Search results

Title: Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins.
Creator: 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
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Abstract/Description: 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.
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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: Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth.
Creator: Tang, Hengli, Hammack, Christy, Ogden, Sarah C, Wen, Zhexing, Qian, Xuyu, Li, Yujing, Yao, Bing, Shin, Jaehoon, Zhang, Feiran, Lee, Emily M, Christian, Kimberly M, Didier, Ruth...
Show moreTang, Hengli, Hammack, Christy, Ogden, Sarah C, Wen, Zhexing, Qian, Xuyu, Li, Yujing, Yao, Bing, Shin, Jaehoon, Zhang, Feiran, Lee, Emily M, Christian, Kimberly M, Didier, Ruth A, Jin, Peng, Song, Hongjun, Ming, Guo-Li
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Abstract/Description: The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection...
Show moreThe suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
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Date Issued: 2016-05-05
Identifier: FSU_pmch_26952870, 10.1016/j.stem.2016.02.016, PMC5299540, 26952870, 26952870, S1934-5909(16)00106-5
Format: Citation

Title: Zika virus directly infects peripheral neurons and induces cell death.
Creator: Oh, Yohan, Zhang, Feiran, Wang, Yaqing, Lee, Emily M, Choi, In Young, Lim, Hotae, Mirakhori, Fahimeh, Li, Ronghua, Huang, Luoxiu, Xu, Tianlei, Wu, Hao, Li, Cui, Qin, Cheng-Feng,...
Show moreOh, Yohan, Zhang, Feiran, Wang, Yaqing, Lee, Emily M, Choi, In Young, Lim, Hotae, Mirakhori, Fahimeh, Li, Ronghua, Huang, Luoxiu, Xu, Tianlei, Wu, Hao, Li, Cui, Qin, Cheng-Feng, Wen, Zhexing, Wu, Qing-Feng, Tang, Hengli, Xu, Zhiheng, Jin, Peng, Song, Hongjun, Ming, Guo-Li, Lee, Gabsang
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Abstract/Description: Zika virus (ZIKV) infection is associated with neurological disorders of both the CNS and peripheral nervous systems (PNS), yet few studies have directly examined PNS infection. Here we show that intraperitoneally or intraventricularly injected ZIKV in the mouse can infect and impact peripheral neurons in vivo. Moreover, ZIKV productively infects stem-cell-derived human neural crest cells and peripheral neurons in vitro, leading to increased cell death, transcriptional dysregulation and cell...
Show moreZika virus (ZIKV) infection is associated with neurological disorders of both the CNS and peripheral nervous systems (PNS), yet few studies have directly examined PNS infection. Here we show that intraperitoneally or intraventricularly injected ZIKV in the mouse can infect and impact peripheral neurons in vivo. Moreover, ZIKV productively infects stem-cell-derived human neural crest cells and peripheral neurons in vitro, leading to increased cell death, transcriptional dysregulation and cell-type-specific molecular pathology.
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Date Issued: 2017-09-01
Identifier: FSU_pmch_28758997, 10.1038/nn.4612, PMC5575960, 28758997, 28758997, nn.4612
Format: Citation

Title: Zika virus and neural developmental defects: building a case for a cause.
Creator: Ogden, Sarah C., Hammack, Christy, Tang, Hengli
Date Issued: 2016-05
Identifier: FSU_libsubv1_wos_000375885300013, 10.1007/s11427-016-5053-2
Format: Citation

Title: Why Does The Magnitude Of Genotype-by-environment Interaction Vary?.
Creator: Saltz, Julia B., Bell, Alison M., Flint, Jonathan, Gomulkiewicz, Richard, Hughes, Kimberly A., Keagy, Jason
Abstract/Description: Genotype-by-environment interaction (GxE), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. GxE has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although GxE has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why GxE is so evident in some traits and...
Show moreGenotype-by-environment interaction (GxE), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. GxE has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although GxE has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why GxE 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 GxE. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in GxE and suggest some important next steps.
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Date Issued: 2018-06-01
Identifier: FSU_libsubv1_wos_000436799100031, 10.1002/ece3.4128
Format: Citation

Title: Why does the magnitude of genotype-by-environment interaction vary?.
Creator: Saltz, Julia B, Bell, Alison M, Flint, Jonathan, Gomulkiewicz, Richard, Hughes, Kimberly A, Keagy, Jason
Abstract/Description: 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.
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Date Issued: 2018-05-08
Identifier: FSU_pmch_29988442, 10.1002/ece3.4128, PMC6024136, 29988442, 29988442, ECE34128
Format: Citation

Title: Viral recombination blurs taxonomic lines: examination of single-stranded DNA viruses in a wastewater treatment plant..
Creator: Pearson, Victoria M, Caudle, S Brian, Rokyta, Darin R
Abstract/Description: Understanding the structure and dynamics of microbial communities, especially those of economic concern, is of paramount importance to maintaining healthy and efficient microbial communities at agricultural sites and large industrial cultures, including bioprocessors. Wastewater treatment plants are large bioprocessors which receive water from multiple sources, becoming reservoirs for the collection of many viral families that infect a broad range of hosts. To examine this complex collection...
Show moreUnderstanding the structure and dynamics of microbial communities, especially those of economic concern, is of paramount importance to maintaining healthy and efficient microbial communities at agricultural sites and large industrial cultures, including bioprocessors. Wastewater treatment plants are large bioprocessors which receive water from multiple sources, becoming reservoirs for the collection of many viral families that infect a broad range of hosts. To examine this complex collection of viruses, full-length genomes of circular ssDNA viruses were isolated from a wastewater treatment facility using a combination of sucrose-gradient size selection and rolling-circle amplification and sequenced on an Illumina MiSeq. Single-stranded DNA viruses are among the least understood groups of microbial pathogens due to genomic biases and culturing difficulties, particularly compared to the larger, more often studied dsDNA viruses. However, the group contains several notable well-studied examples, including agricultural pathogens which infect both livestock and crops ( and ), and model organisms for genetics and evolution studies (). Examination of the collected viral DNA provided evidence for 83 unique genotypic groupings, which were genetically dissimilar to known viral types and exhibited broad diversity within the community. Furthermore, although these genomes express similarities to known viral families, such as , , and , many are so divergent that they may represent new taxonomic groups. This study demonstrated the efficacy of the protocol for separating bacteria and large viruses from the sought after ssDNA viruses and the ability to use this protocol to obtain an in-depth analysis of the diversity within this group.
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Date Issued: 2016-10-18
Identifier: FSU_pmch_27781171, 10.7717/peerj.2585, PMC5075696, 27781171, 27781171, 2585
Format: Citation

