Faculty Bibliography

Muscle, cutaneous and joint afferents continuously signal information about the position and movement of individual joints. How does the nervous system extract more global information, for example about the position of the foot in space? To study this question we used microelectrode arrays to record impulses simultaneously from up to 100 discriminable nerve cells in the L6 and L7 dorsal root ganglia (DRG) of the anaesthetized cat. When the hindlimb was displaced passively with a random trajectory, the firing rate of the neurones could be predicted from a linear sum of positions and velocities in Cartesian (x, y), polar or joint angular coordinates. The process could also be reversed to predict the kinematics of the limb from the firing rates of the neurones with an accuracy of 1-2 cm. Predictions of position and velocity could be combined to give an improved fit to limb position. Decoders trained using random movements successfully predicted cyclic movements and movements in which the limb was displaced from a central point to various positions in the periphery. A small number of highly informative neurones (6-8) could account for over 80% of the variance in position and a similar result was obtained in a realistic limb model. In conclusion, this work illustrates how populations of sensory receptors may encode a sense of limb position and how the firing of even a small number of neurones can be used to decode the position of the limb in space.

Recent advances in CT technology have allowed the development of systems with multiple rows of detectors and rapid rotation. These new imaging systems have permitted the acquisition of high resolution, spatially registered, and cardiac gated 3D heart data. In this paper, we present a framework that makes use of these data to reconstruct the 3D cardiac anatomy with resolutions that were not previously possible. We use an improved 3D hybrid segmentation framework which integrates Gibbs prior models, deformable models, and the marching cubes method to achieve a sub-pixel accuracy of the reconstruction of cardiac objects. To improve the convergence at concavities on the object surface, we introduce a new type of external force, which we call the scalar gradient. The scalar gradient is derived from a gray level edge map using local configuration information and can help the deformable models converge into deep concavities on object's surface. The 3D segmentation and reconstruction have been conducted on 8 high quality CT data sets. Important features, such as the structure of papillary muscles, have been well captured, which may lead to a new understanding of the cardiac anatomy and function. All experimental results have been evaluated by clinical experts and the validation shows the method has a very strong performance

In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma. The questionnaire consisted of 8 questions rated by the patient on a visual analog scale. Patients completed the questionnaire at the time of initial presentation before surgical treatment. None of the patients were taking analgesics. The responses were then scored and compiled with patient data and pathology reports. Of the 15 completed questionnaires, 14 patients reported some level of functional restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average, patients experienced significantly higher function-related, rather than spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher level of function-related pain intensity and sharpness than women had (n = 7). There was a strong correlation between nodal disease and increased levels of spontaneous intensity, sharpness, throbbing, and overall functional restriction. PERSPECTIVE: The results of this study indicate the heterogeneous nature and function dependence of oral cancer pain. The questionnaire we have developed in this study will allow for correlations between pain parameters and specific tumor biology in future studies

Amyloid plaques are a hallmark of Alzheimer disease, but their importance in its pathogenesis is controversial. By neuronal labeling and transcranial two-photon imaging, we show in a transgenic mouse model of Alzheimer disease that dendrites passing through or near fibrillar amyloid deposits undergo spine loss and shaft atrophy, and nearby axons develop large varicosities, together leading to neurite breakage and large-scale, permanent disruption of neuronal connections. Thus, fibrillar amyloid deposition is more detrimental to neuronal circuitry than previously thought, underscoring the importance of prevention and early clearance of plaques

One of the major limitations in the current set of techniques available to neuroscientists is a dearth of methods for imaging individual cells deep within the brains of live animals. To overcome this limitation, we developed two forms of minimally invasive fluorescence microendoscopy and tested their abilities to image cells in vivo. Both one- and two-photon fluorescence microendoscopy are based on compound gradient refractive index (GRIN) lenses that are 350-1,000 microm in diameter and provide micron-scale resolution. One-photon microendoscopy allows full-frame images to be viewed by eye or with a camera, and is well suited to fast frame-rate imaging. Two-photon microendoscopy is a laser-scanning modality that provides optical sectioning deep within tissue. Using in vivo microendoscopy we acquired video-rate movies of thalamic and CA1 hippocampal red blood cell dynamics and still-frame images of CA1 neurons and dendrites in anesthetized rats and mice. Microendoscopy will help meet the growing demand for in vivo cellular imaging created by the rapid emergence of new synthetic and genetically encoded fluorophores that can be used to label specific brain areas or cell classes.

