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- Title
- Role of Olfaction for Eating Behavior.
- Creator
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Fadool, Debra Ann, Kolling, Louis John
- Abstract/Description
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Our olfactory system not only detects chemicals in the external environment but also subserves to detect the chemicals in our internal environment - the chemistry of energy homeostasis and metabolism. Olfaction guides our eating behavior using an array of neuroendocrine molecules that are detected across the main olfactory epithelium, the olfactory bulb, and higher cortical regions. Both metabolic state (fasting, satiation) and metabolic balance (obesity, metabolic disease) can affect...
Show moreOur olfactory system not only detects chemicals in the external environment but also subserves to detect the chemicals in our internal environment - the chemistry of energy homeostasis and metabolism. Olfaction guides our eating behavior using an array of neuroendocrine molecules that are detected across the main olfactory epithelium, the olfactory bulb, and higher cortical regions. Both metabolic state (fasting, satiation) and metabolic balance (obesity, metabolic disease) can affect olfactory-regulated eating behaviors. This review will delve into the physiological and behavioral link between olfaction, metabolism, eating, and health.
Show less - Date Issued
- 2020
- Identifier
- FSU_libsubv1_scholarship_submission_1602514625_d9f0b4ca
- Format
- Citation
- Title
- Consumption Of Benthic Cyanobacterial Mats On A Caribbean Coral Reef.
- Creator
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Cissell, Ethan C., Manning, Joshua C., McCoy, Sophie J.
- Abstract/Description
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Herbivory is an important process in the general structuring of coral reef benthic communities. However, evidence of its ability to control coral reef benthic cyanobacterial mats, which have recently proliferated on reefs worldwide, remains ambivalent. Here, we report that the French Angelfish (Pomacanthus paru), Striped Parrotfish (Scarus iseri), Rock Beauty (Holacanthus tricolor), Ocean Surgeonfish (Acanthurus bahianus), Blue Parrotfish (Scarus coeruleus), and Atlantic Blue Tang (Acanthurus...
Show moreHerbivory is an important process in the general structuring of coral reef benthic communities. However, evidence of its ability to control coral reef benthic cyanobacterial mats, which have recently proliferated on reefs worldwide, remains ambivalent. Here, we report that the French Angelfish (Pomacanthus paru), Striped Parrotfish (Scarus iseri), Rock Beauty (Holacanthus tricolor), Ocean Surgeonfish (Acanthurus bahianus), Blue Parrotfish (Scarus coeruleus), and Atlantic Blue Tang (Acanthurus coeruleus) consume benthic cyanobacterial mats on coral reefs in Bonaire, Netherlands. We documented the foraging patterns of P. paru and S. iseri, and found that benthic cyanobacterial mats comprised 36.7%+/- 5.8% and 15.0% +/- 1.53% (mean +/- standard error) of the total bites taken by P. paru and S. iseri respectively. This magnitude of consumption suggests that grazing by reef fishes may represent a potentially important, but previously undocumented, top-down control on benthic cyanobacterial mats on Caribbean reefs.
Show less - Date Issued
- ue Sep 03 00:00:00 ED
- Identifier
- FSU_libsubv1_wos_000483700400026, 10.1038/s41598-019-49126-9
- Format
- Citation
- Title
- Targeted disruption of the endogenous zebrafish locus as models of rapid rod photoreceptor degeneration.
- Creator
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Zelinka, Christopher P, Sotolongo-Lopez, Mailin, Fadool, James M
- Abstract/Description
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Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness. RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and...
Show moreRetinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness. RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish locus, . One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA). Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring. Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes. Using gRNAs that targeted highly conserved regions of , a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors. No effect on cones was observed. Targeting the 5'-coding sequence of led to the recovery of several indels similar to disease-associated alleles. A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity. Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival. Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15. Larvae heterozygous for either of the alleles demonstrated rapid rod degeneration. Targeting of the 3'-coding region of resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339. Both alleles resulted in rod death in a dominant inheritance pattern. Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane. The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease. These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
Show less - Date Issued
- 2018-08-27
- Identifier
- FSU_pmch_30210230, PMC6128699, 30210230, 30210230
- Format
- Citation
- Title
- Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.
- Creator
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Koohy, Hashem, Bolland, Daniel J, Matheson, Louise S, Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Várnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy,...
Show moreKoohy, Hashem, Bolland, Daniel J, Matheson, Louise S, Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Várnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy, Manzano Garcia, Raquel, Wingett, Steven W, Freire-Pritchett, Paula, Nagano, Takashi, Hawkins, Phillip, Stephens, Len, Elderkin, Sarah, Spivakov, Mikhail, Fraser, Peter, Corcoran, Anne E, Varga-Weisz, Patrick D
Show less - Abstract/Description
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Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from...
Show moreAging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Show less - Date Issued
- 2018-09-05
- Identifier
- FSU_pmch_30180872, 10.1186/s13059-018-1489-y, PMC6124017, 30180872, 30180872, 10.1186/s13059-018-1489-y
- Format
- Citation
- Title
- Chromatin structure profile data from DNS-seq: Differential nuclease sensitivity mapping of four reference tissues of B73 maize ( L)..
- Creator
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Turpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H,...
Show moreTurpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H, Zhang, Jinfeng, Bass, Hank W
Show less - Abstract/Description
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Presented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference...
Show morePresented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference profiles. The data repository for the sequence data is the NCBI SRA, BioProject Accession 8.
Show less - Date Issued
- 2018-08-10
- Identifier
- FSU_pmch_30175199, 10.1016/j.dib.2018.08.015, PMC6117953, 30175199, 30175199, S2352-3409(18)30865-5
- Format
- Citation
- Title
- Loss of SETDB1 decompacts the inactive X chromosome in part through reactivation of an enhancer in the IL1RAPL1 gene.
- Creator
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Sun, Zhuo, Chadwick, Brian P
- Abstract/Description
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The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we...
Show moreThe product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Close examination revealed a 0.5 Mb region of the Xi that transitioned from H3K9me3 heterochromatin to euchromatin within the 3' end of the IL1RAPL1 gene that is part of a common chromosome fragile site that is frequently deleted or rearranged in patients afflicted with intellectual disability and other neurological ailments. Centrally located within this interval is a powerful enhancer adjacent to an ERVL-MaLR element. In the absence of SETDB1, the enhancer is reactivated on the Xi coupled with bidirectional transcription from the ERVL-MaLR element. Xa deletion of the enhancer/ERVL-MaLR resulted in loss of full-length IL1RAPL1 transcript in cis, coupled with trans decompaction of the Xi chromosome territory, whereas Xi deletion increased detection of full-length IL1RAPL1 transcript in trans, but did not impact Xi compaction. These data support a critical role for SETDB1 in maintaining the ERVL-MaLR element and adjacent enhancer in the 3' end of the IL1RAPL1 gene in a silent state to facilitate Xi compaction.
Show less - Date Issued
- 2018-08-13
- Identifier
- FSU_pmch_30103804, 10.1186/s13072-018-0218-9, PMC6088404, 30103804, 30103804, 10.1186/s13072-018-0218-9
- Format
- Citation
- Title
- Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs.
- Creator
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Westervelt, Natalia, Chadwick, Brian P
- Abstract/Description
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Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA...
Show moreAppreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.
Show less - Date Issued
- 2018-09-01
- Identifier
- FSU_pmch_30102341, 10.1093/gbe/evy176, PMC6125249, 30102341, 30102341, 5068191
- Format
- Citation
- Title
- Phylogenomics uncovers early hybridization and adaptive loci shaping the radiation of Lake Tanganyika cichlid fishes.
- Creator
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Irisarri, Iker, Singh, Pooja, Koblmüller, Stephan, Torres-Dowdall, Julián, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R, Lemmon, Emily Moriarty,...
Show moreIrisarri, Iker, Singh, Pooja, Koblmüller, Stephan, Torres-Dowdall, Julián, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R, Lemmon, Emily Moriarty, Thallinger, Gerhard G, Sturmbauer, Christian, Meyer, Axel
Show less - Abstract/Description
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Lake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using...
