Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120: Mechanistic and Therapeutic Implications

The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs). These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and MMP-9 were upregulated following gp120-injection. Gp120 reduced laminin and tight junction proteins. Reactive oxygen species (ROS) activate MMPs. Injecting gp120 induced lipid peroxidation. Gene transfer of antioxidant enzymes protected against gp120-induced BBB abnormalities. NMDA upregulates the proform of MMP-9. Using the NMDA receptor (NMDAR-1) inhibitor, memantine, we observed partial protection from gp120-induced BBB injury. Thus, (1) HIV-envelope gp120 disrupts the BBB; (2) this occurs via lesions in brain microvessels, MMP activation and degradation of vascular basement membrane and vascular tight junctions; (3) NMDAR-1 activation plays a role in this BBB injury; and (4) antioxidant gene delivery as well as NMDAR-1 antagonists may protect the BBB

Simulator Training Improves Driver Efficiency: Transfer from the Simulator to the Real World

Here we report the results of a fuel management simulation study to quantify the improvement in fuel efficiency for CDL truck drivers. Forty drivers were selected from a local commercial trucking company that maintained precise records on drivers’ history, fuel efficiency, type of vehicles driven, and trucking routes. These drivers participated in a two-hour training program that focused on ways to optimize shifting to maximize fuel efficiency (e.g., progressive shifting, double clutching, timing, and appropriate gear selection). Transfer of training was assessed over a six-month interval using measures of fuel consumption obtained by drivers in their own vehicles driving their normal route. Training increased fuel efficiency by an average of 2.8% over the six-month interval. Analyses indicated that the benefits of training persisted throughout the posttraining interval. These training benefits were obtained even for the subset of drivers who changed vehicles after training, indicating that drivers learned a general skill that transferred from one vehicle to another. Additional analyses focused on which drivers benefited the most from training. We sorted the drivers into one of four groups, based on pre-training fuel efficiency. Our analysis indicated that those drivers with the lowest pre-training fuel efficiency benefited most from training (with over 7% improvement in fuel efficiency), while those with the highest pre-training fuel efficiency did not benefit significantly from training. Together, our data validated the transfer of simulator training to realworld driving, as drivers incorporated the methods of optimal shifting into their driving practices. Moreover, the benefits of training appear to be durable and tend to benefit most those drivers whose performance was initially below the median on fuel efficienc

Simulator Training Improves Driver Efficiency: Transfer from the Simulator to the Real World

Here we report the results of a fuel management simulation study to quantify the improvement in fuel efficiency for CDL truck drivers. Forty drivers were selected from a local commercial trucking company that maintained precise records on drivers’ history, fuel efficiency, type of vehicles driven, and trucking routes. These drivers participated in a two-hour training program that focused on ways to optimize shifting to maximize fuel efficiency (e.g., progressive shifting, double clutching, timing, and appropriate gear selection). Transfer of training was assessed over a six-month interval using measures of fuel consumption obtained by drivers in their own vehicles driving their normal route. Training increased fuel efficiency by an average of 2.8% over the six-month interval. Analyses indicated that the benefits of training persisted throughout the posttraining interval. These training benefits were obtained even for the subset of drivers who changed vehicles after training, indicating that drivers learned a general skill that transferred from one vehicle to another. Additional analyses focused on which drivers benefited the most from training. We sorted the drivers into one of four groups, based on pre-training fuel efficiency. Our analysis indicated that those drivers with the lowest pre-training fuel efficiency benefited most from training (with over 7% improvement in fuel efficiency), while those with the highest pre-training fuel efficiency did not benefit significantly from training. Together, our data validated the transfer of simulator training to realworld driving, as drivers incorporated the methods of optimal shifting into their driving practices. Moreover, the benefits of training appear to be durable and tend to benefit most those drivers whose performance was initially below the median on fuel efficienc

Creativity in the Wild: Improving Creative Reasoning through Immersion in Natural Settings

