Interactive Mapping with Leaflet

Interactive mapping classroom project designed for the graduate course, "Art/History in the Digital Age," taught at Binghamton University in Fall 2020

The Formation and Stability of DC-SIGN Microdomains Require its Extracellular Moiety: DC-SIGN Microdomains Require Extracellular Moiety

DC-SIGN (Dendritic cell-specific ICAM-3-grabbing non-integrin) is a Ca2+-dependent transmembrane lectin that binds a large variety of pathogens and facilitates their uptake for subsequent antigen presentation. This receptor is present in cell surface microdomains, but factors involved in microdomain formation and their exceptional stability are not clear. To determine which domain/motif of DC-SIGN facilitates its presence in microdomains, we studied mutations at key locations including truncation of the cytoplasmic tail, and ectodomain mutations that resulted in removal of the N-linked glycosylation site, the tandem repeats and the carbohydrate recognition domain (CRD) as well as modification of the calcium sites in the CRD required for carbohydrate binding. Confocal imaging and FRAP measurements showed that the cytoplasmic domain and N-linked glycosylation site do not affect the ability of DC-SIGN to form stable microdomains. However, truncation of the CRD results in complete loss of visible microdomains and subsequent lateral diffusion of the mutants. Apart from cell adhesions, membrane domains are thought to be localized primarily via the cytoskeleton. By contrast, we propose that interactions between the CRD of DC-SIGN and the extracellular matrix and/or cis interactions with transmembrane scaffolding protein(s) play an essential role in organizing these microdomains

Incorporating systems thinking and sustainability within civil and environmental engineering curricula at UVM

As part of an NSF Department Level Reform (DLR) grant, the civil and environmental engineering programs at the University of Vermont (UVM) incorporated systems thinking and a systems approach to engineering problem solving within their programs. A systems thinking approach regards social, environmental and economic factors as necessary components of the problem solution. Because it is a whole systems approach it also encompasses sustainability. We have integrated systems thinking in the following ways; 1) new material has been included into key courses (e.g. the first-year introductory and senior design courses), 2) a sequence of three related environmental and transportation systems courses have been included within the curricula (i.e., Introduction to Systems, Decision Making, and Modeling), and 3) service-learning (S-L) projects have been integrated into key required courses as a way of practicing a systems approach. This culminates in the senior design course in which many of the projects specifically focus on sustainability. A variety of assessment methods have been implemented as part of our reform including student surveys, focus groups, faculty interviews, and assessment of student work. We specifically designed a survey tool that addressed sustainability understanding (both open ended and Likert scale). The survey was given to first-year first semester (FYFS) civil and environmental engineering students, FYFS environmental science students, and senior civil and environmental engineering students. Approximately 50% of the incoming civil and environmental engineering students could not define or give reasonable examples of what sustainability means, while their counterparts in environmental science showed that almost 100% could provide a good definition and provide reasonable examples of sustainability. However, by the end of the introductory course in engineering, the majority of the engineering students had a good working definition of sustainability and examples. Female students in both groups showed a statistically significantly higher interest in learning about sustainability than their male counterparts. © 2011 American Society for Engineering Education

Distribution and lateral mobility of DC-SIGN on immature dendritic cells-implications for pathogen uptake

The receptor C-type lectin DC-SIGN (CD209) is expressed by immature dendritic cells, functioning as an antigen capture receptor and cell adhesion molecule. Various microbes, including HIV-1, can exploit binding to DC-SIGN to gain entry to dendritic cells. DC-SIGN forms discrete nanoscale clusters on immature dendritic cells that are thought to be important for viral binding. We confirmed that these DC-SIGN clusters also exist both in live dendritic cells and in cell lines that ectopically express DC-SIGN. Moreover, DC-SIGN has an unusual polarized lateral distribution in the plasma membrane of dendritic cells and other cells: the receptor is preferentially localized to the leading edge of the dendritic cell lamellipod and largely excluded from the ventral plasma membrane. Colocalization of DC-SIGN clusters with endocytic activity demonstrated that surface DC-SIGN clusters are enriched near the leading edge, whereas endocytosis of these clusters occurred preferentially at lamellar sites posterior to the leading edge. Therefore, we predicted that DC-SIGN clusters move from the leading edge to zones of internalization. Two modes of lateral mobility were evident from the trajectories of DC-SIGN clusters at the leading edge, directed and non-directed mobility. Clusters with directed mobility moved in a highly linear fashion from the leading edge to rearward locations in the lamella at remarkably high velocity (1420+/-260 nm/second). Based on these data, we propose that DC-SIGN clusters move from the leading edge--where the dendritic cell is likely to encounter pathogens in tissue--to a medial lamellar site where clusters enter the cell via endocytosis. Immature dendritic cells may acquire and internalize HIV and other pathogens by this process

Super-Resolution Imaging of C-Type Lectin and Influenza Hemagglutinin Nanodomains on Plasma Membranes Using Blink Microscopy