Show moreLake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using anchored phylogenomics and uncover hybridization at its base, as well as early in the haplochromine radiation. This suggests that hybridization might have facilitated these speciation bursts. Time-calibrated trees support that the radiation of Tanganyika cichlids coincided with lake formation and that Gondwanan vicariance concurred with the earliest splits in the cichlid family tree. Genes linked to key innovations show signals of introgression or positive selection following colonization of lake habitats and species' dietary adaptations are revealed as major drivers of colour vision evolution. These findings shed light onto the processes shaping the evolution of adaptive radiations.
Show less - Date Issued
- 2018-08-08
- Identifier
- FSU_pmch_30089797, 10.1038/s41467-018-05479-9, PMC6082878, 30089797, 30089797, 10.1038/s41467-018-05479-9
- Format
- Citation
- Title
- Interactive effects of precipitation and nitrogen enrichment on multi-trophic dynamics in plant-arthropod communities.
- Creator
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Griffith, Kaitlin A, Grinath, Joshua B
- Abstract/Description
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Patterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear....
Show morePatterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear. We investigated the influence of precipitation and N enrichment on ecological dynamics across three trophic levels, hypothesizing that herbivores and plants would exhibit synergistic responses to the combined influence of precipitation, N amendments and predators. To test this, we conducted a field experiment with arthropods on two model plant species, Nicotiana tabacum and Nicotiana rustica. First, we characterized the plant-arthropod assemblages, finding that N. tabacum hosted greater abundances of caterpillars, while N. rustica hosted more sap-sucking herbivores. Next, we evaluated the effects of rainwater, soil N, and predatory spider manipulations for both plant-arthropod assemblages. On N. tabacum, water and N availability had an interactive effect on caterpillars, where caterpillars were most abundant with rainwater additions and least abundant when both rainwater and N were added. For N. rustica, foliar chemistry had a synergistic response to all three experimental factors. Compared to spider-absent conditions, leaf N concentration increased and C/N decreased when spiders were present, but this response only occurred under high water and N availability. Spiders indirectly altered plant chemistry via a facilitative effect of spiders on sap-sucking herbivores, potentially due to intra-guild predation, and a positive effect of sap-suckers on foliar N concentration. Our study suggests that predictions of the ecological impacts of altered precipitation and N deposition may need to account for the effects of resource co-limitation on dynamics across trophic levels.
Show less - Date Issued
- 2018-08-02
- Identifier
- FSU_pmch_30070991, 10.1371/journal.pone.0201219, PMC6072000, 30070991, 30070991, PONE-D-17-40079
- Format
- Citation
- Title
- Venom Complexity in a Pitviper Produced by Facultative Parthenogenesis.
- Creator
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Calvete, J J, Casewell, N R, Hernández-Guzmán, U, Quesada-Bernat, S, Sanz, L, Rokyta, D R, Storey, D, Albulescu, L-O, Wüster, W, Smith, C F, Schuett, G W, Booth, W
- Abstract/Description
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Facultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However,...
Show moreFacultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However, terminal fusion automixis is believed to result in near genome-wide reductions in heterozygosity; thus, FP seems likely to affect key phenotypic characters, yet this remains almost completely unstudied. Snake venom is a complex phenotypic character primarily used to subjugate prey and is thus tightly linked to individual fitness. Surprisingly, the composition and function of venom produced by a parthenogenetic pitviper exhibits a high degree of similarity to that of its mother and conspecifics from the same population. Therefore, the apparent loss of allelic diversity caused by FP appears unlikely to have a significant impact on the prey-capturing ability of this snake. Accordingly, the pitviper offspring produced by FP retained complex phenotypic characteristics associated with fitness. This result reinforces the potential ecological and evolutionary importance of FP and questions our understanding of the inheritance of venom-associated genes.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_pmch_30068934, 10.1038/s41598-018-29791-y, PMC6070573, 30068934, 30068934, 10.1038/s41598-018-29791-y
- Format
- Citation
- Title
- Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions..
- Creator
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Schoenfelder, Stefan, Javierre, Biola-Maria, Furlan-Magaril, Mayra, Wingett, Steven W, Fraser, Peter
- Abstract/Description
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The three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to...
Show moreThe three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to their target genes is thus crucial to understand gene expression control. We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. In PCHi-C, highly complex Hi-C libraries are specifically enriched for promoter sequences through in-solution hybrid selection with thousands of biotinylated RNA baits complementary to the ends of all promoter-containing restriction fragments. The aim is to then pull-down promoter sequences and their frequent interaction partners such as enhancers and other potential regulatory elements. After high-throughput paired-end sequencing, a statistical test is applied to each promoter-ligated restriction fragment to identify significant PIRs at the restriction fragment level. We have used PCHi-C to generate an atlas of long-range promoter interactions in dozens of human and mouse cell types. These promoter interactome maps have contributed to a greater understanding of mammalian gene expression control by assigning putative regulatory regions to their target genes and revealing preferential spatial promoter-promoter interaction networks. This information also has high relevance to understanding human genetic disease and the identification of potential disease genes, by linking non-coding disease-associated sequence variants in or near control sequences to their target genes.
Show less - Date Issued
- 2018-06-28
- Identifier
- FSU_pmch_30010637, 10.3791/57320, PMC6102006, 30010637, 30010637
- Format
- Citation
- Title
- Why does the magnitude of genotype-by-environment interaction vary?.
- Creator
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Saltz, Julia B, Bell, Alison M, Flint, Jonathan, Gomulkiewicz, Richard, Hughes, Kimberly A, Keagy, Jason
- Abstract/Description
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Genotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and...
Show moreGenotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and populations, but minimal or absent in others. To encourage synthetic research in this area, we review diverse hypotheses for the underlying biological causes of variation in G × E. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in G × E and suggest some important next steps.
Show less - Date Issued
- 2018-05-08
- Identifier
- FSU_pmch_29988442, 10.1002/ece3.4128, PMC6024136, 29988442, 29988442, ECE34128
- Format
- Citation
- Title
- Unique maternal and environmental effects on the body morphology of the Least Killifish, .
- Creator
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Landy, J Alex, Travis, Joseph
- Abstract/Description
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An important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity....
Show moreAn important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity. Here, we report the results of an experiment with males from two populations of the poeciliid fish, , designed to examine the relative influence of environmental maternal effects and environmental effects experienced during growth and development on body morphology, and, in addition, whether the balance among those effects is unique to each population. We used a factorial design that varied thermal environment and water chemistry experienced by mothers and thermal environment and water chemistry experienced by offspring. We found substantial differences between the two populations in their maternal and offspring norms of reaction of male body morphology to differences in thermal environment and water chemistry. We also found that the balance between maternal effects and postparturition environmental effects differed from one thermal regime to another and among traits. These results indicate that environmental maternal effects can be decidedly population-specific and, as a result, might either contribute to the appearance of or blur evidence for local adaptation. These results also suggest that local adaptation might also occur through the evolution of maternal norms of reaction to important, and varying, environmental factors.
Show less - Date Issued
- 2018-05-24
- Identifier
- FSU_pmch_29988417, 10.1002/ece3.4166, PMC6024122, 29988417, 29988417, ECE34166
- Format
- Citation
- Title
- An hPSC-Derived Tissue-Resident Macrophage Model Reveals Differential Responses of Macrophages to ZIKV and DENV Infection.
- Creator
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Lang, Jianshe, Cheng, Yichen, Rolfe, Alyssa, Hammack, Christy, Vera, Daniel, Kyle, Kathleen, Wang, Jingying, Meissner, Torsten B, Ren, Yi, Cowan, Chad, Tang, Hengli
- Abstract/Description
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Zika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly...
