Search results

Title: Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in .
Creator: Krishnan, Harini C, Gandour, Catherine E, Ramos, Joshua L, Wrinkle, Mariah C, Sanchez-Pacheco, Joseph J, Lyons, Lisa C
Abstract/Description: Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context...
Show moreInsufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish as an effective model system for studying the interactions between sleep and memory formation.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27748243, 10.5665/sleep.6320, PMC5103805, 27748243, 27748243, sp-00313-16
Format: Citation

Title: Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities..
Creator: Ming, Guo-Li, Tang, Hengli, Song, Hongjun
Abstract/Description: The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological...
Show moreThe re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing. Here we review the remarkable progress in stem cell-based ZIKV research and discuss current challenges and future opportunities.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27912090, 10.1016/j.stem.2016.11.014, PMC5218815, 27912090, 27912090, S1934-5909(16)30415-5
Format: Citation

Title: Advancing Behavioural Genomics By Considering Timescale.
Creator: Rittschof, Clare C., Hughes, Kimberly A.
Abstract/Description: Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain...
Show moreAnimal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early life social trauma to understanding the evolution of trait plasticity.
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Date Issued: 2018-02-12
Identifier: FSU_libsubv1_wos_000424747100001, 10.1038/s41467-018-02971-0
Format: Citation

Title: Advancing behavioural genomics by considering timescale.
Creator: Rittschof, Clare C, Hughes, Kimberly A
Abstract/Description: Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain...
Show moreAnimal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early life social trauma to understanding the evolution of trait plasticity.
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Date Issued: 2018-02-12
Identifier: FSU_pmch_29434301, 10.1038/s41467-018-02971-0, PMC5809431, 29434301, 29434301, 10.1038/s41467-018-02971-0
Format: Citation

Title: Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster.
Creator: De Nobrega, Aliza K, Mellers, Alana P, Lyons, Lisa C
Abstract/Description: Alcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens....
Show moreAlcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens. Decreased circadian modulation is correlated with significantly greater alcohol sensitivity during the subjective day. The circadian clock modulates alcohol-induced mortality in younger flies with increased mortality following alcohol exposure at night. Older flies exhibit significantly longer recovery times following alcohol-induced sedation and increased mortality following binge-like or chronic alcohol exposure. Flies rendered arrhythmic either genetically or environmentally exhibit significantly increased alcohol sensitivity, longer recovery times and increased mortality. We hypothesize that the circadian clock phase specifically buffers behavioral and cellular alcohol sensitivity with this protection diminishing as the circadian clock weakens with age.
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Date Issued: 2017-10-15
Identifier: FSU_pmch_28750752, 10.1016/j.exger.2017.07.014, PMC6158789, 28750752, 28750752, S0531-5565(17)30055-4
Format: Citation

Title: AIM2 inflammasome activation and regulation: A structural perspective..
Creator: Wang, Bing, Yin, Qian
Abstract/Description: Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple...
Show moreAbsent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes. In this review, we track the AIM2 inflammasome activation process step by step, using high-resolution structures to illustrate the overall architecture of AIM2 inflammasome and its assembly and regulatory mechanisms.
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Date Issued: 2017-12-01
Identifier: FSU_pmch_28813641, 10.1016/j.jsb.2017.08.001, PMC5733693, 28813641, 28813641, S1047-8477(17)30132-6
Format: Citation

Title: Allele-specific Control Of Replication Timing And Genome Organization During Development.
Creator: Rivera-Mulia, Juan Carlos, Dimond, Andrew, Vera, Daniel, Trevilla-Garcia, Claudia, Sasaki, Takayo, Zimmerman, Jared, Dupont, Catherine, Gribnau, Joost, Fraser, Peter, Gilbert,...
Show moreRivera-Mulia, Juan Carlos, Dimond, Andrew, Vera, Daniel, Trevilla-Garcia, Claudia, Sasaki, Takayo, Zimmerman, Jared, Dupont, Catherine, Gribnau, Joost, Fraser, Peter, Gilbert, David M.
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Abstract/Description: DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus x castaneus mouse crosses and exploited the high single-nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C),...
Show moreDNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus x castaneus mouse crosses and exploited the high single-nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq), and chromatin accessibility (ATAC-seq). We also present HARP, a new computational tool for sorting SNPs in phased genomes to efficiently measure allele-specific genome-wide data. Analysis of six different hybrid mESC clones with different genomes (C57BL/ 6,129 /sv, and CAST/ Ei), parental configurations, and gender revealed significant RT asynchrony between alleles across similar to 12% of the autosomal genome linked to subspecies genomes but not to parental origin, growth conditions, or gender. RT asynchrony in mESCs strongly correlated with changes in Hi-C compartments between alleles but not as strongly with SNP density, gene expression, imprinting, or chromatin accessibility. We then tracked mESC RT asynchronous regions during development by analyzing differentiated cell types, including extraembryonic endoderm stem (XEN) cells, four male and female primary mouse embryonic fibroblasts (MEFs), and neural precursor cells (NPCs) differentiated in vitro from mESCs with opposite parental configurations. We found that RT asynchrony and allelic discordance in Hi-C compartments seen in mESCs were largely lost in all differentiated cell types, accompanied by novel sites of allelic asynchrony at a considerably smaller proportion of the genome, suggesting that genome organization of homologs converges to similar folding patterns during cell fate commitment.
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Date Issued: 2018-06-01
Identifier: FSU_libsubv1_wos_000436084800005, 10.1101/gr.232561.117
Format: Citation

Title: Anatomy and osteohistology of the basal hadrosaurid dinosaur Eotrachodon from the uppermost Santonian (Cretaceous) of southern Appalachia.
Creator: Prieto-Márquez, Albert, Erickson, Gregory M, Ebersole, Jun A
Abstract/Description: The cranial and postcranial anatomy of the basal hadrosaurid dinosaur Eotrachodon orientalis, from the uppermost Santonian of southern Appalachia (southeastern U.S.A.), is described in detail. This animal is the only known pre-Campanian non-lambeosaurine hadrosaurid, and the most complete hadrosauroid known from Appalachia. E. orientalis possesses a mosaic of plesiomorphic and derived characters in the context of Hadrosauroidea. Characters shared with basal hadrosauroids include a short and...
Show moreThe cranial and postcranial anatomy of the basal hadrosaurid dinosaur Eotrachodon orientalis, from the uppermost Santonian of southern Appalachia (southeastern U.S.A.), is described in detail. This animal is the only known pre-Campanian non-lambeosaurine hadrosaurid, and the most complete hadrosauroid known from Appalachia. E. orientalis possesses a mosaic of plesiomorphic and derived characters in the context of Hadrosauroidea. Characters shared with basal hadrosauroids include a short and sloping maxillary ectopterygoid shelf, caudally prominent maxillary jugal process, one functional tooth per alveolus on the maxillary occlusal plane, a jugal rostral process with a shallow caudodorsal margin and medioventrally facing articular facet, a vertical dentary coronoid process with a poorly expanded apex, and tooth crowns with accessory ridges. Derived characters shared with other hadrosaurids include a circumnarial depression compartmented into three fossae (as in brachylophosaurins and Edmontosaurus), a thin everted premaxillary oral margin (as in Gryposaurus, Prosaurolophus, and Saurolophus), and a maxilla with a deep and rostrocaudally extensive rostrodorsal region with a steeply sloping premaxillary margin (as in Gryposaurus). Eotrachodon orientalis differs primarily from the other hadrosauroid from the Mooreville Chalk of Alabama, Lophorhothon atopus, in having a slender and crestless nasal whose caudodorsal margin is not invaded by the circumnarial depression. Hadrosaurus foulkii, the only other known hadrosaurid from Appalachia, is distinct from E. orientalis in having dentary teeth lacking accessory ridges and a dorsally curved shaft of the ischium. A histological section of the tibia of the E. orientalis holotype (MSC 7949) suggests that this individual was actively growing at the time of death and, thus, had the potential to become a larger animal later in development.
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Date Issued: 2016-04-14
Identifier: FSU_pmch_27114863, 10.7717/peerj.1872, PMC4841272, 27114863, 27114863, 1872
Format: Citation

