Christopher Lowry - US grants

0824829
Becker


This proposal seeks funding to acquire a fiber optic temperature sensing distributed network for hydrological research and education. The distributed temperature sensing (DTC) system acquires data by tracking the time-of-flight and backscatter from a light pulse sent through a fiber optic cable. These characteristics allow the system to calculate temperature. Different scattering mechanisms are available, but a Raman scattering device is requested. The instrument uses the ratio of anti-Stokes/Stokes backscatter to differentiate the temperature of the cable, which is known to the unknown ?outside? temperature. Two point calibrations are performed before each deployment. Understanding elemental, carbon and contaminant flow in the Great Lakes system requires a better understanding of ground-water and surface water flow regimes and interactions. Understanding non-point-source loadings to the Great Lakes requires better estimates of groundwater recharge. In addition, water use issues (like diversion for other purposes) will have unknown impacts on the Great Lakes hydrology, ecology and environment. By using DTS employments, temperature differentials can be measured as a proxy for stream recharge rates in representative basins of the Great Lakes. These measurements will be higher resolution both in terms of spatial and temporal scales relative to a gauging station approach. The PIs will also perform studies to enhance DTS technology by investigating the relationship between fiber optic cable temperature and groundwater fluid velocity. A cable buried within a permeable reactive barrier at a contaminated site will be used for this investigation. A current will be induced across the cable such that stagnant waters will offer less heat flux ? a proxy for flow. Another application for the fiber optic cable will be to assess the flow regime adjacent to and brought about by large woody debris in riverine and stream systems. Preliminary experiments using artificially-cooled water were able to delineate water masses of differing temperatures. Additionally, the cable will be moored in a ?serpentine? fashion in a near-shore region of Lake Ontario in order to study the development of thermal bars in spring and fall. Thermal bars are important for nutrient and contaminant cycling, yet are understudied in high-resolution. Finally, the cable instrument will be used for understanding wetland restoration and hydroelectric discharge studies. The instrument will be incorporated into an existing group of equipment managed and prioritized by the IGERT steering committee. It will be housed in the Department of Civil, Structural, and Environmental Engineering. Outside IGERT users will be required to pay a usage fee. Cables are fragile and require frequent replacement. Researchers using the system will be required to budget for replacement cabling. Course fees will also help offset cable replacement costs.

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Recent studies in humans have demonstrated that holding a warm cup of coffee, as opposed to a cold cup of coffee, increases pro-social behavior, without any conscious awareness by the individual of the effects of temperature on their behavior. Although the mechanisms involved have not been defined, these findings suggest that there are mechanisms through which sensation of warm temperature in the skin can affect social behavior. Preliminary data from the Lowry laboratory suggest that a subpopulation of neurons in the brainstem that produce the brain chemical serotonin may be responsible for the effects of temperature on social behavior. Furthermore, these preliminary data suggest that a temperature-sensitive protein, temperature-activated transient receptor potential (TRP) ion channel 4 (TRPv4), may be responsible for sensing temperature changes in the skin that lead to activation of serotonergic neurons. The PI will test the hypotheses that (1) the neuronal activity of a subset of serotonergic neurons in the brain responds to increases in temperature via mechanisms involving TRPv4 activation, and (2) activation of TRPv4 leads to decreased anxiety-related behaviors and, conversely, increases in social interaction.
Anatomical, electrophysiological, pharmacological, and behavioral approaches will be used to investigate the role of a subset of serotonergic neurons in both sensing temperature and regulating behavior. Warm temperature is expected to activate a subset of serotonergic neurons projecting to brain structures involved in regulation of social behavior. This activation of serotonergic neurons by warm temperature is also expected to be dependent on activation of the temperature-sensitive channel TRPv4. This research will provide new information relevant to the effects of thermal stimuli on a highly conserved neurotransmitter system, the serotonergic system, and on emotional and social behavior, new information that has application across vertebrate and invertebrate taxa. This project will provide valuable training opportunities for graduate and undergraduate students as well as incorporating outreach and research mentoring for underrepresented high school students in the nearby community.