Show moreZika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly activates macrophage migration inhibitory factor (MIF) secretion and decreases macrophage migration. Neutralization of MIF leads to improved migratory ability of DENV-infected macrophages. In contrast, ZIKV-infected macrophages exhibit prolonged migration and express low levels of pro-inflammatory cytokines and chemokines. Mechanistically, ZIKV disrupts the nuclear factor κB (NF-κB)-MIF positive feedback loop by inhibiting the NF-κB signaling pathway. Our results demonstrate the utility of hPSC-derived macrophages in infectious disease modeling and suggest that the distinct impact of ZIKV and DENV on macrophage immune response may underlie different pathogenesis of Zika and dengue diseases.
Show less - Date Issued
- 2018-08-14
- Identifier
- FSU_pmch_29983385, 10.1016/j.stemcr.2018.06.006, PMC6092684, 29983385, 29983385, S2213-6711(18)30269-8
- Format
- Citation
- Title
- Phylogenomic evidence overturns current conceptions of social evolution in wasps (Vespidae).
- Creator
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Piekarski, P K, Carpenter, J M, Lemmon, A R, Moriarty Lemmon, E, Sharanowski, B J
- Abstract/Description
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The hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral...
Show moreThe hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral castes → eusociality with preimaginal caste-biasing → morphologically differentiated castes). Here we infer the phylogeny of Vespidae using sequence data generated via anchored hybrid enrichment from 378 loci across 136 vespid species and perform ancestral state reconstructions to test whether rudimentary and monomorphic castes characterized the initial stages of eusocial evolution. Our results reject the single origin of eusociality hypothesis, contest the supposition that eusociality emerged from a casteless nest-sharing ancestor, and suggest that eusociality in Polistinae + Vespinae began with castes having morphological differences. An abrupt appearance of castes with ontogenetically established morphophysiological differences conflicts with the current conception of stepwise social evolution and suggests that the climb up the ladder of sociality does not occur through sequential mutation. Phenotypic plasticity and standing genetic variation could explain how cooperative brood care evolved in concert with nest-sharing and how morphologically dissimilar castes arose without a rudimentary intermediate. Furthermore, preimaginal caste-biasing at the outset of eusociality implicates a subsocial route to eusociality in Polistinae + Vespinae, emphasizing the role of mother-daughter interactions and subfertility (i.e. the cost component of kin selection) in the origin of workers.
Show less - Date Issued
- 2018-06-19
- Identifier
- FSU_pmch_29924339, 10.1093/molbev/msy124, PMC6107056, 29924339, 29924339, 5040136
- Format
- Citation
- Title
- Evaluating the Performance of De Novo Assembly Methods for Venom-Gland Transcriptomics.
- Creator
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Holding, Matthew L, Margres, Mark J, Mason, Andrew J, Parkinson, Christopher L, Rokyta, Darin R
- Abstract/Description
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Venom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a...
Show moreVenom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a bioinformatic problem with several possible solutions. Several methods have been employed to assemble venom-gland transcriptomes, with the Trinity assembler being the most commonly applied among them. Although previous evidence of variation in performance among assembly software exists, particularly regarding recovery of difficult-to-assemble multigene families such as snake venom metalloproteinases, much work to date still employs a single assembly method. We evaluated the performance of several commonly used de novo assembly methods for the recovery of both nontoxin transcripts and complete, high-quality venom-gene transcripts across eleven snake and four scorpion transcriptomes. We varied -mer sizes used by some assemblers to evaluate the impact of -mer length on transcript recovery. We showed that the recovery of nontoxin transcripts and toxin transcripts is best accomplished through different assembly software, with SDT at smaller -mer lengths and Trinity being best for nontoxin recovery and a combination of SeqMan NGen and a seed-and-extend approach implemented in Extender as the best means of recovering a complete set of toxin transcripts. In particular, Extender was the only means tested capable of assembling multiple isoforms of the diverse snake venom metalloproteinase family, while traditional approaches such as Trinity recovered at most one metalloproteinase transcript. Our work demonstrated that traditional metrics of assembly performance are not predictive of performance in the recovery of complete and high quality toxin genes. Instead, effective venom-gland transcriptomic studies should combine and quality-filter the results of several assemblers with varying algorithmic strategies.
Show less - Date Issued
- 2018-06-19
- Identifier
- FSU_pmch_29921759, 10.3390/toxins10060249, PMC6024825, 29921759, 29921759, toxins10060249
- Format
- Citation
- Title
- Distinct tissue-specific transcriptional regulation revealed by gene regulatory networks in maize.
- Creator
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Huang, Ji, Zheng, Juefei, Yuan, Hui, McGinnis, Karen
- Abstract/Description
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Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM...
Show moreTranscription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize. Although many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm. By combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/ ), for easy querying. All source code and data are available at Github ( https://github.com/timedreamer/maize_tissue-specific_GRN ).
Show less - Date Issued
- 2018-06-07
- Identifier
- FSU_pmch_29879919, 10.1186/s12870-018-1329-y, PMC6040155, 29879919, 29879919, 10.1186/s12870-018-1329-y
- Format
- Citation
- Title
- Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry..
- Creator
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Yang, Shu, Xu, Miao, Lee, Emily M, Gorshkov, Kirill, Shiryaev, Sergey A, He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella,...
Show moreYang, Shu, Xu, Miao, Lee, Emily M, Gorshkov, Kirill, Shiryaev, Sergey A, He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella, Farhy, Chen, Huang, Chun-Teng, Zhang, Zirui, Zhu, Wenjun, Wu, Yuying, Zhou, Yi, Song, Guang, Zhu, Heng, Shamim, Khalida, Martínez-Romero, Carles, García-Sastre, Adolfo, Preston, Richard A, Jayaweera, Dushyantha T, Huang, Ruili, Huang, Wenwei, Xia, Menghang, Simeonov, Anton, Ming, Guoli, Qiu, Xiangguo, Terskikh, Alexey V, Tang, Hengli, Song, Hongjun, Zheng, Wei
Show less - Abstract/Description
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The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption...
Show moreThe re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.
Show less - Date Issued
- 2018-06-05
- Identifier
- FSU_pmch_29872540, 10.1038/s41421-018-0034-1, PMC5986771, 29872540, 29872540, 34
- Format
- Citation
- Title
- The half-bridge component Kar1 promotes centrosome separation and duplication during budding yeast meiosis.
- Creator
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Agarwal, Meenakshi, Jin, Hui, McClain, Melainia, Fan, Jinbo, Koch, Bailey A, Jaspersen, Sue L, Yu, Hong-Guo
- Abstract/Description
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The budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid...
Show moreThe budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid segregation in meiosis II. How SPB duplication and separation are regulated during meiosis remains to be elucidated, and whether regulation in meiosis differs from that in mitosis is unclear. Here we show that overproduction of the half-bridge component Kar1 leads to premature SPB separation during meiosis. Furthermore, excessive Kar1 induces SPB overduplication to form supernumerary SPBs, leading to chromosome missegregation and erroneous ascospore formation. Kar1--mediated SPB duplication bypasses the requirement of dephosphorylation of Sfi1, another half-bridge component previously identified as a licensing factor. Our results therefore reveal an unexpected role of Kar1 in licensing meiotic SPB duplication and suggest a unique mechanism of SPB regulation during budding yeast meiosis.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_pmch_29847244, 10.1091/mbc.E18-03-0163, PMC6085829, 29847244, 29847244
- Format
- Citation
- Title
- Quantitative Morphological Variation in the Developing Wing.
- Creator
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Matamoro-Vidal, Alexis, Huang, Yunxian, Salazar-Ciudad, Isaac, Shimmi, Osamu, Houle, David
- Abstract/Description
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Quantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental...
Show moreQuantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental stages were studied: late larval third instar, post-pupariation and in the adult fly. We studied wild-type animals in addition to mutants of two genes ( and ) that have known effects on adult wing shape and size. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. In addition we provide linear rules allowing us to link wing morphology in the larva, with wing morphology in the pupa. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.
Show less - Date Issued
- 2018-07-02
- Identifier
- FSU_pmch_29844017, 10.1534/g3.118.200372, PMC6027878, 29844017, 29844017, g3.118.200372
- Format
- Citation
- Title
- Spindly is required for rapid migration of human cells.
