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- Title
- Role of Olfaction for Eating Behavior.
- Creator
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Fadool, Debra Ann, Kolling, Louis John
- Abstract/Description
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Our olfactory system not only detects chemicals in the external environment but also subserves to detect the chemicals in our internal environment - the chemistry of energy homeostasis and metabolism. Olfaction guides our eating behavior using an array of neuroendocrine molecules that are detected across the main olfactory epithelium, the olfactory bulb, and higher cortical regions. Both metabolic state (fasting, satiation) and metabolic balance (obesity, metabolic disease) can affect...
Show moreOur olfactory system not only detects chemicals in the external environment but also subserves to detect the chemicals in our internal environment - the chemistry of energy homeostasis and metabolism. Olfaction guides our eating behavior using an array of neuroendocrine molecules that are detected across the main olfactory epithelium, the olfactory bulb, and higher cortical regions. Both metabolic state (fasting, satiation) and metabolic balance (obesity, metabolic disease) can affect olfactory-regulated eating behaviors. This review will delve into the physiological and behavioral link between olfaction, metabolism, eating, and health.
Show less - Date Issued
- 2020
- Identifier
- FSU_libsubv1_scholarship_submission_1602514625_d9f0b4ca
- Format
- Citation
- Title
- Challenges And Guidelines Toward 4d Nucleome Data And Model Standards.
- Creator
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Marti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi,...
Show moreMarti-Renom, Marc A., Almouzni, Genevieve, Bickmore, Wendy A., Bystricky, Kerstin, Cavalli, Giacomo, Fraser, Peter, Gasser, Susan M., Giorgetti, Luca, Heard, Edith, Nicodemi, Mario, Nollmann, Marcelo, Orozco, Modesto, Pombo, Ana, Torres-Padilla, Maria-Elena
Show less - Abstract/Description
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Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its...
Show moreDue to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate. However, the rapid evolution of methods and the increasing complexity of data can result in ambiguity and reproducibility challenges, which may hamper the progress of this field. Here, we describe such challenges ahead and provide guidelines to think about strategies for shared standardized validation of experimental 4D nucleome data sets and models.
Show less - Date Issued
- 2018-10-01
- Identifier
- FSU_libsubv1_wos_000446047000006, 10.1038/s41588-018-0236-3
- Format
- Citation
- Title
- The Role Of Geography In Adaptive Radiation.
- Creator
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Schenk, John J., Steppan, Scott J.
- Abstract/Description
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Although the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for...
Show moreAlthough the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for geographic transitions during adaptive radiations. We reconstructed a time-calibrated phylogeny from four nuclear genes and one mitochondrial gene for 77% of sigmodontine diversity. Historical biogeography was reconstructed among 14 regions, for which we applied a sliding-window approach to estimate regional transition rates through time. We compared these rate patterns and measured whether regions consisted of species that were more phylogenetically related than expected by chance. Following the initial South American colonization around 7 million years ago, multiple expansions from northern regions correlated with a burst of speciation. Subsequently, both diversification and regional transition rates decreased overall and within the majority of regions. Despite high regional transition rates, nearly all regional assemblages were phylogenetically clustered, indicating that within-region diversification was common. We conclude that biogeographic complexity and partitioning played a profound role in the adaptive radiation of the South American Sigmodontinae (Oryzomyalia), the degree to which is determined by the relative scales of spatial variation and dispersal abilities.
Show less - Date Issued
- 2018-10-01
- Identifier
- FSU_libsubv1_wos_000444262900004, 10.1086/699221
- Format
- Citation
- Title
- Genome Organization And Chromatin Analysis Identify Transcriptional Downregulation Of Insulin-like Growth Factor Signaling As A Hallmark Of Aging In Developing B Cells.
- Creator
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Koohy, Hashem, Bolland, Daniel J., Matheson, Louise S., Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Varnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy...
Show moreKoohy, Hashem, Bolland, Daniel J., Matheson, Louise S., Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Varnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy, Garcia, Raquel Manzano, Wingett, Steven W., Freire-Pritchett, Paula, Nagano, Takashi, Hawkins, Phillip, Stephens, Len, Elderkin, Sarah, Spivakov, Mikhail, Fraser, Peter, Corcoran, Anne E., Varga-Weisz, Patrick D.
Show less - Abstract/Description
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Background: Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Results: Our analysis reveals that the expression levels of most genes are generally preserved in B cell...
Show moreBackground: Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Results: Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. Conclusions: Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Show less - Date Issued
- 2018-09-05
- Identifier
- FSU_libsubv1_wos_000443725200001, 10.1186/s13059-018-1489-y
- Format
- Citation
- Title
- Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.
- Creator
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Koohy, Hashem, Bolland, Daniel J, Matheson, Louise S, Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Várnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy,...
Show moreKoohy, Hashem, Bolland, Daniel J, Matheson, Louise S, Schoenfelder, Stefan, Stellato, Claudia, Dimond, Andrew, Várnai, Csilla, Chovanec, Peter, Chessa, Tamara, Denizot, Jeremy, Manzano Garcia, Raquel, Wingett, Steven W, Freire-Pritchett, Paula, Nagano, Takashi, Hawkins, Phillip, Stephens, Len, Elderkin, Sarah, Spivakov, Mikhail, Fraser, Peter, Corcoran, Anne E, Varga-Weisz, Patrick D
Show less - Abstract/Description
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Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from...
Show moreAging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Show less - Date Issued
- 2018-09-05
- Identifier
- FSU_pmch_30180872, 10.1186/s13059-018-1489-y, PMC6124017, 30180872, 30180872, 10.1186/s13059-018-1489-y
- Format
- Citation
- Title
- Improved Estimates Of Net Primary Production, Growth, And Standing Crop Of Macrocystis Pyrifera In Southern California.
