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1921. Arabidopsis AtMORC4 and AtMORC7 Form Nuclear Bodies and Repress a Large Number of Protein-Coding Genes

Title Tesim:
Arabidopsis AtMORC4 and AtMORC7 Form Nuclear Bodies and Repress a Large Number of Protein-Coding Genes
Creator:
Moissiard, Guillaume, Jacobsen, Steven E., Wang, Haifeng, Pastor, William A., Wohlschlegel, James A., Kasmi, Farid El, Vashisht, Ajay A., Papikian, Ashot, Husmann, Dylan, Dangl, Jeffery L., Harris, C. Jake, and Liu, Wanlu
Date of publication:
2016
Abstract Tesim:
The MORC family of GHKL ATPases are an enigmatic class of proteins with diverse chromatin related functions. In Arabidopsis, AtMORC1, AtMORC2, and AtMORC6 act together in heterodimeric complexes to mediate transcriptional silencing of methylated DNA elements. Here, we studied Arabidopsis AtMORC4 and AtMORC7. We found that, in contrast to AtMORC1,2,6, they act to suppress a wide set of non-methylated protein-coding genes that are enriched for those involved in pathogen response. Furthermore, atmorc4 atmorc7 double mutants show a pathogen response phenotype. We found that AtMORC4 and AtMORC7 form homomeric complexes in vivo and are concentrated in discrete nuclear bodies adjacent to chromocenters. Analysis of an atmorc1,2,4,5,6,7 hextuple mutant demonstrates that transcriptional de-repression is largely uncoupled from changes in DNA methylation in plants devoid of MORC function. However, we also uncover a requirement for MORC in both DNA methylation and silencing at a small but distinct subset of RNA-directed DNA methylation target loci. These regions are characterized by poised transcriptional potential and a low density of sites for symmetric cytosine methylation. These results provide insight into the biological function of MORC proteins in higher eukaryotes.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology
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/a1be-wt65
Identifier:
PMCID: PMC4865129, Onescience id: 9fc6cea3fcc56115a0999dacf4c40685eb2004d7, PMID: 27171361, and Publisher DOI: https://doi.org/10.1371/journal.pgen.1005998
ISSN:
1553-7404 and 1553-7390
Journal Issue:
5
Journal Title:
PLoS Genetics
Journal Volume:
12
Keyword:
Research Article, Epigenetics, Chromatin modification, Transposable Elements, Staining, QH426-470, DNA methylation, Arabidopsis Thaliana, DNA modification, Chromatin, Genetic Elements, Gene Expression, Biology and life sciences, Biochemistry, Genetic Loci, Chromosome biology, Gene expression, Brassica, Research and analysis methods, DAPI staining, Research and Analysis Methods, Genetics, Biology and Life Sciences, Chromosome Biology, and Specimen preparation and treatment
Language Label:
English
ORCID:
, 0000-0003-2434-4660, and 0000-0001-5120-0377
Other Affiliation:
Department of Molecular; Cell and Developmental Biology; University of California at Los Angeles, Howard Hughes Medical Institute; University of California at Los Angeles, Basic Forestry and Proteomics Research Center; Haixia Institute of Science and Technology (HIST); Fujian Agriculture and Forestry University, Fujian Province Key Laboratory of Plant Virology; Institute of Plant Virology; Fujian Agriculture and Forestry University, Department of Biological Chemistry; David Geffen School of Medicine; University of California; Los Angeles, and University of North Carolina at Chapel Hill
Page Start:
e1005998
Person:
Moissiard, Guillaume, Jacobsen, Steven E., Wang, Haifeng, Pastor, William A., Wohlschlegel, James A., Kasmi, Farid El, Vashisht, Ajay A., Papikian, Ashot, Husmann, Dylan, Dangl, Jeffery L., Harris, C. Jake, and Liu, Wanlu
Rights Statement Label:
In Copyright
Source:
jw827h88w