- Creator
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Conte, Claudia, Baird, Michelle A, Davidson, Michael W, Griffis, Eric R
- Abstract/Description
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Dynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular...
Show moreDynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular localization. Spindly is a protein that targets dynein/dynactin to kinetochores in mitosis and can activate its motility However, no role for Spindly in interphase dynein/dynactin function has been found. We show that Spindly binds to the cell cortex and microtubule tips and colocalizes with dynein/dynactin at the leading edge of migrating U2OS cells and primary fibroblasts. U2OS cells that lack Spindly migrated slower in 2D than control cells, although centrosome polarization appeared to happen properly in the absence of Spindly. Re-expression of Spindly rescues migration, but the expression of a mutant, which is defective for dynactin binding, failed to rescue this defect. Taken together, these data demonstrate that Spindly plays an important role in mediating a subset of dynein/dynactin's function in cell migration.
Show less - Date Issued
- 2018-05-29
- Identifier
- FSU_pmch_29685992, 10.1242/bio.033233, PMC5992534, 29685992, 29685992, bio.033233
- Format
- Citation
- Title
- Elevated Anxiety and Impaired Attention in Super-Smeller, Kv1.3 Knockout Mice.
- Creator
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Huang, Zhenbo, Hoffman, Carlie A, Chelette, Brandon M, Thiebaud, Nicolas, Fadool, Debra A
- Abstract/Description
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It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is...
Show moreIt has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3-/-), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3-/- mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3-/- mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3-/- mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3-/- mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3-/- mice may have behaviors associated with inattentiveness.
Show less - Date Issued
- 2018-03-19
- Identifier
- FSU_pmch_29615878, 10.3389/fnbeh.2018.00049, PMC5867313, 29615878, 29615878
- Format
- Citation
- Title
- Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.
- Creator
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Marchal, Claire, Sasaki, Takayo, Vera, Daniel, Wilson, Korey, Sima, Jiao, Rivera-Mulia, Juan Carlos, Trevilla-García, Claudia, Nogues, Coralin, Nafie, Ebtesam, Gilbert, David M
- Abstract/Description
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This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension...
Show moreThis protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.
Show less - Date Issued
- 2018-05-01
- Identifier
- FSU_pmch_29599440, 10.1038/nprot.2017.148, PMC6044726, 29599440, 29599440, nprot.2017.148
- Format
- Citation
- Title
- Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven by Four Toxin Families.
- Creator
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Strickland, Jason L, Mason, Andrew J, Rokyta, Darin R, Parkinson, Christopher L
- Abstract/Description
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Phenotypic diversity generated through altered gene expression is a primary mechanism facilitating evolutionary response in natural systems. By linking the phenotype to genotype through transcriptomics, it is possible to determine what changes are occurring at the molecular level. High phenotypic diversity has been documented in rattlesnake venom, which is under strong selection due to its role in prey acquisition and defense. Rattlesnake venom can be characterized by the presence (Type A) or...
Show morePhenotypic diversity generated through altered gene expression is a primary mechanism facilitating evolutionary response in natural systems. By linking the phenotype to genotype through transcriptomics, it is possible to determine what changes are occurring at the molecular level. High phenotypic diversity has been documented in rattlesnake venom, which is under strong selection due to its role in prey acquisition and defense. Rattlesnake venom can be characterized by the presence (Type A) or absence (Type B) of a type of neurotoxic phospholipase A 2 (PLA 2 ), such as Mojave toxin, that increases venom toxicity. Mojave rattlesnakes (), represent this diversity as both venom types are found within this species and within a single panmictic population in the Sonoran Desert. We used comparative venom gland transcriptomics of nine specimens of from this region to test whether expression differences explain diversity within and between venom types. Type A individuals expressed significantly fewer toxins than Type B individuals owing to the diversity of C-type lectins (CTLs) and snake venom metalloproteinases (SVMPs) found in Type B animals. As expected, both subunits of Mojave toxin were exclusively found in Type A individuals but we found high diversity in four additional PLA 2 s that was not associated with a venom type. Myotoxin expression and toxin number variation was not associated with venom type, and myotoxin had the highest range of expression of any toxin class. Our study represents the most comprehensive transcriptomic profile of the venom type dichotomy in rattlesnakes and . Even intra-specifically, Mojave rattlesnakes showcase the diversity of snake venoms and illustrate that variation within venom types blurs the distinction of the venom dichotomy.
Show less - Date Issued
- 2018-03-23
- Identifier
- FSU_pmch_29570631, 10.3390/toxins10040135, PMC5923301, 29570631, 29570631, toxins10040135
- Format
- Citation
- Title
- Advancing behavioural genomics by considering timescale.
- Creator
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Rittschof, Clare C, Hughes, Kimberly A
- Abstract/Description
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Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain...
Show moreAnimal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early life social trauma to understanding the evolution of trait plasticity.
Show less - Date Issued
- 2018-02-12
- Identifier
- FSU_pmch_29434301, 10.1038/s41467-018-02971-0, PMC5809431, 29434301, 29434301, 10.1038/s41467-018-02971-0
- Format
- Citation
- Creator
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De Nobrega, Aliza K, Lyons, Lisa C
- Abstract/Description
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Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with...
Show moreEndogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as , have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between and mammalian systems. Research in provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.
Show less - Date Issued
- 2017-01-01
- Identifier
- FSU_pmch_29391952, 10.1155/2017/4723836, PMC5748135, 29391952, 29391952
- Format
- Citation
- Title
- Single-cell replication profiling to measure stochastic variation in mammalian replication timing.
- Creator
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Dileep, Vishnu, Gilbert, David M
- Abstract/Description
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Mammalian DNA replication is regulated via multi-replicon segments that replicate in a defined temporal order during S-phase. Further, early/late replication of RDs corresponds to active/inactive chromatin interaction compartments. Although replication origins are selected stochastically, variation in replication timing is poorly understood. Here we devise a strategy to measure variation in replication timing using DNA copy number in single mouse embryonic stem cells. We find that borders...
Show moreMammalian DNA replication is regulated via multi-replicon segments that replicate in a defined temporal order during S-phase. Further, early/late replication of RDs corresponds to active/inactive chromatin interaction compartments. Although replication origins are selected stochastically, variation in replication timing is poorly understood. Here we devise a strategy to measure variation in replication timing using DNA copy number in single mouse embryonic stem cells. We find that borders between replicated and unreplicated DNA are highly conserved between cells, demarcating active and inactive compartments of the nucleus. Fifty percent of replication events deviated from their average replication time by ± 15% of S phase. This degree of variation is similar between cells, between homologs within cells and between all domains genomewide, regardless of their replication timing. These results demonstrate that stochastic variation in replication timing is independent of elements that dictate timing or extrinsic environmental variation.
Show less - Date Issued
- 2018-01-30
- Identifier
- FSU_pmch_29382831, 10.1038/s41467-017-02800-w, PMC5789892, 29382831, 29382831, 10.1038/s41467-017-02800-w
- Format
- Citation
- Title
- Impacts of the Deepwater Horizon oil spill evaluated using an end-to-end ecosystem model.
- Creator
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Ainsworth, Cameron H, Paris, Claire B, Perlin, Natalie, Dornberger, Lindsey N, Patterson, William F, Chancellor, Emily, Murawski, Steve, Hollander, David, Daly, Kendra, Romero,...
Show moreAinsworth, Cameron H, Paris, Claire B, Perlin, Natalie, Dornberger, Lindsey N, Patterson, William F, Chancellor, Emily, Murawski, Steve, Hollander, David, Daly, Kendra, Romero, Isabel C, Coleman, Felicia, Perryman, Holly
Show less - Abstract/Description
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We use a spatially explicit biogeochemical end-to-end ecosystem model, Atlantis, to simulate impacts from the Deepwater Horizon oil spill and subsequent recovery of fish guilds. Dose-response relationships with expected oil concentrations were utilized to estimate the impact on fish growth and mortality rates. We also examine the effects of fisheries closures and impacts on recruitment. We validate predictions of the model by comparing population trends and age structure before and after the...
