Faculty Bibliography

The four choroid plexuses in the brain ventricles are not identical, but differences among them have rarely been studied. The present work concerns the inflammatory and hemorrhagic choroid plexitis produced in Lewis rats by a single gavage of cholecalciferol (vitamin D(3)) or related steroids with vitamin D activity. Plexitis was very severe in the fourth ventricular plexus, somewhat less severe in the lateral ventricular plexuses, and almost absent in the third ventricular plexus. These findings were compared to the scanty data from the literature on differences among the plexuses.

Cyclophilin D (CypD, encoded by Ppif) is an integral part of the mitochondrial permeability transition pore, whose opening leads to cell death. Here we show that interaction of CypD with mitochondrial amyloid-beta protein (Abeta) potentiates mitochondrial, neuronal and synaptic stress. The CypD-deficient cortical mitochondria are resistant to Abeta- and Ca(2+)-induced mitochondrial swelling and permeability transition. Additionally, they have an increased calcium buffering capacity and generate fewer mitochondrial reactive oxygen species. Furthermore, the absence of CypD protects neurons from Abeta- and oxidative stress-induced cell death. Notably, CypD deficiency substantially improves learning and memory and synaptic function in an Alzheimer's disease mouse model and alleviates Abeta-mediated reduction of long-term potentiation. Thus, the CypD-mediated mitochondrial permeability transition pore is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of Alzheimer's disease. Blockade of CypD may be a therapeutic strategy in Alzheimer's disease.

BACKGROUND: Oral cancer continues to be diagnosed and treated at a late stage, which has a negative effect on outcomes. This study identified and quantified delays in diagnosis and treatment. METHODS: The authors conducted a study that included all new patients seen in the Department of Oral and Maxillofacial Surgery, University of California, San Francisco, between 2003 and 2007 who had a diagnosis of squamous cell carcinoma of the oral cavity. They identified the time intervals for six stages, beginning with the time at which patients first became aware of symptoms and ending with the time at which definitive treatment began. RESULTS: The total time from patients' first sign or symptoms to commencement of treatment was a mean of 205.9 days (range, 52-786 days). The longest delay was from the time symptoms first appeared to the initial visit to a health care professional (mean time, 104.7 days; range, 0-730 days). CONCLUSIONS: Health care professionals need to place greater emphasis on patient education to encourage early self-referrals. CLINICAL IMPLICATIONS: Patients should be encouraged to visit a health care professional when signs or symptoms of oral cancer first develop

It is evident from a wide range of experimental findings that ion channel gating is inherently stochastic. The issue of 'memory effects' (diffusional retardation due to local changes in water viscosity) in ionic flow has been recently addressed using Brownian dynamics simulations. The results presented indicate such memory effects are negligible, unless the diffusional barrier is much higher than that of free solute. In this paper using differential stochastic methods we conclude that the Markovian property of exponential dwell times gives rise to a high barrier, resulting in diffusional memory effects that cannot be ignored in determining ionic flow through channels. We have addressed this question using a generalized Langevin equation that contains a combination of Markovian and non-Markovian processes with different time scales. This approach afforded the development of an algorithm that describes an oscillatory ionic diffusional sequence. The resulting oscillatory function behavior, with exponential decay, was obtained at the weak non-Markovian limit with two distinct time scales corresponding to the processes of ionic diffusion and drift. This will be analyzed further in future studies using molecular dynamics simulations. We propose that the rise of time scales and memory effects is related to differences of shear viscosity in the cytoplasm and extracellular matrix

Many vertebrate motor and sensory systems 'decussate' or cross the midline to the opposite side of the body. The successful crossing of millions of axons during development requires a complex of tightly controlled regulatory processes. Because these processes have evolved in many distinct systems and organisms, it seems reasonable to presume that decussation confers a significant functional advantage--yet if this is so, the nature of this advantage is not understood. In this article, we examine constraints imposed by topology on the ways that a three-dimensional processor and environment can be wired together in a continuous, somatotopic, way. We show that as the number of wiring connections grows, decussated arrangements become overwhelmingly more robust against wiring errors than seemingly simpler same-sided wiring schemes. These results provide a predictive approach for understanding how 3D networks must be wired if they are to be robust, and therefore have implications both for future large-scale computational networks and for complex biomedical devices

We propose an efficient methodology for comparing computational models of a perceptually discriminable quantity. Rather than comparing model responses to subjective responses on a set of pre-selected stimuli, the stimuli are computer-synthesized so as to optimally distinguish the models. Specifically, given two computational models that take a stimulus as an input and predict a perceptually discriminable quantity, we first synthesize a pair of stimuli that maximize/minimize the response of one model while holding the other fixed. We then repeat this procedure, but with the roles of the two models reversed. Subjective testing on pairs of such synthesized stimuli provides a strong indication of the relative strengths and weaknesses of the two models. Specifically, the model whose extremal stimulus pairs are easier for subjects to discriminate is the better model. Moreover, careful study of the synthesized stimuli may suggest potential ways to improve a model or to combine aspects of multiple models. We demonstrate the methodology for two example perceptual quantities: contrast and image quality

With their unique ability to differentiate into all cell types, embryonic stem (ES) cells hold great therapeutic promise. To improve the efficiency of embryoid body (EB)-mediated ES cell differentiation, we studied murine EBs on the basis of their size and found that EBs with an intermediate size (diameter 100-300 microm) are the most proliferative, hold the greatest differentiation potential, and have the lowest rate of cell death. In an attempt to promote the formation of this subpopulation, we surveyed several biocompatible substrates with different surface chemical parameters and identified a strong correlation between hydrophobicity and EB development. Using self-assembled monolayers of various lengths of alkanethiolates on gold substrates, we directly tested this correlation and found that surfaces that exhibit increasing hydrophobicity enrich for the intermediate-size EBs. When this approach was applied to the human ES cell system, similar phenomena were observed. Our data demonstrate that hydrophobic surfaces serve as a platform to deliver uniform EB populations and may significantly improve the efficiency of ES cell differentiation.