1922. A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity

Title Tesim:
A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity
Creator:
Brandt, Alicia T., Volkan, Pelin Cayirlioglu, Okuwa, Sumie, Maciejewski, Abigail, Reinhold, Dominik, Jones, Corbin D., Barish, Scott, and Li, Qingyun
Date of publication:
2016
Abstract Tesim:
Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1–4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology and Carolina Center for Genome 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/hgm6-fy42
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pgen.1005780, Onescience id: 185d3442c692cb753dfe6861c217fddc6115659a, PMID: 26765103, and PMCID: PMC4713227
ISSN:
1553-7390 and 1553-7404
Journal Issue:
1
Journal Title:
PLoS Genetics
Journal Volume:
12
Keyword:
dachsous protein, Drosophila, Gene Expression Regulation, Developmental, Imaginal Discs, Gene Regulatory Networks, Olfactory Receptor Neurons, ap protein, Drosophila, Smell, Drosophila Proteins, Animals, Drosophila melanogaster, Transcription Factors, Nerve Net, Bric-a-brac protein 1, Drosophila, Cadherins, Cell Differentiation, DNA-Binding Proteins, and LIM-Homeodomain Proteins
Language Label:
English
ORCID:
Other Affiliation:
Duke Institute for Brain Sciences; Duke University, Department of Biology; Duke University, Department of Mathematics and Computer Science; Clark University, and Carolina Center for Genome Sciences
Page Start:
e1005780
Person:
Brandt, Alicia T., Volkan, Pelin Cayirlioglu, Okuwa, Sumie, Maciejewski, Abigail, Reinhold, Dominik, Jones, Corbin D., Barish, Scott, and Li, Qingyun
Rights Statement Label:
In Copyright
Source:
k0698d79g

1923. A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere

Title Tesim:
A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere
Creator:
Hine, Rebecca M., Snider, Chloe E., Tsabar, Michael, Harrison, Benjamin, Eldridge, Brittany, Haber, James E., Bloom, Kerry, Haase, Julian, and Kaminsky, Lila
Date of publication:
2016
Abstract Tesim:
Transcriptional inactivation of the budding yeast centromere has been a widely used tool in studies of chromosome segregation and aneuploidy. In haploid cells when an essential chromosome contains a single conditionally inactivated centromere (GAL-CEN), cell growth rate is slowed and segregation fidelity is reduced; but colony formation is nearly 100%. Pedigree analysis revealed that only 30% of the time both mother and daughter cell inherit the GAL-CEN chromosome. The reduced segregation capacity of the GAL-CEN chromosome is further compromised upon reduction of pericentric cohesin (mcm21∆), as reflected in a further diminishment of the Mif2 kinetochore protein at GAL-CEN. By redistributing cohesin from the nucleolus to the pericentromere (by deleting SIR2), there is increased presence of the kinetochore protein Mif2 at GAL-CEN and restoration of cell viability. These studies identify the ability of cohesin to promote chromosome segregation via kinetochore assembly, in a situation where the centromere has been severely compromised.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology
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/10.17615/919q-w705
Identifier:
PMCID: PMC4851351, PMID: 27128635, Onescience id: f2cb02b93117b1899122fa5cac1bb50105311e64, and Publisher DOI: https://doi.org/10.1371/journal.pgen.1006021
ISSN:
1553-7404 and 1553-7390
Journal Issue:
4
Journal Title:
PLoS Genetics
Journal Volume:
12
Keyword:
Organic Compounds, Chromosomes, Chemical Compounds, Chromosome Biology, Cell Biology, Cell Cycle and Cell Division, Organic Chemistry, Metaphase, Chromosome Structure and Function, Centromeres, QH426-470, Chromosomal Disorders, Research Article, Monosaccharides, Anaphase, Biology and Life Sciences, Genetics, Galactose, Carbohydrates, Cell Processes, Medicine and Health Sciences, Physical Sciences, Glucose, Chemistry, and Clinical Genetics
Language Label:
English
ORCID:
and 0000-0003-2000-8301
Other Affiliation:
Department of Biology and Rosenstiel Basic Medical Sciences Research Center; Brandeis University
Page Start:
e1006021
Person:
Hine, Rebecca M., Snider, Chloe E., Tsabar, Michael, Harrison, Benjamin, Eldridge, Brittany, Haber, James E., Bloom, Kerry, Haase, Julian, and Kaminsky, Lila
Rights Statement Label:
In Copyright
Source:
xp68kn482