Show moreWe use a spatially explicit biogeochemical end-to-end ecosystem model, Atlantis, to simulate impacts from the Deepwater Horizon oil spill and subsequent recovery of fish guilds. Dose-response relationships with expected oil concentrations were utilized to estimate the impact on fish growth and mortality rates. We also examine the effects of fisheries closures and impacts on recruitment. We validate predictions of the model by comparing population trends and age structure before and after the oil spill with fisheries independent data. The model suggests that recruitment effects and fishery closures had little influence on biomass dynamics. However, at the assumed level of oil concentrations and toxicity, impacts on fish mortality and growth rates were large and commensurate with observations. Sensitivity analysis suggests the biomass of large reef fish decreased by 25% to 50% in areas most affected by the spill, and biomass of large demersal fish decreased even more, by 40% to 70%. Impacts on reef and demersal forage caused starvation mortality in predators and increased reliance on pelagic forage. Impacts on the food web translated effects of the spill far away from the oiled area. Effects on age structure suggest possible delayed impacts on fishery yields. Recovery of high-turnover populations generally is predicted to occur within 10 years, but some slower-growing populations may take 30+ years to fully recover.
Show less - Date Issued
- 2018-01-25
- Identifier
- FSU_pmch_29370187, 10.1371/journal.pone.0190840, PMC5784916, 29370187, 29370187, PONE-D-17-15401
- Format
- Citation
- Title
- Screening of Lipid Composition for Scalable Fabrication of Solvent-Free Lipid Microarrays.
- Creator
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Ghazanfari, Lida, Lenhert, Steven
- Abstract/Description
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Liquid microdroplet arrays on surfaces are a promising approach to the miniaturization of laboratory processes such as high-throughput screening. The fluid nature of these droplets poses unique challenges and opportunities in their fabrication and application, particularly for the scalable integration of multiple materials over large areas and immersion into cell culture solution. Here, we use pin spotting and nanointaglio printing to screen a library of lipids and their mixtures for their...
Show moreLiquid microdroplet arrays on surfaces are a promising approach to the miniaturization of laboratory processes such as high-throughput screening. The fluid nature of these droplets poses unique challenges and opportunities in their fabrication and application, particularly for the scalable integration of multiple materials over large areas and immersion into cell culture solution. Here, we use pin spotting and nanointaglio printing to screen a library of lipids and their mixtures for their compatibility with these fabrication processes, as well as stability upon immersion into aqueous solution. More than 200 combinations of natural and synthetic oils composed of fatty acids, triglycerides, and hydrocarbons were tested for their pin-spotting and nanointaglio print quality and their ability to contain the fluorescent compound tetramethylrhodamine B isothiocyanate (TRITC) upon immersion in water. A combination of castor oil and hexanoic acid at the ratio of 1:1 (w/w) was found optimal for producing reproducible patterns that are stable upon immersion into water. This method is capable of large-scale nanomaterials integration.
Show less - Date Issued
- 2016-12-01
- Identifier
- FSU_pmch_29333429, 10.3389/fmats.2016.00055, PMC5761732, 29333429, 29333429
- Format
- Citation
- Title
- Synchrotron-generated microbeams induce hippocampal transections in rats.
- Creator
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Fardone, Erminia, Pouyatos, Benoît, Bräuer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Hervè, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe,...
Show moreFardone, Erminia, Pouyatos, Benoît, Bräuer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Hervè, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe, Le Duc, Geraldine, Bravin, Alberto, Romanelli, Pantaleo
Show less - Abstract/Description
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Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the...
Show moreSynchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.
Show less - Date Issued
- 2018-01-09
- Identifier
- FSU_pmch_29317649, 10.1038/s41598-017-18000-x, PMC5760574, 29317649, 29317649, 10.1038/s41598-017-18000-x
- Format
- Citation
- Title
- Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in epithelial tumors.
- Creator
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Shu, Zhiqiang, Huang, Yi-Chun, Palmer, William H, Tamori, Yoichiro, Xie, Gengqiang, Wang, Hui, Liu, Nan, Deng, Wu-Min
- Abstract/Description
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Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) (), combined with overexpression of an active form of oncogene ( ), and...
Show moreDespite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) (), combined with overexpression of an active form of oncogene ( ), and identified 51 mature miRNAs that changed significantly in tumorous discs. Followed by tumor enhancer and suppressor screens in sensitized genetic backgrounds, we identified 10 tumor-enhancing (TE) miRNAs and 11 tumor-suppressing (TS) miRNAs that contributed to the nTSG defect-induced tumorigenesis. Among these, four TE and three TS miRNAs have human homologs. From this study, we also identified 29 miRNAs that individually had no obvious role in enhancing or alleviating tumorigenesis despite their changed expression levels in nTSG tumors. This systematic analysis, which includes both RNA-Seq and functional studies, helps to categorize miRNAs into different groups based on their expression profile and functional relevance in epithelial tumorigenesis, whereas the evolutionarily conserved TE and TS miRNAs provide potential therapeutic targets for epithelial tumor treatment.
Show less - Date Issued
- 2017-11-01
- Identifier
- FSU_pmch_29312571, 10.18632/oncotarget.22226, PMC5752484, 29312571, 29312571, 22226
- Format
- Citation
- Title
- Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy.
- Creator
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Ilyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Väisänen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Söderlund...
Show moreIlyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Väisänen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Söderlund-Venermo, Maria, Agbandje-McKenna, Mavis
Show less - Abstract/Description
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Bufavirus strain 1 (BuV1), a member of the genus of the , was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and...
Show moreBufavirus strain 1 (BuV1), a member of the genus of the , was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and image reconstruction to 2.84, 3.79, and 3.25 Å, respectively. The BuVs, 65-73% identical in amino acid sequence, conserve the major viral protein, VP2, structure and general capsid surface features of parvoviruses. These include a core β-barrel (βB-βI), α-helix A, and large surface loops inserted between these elements in VP2. The capsid contains depressions at the icosahedral 2-fold and around the 5-fold axes, and has three separated protrusions surrounding the 3-fold axes. Structure comparison among the BuVs and to available parvovirus structures revealed capsid surface variations and capsid 3-fold protrusions that depart from the single pinwheel arrangement of the animal protoparvoviruses. These structures provide a platform to begin the molecular characterization of these potentially pathogenic viruses.
Show less - Date Issued
- 2018-01-04
- Identifier
- FSU_pmch_29300333, 10.3390/v10010022, PMC5795435, 29300333, 29300333, v10010022
- Format
- Citation
- Title
- Bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors.
- Creator
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Sima, Jiao, Bartlett, Daniel A, Gordon, Molly R, Gilbert, David M
- Abstract/Description
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The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of ∼200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiPSCs) and...
Show moreThe role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of ∼200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiPSCs) and established distinct RT patterns. An E-BAC harboring an early replicating chromosomal region replicated early during S phase, while E-BACs derived from RT transition regions (TTRs) and late replicating regions replicated in mid to late S phase. Analysis of E-BAC interactions with cellular chromatin (4C-seq) revealed that the early replicating E-BAC interacted broadly throughout the genome and preferentially with the early replicating compartment of the nucleus. In contrast, mid- to late-replicating E-BACs interacted with more specific late replicating chromosomal segments, some of which were shared between different E-BACs. Together, we describe a versatile system in which to study the structure and function of chromosomal segments that are stably maintained separately from the influence of cellular chromosome context.
Show less - Date Issued
- 2018-02-28
- Identifier
- FSU_pmch_29294101, 10.1093/nar/gkx1265, PMC5829748, 29294101, 29294101, 4774271
- Format
- Citation
- Title
- Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.
- Creator
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Zuo, L-L, Zhang, J, Liu, L-Z, Zhou, Q, Du, S-J, Xin, S-Y, Ning, Z-P, Yang, J, Yu, H-B, Yue, W-X, Wang, J, Zhu, F-X, Li, G-Y, Lu, J-H
- Abstract/Description
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Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in...
