2,674 research outputs found

    Heterogeneous and rate-dependent streptavidin-biotin unbinding revealed by high-speed force spectroscopy and atomistic simulations

    Get PDF
    Receptor-ligand interactions are essential for biological function and their binding strength is commonly explained in terms of static lock-and-key models based on molecular complementarity. However, detailed information of the full unbinding pathway is often lacking due, in part, to the static nature of atomic structures and ensemble averaging inherent to bulk biophysics approaches. Here we combine molecular dynamics and high-speed force spectroscopy on the streptavidin-biotin complex to determine the binding strength and unbinding pathways over the widest dynamic range. Experiment and simulation show excellent agreement at overlapping velocities and provided evidence of the unbinding mechanisms. During unbinding, biotin crosses multiple energy barriers and visits various intermediate states far from the binding pocket while streptavidin undergoes transient induced fits, all varying with loading rate. This multistate process slows down the transition to the unbound state and favors rebinding, thus explaining the long lifetime of the complex. We provide an atomistic, dynamic picture of the unbinding process, replacing a simple two-state picture with one that involves many routes to the lock and rate-dependent induced-fit motions for intermediates, which might be relevant for other receptor-ligand bonds.Comment: 21 pages, 4 figure

    EPSRC IMPACT Exhibition

    Get PDF
    This exhibition was conceived by Dunne (PI) and comprised 16 mixed-media speculative design research projects. It marked the culmination of an EPSRC-funded initiative also partly supported by NESTA. Dunne supervised and then curated the projects by staff, graduates and students of the RCA Design Interactions programme. Each was conducted in collaboration with an external research partner organisation already supported by the EPSRC. The topics covered ranged from renewable energy devices and security technologies to the emerging fields of synthetic biology and quantum computing. Dunne and an advisory panel from EPSRC and NESTA selected themes on the basis of diversity of topic, design opportunities, intellectual and creative challenges, and public relevance. Dunne invited the designers to take a radical, interrogative approach, exploring the social, ethical and political implications of the research. Each designer visited the relevant science lab, consulted with the scientists throughout the project, and participated in a one-day workshop hosted by NESTA between scientists and designers on such forms of collaboration. Designers carried out literature, journal, and project surveys before developing their projects through iterative prototypes. The exhibition, held at the RCA in 2010, was considered by EPSRC to offer a powerful insight into how today’s research might transform our experience of the world. It was reviewed in the Guardian (2010), Wired (2010) and Design Week (2010). Dunne presented ‘IMPACT!’ in conferences including the IDA Congress, ‘Design at the Edges’, Taipei (2011) and at the Wellcome Trust, London (2011). He gave a related lecture to researchers at Microsoft Research Asia, Beijing (2011). Individual exhibits from the project featured in exhibitions: Museum of Modern Art (2011), National Museum of China (2011); Z33 (2010–11); Wellcome Trust (2010–11); Saint-Étienne International Design Biennial (2010); Ars Electronica (2010); The Times Cheltenham Science Festival (2010); and V2_, Institute for the Unstable Media (2010)

    Using Unmanned Aerial Systems for Deriving Forest Stand Characteristics in Mixed Hardwoods of West Virginia

    Get PDF
    Forest inventory information is a principle driver for forest management decisions. Information gathered through these inventories provides a summary of the condition of forested stands. The method by which remote sensing aids land managers is changing rapidly. Imagery produced from unmanned aerial systems (UAS) offer high temporal and spatial resolutions to small-scale forest management. UAS imagery is less expensive and easier to coordinate to meet project needs compared to traditional manned aerial imagery. This study focused on producing an efficient and approachable work flow for producing forest stand board volume estimates from UAS imagery in mixed hardwood stands of West Virginia. A supplementary aim of this project was to evaluate which season was best to collect imagery for forest inventory. True color imagery was collected with a DJI Phantom 3 Professional UAS and was processed in Agisoft Photoscan Professional. Automated tree crown segmentation was performed with Trimble eCognition Developer’s multi-resolution segmentation function with manual optimization of parameters through an iterative process. Individual tree volume metrics were derived from field data relationships and volume estimates were processed in EZ CRUZ forest inventory software. The software, at best, correctly segmented 43% of the individual tree crowns. No correlation between season of imagery acquisition and quality of segmentation was shown. Volume and other stand characteristics were not accurately estimated and were faulted by poor segmentation. However, the imagery was able to capture gaps consistently and provide a visualization of forest health. Difficulties, successes and time required for these procedures were thoroughly noted

