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UNC-authored articles published by Frontiers
Works (698)
651. A Monte Carlo Evaluation of Weighted Community Detection Algorithms
- Title Tesim:
- A Monte Carlo Evaluation of Weighted Community Detection Algorithms
- Creator:
- Steinley, Doug, Henry, Teague, Fair, Damien A., and Gates, Kathleen M.
- Date of publication:
- 2016
- Abstract Tesim:
- The past decade has been marked with a proliferation of community detection algorithms that aim to organize nodes (e.g., individuals, brain regions, variables) into modular structures that indicate subgroups, clusters, or communities. Motivated by the emergence of big data across many fields of inquiry, these methodological developments have primarily focused on the detection of communities of nodes from matrices that are very large. However, it remains unknown if the algorithms can reliably detect communities in smaller graph sizes (i.e., 1000 nodes and fewer) which are commonly used in brain research. More importantly, these algorithms have predominantly been tested only on binary or sparse count matrices and it remains unclear the degree to which the algorithms can recover community structure for different types of matrices, such as the often used cross-correlation matrices representing functional connectivity across predefined brain regions. Of the publicly available approaches for weighted graphs that can detect communities in graph sizes of at least 1000, prior research has demonstrated that Newman's spectral approach (i.e., Leading Eigenvalue), Walktrap, Fast Modularity, the Louvain method (i.e., multilevel community method), Label Propagation, and Infomap all recover communities exceptionally well in certain circumstances. The purpose of the present Monte Carlo simulation study is to test these methods across a large number of conditions, including varied graph sizes and types of matrix (sparse count, correlation, and reflected Euclidean distance), to identify which algorithm is optimal for specific types of data matrices. The results indicate that when the data are in the form of sparse count networks (such as those seen in diffusion tensor imaging), Label Propagation and Walktrap surfaced as the most reliable methods for community detection. For dense, weighted networks such as correlation matrices capturing functional connectivity, Walktrap consistently outperformed the other approaches for recovering communities.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Psychology and Neuroscience
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/th2y-ze35
- Identifier:
- PMID: 27891087, Onescience id: 7bc980e9720802b0c5d5fa697008ca9086d85c37, Publisher DOI: https://doi.org/10.3389/fninf.2016.00045, and PMCID: PMC5102890
- ISSN:
- 1662-5196
- Journal Title:
- Frontiers in Neuroinformatics
- Journal Volume:
- 10
- Keyword:
- functional connectivity, community detection, Monte Carlo simulations, Cluster analysis, and fMRI methods
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Psychological Sciences; University of Missouri and Departments of Behavioral Neuroscience and Psychiatry; Oregon Health and Sciences University
- Person:
- Steinley, Doug, Henry, Teague, Fair, Damien A., and Gates, Kathleen M.
- Rights Statement Label:
- In Copyright
- Source:
- r494vr00c
652. Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation
- Title Tesim:
- Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation
- Creator:
- Justen, Marissa A., Lai, Mandy, Kato, Hiroyuki K., Gillet, Shea N., and Isaacson, Jeffry S.
- Date of publication:
- 2018
- Abstract Tesim:
- Projections from auditory cortex to the amygdala are thought to contribute to the induction of auditory fear learning. In addition, fear conditioning has been found to enhance cortical responses to conditioned tones, suggesting that cortical plasticity contributes to fear learning. However, the functional role of auditory cortex in the retrieval of fear memories is unclear and how fear learning regulates cortical sensory representations is not well understood. To address these questions, we use acute optogenetic silencing and chronic two-photon calcium imaging in mouse auditory cortex during fear learning. Longitudinal imaging of neuronal ensemble activity reveals that discriminative fear learning modulates cortical sensory representations via the suppression of cortical habituation.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Psychiatry
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/6ywy-ps73
- Identifier:
- PMID: 29375323, Publisher DOI: https://doi.org/10.3389/fncir.2017.00112, Onescience id: bc0151e1fcfc91eaf9b5d4347fa6ed4545b36aaa, and PMCID: PMC5767681
- ISSN:
- 1662-5110
- Journal Title:
- Frontiers in Neural Circuits
- Journal Volume:
- 11
- Keyword:
- learning and memory, auditory cortex, interneurons, somatostatin, cortical circuits, GCaMP, and fear conditioning
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Biological Sciences; University of California; San Diego and Department of Neurosciences; Center for Neural Circuits and Behavior; University of California; San Diego
- Person:
- Justen, Marissa A., Lai, Mandy, Kato, Hiroyuki K., Gillet, Shea N., and Isaacson, Jeffry S.