Show moreNasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-β downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-β. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.
Show less - Date Issued
- 2017-12-22
- Identifier
- FSU_pmch_29284791, 10.1038/s41389-017-0005-7, PMC5865538, 29284791, 29284791, 10.1038/s41389-017-0005-7
- Format
- Citation
- Title
- Challenges And Guidelines Toward 4d Nucleome Data And Model Standards.
- Creator
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Marti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi,...
Show moreMarti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi, Mario, Nollmann, Marcelo, Orozco, Modesto, Pombo, Ana, Torres-Padilla, Maria-Elena
Show less - Abstract/Description
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Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its...
Show moreDue to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate. However, the rapid evolution of methods and the increasing complexity of data can result in ambiguity and reproducibility challenges, which may hamper the progress of this field. Here, we describe such challenges ahead and provide guidelines to think about strategies for shared standardized validation of experimental 4D nucleome data sets and models.
Show less - Date Issued
- 2018-10-01
- Identifier
- FSU_libsubv1_wos_000446047000006, 10.1038/s41588-018-0236-3
- Format
- Citation
- Title
- DNA replication timing alterations identify common markers between distinct progeroid diseases.
- Creator
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Rivera-Mulia, Juan Carlos, Desprat, Romain, Trevilla-Garcia, Claudia, Cornacchia, Daniela, Schwerer, Hélène, Sasaki, Takayo, Sima, Jiao, Fells, Tyler, Studer, Lorenz, Lemaitre,...
Show moreRivera-Mulia, Juan Carlos, Desprat, Romain, Trevilla-Garcia, Claudia, Cornacchia, Daniela, Schwerer, Hélène, Sasaki, Takayo, Sima, Jiao, Fells, Tyler, Studer, Lorenz, Lemaitre, Jean-Marc, Gilbert, David M
Show less - Abstract/Description
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Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Different causal mutations have been identified, but no molecular alterations have been identified that are in common to these diseases. DNA replication timing (RT) is a robust cell type-specific epigenetic feature highly conserved in the same cell types from different individuals but altered in disease. Here, we characterized DNA RT program alterations in Hutchinson-Gilford progeria syndrome (HGPS) and...
Show moreProgeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Different causal mutations have been identified, but no molecular alterations have been identified that are in common to these diseases. DNA replication timing (RT) is a robust cell type-specific epigenetic feature highly conserved in the same cell types from different individuals but altered in disease. Here, we characterized DNA RT program alterations in Hutchinson-Gilford progeria syndrome (HGPS) and Rothmund-Thomson syndrome (RTS) patients compared with natural aging and cellular senescence. Our results identified a progeroid-specific RT signature that is common to cells from three HGPS and three RTS patients and distinguishes them from healthy individuals across a wide range of ages. Among the RT abnormalities, we identified the tumor protein p63 gene () as a gene marker for progeroid syndromes. By using the redifferentiation of four patient-derived induced pluripotent stem cells as a model for the onset of progeroid syndromes, we tracked the progression of RT abnormalities during development, revealing altered RT of the gene as an early event in disease progression of both HGPS and RTS. Moreover, the RT abnormalities in progeroid patients were associated with altered isoform expression of Our findings demonstrate the value of RT studies to identify biomarkers not detected by other methods, reveal abnormal RT as an early event in progeroid disease progression, and suggest gene regulation as a potential therapeutic target.
Show less - Date Issued
- 2017-12-19
- Identifier
- FSU_pmch_29196523, 10.1073/pnas.1711613114, PMC5754778, 29196523, 29196523, 1711613114
- Format
- Citation
- Title
- Geographic variation in hybridization across a reinforcement contact zone of chorus frogs ().
- Creator
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Lemmon, Emily Moriarty, Juenger, Thomas E
- Abstract/Description
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Reinforcement contact zones, which are secondary contact zones where species are diverging in reproductive behaviors due to selection against hybridization, represent natural laboratories for studying speciation-in-action. Here, we examined replicate localities across the entire reinforcement contact zone between North American chorus frogs and to investigate geographic variation in hybridization frequencies and to assess whether reinforcement may have contributed to increased genetic...
Show moreReinforcement contact zones, which are secondary contact zones where species are diverging in reproductive behaviors due to selection against hybridization, represent natural laboratories for studying speciation-in-action. Here, we examined replicate localities across the entire reinforcement contact zone between North American chorus frogs and to investigate geographic variation in hybridization frequencies and to assess whether reinforcement may have contributed to increased genetic divergence within species. Previous work indicated these species have undergone reproductive character displacement (RCD) in male acoustic signals and female preferences due to reinforcement. We also examined acoustic signal variation across the contact zone to assess whether signal characteristics reliably predict hybrid index and to elucidate whether the degree of RCD predicts hybridization rate. Using microsatellites, mitochondrial sequences, and acoustic signal information from >1,000 individuals across >50 localities and ten sympatric focal regions, we demonstrate: (1) hybridization occurs and (2) varies substantially across the geographic range of the contact zone, (3) hybridization is asymmetric and in the direction predicted from observed patterns of asymmetric RCD, (4) in one species, genetic distance is higher between conspecific localities where one or both have been reinforced than between nonreinforced localities, after controlling for geographic distance, (5) acoustic signal characters strongly predict hybrid index, and (6) the degree of RCD does not strongly predict admixture levels. By showing that hybridization occurs in all sympatric localities, this study provides the fifth and final line of evidence that reproductive character displacement is due to reinforcement in the chorus frog contact zone. Furthermore, this work suggests that the dual action of cascade reinforcement and partial geographic isolation is promoting genetic diversification within one of the reinforced species.
Show less - Date Issued
- 2017-10-11
- Identifier
- FSU_pmch_29187984, 10.1002/ece3.3443, PMC5696400, 29187984, 29187984, ECE33443
- Format
- Citation
- Title
- Vertical organization of the division of labor within nests of the Florida harvester ant, Pogonomyrmex badius.
- Creator
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Tschinkel, Walter R, Hanley, Nicholas
- Abstract/Description
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In the Florida harvester ant, Pogonomyrmex badius, foragers occur only in the top 15 cm of the nest, whereas brood and brood-care workers reside mostly in the deepest regions, yet the food and seeds foragers collect must be transported downward 30 to 80 cm to seed chambers and up to 2 m to brood chambers. Using mark-recapture techniques with fluorescent printer's ink, we identified a class of workers that ranges widely within the vertical structure of the nest, rapidly moving materials...
Show moreIn the Florida harvester ant, Pogonomyrmex badius, foragers occur only in the top 15 cm of the nest, whereas brood and brood-care workers reside mostly in the deepest regions, yet the food and seeds foragers collect must be transported downward 30 to 80 cm to seed chambers and up to 2 m to brood chambers. Using mark-recapture techniques with fluorescent printer's ink, we identified a class of workers that ranges widely within the vertical structure of the nest, rapidly moving materials dropped by foragers in the upper regions downward, and excavated soil from deeper upward. Within the nest, only 5% of foragers were recovered below 20 cm depth, but about 30% of transfer workers and 82% of unmarked workers were found there. Below 70 cm depth, 90% of workers were unmarked, and were probably involved mostly in brood care. During the summer, the transfer workers comprise about a quarter of the nest population, while foragers make up about 40%. Workers marked as transfer workers later appear as foragers, while those marked as foragers die and disappear from the foraging population, suggesting that transfer workers are younger, and age into foraging. The importance of these findings for laboratory studies of division of labor are discussed. The efficient allocation of labor is a key component of superorganismal fitness.
Show less - Date Issued
- 2017-11-28
- Identifier
- FSU_pmch_29182686, 10.1371/journal.pone.0188630, PMC5705139, 29182686, 29182686, PONE-D-17-32984
- Format
- Citation
- Title
- Correction for Avey et al., "Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36".