- Creator
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Rassweiler, Andrew, Reed, Daniel C., Harrer, Shannon L., Nelson, J. Clint
- Abstract/Description
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The giant kelp Macrocystis pyrifera forms subtidal forests on shallow reefs in temperate regions of the world. It is one of the fastest-growing multicellular autotrophs on Earth and its high productivity supports diverse marine food webs. In 2008, we published a method for estimating biomass and net primary production (NPP) of giant kelp along with five years of data, to provide a more integrated measure of NPP than those yielded by previous methods. Our method combines monthly field...
Show moreThe giant kelp Macrocystis pyrifera forms subtidal forests on shallow reefs in temperate regions of the world. It is one of the fastest-growing multicellular autotrophs on Earth and its high productivity supports diverse marine food webs. In 2008, we published a method for estimating biomass and net primary production (NPP) of giant kelp along with five years of data, to provide a more integrated measure of NPP than those yielded by previous methods. Our method combines monthly field measurements of standing crop and loss rates with a model of kelp biomass dynamics to estimate instantaneous mass-specific growth rates and NPP for each season of each year. We have since improved our approach to account for several previously unresolved sources of biomass loss. These improvements have led to a near doubling of our prior estimates of growth and NPP. At our site with the most persistent stand of giant kelp, NPP averages similar to 5.2 kg dry mass.m(-2).yr(-1) and results from the rapid growth (similar to 3.5% per d) of a relatively small standing biomass (similar to 0.4 kg dry mass/m(2) on average) that turns over similar to 12 times annually. Here we provide revised estimates of seasonal biomass, growth, and NPP for the five years covered by our previous publication (2002-2006), along with more than a decade of additional data (2007-2017). We also present updated relationships for predicting giant kelp biomass and NPP from much more easily obtained measurements of frond density. These data can be used to understand the mechanisms that drive variation in giant kelp NPP at a wide range of temporal scales. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper.
Show less - Date Issued
- 2018-09-01
- Identifier
- FSU_libsubv1_wos_000443558200024, 10.1002/ecy.2440
- Format
- Citation
- Title
- Characterization Of The Icce Repea In Mammals Reveals An Evolutionary Relationship With The Dxz4 Macrosatellite Through Conserved Ctcf Binding Motifs.
- Creator
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Westervelt, Natalia, Chadwick, Brian P.
- Abstract/Description
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Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA...
Show moreAppreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.
Show less - Date Issued
- 2018-09-01
- Identifier
- FSU_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
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Westervelt, Natalia, Chadwick, Brian P
- Abstract/Description
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Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA...
Show moreAppreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.
Show less - Date Issued
- 2018-09-01
- Identifier
- FSU_pmch_30102341, 10.1093/gbe/evy176, PMC6125249, 30102341, 30102341, 5068191
- Format
- Citation
- Title
- Targeted disruption of the endogenous zebrafish locus as models of rapid rod photoreceptor degeneration.
- Creator
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Zelinka, Christopher P, Sotolongo-Lopez, Mailin, Fadool, James M
- Abstract/Description
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Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness. RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and...
Show moreRetinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness. RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish locus, . One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA). Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring. Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes. Using gRNAs that targeted highly conserved regions of , a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors. No effect on cones was observed. Targeting the 5'-coding sequence of led to the recovery of several indels similar to disease-associated alleles. A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity. Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival. Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15. Larvae heterozygous for either of the alleles demonstrated rapid rod degeneration. Targeting of the 3'-coding region of resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339. Both alleles resulted in rod death in a dominant inheritance pattern. Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane. The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease. These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
Show less - Date Issued
- 2018-08-27
- Identifier
- FSU_pmch_30210230, PMC6128699, 30210230, 30210230
- Format
- Citation
- Title
- An Hpsc-derived Tissue-resident Macrophage Model Reveals Differential Responses Of Macrophages To Zikv And Deny Infection.
- Creator
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Lang, Jianshe, Cheng, Yichen, Rolfe, Alyssa, Hammack, Christy, Vera, Daniel, Kyle, Kathleen, Wang, Jingying, Meissner, Torsten B., Ren, Yi, Cowan, Chad, Tang, Hengli
- Abstract/Description
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Zika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly...
Show moreZika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly activates macrophage migration inhibitory factor (MIF) secretion and decreases macrophage migration. Neutralization of MIF leads to improved migratory ability of DENV-infected macrophages. In contrast, ZIKV-infected macrophages exhibit prolonged migration and express low levels of pro-inflammatory cytokines and chemokines. Mechanistically, ZIKV disrupts the nuclear factor kappa B (NF-kappa B)-MIF positive feedback loop by inhibiting the NF-kappa B signaling pathway. Our results demonstrate the utility of hPSC-derived macrophages in infectious disease modeling and suggest that the distinct impact of ZIKV and DENV on macrophage immune response may underlie different pathogenesis of Zika and dengue diseases.
Show less - Date Issued
- 2018-08-14
- Identifier
- FSU_libsubv1_wos_000441583100006, 10.1016/j.stemcr.2018.06.006
- Format
- Citation
- Title
- An hPSC-Derived Tissue-Resident Macrophage Model Reveals Differential Responses of Macrophages to ZIKV and DENV Infection.
- Creator
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Lang, Jianshe, Cheng, Yichen, Rolfe, Alyssa, Hammack, Christy, Vera, Daniel, Kyle, Kathleen, Wang, Jingying, Meissner, Torsten B, Ren, Yi, Cowan, Chad, Tang, Hengli
- Abstract/Description
-
Zika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly...