- Rights Statement Label:
- In Copyright
- Source:
- ks65hj036
653. Sparse and Specific Coding during Information Transmission between Co-cultured Dentate Gyrus and CA3 Hippocampal Networks
- Title Tesim:
- Sparse and Specific Coding during Information Transmission between Co-cultured Dentate Gyrus and CA3 Hippocampal Networks
- Creator:
- Brewer, Gregory J., Demarse, Thomas B., Wheeler, Bruce C., Thiagarajan, Srikanth, and Poli, Daniele
- Date of publication:
- 2017
- Abstract Tesim:
- To better understand encoding and decoding of stimulus information in two specific hippocampal sub-regions, we isolated and co-cultured rat primary dentate gyrus (DG) and CA3 neurons within a two-chamber device with axonal connectivity via micro-tunnels. We tested the hypothesis that, in these engineered networks, decoding performance of stimulus site information would be more accurate when stimuli and information flow occur in anatomically correct feed-forward DG to CA3 vs. CA3 back to DG. In particular, we characterized the neural code of these sub-regions by measuring sparseness and uniqueness of the responses evoked by specific paired-pulse stimuli. We used the evoked responses in CA3 to decode the stimulation sites in DG (and vice-versa) by means of learning algorithms for classification (support vector machine, SVM). The device was placed over an 8 × 8 grid of extracellular electrodes (micro-electrode array, MEA) in order to provide a platform for monitoring development, self-organization, and improved access to stimulation and recording at multiple sites. The micro-tunnels were designed with dimensions 3 × 10 × 400 μm allowing axonal growth but not migration of cell bodies and long enough to exclude traversal by dendrites. Paired-pulse stimulation (inter-pulse interval 50 ms) was applied at 22 different sites and repeated 25 times in each chamber for each sub-region to evoke time-locked activity. DG-DG and CA3-CA3 networks were used as controls. Stimulation in DG drove signals through the axons in the tunnels to activate a relatively small set of specific electrodes in CA3 (sparse code). CA3-CA3 and DG-DG controls were less sparse in coding than CA3 in DG-CA3 networks. Using all target electrodes with the three highest spike rates (14%), the evoked responses in CA3 specified each stimulation site in DG with optimum uniqueness of 64%. Finally, by SVM learning, these evoked responses in CA3 correctly decoded the stimulation sites in DG for 43% of the trials, significantly higher than the reverse, i.e., how well-recording in DG could predict the stimulation site in CA3. In conclusion, our co-cultured model for the in vivo DG-CA3 hippocampal network showed sparse and specific responses in CA3, selectively evoked by each stimulation site in DG.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Neurology
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/y6eq-qc97
- Identifier:
- PMCID: PMC5337490, Publisher DOI: https://doi.org/10.3389/fncir.2017.00013, Onescience id: bab427bee9e6425f989ca1f716fb737baf48de97, and PMID: 28321182
- ISSN:
- 1662-5110
- Journal Title:
- Frontiers in Neural Circuits
- Journal Volume:
- 11
- Keyword:
- machine learning, CA3, Microelectrodes, CA3 Region, Hippocampal, Evoked Potentials, hippocampus, Dentate Gyrus, decoding, Rats, Nerve Net, micro-electrode array, network, Neurons, Cells, Cultured, DG, neural code, Animals, Models, Neurological, and Machine Learning
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Biomedical Engineering; University of California, Memory Impairments and Neurological Disorders (MIND) Institute; University of California, Department of Biomedical Engineering; University of Florida, and Department of Bioengineering; University of California
- Person:
- Brewer, Gregory J., Demarse, Thomas B., Wheeler, Bruce C., Thiagarajan, Srikanth, and Poli, Daniele
- Rights Statement Label:
- In Copyright
- Source:
- 3t945w56b
654. Radiate and Planar Multipolar Neurons of the Mouse Anteroventral Cochlear Nucleus: Intrinsic Excitability and Characterization of their Auditory Nerve Input
- Title Tesim:
- Radiate and Planar Multipolar Neurons of the Mouse Anteroventral Cochlear Nucleus: Intrinsic Excitability and Characterization of their Auditory Nerve Input
- Creator:
- Xie, Ruili and Manis, Paul B.
