magnetoencephalographic measures in order to test whether different senses of the same word involve identity or mere formal and semantic similarity. Our results show that polysemy effects are clearly distinct from similarity effects bilaterally. In the left hemisphere, sense-relatedness elicited shorter latencies of the M350 source, which has been hypothesized to index lexical activation. Concurrent activity in the right hemisphere, on the other hand, peaked later for sense-related than for unrelated target stimuli, suggesting competition between related senses. The obtained pattern of results supports models in which the representation of polysemy involves both representational identity and difference: Related senses connect to same abstract lexical representation, but are distinctly listed within that representation

Cardiovascular Magnetic Resonance (CVMR) imaging has proven to be of clinical value for non-invasive diagnostic imaging of cardiovascular diseases. CVMR requires rapid imaging; however, the speed of conventional MRI is fundamentally limited due to its sequential approach to image acquisition, in which data points are collected one after the other in the presence of sequentially-applied magnetic field gradients and radiofrequency pulses. Parallel MRI uses arrays of radiofrequency coils to acquire multiple data points simultaneously, and thereby to increase imaging speed and efficiency beyond the limits of purely gradient-based approaches. The resulting improvements in imaging speed can be used in various ways, including shortening long examinations, improving spatial resolution and anatomic coverage, improving temporal resolution, enhancing image quality, overcoming physiological constraints, detecting and correcting for physiologic motion, and streamlining work flow. Examples of these strategies will be provided in this review, after some of the fundamentals of parallel imaging methods now in use for cardiovascular MRI are outlined. The emphasis will rest upon basic principles and clinical state-of-the art cardiovascular MRI applications. In addition, practical aspects such as signal-to-noise ratio considerations, tailored parallel imaging protocols and potential artifacts will be discussed, and current trends and future directions will be explored.

In non-avian reptiles the medial and dorsal cortices are putative homologues of the hippocampal formation in mammals and birds. Studies on mammals and birds commonly report neuro-ecological correlations between hippocampal volume and aspects of spatial ecology. We examined the relationship between putative homologous cortical volumes and spatial use in a population of the squamate reptile, Agkistrodon piscivorus, that exhibits sex differences in spatial use. Do male A. piscivorus that inhabit larger home ranges than females also have larger putative hippocampal volumes? Male and female brains were sectioned and digitized to quantify regional cortical volumes. Although sex differences in dorsal cortex volume were not observed, males had a significantly larger medial cortex relative to telencephalon volume. Similar to studies on mammals and birds, relative hippocampal or medial cortex volume was positively correlated with patterns of spatial use. We demonstrate volumetric sex differences within a reptilian putative hippocampal homologue

The development of gene array techniques to quantify expression levels of dozens to thousands of genes simultaneously within selected tissue samples from control and diseased brain has enabled researchers to generate expression profiles of vulnerable neuronal populations in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, and Creutzfeld-Jakob disease. Intriguingly, gene expression analysis reveals that vulnerable brain regions in many of these diseases share putative pathogenetic alterations in common classes of genes, including decrements in synaptic transcript levels and increments in immune response transcripts. Thus, gene expression profiles of diseased neuronal populations may reveal mechanistic clues to the molecular pathogenesis underlying various neurological diseases and aid in identifying potential therapeutic targets. This chapter will review how regional and single cell gene array technologies have advanced our understanding of the genetics of human neurological disease.