When an organism is exposed to a wide range of stressors, a neuroendocrine cascade leads to the release of stress hormones (corticosteroids) into the bloodstream. The corticosteroids produce changes in physiology and brain function that are crucial for dealing with emergencies, but persistent elevation of corticosteroids produce the well known deleterious effects of stress. All vertebrates need a rapid and robust stress response as well as an effective means of terminating this response. The brain mechanisms that terminate this response remain poorly understood. These studies investigate a novel mechanism through which stress hormones could provide negative feedback to terminate the stress response. Collaborative experiments will be conducted at Arizona State University, University of Colorado and University of South Dakota to test the hypothesis that corticosteroids block clearance of the neurotransmitter serotonin in specific brain regions during a stress response leading to negative feedback and associated changes in behavior. State-of-the-art neurochemical, brain imaging and behavioral studies will determine whether corticosteroids block serotonin transport via a newly described transporter in brain, leading to enhanced serotonin signaling and suppression of the stress response. These studies will also serve to train students (graduate, undergraduate, and high school) and post-doctoral researchers in cutting-edge neuroscience research. The research training provided by the principle investigators (PIs) is important for encouraging young students to appreciate scientific reasoning and pursue careers in science. Collectively, the PIs have sponsored over 100 undergraduate research projects from students with diverse backgrounds, and each of the PIs also has a long track record of dedication to graduate student education and research. With these studies, each PI will continue to make explicit efforts to reach out to economically disadvantaged or underrepresented groups.

DESCRIPTION (provided by applicant): Evidence supports the hypothesis that genetic influences, together with adverse experience, either during early life or during adulthood, contribute to the vulnerability of individuals to stress-related neuropsychiatric disorders, including anxiety and depression. One mechanism through which these factors may influence vulnerability to these disorders is through effects on monoaminergic systems, including brainstem serotonergic systems that are thought to play an important role in the development and pathophysiology of stress-related psychiatric disorders. We propose to study how exposure to stress activates serotonergic systems. Such studies are a prerequisite for understanding how chronic stress leads to dysfunction of serotonergic systems and, ultimately, the mechanisms underlying dysregulation of serotonergic systems in patients with stress- related psychiatric disorders. The proposed studies are designed to lead to novel strategies for preventing the onset of stress-related mental disease. The overall hypothesis is that stress-induced increases in serotonergic activity depend on activation of projections from the central amygdaloid nucleus (CE) to the caudal dorsal raphe nucleus (DR). The CE is an important component of brain circuits regulating autonomic and behavioral responses to stress and fear-related stimuli, while the DR is the main source of serotonergic innervation of limbic forebrain structures regulating anxiety and mood. First, we will test the hypothesis that stress-induced activation of serotonergic systems depends on activation of CRF2 receptors within the caudal DR. Second, we will test the hypothesis that stress-induced activation of serotonergic systems is dependent on norepinephrine (NE) signaling in the CE. Third, we will test the hypothesis that the CE acts as a "coincidence detector" where stress-induced elevation of glucocorticoid hormones and stress-induced NE release within the CE act synergistically to increase mesolimbocortical serotonergic activity and TPH activity. We will also test the hypothesis that the mechanism underlying this "coincidence detection" is glucocorticoid-mediated blockade of NE clearance by the low-affinity, high-capacity, corticosterone-sensitive transporter, organic cation transporter 3 (OCT3). OCT3 is known to mediate "uptake 2," an alternative uptake mechanism for monoamines recently characterized in rat brain. These hypotheses will be tested using site-specific activation and blockade of specific receptors, measurement of serotonergic activity using microdialysis, and measurement of in vivo tryptophan hydroxylase activity. These studies are designed to provide new and important information related to the neural mechanisms through which stressful experiences activate serotonergic systems. Understanding the mechanisms involved in stress-induced activation of brain serotonergic systems may allow attenuation or prevention of long-term detrimental consequences of stress in individuals that are believed to be vulnerable to stress-induced neuropsychiatric disorders, either by virtue of genetic susceptibility, adverse early life experience, or chronic or intermittent exposure to a stressful environment. Stress-related neuropsychiatric disorders including anxiety disorders and depression represent a significant public health problem. For example, unipolar depression is projected to rank second, behind ischemic heart disease, as a cause of disability adjusted life years (DALYs) by the year 2020. This projected outcome demands that we begin to explore mechanisms that precipitate the onset of stress-related disease, so that we can ultimately prevent mental disease in susceptible individuals. This proposal is designed to address this important need by investigating mechanisms through which stress activates serotonergic systems that are thought to be central to both the etiology and pathophysiology of stress-related mental disease.