- Date of publication:
- 2017
- Abstract Tesim:
- Radiate and planar neurons are the two major types of multipolar neurons in the ventral cochlear nucleus (VCN). Both cell types receive monosynaptic excitatory synaptic inputs from the auditory nerve, but have different responses to sound and project to different target regions and cells. Although the intrinsic physiology and synaptic inputs to planar neurons have been previously characterized, the radiate neurons are less common and have not been as well studied. We studied both types of multipolar neurons and characterized their properties including intrinsic excitability, synaptic dynamics of their auditory nerve inputs, as well as their neural firing properties to auditory nerve stimulation. Radiate neurons had a faster member time constant and higher threshold current to fire spikes than planar neurons, but the maximal firing rate is the same for both cell types upon large current injections. Compared to planar neurons, radiate neurons showed spontaneous postsynaptic currents with smaller size, and slower but variable kinetics. Auditory nerve stimulation progressively recruited synaptic inputs that were smaller and slower in radiate neurons, over a broader range of stimulus strength. Synaptic inputs to radiate neurons showed less depression than planar neurons during low rates of repetitive activity, but the synaptic depression at higher rates was similar between two cell types. However, due to the slow kinetics of the synaptic inputs, synaptic transmission in radiate neurons showed prominent temporal summation that contributed to greater synaptic depolarization and a higher firing rate for repetitive auditory nerve stimulation at high rates. Taken together, these results show that radiate multipolar neurons integrate a large number of weak synaptic inputs over a broad dynamic range, and have intrinsic and synaptic properties that are distinct from planar multipolar neurons. These properties enable radiate neurons to generate powerful inhibitory inputs to target neurons during high levels of afferent activity. Such robust inhibition is expected to dynamically modulate the excitability of many cell types in the cochlear nuclear complex.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Otolaryngology/Head and Neck Surgery
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/mj27-3229
- Identifier:
- PMCID: PMC5651243, Onescience id: 1d0a903c6a641dfa96d39c634e9b53593099fe6c, PMID: 29093666, and Publisher DOI: https://doi.org/10.3389/fncir.2017.00077
- ISSN:
- 1662-5110
- Journal Title:
- Frontiers in Neural Circuits
- Journal Volume:
- 11
- Keyword:
- synaptic dynamics, Stellate neuron, RC321-571, stellate neuron, radiate, planar, Neurosciences. Biological psychiatry. Neuropsychiatry, inhibition, Excitatory synaptic transmission, Cochlear Nucleus, cochlear nucleus, and auditory nerve input
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Neurosciences; University of Toledo and Department of Cell Biology and Physiology
- Person:
- Xie, Ruili and Manis, Paul B.
- Rights Statement Label:
- In Copyright
- Source:
- 9z903465b
655. NCAM Regulates Inhibition and Excitability in Layer 2/3 Pyramidal Cells of Anterior Cingulate Cortex
- Title Tesim:
- NCAM Regulates Inhibition and Excitability in Layer 2/3 Pyramidal Cells of Anterior Cingulate Cortex
- Creator:
- Kasten, Michael R., Sullivan, Chelsea S., Maness, Patricia F., Manis, Paul B., Zhang, Xuying, and Kratz, Megan B.