Show moreZika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly activates macrophage migration inhibitory factor (MIF) secretion and decreases macrophage migration. Neutralization of MIF leads to improved migratory ability of DENV-infected macrophages. In contrast, ZIKV-infected macrophages exhibit prolonged migration and express low levels of pro-inflammatory cytokines and chemokines. Mechanistically, ZIKV disrupts the nuclear factor κB (NF-κB)-MIF positive feedback loop by inhibiting the NF-κB signaling pathway. Our results demonstrate the utility of hPSC-derived macrophages in infectious disease modeling and suggest that the distinct impact of ZIKV and DENV on macrophage immune response may underlie different pathogenesis of Zika and dengue diseases.
Show less - Date Issued
- 2018-08-14
- Identifier
- FSU_pmch_29983385, 10.1016/j.stemcr.2018.06.006, PMC6092684, 29983385, 29983385, S2213-6711(18)30269-8
- Format
- Citation
- Title
- Loss Of Setdb1 Decompacts The Inactive X Chromosome In Part Through Reactivation Of An Enhancer In The Il1rapl1 Gene.
- Creator
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Sun, Zhuo, Chadwick, Brian P.
- Abstract/Description
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Background: The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Results: Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi...
Show moreBackground: The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Results: Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Close examination revealed a 0.5 Mb region of the Xi that transitioned from H3K9me3 heterochromatin to euchromatin within the 3' end of the IL1RAPL1 gene that is part of a common chromosome fragile site that is frequently deleted or rearranged in patients afflicted with intellectual disability and other neurological ailments. Centrally located within this interval is a powerful enhancer adjacent to an ERVL-MaLR element. In the absence of SETDB1, the enhancer is reactivated on the Xi coupled with bidirectional transcription from the ERVL-MaLR element. Xa deletion of the enhancer/ERVL-MaLR resulted in loss of full-length IL1RAPL1 transcript in cis, coupled with trans decompaction of the Xi chromosome territory, whereas Xi deletion increased detection of full-length IL1RAPL1 transcript in trans, but did not impact Xi compaction. Conclusions: These data support a critical role for SETDB1 in maintaining the ERVL-MaLR element and adjacent enhancer in the 3' end of the IL1RAPL1 gene in a silent state to facilitate Xi compaction.
Show less - Date Issued
- 2018-08-13
- Identifier
- FSU_libsubv1_wos_000441459500001, 10.1186/s13072-018-0218-9
- Format
- Citation
- Title
- Loss of SETDB1 decompacts the inactive X chromosome in part through reactivation of an enhancer in the IL1RAPL1 gene.
- Creator
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Sun, Zhuo, Chadwick, Brian P
- Abstract/Description
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The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we...
Show moreThe product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Close examination revealed a 0.5 Mb region of the Xi that transitioned from H3K9me3 heterochromatin to euchromatin within the 3' end of the IL1RAPL1 gene that is part of a common chromosome fragile site that is frequently deleted or rearranged in patients afflicted with intellectual disability and other neurological ailments. Centrally located within this interval is a powerful enhancer adjacent to an ERVL-MaLR element. In the absence of SETDB1, the enhancer is reactivated on the Xi coupled with bidirectional transcription from the ERVL-MaLR element. Xa deletion of the enhancer/ERVL-MaLR resulted in loss of full-length IL1RAPL1 transcript in cis, coupled with trans decompaction of the Xi chromosome territory, whereas Xi deletion increased detection of full-length IL1RAPL1 transcript in trans, but did not impact Xi compaction. These data support a critical role for SETDB1 in maintaining the ERVL-MaLR element and adjacent enhancer in the 3' end of the IL1RAPL1 gene in a silent state to facilitate Xi compaction.
Show less - Date Issued
- 2018-08-13
- Identifier
- FSU_pmch_30103804, 10.1186/s13072-018-0218-9, PMC6088404, 30103804, 30103804, 10.1186/s13072-018-0218-9
- Format
- Citation
- Title
- Chromatin structure profile data from DNS-seq: Differential nuclease sensitivity mapping of four reference tissues of B73 maize ( L)..
- Creator
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Turpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H,...
Show moreTurpin, Zachary M, Vera, Daniel L, Savadel, Savannah D, Lung, Pei-Yau, Wear, Emily E, Mickelson-Young, Leigh, Thompson, William F, Hanley-Bowdoin, Linda, Dennis, Jonathan H, Zhang, Jinfeng, Bass, Hank W
Show less - Abstract/Description
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Presented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference...
Show morePresented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize () inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference profiles. The data repository for the sequence data is the NCBI SRA, BioProject Accession 8.
Show less - Date Issued
- 2018-08-10
- Identifier
- FSU_pmch_30175199, 10.1016/j.dib.2018.08.015, PMC6117953, 30175199, 30175199, S2352-3409(18)30865-5
- Format
- Citation
- Title
- Phylogenomics Uncovers Early Hybridization And Adaptive Loci Shaping The Radiation Of Lake Tanganyika Cichlid Fishes.
- Creator
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Irisarri, Iker, Singh, Pooja, Koblmuller, Stephan, Torres-Dowdall, Julian, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R., Lemmon, Emily Moriarty,...
Show moreIrisarri, Iker, Singh, Pooja, Koblmuller, Stephan, Torres-Dowdall, Julian, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R., Lemmon, Emily Moriarty, Thallinger, Gerhard G., Sturmbauer, Christian, Meyer, Axel
Show less - Abstract/Description
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Lake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using...
Show moreLake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using anchored phylogenomics and uncover hybridization at its base, as well as early in the haplochromine radiation. This suggests that hybridization might have facilitated these speciation bursts. Time-calibrated trees support that the radiation of Tanganyika cichlids coincided with lake formation and that Gondwanan vicariance concurred with the earliest splits in the cichlid family tree. Genes linked to key innovations show signals of introgression or positive selection following colonization of lake habitats and species' dietary adaptations are revealed as major drivers of colour vision evolution. These findings shed light onto the processes shaping the evolution of adaptive radiations.