Using California's Drought to Analyze Groundwater Inputs from Fractured Bedrock to Alpine Meadows

Quantifying the contribution from groundwater is critical for understanding alpine water supply during both drought and future climate change. Past hydrologic studies in high-elevation mountain meadows have focused on water derived from snowmelt, streams, and adjacent hillslopes to support alpine vegetation. Given California's multi-year drought, one can better identify previously unrecognized groundwater contributions to high-elevation meadows from underlying bedrock. This project will sample and better define the deep groundwater component of the Sierra system through chemical and isotopic means. The project will develop connections to scientists at national labs; and two graduate students will gain field experience, learn new field methods, and participate in laboratory analysis. The Sierra Nevada National Parks and Forests represent an important outdoor classroom for education of the general public in the natural sciences. All project results will be given to the National Park Service for incorporation into their outdoor education programs.

This investigation will take advantage of the current drought when contributions from flowpaths in deep fractured bedrock will yield a high-fidelity geochemical signal that will enable quantification of the location and volume of groundwater entering meadows from bedrock sources. This project will demonstrate a computational methodology for geochemical deconvolution of deep bedrock groundwater and shallow groundwater geochemical signals that can be transferred to other high-elevation meadows where groundwater input has generally been unrecognized. This project will investigate a suite of naturally occurring geochemical tracers in Yosemite groundwater wells to identify the locations of groundwater discharge from fractured bedrock contributing to meadows in the Sierra Nevada Mountains of California. New methods of groundwater sampling for noble gas and isotopic tracers will be developed. Samples of groundwater and stream water will be analyzed for multiple chemical constituents through collaboration with the scientists at Lawrence Livermore National Lab.

This research is designed to engage public participation in data collection and the development of a stream discharge, stream temperature, and aquatic species habitat forecasting model. Through the use of citizen-based observations of stream height and stream temperature, this approach will demonstrate how citizen-derived observations can contribute to forecasts of stream discharge, stream temperature, and identification of freshwater fish habitat. Freshwater fishes have significant ecological, economic, and recreational importance across the United States. However, freshwater species are among the most endangered groups of organisms in North America, largely due to the impact of human activities. Accurate representations of freshwater species habitat are needed to develop approaches to balance the needs of society with the conservation of freshwater resources. This can be accomplished through the collection of observed data by government and research organizations or by computer modeling of habitat, whereby the quality of the model depends upon the availability of observed data. However, the amount of observed data for freshwater systems has been declining due to decreases in funding. The data that do exist are generally focused on large rivers that are important for urban communities (i.e., flooding, water supply), which are locations not always relevant to freshwater species whose habitat often occurs in smaller headwater streams. Local communities of recreational users and their mobile phones offer an opportunity to close this data-availability gap through citizen science. As regular users of shared resources, like streams and waterways, outdoor enthusiasts have valuable knowledge of specific locations. This knowledge is vastly underutilized by scientific communities. This project will harness information and data collected by members of local communities and develop an approach for data collection, storage, and integration with computer models that can predict streamflow, stream temperature, and freshwater species habitat, which can then aid in sustainable management of these resources. The Boyne River Basin in Michigan, USA will be used as a test location, but the techniques can be used in watersheds throughout the world.

