Serum profiling and biomarker discovery of rat mammary tumors using mass-coded abundance tags (MCAT)

Advances in Mass-spectrometry techniques allow for the rapid processing and evaluation of complex biological mixtures such as blood/serum. These samples represent a protein rich environment as well as a sentinel monitoring system of the entire organism. The central tenet of these studies is that changes in the microenvironment of a tissue, brought about by a disease process, will lead to sufficient changes in the protein and peptide pattern of the serum, such that the differences can be accurately detected and correctly associated with a particular disease state. Using mass-spectrometry approaches we have developed techniques that allow us to compare samples from tumor-free and tumor present serum samples simultaneously to find biomarkers that indicate the presence of cancer. To examine potentially important but less abundant proteins, ultrafiltration (UF) was used to eliminate the more abundant proteins and combine this with the non-isotopic peptide tags (S-methylthioacetimidate and S-methyl thiopropionimidate) described by Beardsley and Reilley (J. Proteome Res. 2: 15-21, 2003) to differentiate our samples. Use of these mass-coded abundance tags (MCAT) allows for simultaneous evaluation of serum samples from tumor present, and tumor free animals. Using an oa time-of-flight mass-spectrometer (Q-tof) with electrospray ionization we produce high quality spectrums to screen for peptides that have only one tag. Specificity of tagging increases the likelihood that the peptide resulted from a protein unique to either the control or conditioned state. Using the ms/ms function of the Q-tof we sequence the peptide and identify the parent protein. Specifically, our lab is using UF, MCAT and the Q-tof to evaluate rat models of chemically-induced tumors. By using animal models we overcome much of the variability that may exist in human serum samples due to differences in gender, diet and cancer initiation. We have shown that these systems allow for the identification of both small molecules such as Alpha S1 casein precursor (24 kDa) as well as proteins greater than the MCO such as Fibrinogen alpha/alpha E precursor and Coagulation factor 2 (86 and 70 kDa, respectively). With positive sequence identification we can now evaluate the tumors themselves to determine if the proteins are over-expressed in the tumor vs. normal tissues. Using this method of “bottom-up” analysis provides information on the nature and composition of our samples to more rapidly identify those proteins that are unique to the tumor state of the animals

Using NASA Remotely Sensed Data to Help Characterize Environmental Risk Factors for National Public Health Applications

NASA Marshall Space Flight Center is collaborating with the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) National Center for Public Health Informatics to address issues of environmental health and enhance public health decision making by utilizing NASA remotely sensed data and products. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the linked data sets and associated analyses to local, state and federal end-user groups. Three daily environmental data sets will be developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid utilizing the US Environmental Protection Agency (EPA) ground observations and NASA's MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Solar Insolation (SI) using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental data sets will be linked with public health data from the UAB REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline and other health outcomes. These environmental datasets and public health linkage analyses will be disseminated to end-users for decision making through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system

Public Health Applications of Remotely-sensed Environmental Datasets for the Conterminous United States

NASA Marshall Space Flight Center is collaborating with the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) National Center for Public Health Informatics to address issues of environmental health and enhance public health decision-making using NASA remotely-sensed data and products. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the linked data sets and associated analyses to local, state and federal end-user groups. Three daily environmental data sets were developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid using the US Environmental Protection Agency (EPA) ground observations and NASA's MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Incoming Solar Radiation (Insolation) and heat-related products using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental data sets were linked with public health data from the UAB REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline, stroke and other health outcomes. These environmental datasets and the results of the public health linkage analyses will be disseminated to end-users for decision-making through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system and through peer-reviewed publications respectively. The linkage of these data with the CDC WONDER system substantially expands public access to NASA data, making their use by a wide range of decision makers feasible. By successful completion of this research, decision-making activities, including policy-making and clinical decision-making, can be positively affected through utilization of the data products and analyses provided on the CDC WONDER system

AVAST Survey 0.4-1.0 {\mu}m Spectroscopy of Igneous Asteroids in the Inner and Middle Main Belt

We present the spectra of 60 asteroids, including 47 V-types observed during the first phase of the Adler V-Type Asteroid (AVAST) Survey. SDSS photometry was used to select candidate V-type asteroids for follow up by nature of their very blue $i-z$ color. 47 of the 61 observed candidates were positively classified as V-type asteroids, while an additional six show indications of a 0.9 $\mu$m feature consistent with V-type spectra, but not sufficient for formal classification. Four asteroids were found to be S-type, all of which had $i-z$ values very near the adopted AVAST selection criteria of $i-z \le -0.2$, including one candidate observed well outside the cut (at a mean $i-z$ of -0.11). Three A-type asteroids were also identified. Six V-type asteroids were observed beyond the 3:1 mean motion resonance with Jupiter, including the identification of two new V-type asteroids (63085 and 105041) at this distance. Six V-type asteroids were observed with low ($<5\deg$) orbital inclination, outside of the normal dynamical range of classic Vestoids, and are suggestive of a non-Vesta origin for at least some of the population.Comment: 1 table, 3 figures, To appear to Icaru

It's the Heat AND the Humidity - Assessment of Extreme Heat Scenarios to Enable the Assessment of Climate Impacts on Public Health

No abstract availabl

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Using NASA Environmental Data to Enhance Public Health Decision Making

The Universities Space Research Association at the NASA Marshall Space Flight Center is collaborating with the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) to address issues of environmental health and enhance public health decision making by utilizing NASA remotely sensed data and products. The objectives of this collaboration are to develop high-quality spatial data sets of environmental variables, and deliver the data sets and associated analyses to local, state and federal end-user groups. These data can be linked spatially and temporally to public health data, such as mortality and disease morbidity, for further analysis and decision making. Three daily environmental data sets have been developed for the conterminous U.S. on different spatial resolutions for the time period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid utilizing the US Environmental Protection Agency (EPA) ground observations and NASA s MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Solar Insolation (SI) and maximum and minimum air temperature using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental data sets will be linked with public health data from the UAB REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline and other health outcomes. These environmental datasets and public health linkage analyses will be made available to public health professionals, researchers and the general public through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system and through peer reviewed publications. To date, two of the data sets have been released to the public in CDC WONDER, Daily Air Temperature and Heat Index for years 1979-2010, and Daily Fine Particulate Matter (PM2.5) air quality measures for years 2003-2008. These data in CDC WONDER can be aggregated to the county-level, state-level, or regional-level as per users need and downloaded in tabular, graphical, and map formats. The summary statistical output are available to web and app developers via the WONDER Application Programming Interface (API). The linkage of these data with the CDC WONDER system provides a significant addition to CDC WONDER, allowing public health researchers and policy makers to better include environmental exposure data in the context of other health data available in CDC WONDER online system. It also substantially expands public access to NASA environmental data, making their use by a wide range of decision makers feasible