Show less - Date Issued
- 2018-08-08
- Identifier
- FSU_libsubv1_wos_000440982800001, 10.1038/s41467-018-05479-9
- Format
- Citation
- Title
- Phylogenomics uncovers early hybridization and adaptive loci shaping the radiation of Lake Tanganyika cichlid fishes.
- Creator
-
Irisarri, Iker, Singh, Pooja, Koblmüller, Stephan, Torres-Dowdall, Julián, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R, Lemmon, Emily Moriarty,...
Show moreIrisarri, Iker, Singh, Pooja, Koblmüller, Stephan, Torres-Dowdall, Julián, Henning, Frederico, Franchini, Paolo, Fischer, Christoph, Lemmon, Alan R, Lemmon, Emily Moriarty, Thallinger, Gerhard G, Sturmbauer, Christian, Meyer, Axel
Show less - Abstract/Description
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Lake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using...
Show moreLake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using anchored phylogenomics and uncover hybridization at its base, as well as early in the haplochromine radiation. This suggests that hybridization might have facilitated these speciation bursts. Time-calibrated trees support that the radiation of Tanganyika cichlids coincided with lake formation and that Gondwanan vicariance concurred with the earliest splits in the cichlid family tree. Genes linked to key innovations show signals of introgression or positive selection following colonization of lake habitats and species' dietary adaptations are revealed as major drivers of colour vision evolution. These findings shed light onto the processes shaping the evolution of adaptive radiations.
Show less - Date Issued
- 2018-08-08
- Identifier
- FSU_pmch_30089797, 10.1038/s41467-018-05479-9, PMC6082878, 30089797, 30089797, 10.1038/s41467-018-05479-9
- Format
- Citation
- Title
- Interactive Effects Of Precipitation And Nitrogen Enrichment On Multi-trophic Dynamics In Plant-arthropod Communities.
- Creator
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Griffith, Kaitlin A., Grinath, Joshua B.
- Abstract/Description
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Patterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear....
Show morePatterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear. We investigated the influence of precipitation and N enrichment on ecological dynamics across three trophic levels, hypothesizing that herbivores and plants would exhibit synergistic responses to the combined influence of precipitation, N amendments and predators. To test this, we conducted a field experiment with arthropods on two model plant species, Nicotiana tabacum and Nicotiana rustica. First, we characterized the plant-arthropod assemblages, finding that N.tabacum hosted greater abundances of caterpillars, while N. rustica hosted more sap-sucking herbivores. Next, we evaluated the effects of rainwater, soil N, and predatory spider manipulations for both plantarthropod assemblages. On N. tabacum, water and N availability had an interactive effect on caterpillars, where caterpillars were most abundant with rainwater additions and least abundant when both rainwater and N were added. For N. rustica, foliar chemistry had a synergistic response to all three experimental factors. Compared to spider-absent conditions, leaf N concentration increased and C/N decreased when spiders were present, but this response only occurred under high water and N availability. Spiders indirectly altered plant chemistry via a facilitative effect of spiders on sap-sucking herbivores, potentially due to intra-guild predation, and a positive effect of sap-suckers on foliar N concentration. Our study suggests that predictions of the ecological impacts of altered precipitation and N deposition may need to account for the effects of resource co-limitation on dynamics across trophic levels.
Show less - Date Issued
- 2018-08-02
- Identifier
- FSU_libsubv1_wos_000440778600029, 10.1371/journal.pone.0201219
- Format
- Citation
- Title
- Interactive effects of precipitation and nitrogen enrichment on multi-trophic dynamics in plant-arthropod communities.
- Creator
-
Griffith, Kaitlin A, Grinath, Joshua B
- Abstract/Description
-
Patterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear....
Show morePatterns of precipitation and nitrogen (N) deposition are changing in ecosystems worldwide. Simultaneous increases in precipitation and N deposition can relieve co-limiting soil resource conditions for plants and result in synergistic plant responses, which may affect animals and plant responses to higher trophic levels. However, the potential for synergistic effects of precipitation and N deposition on animals and plant responses to herbivores and predators (via trophic cascades) is unclear. We investigated the influence of precipitation and N enrichment on ecological dynamics across three trophic levels, hypothesizing that herbivores and plants would exhibit synergistic responses to the combined influence of precipitation, N amendments and predators. To test this, we conducted a field experiment with arthropods on two model plant species, Nicotiana tabacum and Nicotiana rustica. First, we characterized the plant-arthropod assemblages, finding that N. tabacum hosted greater abundances of caterpillars, while N. rustica hosted more sap-sucking herbivores. Next, we evaluated the effects of rainwater, soil N, and predatory spider manipulations for both plant-arthropod assemblages. On N. tabacum, water and N availability had an interactive effect on caterpillars, where caterpillars were most abundant with rainwater additions and least abundant when both rainwater and N were added. For N. rustica, foliar chemistry had a synergistic response to all three experimental factors. Compared to spider-absent conditions, leaf N concentration increased and C/N decreased when spiders were present, but this response only occurred under high water and N availability. Spiders indirectly altered plant chemistry via a facilitative effect of spiders on sap-sucking herbivores, potentially due to intra-guild predation, and a positive effect of sap-suckers on foliar N concentration. Our study suggests that predictions of the ecological impacts of altered precipitation and N deposition may need to account for the effects of resource co-limitation on dynamics across trophic levels.
Show less - Date Issued
- 2018-08-02
- Identifier
- FSU_pmch_30070991, 10.1371/journal.pone.0201219, PMC6072000, 30070991, 30070991, PONE-D-17-40079
- Format
- Citation
- Title
- The Half-bridge Component Kar1 Promotes Centrosome Separation And Duplication During Budding Yeast Meiosis.
