Toward Understanding the Role of Amot80 Lipid Binding in Cellular Proliferation and Migration

poster abstractsAmots are adaptor proteins which coordinate signaling that controls cellular differentiation and proliferation, and their Amot coiled-coil homology (ACCH) domain is able to bind lipids with specificity which leads to membrane deformation and targets transcription factors to the nucleus. Understanding the biophysical mechanisms involved in lipid binding may provide pathways to modulate protein sorting and downstream signaling events inducing cellular differentiation, cancer cell proliferation, and migration. At this time, all work reported on signaling based on Amot expression is unable to distinguish between the role of the Amot80 and the 130 family members as they share a common ACCH domain. The goal of this project is to specifically relate the Amot80 ACCH lipid binding with function related to cancer phenotypes Mutations were carried forward based on lipid sedimentation, FRET, and SAXS assays against the ACCH domain of the protein. Site-directed mutagenesis was then employed to probe the specific contributions of 7 selected lysines and arginines toward lipid head-group binding in the full length protein. The polarity/scaffolding signaling effect of mutations in the Amot80 will be monitored by matrigel, accumulation/cell counting, and titrated thymidine incorporation assays. Cell morphology will be imaged by confocal imaging, and cellular migration will be recorded by video. The effects on YAP1/2 and MAPK activation will be assessed by immunoblot analysis. The changes will then be correlated in extracellular scaffolding and migration with immunoblots and cellular staining. Likewise, effects on proliferation will be monitored by MTT assays. The hypothesis of this aim is that modulation of Amot’s ability to bind selective lipids will interrupt the signaling pathways leading to cellular migration, differentiation, and proliferation. This work was supported by the IUPUI Undergraduate Research Opportunities Program (UROP) and NIH K01CA169078-01

High-resolution investigations of Transverse Aeolian Ridges on Mars

Transverse Aeolian Ridges (TARs) are the most pervasive aeolian feature on Mars. Their small size requires high-resolution data for thorough analyses. We have utilized Mars Reconnaissance Orbiter (MRO) Context Camera (CTX) and High Resolution Image Stereo Experiment (HiRISE) images, along with MRO Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) spectroscopic data to study TARs in detail. TAR deposits, along with related dark dune material and layered terrains, have been mapped in six study areas in order to identify sediment pathways and determine whether TARs are sourced locally or from global wind-borne materials. TAR morphology and orientation were mapped in grids within each study area; the results show that TARs are probably locally sourced. We constructed four HiRISE Digital Terrain Models (DTMs) to measure TAR heights, widths, spacing, areas, symmetry, and to calculate sediment volumes. Results show that TARs have average heights of ∼1.5 m, are very symmetrical, and are similar in form to terrestrial megaripples. Orthorectified HiRISE images taken 3 years apart were analyzed for TAR movement and none was found. Superposed craters on equatorial TARs give ages of ∼2 Ma, suggesting that these are relatively ancient and generally inactive aeolian deposits. CRISM data were analyzed over TAR deposits, dark dune material, and light-toned terrains. Although the surfaces were somewhat obscured by dust cover, the results did not show any remarkable difference between TARs and other deposits. We conclude that TARs may be sourced from local materials and form in a similar way to terrestrial megaripples

Knowledge, Leadership and the Role of Spirituality: An Exploration of Principal as Spiritual Leader

Recent scholarship (Knapp, Copland, Honig, Plecki & Portin, 2010; Louis, Leithwood, Wahlstrom, Anderson et al., 2010) demonstrates the impact of school leadership on student success. Using the research model of the ISSPP (Day, 2010), a team of researchers utilized a dynamic approach to identify leadership practices and beliefs that could be attributed to rises in student achievement and diminishing achievement gaps. In this paper, we present a cross-case analysis of three elementary schools in the southeastern US. Our findings highlight one particular aspect of these practices and beliefs: spirituality

The glacial geomorphology of the western cordilleran ice sheet and Ahklun ice cap, Southern Alaska