- Date of publication:
- 2017
- Abstract Tesim:
- The neural cell adhesion molecule (NCAM), has been shown to be an obligate regulator of synaptic stability and pruning during critical periods of cortical maturation. However, the functional consequences of NCAM deletion on the organization of inhibitory circuits in cortex are not known. In vesicular gamma-amino butyric acid (GABA) transporter (VGAT)-channelrhodopsin2 (ChR2)-enhanced yellow fluorescent protein (EYFP) transgenic mice, NCAM is expressed postnatally at perisomatic synaptic puncta of EYFP-labeled parvalbumin, somatostatin and calretinin-positive interneurons, and in the neuropil in the anterior cingulate cortex (ACC). To investigate how NCAM deletion affects the spatial organization of inhibitory inputs to pyramidal cells, we used laser scanning photostimulation in brain slices of VGAT-ChR2-EYFP transgenic mice crossed to either NCAM-null or wild type (WT) mice. Laser scanning photostimulation revealed that NCAM deletion increased the strength of close-in inhibitory connections to layer 2/3 pyramidal cells of the ACC. In addition, in NCAM-null mice, the intrinsic excitability of pyramidal cells increased, whereas the intrinsic excitability of GABAergic interneurons did not change. The increase in inhibitory tone onto pyramidal cells, and the increased pyramidal cell excitability in NCAM-null mice will alter the delicate coordination of excitation and inhibition (E/I coordination) in the ACC, and may be a factor contributing to circuit dysfunction in diseases such as schizophrenia and bipolar disorder, in which NCAM has been implicated.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Otolaryngology/Head and Neck Surgery and Department of Biochemistry and Biophysics
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/wpdx-vw85
- Identifier:
- Publisher DOI: https://doi.org/10.3389/fncir.2017.00019, PMID: 28386219, PMCID: PMC5362729, and Onescience id: 828d5eb116ded1017b32462c5bce5be8eab1b30c
- ISSN:
- 1662-5110
- Journal Title:
- Frontiers in Neural Circuits
- Journal Volume:
- 11
- Keyword:
- Mice, Mice, Transgenic, Neural Cell Adhesion Molecules, channelrhodopsin, Mice, Inbred C57BL, laser scanning photostimulation, patch clamp, Electrophysiological Phenomena, Animals, brain slice, Patch-Clamp Techniques, Mice, Mutant Strains, Neural Inhibition, mouse, Gyrus Cinguli, Pyramidal Cells, and Microscopy, Confocal
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Cell Biology and Physiology
- Person:
- Kasten, Michael R., Sullivan, Chelsea S., Maness, Patricia F., Manis, Paul B., Zhang, Xuying, and Kratz, Megan B.
- Rights Statement Label:
- In Copyright
- Source:
- 3t945w552
656. Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect
- Title Tesim:
- Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect
- Creator:
- Yelamanchili, Sowmya V., Li, Min, Fox, Howard S., Lamberty, Benjamin G., Morsey, Brenda M., Emanuel, Katy, Harrison, Emily B., and Kelso, Matthew L.
- Date of publication:
- 2017
- Abstract Tesim:
- Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out (KO) mice expression of type I interferons IFNα and IFNβ, as well as IFN regulatory factor 1 and IFN-induced chemokine CXCL10 was decreased after TBI relative to wild type (WT) mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluoro-jade C (FJC) staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI.
- Resource type:
- Article
- Affiliation Label Tesim:
- University of North Carolina at Chapel Hill
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/xp9j-nr14
- Identifier:
- Onescience id: 8431bda470f24df616ac550a462cc22cd7f4e60d, Publisher DOI: https://doi.org/10.3389/fnmol.2017.00228, PMCID: PMC5532436, and PMID: 28804446
- ISSN:
- 1662-5099
- Journal Title:
- Frontiers in Molecular Neuroscience
- Journal Volume:
- 10
- Keyword:
- neuronal injury, injury, MicroRNAs, neurodegeneration, miR-155, Nuclear miRNA, inflammation, brian injury, gene expression, neuroinflammation., and type 1 interferons
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Pharmacology and Experimental Neuroscience; College of Medicine; University of Nebraska Medical Center, Creighton University, Medpace Reference Laboratories, and Department of Pharmacy Practice; College of Pharmacy; University of Nebraska Medical Center
- Person:
- Yelamanchili, Sowmya V., Li, Min, Fox, Howard S., Lamberty, Benjamin G., Morsey, Brenda M., Emanuel, Katy, Harrison, Emily B., and Kelso, Matthew L.
- Rights Statement Label:
- In Copyright
- Source:
- tm70n114m
657. The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM
- Title Tesim:
- The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM
- Creator:
- Carroll, Ian, Goh, Yong Jun, Barrangou, Rodolphe, O'Flaherty, Sarah, Klaenhammer, Todd R., and Johnson, Brant R.