1924. A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S

Title Tesim:
A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S
Creator:
Shiver, Anthony L., Krogan, Nevan, Typas, Athanasios, Kritikos, George, Osadnik, Hendrik, Gross, Carol A., and Li, Bo
Date of publication:
2016
Abstract Tesim:
Fighting antibiotic resistance requires a deeper understanding of the genetic factors that determine the antibiotic susceptibility of bacteria. Here we describe a chemical-genomic screen in Escherichia coli K-12 that was designed to discover new aspects of antibiotic resistance by focusing on a set of 26 antibiotics and other stresses with poorly characterized mode-of-action and determinants of resistance. We show that the screen identifies new resistance determinants for these antibiotics including a common signature from two antimicrobials, kasugamycin and blasticidin S, used to treat crop diseases like rice blast and fire blight. Following this signature, we further investigated the mechanistic basis for susceptibility to kasugamycin and blasticidin S in E. coli using both genetic and biochemical approaches. We provide evidence that these compounds hijack an overlapping set of peptide ABC-importers to enter the bacterial cell. Loss of uptake may be an underappreciated mechanism for the development of kasugamycin resistance in bacterial plant pathogens.
Resource type:
Article
Affiliation Label Tesim:
Department of Chemistry
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/cm14-ej49
Identifier:
PMCID: PMC4927156, Publisher DOI: https://doi.org/10.1371/journal.pgen.1006124, Onescience id: 6b50f2d08cef02af6f0d79857b84ef8a12448e10, and PMID: 27355376
ISSN:
1553-7390 and 1553-7404
Journal Issue:
6
Journal Title:
PLoS Genetics
Journal Volume:
12
Keyword:
Escherichia coli K12, Crops, Agricultural, Plants, Plant Diseases, Nucleosides, Drug Resistance, Microbial, Aminoglycosides, Genomics, blasticidin S, and Anti-Bacterial Agents
Language Label:
English
ORCID:
and 0000-0002-1624-1322
Other Affiliation:
Graduate Group in Biophysics; University of California; San Francisco, Department of Cellular and Molecular Pharmacology; University of California; San Francisco, QB3; California Institute for Quantitative Biosciences, Gladstone Institutes, European Molecular Biology Laboratory; Genome Biology Unit, Department of Microbiology and Immunology; University of California; San Francisco, and Department of Cell and Tissue Biology; University of California
Page Start:
e1006124
Person:
Shiver, Anthony L., Krogan, Nevan, Typas, Athanasios, Kritikos, George, Osadnik, Hendrik, Gross, Carol A., and Li, Bo
Rights Statement Label:
In Copyright
Source:
vm40xx649

1925. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation

Title Tesim:
Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation
Creator:
Henriquez, Craig S., Fröhlich, Flavio, and Li, Guoshi
Date of publication:
2017
Abstract Tesim:
The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.
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/haq0-te82
Identifier:
PMID: 29073146, Onescience id: 105109ff3b95248c3937de13eb9f909f8dc5529f, Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005797, and PMCID: PMC5675460
ISSN:
1553-7358 and 1553-734X
Journal Issue:
10
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Computer Simulation, Norepinephrine, Deep Brain Stimulation, Acetylcholine, Thalamus, Neurotransmitter Agents, Oscillometry, Feedback, Physiological, Synaptic Transmission, Biological Clocks, Models, Neurological, Nerve Net, and Humans
Language Label:
English
ORCID:
0000-0002-5395-3767, , and 0000-0002-8984-4722
Other Affiliation:
Department of Biomedical Engineering; Duke University, UNC Neuroscience Center, Department of Biomedical Engineering - Biomedical Engineering, Department of Neurology, and Department of Cell Biology and Physiology
Page Start:
e1005797
Person:
Henriquez, Craig S., Fröhlich, Flavio, and Li, Guoshi
Rights Statement Label:
In Copyright
Source:
vd66w5115