The goal of this research is to develop techniques that integrate citizen science hydrology and stream temperature data with eco-hydrological models. Specifically, this research is designed to fully couple citizen participation in the development of a real-time stream discharge, temperature, and aquatic species habitat forecasting model framework. The project will install CrowdHydrology (a citizen science network that collects hydrologic data) equipment throughout the Boyne River Basin. The local community can then text (via cellphone) stream level and stream temperature data to the CrowdHydrology platform. These citizen science data will then be transformed and input into an eco-hydrological model for near real-time simulations of streamflow, stream temperature, and aquatic species habitat. This approach will demonstrate how citizen-derived observations can contribute to the modeling of stream discharge, stream temperature, and aquatic species habitat. The model simulations and forecasts (one week ahead), including stream flows, temperatures, and habitat distributions, will be presented in tables and simple spatial plots available for download on the CrowdHydrology website (http://www.crowdhydrology.com)

Project Summary Immunoregulation, indicated by a balanced expansion of effector T-cell populations and regulatory T cells (Treg), is known to be driven by microbial signals, mainly by organisms with which mammals coevolved, including: (i) the commensal microbiota, which have been altered by the Western lifestyle, including a diet that is commonly low in microbiota-accessible carbohydrates; (ii), pathogens associated with the ?old infections? that were present throughout life in evolving human hunter-gatherer populations; and (iii) organisms from the natural environment with which humans were inevitably in daily contact (and so had to be tolerated by the immune system). Immunoregulation is thought to be compromised in modern high-income settings due to reduced contact with these three categories of organisms. A failure of immunoregulation, attributable to reduced exposure to the microbial environment within which the mammalian immune system evolved, is thought to be one factor contributing to recent increases in stress-related and chronic inflammatory disorders in high-income countries. Immunization with one of these ?old friends?, in the form of a heat-killed preparation of Mycobacterium vaccae, a nonpathogenic, environmental saprophyte with anti-inflammatory and immunoregulatory properties, has been shown to increase stress resilience in mice, as measured by prevention of stress-induced increases in anxiety, prevention of stress-induced exaggeration of spontaneous colitis and prevention of chemically induced colitis in a model of inflammatory bowel disease. However, the mechanisms through which M. vaccae mediates is stress protective effects on behavior, at the level of the central nervous system, are not known. Our preliminary data demonstrate that immunization with M. vaccae increases expression of the anti-inflammatory cytokine, interleukin (IL)-4, in the rat brain, prevents stress- induced priming of hippocampal microglia, and prevents stress-induced decreases in juvenile social investigation in rats. In this R21 proposal, we propose to determine, using male and female rats, if the stress- protective effects of immunization with M. vaccae, as measured by prevention of inescapable stress (IS)- induced increases in anxiety, conditioned fear, and escape deficits, and prevention of priming of hippocampal microglia, are dependent on increases in IL-4. We will also determine, for the first time, if IL-4 is sufficient to protect against IS-induced behavioral deficits. Finally, we will determine if the stress-protective effects of immunization with M. vaccae involve inhibition of specific neural circuits involved in mediating the behavioral sequelae of IS, including locus coeruleus, lateral habenula, and bed nucleus of the stria terminalis projections to the serotonergic dorsal raphe nucleus. Together, the proposed studies will provide the first detailed investigation of neural mechanisms through which immunization with M. vaccae promotes stress resilience.