Title: Anchored Enrichment Dataset For True Flies (order Diptera) Reveals Insights Into The Phylogeny Of Flower Flies (family Syrphidae).
Creator: Young, Andrew Donovan, Lemmon, Alan R., Skevington, Jeffrey H., Mengual, Ximo, Stahls, Gunilla, Reemer, Menno, Jordaens, Kurt, Kelso, Scott, Lemmon, Emily Moriarty, Hauser,...
Show moreYoung, Andrew Donovan, Lemmon, Alan R., Skevington, Jeffrey H., Mengual, Ximo, Stahls, Gunilla, Reemer, Menno, Jordaens, Kurt, Kelso, Scott, Lemmon, Emily Moriarty, Hauser, Martin, De Meyer, Marc, Misof, Bernhard, Wiegmann, Brian M.
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Abstract/Description: Background: Anchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly...
Show moreBackground: Anchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly diverse nature, importance as pollinators, and historical instability with regard to subfamilial and tribal classification, Syrphidae (flower flies or hoverflies) are an ideal candidate for anchored hybrid enrichment-based phylogenetics, especially since recent molecular phylogenies of the syrphids using only a few markers have resulted in highly unresolved topologies. Over 6200 syrphids are currently known and uncovering their phylogeny will help us to understand how these species have diversified, providing insight into an array of ecological processes, from the development of adult mimicry, the origin of adult migration, to pollination patterns and the evolution of larval resource utilization. Results: We present the first use of anchored hybrid enrichment in insect phylogenetics on a dataset containing 30 flower fly species from across all four subfamilies and 11 tribes out of 15. To produce a phylogenetic hypothesis, 559 loci were sampled to produce a final dataset containing 217,702 sites. We recovered a well resolved topology with bootstrap support values that were almost universally >95 %. The subfamily Eristalinae is recovered as paraphyletic, with the strongest support for this hypothesis to date. The ant predators in the Microdontinae are sister to all other syrphids. Syrphinae and Pipizinae are monophyletic and sister to each other. Larval predation on soft-bodied hemipterans evolved only once in this family. Conclusions: Anchored hybrid enrichment was successful in producing a robustly supported phylogenetic hypothesis for the syrphids. Subfamilial reconstruction is concordant with recent phylogenetic hypotheses, but with much higher support values. With the newly designed probe kit this analysis could be rapidly expanded with further sampling, opening the door to more comprehensive analyses targeting problem areas in syrphid phylogenetics and ecology.
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Date Issued: 2016-06-29
Identifier: FSU_libsubv1_wos_000378675500003, 10.1186/s12862-016-0714-0
Format: Citation

Title: Anchored enrichment dataset for true flies (order Diptera) reveals insights into the phylogeny of flower flies (family Syrphidae).
Creator: Young, Andrew Donovan, Lemmon, Alan R, Skevington, Jeffrey H, Mengual, Ximo, Ståhls, Gunilla, Reemer, Menno, Jordaens, Kurt, Kelso, Scott, Lemmon, Emily Moriarty, Hauser, Martin...
Show moreYoung, Andrew Donovan, Lemmon, Alan R, Skevington, Jeffrey H, Mengual, Ximo, Ståhls, Gunilla, Reemer, Menno, Jordaens, Kurt, Kelso, Scott, Lemmon, Emily Moriarty, Hauser, Martin, De Meyer, Marc, Misof, Bernhard, Wiegmann, Brian M
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Abstract/Description: Anchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly diverse...
Show moreAnchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly diverse nature, importance as pollinators, and historical instability with regard to subfamilial and tribal classification, Syrphidae (flower flies or hoverflies) are an ideal candidate for anchored hybrid enrichment-based phylogenetics, especially since recent molecular phylogenies of the syrphids using only a few markers have resulted in highly unresolved topologies. Over 6200 syrphids are currently known and uncovering their phylogeny will help us to understand how these species have diversified, providing insight into an array of ecological processes, from the development of adult mimicry, the origin of adult migration, to pollination patterns and the evolution of larval resource utilization. We present the first use of anchored hybrid enrichment in insect phylogenetics on a dataset containing 30 flower fly species from across all four subfamilies and 11 tribes out of 15. To produce a phylogenetic hypothesis, 559 loci were sampled to produce a final dataset containing 217,702 sites. We recovered a well resolved topology with bootstrap support values that were almost universally >95 %. The subfamily Eristalinae is recovered as paraphyletic, with the strongest support for this hypothesis to date. The ant predators in the Microdontinae are sister to all other syrphids. Syrphinae and Pipizinae are monophyletic and sister to each other. Larval predation on soft-bodied hemipterans evolved only once in this family. Anchored hybrid enrichment was successful in producing a robustly supported phylogenetic hypothesis for the syrphids. Subfamilial reconstruction is concordant with recent phylogenetic hypotheses, but with much higher support values. With the newly designed probe kit this analysis could be rapidly expanded with further sampling, opening the door to more comprehensive analyses targeting problem areas in syrphid phylogenetics and ecology.
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Date Issued: 2016-06-29
Identifier: FSU_pmch_27357120, 10.1186/s12862-016-0714-0, PMC4928351, 27357120, 27357120, 10.1186/s12862-016-0714-0
Format: Citation

Title: Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.
Creator: Cheng, Zhijian, Zhu, Wen, Cao, Kai, Wu, Fei, Li, Jin, Wang, Guoyu, Li, Haopen, Lu, Ming, Ren, Yi, He, Xijing
Abstract/Description: Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil...
Show moreNeural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor- (TNF-), interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-, IL-1, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF- and IL-1 by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-, IL-1, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.
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Date Issued: 2016-09
Identifier: FSU_libsubv1_wos_000385525500008, 10.3390/ijms17091380
Format: Citation