1926. Transmembrane helical interactions in the CFTR channel pore

Title Tesim:
Transmembrane helical interactions in the CFTR channel pore
Creator:
He, Lihua, Riordan, John R., Das, Jhuma, Cui, Liying, Dokholyan, Nikolay V., and Aleksandrov, Andrei A.
Date of publication:
2017
Abstract Tesim:
Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF). Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF) and develop an inward (IWF) facing model employing an integrated experimental-molecular dynamics simulation (200 ns) approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs) of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.
Resource type:
Article
Affiliation Label Tesim:
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/qpwq-8t78
Identifier:
Onescience id: 5722cd8e12c603a00409659740713102580c59ad, PMCID: PMC5501672, Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005594, and PMID: 28640808
ISSN:
1553-7358 and 1553-734X
Journal Issue:
6
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Chlorine, Cell Membrane, Amino Acid Motifs, Models, Chemical, Molecular Dynamics Simulation, Binding Sites, Cell Membrane Permeability, Cystic Fibrosis Transmembrane Conductance Regulator, Diffusion, and Protein Binding
Language Label:
English
ORCID:
and 0000-0003-3548-3105
Other Affiliation:
Cystic Fibrosis and Pulmonary Diseases Research and Treatment Center
Page Start:
e1005594
Person:
He, Lihua, Riordan, John R., Das, Jhuma, Cui, Liying, Dokholyan, Nikolay V., and Aleksandrov, Andrei A.
Rights Statement Label:
In Copyright
Source:
7s75dj45z

1927. Testing the limits of gradient sensing

Title Tesim:
Testing the limits of gradient sensing
Creator:
Elston, Timothy C. and Lakhani, Vinal
Date of publication:
2017
Abstract Tesim:
The ability to detect a chemical gradient is fundamental to many cellular processes. In multicellular organisms gradient sensing plays an important role in many physiological processes such as wound healing and development. Unicellular organisms use gradient sensing to move (chemotaxis) or grow (chemotropism) towards a favorable environment. Some cells are capable of detecting extremely shallow gradients, even in the presence of significant molecular-level noise. For example, yeast have been reported to detect pheromone gradients as shallow as 0.1 nM/μm. Noise reduction mechanisms, such as time-averaging and the internalization of pheromone molecules, have been proposed to explain how yeast cells filter fluctuations and detect shallow gradients. Here, we use a Particle-Based Reaction-Diffusion model of ligand-receptor dynamics to test the effectiveness of these mechanisms and to determine the limits of gradient sensing. In particular, we develop novel simulation methods for establishing chemical gradients that not only allow us to study gradient sensing under steady-state conditions, but also take into account transient effects as the gradient forms. Based on reported measurements of reaction rates, our results indicate neither time-averaging nor receptor endocytosis significantly improves the cell’s accuracy in detecting gradients over time scales associated with the initiation of polarized growth. Additionally, our results demonstrate the physical barrier of the cell membrane sharpens chemical gradients across the cell. While our studies are motivated by the mating response of yeast, we believe our results and simulation methods will find applications in many different contexts.
Resource type:
Article
Affiliation Label Tesim:
Curriculum in Bioinformatics and Computational Biology
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/x5k3-4a17
Identifier:
PMID: 28207738, Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005386, Onescience id: a3cd881293e167ef5584d35d37a3c5cb58f36c20, and PMCID: PMC5347372
ISSN:
1553-734X and 1553-7358
Journal Issue:
2
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Models, Biological, Cell Membrane, Computer Simulation, Pheromones, Chemotaxis, Models, Chemical, Receptors, Pheromone, Models, Statistical, Saccharomyces cerevisiae, and Diffusion
Language Label:
English
ORCID:
Other Affiliation:
Department of Pharmacology and Battelle Center for Mathematical Medicine; Research Institute at Nationwide Children’s Hospital
Page Start:
e1005386
Person:
Elston, Timothy C. and Lakhani, Vinal
Rights Statement Label:
In Copyright
Source:
5425kg83x