- Date of publication:
- 2017
- Abstract Tesim:
- Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S-) layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs). Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs). In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578), was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX) demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Medicine and School of Medicine
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/wt6d-cv81
- Identifier:
- PMCID: PMC5491966, Publisher DOI: https://doi.org/10.3389/fmicb.2017.01185, Onescience id: 8b73a2cfc1be5b766f6f8cf6be3f64bfb2891ab9, and PMID: 28713337
- ISSN:
- 1664-302X
- Journal Title:
- Frontiers in Microbiology
- Journal Volume:
- 8
- Keyword:
- intestinal barrier integrity, Lactobacillus, probiotic, S-layer, fibronectin, mucin, Microbiology, serine protease, Original Research, and S-layer associated proteins
- Language Label:
- English
- ORCID:
- Other Affiliation:
- School of Medicine, Department of Food; Bioprocessing and Nutrition Sciences; North Carolina State University, and College of Agriculture and Life Sciences; North Carolina State University
- Person:
- Carroll, Ian, Goh, Yong Jun, Barrangou, Rodolphe, O'Flaherty, Sarah, Klaenhammer, Todd R., and Johnson, Brant R.
- Rights Statement Label:
- In Copyright
- Source:
- 5712mc57j
658. Differential Growth of Francisella tularensis, Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of Ft SchuS4 to Immunized Animals
- Title Tesim:
- Differential Growth of Francisella tularensis, Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of Ft SchuS4 to Immunized Animals
- Creator:
- Wolfgeher, Donald, Hazlett, Karsten R.O., Bakshi, Chandra S., Rosa, Sarah J., Franz, Brian J., Kristjansdottir, Kolbrun, Singh, Anju, Kumar, Sudeep, Sellati, Timothy J., Barry, Eileen M., Namjoshi, Prachi, Gosselin, Edmund J., Sunagar, Raju, Reed, Douglas S., Holland, Kristen M., Zarrella, Tiffany M., and Kron, Stephen J.
- Date of publication:
- 2017
- Abstract Tesim:
- The gram-negative bacterium Francisella tularensis (Ft) is both a potential biological weapon and a naturally occurring microbe that survives in arthropods, fresh water amoeba, and mammals with distinct phenotypes in various environments. Previously, we used a number of measurements to characterize Ft grown in Brain-Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and (2) slightly more virulent in naïve animals, compared to Ft grown in Mueller Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB repress expression of select Ft virulence factors by an unknown mechanism. Here, we tested the hypotheses that Ft grown in BHI (BHI-Ft) accurately displays a full protein composition more similar to that reported for infection-derived Ft and that this similarity would make BHI-Ft more susceptible to pre-existing, vaccine-induced immunity than MHB-Ft. We performed comprehensive proteomic analysis of Ft grown in MHB, BHI, and BHI supplemented with casamino acids (BCA) and compared our findings to published “omics” data derived from Ft grown in vivo. Based on the abundance of ~1,000 proteins, the fingerprint of BHI-Ft is one of nutrient-deprived bacteria that—through induction of a stringent-starvation-like response—have induced the FevR regulon for expression of the bacterium's virulence factors, immuno-dominant antigens, and surface-carbohydrate synthases. To test the notion that increased abundance of dominant antigens expressed by BHI-Ft would render these bacteria more susceptible to pre-existing, vaccine-induced immunity, we employed a battery of LVS-vaccination and S4-challenge protocols using MHB- and BHI-grown Ft S4. Contrary to our hypothesis, these experiments reveal that LVS-immunization provides a barrier to infection that is significantly more effective against an MHB-S4 challenge than a BHI-S4 challenge. The differences in apparent virulence to immunized mice are profoundly greater than those observed with primary infection of naïve mice. Our findings suggest that tularemia vaccination studies should be critically evaluated in regard to the growth conditions of the challenge agent.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Genetics
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/948f-w826
- Identifier:
- Onescience id: 566515c58dd37d982717016fd4edca1b0606952c, PMCID: PMC5479911, PMID: 28690600, and Publisher DOI: https://doi.org/10.3389/fmicb.2017.01158
- ISSN:
- 1664-302X
- Journal Title:
- Frontiers in Microbiology
- Journal Volume:
- 8
- Keyword:
- virulence factor, Bacterial media, bacterial adaptation, bacterial media, bacterial capsules, Bacterial Capsules, tularemia immunization, and Tularemia Immunization