- Creator
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Agarwal, Meenakshi, Jin, Hui, McClain, Melainia, Fan, Jinbo, Koch, Bailey A., Jaspersen, Sue L., Yu, Hong-Guo
- Abstract/Description
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The budding yeast centrosome, often called the spindle pole body (SPB), nudeates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid...
Show moreThe budding yeast centrosome, often called the spindle pole body (SPB), nudeates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid segregation in meiosis II. How SPB duplication and separation are regulated during meiosis remains to be elucidated, and whether regulation in meiosis differs from that in mitosis is unclear. Here we show that overproduction of the half-bridge component Kar1 leads to premature SPB separation during meiosis. Furthermore, excessive Kar1 induces SPB overduplication to form supernumerary SPBs, leading to chromosome missegregation and erroneous ascospore formation. Kar1-mediated SPB duplication bypasses the requirement of dephosphorylation of Sfi1, another half-bridge component previously identified as a licensing factor. Our results therefore reveal an unexpected role of Kar1 in licensing meiotic SPB duplication and suggest a unique mechanism of SPB regulation during budding yeast meiosis.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_libsubv1_wos_000446089500003, 10.1091/mbc.E18-03-0163
- Format
- Citation
- Title
- Venom Complexity In A Pitviper Produced By Facultative Parthenogenesis.
- Creator
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Calvete, J. J., Casewell, N. R., Hernandez-Guzman, U., Quesada-Bernat, S., Sanz, L., Rokyta, D. R., Storey, D., Albulescu, L.-O., Wuster, W., Smith, C. F., Schuett, G. W., Booth...
Show moreCalvete, J. J., Casewell, N. R., Hernandez-Guzman, U., Quesada-Bernat, S., Sanz, L., Rokyta, D. R., Storey, D., Albulescu, L.-O., Wuster, W., Smith, C. F., Schuett, G. W., Booth, W.
Show less - Abstract/Description
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Facultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However,...
Show moreFacultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However, terminal fusion automixis is believed to result in near genome-wide reductions in heterozygosity; thus, FP seems likely to affect key phenotypic characters, yet this remains almost completely unstudied. Snake venom is a complex phenotypic character primarily used to subjugate prey and is thus tightly linked to individual fitness. Surprisingly, the composition and function of venom produced by a parthenogenetic pitviper exhibits a high degree of similarity to that of its mother and conspecifics from the same population. Therefore, the apparent loss of allelic diversity caused by FP appears unlikely to have a significant impact on the prey-capturing ability of this snake. Accordingly, the pitviper offspring produced by FP retained complex phenotypic characteristics associated with fitness. This result reinforces the potential ecological and evolutionary importance of FP and questions our understanding of the inheritance of venom-associated genes.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_libsubv1_wos_000440411300024, 10.1038/s41598-018-29791-y
- Format
- Citation
- Title
- The half-bridge component Kar1 promotes centrosome separation and duplication during budding yeast meiosis.
- Creator
-
Agarwal, Meenakshi, Jin, Hui, McClain, Melainia, Fan, Jinbo, Koch, Bailey A, Jaspersen, Sue L, Yu, Hong-Guo
- Abstract/Description
-
The budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid...
Show moreThe budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid segregation in meiosis II. How SPB duplication and separation are regulated during meiosis remains to be elucidated, and whether regulation in meiosis differs from that in mitosis is unclear. Here we show that overproduction of the half-bridge component Kar1 leads to premature SPB separation during meiosis. Furthermore, excessive Kar1 induces SPB overduplication to form supernumerary SPBs, leading to chromosome missegregation and erroneous ascospore formation. Kar1--mediated SPB duplication bypasses the requirement of dephosphorylation of Sfi1, another half-bridge component previously identified as a licensing factor. Our results therefore reveal an unexpected role of Kar1 in licensing meiotic SPB duplication and suggest a unique mechanism of SPB regulation during budding yeast meiosis.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_pmch_29847244, 10.1091/mbc.E18-03-0163, PMC6085829, 29847244, 29847244
- Format
- Citation
- Title
- Venom Complexity in a Pitviper Produced by Facultative Parthenogenesis.
- Creator
-
Calvete, J J, Casewell, N R, Hernández-Guzmán, U, Quesada-Bernat, S, Sanz, L, Rokyta, D R, Storey, D, Albulescu, L-O, Wüster, W, Smith, C F, Schuett, G W, Booth, W
- Abstract/Description
-
Facultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However,...
Show moreFacultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However, terminal fusion automixis is believed to result in near genome-wide reductions in heterozygosity; thus, FP seems likely to affect key phenotypic characters, yet this remains almost completely unstudied. Snake venom is a complex phenotypic character primarily used to subjugate prey and is thus tightly linked to individual fitness. Surprisingly, the composition and function of venom produced by a parthenogenetic pitviper exhibits a high degree of similarity to that of its mother and conspecifics from the same population. Therefore, the apparent loss of allelic diversity caused by FP appears unlikely to have a significant impact on the prey-capturing ability of this snake. Accordingly, the pitviper offspring produced by FP retained complex phenotypic characteristics associated with fitness. This result reinforces the potential ecological and evolutionary importance of FP and questions our understanding of the inheritance of venom-associated genes.
Show less - Date Issued
- 2018-08-01
- Identifier
- FSU_pmch_30068934, 10.1038/s41598-018-29791-y, PMC6070573, 30068934, 30068934, 10.1038/s41598-018-29791-y
- Format
- Citation
- Title
- Postsynaptic Fmrp Regulates Synaptogenesis In Vivo In The Developing Cochlear Nucleus.
- Creator
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Wang, Xiaoyu, Zorio, Diego A. R., Schecterson, Leslayann, Lu, Yong, Wang, Yuan
- Abstract/Description
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A global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of...
Show moreA global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of postsynaptic bushy neurons. In ovo electroporation of drug-inducible Fmr1-shRNA constructs produced a mosaicism of FMRP expression in chicken (either sex) bushy neurons, leading to reduced FMRP levels in transfected, but not neighboring nontransfected, neurons. Structural analyses revealed that postsynaptic FMRP reduction led to smaller size and abnormal morphology of individual presynaptic endbulbs at both early and later developmental stages. We further examined whether FMRP reduction affects dendritic development, as a potential mechanism underlying defective endbulb formation. Normally, chicken bushy neurons grow extensive dendrites at early stages and retract these dendrites when endbulbs begin to form. Neurons transfected with Fmr1 shRNA exhibited a remarkable delay in branch retraction, failing to provide necessary somatic surface for timely formation and growth of large endbulbs. Patch-clamp recording verified functional consequences of dendritic and synaptic deficits on neurotransmission, showing smaller amplitudes and slower kinetics of spontaneous and evoked EPSCs. Together, these data demonstrate that proper levels of postsynaptic FMRP are required for timely maturation of somatodendritic morphology, a delay of which may affect synaptogenesis and thus contribute to long-lasting deficits of excitatory synapses.
Show less - Date Issued
- 2018-07-18
- Identifier
- FSU_libsubv1_wos_000439698400004, 10.1523/JNEUROSCI.0665-18.2018
- Format
- Citation
- Title
- Quantitative Morphological Variation in the Developing Wing.
- Creator
-
Matamoro-Vidal, Alexis, Huang, Yunxian, Salazar-Ciudad, Isaac, Shimmi, Osamu, Houle, David
- Abstract/Description
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Quantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental...
Show moreQuantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental stages were studied: late larval third instar, post-pupariation and in the adult fly. We studied wild-type animals in addition to mutants of two genes ( and ) that have known effects on adult wing shape and size. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. In addition we provide linear rules allowing us to link wing morphology in the larva, with wing morphology in the pupa. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.
Show less - Date Issued
- 2018-07-02
- Identifier
- FSU_pmch_29844017, 10.1534/g3.118.200372, PMC6027878, 29844017, 29844017, g3.118.200372
- Format
- Citation
- Title
- Promoter Interactome Of Human Embryonic Stem Cell-derived Cardiomyocytes Connects Gwas Regions To Cardiac Gene Networks.
- Creator
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Choy, Mun-Kit, Javierre, Biola M., Williams, Simon G., Baross, Stephanie L., Liu, Yingjuan, Wingett, Steven W., Akbarov, Artur, Wallace, Chris, Freire-Pritchett, Paula, Rugg...
Show moreChoy, Mun-Kit, Javierre, Biola M., Williams, Simon G., Baross, Stephanie L., Liu, Yingjuan, Wingett, Steven W., Akbarov, Artur, Wallace, Chris, Freire-Pritchett, Paula, Rugg-Gunn, Peter J., Spivakov, Mikhail, Fraser, Peter, Keavney, Bernard D.
Show less - Abstract/Description
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Long-range chromosomal interactions bring distal regulatory elements and promoters together to regulate gene expression in biological processes. By performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key mechanism by which enhancers contact their target genes after hESC-CM differentiation from hESCs. We also show that the promoter interactome of hESC-CMs is associated with expression...
Show moreLong-range chromosomal interactions bring distal regulatory elements and promoters together to regulate gene expression in biological processes. By performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key mechanism by which enhancers contact their target genes after hESC-CM differentiation from hESCs. We also show that the promoter interactome of hESC-CMs is associated with expression quantitative trait loci (eQTLs) in cardiac left ventricular tissue; captures the dynamic process of genome reorganisation after hESC-CM differentiation; overlaps genome-wide association study (GWAS) regions associated with heart rate; and identifies new candidate genes in such regions. These findings indicate that regulatory elements in hESC-CMs identified by our approach control gene expression involved in ventricular conduction and rhythm of the heart. The study of promoter interactions in other hESC-derived cell types may be of utility in functional investigation of GWAS-associated regions.
Show less - Date Issued
- 2018-06-28
- Identifier
- FSU_libsubv1_wos_000436548700017, 10.1038/s41467-018-04931-0
- Format
- Citation
- Title
- Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions..
- Creator
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Schoenfelder, Stefan, Javierre, Biola-Maria, Furlan-Magaril, Mayra, Wingett, Steven W, Fraser, Peter
- Abstract/Description
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The three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to...
Show moreThe three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to their target genes is thus crucial to understand gene expression control. We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. In PCHi-C, highly complex Hi-C libraries are specifically enriched for promoter sequences through in-solution hybrid selection with thousands of biotinylated RNA baits complementary to the ends of all promoter-containing restriction fragments. The aim is to then pull-down promoter sequences and their frequent interaction partners such as enhancers and other potential regulatory elements. After high-throughput paired-end sequencing, a statistical test is applied to each promoter-ligated restriction fragment to identify significant PIRs at the restriction fragment level. We have used PCHi-C to generate an atlas of long-range promoter interactions in dozens of human and mouse cell types. These promoter interactome maps have contributed to a greater understanding of mammalian gene expression control by assigning putative regulatory regions to their target genes and revealing preferential spatial promoter-promoter interaction networks. This information also has high relevance to understanding human genetic disease and the identification of potential disease genes, by linking non-coding disease-associated sequence variants in or near control sequences to their target genes.
Show less - Date Issued
- 2018-06-28
- Identifier
- FSU_pmch_30010637, 10.3791/57320, PMC6102006, 30010637, 30010637
- Format
- Citation
- Title
- Evaluating the Performance of De Novo Assembly Methods for Venom-Gland Transcriptomics.