- Creator
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Avey, Denis, Tepper, Sarah, Pifer, Benjamin, Bahga, Amritpal, Williams, Hunter, Gillen, Joseph, Li, Wenwei, Ogden, Sarah, Zhu, Fanxiu
- Date Issued
- 2017-11-14
- Identifier
- FSU_pmch_29138329, 10.1128/JVI.01484-17, PMC5686716, 29138329, 29138329, 91/23/e01484-17
- Format
- Citation
- Title
- A genome-wide phylogeny of jumping spiders (Araneae, Salticidae), using anchored hybrid enrichment.
- Creator
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Maddison, Wayne P, Evans, Samuel C, Hamilton, Chris A, Bond, Jason E, Lemmon, Alan R, Lemmon, Emily Moriarty
- Abstract/Description
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We present the first genome-wide molecular phylogeny of jumping spiders (Araneae: Salticidae), inferred from Anchored Hybrid Enrichment (AHE) sequence data. From 12 outgroups plus 34 salticid taxa representing all but one subfamily and most major groups recognized in previous work, we obtained 447 loci totalling 96,946 aligned nucleotide sites. Our analyses using concatenated likelihood, parsimony, and coalescent methods (ASTRAL and SVDQuartets) strongly confirm most previous results,...
Show moreWe present the first genome-wide molecular phylogeny of jumping spiders (Araneae: Salticidae), inferred from Anchored Hybrid Enrichment (AHE) sequence data. From 12 outgroups plus 34 salticid taxa representing all but one subfamily and most major groups recognized in previous work, we obtained 447 loci totalling 96,946 aligned nucleotide sites. Our analyses using concatenated likelihood, parsimony, and coalescent methods (ASTRAL and SVDQuartets) strongly confirm most previous results, resolving as monophyletic the Spartaeinae, Salticinae (with the hisponines sister), Salticoida, Amycoida, Saltafresia, and Simonida. The agoriines, previously difficult to place beyond subfamily, are finally placed confidently within the saltafresians as relatives of the chrysillines and hasariines. Relationships among the baviines, astioids, marpissoids, and saltafresians remain uncertain, though our analyses tentatively conclude the first three form a clade together. Deep relationships, among the seven subfamilies, appear to be largely resolved, with spartaeines, lyssomanines, and asemoneines forming a clade. In most analyses, (representing the onomastines) is strongly supported as sister to the hisponines plus salticines. Overall, the much-improved resolution of many deep relationships despite a relatively sparse taxon sample suggests AHE is a promising technique for salticid phylogenetics.
Show less - Date Issued
- 2017-09-04
- Identifier
- FSU_pmch_29134008, 10.3897/zookeys.695.13852, PMC5673835, 29134008, 29134008
- Format
- Citation
- Title
- Rat sensorimotor cortex tolerance to parallel transections induced by synchrotron-generated X-ray microbeams.
- Creator
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Fardone, Erminia, Bravin, Alberto, Conti, Alfredo, Bräuer-Krisch, Elke, Requardt, Herwig, Bucci, Domenico, Le Duc, Geraldine, Battaglia, Giuseppe, Romanelli, Pantaleo
- Abstract/Description
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Microbeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats...
Show moreMicrobeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats underwent irradiation with arrays of parallel microbeams. Beam thickness, spacing and incident dose were 100 or 600 µm, 400 or 1200 µm and 360 or 150 Gy, respectively. Motor performance was carried over a 3-month period. Three months after irradiation rats were sacrificed to evaluate the effects of irradiation on brain tissues by histology and immunohistochemistry. Microbeam irradiation of sensorimotor cortex did not affect weight gain and motor performance. No gross signs of paralysis or paresis were also observed. The cortical architecture was not altered, despite the presence of cell death along the irradiation path. Reactive gliosis was evident in the microbeam path of rats irradiated with 150 Gy, whereas no increase was observed in rats irradiated with 360 Gy.
Show less - Date Issued
- 2017-10-30
- Identifier
- FSU_pmch_29085040, 10.1038/s41598-017-14757-3, PMC5662592, 29085040, 29085040, 10.1038/s41598-017-14757-3
- Format
- Citation
- Title
- Genome-wide Analysis Of Replication Timing By Next-generation Sequencing With E/l Repli-seq.
- Creator
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Marchal, Claire, Sasaki, Takayo, Vera, Daniel, Wilson, Korey, Sima, Jiao, Rivera-Mulia, Juan Carlos, Trevilla-Garcia, Claudia, Nogues, Coralin, Nafie, Ebtesam, Gilbert, David M.
- Abstract/Description
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Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early-and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next...
Show moreCycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early-and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.
Show less - Date Issued
- 2018-05-01
- Identifier
- FSU_libsubv1_wos_000431191400002, 10.1038/nprot.2017.148
- Format
- Citation
- Title
- Mutation-Driven Parallel Evolution during Viral Adaptation.
- Creator
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Sackman, Andrew M, McGee, Lindsey W, Morrison, Anneliese J, Pierce, Jessica, Anisman, Jeremy, Hamilton, Hunter, Sanderbeck, Stephanie, Newman, Cayla, Rokyta, Darin R
- Abstract/Description
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Convergent evolution has been demonstrated across all levels of biological organization, from parallel nucleotide substitutions to convergent evolution of complex phenotypes, but whether instances of convergence are the result of selection repeatedly finding the same optimal solution to a recurring problem or are the product of mutational biases remains unsettled. We generated 20 replicate lineages allowed to fix a single mutation from each of four bacteriophage genotypes under identical...
Show moreConvergent evolution has been demonstrated across all levels of biological organization, from parallel nucleotide substitutions to convergent evolution of complex phenotypes, but whether instances of convergence are the result of selection repeatedly finding the same optimal solution to a recurring problem or are the product of mutational biases remains unsettled. We generated 20 replicate lineages allowed to fix a single mutation from each of four bacteriophage genotypes under identical selective regimes to test for parallel changes within and across genotypes at the levels of mutational effect distributions and gene, protein, amino acid, and nucleotide changes. All four genotypes shared a distribution of beneficial mutational effects best approximated by a distribution with a finite upper bound. Parallel adaptation was high at the protein, gene, amino acid, and nucleotide levels, both within and among phage genotypes, with the most common first-step mutation in each background fixing on an average in 7 of 20 replicates and half of the substitutions in two of the four genotypes occurring at shared sites. Remarkably, the mutation of largest beneficial effect that fixed for each genotype was never the most common, as would be expected if parallelism were driven by selection. In fact, the mutation of smallest benefit for each genotype fixed in a total of 7 of 80 lineages, equally as often as the mutation of largest benefit, leading us to conclude that adaptation was largely mutation-driven, such that mutational biases led to frequent parallel fixation of mutations of suboptimal effect.
Show less - Date Issued
- 2017-12-01
- Identifier
- FSU_pmch_29029274, 10.1093/molbev/msx257, PMC5850295, 29029274, 29029274, 4259274
- Format
- Citation
- Title
- Competing scaffolding proteins determine capsid size during mobilization of pathogenicity islands.
- Creator
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Dearborn, Altaira D, Wall, Erin A, Kizziah, James L, Klenow, Laura, Parker, Laura K, Manning, Keith A, Spilman, Michael S, Spear, John M, Christie, Gail E, Dokland, Terje
- Abstract/Description
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pathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80α and SaPI1 procapsids to near-atomic...
Show morepathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80α and SaPI1 procapsids to near-atomic resolution by cryo-electron microscopy, and show that CpmB competes with the 80α scaffolding protein (SP) for a binding site on the capsid protein (CP), and works by altering the angle between capsomers. We probed these interactions genetically and identified second-site suppressors of lethal mutations in SP. Our structures show, for the first time, the detailed interactions between SP and CP in a bacteriophage, providing unique insights into macromolecular assembly processes.
Show less - Date Issued
- 2017-10-06
- Identifier
- FSU_pmch_28984245, 10.7554/eLife.30822, PMC5644958, 28984245, 28984245, 30822
- Format
- Citation
- Title
- Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain.