Title: Applying systems-level spectral imaging and analysis to reveal the organelle interactome.
Creator: Valm, Alex M, Cohen, Sarah, Legant, Wesley R, Melunis, Justin, Hershberg, Uri, Wait, Eric, Cohen, Andrew R, Davidson, Michael W, Betzig, Eric, Lippincott-Schwartz, Jennifer
Abstract/Description: The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts...
Show moreThe organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions. However, the spatial and temporal organization of organelles within the cell remains poorly characterized, as fluorescence imaging approaches are limited in the number of different labels that can be distinguished in a single image. Here we present a systems-level analysis of the organelle interactome using a multispectral image acquisition method that overcomes the challenge of spectral overlap in the fluorescent protein palette. We used confocal and lattice light sheet instrumentation and an imaging informatics pipeline of five steps to achieve mapping of organelle numbers, volumes, speeds, positions and dynamic inter-organelle contacts in live cells from a monkey fibroblast cell line. We describe the frequency and locality of two-, three-, four- and five-way interactions among six different membrane-bound organelles (endoplasmic reticulum, Golgi, lysosome, peroxisome, mitochondria and lipid droplet) and show how these relationships change over time. We demonstrate that each organelle has a characteristic distribution and dispersion pattern in three-dimensional space and that there is a reproducible pattern of contacts among the six organelles, that is affected by microtubule and cell nutrient status. These live-cell confocal and lattice light sheet spectral imaging approaches are applicable to any cell system expressing multiple fluorescent probes, whether in normal conditions or when cells are exposed to disturbances such as drugs, pathogens or stress. This methodology thus offers a powerful descriptive tool and can be used to develop hypotheses about cellular organization and dynamics.
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Date Issued: 2017-06-01
Identifier: FSU_pmch_28538724, 10.1038/nature22369, PMC5536967, 28538724, 28538724, nature22369
Format: Citation

Title: Atomic Resolution Structures Of Human Bufaviruses Determined By Cryo-electron Microscopy.
Creator: Ilyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Vaisanen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J. Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Soderlund...
Show moreIlyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Vaisanen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J. Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Soderlund-Venermo, Maria, Agbandje-McKenna, Mavis
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Abstract/Description: Bufavirus strain 1 (BuV1), a member of the Protoparvovirus genus of the Parvoviridae, was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by...
Show moreBufavirus strain 1 (BuV1), a member of the Protoparvovirus genus of the Parvoviridae, was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and image reconstruction to 2.84, 3.79, and 3.25 angstrom, respectively. The BuVs, 65-73% identical in amino acid sequence, conserve the major viral protein, VP2, structure and general capsid surface features of parvoviruses. These include a core -barrel (B-I), -helix A, and large surface loops inserted between these elements in VP2. The capsid contains depressions at the icosahedral 2-fold and around the 5-fold axes, and has three separated protrusions surrounding the 3-fold axes. Structure comparison among the BuVs and to available parvovirus structures revealed capsid surface variations and capsid 3-fold protrusions that depart from the single pinwheel arrangement of the animal protoparvoviruses. These structures provide a platform to begin the molecular characterization of these potentially pathogenic viruses.
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Date Issued: 2018-01
Identifier: FSU_libsubv1_wos_000424414900022, 10.3390/v10010022
Format: Citation

Title: Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy.
Creator: Ilyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Väisänen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Söderlund...
Show moreIlyas, Maria, Mietzsch, Mario, Kailasan, Shweta, Väisänen, Elina, Luo, Mengxiao, Chipman, Paul, Smith, J Kennon, Kurian, Justin, Sousa, Duncan, McKenna, Robert, Söderlund-Venermo, Maria, Agbandje-McKenna, Mavis
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Abstract/Description: Bufavirus strain 1 (BuV1), a member of the genus of the , was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and...
Show moreBufavirus strain 1 (BuV1), a member of the genus of the , was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and image reconstruction to 2.84, 3.79, and 3.25 Å, respectively. The BuVs, 65-73% identical in amino acid sequence, conserve the major viral protein, VP2, structure and general capsid surface features of parvoviruses. These include a core β-barrel (βB-βI), α-helix A, and large surface loops inserted between these elements in VP2. The capsid contains depressions at the icosahedral 2-fold and around the 5-fold axes, and has three separated protrusions surrounding the 3-fold axes. Structure comparison among the BuVs and to available parvovirus structures revealed capsid surface variations and capsid 3-fold protrusions that depart from the single pinwheel arrangement of the animal protoparvoviruses. These structures provide a platform to begin the molecular characterization of these potentially pathogenic viruses.
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Date Issued: 2018-01-04
Identifier: FSU_pmch_29300333, 10.3390/v10010022, PMC5795435, 29300333, 29300333, v10010022
Format: Citation

Title: Automatic stage identification of Drosophila egg chamber based on DAPI images.
Creator: Jia, Dongyu, Xu, Qiuping, Xie, Qian, Mio, Washington, Deng, Wu-Min
Abstract/Description: The Drosophila egg chamber, whose development is divided into 14 stages, is a well-established model for developmental biology. However, visual stage determination can be a tedious, subjective and time-consuming task prone to errors. Our study presents an objective, reliable and repeatable automated method for quantifying cell features and classifying egg chamber stages based on DAPI images. The proposed approach is composed of two steps: 1) a feature extraction step and 2) a statistical...
Show moreThe Drosophila egg chamber, whose development is divided into 14 stages, is a well-established model for developmental biology. However, visual stage determination can be a tedious, subjective and time-consuming task prone to errors. Our study presents an objective, reliable and repeatable automated method for quantifying cell features and classifying egg chamber stages based on DAPI images. The proposed approach is composed of two steps: 1) a feature extraction step and 2) a statistical modeling step. The egg chamber features used are egg chamber size, oocyte size, egg chamber ratio and distribution of follicle cells. Methods for determining the on-site of the polytene stage and centripetal migration are also discussed. The statistical model uses linear and ordinal regression to explore the stage-feature relationships and classify egg chamber stages. Combined with machine learning, our method has great potential to enable discovery of hidden developmental mechanisms.
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Date Issued: 2016-01-06
Identifier: FSU_libsubv1_wos_000368658200001, 10.1038/srep18850
Format: Citation

Title: Automatic stage identification of Drosophila egg chamber based on DAPI images.
Creator: Jia, Dongyu, Xu, Qiuping, Xie, Qian, Mio, Washington, Deng, Wu-Min
Abstract/Description: The Drosophila egg chamber, whose development is divided into 14 stages, is a well-established model for developmental biology. However, visual stage determination can be a tedious, subjective and time-consuming task prone to errors. Our study presents an objective, reliable and repeatable automated method for quantifying cell features and classifying egg chamber stages based on DAPI images. The proposed approach is composed of two steps: 1) a feature extraction step and 2) a statistical...
Show moreThe Drosophila egg chamber, whose development is divided into 14 stages, is a well-established model for developmental biology. However, visual stage determination can be a tedious, subjective and time-consuming task prone to errors. Our study presents an objective, reliable and repeatable automated method for quantifying cell features and classifying egg chamber stages based on DAPI images. The proposed approach is composed of two steps: 1) a feature extraction step and 2) a statistical modeling step. The egg chamber features used are egg chamber size, oocyte size, egg chamber ratio and distribution of follicle cells. Methods for determining the on-site of the polytene stage and centripetal migration are also discussed. The statistical model uses linear and ordinal regression to explore the stage-feature relationships and classify egg chamber stages. Combined with machine learning, our method has great potential to enable discovery of hidden developmental mechanisms.
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Date Issued: 2016-01-06
Identifier: FSU_pmch_26732176, 10.1038/srep18850, PMC4702167, 26732176, 26732176, srep18850
Format: Citation

Title: Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.
Creator: Bell, Genevieve A, Fadool, Debra Ann
Abstract/Description: Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the...
Show moreIntranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.
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Date Issued: 2017-05-15
Identifier: FSU_pmch_28259806, 10.1016/j.physbeh.2017.02.044, PMC5639911, 28259806, 28259806, S0031-9384(16)30820-4
Format: Citation