Title: Viral Recombination Blurs Taxonomic Lines: Examination Of Single-stranded Dna Viruses In A Wastewater Treatment Plant.
Creator: Pearson, Victoria M., Caudle, S. Brian, Rokyta, Darin R.
Abstract/Description: Understanding the structure and dynamics of microbial communities, especially those of economic concern, is of paramount importance to maintaining healthy and efficient microbial communities at agricultural sites and large industrial cultures, including bioprocessors. Wastewater treatment plants are large bioprocessors which receive water from multiple sources, becoming reservoirs for the complex collection of many viral families that infect a broad range of hosts. To examine this collection...
Show moreUnderstanding the structure and dynamics of microbial communities, especially those of economic concern, is of paramount importance to maintaining healthy and efficient microbial communities at agricultural sites and large industrial cultures, including bioprocessors. Wastewater treatment plants are large bioprocessors which receive water from multiple sources, becoming reservoirs for the complex collection of many viral families that infect a broad range of hosts. To examine this collection of viruses, full-length genomes of circular ssDNA viruses were isolated from a wastewater treatment facility using a combination of sucrose-gradient size selection and rolling-circle amplification and sequenced on an Illumina MSeq. Single-stranded DNA viruses are among the least understood groups of microbial pathogens due to genomic biases and culturing difficulties, particularly compared to the larger, more often studied dsDNA viruses. However, the group contains several notable well-studied examples, including agricultural pathogens which infect both livestock and crops (Circoviridae and Geminiviridae), and model organisms for genetics and evolution studies (Microviridae). Examination of the collected viral DNA provided evidence for 83 unique genotypic groupings, which were genetically dissimilar to known viral types and exhibited broad diversity within the community. Furthermore, although these genomes express similarities to known viral families, such as Circoviridae, Geminiviridae, and Microviridae, many are so divergent that they may represent new taxonomic groups. This study demonstrated the efficacy of the protocol for separating bacteria and large viruses from the sought after ssDNA viruses and the ability to use this protocol to obtain an in-depth analysis of the diversity within this group.
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Date Issued: 2016-10-18
Identifier: FSU_libsubv1_wos_000385583100006, 10.7717/peerj.2585
Format: Citation

Title: Vertical organization of the division of labor within nests of the Florida harvester ant, Pogonomyrmex badius.
Creator: Tschinkel, Walter R, Hanley, Nicholas
Abstract/Description: 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.
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Date Issued: 2017-11-28
Identifier: FSU_pmch_29182686, 10.1371/journal.pone.0188630, PMC5705139, 29182686, 29182686, PONE-D-17-32984
Format: Citation

Title: Venom Complexity in a Pitviper Produced by Facultative Parthenogenesis.
Creator: 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: 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.
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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: Venom Complexity In A Pitviper Produced By Facultative Parthenogenesis.
Creator: Calvete, J. J., Casewell, N. R., Hernandez-Guzman, U., Quesada-Bernat, S., Sanz, L., Rokyta, D. R., Storey, D., Albulescu, L.-O., Wuster, W., Smith, C. F., Schuett, G. W., Booth...
Show moreCalvete, J. J., Casewell, N. R., Hernandez-Guzman, U., Quesada-Bernat, S., Sanz, L., Rokyta, D. R., Storey, D., Albulescu, L.-O., Wuster, W., Smith, C. F., Schuett, G. W., Booth, W.
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Abstract/Description: 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.
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Date Issued: 2018-08-01
Identifier: FSU_libsubv1_wos_000440411300024, 10.1038/s41598-018-29791-y
Format: Citation

Title: Variation In Plant-mediated Intra- And Interspecific Interactions Among Insect Herbivores: Effects Of Host Genotype.
Creator: McNutt, David W., Underwood, Nora
Abstract/Description: Many studies show that indirect interactions between insect herbivores via shared host plants are common and often mediated by plant-induced responses to damage. However, we lack some types of data that will be needed to model how plant-mediated interactions on individual plants contribute to the population dynamics of interacting herbivores. Specifically, there are few simultaneous characterizations of both the intra- and interspecific effects that are mediated by the host plant, as well as...
Show moreMany studies show that indirect interactions between insect herbivores via shared host plants are common and often mediated by plant-induced responses to damage. However, we lack some types of data that will be needed to model how plant-mediated interactions on individual plants contribute to the population dynamics of interacting herbivores. Specifically, there are few simultaneous characterizations of both the intra- and interspecific effects that are mediated by the host plant, as well as host plant constitutive resistance. Additionally, as herbivores are likely to move among plants that differ in quality, we must consider how this set of intra- and interspecific effects differs among plant genotypes-that is, how plant-mediated effects genetically vary or covary. We examined how the set of intra- and interspecific indirect effects involving the insect folivores Leptinotarsa juncta and Manduca sexta varies across different genotypes of a shared host plant, Solanum carolinense. We damaged 12 plant genotypes using both herbivore species, then measured effects on the growth of both con- and heterospecifics, as well as constitutive resistance to each herbivore. We then tested for genetic variation and covariation in plant-mediated effects and constitutive resistance among plant genotypes. We found that on average, there were significant negative intraspecific plant-mediated effects on the growth rate of both herbivores, as well as asymmetric negative interspecific effects of M. sexta on L. juncta. Both intra- and interspecific effects varied across plant genotypes. For example, the interspecific effect of M. sexta on L. juncta ranged from significantly negative to significantly positive. Additionally, there were strong correlations among the individual effects mediated by S. carolinense, particularly between constitutive resistance and both intra- and interspecific effects. We find that these genetic correlations might limit the types and strength of interactions that take place across multiple genotypes of the same plant species. Our results suggest that future models of plant-mediated interactions between herbivores should account for patterns of genetic variation and covariation when scaling from individual interactions to population-level processes.
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Date Issued: 2016-10
Identifier: FSU_libsubv1_wos_000387216300050, 10.1002/ecs2.1520
Format: Citation

Title: Valproic Acid for a Treatment of Retinitis Pigmentosa: Reasons for Optimism and Caution..
Creator: Todd, Levi, Zelinka, Christopher
Date Issued: 2017-05-24
Identifier: FSU_pmch_28539347, 10.1523/JNEUROSCI.0774-17.2017, PMC5456104, 28539347, 28539347, 37/21/5215
Format: Citation

Title: Unique Maternal And Environmental Effects On The Body Morphology Of The Least Killifish, Heterandria Formosa.
Creator: Landy, J. Alex, Travis, Joseph
Abstract/Description: 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, Heterandria formosa, 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.
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Date Issued: 2018-06-01
Identifier: FSU_libsubv1_wos_000436799100024, 10.1002/ece3.4166
Format: Citation

Title: Unique maternal and environmental effects on the body morphology of the Least Killifish, .
Creator: Landy, J Alex, Travis, Joseph
Abstract/Description: 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.
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Date Issued: 2018-05-24
Identifier: FSU_pmch_29988417, 10.1002/ece3.4166, PMC6024122, 29988417, 29988417, ECE34166
Format: Citation

Title: Transcriptome Dataset of Halophyte Beach Morning Glory, a Close Wild Relative of Sweet Potato.
Creator: Reid, Robert W, Luo, Yan, Yan, Sue, Miller, Thomas E, Song, Bao-Hua
Date Issued: 2016-08-24
Identifier: FSU_pmch_27605930, 10.3389/fpls.2016.01267, PMC4995209, 27605930, 27605930
Format: Citation