- Creator
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Holding, Matthew L, Margres, Mark J, Mason, Andrew J, Parkinson, Christopher L, Rokyta, Darin R
- Abstract/Description
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Venom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a...
Show moreVenom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a bioinformatic problem with several possible solutions. Several methods have been employed to assemble venom-gland transcriptomes, with the Trinity assembler being the most commonly applied among them. Although previous evidence of variation in performance among assembly software exists, particularly regarding recovery of difficult-to-assemble multigene families such as snake venom metalloproteinases, much work to date still employs a single assembly method. We evaluated the performance of several commonly used de novo assembly methods for the recovery of both nontoxin transcripts and complete, high-quality venom-gene transcripts across eleven snake and four scorpion transcriptomes. We varied -mer sizes used by some assemblers to evaluate the impact of -mer length on transcript recovery. We showed that the recovery of nontoxin transcripts and toxin transcripts is best accomplished through different assembly software, with SDT at smaller -mer lengths and Trinity being best for nontoxin recovery and a combination of SeqMan NGen and a seed-and-extend approach implemented in Extender as the best means of recovering a complete set of toxin transcripts. In particular, Extender was the only means tested capable of assembling multiple isoforms of the diverse snake venom metalloproteinase family, while traditional approaches such as Trinity recovered at most one metalloproteinase transcript. Our work demonstrated that traditional metrics of assembly performance are not predictive of performance in the recovery of complete and high quality toxin genes. Instead, effective venom-gland transcriptomic studies should combine and quality-filter the results of several assemblers with varying algorithmic strategies.
Show less - Date Issued
- 2018-06-19
- Identifier
- FSU_pmch_29921759, 10.3390/toxins10060249, PMC6024825, 29921759, 29921759, toxins10060249
- Format
- Citation
- Title
- Phylogenomic evidence overturns current conceptions of social evolution in wasps (Vespidae).
- Creator
-
Piekarski, P K, Carpenter, J M, Lemmon, A R, Moriarty Lemmon, E, Sharanowski, B J
- Abstract/Description
-
The hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral...
Show moreThe hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral castes → eusociality with preimaginal caste-biasing → morphologically differentiated castes). Here we infer the phylogeny of Vespidae using sequence data generated via anchored hybrid enrichment from 378 loci across 136 vespid species and perform ancestral state reconstructions to test whether rudimentary and monomorphic castes characterized the initial stages of eusocial evolution. Our results reject the single origin of eusociality hypothesis, contest the supposition that eusociality emerged from a casteless nest-sharing ancestor, and suggest that eusociality in Polistinae + Vespinae began with castes having morphological differences. An abrupt appearance of castes with ontogenetically established morphophysiological differences conflicts with the current conception of stepwise social evolution and suggests that the climb up the ladder of sociality does not occur through sequential mutation. Phenotypic plasticity and standing genetic variation could explain how cooperative brood care evolved in concert with nest-sharing and how morphologically dissimilar castes arose without a rudimentary intermediate. Furthermore, preimaginal caste-biasing at the outset of eusociality implicates a subsocial route to eusociality in Polistinae + Vespinae, emphasizing the role of mother-daughter interactions and subfertility (i.e. the cost component of kin selection) in the origin of workers.
Show less - Date Issued
- 2018-06-19
- Identifier
- FSU_pmch_29924339, 10.1093/molbev/msy124, PMC6107056, 29924339, 29924339, 5040136
- Format
- Citation
- Title
- Distinct Tissue-specific Transcriptional Regulation Revealed By Gene Regulatory Networks In Maize.
- Creator
-
Huang, Ji, Zheng, Juefei, Yuan, Hui, McGinnis, Karen
- Abstract/Description
-
Background: Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf,...
Show moreBackground: Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize. Results: Although many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm. Conclusions: By combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/), for easy querying. All source code and data are available at Github (https://github.com/timedreamer/maize_tissue-specific_GRN).
Show less - Date Issued
- 2018-06-07
- Identifier
- FSU_libsubv1_wos_000434971800002, 10.1186/s12870-018-1329-y
- Format
- Citation
- Title
- Distinct tissue-specific transcriptional regulation revealed by gene regulatory networks in maize.
- Creator
-
Huang, Ji, Zheng, Juefei, Yuan, Hui, McGinnis, Karen
- Abstract/Description
-
Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM...
Show moreTranscription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize. Although many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm. By combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/ ), for easy querying. All source code and data are available at Github ( https://github.com/timedreamer/maize_tissue-specific_GRN ).
Show less - Date Issued
- 2018-06-07
- Identifier
- FSU_pmch_29879919, 10.1186/s12870-018-1329-y, PMC6040155, 29879919, 29879919, 10.1186/s12870-018-1329-y
- Format
- Citation
- Title
- Emetine Inhibits Zika And Ebola Virus Infections Through Two Molecular Mechanisms: Inhibiting Viral Replication And Decreasing Viral Entry.
- Creator
-
Yang, Shu, Xu, Miao, Lee, Emily M., Gorshkov, Kirill, Shiryaev, Sergey A., He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella,...
Show moreYang, Shu, Xu, Miao, Lee, Emily M., Gorshkov, Kirill, Shiryaev, Sergey A., He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella, Farhy, Chen, Huang, Chun-Teng, Zhang, Zirui, Zhu, Wenjun, Wu, Yuying, Zhou, Yi, Song, Guang, Zhu, Heng, Shamim, Khalida, Martinez-Romero, Carles, Garcia-Sastre, Adolfo, Preston, Richard A., Jayaweera, Dushyantha T., Huang, Ruili, Huang, Wenwei, Xia, Menghang, Simeonov, Anton, Ming, Guoli, Qiu, Xiangguo, Terskikh, Alexey, Tang, Hengli, Song, Hongjun, Zheng, Wei
Show less - Abstract/Description
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The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and...
