Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine-storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function.

Face encoding and recognition in the human brain.

A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition. The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.

Mutagenesis in the C-terminal region of human interleukin 5 reveals a central patch for receptor alpha chain recognition.

Cassette mutagenesis was used to identify side chains in human interleukin 5 (hIL-5) that mediate binding to hIL-5 receptor alpha chain (hIL-5R alpha). A series of single alanine substitutions was introduced into a stretch of residues in the C-terminal region, including helix D, which previously had been implicated in receptor alpha chain recognition and which is aligned on the IL-5 surface so as to allow the topography of receptor binding residues to be examined. hIL-5 and single site mutants were expressed in COS cells, their interactions with hIL-5R alpha were measured by a sandwich surface plasmon resonance biosensor method, and their biological activities were measured by an IL-5-dependent cell proliferation assay. A pattern of mutagenesis effects was observed, with greatest impact near the interface between the two four-helix bundles of IL-5, in particular at residues Glu-110 and Trp-111, and least at the distal ends of the D helices. This pattern suggests the possibility that residues near the interface of the two four-helix bundles in hIL-5 comprise a central patch or hot spot, which constitutes an energetically important alpha chain recognition site. This hypothesis suggests a structural explanation for the 1:1 stoichiometry observed for the complex of hIL-5 with hIL-5R alpha.

D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.

Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.

Towards Closed-loop Deep Brain Stimulation: Behavior Recognition from Human STN

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson’s disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient’s behavior. Thus behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. This thesis proposes novel detection and classification techniques for behavior recognition based on deep brain LFP. Behavior detection from such signals is the vital step in developing the next generation of closed-loop DBS devices. LFP recordings from 13 subjects are utilized in this study to design and evaluate our method. Recordings were performed during the surgery and the subjects were asked to perform various behavioral tasks. Various techniques are used understand how the behaviors modulate the STN. One method studies the time-frequency patterns in the STN LFP during the tasks. Another method measures the temporal inter-hemispheric connectivity of the STN as well as the connectivity between STN and Pre-frontal Cortex (PFC). Experimental results demonstrate that different behaviors create different m odulation patterns in STN and it’s connectivity. We use these patterns as features to classify behaviors. A method for single trial recognition of the patient’s current task is proposed. This method uses wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. As the next step, a practical behavior detection method which asynchronously detects behaviors is proposed. This method does not use any priori knowledge of behavior onsets and is capable of asynchronously detect the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity and to detect the finger movements. Our experimental results using STN LFP recorded from eight patients with PD demonstrate this is a promising approach for behavior detection and developing novel closed-loop DBS systems.

Human-computer interaction for optical music recognition tasks

The need to digitise music scores has led to the development of Optical Music Recognition (OMR) tools. Unfortunately, the performance of these systems is still far from providing acceptable results. This situation forces the user to be involved in the process due to the need of correcting the mistakes made during recognition. However, this correction is performed over the output of the system, so these interventions are not exploited to improve the performance of the recognition. This work sets the scenario in which human and machine interact to accurately complete the OMR task with the least possible effort for the user.

Mixed human saliva, its variations in composition and amylolytic power and the action of its freed enzyme, a series of observations and experiments from a chemical standpoint; submitted in partial fulfillment of the requirements for the degree of M.S. [in the] University of California.

Type-written manuscript.

An inquiry into the means of improving medical knowledge : by examining all those methods which have hindered, or increased its improvement in all past Ages : to which is added, an explanation of the motion and action of fire, in and upon the human body, both in continuing life, and in producing and curing diseases .../

Mode of access: Internet.

Human Resources and Support ethics action plan.

Mode of access: Internet.

Affirmative action plan for Illinois Department of Human Rights /

Description based on: 1987; title from cover.

Affirmative action plan for Illinois Department of Human Rights /

Description based on: 2003/2004.

Affirmative action plan for the handicapped for Illinois Department of Human Rights /

"July 1, 1987."

Affirmative action plan for Illinois Department of Human Rights /

Description based on: 1981.