Title: Transcriptome Dataset Of Halophyte Beach Morning Glory, A Close Wild Relative Of Sweet Potato.
Creator: Reid, Robert W., Luo, Yan, Yan, Sue, Miller, Thomas E., Song, Bao-Hua
Date Issued: 2016-08-24
Identifier: FSU_libsubv1_wos_000381854100001, 10.3389/fpls.2016.01267
Format: Citation

Title: Tissue-Intrinsic Tumor Hotspots: Terroir for Tumorigenesis..
Creator: Tamori, Yoichiro, Deng, Wu-Min
Abstract/Description: Epithelial tissues are highly organized systems with a remarkable homeostatic ability to maintain morphology through regulation of cellular proliferation and tissue integrity. This robust self-organizing system is progressively disrupted during tumor development. Recent studies of conserved tumor-suppressor genes in Drosophila showed how protumor cells deviate from the robustly organized tissue microenvironment to take the first steps into becoming aggressive tumors. Here we review the 'tumor...
Show moreEpithelial tissues are highly organized systems with a remarkable homeostatic ability to maintain morphology through regulation of cellular proliferation and tissue integrity. This robust self-organizing system is progressively disrupted during tumor development. Recent studies of conserved tumor-suppressor genes in Drosophila showed how protumor cells deviate from the robustly organized tissue microenvironment to take the first steps into becoming aggressive tumors. Here we review the 'tumor hotspot' hypothesis that explains how the tissue-intrinsic local microenvironment has a pivotal role in the initial stage of tumorigenesis in Drosophila epithelia and discuss comparable mechanisms in mammalian tissues.
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Date Issued: 2017-04-01
Identifier: FSU_pmch_28718438, 10.1016/j.trecan.2017.03.003, PMC5518481, 28718438, 28718438, S2405-8033(17)30058-4
Format: Citation

Title: Thrombopoietin Signaling To Chromatin Elicits Rapid And Pervasive Epigenome Remodeling Within Poised Chromatin Architectures.
Creator: Comoglio, Federico, Park, Hyun Jung, Schoenfelder, Stefan, Barozzi, Iros, Bode, Daniel, Fraser, Peter, Green, Anthony R.
Abstract/Description: Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relationship between cis-regulatory activity...
Show moreThrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relationship between cis-regulatory activity and chromatin architecture. We show that TPO profoundly alters the transcriptome of HSPCs, with key hematopoietic regulators being transcriptionally repressed within 30 min of TPO. By examining cis-regulatory dynamics and chromatin architectures, we demonstrate that these changes are accompanied by rapid and extensive epigenome remodeling of cis-regulatory landscapes that is spatially coordinated within topologically associating domains (TADs). Moreover, TPO-responsive enhancers are spatially clustered and engage in preferential homotypic intra-and inter-TAD interactions that are largely refractory to TPO signaling. By further examining the link between cis-regulatory dynamics and chromatin looping, we show that rapid modulation of cis-regulatory activity is largely independent of chromatin looping dynamics. Finally, we show that, although activated and repressed cis-regulatory elements share remarkably similar DNA sequence compositions, transcription factor binding patterns accurately predict rapid cis-regulatory responses to TPO.
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Date Issued: 2018-03
Identifier: FSU_libsubv1_wos_000426355600003, 10.1101/gr.227272.117
Format: Citation

Title: Thalassiosira Mala (bacillariophyta), A Potentially Harmful, Marine Diatom From Chilka Lake And Other Coastal Localities Of Odisha, India: Nomenclature, Frustule Morphology And Global Biogeography.
Creator: Prasad, Akshinthala K. S. K., Nienow, James A., Lochner, Eric
Abstract/Description: Our examination of net phytoplankton collected from coastal localities in Odisha on the east coast of India, including Chilka Lake, Chandrabhaga Beach and Puri, in December 2015, revealed the overwhelming dominance of Thalassiosira mala, a gelatinous colony-forming, potentially harmful, marine planktonic diatom. The large numbers of cells allowed us to observe details of the cingulum not previously reported. The epicingulum is composed of four open bands including an areolated valvocopula, an...
Show moreOur examination of net phytoplankton collected from coastal localities in Odisha on the east coast of India, including Chilka Lake, Chandrabhaga Beach and Puri, in December 2015, revealed the overwhelming dominance of Thalassiosira mala, a gelatinous colony-forming, potentially harmful, marine planktonic diatom. The large numbers of cells allowed us to observe details of the cingulum not previously reported. The epicingulum is composed of four open bands including an areolated valvocopula, an areolated copula and two non-areolated pleurae. The immature hypocingulum includes at least two bands. Openings of alternate bands are arranged in a dextral pattern. Based on previous reports from the west coast and our current findings, Thalassiosira mala appears to be a common, widely distributed primary producer in Indian coastal waters. The presence of morphologically similar species, especially those < 20 mu m in diameter, underscores the importance of reliable species-level taxonomy using appropriate techniques for meaningful ecological and biogeographic considerations and for monitoring potentially harmful algae in India's economically important coastal waters. Published reports suggest that Thalassiosira mala is widely distributed in temperate and tropical waters, present in 26 of 232 ecoregions and 18 of 62 provinces recognized in a recent classification of coastal marine ecoregions.
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Date Issued: 2018-03
Identifier: FSU_libsubv1_wos_000426370500007, 10.1007/s12038-018-9730-0
Format: Citation

Title: Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors.
Creator: Feng, Jian, Pena, Catherine J, Purushothaman, Immanuel, Engmann, Olivia, Walker, Deena, Brown, Amber N, Issler, Orna, Doyle, Marie, Harrigan, Eileen, Mouzon, Ezekiell, Vialou,...
Show moreFeng, Jian, Pena, Catherine J, Purushothaman, Immanuel, Engmann, Olivia, Walker, Deena, Brown, Amber N, Issler, Orna, Doyle, Marie, Harrigan, Eileen, Mouzon, Ezekiell, Vialou, Vincent, Shen, Li, Dawlaty, Meelad M, Jaenisch, Rudolf, Nestler, Eric J
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Abstract/Description: Depression is a leading cause of disease burden, yet current therapies fully treat
Show moreDepression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here we examined a possible role for the DNA dioxygenase, ten-eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region. We show decreased Tet1 expression in NAc in stress-susceptible mice only. Surprisingly, selective knockout of Tet1 in NAc neurons of adult mice produced antidepressant-like effects in several behavioral assays. To identify Tet1 targets that mediate these actions, we performed RNAseq on NAc after conditional deletion of Tet1 and found that immune-related genes are the most highly dysregulated. Moreover, many of these genes are also upregulated in the NAc of resilient mice after chronic social defeat stress. These findings reveal a novel role for TET1, an enzyme important for DNA hydroxymethylation, in the brain's reward circuitry in modulating stress responses in mice. We also identify a subset of genes that are regulated by TET1 in this circuitry. These findings provide new insight into the pathophysiology of depression, which can aid in future antidepressant drug discovery efforts.
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Date Issued: 2017-07-01
Identifier: FSU_pmch_28074830, 10.1038/npp.2017.6, PMC5518912, 28074830, 28074830, npp20176
Format: Citation