AbstractDendritic cells express DC-SIGN, a C-type lectin (CTL) that binds a variety of pathogens and facilitates their uptake for subsequent antigen presentation. DC-SIGN forms remarkably stable microdomains on the plasma membrane. However, inner leaflet lipid markers are able to diffuse through these microdomains suggesting that, rather than being densely packed with DC-SIGN proteins, an elemental substructure exists. Therefore, a super-resolution imaging technique, Blink Microscopy (Blink), was applied to further investigate the lateral distribution of DC-SIGN. Blink indicates that DC-SIGN, another CTL (CD206), and influenza hemagglutinin (HA) are all localized in small (∼80 nm in diameter) nanodomains. DC-SIGN and CD206 nanodomains are randomly distributed on the plasma membrane, whereas HA nanodomains cluster on length scales up to several microns. We estimate, as a lower limit, that DC-SIGN and HA nanodomains contain on average two tetramers or two trimers, respectively, whereas CD206 is often nonoligomerized. Two-color Blink determined that different CTLs rarely occupy the same nanodomain, although they appear colocalized using wide-field microscopy. What to our knowledge is a novel domain structure emerges in which elemental nanodomains, potentially capable of binding viruses, are organized in a random fashion; evidently, these nanodomains can be clustered into larger microdomains that act as receptor platforms for larger pathogens like yeasts

Comparison of Areas in Shadow from Imaging and Altimetry in the North Polar Region of Mercury and Implications for Polar Ice Deposits

Earth-based radar observations and results from the MESSENGER mission have provided strong evidence that permanently shadowed regions near Mercury's poles host deposits of water ice. MESSENGER's complete orbital image and topographic datasets enable Mercury's surface to be observed and modeled under an extensive range of illumination conditions. The shadowed regions of Mercury's north polar region from 65 deg N to 90 deg N were mapped by analyzing Mercury Dual Imaging System (MDIS) images and by modeling illumination with Mercury Laser Altimeter (MLA) topographic data. The two independent methods produced strong agreement in identifying shadowed areas. All large radar-bright deposits, those hosted within impact craters greater than or equal to 6 km in diameter, collocate with regions of shadow identified by both methods. However, only approximately 46% of the persistently shadowed areas determined from images and approximately 43% of the permanently shadowed areas derived from altimetry host radar-bright materials. Some sizable regions of shadow that do not host radar-bright deposits experience thermal conditions similar to those that do. The shadowed craters that lack radar-bright materials show a relation with longitude that is not related to the thermal environment, suggesting that the Earth-based radar observations of these locations may have been limited by viewing geometry, but it is also possible that water ice in these locations is insulated by anomalously thick lag deposits or that these shadowed regions do not host water ice

Localization of DIR1 at the tissue, cellular and subcellular levels during Systemic Acquired Resistance in Arabidopsis using DIR1:GUS and DIR1:EGFP reporters

<p>Abstract</p> <p>Background</p> <p>Systemic Acquired Resistance (SAR) is an induced resistance response to pathogens, characterized by the translocation of a long-distance signal from induced leaves to distant tissues to prime them for increased resistance to future infection. DEFECTIVE in INDUCED RESISTANCE 1 (DIR1) has been hypothesized to chaperone a small signaling molecule to distant tissues during SAR in <it>Arabidopsis</it>.</p> <p>Results</p> <p>DIR1 promoter:DIR1-GUS/<it>dir1-1 </it>lines were constructed to examine DIR1 expression. DIR1 is expressed in seedlings, flowers and ubiquitously in untreated or mock-inoculated mature leaf cells, including phloem sieve elements and companion cells. Inoculation of leaves with SAR-inducing avirulent or virulent <it>Pseudomonas syringae </it>pv <it>tomato </it>(<it>Pst</it>) resulted in Type III Secretion System-dependent suppression of DIR1 expression in leaf cells. Transient expression of fluorescent fusion proteins in tobacco and intercellular washing fluid experiments indicated that DIR1's ER signal sequence targets it for secretion to the cell wall. However, DIR1 expressed without a signal sequence rescued the <it>dir1-1 </it>SAR defect, suggesting that a cytosolic pool of DIR1 is important for the SAR response.</p> <p>Conclusions</p> <p>Although expression of DIR1 decreases during SAR induction, the protein localizes to all living cell types of the vasculature, including companion cells and sieve elements, and therefore DIR1 is well situated to participate in long-distance signaling during SAR.</p

International Society for Pharmacoeconomics and Outcomes Research Comments on the American Society of Clinical Oncology Value Framework

As members of the International Society for Pharmacoeconomics and Outcomes Research, we read with great interest the new American Society of Clinical Oncology (ASCO) conceptual framework to assess the value of cancer treatment options.1 We applaud the Value in Cancer Care Task Force for proposing a conceptual framework to support clinicians and patients in assessing the value of new cancer treatments. We acknowledge the challenges facing clinician–patient decision making, particularly concerning cancer treatments. Like ASCO, we recognize that the cost of treatments is increasingly being placed on patients through cost sharing and that engaging patients as part of making individual treatment decisions is of high importance. The ASCO framework highlights the growing tension among patients, insurance companies, and product manufacturers in a dynamic health care environment. In that light, the framework deserves a field test, and we look forward to seeing the outcome of that experience. We also appreciate the opportunity to offer comments and suggestions on the ASCO framework at this early stage, and our membership stands ready to support ASCO in future enhancements