1928. Probabilistic fluorescence-based synapse detection

Title Tesim:
Probabilistic fluorescence-based synapse detection
Creator:
Sapiro, Guillermo, Aguerrebere, Cecilia, Collman, Forrest, Smith, Stephen J., Vogelstein, Joshua T., Micheva, Kristina D., Simhal, Anish K., and Weinberg, Richard J.
Date of publication:
2017
Abstract Tesim:
Deeper exploration of the brain’s vast synaptic networks will require new tools for high-throughput structural and molecular profiling of the diverse populations of synapses that compose those networks. Fluorescence microscopy (FM) and electron microscopy (EM) offer complementary advantages and disadvantages for single-synapse analysis. FM combines exquisite molecular discrimination capacities with high speed and low cost, but rigorous discrimination between synaptic and non-synaptic fluorescence signals is challenging. In contrast, EM remains the gold standard for reliable identification of a synapse, but offers only limited molecular discrimination and is slow and costly. To develop and test single-synapse image analysis methods, we have used datasets from conjugate array tomography (cAT), which provides voxel-conjugate FM and EM (annotated) images of the same individual synapses. We report a novel unsupervised probabilistic method for detection of synapses from multiplex FM (muxFM) image data, and evaluate this method both by comparison to EM gold standard annotated data and by examining its capacity to reproduce known important features of cortical synapse distributions. The proposed probabilistic model-based synapse detector accepts molecular-morphological synapse models as user queries, and delivers a volumetric map of the probability that each voxel represents part of a synapse. Taking human annotation of cAT EM data as ground truth, we show that our algorithm detects synapses from muxFM data alone as successfully as human annotators seeing only the muxFM data, and accurately reproduces known architectural features of cortical synapse distributions. This approach opens the door to data-driven discovery of new synapse types and their density. We suggest that our probabilistic synapse detector will also be useful for analysis of standard confocal and super-resolution FM images, where EM cross-validation is not practical.
Resource type:
Article
Affiliation Label Tesim:
Department of Cell Biology and Physiology
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/ez1y-3m96
Identifier:
Onescience id: 12dc9fa7defd959e2c49c861afa3aadf66cc9ce8, PMCID: PMC5411093, Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005493, and PMID: 28414801
ISSN:
1553-734X and 1553-7358
Journal Issue:
4
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Image Processing, Computer-Assisted, Tomography, Microscopy, Electron, Cerebral Cortex, Algorithms, Animals, Models, Statistical, Synapses, Optical Imaging, Computational Biology, and Humans
Language Label:
English
ORCID:
and 0000-0001-7848-3565
Other Affiliation:
Department of Biomedical Engineering; Department of Computer Science; Department of Mathematics; Duke University, Electrical and Computer Engineering; Duke University, Synapse Biology; Allen Institute for Brain Sciences, Department of Biomedical Engineering; Johns Hopkins University, and Molecular and Cellular Physiology; Stanford University School of Medicine
Page Start:
e1005493
Person:
Sapiro, Guillermo, Aguerrebere, Cecilia, Collman, Forrest, Smith, Stephen J., Vogelstein, Joshua T., Micheva, Kristina D., Simhal, Anish K., and Weinberg, Richard J.
Rights Statement Label:
In Copyright
Source:
ft848x01q

1929. Breakdown of local information processing may underlie isoflurane anesthesia effects

Title Tesim:
Breakdown of local information processing may underlie isoflurane anesthesia effects
Creator:
Priesemann, Viola, Rudelt, Lucas, Wibral, Michael, Hutt, Axel, Fröhlich, Flavio, Sellers, Kristin K., and Wollstadt, Patricia
Date of publication:
2017
Abstract Tesim:
The disruption of coupling between brain areas has been suggested as the mechanism underlying loss of consciousness in anesthesia. This hypothesis has been tested previously by measuring the information transfer between brain areas, and by taking reduced information transfer as a proxy for decoupling. Yet, information transfer is a function of the amount of information available in the information source—such that transfer decreases even for unchanged coupling when less source information is available. Therefore, we reconsidered past interpretations of reduced information transfer as a sign of decoupling, and asked whether impaired local information processing leads to a loss of information transfer. An important prediction of this alternative hypothesis is that changes in locally available information (signal entropy) should be at least as pronounced as changes in information transfer. We tested this prediction by recording local field potentials in two ferrets after administration of isoflurane in concentrations of 0.0%, 0.5%, and 1.0%. We found strong decreases in the source entropy under isoflurane in area V1 and the prefrontal cortex (PFC)—as predicted by our alternative hypothesis. The decrease in source entropy was stronger in PFC compared to V1. Information transfer between V1 and PFC was reduced bidirectionally, but with a stronger decrease from PFC to V1. This links the stronger decrease in information transfer to the stronger decrease in source entropy—suggesting reduced source entropy reduces information transfer. This conclusion fits the observation that the synaptic targets of isoflurane are located in local cortical circuits rather than on the synapses formed by interareal axonal projections. Thus, changes in information transfer under isoflurane seem to be a consequence of changes in local processing more than of decoupling between brain areas. We suggest that source entropy changes must be considered whenever interpreting changes in information transfer as decoupling.
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/e575-c351
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005511, Onescience id: 44ea439d5fc1ff785cb3975929de05a758660dc9, PMID: 28570661, and PMCID: PMC5453425
ISSN:
1553-7358 and 1553-734X
Journal Issue:
6
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Prefrontal Cortex, Signal Filtering, Information Processing, Bandpass Filters, Research Article, Physical Sciences, Physics, Anatomy, Quantitative Biology - Neurons and Cognition, Entropy, Biology and Life Sciences, Vertebrates, Drug Therapy, Engineering and Technology, Ferrets, Information Technology, Combinatorics, Anesthesia, Computer and Information Sciences, Pharmaceutics, Local and Regional Anesthesia, Signal Processing, QH301-705.5, Amniotes, Mathematics, Permutation, Brain, Animals, Thermodynamics, Anesthesiology, and Ma
Language Label:
English
ORCID:
, 0000-0002-5774-3759, 0000-0001-8010-5862, and 0000-0002-7105-5207
Other Affiliation:
Max Planck Institute for Dynamics and Self-Organization, Bernstein Center for Computational Neuroscience; BCCN, MEG Unit; Brain Imaging Center; Goethe University, Deutscher Wetterdienst, Department of Mathematics and Statistics; University of Reading, Neuroscience Curriculum, UNC Neuroscience Center, Department of Biomedical Engineering - Biomedical Engineering, Department of Cell Biology and Physiology, and Department of Neurology
Page Start:
e1005511
Person:
Priesemann, Viola, Rudelt, Lucas, Wibral, Michael, Hutt, Axel, Fröhlich, Flavio, Sellers, Kristin K., and Wollstadt, Patricia
Rights Statement Label:
In Copyright
Source:
jm214v46m