Title: Targeted disruption of the endogenous zebrafish locus as models of rapid rod photoreceptor degeneration.
Creator: Zelinka, Christopher P, Sotolongo-Lopez, Mailin, Fadool, James M
Abstract/Description: 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.
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Date Issued: 2018-08-27
Identifier: FSU_pmch_30210230, PMC6128699, 30210230, 30210230
Format: Citation

Title: Take a look at plant DNA replication: Recent insights and new questions..
Creator: Savadel, Savannah D, Bass, Hank W
Abstract/Description: Recent advances in replicative DNA labeling technology have allowed new ways to study DNA replication in living plants. Temporal and spatial aspects of DNA replication programs are believed to derive from genomic structure and function. Bass et al. (2015) recently visualized DNA synthesis using 3D microscopy of nuclei at three sub-stages of S phase: early, middle and late. This addendum expands on that study by comparing plant and animal DNA replication patterns, by considering implications...
Show moreRecent advances in replicative DNA labeling technology have allowed new ways to study DNA replication in living plants. Temporal and spatial aspects of DNA replication programs are believed to derive from genomic structure and function. Bass et al. (2015) recently visualized DNA synthesis using 3D microscopy of nuclei at three sub-stages of S phase: early, middle and late. This addendum expands on that study by comparing plant and animal DNA replication patterns, by considering implications of the two-compartment model of euchromatin, and by exploring the meaning of the DNA labeling signals inside the nucleolus. Finally, we invite the public to explore and utilize 300 image data sets through OMERO, a teaching and research web resource for visualization, management, or analysis of microscopic data.
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Date Issued: 2017-04-03
Identifier: FSU_pmch_28375043, 10.1080/15592324.2017.1311437, PMC5437822, 28375043, 28375043
Format: Citation

Title: Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in epithelial tumors.
Creator: Shu, Zhiqiang, Huang, Yi-Chun, Palmer, William H, Tamori, Yoichiro, Xie, Gengqiang, Wang, Hui, Liu, Nan, Deng, Wu-Min
Abstract/Description: 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.
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Date Issued: 2017-11-01
Identifier: FSU_pmch_29312571, 10.18632/oncotarget.22226, PMC5752484, 29312571, 29312571, 22226
Format: Citation

Title: Synergistic Pleiotropy Overrides the Costs of Complexity in Viral Adaptation.
Creator: McGee, Lindsey W, Sackman, Andrew M, Morrison, Anneliese J, Pierce, Jessica, Anisman, Jeremy, Rokyta, Darin R
Abstract/Description: Adaptive evolution progresses as a series of steps toward a multidimensional phenotypic optimum, and organismal or environmental complexity determines the number of phenotypic dimensions, or traits, under selection. Populations evolving in complex environments may experience costs of complexity such that improvement in one or more traits is impeded by selection on others. We compared the fitness effects of the first fixed mutations for populations of single-stranded DNA bacteriophage evolving...
Show moreAdaptive evolution progresses as a series of steps toward a multidimensional phenotypic optimum, and organismal or environmental complexity determines the number of phenotypic dimensions, or traits, under selection. Populations evolving in complex environments may experience costs of complexity such that improvement in one or more traits is impeded by selection on others. We compared the fitness effects of the first fixed mutations for populations of single-stranded DNA bacteriophage evolving under simple selection for growth rate to those of populations evolving under more complex selection for growth rate as well as capsid stability. We detected a cost of complexity manifested as a smaller growth rate improvement for mutations fixed under complex conditions. We found that, despite imposing a cost for growth rate improvement, strong complex selection resulted in the greatest overall fitness improvement, even for single mutations. Under weaker secondary selective pressures, tradeoffs between growth rate and stability were pervasive, but strong selection on the secondary trait resulted largely in mutations beneficial to both traits. Strength of selection therefore determined the nature of pleiotropy governing observed trait evolution, and strong positive selection forced populations to find mutations that improved multiple traits, thereby overriding costs incurred as a result of a more complex selective environment. The costs of complexity, however, remained substantial when considering the effects on a single trait in the context of selection on multiple traits.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_26564159, 10.1534/genetics.115.181628, PMC4701092, 26564159, 26564159, genetics.115.181628
Format: Citation

Title: Synchrotron-generated microbeams induce hippocampal transections in rats.
Creator: 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
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Abstract/Description: 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.
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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: Synchrotron-generated Microbeams Induce Hippocampal Transections In Rats.
Creator: Fardone, Erminia, Pouyatos, Benoit, Brauer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Herve, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe,...
Show moreFardone, Erminia, Pouyatos, Benoit, Brauer-Krisch, Elke, Bartzsch, Stefan, Mathieu, Herve, Requardt, Herwig, Bucci, Domenico, Barbone, Giacomo, Coan, Paola, Battaglia, Giuseppe, Le Duc, Geraldine, Bravin, Alberto, Romanelli, Pantaleo
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Abstract/Description: 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 gamma-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.
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Date Issued: 2018-01-09
Identifier: FSU_libsubv1_wos_000419659800019, 10.1038/s41598-017-18000-x
Format: Citation

Title: Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.
Creator: Hu, Guiqing, Liu, Jun, Roux, Kenneth H, Taylor, Kenneth A
Abstract/Description: The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and...
Show moreThe human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the rapid freezing step, which were separated using statistical analysis. Our results show that the CD4-induced conformational dynamics of the spike enhances binding of the antibody.
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Date Issued: 2017-07-27
Identifier: FSU_pmch_28539445, 10.1128/JVI.00134-17, PMC5533903, 28539445, 28539445, JVI.00134-17
Format: Citation

Title: Structural Insights into Human Bocaparvoviruses.
Creator: Mietzsch, Mario, Kailasan, Shweta, Garrison, Jamie, Ilyas, Maria, Chipman, Paul, Kantola, Kalle, Janssen, Mandy E, Spear, John, Sousa, Duncan, McKenna, Robert, Brown, Kevin,...
Show moreMietzsch, Mario, Kailasan, Shweta, Garrison, Jamie, Ilyas, Maria, Chipman, Paul, Kantola, Kalle, Janssen, Mandy E, Spear, John, Sousa, Duncan, McKenna, Robert, Brown, Kevin, Söderlund-Venermo, Maria, Baker, Timothy, Agbandje-McKenna, Mavis
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Abstract/Description: Bocaparvoviruses are emerging pathogens of the family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1,...
Show moreBocaparvoviruses are emerging pathogens of the family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 Å by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. Human bocaviruses are one of only a few members of the family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.
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Date Issued: 2017-05-12
Identifier: FSU_pmch_28331084, 10.1128/JVI.00261-17, PMC5432872, 28331084, 28331084, JVI.00261-17
Format: Citation

