Faculty Bibliography

One of the earliest steps of embryonic development is the establishment of polarity along the anteroposterior axis. Extensive studies of Drosophila embryonic development have elucidated mechanisms for establishing polarity, while studies with other model systems have found that many of these molecular components are conserved through evolution. One exception is Bicoid, the master organizer of anterior development in Drosophila and higher dipterans, which is not conserved. Thus, the study of anteroposterior patterning in insects that lack Bicoid can provide insight into the evolution of the diversity of body plan patterning networks. To this end, we have established the long germ parasitic wasp Nasonia vitripennis as a model for comparative studies with Drosophila. Here we report that, in Nasonia, a gradient of localized caudal mRNA directs posterior patterning, whereas, in Drosophila, the gradient of maternal Caudal protein is established through translational repression by Bicoid of homogeneous caudal mRNA. Loss of caudal function in Nasonia results in severe segmentation defects. We show that Nasonia caudal is an activator of gap gene expression that acts far towards the anterior of the embryo, placing it atop a cascade of early patterning. By contrast, activation of gap genes in flies relies on redundant functions of Bicoid and Caudal, leading to a lack of dramatic action on gap gene expression: caudal instead plays a limited role as an activator of pair-rule gene expression. These studies, together with studies in short germ insects, suggest that caudal is an ancestral master organizer of patterning, and that its role has been reduced in higher dipterans such as Drosophila.

Accuracy of shifting movements between two notes was examined in nine cellists (intermediate-professional skill levels). Three pairs of notes separated by different distances were tested under the same movement rate. Finger position on the string was measured by a circuit. Angular velocities of the left upper arm and forearm were measured by two angular velocity sensors; thus elbow angular velocity during shifts was estimated. Results showed that with increased elbow velocity and shifting distance endpoint variability stayed constant. The force of gravity assisted elbow extension during shifts toward higher pitched notes compared to flexion towards lower pitched notes, but faster movement velocity did not result in increased landing variability. Performance for note E on the A string was found to be less variable than other notes, suggesting that physical cue from the cello body geometry was used as a landmark for finger position. Cutaneous feedback from the thumb when hitting the body-neck junction enabled faster elbow extension velocity compared to shifts towards other notes. Cellists who showed higher performance accuracy also showed higher perceptual ability and performance proficiency. These results suggest that long-term over-training of fast and accurate movements enables musicians to maintain accuracy and variability across different movement distances and velocities. Higher perceptual ability and performance proficiency are correlated with increased accuracy but not lower variability, indicating although perceptual ability and performance proficiency are important for pitch accuracy, movement variability is still constrained by the capacity of the motor system, which is highly fine-tuned and different than non-musicians.

Diseases of the small airspaces represent an increasingly important health problem. Asthma is primarily a disease of airway dysfunction, while chronic obstructive pulmonary disease (COPD) is associated with abnormalities in both the small airways and the alveoli. Conventional diffusion magnetic resonance imaging (MRI) of hyperpolarized noble gases, because of the short T(2)* of the gas, is only capable of monitoring diffusion over short times and hence only short distances. Diffusion imaging is therefore only sensitive to changes in small structures of the lung (primarily the alveoli), and will not adequately interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In this communication we present a new method, termed diffusional kurtosis imaging (DKI), that is particularly sensitive to diffusion over longer distances. DKI may therefore be more sensitive to abnormalities in the bronchioles and bronchi than conventional diffusion imaging. Preliminary DKI measurements on healthy human subjects and one patient with symptoms suggestive of small airway disease are presented. Although the apparent diffusion coefficient (ADC) in the patient was similar to that in the normal controls, diffusional kurtosis was markedly reduced. This suggests that DKI measurements may be useful for assessing diseases of the small airways. Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc

Recent advances in molecular genetics have produced many novel strategies for directing the expression of both functional and regulatory elements in transgenic mice. With the application of such approaches, the specific populations that comprise CNS networks can be both visualized and manipulated. Transgenic methods now range from the use of specific enhancer elements and large genomic regions assembled using BACs and PACs, to the use of gene targeting to a specific locus. In addition, the advent of transactivators and site-specific recombinases has provided unprecedented spatial and temporal control for directing expression in the CNS using a combination of appropriate alleles. As a result, the promise of being able to use transgenics to target specific neuronal populations is now being realized