During the late Wisconsinan, Southern Alaska was covered by two large ice masses; the western arm of the Cordilleran Ice Sheet and the Ahklun Mountains Ice Cap. Compared to the other ice sheets that existed during this period (e.g. the British-Irish, Laurentide and Fennoscandian ice sheets), little is known about the geomorphology they left behind. This limits our understanding of their flow pattern and retreat. Here we present systematic mapping of the glacial geomorphology of the two ice masses which existed in Southern Alaska. Due to spatially variable data availability, mapping was conducted using digital elevation models and satellite images of varying resolutions. Offshore, we map the glacial geomorphology using available bathymetric data. For the first time, we document >5000 subglacial lineations, recording ice flow direction. The distribution of moraines is presented, as well as features related to glacial meltwater drainage patterns (eskers and meltwater channels). Prominent troughs were also mapped on Alaska's continental shelf. This map provides the data required for a glacial inversion of these palaeo-ice masses

On-site treatment of exertional heat stroke

Background: Exertional heat stroke is a devastating condition that can cause significant morbidity and mortality. Rapid cooling is the most effective means of treating heat stroke, but little is published on the safety and logistics of cooling patients on site at a major sporting event. Purpose: To describe an on-site exertional heat stroke treatment protocol and to compare the outcomes of patients treated on site to those transferred to hospitals. Study Design: Descriptive epidemiological study. Methods: Using race-day medical records and ambulance run sheets, patients who developed exertional heat stroke at the Indianapolis half-marathon from 2005 to 2012 were identified. Exertional heat stroke was defined as runners with a core temperature measured with a rectal thermometer greater than 102°F and altered mental status. Clinical information and patient outcomes were abstracted from the race medical tent and hospital charts by 3 separate trained reviewers using structured methods and a data collection form. Two reviewers, using a RedCAP database and dual-data entry, abstracted records for each patient. A third arbitrated all discrepancies between reviewers. Clinical signs, treatments, and outcomes were calculated using descriptive statistics, and data were grouped and compared for patients treated on site or transferred to local hospitals for treatment. Results: Over 235,000 athletes participated in the event over the 8-year period, with 696 seeking medical care. A total of 32 heat stroke victims were identified during the study period; of these, 22 were treated on site. Of these, 68% were treated with cold-water immersion and 59% were discharged home from the race. Ten exertional heat stroke patients were transported from the race course to local hospitals. None of them underwent cold-water immersion, and 40% of them were subsequently discharged home. No patients in the study died. Conclusion: On-site treatment of athletes who develop exertional heat stroke appears to be both safe and effective. On-site treatment may decrease the local burden of critically ill patients to emergency departments during large athletic events

pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of cl-Par-4, with high disorder and aggregation at neutral pH, but a largely folded, non-aggregated conformation at acidic p

Recent advances in exciton based quantum information processing in quantum dot nanostructures

Recent experimental developments in the field of semiconductor quantum dot spectroscopy will be discussed. First we report about single quantum dot exciton two-level systems and their coherent properties in terms of single qubit manipulations. In the second part we report on coherent quantum coupling in a prototype "two-qubit" system consisting of a vertically stacked pair of quantum dots. The interaction can be tuned in such quantum dot molecule devices using an applied voltage as external parameter.Comment: 37 pages, 15 figures, submitted to New Journal of Physics, focus issue on Solid State Quantum Information, added reference

Modulation of human airway barrier functions during Burkholderia thailandensis and Francisella tularensis Infection: Running Title: Airway Barrier Functions during Bacterial Infections

The bronchial epithelium provides protection against pathogens from the inhaled environment through the formation of a highly-regulated barrier. In order to understand the pulmonary diseases melioidosis and tularemia caused by Burkholderia thailandensis and Fransicella tularensis, respectively, the barrier function of the human bronchial epithelium were analysed. Polarised 16HBE14o- or differentiated primary human bronchial epithelial cells (BECs) were exposed to increasing multiplicities of infection (MOI) of B. thailandensis or F. tularensis Live Vaccine Strain and barrier responses monitored over 24–72 h. Challenge of polarized BECs with either bacterial speciescaused an MOI- and time-dependent increase in ionic permeability, disruption of tight junctions, and bacterial passage from the apical to the basolateral compartment. B. thailandensis was found to be more invasive than F. tularensis. Both bacterial species induced an MOI-dependent increase in TNF-α release. An increase in ionic permeability and TNF-α release was induced by B. thailandensis in differentiated BECs. Pretreatment of polarised BECs with the corticosteroid fluticasone propionate reduced bacterial-dependent increases in ionic permeability, bacterial passage, and TNF-α release.TNF blocking antibody Enbrel® reduced bacterial passage only. BEC barrier properties are disrupted during respiratory bacterial infections and targeting with corticosteroids or anti-TNF compounds may represent a therapeutic option