- Creator
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Nätt, Daniel, Barchiesi, Riccardo, Murad, Josef, Feng, Jian, Nestler, Eric J, Champagne, Frances A, Thorsell, Annika
- Abstract/Description
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Childhood malnutrition is a risk factor for mental disorders, such as major depression and anxiety. Evidence shows that similar early life adversities induce sex-dependent epigenetic reprogramming. However, little is known about how genes are specifically affected by early malnutrition and the implications for males and females respectively. One relevant target is neuropeptide Y (NPY), which regulates both stress and food-intake. We studied maternal low protein diet (LPD) during pregnancy...
Show moreChildhood malnutrition is a risk factor for mental disorders, such as major depression and anxiety. Evidence shows that similar early life adversities induce sex-dependent epigenetic reprogramming. However, little is known about how genes are specifically affected by early malnutrition and the implications for males and females respectively. One relevant target is neuropeptide Y (NPY), which regulates both stress and food-intake. We studied maternal low protein diet (LPD) during pregnancy/lactation in mice. Male, but not female, offspring of LPD mothers consistently displayed anxiety- and depression-like behaviors under acute stress. Transcriptome-wide analysis of the effects of acute stress in the amygdala, revealed a list of transcription factors affected by either sex or perinatal LPD. Among these immediate early genes (IEG), members of the Early growth response family (Egr1/2/4) were consistently upregulated by perinatal LPD in both sexes. EGR1 also bound the NPY receptor Y1 gene (Npy1r), which co-occurred with sex-specific effects of perinatal LPD on both Npy1r DNA-methylation and gene transcription. Our proposed pathway connecting early malnutrition, sex-independent regulatory changes in Egr1, and sex-specific epigenetic reprogramming of its effector gene, Npy1r, represents the first molecular evidence of how early life risk factors may generate sex-specific epigenetic effects relevant for mental disorders.
Show less - Date Issued
- 2017-09-11
- Identifier
- FSU_pmch_28894112, 10.1038/s41598-017-10803-2, PMC5593991, 28894112, 28894112, 10.1038/s41598-017-10803-2
- Format
- Citation
- Title
- The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription.
- Creator
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Zouaz, Amel, Auradkar, Ankush, Delfini, Marie Claire, Macchi, Meiggie, Barthez, Marine, Ela Akoa, Serge, Bastianelli, Leila, Xie, Gengqiang, Deng, Wu-Min, Levine, Stuart S,...
Show moreZouaz, Amel, Auradkar, Ankush, Delfini, Marie Claire, Macchi, Meiggie, Barthez, Marine, Ela Akoa, Serge, Bastianelli, Leila, Xie, Gengqiang, Deng, Wu-Min, Levine, Stuart S, Graba, Yacine, Saurin, Andrew J
Show less - Abstract/Description
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In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that...
Show moreIn metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature. We found that AbdA binding to M1BP-regulated genes results in reduction in PcG binding, the release of paused Pol II, increases in promoter H3K4me3 histone marks and increased gene transcription. Linking transcription factors, PcG proteins and paused Pol II states, these data identify a two-step mechanism of Hox-driven transcription, with M1BP binding leading to Pol II recruitment followed by AbdA targeting, which results in a change in the chromatin landscape and enhanced transcription.
Show less - Date Issued
- 2017-10-02
- Identifier
- FSU_pmch_28871058, 10.15252/embj.201695751, PMC5623858, 28871058, 28871058, embj.201695751
- Format
- Citation
- Title
- Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins.
- Creator
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Yoon, Ki-Jun, Song, Guang, Qian, Xuyu, Pan, Jianbo, Xu, Dan, Rho, Hee-Sool, Kim, Nam-Shik, Habela, Christa, Zheng, Lily, Jacob, Fadi, Zhang, Feiran, Lee, Emily M, Huang, Wei-Kai...
Show moreYoon, Ki-Jun, Song, Guang, Qian, Xuyu, Pan, Jianbo, Xu, Dan, Rho, Hee-Sool, Kim, Nam-Shik, Habela, Christa, Zheng, Lily, Jacob, Fadi, Zhang, Feiran, Lee, Emily M, Huang, Wei-Kai, Ringeling, Francisca Rojas, Vissers, Caroline, Li, Cui, Yuan, Ling, Kang, Koeun, Kim, Sunghan, Yeo, Junghoon, Cheng, Yichen, Liu, Sheng, Wen, Zhexing, Qin, Cheng-Feng, Wu, Qingfeng, Christian, Kimberly M, Tang, Hengli, Jin, Peng, Xu, Zhiheng, Qian, Jiang, Zhu, Heng, Song, Hongjun, Ming, Guo-Li
Show less - Abstract/Description
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Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn...
Show moreZika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components. Functionally, ZIKV-NS2A, but not DENV-NS2A, destabilizes the AJ complex, resulting in impaired AJ formation and aberrant radial glial fiber scaffolding in the embryonic mouse cortex. Similarly, ZIKA-NS2A, but not DENV-NS2A, reduces radial glial cell proliferation and causes AJ deficits in human forebrain organoids. Together, our results reveal pathogenic mechanisms underlying ZIKV infection in the developing mammalian brain.
Show less - Date Issued
- 2017-09-07
- Identifier
- FSU_pmch_28826723, 10.1016/j.stem.2017.07.014, PMC5600197, 28826723, 28826723, S1934-5909(17)30293-X
- Format
- Citation
- Title
- AIM2 inflammasome activation and regulation: A structural perspective..
- Creator
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Wang, Bing, Yin, Qian
- Abstract/Description
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Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple...
Show moreAbsent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes. In this review, we track the AIM2 inflammasome activation process step by step, using high-resolution structures to illustrate the overall architecture of AIM2 inflammasome and its assembly and regulatory mechanisms.
Show less - Date Issued
- 2017-12-01
- Identifier
- FSU_pmch_28813641, 10.1016/j.jsb.2017.08.001, PMC5733693, 28813641, 28813641, S1047-8477(17)30132-6
- Format
- Citation
- Title
- Muroid rodent phylogenetics: 900-species tree reveals increasing diversification rates..
- Creator
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Steppan, Scott J, Schenk, John J
- Abstract/Description
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We combined new sequence data for more than 300 muroid rodent species with our previously published sequences for up to five nuclear and one mitochondrial genes to generate the most widely and densely sampled hypothesis of evolutionary relationships across Muroidea. An exhaustive screening procedure for publically available sequences was implemented to avoid the propagation of taxonomic errors that are common to supermatrix studies. The combined data set of carefully screened sequences...
Show moreWe combined new sequence data for more than 300 muroid rodent species with our previously published sequences for up to five nuclear and one mitochondrial genes to generate the most widely and densely sampled hypothesis of evolutionary relationships across Muroidea. An exhaustive screening procedure for publically available sequences was implemented to avoid the propagation of taxonomic errors that are common to supermatrix studies. The combined data set of carefully screened sequences derived from all available sequences on GenBank with our new data resulted in a robust maximum likelihood phylogeny for 900 of the approximately 1,620 muroids. Several regions that were equivocally resolved in previous studies are now more decisively resolved, and we estimated a chronogram using 28 fossil calibrations for the most integrated age and topological estimates to date. The results were used to update muroid classification and highlight questions needing additional data. We also compared the results of multigene supermatrix studies like this one with the principal published supertrees and concluded that the latter are unreliable for any comparative study in muroids. In addition, we explored diversification patterns as an explanation for why muroid rodents represent one of the most species-rich groups of mammals by detecting evidence for increasing net diversification rates through time across the muroid tree. We suggest the observation of increasing rates may be due to a combination of parallel increases in rate across clades and high average extinction rates. Five increased diversification-rate-shifts were inferred, suggesting that multiple, but perhaps not independent, events have led to the remarkable species diversity in the superfamily. Our results provide a phylogenetic framework for comparative studies that is not highly dependent upon the signal from any one gene.
Show less - Date Issued
- 2017-08-16
- Identifier
- FSU_pmch_28813483, 10.1371/journal.pone.0183070, PMC5559066, 28813483, 28813483, PONE-D-16-50122
- Format
- Citation