A scalable adaptive optics (AO) control system architecture composed of asynchronous control clusters based on the stochastic parallel gradient descent (SPGD) optimization technique is discussed. It is shown that subdivision of the control channels into asynchronous SPGD clusters improves the AO system performance by better utilizing individual and/or group characteristics of adaptive system components. Results of numerical simulations are presented for two different adaptive receiver systems based on asynchronous SPGD clusters-one with a single deformable mirror with Zernike response functions and a second with tip-tilt and segmented wavefront correctors. We also discuss adaptive wavefront control based on asynchronous parallel optimization of several local performance metrics-a control architecture referred to as distributed adaptive optics (DAO). Analysis of the DAO system architecture demonstrated the potential for significant increase of the adaptation process convergence rate that occurs due to partial decoupling of the system control clusters optimizing individual performance metrics

Intracellular recording and single-cell labeling were combined to investigate the oculomotor circuitry of the goldfish cerebellar vestibulolateral lobe, consisting of the eminentia granularis (Egr) and caudal lobe. Purkinje cells exhibiting highly conserved vertebrate electrophysiological and morphological properties provide the direct output from the caudal lobe to the vestibular nuclei. Biocytin labeling of the Egr distinguished numerous hindbrain precerebellar sources that could be divided into either putative mechano- or vestibulosensitive nuclei based on cellular location and axon trajectories. Precerebellar neurons in a hindbrain nucleus, called Area II, were electrophysiologically characterized after antidromic activation from the Egr (>50% bilateral) and their morphology analyzed after intracellular biocytin labeling (n = 28). Bipolar spindle-shaped somas ranged widely in size with comparably scaled dendritic arbors exhibiting largely closed field configuration. Area II neurons (85%) projected to the ipsilateral Egr with most (93%) sending a collateral through the cerebellar commissure to the contralateral Egr; however, 15% projected to the contralateral Egr by crossing in the ventral hindbrain. Axon terminals in the vestibular nucleus were the only collaterals within the hindbrain. Every Area II neuron received a disynaptic EPSP after contralateral horizontal canal nerve stimulation and a disynaptic IPSP, preceded by a small EPSP (>50%), after ipsilateral activation. Vestibular synaptic potentials were of varying shape/amplitude, unrelated to neuron location in the nucleus, and thus likely a correlate of somadendritic size. The exceptional separation of eye position and eye velocity signals into two separate hindbrain nuclei represents an ideal model for understanding the precerebellar projection to the vestibulocerebellum

Sonic hedgehog has received an enormous amount of attention since its role as a morphogen that directs ventral patterning in the spinal cord was discovered a decade ago. Since that time, a bewildering array of information has been generated concerning both the components of the hedgehog signalling pathway and the remarkable number of contexts in which it functions. Nowhere is this more evident than in the nervous system, where hedgehog signalling has been implicated in events as disparate as axonal guidance and stem cell maintenance. Here we review our present knowledge of the hedgehog signalling pathway and speculate about areas in which further insights into this versatile pathway might be forthcoming

It is well-established that the endoplasmic reticulum is the major site of phosphatidylinositol (PtdIns) synthesis. The PtdIns synthetic ability of other organelles, such as plasma membrane and nucleus, remains controversial. In the present study, we re-examine this question by comparing PtdIns synthesis in isolated cytoplasts (enucleated cells) with that in corresponding karyoplasts (nuclei surrounded by plasma membrane but lacking most cytoplasmic components). We report that cytoplasts are competent to carry out both basal and stimulated PtdIns synthesis as well as polyphosphoinositide hydrolysis, while karyoplasts can neither synthesize PtdIns nor hydrolyze phosphoinositides in response to agonists. The karyoplasts are, however, capable of synthesizing phosphatidylcholine (PtdCho), as previously reported. From these data, we conclude that PtdIns synthesis is limited to cytoplasmic components, and cannot be sustained by either plasma membrane or nucleus under conditions that permit robust PtdCho synthesis