Title: Bacterial Artificial Chromosomes Establish Replication Timing And Sub-nuclear Compartment De Novo As Extra-chromosomal Vectors.
Creator: Sima, Jiao, Bartlett, Daniel A., Gordon, Molly R., Gilbert, David M.
Abstract/Description: The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of similar to 200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiP-SCs)...
Show moreThe role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of similar to 200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiP-SCs) and established distinct RT patterns. An E-BAC harboring an early replicating chromosomal region replicated early during S phase, while E-BACs derived from RT transition regions (TTRs) and late replicating regions replicated in mid to late S phase. Analysis of E-BAC interactions with cellular chromatin (4C-seq) revealed that the early replicating E-BAC interacted broadly throughout the genome and preferentially with the early replicating compartment of the nucleus. In contrast, mid-to late-replicating E-BACs interacted with more specific late replicating chromosomal segments, some of which were shared between different E-BACs. Together, we describe a versatile system in which to study the structure and function of chromosomal segments that are stably maintained separately from the influence of cellular chromosome context.
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Date Issued: 2018-02-28
Identifier: FSU_libsubv1_wos_000426293300025, 10.1093/nar/gkx1265
Format: Citation

Title: Bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors.
Creator: Sima, Jiao, Bartlett, Daniel A, Gordon, Molly R, Gilbert, David M
Abstract/Description: The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of ∼200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiPSCs) and...
Show moreThe role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of ∼200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiPSCs) and established distinct RT patterns. An E-BAC harboring an early replicating chromosomal region replicated early during S phase, while E-BACs derived from RT transition regions (TTRs) and late replicating regions replicated in mid to late S phase. Analysis of E-BAC interactions with cellular chromatin (4C-seq) revealed that the early replicating E-BAC interacted broadly throughout the genome and preferentially with the early replicating compartment of the nucleus. In contrast, mid- to late-replicating E-BACs interacted with more specific late replicating chromosomal segments, some of which were shared between different E-BACs. Together, we describe a versatile system in which to study the structure and function of chromosomal segments that are stably maintained separately from the influence of cellular chromosome context.
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Date Issued: 2018-02-28
Identifier: FSU_pmch_29294101, 10.1093/nar/gkx1265, PMC5829748, 29294101, 29294101, 4774271
Format: Citation

Title: The Biomechanics Behind Extreme Osteophagy In Tyrannosaurus Rex.
Creator: Gignac, Paul M., Erickson, Gregory M.
Abstract/Description: Most carnivorous mammals can pulverize skeletal elements by generating tooth pressures between occluding teeth that exceed cortical bone shear strength, thereby permitting access to marrow and phosphatic salts. Conversely, carnivorous reptiles have non-occluding dentitions that engender negligible bone damage during feeding. As a result, most reptilian predators can only consume bones in their entirety. Nevertheless, North American tyrannosaurids, including the giant (13 metres [m]) theropod...
Show moreMost carnivorous mammals can pulverize skeletal elements by generating tooth pressures between occluding teeth that exceed cortical bone shear strength, thereby permitting access to marrow and phosphatic salts. Conversely, carnivorous reptiles have non-occluding dentitions that engender negligible bone damage during feeding. As a result, most reptilian predators can only consume bones in their entirety. Nevertheless, North American tyrannosaurids, including the giant (13 metres [m]) theropod dinosaur Tyrannosaurus rex stand out for habitually biting deeply into bones, pulverizing and digesting them. How this mammal-like capacity was possible, absent dental occlusion, is unknown. Here we analyzed T. rex feeding behaviour from trace evidence, estimated bite forces and tooth pressures, and studied tooth-bone contacts to provide the answer. We show that bone pulverization was made possible through a combination of: (1) prodigious bite forces (8,526-34,522 newtons [N]) and tooth pressures (718-2,974 megapascals [MPa]) promoting crack propagation in bones, (2) tooth form and dental arcade configurations that concentrated shear stresses, and (3) repetitive, localized biting. Collectively, these capacities and behaviors allowed T. rex to finely fragment bones and more fully exploit large dinosaur carcasses for sustenance relative to competing carnivores.
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Date Issued: 2017-05-17
Identifier: FSU_libsubv1_wos_000401511100019, 10.1038/s41598-017-02161-w
Format: Citation

Title: Bioturbation By The Fungus-gardening Ant, Trachymyrmex Septentrionalis.
Creator: Tschinkel, Walter R., Seal, Jon N.
Abstract/Description: Soil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of...
Show moreSoil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of different colored sand. The amount of each color of sand deposited on the surface was determined from April to November 2015. In November, colonies were excavated and the color and amount of sand deposited below ground (mostly as backfill in chambers) was determined. Extrapolated to one ha, T. septentrionalis deposited 800 kg of sand per annum on the surface, and an additional 200 kg (17% of the total excavated) below ground. On average, this mixes 1.3% of the sand from other layers within the top meter of soil per millennium, but this mixing is unlikely to be homogeneous, and probably occurs as "hotspots" in both horizontal and vertical space. Such mixing is discussed as a challenge to sediment dating by optically stimulated luminescence (OSL).
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Date Issued: 2016-07-08
Identifier: FSU_libsubv1_wos_000380005400162, 10.1371/journal.pone.0158920
Format: Citation

Title: Bioturbation by the Fungus-Gardening Ant, Trachymyrmex septentrionalis.
Creator: Tschinkel, Walter R, Seal, Jon N
Abstract/Description: Soil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of...
Show moreSoil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of different colored sand. The amount of each color of sand deposited on the surface was determined from April to November 2015. In November, colonies were excavated and the color and amount of sand deposited below ground (mostly as backfill in chambers) was determined. Extrapolated to one ha, T. septentrionalis deposited 800 kg of sand per annum on the surface, and an additional 200 kg (17% of the total excavated) below ground. On average, this mixes 1.3% of the sand from other layers within the top meter of soil per millennium, but this mixing is unlikely to be homogeneous, and probably occurs as "hotspots" in both horizontal and vertical space. Such mixing is discussed as a challenge to sediment dating by optically stimulated luminescence (OSL).
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Date Issued: 2016-07-08
Identifier: FSU_pmch_27391485, 10.1371/journal.pone.0158920, PMC4938500, 27391485, 27391485, PONE-D-16-06201
Format: Citation