Title: Structural Insights Into Human Bocaparvoviruses.
Creator: Mietzsch, Mario, Kailasan, Shweta, Garrison, Jamie, Ilyas, Maria, Chipman, Paul, Kantola, Kalle, Janssen, Mandy E., Spear, John, Sousa, Duncan, McKenna, Robert, Brown, Kevin,...
Show moreMietzsch, Mario, Kailasan, Shweta, Garrison, Jamie, Ilyas, Maria, Chipman, Paul, Kantola, Kalle, Janssen, Mandy E., Spear, John, Sousa, Duncan, McKenna, Robert, Brown, Kevin, Soederlund-Venermo, Maria, Baker, Timothy, Agbandje-McKenna, Mavis
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Abstract/Description: Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures...
Show moreBocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 angstrom by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. IMPORTANCE Human bocaviruses are one of only a few members of the Parvoviridae family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.
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Date Issued: 2017-06
Identifier: FSU_libsubv1_wos_000402166500018, 10.1128/JVI.00261-17
Format: Citation

Title: Structural Heterogeneity in Pre-40S Ribosomes.
Creator: Johnson, Matthew C, Ghalei, Homa, Doxtader, Katelyn A, Karbstein, Katrin, Stroupe, M Elizabeth
Abstract/Description: Late-stage 40S ribosome assembly is a highly regulated dynamic process that occurs in the cytoplasm, alongside the full translation machinery. Seven assembly factors (AFs) regulate and facilitate maturation, but the mechanisms through which they work remain undetermined. Here, we present a series of structures of the immature small subunit (pre-40S) determined by three-dimensional (3D) cryoelectron microscopy with 3D sorting to assess the molecule's heterogeneity. These structures demonstrate...
Show moreLate-stage 40S ribosome assembly is a highly regulated dynamic process that occurs in the cytoplasm, alongside the full translation machinery. Seven assembly factors (AFs) regulate and facilitate maturation, but the mechanisms through which they work remain undetermined. Here, we present a series of structures of the immature small subunit (pre-40S) determined by three-dimensional (3D) cryoelectron microscopy with 3D sorting to assess the molecule's heterogeneity. These structures demonstrate an extensive structural heterogeneity of interface AFs that likely regulates subunit joining during 40S maturation. We also present structural models for the beak and the platform, two regions where the low resolution of previous studies did not allow for localization of AFs and the rRNA, respectively. These models are supported by biochemical analyses using point variants and suggest that maturation of the 18S 3' end is regulated by dissociation of the AF Dim1 from the subunit interface, consistent with previous biochemical analyses.
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Date Issued: 2017-02-07
Identifier: FSU_pmch_28111018, 10.1016/j.str.2016.12.011, PMC5314460, 28111018, 28111018, S0969-2126(16)30401-4
Format: Citation

Title: Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like.
Creator: Ebrahim, Seham, Avenarius, Matthew R, Grati, M'hamed, Krey, Jocelyn F, Windsor, Alanna M, Sousa, Aurea D, Ballesteros, Angela, Cui, Runjia, Millis, Bryan A, Salles, Felipe T,...
Show moreEbrahim, Seham, Avenarius, Matthew R, Grati, M'hamed, Krey, Jocelyn F, Windsor, Alanna M, Sousa, Aurea D, Ballesteros, Angela, Cui, Runjia, Millis, Bryan A, Salles, Felipe T, Baird, Michelle A, Davidson, Michael W, Jones, Sherri M, Choi, Dongseok, Dong, Lijin, Raval, Manmeet H, Yengo, Christopher M, Barr-Gillespie, Peter G, Kachar, Bechara
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Abstract/Description: Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a...
Show moreHair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell.
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Date Issued: 2016-03-01
Identifier: FSU_pmch_26926603, 10.1038/ncomms10833, PMC4773517, 26926603, 26926603, ncomms10833
Format: Citation

Title: Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.
Creator: Sasaki, Takayo, Rivera-Mulia, Juan Carlos, Vera, Daniel, Zimmerman, Jared, Das, Sunny, Padget, Michelle, Nakamichi, Naoto, Chang, Bill H, Tyner, Jeff, Druker, Brian J, Weng,...
Show moreSasaki, Takayo, Rivera-Mulia, Juan Carlos, Vera, Daniel, Zimmerman, Jared, Das, Sunny, Padget, Michelle, Nakamichi, Naoto, Chang, Bill H, Tyner, Jeff, Druker, Brian J, Weng, Andrew P, Civin, Curt I, Eaves, Connie J, Gilbert, David M
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Abstract/Description: Genome-wide DNA replication timing (RT) profiles reflect the global three-dimensional chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of cellular epigenetic state. Thus, normal differentiation involves reproducible changes in RT, and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human...
Show moreGenome-wide DNA replication timing (RT) profiles reflect the global three-dimensional chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of cellular epigenetic state. Thus, normal differentiation involves reproducible changes in RT, and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro. In contrast, the ability of many human ALL cell populations to expand when transplanted into highly immunodeficient mice is well documented. To examine the stability of DNA RT profiles of serially passaged xenografts of primary human B- and T-ALL cells, we first devised a method that circumvents the need for bromodeoxyuridine incorporation to distinguish early versus late S-phase cells. Using this and more standard protocols, we found consistently strong retention in xenografts of the original patient-specific RT features. Moreover, in a case in which genomic analyses indicated changing subclonal dynamics in serial passages, the RT profiles tracked concordantly. These results indicate that DNA RT is a relatively stable feature of human ALLs propagated in immunodeficient mice. In addition, they suggest the power of this approach for future interrogation of the origin and consequences of altered DNA RT in ALL.
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Date Issued: 2017-07-01
Identifier: FSU_pmch_28433605, 10.1016/j.exphem.2017.04.004, PMC5491210, 28433605, 28433605, S0301-472X(17)30136-4
Format: Citation

Title: Spindly is required for rapid migration of human cells.
Creator: Conte, Claudia, Baird, Michelle A, Davidson, Michael W, Griffis, Eric R
Abstract/Description: 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.
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Date Issued: 2018-05-29
Identifier: FSU_pmch_29685992, 10.1242/bio.033233, PMC5992534, 29685992, 29685992, bio.033233
Format: Citation

Title: Spindly Is Required For Rapid Migration Of Human Cells.
Creator: Conte, Claudia, Baird, Michelle A., Davidson, Michael W., Griffis, Eric R.
Abstract/Description: 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 in vitro. 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.
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Date Issued: 2018-05-01
Identifier: FSU_libsubv1_wos_000434210800009, 10.1242/bio.033233
Format: Citation

Title: Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification.
Creator: Wilson, Korey A, Elefanty, Andrew G, Stanley, Edouard G, Gilbert, David M
Abstract/Description: Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence...
Show moreLineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification.
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Date Issued: 2016-09-16
Identifier: FSU_pmch_27433885, 10.1080/15384101.2016.1203492, PMC5026818, 27433885, 27433885
Format: Citation