The GLP-1 receptor is a Class B heptahelical G-protein-coupled receptor that stimulates cAMP production in pancreatic beta-cells. GLP-1 utilizes this receptor to activate two distinct classes of cAMP-binding proteins: protein kinase A (PKA) and the Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). Actions of GLP-1 mediated by PKA and Epac include the recruitment and priming of secretory granules, thereby increasing the number of granules available for Ca(2+)-dependent exocytosis. Simultaneously, GLP-1 promotes Ca(2+) influx and mobilizes an intracellular source of Ca(2+). GLP-1 sensitizes intracellular Ca(2+) release channels (ryanodine and IP (3) receptors) to stimulatory effects of Ca(2+), thereby promoting Ca(2+)-induced Ca(2+) release (CICR). In the model presented here, CICR activates mitochondrial dehydrogenases, thereby upregulating glucose-dependent production of ATP. The resultant increase in cytosolic [ATP]/[ADP] concentration ratio leads to closure of ATP-sensitive K(+) channels (K-ATP), membrane depolarization, and influx of Ca(2+) through voltage-dependent Ca(2+) channels (VDCCs). Ca(2+) influx stimulates exocytosis of secretory granules by promoting their fusion with the plasma membrane. Under conditions where Ca(2+) release channels are sensitized by GLP-1, Ca(2+) influx also stimulates CICR, generating an additional round of ATP production and K-ATP channel closure. In the absence of glucose, no 'fuel' is available to support ATP production, and GLP-1 fails to stimulate insulin secretion. This new 'feed-forward' hypothesis of beta-cell stimulus-secretion coupling may provide a mechanistic explanation as to how GLP-1 exerts a beneficial blood glucose-lowering effect in type 2 diabetic subjects

The development of spatial vision is relatively well documented in human and nonhuman primates. However, little is known about the development of sensitivity to motion. We measured the development of sensitivity to direction of motion, and the relationship between motion and contrast sensitivity in macaque monkeys as a function of age. Monkeys (Macaca nemestrina, aged between 10 days and 3 years) discriminated direction of motion in random-dot kinematograms. The youngest monkeys showed directionally selective orienting and the ability to integrate motion signals at large dot displacements and fast speeds. With age, coherence sensitivity improved for all spatial and temporal dot displacements tested. The temporal interval between the dots was far less important than the spatial offset in determining the animals' performance at all but the youngest ages. Motion sensitivity improved well beyond the end of the first postnatal year, when mid-spatial-frequency contrast sensitivity reached asymptote, and continued for at least 3 years. Sensitivity to contrast at high spatial frequencies also continued to develop beyond the end of the first year. We conclude that the development of motion sensitivity depends on mechanisms beyond the low-level filters presumed to limit acuity and contrast sensitivity, and most likely reflects the function of extrastriate visual areas

The rbcL sequences of 106 specimens representing 28 species of the four recognized sections of Orobanche were analyzed and compared. Most sequences represent pseudogenes with premature stop codons. This study confirms that the American lineage (sects. Gymnocaulis and Myzorrhiza) contains potentially functional rbcL-copies with intact open reading frames and low rates of non-synonymous substitutions. For the first time, this is also shown for a member of the Eurasian lineage, O. coerulescens of sect. Orobanche, while all other investigated species of sects. Orobanche and Trionychon contain pseudogenes with distorted reading frames and significantly higher rates of non-synonymous substitutions. Phylogenetic analyses of the rbcL sequences give equivocal results concerning the monophyly of Orobanche, and the American lineage might be more closely related to Boschniakia and Cistanche than to the other sections of Orobanche. Additionally, species of sect. Trionychon phylogenetically nest in sect. Orobanche. This is in concordance with results from other plastid markers (rps2 and matK), but in disagreement with other molecular (nuclear ITS), morphological, and karyological data. This might indicate that the ancestor of sect. Trionychon has captured the plastid genome, or parts of it, of a member of sect. Orobanche. Apart from the phylogenetically problematic position of sect. Trionychon, the phylogenetic relationships within sect. Orobanche are similar to those inferred from nuclear ITS data and are close to the traditional groupings traditionally recognized based on morphology. The intraspecific variation of rbcL is low and is neither correlated with intraspecific morphological variability nor with host range. Ancestral character reconstruction using parsimony suggests that the ancestor of O. sect. Orobanche had a narrow host range