    The role of food odor in invertebrate foraging

    Get PDF
    Foraging for food is an integral part of animal survival. In small insects and inverte-brates, multisensory information and optimized locomotion strategies are used toeffectively forage in patchy and complex environments. Here, the importance ofolfactory cues for effective invertebrate foraging is discussed in detail. We reviewhow odors are used by foragers to move toward a likely food source and the recentmodels that describe this sensory-driven behavior. We argue that smell serves a sec-ond function by priming an organism for the efficient exploitation of food. Byappraising food odors, invertebrates can establish preferences and better adapt totheir ecological niches, thereby promoting survival. The smell of food pre-preparesthe gastrointestinal system and primes feeding motor programs for more effectiveingestion as well. Optimizing resource utilization affects longevity and reproductionas a result, leading to drastic changes in survival. We propose that models of foragingbehavior should include odor priming, and illustrate this with a simple toy modelbased on the marginal value theorem. Lastly, we discuss the novel techniques andassays in invertebrate research that could investigate the interactions between odorsensing and food intake. Overall, the sense of smell is indispensable for efficient for-aging and influences not only locomotion, but also organismal physiology, whichshould be reflected in behavioral modeling

    Spartan Daily March 20, 2013

    Get PDF
    Volume 140, Issue 29https://scholarworks.sjsu.edu/spartandaily/1396/thumbnail.jp

    Sphingosine-1-phosphate promotes the persistence of activated CD4 T cells in inflamed sites

    Get PDF
    Inflammation can be protective or pathogenic depending on context and timeframe. Acute inflammation, including the accumulation of CD4 T cells, accompanies protective immune responses to pathogens, but the presence of activated CD4 T cells at sites of inflammation is associated with chronic inflammatory disease. While significant progress has been made in understanding the migration of CD4 T cells into inflamed sites, the signals that lead to their persistence are poorly characterized. Using a murine ear model of acute inflammation and intravital two-photon imaging, we have dissected the signals that mediate CD4 T cell persistence. We report the unexpected finding that the bioactive lipid, sphingosine-1-phosphate (S1P), is both necessary and sufficient for the persistence of activated CD4 T cells at peripheral tissues in acute inflammation. S1P mediated the enhanced motility of CD4 T cells at inflamed tissues but did not affect their migration to the downstream draining lymph node. We found that sphingosine kinase-1, which regulates S1P production is increased at inflamed sites in mice and in patients with the chronic inflammatory disease, rheumatoid arthritis. Together, these data suggest that S1P, or its regulators, may be key targets to promote or disrupt accumulation of CD4 T cells at inflamed tissues

    Longitudinal Study of the Attitudes and Behaviors of Environmental Education Program Participants.

    Get PDF
    The goal of this longitudinal study was to measure the attitudes and behaviors of participants of the Marsh Maneuvers program over the course of the last 25 years. The goal of the Marsh Maneuvers program is to educate students into becoming environmentally literate adults. Environmental literacy is considered herein to be people possessing knowledge about and positive attitudes and behaviors towards the environment. Although students learn basic science and environmental knowledge in the classroom, true environmental literacy is believed to require more hands-on understanding of the material. To evaluate the effectiveness of the program, the following three objectives were completed. Lesson plans for the Marsh Maneuvers camp were developed in order to identify specific concepts being taught. The short-term knowledge retention of the Marsh Maneuvers participants was analyzed using pre-and posttests. Finally, the long-term impact of the Marsh Maneuvers program over the past 25 years was determined using a survey. When analyzing the short-term retention results, there was a 36% average increase in knowledge between pre and posttests, which was significant. Nontraditional education programs are designed to overcome barriers that can be presented in a traditional classroom setting (gender, age, GPA). All participants, regardless of gender, age, or GPA, saw an increase in knowledge during the program. The long-term survey results showed that Marsh Maneuvers participants had slightly more positive attitudes and behaviors. The Marsh Maneuvers participants demonstrated environmental knowledge similar to the control group with only one question being statistically significant between the two groups. Marsh Maneuvers is an effective informal education program to increase environmental literacy for 4-H members in Louisiana based on short and long term study results

    Water Current, Volume 46, No. 1, Winter 2014

    Get PDF
    Planning Continues on July 2014 NU Water and Natural Resources Tour Neale Joins DWFI as Director of Research Meet the Faculty: Dr. Sathaporn (Tong) Onanong From the Director, Chittaranjan Ray: Progress in Moving the Ball Forward WRAP Meets in January Water Center Hosts January Faculty Retreat Annual NU Water Lectures Run Through April Third Edition Groundwater Atlas Available Sixth Annual Global Water for Food Conference Travels to Seattle UNL Research Raises Concerns About Future Global Crop Yield Projections January Scouting and Set-up Trip for the July 15-18 Summer Water and Natural Resources Tour Water Leaders Academy Project Yields VideoGage Pages Bishop Receives 2013 Kremer Award Fritz Leads Research Project on Amazon Biodiversity USGS to Once Again Track Water Use by Power Plants Consider Using Native Plants in Home Landscapes Kazakhstan Graduate Student Studying at NU Water Sciences Laborator
    • …
    corecore