Title: Bottom-up And Top-down Controls On Coral Reef Sponges: Disentangling Within-habitat And Between-habitat Processes.
Creator: Wulff, Janie
Abstract/Description: Polarized debates about top-down vs. bottom-up control have given way to more nuanced understanding of control by both resources and consumers in many systems, but coral reef sponges have recently been asserted to differ from other groups in being controlled exclusively top-down. This assertion has been countered by reports of exclusively bottom-up control, with both conclusions based on studies of the same species. Accelerating deterioration of coral reefs motivates knowing the contexts in...
Show morePolarized debates about top-down vs. bottom-up control have given way to more nuanced understanding of control by both resources and consumers in many systems, but coral reef sponges have recently been asserted to differ from other groups in being controlled exclusively top-down. This assertion has been countered by reports of exclusively bottom-up control, with both conclusions based on studies of the same species. Accelerating deterioration of coral reefs motivates knowing the contexts in which either consumers or nutrients or both control key ecosystem role players like sponges. Accordingly, genotype-and size-controlled individuals of 12 common Caribbean reef sponge species were transplanted, in the field, into five circumstances differing in predators, competitors, and the picoplankton consumed by sponges. Growth and survival of the experimental transplants for periods of 1-9 yr revealed context-dependent control of sponges. Primary control of growth was bottom-up, with more picoplankton resulting in consistent and sustained higher growth rates for all 12 of these ecologically and phylogenetically diverse species. Top-down control was not detected within-habitat, on the coral reef. However, between-habitat control was by predation and competition, with reef sponges excluded from adjacent seagrass meadows by spongivorous starfish, and excluded from mangrove prop roots by faster-growing mangrove sponges. These results highlight the strong importance of experimental design details that consider behavior idiosyncrasies, sufficiently long time scales, and appropriate division of species into categories. Diametrically opposite results from studies of the same species also illustrate the inherently greater difficulty of detecting bottom-up processes and the importance of distinguishing within-habitat vs. between-habitat patterns and processes.
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Date Issued: 2017-04
Identifier: FSU_libsubv1_wos_000398175200024
Format: Citation

Title: Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.
Creator: Qian, Xuyu, Nguyen, Ha Nam, Song, Mingxi M, Hadiono, Christopher, Ogden, Sarah C, Hammack, Christy, Yao, Bing, Hamersky, Gregory R, Jacob, Fadi, Zhong, Chun, Yoon, Ki-Jun, Jeang...
Show moreQian, Xuyu, Nguyen, Ha Nam, Song, Mingxi M, Hadiono, Christopher, Ogden, Sarah C, Hammack, Christy, Yao, Bing, Hamersky, Gregory R, Jacob, Fadi, Zhong, Chun, Yoon, Ki-Jun, Jeang, William, Lin, Li, Li, Yujing, Thakor, Jai, Berg, Daniel A, Zhang, Ce, Kang, Eunchai, Chickering, Michael, Nauen, David, Ho, Cheng-Ying, Wen, Zhexing, Christian, Kimberly M, Shi, Pei-Yong, Maher, Brady J, Wu, Hao, Jin, Peng, Tang, Hengli, Song, Hongjun, Ming, Guo-Li
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Abstract/Description: Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a...
Show moreCerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our brain-region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.
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Date Issued: 2016-05-19
Identifier: FSU_pmch_27118425, 10.1016/j.cell.2016.04.032, PMC4900885, 27118425, 27118425, S0092-8674(16)30467-6
Format: Citation

Title: A bright cyan-excitable orange fluorescent protein facilitates dual-emission microscopy and enhances bioluminescence imaging in vivo.
Creator: Chu, Jun, Oh, Younghee, Sens, Alex, Ataie, Niloufar, Dana, Hod, Macklin, John J, Laviv, Tal, Welf, Erik S, Dean, Kevin M, Zhang, Feijie, Kim, Benjamin B, Tang, Clement Tran, Hu,...
Show moreChu, Jun, Oh, Younghee, Sens, Alex, Ataie, Niloufar, Dana, Hod, Macklin, John J, Laviv, Tal, Welf, Erik S, Dean, Kevin M, Zhang, Feijie, Kim, Benjamin B, Tang, Clement Tran, Hu, Michelle, Baird, Michelle A, Davidson, Michael W, Kay, Mark A, Fiolka, Reto, Yasuda, Ryohei, Kim, Douglas S, Ng, Ho-Leung, Lin, Michael Z
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Abstract/Description: Orange-red fluorescent proteins (FPs) are widely used in biomedical research for multiplexed epifluorescence microscopy with GFP-based probes, but their different excitation requirements make multiplexing with new advanced microscopy methods difficult. Separately, orange-red FPs are useful for deep-tissue imaging in mammals owing to the relative tissue transmissibility of orange-red light, but their dependence on illumination limits their sensitivity as reporters in deep tissues. Here we...
Show moreOrange-red fluorescent proteins (FPs) are widely used in biomedical research for multiplexed epifluorescence microscopy with GFP-based probes, but their different excitation requirements make multiplexing with new advanced microscopy methods difficult. Separately, orange-red FPs are useful for deep-tissue imaging in mammals owing to the relative tissue transmissibility of orange-red light, but their dependence on illumination limits their sensitivity as reporters in deep tissues. Here we describe CyOFP1, a bright, engineered, orange-red FP that is excitable by cyan light. We show that CyOFP1 enables single-excitation multiplexed imaging with GFP-based probes in single-photon and two-photon microscopy, including time-lapse imaging in light-sheet systems. CyOFP1 also serves as an efficient acceptor for resonance energy transfer from the highly catalytic blue-emitting luciferase NanoLuc. An optimized fusion of CyOFP1 and NanoLuc, called Antares, functions as a highly sensitive bioluminescent reporter in vivo, producing substantially brighter signals from deep tissues than firefly luciferase and other bioluminescent proteins.
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Date Issued: 2016-07-01
Identifier: FSU_pmch_27240196, 10.1038/nbt.3550, PMC4942401, 27240196, 27240196, nbt.3550
Format: Citation

Title: Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.
Creator: Zuo, L-L, Zhang, J, Liu, L-Z, Zhou, Q, Du, S-J, Xin, S-Y, Ning, Z-P, Yang, J, Yu, H-B, Yue, W-X, Wang, J, Zhu, F-X, Li, G-Y, Lu, J-H
Abstract/Description: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in...
Show moreNasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-β downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-β. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.
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Date Issued: 2017-12-22
Identifier: FSU_pmch_29284791, 10.1038/s41389-017-0005-7, PMC5865538, 29284791, 29284791, 10.1038/s41389-017-0005-7
Format: Citation

Title: Cell-cycle dynamics of chromosomal organization at single-cell resolution.
Creator: Nagano, Takashi, Lubling, Yaniv, Várnai, Csilla, Dudley, Carmel, Leung, Wing, Baran, Yael, Mendelson Cohen, Netta, Wingett, Steven, Fraser, Peter, Tanay, Amos
Abstract/Description: Chromosomes in proliferating metazoan cells undergo marked structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures that facilitate chromosome segregation, and decondensed interphase structures that accommodate transcription, gene silencing and DNA replication. Here we use single-cell Hi-C (high-resolution chromosome conformation capture) analysis to study chromosome conformations in thousands of individual cells, and discover a continuum of cis...
Show moreChromosomes in proliferating metazoan cells undergo marked structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures that facilitate chromosome segregation, and decondensed interphase structures that accommodate transcription, gene silencing and DNA replication. Here we use single-cell Hi-C (high-resolution chromosome conformation capture) analysis to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological-associated domains (TADs), contact insulation and long-range loops, all defined by bulk Hi-C maps, are governed by distinct cell-cycle dynamics. In particular, DNA replication correlates with a build-up of compartments and a reduction in TAD insulation, while loops are generally stable from G1 to S and G2 phase. Whole-genome three-dimensional structural models reveal a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data therefore allow re-interpretation of chromosome conformation maps through the prism of the cell cycle.
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Date Issued: 2017-07-05
Identifier: FSU_pmch_28682332, 10.1038/nature23001, PMC5567812, 28682332, 28682332, nature23001
Format: Citation

Title: Challenges And Guidelines Toward 4d Nucleome Data And Model Standards.
Creator: Marti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi,...
Show moreMarti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi, Mario, Nollmann, Marcelo, Orozco, Modesto, Pombo, Ana, Torres-Padilla, Maria-Elena
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Abstract/Description: Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its...
Show moreDue to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate. However, the rapid evolution of methods and the increasing complexity of data can result in ambiguity and reproducibility challenges, which may hamper the progress of this field. Here, we describe such challenges ahead and provide guidelines to think about strategies for shared standardized validation of experimental 4D nucleome data sets and models.
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Date Issued: 2018-10-01
Identifier: FSU_libsubv1_wos_000446047000006, 10.1038/s41588-018-0236-3
Format: Citation

Title: Characterization Of The Icce Repea In Mammals Reveals An Evolutionary Relationship With The Dxz4 Macrosatellite Through Conserved Ctcf Binding Motifs.
Creator: Westervelt, Natalia, Chadwick, Brian P.
Abstract/Description: Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA...
Show moreAppreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.
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Date Issued: 2018-09-01
Identifier: FSU_libsubv1_wos_000446102700004, 10.1093/gbe/evy176
Format: Citation

Title: Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs.
Creator: Westervelt, Natalia, Chadwick, Brian P
Abstract/Description: Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA...
Show moreAppreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.
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Date Issued: 2018-09-01
Identifier: FSU_pmch_30102341, 10.1093/gbe/evy176, PMC6125249, 30102341, 30102341, 5068191
Format: Citation

Title: Chromatin structure profile data from DNS-seq: Differential nuclease sensitivity mapping of four reference tissues of B73 maize ( L)..
Creator: Turpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H,...
Show moreTurpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H, Zhang, Jinfeng, Bass, Hank W
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Abstract/Description: Presented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference...
Show morePresented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference profiles. The data repository for the sequence data is the NCBI SRA, BioProject Accession 8.
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Date Issued: 2018-08-10
Identifier: FSU_pmch_30175199, 10.1016/j.dib.2018.08.015, PMC6117953, 30175199, 30175199, S2352-3409(18)30865-5
Format: Citation

Title: Cleavage Of The Sun-domain Protein Mps3 At Its N-terminus Regulates Centrosome Disjunction In Budding Yeast Meiosis.
Creator: Li, Ping, Jin, Hui, Koch, Bailey A., Abblett, Rebecca L., Han, Xuemei, Yates, John R., Yu, Hong-Guo
Abstract/Description: Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single...
Show moreCentrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized Nterminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery.
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Date Issued: 2017-06
Identifier: FSU_libsubv1_wos_000404512600017, 10.1371/journal.pgen.1006830
Format: Citation

Title: Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis.
Creator: Li, Ping, Jin, Hui, Koch, Bailey A, Abblett, Rebecca L, Han, Xuemei, Yates, John R, Yu, Hong-Guo
Abstract/Description: Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single...
Show moreCentrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery.
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Date Issued: 2017-06-13
Identifier: FSU_pmch_28609436, 10.1371/journal.pgen.1006830, PMC5487077, 28609436, 28609436, PGENETICS-D-17-00030
Format: Citation

Title: Coevolution Leaves A Weak Signal On Ecological Networks.
Creator: Ponisio, Lauren C., M'Gonigle, Leithen K.
Abstract/Description: One of the major challenges in evolutionary ecology is to understand how coevolution shapes species interaction networks. Important topological properties of networks such as nestedness and modularity are thought to be affected by coevolution. However, there has been no test whether coevolution does, in fact, lead to predictable network structure. Here, we investigate the structure of simulated bipartite networks generated under different modes of coevolution. We ask whether evolutionary...
Show moreOne of the major challenges in evolutionary ecology is to understand how coevolution shapes species interaction networks. Important topological properties of networks such as nestedness and modularity are thought to be affected by coevolution. However, there has been no test whether coevolution does, in fact, lead to predictable network structure. Here, we investigate the structure of simulated bipartite networks generated under different modes of coevolution. We ask whether evolutionary processes influence network structure and, furthermore, whether any emergent trends are influenced by the strength or "intimacy" of the species interactions. We find that coevolution leaves a weak and variable signal on network topology, particularly nestedness and modularity, which was not strongly affected by the intimacy of interactions. Our findings indicate that network metrics, on their own, should not be used to make inferences about processes underlying the evolutionary history of communities. Instead, a more holistic approach that combines network approaches with traditional phylogenetic and biogeographic reconstructions is needed.
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Date Issued: 2017-04
Identifier: FSU_libsubv1_wos_000400985300044, 10.1002/ecs2.1798
Format: Citation

Title: Collective Dispersal Leads To Variance In Fitness And Maintains Offspring Size Variation Within Marine Populations.
Creator: Burgess, Scott C., Snyder, Robin E., Rountree, Barry
Abstract/Description: Variance in fitness is well known to influence the outcome of evolution but is rarely considered in the theory of marine reproductive strategies. In coastal environments, turbulent mesoscale eddies can collect larvae into packets, resulting in collective dispersal. Larvae in packets return to the coast or are lost offshore in groups, producing variance in fitness. Using a Markov process to calculate fixation probabilities for competing phenotypes, we examine the evolution of offspring size...
Show moreVariance in fitness is well known to influence the outcome of evolution but is rarely considered in the theory of marine reproductive strategies. In coastal environments, turbulent mesoscale eddies can collect larvae into packets, resulting in collective dispersal. Larvae in packets return to the coast or are lost offshore in groups, producing variance in fitness. Using a Markov process to calculate fixation probabilities for competing phenotypes, we examine the evolution of offspring size and spawning duration in species with benthic adults and pelagic offspring. The offspring size that provides mothers with the highest mean fitness also generates the greatest variance in fitness, but pairwise invasion plots show that bet-hedging strategies are not evolutionarily stable; maximizing expected fitness correctly predicts the unique evolutionarily stable strategy. Nonetheless, fixation can take a long time. We find that selection to increase spawning duration as a risk avoidance strategy to reduce the negative impacts of stochastic recruitment success can allow multiple offspring sizes to coexist in a population for extended periods. This has two important consequences for offspring size: (1) coexistence occurs over a broader range of sizes and is longer when spawning duration is longer because longer spawning durations reduce variation in fitness and increase the time to fixation, and (2) longer spawning durations can compensate for having a nonoptimal size and even allow less optimal sizes to reach fixation. Collective dispersal and longer spawning durations could effectively maintain offspring size variation even in the absence of good and bad years or locations. Empirical comparisons of offspring size would therefore not always reflect environment-specific differences in the optimal size.
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Date Issued: 2018-03
Identifier: FSU_libsubv1_wos_000427588400006, 10.1086/695879
Format: Citation

Title: Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance.
Creator: Martinez, Jessica S, Schlenoff, Joseph B, Keller, Thomas C S
Abstract/Description: Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked,...
Show morePolyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion and migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as 'leader' cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as 'follower' cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization.
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Date Issued: 2016-08-01
Identifier: FSU_pmch_27292313, 10.1016/j.yexcr.2016.06.002, PMC4967014, 27292313, 27292313, S0014-4827(16)30143-4
Format: Citation

Title: Commentary: Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised beta-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopatyh.
Creator: Cole, Lauren A., Dennis, Jonathan H., Chase, P. Bryant
Date Issued: 2016-09-23
Identifier: FSU_libsubv1_wos_000383760700001, 10.3389/fphys.2016.00418
Format: Citation

Title: Commentary: Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised β-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy..
Creator: Cole, Lauren A, Dennis, Jonathan H, Chase, P Bryant
Date Issued: 2016-09-23
Identifier: FSU_pmch_27721795, 10.3389/fphys.2016.00418, PMC5033966, 27721795, 27721795
Format: Citation

Title: Comparative analysis of glucagonergic cells, glia, and the circumferential marginal zone in the reptilian retina.
Creator: Todd, Levi, Suarez, Lilianna, Squires, Natalie, Zelinka, Christopher Paul, Gribbins, Kevin, Fischer, Andy J
Abstract/Description: Retinal progenitors in the circumferential marginal zone (CMZ) and Müller glia-derived progenitors have been well described for the eyes of fish, amphibians, and birds. However, there is no information regarding a CMZ and the nature of retinal glia in species phylogenetically bridging amphibians and birds. The purpose of this study was to examine the retinal glia and investigate whether a CMZ is present in the eyes of reptilian species. We used immunohistochemical analyses to study retinal...
Show moreRetinal progenitors in the circumferential marginal zone (CMZ) and Müller glia-derived progenitors have been well described for the eyes of fish, amphibians, and birds. However, there is no information regarding a CMZ and the nature of retinal glia in species phylogenetically bridging amphibians and birds. The purpose of this study was to examine the retinal glia and investigate whether a CMZ is present in the eyes of reptilian species. We used immunohistochemical analyses to study retinal glia, neurons that could influence CMZ progenitors, the retinal margin, and the nonpigmented epithelium of ciliary body of garter snakes, queen snakes, anole lizards, snapping turtles, and painted turtles. We compare our observations on reptile eyes to the CMZ and glia of fish, amphibians, and birds. In all species, Sox9, Pax6, and the glucocorticoid receptor are expressed by Müller glia and cells at the retinal margin. However, proliferating cells were found only in the CMZ of turtles and not in the eyes of anoles and snakes. Similar to eyes of chickens, the retinal margin in turtles contains accumulations of GLP1/glucagonergic neurites. We find that filamentous proteins, vimentin and GFAP, are expressed by Müller glia, but have different patterns of subcellular localization in the different species of reptiles. We provide evidence that the reptile retina may contain nonastrocytic inner retinal glial cells, similar to those described in the avian retina. We conclude that the retinal glia, glucagonergic neurons, and CMZ of turtles appear to be most similar to those of fish, amphibians, and birds.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_26053997, 10.1002/cne.23823, PMC4659723, 26053997, 26053997
Format: Citation

Title: Comparative Genotype-phenotype Mapping Reveals Distinct Modes of Venom Expression Evolution in the Sympatric Eastern Diamondback Rattlesnake (Crotalus adamanteus) and Eastern Coral SSnake (Micrurus fulvius).
Creator: Margres, Mark, McGivern, James J., Seavy, Margaret, Wray, Kenneth, Facente, Jack, Rokyta, Darin
Abstract/Description: Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process, and thus the genetic basis of adaptive evolution, requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom-gland towards toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype....
Show moreSelection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process, and thus the genetic basis of adaptive evolution, requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom-gland towards toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait, but also have extensive conservation and biomedical implications. Crotalus adamanteus is currently a candidate for Federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species.
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Date Issued: 2014
Identifier: FSU_migr_bio_faculty_publications-0001, 10.1534/genetics.114.172437
Format: Citation

Title: Competing scaffolding proteins determine capsid size during mobilization of pathogenicity islands.
Creator: Dearborn, Altaira D, Wall, Erin A, Kizziah, James L, Klenow, Laura, Parker, Laura K, Manning, Keith A, Spilman, Michael S, Spear, John M, Christie, Gail E, Dokland, Terje
Abstract/Description: pathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80α and SaPI1 procapsids to near-atomic...
Show morepathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80α and SaPI1 procapsids to near-atomic resolution by cryo-electron microscopy, and show that CpmB competes with the 80α scaffolding protein (SP) for a binding site on the capsid protein (CP), and works by altering the angle between capsomers. We probed these interactions genetically and identified second-site suppressors of lethal mutations in SP. Our structures show, for the first time, the detailed interactions between SP and CP in a bacteriophage, providing unique insights into macromolecular assembly processes.
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Date Issued: 2017-10-06
Identifier: FSU_pmch_28984245, 10.7554/eLife.30822, PMC5644958, 28984245, 28984245, 30822
Format: Citation

Title: Comprehensive Nucleosome Mapping Of The Human Genome In Cancer Progression.
Creator: Druliner, Brooke R., Vera, Daniel, Johnson, Ruth, Ruan, Xiaoyang, Apone, Lynn M., Dimalanta, Eileen T., Stewart, Fiona J., Boardman, Lisa, Dennis, Jonathan H.
Abstract/Description: Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and...
Show moreAltered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation.
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Date Issued: 2016-03-22
Identifier: FSU_libsubv1_wos_000375687200013, 10.1101/021618
Format: Citation

Title: Construction and Optimization of a Large Gene Coexpression Network in Maize Using RNA-Seq Data.
Creator: Huang, Ji, Vendramin, Stefania, Shi, Lizhen, McGinnis, Karen M
Abstract/Description: With the emergence of massively parallel sequencing, genomewide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a gene coexpression network (GCN) can be constructed and used for gene function prediction, candidate gene selection, and improving understanding of regulatory pathways....
Show moreWith the emergence of massively parallel sequencing, genomewide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a gene coexpression network (GCN) can be constructed and used for gene function prediction, candidate gene selection, and improving understanding of regulatory pathways. Several GCN studies have been done in maize (), mostly using microarray datasets. To build an optimal GCN from plant materials RNA-Seq data, parameters for expression data normalization and network inference were evaluated. A comprehensive evaluation of these two parameters and a ranked aggregation strategy on network performance, using libraries from 1266 maize samples, were conducted. Three normalization methods and 10 inference methods, including six correlation and four mutual information methods, were tested. The three normalization methods had very similar performance. For network inference, correlation methods performed better than mutual information methods at some genes. Increasing sample size also had a positive effect on GCN. Aggregating single networks together resulted in improved performance compared to single networks.
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Date Issued: 2017-09-01
Identifier: FSU_pmch_28768814, 10.1104/pp.17.00825, PMC5580776, 28768814, 28768814, pp.17.00825
Format: Citation

Title: Consumption Of Benthic Cyanobacterial Mats On A Caribbean Coral Reef.
Creator: Cissell, Ethan C., Manning, Joshua C., McCoy, Sophie J.
Abstract/Description: Herbivory is an important process in the general structuring of coral reef benthic communities. However, evidence of its ability to control coral reef benthic cyanobacterial mats, which have recently proliferated on reefs worldwide, remains ambivalent. Here, we report that the French Angelfish (Pomacanthus paru), Striped Parrotfish (Scarus iseri), Rock Beauty (Holacanthus tricolor), Ocean Surgeonfish (Acanthurus bahianus), Blue Parrotfish (Scarus coeruleus), and Atlantic Blue Tang (Acanthurus...
Show moreHerbivory is an important process in the general structuring of coral reef benthic communities. However, evidence of its ability to control coral reef benthic cyanobacterial mats, which have recently proliferated on reefs worldwide, remains ambivalent. Here, we report that the French Angelfish (Pomacanthus paru), Striped Parrotfish (Scarus iseri), Rock Beauty (Holacanthus tricolor), Ocean Surgeonfish (Acanthurus bahianus), Blue Parrotfish (Scarus coeruleus), and Atlantic Blue Tang (Acanthurus coeruleus) consume benthic cyanobacterial mats on coral reefs in Bonaire, Netherlands. We documented the foraging patterns of P. paru and S. iseri, and found that benthic cyanobacterial mats comprised 36.7%+/- 5.8% and 15.0% +/- 1.53% (mean +/- standard error) of the total bites taken by P. paru and S. iseri respectively. This magnitude of consumption suggests that grazing by reef fishes may represent a potentially important, but previously undocumented, top-down control on benthic cyanobacterial mats on Caribbean reefs.
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Date Issued: ue Sep 03 00:00:00 ED
Identifier: FSU_libsubv1_wos_000483700400026, 10.1038/s41598-019-49126-9
Format: Citation

Title: Correction for Avey et al., "Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36".
Creator: Avey, Denis, Tepper, Sarah, Pifer, Benjamin, Bahga, Amritpal, Williams, Hunter, Gillen, Joseph, Li, Wenwei, Ogden, Sarah, Zhu, Fanxiu
Date Issued: 2017-11-14
Identifier: FSU_pmch_29138329, 10.1128/JVI.01484-17, PMC5686716, 29138329, 29138329, 91/23/e01484-17
Format: Citation

Title: Critical and direct involvement of the CD23 stalk region in IgE binding.
Creator: Selb, Regina, Eckl-Dorna, Julia, Twaroch, Teresa E, Lupinek, Christian, Teufelberger, Andrea, Hofer, Gerhard, Focke-Tejkl, Margarete, Gepp, Barbara, Linhart, Birgit, Breiteneder...
Show moreSelb, Regina, Eckl-Dorna, Julia, Twaroch, Teresa E, Lupinek, Christian, Teufelberger, Andrea, Hofer, Gerhard, Focke-Tejkl, Margarete, Gepp, Barbara, Linhart, Birgit, Breiteneder, Heimo, Ellinger, Adolf, Keller, Walter, Roux, Kenneth H, Valenta, Rudolf, Niederberger, Verena
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Abstract/Description: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head...
Show moreThe low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed. A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23. Our results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
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Date Issued: 2017-01-01
Identifier: FSU_pmch_27343203, 10.1016/j.jaci.2016.04.015, PMC5321597, 27343203, 27343203, S0091-6749(16)30261-5
Format: Citation

Title: The Dead-box Protein Rok1 Orchestrates 40s And 60s Ribosome Assembly By Promoting The Release Of Rrp5 From Pre-40s Ribosomes To Allow For 60s Maturation.
Creator: Khoshnevis, Sohail, Askenasy, Isabel, Johnson, Matthew C., Dattolo, Maria D., Young-Erdos, Crystal L., Stroupe, M. Elizabeth, Karbstein, Katrin
Abstract/Description: DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S...
Show moreDEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked.
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Date Issued: 2016-06
Identifier: FSU_libsubv1_wos_000378611200007, 10.1371/journal.pbio.1002480
Format: Citation

Title: The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.
Creator: Khoshnevis, Sohail, Askenasy, Isabel, Johnson, Matthew C, Dattolo, Maria D, Young-Erdos, Crystal L, Stroupe, M Elizabeth, Karbstein, Katrin
Abstract/Description: DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S...
Show moreDEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked.
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Date Issued: 2016-06-09
Identifier: FSU_pmch_27280440, 10.1371/journal.pbio.1002480, PMC4900678, 27280440, 27280440, PBIOLOGY-D-16-00944
Format: Citation

Title: Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.
Creator: Darrow, Emily M, Huntley, Miriam H, Dudchenko, Olga, Stamenova, Elena K, Durand, Neva C, Sun, Zhuo, Huang, Su-Chen, Sanborn, Adrian L, Machol, Ido, Shamim, Muhammad, Seberg,...
Show moreDarrow, Emily M, Huntley, Miriam H, Dudchenko, Olga, Stamenova, Elena K, Durand, Neva C, Sun, Zhuo, Huang, Su-Chen, Sanborn, Adrian L, Machol, Ido, Shamim, Muhammad, Seberg, Andrew P, Lander, Eric S, Chadwick, Brian P, Aiden, Erez Lieberman
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Abstract/Description: During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge...
Show moreDuring interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging.
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Date Issued: 2016-08-02
Identifier: FSU_pmch_27432957, 10.1073/pnas.1609643113, PMC4978254, 27432957, 27432957, 1609643113
Format: Citation

Title: Differential Regulation of Cyclin E by Yorkie-Scalloped Signaling in Organ Development.
Creator: Shu, Zhiqiang, Deng, Wu-Min
Abstract/Description: Tissue integrity and homeostasis are accomplished through strict spatial and temporal regulation of cell growth and proliferation during development. Various signaling pathways have emerged as major growth regulators across metazoans; yet, how differential growth within a tissue is spatiotemporally coordinated remains largely unclear. Here, we report a role of a growth modulator Yorkie (), the homolog of Yes-associated protein (YAP), that differentially regulates its targets in wing imaginal...
Show moreTissue integrity and homeostasis are accomplished through strict spatial and temporal regulation of cell growth and proliferation during development. Various signaling pathways have emerged as major growth regulators across metazoans; yet, how differential growth within a tissue is spatiotemporally coordinated remains largely unclear. Here, we report a role of a growth modulator Yorkie (), the homolog of Yes-associated protein (YAP), that differentially regulates its targets in wing imaginal discs; whereby Yki interacts with its transcriptional partner, Scalloped (), the homolog of the TEAD/TEF family transcription factor in mammals, to control an essential cell cycle regulator Cyclin E (CycE). Interestingly, when Yki was coexpressed with Fizzy-related (), a endocycle inducer and homolog of Cdh1 in mammals, surrounding hinge cells displayed larger nuclear size than distal pouch cells. The observed size difference is attributable to differential regulation of CycE, a target of Yki and Sd, the latter of which can directly bind to regulatory sequences, and is expressed only in the pouch region of the wing disc starting from the late second-instar larval stage. During earlier stages of larval development, when Sd expression was not detected in the wing disc, coexpression of Fzr and Yki did not cause size differences between cells along the proximal-distal axis of the disc. We show that ectopic CycE promoted cell proliferation and apoptosis, and inhibited transcriptional activity of Yki targets. These findings suggest that spatiotemporal expression of transcription factor Sd induces differential growth regulation by Yki during wing disc development, highlighting coordination between Yki and CycE to control growth and maintain homeostasis.
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Date Issued: 2017-03-10
Identifier: FSU_pmch_28143945, 10.1534/g3.117.039065, PMC5345706, 28143945, 28143945, g3.117.039065
Format: Citation

Department of Biological Science (246)	+ -
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