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Department of Molecular Genetics and Cell Biology; University of Chicago, Department of Immunology and Microbial Disease; Albany Medical College, Department of Microbiology and Immunology; New York Medical College, Department of Biomedical Sciences; Midwestern University, Trudeau Institute, Drug Discovery Division; Department of Infectious Diseases; Southern Research, School of Medicine; University of Maryland, and Center for Vaccine Research; University of Pittsburgh
- Person:
- Wolfgeher, Donald, Hazlett, Karsten R.O., Bakshi, Chandra S., Rosa, Sarah J., Franz, Brian J., Kristjansdottir, Kolbrun, Singh, Anju, Kumar, Sudeep, Sellati, Timothy J., Barry, Eileen M., Namjoshi, Prachi, Gosselin, Edmund J., Sunagar, Raju, Reed, Douglas S., Holland, Kristen M., Zarrella, Tiffany M., and Kron, Stephen J.
- Rights Statement Label:
- In Copyright
- Source:
- 9593v1286
659. A Multi-season Investigation of Microbial Extracellular Enzyme Activities in Two Temperate Coastal North Carolina Rivers: Evidence of Spatial but Not Seasonal Patterns
- Title Tesim:
- A Multi-season Investigation of Microbial Extracellular Enzyme Activities in Two Temperate Coastal North Carolina Rivers: Evidence of Spatial but Not Seasonal Patterns
- Creator:
- Bullock, Avery, Arnosti, Carol, Ghobrial, Sherif, Smith, Shannon, Ziervogel, Kai, and McKee, Brent
- Date of publication:
- 2017
- Abstract Tesim:
- Riverine systems are important sites for the production, transport, and transformation of organic matter. Much of the organic matter processing is carried out by heterotrophic microbial communities, whose activities may be spatially and temporally variable. In an effort to capture and evaluate some of this variability, we sampled four sites—two upstream and two downstream—at each of two North Carolina rivers (the Neuse River and the Tar-Pamlico River) ca. twelve times over a time period of 20 months from 2010 to 2012. At all of the sites and dates, we measured the activities of extracellular enzymes used to hydrolyze polysaccharides and peptides, and thus to initiate heterotrophic carbon processing. We additionally measured bacterial abundance, bacterial production, phosphatase activities, and dissolved organic carbon (DOC) concentrations. Concurrent collection of physical data (stream flow, temperature, salinity, dissolved oxygen) enabled us to explore possible connections between physiochemical parameters and microbial activities throughout this time period. The two rivers, both of which drain into Pamlico Sound, differed somewhat in microbial activities and characteristics: the Tar-Pamlico River showed higher β-glucosidase and phosphatase activities, and frequently had higher peptidase activities at the lower reaches, than the Neuse River. The lower reaches of the Neuse River, however, had much higher DOC concentrations than any site in the Tar River. Both rivers showed activities of a broad range of polysaccharide hydrolases through all stations and seasons, suggesting that the microbial communities are well-equipped to access enzymatically a broad range of substrates. Considerable temporal and spatial variability in microbial activities was evident, variability that was not closely related to factors such as temperature and season. However, Hurricane Irene's passage through North Carolina coincided with higher concentrations of DOC at the downstream sampling sites of both rivers. This DOC maximum persisted into the month following the hurricane, when it continued to stimulate bacterial protein production and phosphatase activity in the Neuse River, but not in the Tar-Pamlico River. Microbial community activities are related to a complex array of factors, whose interactions vary considerably with time and space.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Marine Sciences
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/8qvk-km11
- Identifier:
- PMID: 29312262, Publisher DOI: https://doi.org/10.3389/fmicb.2017.02589, Onescience id: 538bc6858e47fb6f3c82fc299b56fb16fb6f7d46, and PMCID: PMC5743733
- ISSN:
- 1664-302X
- Journal Title:
- Frontiers in Microbiology
- Journal Volume:
- 8
- Keyword:
- enzyme activities, peptidase, DOC, Tar River, Neuse River, bacterial production, Hurricane Irene, and glucosidase
- Language Label:
- English
- ORCID:
- Other Affiliation:
- Institute for the Study of Earth; Oceans and Space; University of New Hampshire
- Person:
- Bullock, Avery, Arnosti, Carol, Ghobrial, Sherif, Smith, Shannon, Ziervogel, Kai, and McKee, Brent
- Rights Statement Label:
- In Copyright
- Source:
- j96025650
660. Visualizing Evolutionary Relationships of Multidomain Proteins: An Example from Receiver (REC) Domains of Sensor Histidine Kinases in the Candidatus Maribeggiatoa str. Orange Guaymas Draft Genome
- Title Tesim:
- Visualizing Evolutionary Relationships of Multidomain Proteins: An Example from Receiver (REC) Domains of Sensor Histidine Kinases in the Candidatus Maribeggiatoa str. Orange Guaymas Draft Genome
- Creator:
- MacGregor, Barbara J.