Title: Sliding of centrosome-unattached microtubules defines key features of neuronal phenotype.
Creator: Rao, Anand N, Falnikar, Aditi, O'Toole, Eileen T, Morphew, Mary K, Hoenger, Andreas, Davidson, Michael W, Yuan, Xiaobing, Baas, Peter W
Abstract/Description: Contemporary models for neuronal migration are grounded in the view that virtually all functionally relevant microtubules (MTs) in migrating neurons are attached to the centrosome, which occupies a position between the nucleus and a short leading process. It is assumed that MTs do not undergo independent movements but rather transduce forces that enable movements of the centrosome and nucleus. The present results demonstrate that although this is mostly true, a small fraction of the MTs are...
Show moreContemporary models for neuronal migration are grounded in the view that virtually all functionally relevant microtubules (MTs) in migrating neurons are attached to the centrosome, which occupies a position between the nucleus and a short leading process. It is assumed that MTs do not undergo independent movements but rather transduce forces that enable movements of the centrosome and nucleus. The present results demonstrate that although this is mostly true, a small fraction of the MTs are centrosome-unattached, and this permits limited sliding of MTs. When this sliding is pharmacologically inhibited, the leading process becomes shorter, migration of the neuron deviates from its normal path, and the MTs within the leading process become buckled. Partial depletion of ninein, a protein that attaches MTs to the centrosome, leads to greater numbers of centrosome-unattached MTs as well as greater sliding of MTs. Concomitantly, the soma becomes less mobile and the leading process acquires an elongated morphology akin to an axon.
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Date Issued: 2016-05-09
Identifier: FSU_pmch_27138250, 10.1083/jcb.201506140, PMC4862329, 27138250, 27138250, jcb.201506140
Format: Citation

Title: Site Fidelity By Bees Drives Pollination Facilitation In Sequentially Blooming Plant Species.
Creator: Ogilvie, Jane E., Thomson, James D.
Abstract/Description: Plant species can influence the pollination and reproductive success of coflowering neighbors that share pollinators. Because some individual pollinators habitually forage in particular areas, it is also possible that plant species could influence the pollination of neighbors that bloom later. When flowers of a preferred forage plant decline in an area, site-fidelity may cause individual flower feeders to stay in an area and switch plant species rather than search for preferred plants in a...
Show morePlant species can influence the pollination and reproductive success of coflowering neighbors that share pollinators. Because some individual pollinators habitually forage in particular areas, it is also possible that plant species could influence the pollination of neighbors that bloom later. When flowers of a preferred forage plant decline in an area, site-fidelity may cause individual flower feeders to stay in an area and switch plant species rather than search for preferred plants in a new location. A newly blooming plant species may quickly inherit a set of visitors from a prior plant species, and therefore experience higher pollination success than it would in an area where the first species never bloomed. To test this, we manipulated the placement and timing of two plant species, Delphinium barbeyi and later-blooming Gentiana parryi. We recorded the responses of individually marked bumble bee pollinators. About 63% of marked individuals returned repeatedly to the same areas to forage on Delphinium. When Delphinium was experimentally taken out of bloom, most of those site-faithful individuals (78%) stayed and switched to Gentiana. Consequently, Gentiana flowers received more visits in areas where Delphinium had previously flowered, compared to areas where Delphinium was still flowering or never occurred. Gentiana stigmas received more pollen in areas where Delphinium disappeared than where it never bloomed, indicating that Delphinium increases the pollination of Gentiana when they are separated in time. Overall, we show that individual bumble bees are often site-faithful, causing one plant species to increase the pollination of another even when separated in time, which is a novel mechanism of pollination facilitation.
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Date Issued: 2016-06
Identifier: FSU_libsubv1_wos_000377219900008, 10.1890/15-0903.1
Format: Citation

Title: Single-cell replication profiling to measure stochastic variation in mammalian replication timing.
Creator: Dileep, Vishnu, Gilbert, David M
Abstract/Description: 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.
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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: Single-cell Replication Profiling To Measure Stochastic Variation In Mammalian Replication Timing.
Creator: Dileep, Vishnu, Gilbert, David M.
Abstract/Description: 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.
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Date Issued: 2018-01-30
Identifier: FSU_libsubv1_wos_000423510600004, 10.1038/s41467-017-02800-w
Format: Citation

Title: Selection To Increase Expression, Not Sequence Diversity, Precedes Gene Family Origin and Expansion in Rattlesnake Venom.
Creator: Margres, Mark J, Bigelow, Alyssa T, Lemmon, Emily Moriarty, Lemmon, Alan R, Rokyta, Darin R
Abstract/Description: Gene duplication is the primary mechanism leading to new genes and phenotypic novelty, but the proximate evolutionary processes underlying gene family origin, maintenance, and expansion are poorly understood. Although sub- and neofunctionalization provide clear long-term advantages, selection does not act with foresight, and unless a redundant gene copy provides an immediate fitness advantage, the copy will most likely be lost. Many models for the evolution of genes immediately following...
Show moreGene duplication is the primary mechanism leading to new genes and phenotypic novelty, but the proximate evolutionary processes underlying gene family origin, maintenance, and expansion are poorly understood. Although sub- and neofunctionalization provide clear long-term advantages, selection does not act with foresight, and unless a redundant gene copy provides an immediate fitness advantage, the copy will most likely be lost. Many models for the evolution of genes immediately following duplication have been proposed, but the robustness and applicability of these models is unclear because of the lack of data at the population level. We used qPCR, protein expression data, genome sequencing, and hybrid enrichment to test three competing models that differ in whether selection favoring the spread of duplicates acts primarily on expression level or sequence diversity for specific toxin-encoding loci in the eastern diamondback rattlesnake (). We sampled 178 individuals and identified significant inter- and intrapopulation variation in copy number, demonstrated that copy number was significantly and positively correlated with protein expression, and found little to no sequence variation across paralogs in all populations. Collectively, these results demonstrate that selection for increased expression, not sequence diversity, was the proximate evolutionary process underlying gene family origin and expansion, providing data needed to resolve the debate over which evolutionary processes govern the fates of gene copies immediately following duplication.
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Date Issued: 2017-07-01
Identifier: FSU_pmch_28476866, 10.1534/genetics.117.202655, PMC5500151, 28476866, 28476866, genetics.117.202655
Format: Citation