1930. A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design

Title Tesim:
A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design
Creator:
Alford, Rebecca F., Gonzales, Lynda, Dolan, Erin L., Leaver-Fay, Andrew, and Gray, Jeffrey J.
Date of publication:
2017
Abstract Tesim:
Computational biology is an interdisciplinary field, and many computational biology research projects involve distributed teams of scientists. To accomplish their work, these teams must overcome both disciplinary and geographic barriers. Introducing new training paradigms is one way to facilitate research progress in computational biology. Here, we describe a new undergraduate program in biomolecular structure prediction and design in which students conduct research at labs located at geographically-distributed institutions while remaining connected through an online community. This 10-week summer program begins with one week of training on computational biology methods development, transitions to eight weeks of research, and culminates in one week at the Rosetta annual conference. To date, two cohorts of students have participated, tackling research topics including vaccine design, enzyme design, protein-based materials, glycoprotein modeling, crowd-sourced science, RNA processing, hydrogen bond networks, and amyloid formation. Students in the program report outcomes comparable to students who participate in similar in-person programs. These outcomes include the development of a sense of community and increases in their scientific self-efficacy, scientific identity, and science values, all predictors of continuing in a science research career. Furthermore, the program attracted students from diverse backgrounds, which demonstrates the potential of this approach to broaden the participation of young scientists from backgrounds traditionally underrepresented in computational biology.
Resource type:
Article
Affiliation Label Tesim:
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/e400-1y21
Identifier:
PMID: 29216185, Onescience id: 33fc854b4052a8b644989b4ac13f24cc2cbf7d54, Publisher DOI: https://doi.org/10.1371/journal.pcbi.1005837, and PMCID: PMC5720517
ISSN:
1553-734X and 1553-7358
Journal Issue:
12
Journal Title:
PLoS Computational Biology
Journal Volume:
13
Keyword:
Humans, Students, Female, Research, Molecular Conformation, Male, Internet, Computational Biology, United States, Universities, Adult, and Self Efficacy
Language Label:
English
ORCID:
, 0000-0003-3724-8408, and 0000-0003-4609-4340
Other Affiliation:
Department of Chemical and Biomolecular Engineering; Johns Hopkins University, Texas Institute for Discovery Education in Science; University of Texas, Department of Biochemistry and Molecular Biology; University of Georgia, and Institute for NanoBioTechnology; Johns Hopkins University
Page Start:
e1005837
Person:
Alford, Rebecca F., Gonzales, Lynda, Dolan, Erin L., Leaver-Fay, Andrew, and Gray, Jeffrey J.
Rights Statement Label:
In Copyright
Source:
9w032805w