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Adults and children are spending more time interacting with media and technology and less time participating in activities in nature. This life-style change clearly has ramifications for our physical well-being, but what impact does this change have on cognition? Higher order cognitive functions including selective attention, problem solving, inhibition, and multi-tasking are all heavily utilized in our modern technology-rich society. Attention Restoration Theory (ART) suggests that exposure to nature can restore prefrontal cortex-mediated executive processes such as these. Consistent with ART, research indicates that exposure to natural settings seems to replenish some, lower-level modules of the executive attentional system. However, the impact of nature on higher-level tasks such as creative problem solving has not been explored. Here we show that four days of immersion in nature, and the corresponding disconnection from multi-media and technology, increases performance on a creativity, problem-solving task by a full 50% in a group of naive hikers. Our results demonstrate that there is a cognitive advantage to be realized if we spend time immersed in a natural setting. We anticipate that this advantage comes from an increase in exposure to natural stimuli that are both emotionally positive and low-arousing and a corresponding decrease in exposure to attention demanding technology, which regularly requires that we attend to sudden events, switch amongst tasks, maintain task goals, and inhibit irrelevant actions or cognitions. A limitation of the current research is the inability to determine if the effects are due to an increased exposure to nature, a decreased exposure to technology, or to other factors associated with spending three days immersed in nature

Zebra Mussel (Dreissena polymorpha) Affects the Feeding Ecology of Early Stage Striped Bass (Morone saxatilis) in the Hudson River Estuary

Variability in the feeding ecology of young fishes over short and long time scales in estuaries is likely to affect population dynamics. We studied 14 years of early stage Striped Bass feeding ecology in the Hudson River Estuary over a 25-year time span, including years in which invasive zebra mussels markedly altered energy flow within the estuary. We predicted that feeding success would be low and that diet composition would be altered during years of high zebra mussel impact, particularly in upriver locations where mussels occur. Feeding success in the short term was indicated by volume of gut contents and in the long term by dry mass at length, i.e. condition; these measures were positively intercorrelated and varied significantly year to year. We tested for associations between condition and multiple biotic and abiotic environmental variables. There was a strong negative effect of zebra mussel grazing rate on condition in upriver locations and a weak positive effect in downriver locations. In upriver locations, condition was 33% higher when local salinity was high and zebra mussel grazing rates were low, whereas in downriver locations, condition was 35% higher when zebra mussel grazing rates and copepod abundance were high and local dissolved oxygen was low. Copepods, amphipods, mysids, and Leptodora constituted the highest prey-specific index of relative importance throughout the estuary. There was no evident effect of the zebra mussel invasion on diet composition. This long-term study corroborates the inferences of earlier studies that zebra mussels reduced early-stage striped bass growth rate

Fatal Distraction? A Comparison of the Cell-phone Driver and the Drunk Driver

We used a high-fidelity driving simulator to compare the performance of cell-phone drivers with drivers who were legally intoxicated from ethanol. When drivers were conversing on either a hand-held or hands-free cell-phone, their reactions were sluggish and they attempted to compensate by driving slower and increasing the following distance from the vehicle immediately in front of them. By contrast, when drivers were legally intoxicated they exhibited a more aggressive driving style, following closer to the vehicle immediately in front of them and applying more force while braking. When controlling for driving difficulty and time on task, cell-phone drivers exhibited greater impairment than intoxicated drivers

Atypical Presentation of Upshaw Schulman Syndrome: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in ADAMTS13 levels which further supported the diagnosis of Upshaw Schulman syndrome. Genomic analysis of ADAMTS13 showed normal sequencing and was not consistent with the diagnosis of Upshaw Schulman syndrome. No prior literature provides an explanation for these findings. This new presentation of a well-classified disease suggests a potential subcategory of TTP that may traditionally be misdiagnosed. Potential explanations for this disease presentation may include IgA-mediated TTP, epigenetic changes of ADAMTS13 expression, or limitations of current testing modalities

