The Mind Research Network - Mental Illness Neuroscience Discovery Grant

The scientific and technological programs of the Mind Research Network (MRN), reflect DOE missions in basic science and associated instrumentation, computational modeling, and experimental techniques. MRN's technical goals over the course of this project have been to develop and apply integrated, multi-modality functional imaging techniques derived from a decade of DOE-support research and technology development

The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level

How much effort is required to accurately describe the complex ecology of a rodent‐borne viral disease?

We use data collected on 18, 1-ha live trapping grids monitored from 1994 through 2005 and on five of those grids through 2013 in the mesic northwestern United States to illustrate the complexity of the deer mouse (Peromyscus maniculatus)/Sin Nombre virus (SNV) host-pathogen system. Important factors necessary to understand zoonotic disease ecology include those associated with distribution and population dynamics of reservoir species as well as infection dynamics. Results are based on more than 851,000 trap nights, 16,608 individual deer mice and 10,572 collected blood samples. Deer mice were distributed throughout every habitat we sampled and were present during every sampling period in all habitats except high altitude habitats over 1900 m. Abundance varied greatly among locations with peak numbers occurring mostly during fall. However, peak rodent abundance occurred during fall, winter and spring during various years on three grids trapped 12 months/yr. Prevalence of antibodies to SNV averaged 3.9% to 22.1% but no grids had mice with antibodies during every month. The maximum period without antibody-positive mice ranged from 1 to 52 months, or even more at high altitude grids where deer mice were not always present. Months without antibody-positive mice were more prevalent during fall than spring. Population fluctuations were not synchronous over broad geographic areas and antibody prevalences were not well spatially consistent, differing greatly over short distances. We observed an apparently negative, but nonstatistically significant relationship between average antibody prevalence and average deer mouse population abundance and a statistically significant positive relationship between the average number of antibody positive mice and average population abundance. We present data from which potential researchers can estimate the effort required to adequately describe the ecology of a rodentborne viral system. We address different factors affecting population dynamics and hantavirus antibody prevalence and discuss the path to understanding a complex rodent-borne disease system as well as the obstacles in that path.Fil: Douglass, Richard J.. University of Montana; Estados UnidosFil: Vadell, María Victoria. Universidad Nacional de San Martín. Instituto de Investigaciones e Ingeniería Ambiental. Laboratorio de Ecología de Enfermedades Transmitidas por Vectores; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Joint Elastic Side-Scattering Lidar and Raman Lidar Measurements of Aerosol Optical Properties in South East Colorado

We describe an experiment, located in south-east Colorado, USA, that measured aerosol optical depth profiles using two Lidar techniques. Two independent detectors measured scattered light from a vertical UV laser beam. One detector, located at the laser site, measured light via the inelastic Raman backscattering process. This is a common method used in atmospheric science for measuring aerosol optical depth profiles. The other detector, located approximately 40km distant, viewed the laser beam from the side. This detector featured a 3.5m2 mirror and measured elastically scattered light in a bistatic Lidar configuration following the method used at the Pierre Auger cosmic ray observatory. The goal of this experiment was to assess and improve methods to measure atmospheric clarity, specifically aerosol optical depth profiles, for cosmic ray UV fluorescence detectors that use the atmosphere as a giant calorimeter. The experiment collected data from September 2010 to July 2011 under varying conditions of aerosol loading. We describe the instruments and techniques and compare the aerosol optical depth profiles measured by the Raman and bistatic Lidar detectors.Comment: 34 pages, 16 figure

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

Mars Tumbleweed: FY2003 Conceptual Design Assessment

NASA LaRC is studying concepts for a new type of Mars exploration vehicle that would be propelled by the wind. Known as the Mars Tumbleweed, it would derive mobility through use of the Martian surface winds. Tumbleweeds could conceivably travel greater distances, cover larger areas of the surface, and provide access to areas inaccessible by conventional vehicles. They would be lightweight and relatively inexpensive, allowing a multiple vehicle network to be deployed on a single mission. Tumbleweeds would be equipped with sensors for conducting science and serve as scouts searching broad areas to identify specific locations for follow-on investigation by other explorers. An extensive assessment of LaRC Tumbleweed concepts was conducted in FY03, including refinement of science mission scenarios, definition of supporting subsystems (structures, power, communications), testing in wind tunnels, and development of a dynamic simulation capability

Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages

OBJECTIVE Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+). METHODS Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention