Aiming High for Virginia Colleges

Considerable discussion about higher education is likely to take place throughout 1999 from the current legislative session through December, when the report of the Governor\u27s Blue Ribbon Commission on Higher Education is anticipated. Because faculty teach, conduct research and provide service to all Virginians, we have a unique perspective on what will be needed to ensure the continuing excellence of higher education in Virginia. Toward that end, we offer the observations below on funding practices, simplifying bureaucratic procedures, improving research and scholarship, and governance in higher education. We believe positive change can make real differences in the quality of the services and programs we provide

Development and deployment of a precision underwater positioning system for in situ laser Raman spectroscopy in the deep ocean

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 52 (2005): 2376-2389, doi:10.1016/j.dsr.2005.09.002.The field of ocean geochemistry has recently been expanded to include in situ laser Raman spectroscopic measurements in the deep ocean. While this technique has proved to be successful for transparent targets, such as fluids and gases, difficulty exists in using deep submergence vehicle manipulators to position and control the very small laser spot with respect to opaque samples of interest, such as many rocks, minerals, bacterial mats, and seafloor gas hydrates. We have developed, tested, and successfully deployed by remotely operated vehicle (ROV) a precision underwater positioner (PUP) which provides the stability and precision movement required to perform spectroscopic measurements using the Deep Ocean In Situ Spectrometer (DORISS) instrument on opaque targets in the deep ocean for geochemical research. The positioner is also adaptable to other sensors, such as electrodes, which require precise control and positioning on the seafloor. PUP is capable of translating the DORISS optical head with a precision of 0.1 mm in three dimensions over a range of at least 15 cm, at depths up to 4000 m, and under the normal range of oceanic conditions (T, P, current velocity). The positioner is controlled, and spectra are obtained, in real time via Ethernet by scientists aboard the surface vessel. This capability has allowed us to acquire high quality Raman spectra of targets such as rocks, shells, and gas hydrates on the seafloor, including the ability to scan the laser spot across a rock surface in sub-millimeter increments to identify the constituent mineral grains. These developments have greatly enhanced the ability to obtain in situ Raman spectra on the seafloor from an enormous range of specimens.Funding was provided by a grant to MBARI from the David and Lucile Packard Foundation

A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors

Cerebral white matter injury (WMI) persistently disrupts myelin regeneration by oligodendrocyte progenitor cells (OPCs). We identified a specific bioactive hyaluronan fragment (bHAf) that downregulates myelin gene expression and chronically blocks OPC maturation and myelination via a tolerance-like mechanism that dysregulates pro-myelination signaling via AKT. Desensitization of AKT occurs via TLR4 but not TLR2 or CD44. OPC differentiation was selectively blocked by bHAf in a maturation-dependent fashion at the late OPC (preOL) stage by a noncanonical TLR4/TRIF pathway that induced persistent activation of the FoxO3 transcription factor downstream of AKT. Activated FoxO3 selectively localized to oligodendrocyte lineage cells in white matter lesions from human preterm neonates and adults with multiple sclerosis. FoxO3 constraint of OPC maturation was bHAf dependent, and involved interactions at the FoxO3 and MBP promoters with the chromatin remodeling factor Brg1 and the transcription factor Olig2, which regulate OPC differentiation. WMI has adapted an immune tolerance–like mechanism whereby persistent engagement of TLR4 by bHAf promotes an OPC niche at the expense of myelination by engaging a FoxO3 signaling pathway that chronically constrains OPC differentiation

A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors

Cerebral white matter injury (WMI) persistently disrupts myelin regeneration by oligodendrocyte progenitor cells (OPCs). We identified a specific bioactive hyaluronan fragment (bHAf) that downregulates myelin gene expression and chronically blocks OPC maturation and myelination via a tolerance-like mechanism that dysregulates pro-myelination signaling via AKT. Desensitization of AKT occurs via TLR4 but not TLR2 or CD44. OPC differentiation was selectively blocked by bHAf in a maturation-dependent fashion at the late OPC (preOL) stage by a noncanonical TLR4/TRIF pathway that induced persistent activation of the FoxO3 transcription factor downstream of AKT. Activated FoxO3 selectively localized to oligodendrocyte lineage cells in white matter lesions from human preterm neonates and adults with multiple sclerosis. FoxO3 constraint of OPC maturation was bHAf dependent, and involved interactions at the FoxO3 and MBP promoters with the chromatin remodeling factor Brg1 and the transcription factor Olig2, which regulate OPC differentiation. WMI has adapted an immune tolerance–like mechanism whereby persistent engagement of TLR4 by bHAf promotes an OPC niche at the expense of myelination by engaging a FoxO3 signaling pathway that chronically constrains OPC differentiation

The mating-specific Gα interacts with a kinesin-14 and regulates pheromone-induced nuclear migration in budding yeast

As a budding yeast cell elongates toward its mating partner, cytoplasmic microtubules connect the nucleus to the cell cortex at the growth tip. The Kar3 kinesin-like motor protein is then thought to stimulate plus-end depolymerization of these microtubules, thus drawing the nucleus closer to the site where cell fusion and karyogamy will occur. Here, we show that pheromone stimulates a microtubule-independent interaction between Kar3 and the mating-specific Gα protein Gpa1 and that Gpa1 affects both microtubule orientation and cortical contact. The membrane localization of Gpa1 was found to polarize early in the mating response, at about the same time that the microtubules begin to attach to the incipient growth site. In the absence of Gpa1, microtubules lose contact with the cortex upon shrinking and Kar3 is improperly localized, suggesting that Gpa1 is a cortical anchor for Kar3. We infer that Gpa1 serves as a positional determinant for Kar3-bound microtubule plus ends during mating. © 2009 by The American Society for Cell Biology

Measurement of Receptor-Activated Phosphoinositide Turnover in Rat Brain: Nonequivalence of Inositol Phosphate and CDP-Diacylglycerol Formation

Two methods for the measurement of receptor-activated phosphoinositide turnover were evaluated for their degree of correspondence in slices of rat brain; they involved the Li + -dependent accumulations of either [ 3 H]-inositol-labeled inositol phosphates or [ 3 H]cytidine-labeled CDP-diacylglycerol. In contrast to the expectation that the ratio of these two responses would remain approximately constant, varying degrees of correspondence were obtained. The two extremes are exemplified by carbachol, which elicited large increases in both inositol phosphate and CDP-diacylglycerol labeling, and endothelin, which gave a robust inositol phosphate response with little or no accumulation of 3 H-CDP-diacylglycerol. No instance of the presence of the latter response in the absence of 3 H-inositol phosphate accumulation was observed. Measurement of 3 H-CDP-diacylglycerol accumulation thus may add additional insight into the regulation of phosphoinositide turnover and the complex actions of Li + .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66135/1/j.1471-4159.1993.tb03258.x.pd

Old English macian, Its Origin and Dissemination

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66612/2/10.1177_007542428601900105.pd

Gas-forming intrahepatic abscess: A possible complication of arterial infusion chemotherapy

Three cases of intrahepatic gas-forming abscesses are presented with liver metastases and indwelling hepatic artery catheters for drug infusion. This may represent a further complication of intrahepatic arterial drug infusion. Possible etiologies along with future prospects for this form of therapy are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48150/1/261_2005_Article_BF01887516.pd