Invasive bivalves in fresh waters : impacts from individuals to ecosystems and possible control strategies

Invasive bivalves may cause great ecological, evolutionary, and economic impacts in freshwater ecosystems. Species such as Corbicula fluminea, Dreissena bugensis, Dreissena polymorpha, Limnoperna fortunei, and Sinanodonta woodiana are widely distributed hyper-successful invaders, but several others not yet invasive (or at least not considered as such) may become so in the near future. These species can affect hydrology, biogeochemical cycling, and biotic interactions through several mechanisms, with impacts ranging from individuals to ecosystems. Freshwater invasive bivalves can create no-analog ecosystems, posing serious difficulties for management, but new techniques are becoming available which may enhance options to detect early introductions and mitigate impacts. Although knowledge about the biology of these bivalves has increased considerably in the last two decades, several fundamental gaps still persist; we suggest new research directions that are worth exploring in the near future.This study was conducted in the scope of the project "ECO-IAS", funded by the Portuguese Foundation for the Science and the Technology and COMPETE funds (Contract: PTDC/AAC-AMB/116685/2010)

Long-term population dynamics of dreissenid mussels (Dreissena polymorpha and D. rostriformis): a cross-system analysis

Dreissenid mussels (including the zebra mussel Dreissena polymorpha and the quagga mussel D. rostriformis) are among the world's most notorious invasive species, with large and widespread ecological and economic effects. However, their long-term population dynamics are poorly known, even though these dynamics are critical to determining impacts and effective management. We gathered and analyzed 67 long-term (>10 yr) data sets on dreissenid populations from lakes and rivers across Europe and North America. We addressed five questions: (1) How do Dreissena populations change through time? (2) Specifi- cally, do Dreissena populations decline substantially after an initial outbreak phase? (3) Do different measures of population performance (biomass or density of settled animals, veliger density, recruitment of young) follow the same patterns through time? (4) How do the numbers or biomass of zebra mussels or of both species combined change after the quagga mussel arrives? (5) How does body size change over time? We also considered whether current data on long-term dynamics of Dreissena populations are adequate for science and management. Individual Dreissena populations showed a wide range of temporal dynamics, but we could detect only two general patterns that applied across many populations: (1) Populations of both species increased rapidly in the first 1-2 yr after appearance, and (2) quagga mussels appeared later than zebra mussels and usually quickly caused large dedines in zebra mussel populations. We found little evidence that combined Dreissena populations declined over the long term. Different measures of population performance were not congruent; the temporal dynamics of one life stage or population attribute cannot generally be accurately inferred from the dynamics of another. We found no consistent patterns in the long-term dynamics of body size. The long-term dynamics of Dreissena populations probably are driven by the ecological characteristics (e.g., predation, nutrient inputs, water temperature) and their temporal changes at individual sites rather than following a generalized time course that applies across many sites. Existing long-term data sets on dreissenid populations, although dearly valuable, are inadequate to meet research and management needs. Data sets could be improved by standardizing sampling designs and methods, routinely collecting more variables, and increasing support

Cell Phone-Induced Perceptual Impairments During Simulated Driving

Our research assessed the effects of cellular phone conversations on driving performance. When subjects were deeply involved in cellular phone conversations using either a hand-held or hands-free device, they were more than twice as likely to miss simulated traffic signals presented at the center of fixation than when they were not distracted by the cell phone conversation. By contrast, performance was not disrupted by listening to radio broadcasts or listening to a book on tape. One might argue that when subjects were conversing on a cell phone that they detected the simulated traffic signals, but that the responses to them were suppressed. To assess this, we examined the implicit perceptual memory for items that were presented at fixation but called for no response. Implicit perceptual memory was strong when subjects were not engaged in a cellphone conversation but impaired when they were so engaged. We suggest that active participation in a cell phone conversation disrupts performance by diverting attention to an engaging cognitive context other than the one immediately associated with driving