Title: A Second Specimen Of Citipati Osmolskae Associated With A Nest Of Eggs From Ukhaa Tolgod, Omnogov Aimag, Mongolia.
Creator: Norell, Mark A., Balanoff, Amy M., Barta, Daniel E., Erickson, Gregory M.
Abstract/Description: Adult dinosaurs preserved attending their nests in brooding positions are among the rarest vertebrate fossils. By far the most common occurrences are members of the dinosaur group Oviraptorosauria. The first finds of these were specimens recovered from the Djadokhta Formation at the Mongolian locality of Ukhaa Tolgod and the Chinese locality of Bayan Mandahu. Since the initial discovery of these specimens, a few more occurrences of nesting oviraptors have been found at other Asian localities....
Show moreAdult dinosaurs preserved attending their nests in brooding positions are among the rarest vertebrate fossils. By far the most common occurrences are members of the dinosaur group Oviraptorosauria. The first finds of these were specimens recovered from the Djadokhta Formation at the Mongolian locality of Ukhaa Tolgod and the Chinese locality of Bayan Mandahu. Since the initial discovery of these specimens, a few more occurrences of nesting oviraptors have been found at other Asian localities. Here we report on a second nesting oviraptorid specimen (IGM 100/1004) sitting in a brooding position atop a nest of eggs from Ukhaa Tolgod, Omnogov, Mongolia. This is a large specimen of the ubiquitous Ukhaa Tolgod taxon Citipati osmolskae. It is approximately 11% larger based on humeral length than the original Ukhaa Tolgod nesting Citipati osmolskae specimen (IGM 100/979), yet eggshell structure and egg arrangement are identical. No evidence for colonial breeding of these animals has been recovered. Reexamination of another "nesting" oviraptorosaur, the holotype of Oviraptor philoceratops (AMNH FARB 6517) indicates that in addition to the numerous partial eggs associated with the original skeleton that originally led to its referral as a protoceratopsian predator, there are the remains of a tiny theropod. This hind limb can be provisionally assigned to Oviraptoridae. It is thus at least possible that some of the eggs associated with the holotype had hatched and the perinates had not left the nest.
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Date Issued: 2018-04-26
Identifier: FSU_libsubv1_wos_000430953800001
Format: Citation

Title: The Seckel Syndrome And Centrosomal Protein Ninein Localizes Asymmetrically To Stem Cell Centrosomes But Is Not Required For Normal Development, Behavior, Or Dna Damage Response In Drosophila.
Creator: Zheng, Yiming, Mennella, Vito, Marks, Steven, Wildonger, Jill, Elnagdi, Esraa, Agard, David, Megraw, Timothy L.
Abstract/Description: Ninein (Nin) is a centrosomal protein whose gene is mutated in Seckel syndrome (SCKL, MIM 210600), an inherited recessive disease that results in primordial dwarfism, cognitive deficiencies, and increased sensitivity to genotoxic stress. Nin regulates neural stem cell self-renewal, interkinetic nuclear migration, and microtubule assembly in mammals. Nin is evolutionarily conserved, yet its role in cell division and development has not been investigated in a model organism. Here we...
Show moreNinein (Nin) is a centrosomal protein whose gene is mutated in Seckel syndrome (SCKL, MIM 210600), an inherited recessive disease that results in primordial dwarfism, cognitive deficiencies, and increased sensitivity to genotoxic stress. Nin regulates neural stem cell self-renewal, interkinetic nuclear migration, and microtubule assembly in mammals. Nin is evolutionarily conserved, yet its role in cell division and development has not been investigated in a model organism. Here we characterize the single Nin orthologue in Drosophila. Drosophila Nin localizes to the periphery of the centrosome but not at centriolar structures as in mammals. However, Nin shares the property of its mammalian orthologue of promoting microtubule assembly. In neural and germline stem cells, Nin localizes asymmetrically to the younger (daughter) centrosome, yet it is not required for the asymmetric division of stem cells. In wing epithelia and muscle, Nin localizes to noncentrosomal microtubule-organizing centers. Surprisingly, loss of nin expression from a nin mutant does not significantly affect embryonic and brain development, fertility, or locomotor performance of mutant flies or their survival upon exposure to DNA-damaging agents. Although it is not essential, our data suggest that Nin plays a supportive role in centrosomal and extracentrosomal microtubule organization and asymmetric stem cell division.
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Date Issued: 2016-06-01
Identifier: FSU_libsubv1_wos_000376777600005, 10.1091/mbc.E15-09-0655
Format: Citation

Title: Screening of Lipid Composition for Scalable Fabrication of Solvent-Free Lipid Microarrays.
Creator: Ghazanfari, Lida, Lenhert, Steven
Abstract/Description: 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.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_29333429, 10.3389/fmats.2016.00055, PMC5761732, 29333429, 29333429
Format: Citation

Title: Role of proteasome-dependent protein degradation in long-term operant memory in Aplysia.
Creator: Lyons, Lisa C, Gardner, Jacob S, Gandour, Catherine E, Krishnan, Harini C
Abstract/Description: We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in Aplysia using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through inhibition of protein synthesis using either anisomycin or rapamycin in conjunction with proteasome inhibition permitted the formation of robust 24 h LTM. Our...
Show moreWe investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in Aplysia using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through inhibition of protein synthesis using either anisomycin or rapamycin in conjunction with proteasome inhibition permitted the formation of robust 24 h LTM. Our studies suggest a primary role for proteasomal activity in facilitation of gene transcription for LTM and raise the possibility that synaptic mechanisms are sufficient to sustain 24 h memory.
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Date Issued: 2016-12-15
Identifier: FSU_pmch_27980077, 10.1101/lm.043794.116, PMC5159658, 27980077, 27980077, 24/1/59
Format: Citation

Title: Role of Olfaction for Eating Behavior.
Creator: Fadool, Debra Ann, Kolling, Louis John
Abstract/Description: 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.
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Date Issued: 2020
Identifier: FSU_libsubv1_scholarship_submission_1602514625_d9f0b4ca
Format: Citation

Title: The Role Of Geography In Adaptive Radiation.
Creator: Schenk, John J., Steppan, Scott J.
Abstract/Description: Although the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for...
Show moreAlthough the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for geographic transitions during adaptive radiations. We reconstructed a time-calibrated phylogeny from four nuclear genes and one mitochondrial gene for 77% of sigmodontine diversity. Historical biogeography was reconstructed among 14 regions, for which we applied a sliding-window approach to estimate regional transition rates through time. We compared these rate patterns and measured whether regions consisted of species that were more phylogenetically related than expected by chance. Following the initial South American colonization around 7 million years ago, multiple expansions from northern regions correlated with a burst of speciation. Subsequently, both diversification and regional transition rates decreased overall and within the majority of regions. Despite high regional transition rates, nearly all regional assemblages were phylogenetically clustered, indicating that within-region diversification was common. We conclude that biogeographic complexity and partitioning played a profound role in the adaptive radiation of the South American Sigmodontinae (Oryzomyalia), the degree to which is determined by the relative scales of spatial variation and dispersal abilities.
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Date Issued: 2018-10-01
Identifier: FSU_libsubv1_wos_000444262900004, 10.1086/699221
Format: Citation