- Date of publication:
- 2016
- Abstract Tesim:
- For multidomain proteins, evolutionary changes may occur at the domain as well as the whole-protein level. An example is presented here, with suggestions for how such complicated relationships might be visualized. Earlier analysis of the Candidatus Maribeggiatoa str. Orange Guaymas (BOGUAY; Gammaproteobacteria) single-filament draft genome found evidence of gene exchange with the phylogenetically distant Cyanobacteria, particularly for sensory and signal transduction proteins. Because these are modular proteins, known to undergo frequent duplication, domain swapping, and horizontal gene transfer, a single domain was chosen for analysis. Recognition (REC) domains are short (~125 amino acids) and well conserved, simplifying sequence alignments and phylogenetic calculations. Over 100 of these were identified in the BOGUAY genome and found to have a wide range of inferred phylogenetic relationships. Two sets were chosen here for detailed study. One set of four BOGUAY ORFs has closest relatives among other Beggiatoaceae and Cyanobacteria. A second set of four has REC domains with more mixed affiliations, including other Beggiatoaceae, several sulfate-reducing Deltaproteobacteria and Firmicutes, magnetotactic Nitrospirae, one Shewanella and one Ferrimonas strain (both Gammaproteobacteria), and numerous Vibrio vulnificus and V. navarrensis strains (also Gammaproteobacteria). For an overview of the possible origins of the whole proteins and the surrounding genomic regions, color-coded BLASTP results were produced and displayed against cartoons showing protein domain structure of predicted genes. This is suggested as a visualization method for investigation of possible horizontally transferred regions, giving more detail than scans of DNA composition and codon usage but much faster than carrying out full phylogenetic analyses for multiple proteins. As expected, most of the predicted sensor histidine kinases investigated have two or more segments with distinct BLASTP affiliations. For the first set of BOGUAY ORFs, the flanking regions were also examined, and the results suggest they are embedded in genomic stretches with complex histories. An automated method of creating such visualizations could be generally useful; a wish list for its features is given.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Marine Sciences
- Deposit Record:
- http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
- Type:
- http://purl.org/dc/dcmitype/Text
- DOI:
- https://doi.org/10.17615/yg2t-2738
- Identifier:
- Onescience id: 2e04f080cbd25c31cdc121c491ed8a1026c66661, PMID: 27895624, Publisher DOI: https://doi.org/10.3389/fmicb.2016.01780, and PMCID: PMC5108060
- ISSN:
- 1664-302X
- Journal Title:
- Frontiers in Microbiology
- Journal Volume:
- 7
- Keyword:
- recognition (REC) domains, multidomain proteins, Beggiatoaceae, sensor histidine kinases, Cyanobacteria, Orange Guaymas Maribeggiatoa, and horizontal gene transfer
- Language Label:
- English
- ORCID:
- Person:
- MacGregor, Barbara J.
- Rights Statement Label:
- In Copyright
- Source:
- v405sg29n
Collection Details
- Total items
-
698
- Size
-
unknown
- Date created
-
May 26, 2022