Flooding is the most damaging natural hazard in the U.S. and around the world, and most flood damage occurs in cities. Yet the ability to know when flooding is happening and communicate that risk to the public and first responders is limited. At the same time there is a surge in digitally connected technologies, many at the fingertips of the general public (e.g., smartphones). The need is for new flood information that can be generated from primary observations that are collected in exactly the right places and times to be coupled with the ability to more effectively communicate this risk to communities. This project will develop the Integrated Flood Stage Observation Network (IFSON), a system that can take in crowd-sourced information on flooding (from cameras, a smartphone app, and social media), intelligently assess flood risk (using machine learning), and communicate those risks in real time. IFSON will be scalable to any community or city and will provide a backbone for new crowd-sourced technologies.

This project will i) integrate several new technologies (each that directly engages with different communities) to provide new insights into and communication capacity around urban flooding hazards, ii) connect a range of communities to each other in near-realtime (from the general public to first responders to infrastructure managers) and develop flood sensing and avoidance capacities that can be used anywhere in the U.S. or even internationally, iii) develop new insights into how urban morphology contributes to flood risk, and iv) leverage prior funding by connecting practitioners from existing sustainability research networks and sending data to CUAHSI and eRams. Additionally, this research will develop outreach activities that will educate the public and practitioners on how flooding hazards occur, their impacts, and how to mitigate risks. The research will directly empower and engage local citizens in flood event reporting and response, and explores a concrete model for what it would mean to have a "smart and connected community" for minimizing flood risk. Although driven by a number of novel technologies and techniques, the central focus of this work is on the interface of community with technology and, in particular, how modern network technologies can engage and bring together ordinary citizens, city planners, first responders, and other local stakeholders within a shared, collaboratively constructed information space; a broad range of educational and outreach opportunities are included to engage stakeholders and amplify project impact. In addition to training students through research positions, the project will create a summer Research Experience for Undergraduates (REU) program. It will also connect with national, state, and local societies across a number of disciplines. For example, the project will work with the City of Phoenix during their Monsoon Preparedness day to educate first responders on how to use project results. Interdisciplinary course modules that show how to engage various communities (including the public, first responders, and infrastructure managers) in mitigating flood risk will be developed and disseminated. Additionally, infrastructure managers will be recruited to participate in workshops on how project data will reveal new insights into the condition of infrastructure and what strategies can be employed to reduce hazards.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Project Summary/Abstract United States military Veterans from recent conflicts are coping with symptoms related to posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and mental health interventions (e.g., medication, psychotherapy), and often symptoms are not significantly improved by traditional treatments. Alternative treatment methods are needed. An underlying feature of PTSD is exaggerated inflammation, both peripherally and in the central nervous system, which is thought to play an important role in the vulnerability to, aggravation of, and perpetuation of adverse consequences of this condition. Therefore, an innovative intervention strategy would be the use of anti-inflammatory/immunoregulatory probiotics to reduce inflammation. In this study, we will investigate the effects of an 8-week oral administration of Lactobacillus rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and immunoregulatory effects on both biological signatures of systemic inflammatory processes and proximal signatures of probiotic administration. LGG is a commensal organism that colonizes the human gut mucosa and suppresses mucosal inflammation via inhibition of the production of proinflammatory cytokines. The specific aim of the study is to identify the effect of probiotics on systemic inflammation, as well as PTSD symptoms, microbiota composition, gut permeability, stress response, and decision-making. Outcomes will be assessed using a longitudinal, double blind, randomized placebo-controlled design. After initial evaluation procedures to confirm PTSD and Functional Bowel Disorder diagnoses, 59 participants will be randomized to probiotic supplementation and 59 will be randomized to placebo supplementation. The proposed line of research addresses the NIH funding opportunity purpose, ?to accelerate translational and clinical Phase IIa? trials regarding ?probiotic[s]? to increase ?understanding regarding underlying mechanisms of their action(s), and variability in responses to these interventions?. Long-term, this study may lead to a paradigm shift in the manner by which we target clinical symptoms associated with PTSD by beginning the process of supporting a multitargeted, neuroprotective approach.