Title: Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction.
Creator: Meyer, Nancy L, Chase, P Bryant
Abstract/Description: Inhibition of striated muscle contraction at resting Ca(2+) depends on the C-terminal half of troponin I (TnI) in thin filaments. Much focus has been on a short inhibitory peptide (Ip) sequence within TnI, but structural studies and identification of disease-associated mutations broadened emphasis to include a larger mobile domain (Md) sequence at the C-terminus of TnI. For Md to function effectively in muscle relaxation, tight mechanical coupling to troponin's core-and thus tropomyosin-is...
Show moreInhibition of striated muscle contraction at resting Ca(2+) depends on the C-terminal half of troponin I (TnI) in thin filaments. Much focus has been on a short inhibitory peptide (Ip) sequence within TnI, but structural studies and identification of disease-associated mutations broadened emphasis to include a larger mobile domain (Md) sequence at the C-terminus of TnI. For Md to function effectively in muscle relaxation, tight mechanical coupling to troponin's core-and thus tropomyosin-is presumably needed. We generated recombinant, human cardiac troponins containing one of two TnI constructs: either an 8-amino acid linker between Md and the rest of troponin (cTnILink8), or an Md deletion (cTnI1-163). Motility assays revealed that Ca(2+)-sensitivity of reconstituted thin filament sliding was markedly increased with cTnILink8 (∼0.9 pCa unit leftward shift of speed-pCa relation compared to WT), and increased further when Md was missing entirely (∼1.4 pCa unit shift). Cardiac Tn's ability to turn off filament sliding at diastolic Ca(2+) was mostly (61%), but not completely eliminated with cTnI1-163. TnI's Md is required for full inhibition of unloaded filament sliding, although other portions of troponin-presumably including Ip-are also necessary. We also confirm that TnI's Md is not responsible for superactivation of actomyosin cycling by troponin.
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Date Issued: 2016-07-01
Identifier: FSU_pmch_26971468, 10.1016/j.abb.2016.03.010, PMC4899117, 26971468, 26971468, S0003-9861(16)30062-5
Format: Citation

Title: RNA helicase Belle/DDX3 regulates transgene expression in Drosophila.
Creator: Lo, Pang-Kuo, Huang, Yi-Chun, Poulton, John S, Leake, Nicholas, Palmer, William H, Vera, Daniel, Xie, Gengqiang, Klusza, Stephen, Deng, Wu-Min
Abstract/Description: Belle (Bel), the Drosophila homolog of the yeast DEAD-box RNA helicase DED1 and human DDX3, has been shown to be required for oogenesis and female fertility. Here we report a novel role of Bel in regulating the expression of transgenes. Abrogation of Bel by mutations or RNAi induces silencing of a variety of P-element-derived transgenes. This silencing effect depends on downregulation of their RNA levels. Our genetic studies have revealed that the RNA helicase Spindle-E (Spn-E), a nuage RNA...
Show moreBelle (Bel), the Drosophila homolog of the yeast DEAD-box RNA helicase DED1 and human DDX3, has been shown to be required for oogenesis and female fertility. Here we report a novel role of Bel in regulating the expression of transgenes. Abrogation of Bel by mutations or RNAi induces silencing of a variety of P-element-derived transgenes. This silencing effect depends on downregulation of their RNA levels. Our genetic studies have revealed that the RNA helicase Spindle-E (Spn-E), a nuage RNA helicase that plays a crucial role in regulating RNA processing and PIWI-interacting RNA (piRNA) biogenesis in germline cells, is required for loss-of-bel-induced transgene silencing. Conversely, Bel abrogation alleviates the nuage-protein mislocalization phenotype in spn-E mutants, suggesting a competitive relationship between these two RNA helicases. Additionally, disruption of the chromatin remodeling factor Mod(mdg4) or the microRNA biogenesis enzyme Dicer-1 (Dcr-1) also alleviates the transgene-silencing phenotypes in bel mutants, suggesting the involvement of chromatin remodeling and microRNA biogenesis in loss-of-bel-induced transgene silencing. Finally we show that genetic inhibition of Bel function leads to de novo generation of piRNAs from the transgene region inserted in the genome, suggesting a potential piRNA-dependent mechanism that may mediate transgene silencing as Bel function is inhibited.
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Date Issued: 2016-04-01
Identifier: FSU_pmch_26900887, 10.1016/j.ydbio.2016.02.014, PMC4814335, 26900887, 26900887, S0012-1606(15)30107-X
Format: Citation

Title: Review: Plant G-quadruplex (G4) motifs in DNA and RNA; abundant, intriguing sequences of unknown function.
Creator: Bass, Hank W, Griffin, Brianna D
Abstract/Description: DNA sequences capable of forming G-quadruplex (G4) structures can be predicted and mapped in plant genomes using computerized pattern search programs. Non-telomeric G4 motifs have recently been found to number in the thousands across many plant species and enriched around gene promoters, prompting speculation that they may represent a newly uncovered and ubiquitous family of cis-acting elements. Comparative analysis shows that monocots exhibit five to ten times higher G4 motif density than...
Show moreDNA sequences capable of forming G-quadruplex (G4) structures can be predicted and mapped in plant genomes using computerized pattern search programs. Non-telomeric G4 motifs have recently been found to number in the thousands across many plant species and enriched around gene promoters, prompting speculation that they may represent a newly uncovered and ubiquitous family of cis-acting elements. Comparative analysis shows that monocots exhibit five to ten times higher G4 motif density than eudicots, but the significance of this difference has not been determined. The vast scale and complexity of G4 functions, actual or theoretical, are reviewed in relation to the multiple modes of action and myriad genetic functions for which G4s have been implicated in DNA and RNA. Future experimental strategies and opportunities include identifying plant G4-interactomes, resolving the structures of G4s with and without their binding partners, and defining molecular mechanisms through reporter gene, genetic, or genome editing approaches. Given the global importance of plants for food, clothing, medicine, and energy, together with the potential role of G4 motifs as a widely conserved set of DNA sequences that could coordinate gene regulation, future plant G4 research holds great potential for use in plant improvement strategies.
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Date Issued: 2018-02-08
Identifier: FSU_libsubv1_scholarship_submission_1518188170_bdd4f8ba, 10.1016/j.plantsci.2018.01.011
Format: Citation

Program in Neuroscience (19)	+ -
Center for Genomics and Personalized Medicine (13)	+ -
Institute of Molecular Biophysics (13)	+ -
Department of Scientific Computing (10)	+ -
National High Magnetic Field Laboratory (9)	+ -

Department of Statistics (5)	+ -
Department of Biomedical Sciences (4)	+ -
Department of Chemistry and Biochemistry (3)	+ -
Center for Brain Repair (2)	+ -
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College of Medicine (1)	+ -
Department of Computer Science (1)	+ -
Department of Physics (1)	+ -
Department of Psychology (1)	+ -

Animals (71)	+ -
Humans (39)	+ -
Mice (20)	+ -
Female (17)	+ -
Male (15)	+ -

Evolution, Molecular (9)	+ -
Protein Binding (9)	+ -
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Nuclear Proteins/metabolism (8)	+ -
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Cell Line (7)	+ -
Time Factors (7)	+ -
Biological Evolution (6)	+ -
Drosophila Proteins/metabolism (6)	+ -
Nuclear Proteins/genetics (6)	+ -
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Signal Transduction (6)	+ -
Transcription Factors/metabolism (6)	+ -
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Cell Proliferation (5)	+ -
Cells, Cultured (5)	+ -
Cryoelectron Microscopy (5)	+ -
Drosophila Proteins/genetics (5)	+ -
Genome (5)	+ -
HEK293 Cells (5)	+ -
Mice, Inbred C57BL (5)	+ -
Mice, Knockout (5)	+ -
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Sequence Analysis, DNA (5)	+ -

text (244)	+ -
journal article (205)	+ -
book part (1)	+ -

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