Characterization of adsorbed protein films by time of flight secondary ion mass spectrometry

Time of flight secondary ion mass spectrometry (ToF-SIMS) is a useful technique in the study of adsorbed protein films because of its high surface sensitivity and chemical selectivity. However, the protein mass spectra generated by ToF-SIMS are complex fragmentation patterns of a polymer consisting of 20 different monomers (i.e., amino acids). Principal component analysis (PCA) was implemented to classify several reference positive ion protein spectra according to protein and substrate type. Furthermore, the positive ion 74/102 and 120/130 SIMS intensity ratios, radiolabeled experiments, and PCA were used to track the relative surface concentrations of bovine serum albumin and bovine fibronectin in a binary adsorption experiment. In all cases, the combination of ToF-SIMS and PCA proved capable in classifying proteins by their type (in the case of pure protein spectra) and relative surface concentration (in the case of the binary protein spectra).     

Targeting the dopamine D<Subscript>1</Subscript> receptor in schizophrenia: insights for cognitive dysfunction

Background and rationale Reinstatement of the function of working memory, the cardinal cognitive process essential for human reasoning and judgment, is potentially the most intractable problem for the treatment of schizophrenia. Since deficits in working memory are associated with dopamine dysregulation and altered D₁ receptor signaling within prefrontal cortex, we present the case for targeting novel drug therapies towards enhancing prefrontal D₁ stimulation for the amelioration of the debilitating cognitive deficits in schizophrenia.Objectives This review examines the role of dopamine in regulating cellular and circuit function within prefrontal cortex in order to understand the significance of the dopamine dysregulation found in schizophrenia and related non-human primate models. By revealing the associations among prefrontal neuronal function, dopamine and D₁ signaling, and cognition, we seek to pinpoint the mechanisms by which dopamine modulates working memory processes and how these mechanisms may be exploited to improve cognitive function.Results and conclusions Dopamine deficiency within dorsolateral prefrontal cortex leads to abnormal recruitment of this region by cognitive tasks. Both preclinical and clinical studies have demonstrated a direct relationship between prefrontal dopamine function and the integrity of working memory, suggesting that insufficient D₁ receptor signaling in this region results in cognitive deficits. Moreover, working memory deficits can be ameliorated by treatments that augment D₁ receptor stimulation, indicating that this target presents a unique opportunity for the restoration of cognitive function in schizophrenia.Dr. Patricia S. Goldman-Rakic passed away July 31, 2003. This review is dedicated to her memory and to her vision of the origins and treatment of cognitive deficits in schizophrenia.     

Estimation of neuronal firing rates with the three-state biological point process model

In the subcortex of the human brain, neuronal firing events are stochastic and the inter-arrival times of action potentials (APs) are highly irregular. It has been shown that stimulation of the subthalamic nucleus (STN), a small subcortical structure located within the basal ganglia, can help ameliorate the motor symptoms associated with Parkinson's disease (PD). However, success of image guided stereotactic surgery is reliant upon the refinement of the anatomic target (in this case the STN) based on micro-electrode recordings (MERs) of background activity and firing rate. In practice MERs must be analysed on-line and in real-time. Currently, the most common method of performing on-line MER analysis is a manual thresholding procedure. However, this is subjective in nature and often complicated by the presence of variable amounts of background noise. Therefore, in this paper, we present an automated adaptive thresholding technique, based on a modified 'top-hat' operator, which detects APs exceeding the local background activity. We then go on to model these inter-arrival times using a coupled Poisson process that provides improved estimates of both inter-burst and intra-burst neuronal firing activity in the STN.     

A Leadership Challenge: Staff Nurse Perceptions After an Organizational TeamSTEPPS Initiative

The purpose of this study was to measure RNs' perceptions of teamwork skills and behaviors in their work environment during a multiphase multisite nursing organizational teamwork development initiative. Teamwork is essential for patient safety in healthcare organizations and nursing teams. Organizational development supporting effective teamwork should include a just culture, engaged leadership, and teamwork training. A cross-sectional survey study of bedside RNs was conducted in one 5-hospital healthcare system after a TeamSTEPPS teamwork training initiative. TeamSTEPPS teamwork training related to improved RN perceptions of leadership. Initiatives to align the perspectives and teamwork efforts of leaders and bedside nurses are indicated and should involve charge nurses in the design.     

Interactions of the streptococcal C5a peptidase with human fibronectin

Group B Streptococci (GBS) is a leading cause of sepsis and meningitis in neonates and immunocompromised adults in western countries. GBS do not bind to fibronectin (Fn) in solution, but will bind to Fn adsorbed onto a solid surface. The reason for the specificity of this binding is unknown. Single molecule force spectroscopy was used to test the hypothesis that GBS, through streptococcal C5a peptidase (ScpB) molecules present on the surface of the bacteria, binds to a motif created by the juxtaposition of multiple adjacent Fn molecules. Atomic force microscopy (AFM) topographical images of adsorbed Fn deposited from various Fn coating concentrations were used to determine the Fn surface concentration. ScpB was tethered to an AFM tip with all surface modifications characterized by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. At the lowest Fn coverages the probability of observing a ScpB–Fn binding event increased linearly with Fn surface coverage. As an Fn monolayer was reached the probability of a ScpB–Fn binding event occurring increased markedly (50 fold), with a concomitant increase in the rupture force from 17 pN to 33 pN. These results are consistent with the hypothesis that ScpB binds to a motif created by the juxtaposition of multiple Fn molecules.