Show moreThe re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.
Show less - Date Issued
- 2018-06-05
- Identifier
- FSU_libsubv1_wos_000434231100001, 10.1038/s41421-018-0034-1
- Format
- Citation
- Title
- Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry..
- Creator
-
Yang, Shu, Xu, Miao, Lee, Emily M, Gorshkov, Kirill, Shiryaev, Sergey A, He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella,...
Show moreYang, Shu, Xu, Miao, Lee, Emily M, Gorshkov, Kirill, Shiryaev, Sergey A, He, Shihua, Sun, Wei, Cheng, Yu-Shan, Hu, Xin, Tharappel, Anil Mathew, Lu, Billy, Pinto, Antonella, Farhy, Chen, Huang, Chun-Teng, Zhang, Zirui, Zhu, Wenjun, Wu, Yuying, Zhou, Yi, Song, Guang, Zhu, Heng, Shamim, Khalida, Martínez-Romero, Carles, García-Sastre, Adolfo, Preston, Richard A, Jayaweera, Dushyantha T, Huang, Ruili, Huang, Wenwei, Xia, Menghang, Simeonov, Anton, Ming, Guoli, Qiu, Xiangguo, Terskikh, Alexey V, Tang, Hengli, Song, Hongjun, Zheng, Wei
Show less - Abstract/Description
-
The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption...
Show moreThe re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.
Show less - Date Issued
- 2018-06-05
- Identifier
- FSU_pmch_29872540, 10.1038/s41421-018-0034-1, PMC5986771, 29872540, 29872540, 34
- Format
- Citation
- Title
- 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.
Show less - Abstract/Description
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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.
Show less - Date Issued
- 2018-06-01
- Identifier
- FSU_libsubv1_wos_000436084800005, 10.1101/gr.232561.117
- Format
- Citation
- Title
- Evaluating The Performance Of De Novo Assembly Methods For Venom-gland Transcriptomics.
- Creator
-
Holding, Matthew L., Margres, Mark J., Mason, Andrew J., Parkinson, Christopher L., Rokyta, Darin R.
- Abstract/Description
-
Venom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a...
Show moreVenom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a bioinformatic problem with several possible solutions. Several methods have been employed to assemble venom-gland transcriptomes, with the Trinity assembler being the most commonly applied among them. Although previous evidence of variation in performance among assembly software exists, particularly regarding recovery of difficult-to-assemble multigene families such as snake venom metalloproteinases, much work to date still employs a single assembly method. We evaluated the performance of several commonly used de novo assembly methods for the recovery of both nontoxin transcripts and complete, high-quality venom-gene transcripts across eleven snake and four scorpion transcriptomes. We varied k-mer sizes used by some assemblers to evaluate the impact of k-mer length on transcript recovery. We showed that the recovery of nontoxin transcripts and toxin transcripts is best accomplished through different assembly software, with SDT at smaller k-mer lengths and Trinity being best for nontoxin recovery and a combination of SeqMan NGen and a seed-and-extend approach implemented in Extender as the best means of recovering a complete set of toxin transcripts. In particular, Extender was the only means tested capable of assembling multiple isoforms of the diverse snake venom metalloproteinase family, while traditional approaches such as Trinity recovered at most one metalloproteinase transcript. Our work demonstrated that traditional metrics of assembly performance are not predictive of performance in the recovery of complete and high quality toxin genes. Instead, effective venom-gland transcriptomic studies should combine and quality-filter the results of several assemblers with varying algorithmic strategies.
Show less - Date Issued
- 2018-06-01
- Identifier
- FSU_libsubv1_wos_000436131800037, 10.3390/toxins10060249
- Format
- Citation
- Title
- Unique Maternal And Environmental Effects On The Body Morphology Of The Least Killifish, Heterandria Formosa.
- Creator
-
Landy, J. Alex, Travis, Joseph
- Abstract/Description
-
An important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity....
Show moreAn important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity. Here, we report the results of an experiment with males from two populations of the poeciliid fish, Heterandria formosa, designed to examine the relative influence of environmental maternal effects and environmental effects experienced during growth and development on body morphology, and, in addition, whether the balance among those effects is unique to each population. We used a factorial design that varied thermal environment and water chemistry experienced by mothers and thermal environment and water chemistry experienced by offspring. We found substantial differences between the two populations in their maternal and offspring norms of reaction of male body morphology to differences in thermal environment and water chemistry. We also found that the balance between maternal effects and postparturition environmental effects differed from one thermal regime to another and among traits. These results indicate that environmental maternal effects can be decidedly population-specific and, as a result, might either contribute to the appearance of or blur evidence for local adaptation. These results also suggest that local adaptation might also occur through the evolution of maternal norms of reaction to important, and varying, environmental factors.
Show less - Date Issued
- 2018-06-01
- Identifier
- FSU_libsubv1_wos_000436799100024, 10.1002/ece3.4166
- Format
- Citation
- Title
- Why Does The Magnitude Of Genotype-by-environment Interaction Vary?.
- Creator
-
Saltz, Julia B., Bell, Alison M., Flint, Jonathan, Gomulkiewicz, Richard, Hughes, Kimberly A., Keagy, Jason
- Abstract/Description
-
Genotype-by-environment interaction (GxE), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. GxE has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although GxE has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why GxE is so evident in some traits and...
Show moreGenotype-by-environment interaction (GxE), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. GxE has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although GxE has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why GxE is so evident in some traits and populations, but minimal or absent in others. To encourage synthetic research in this area, we review diverse hypotheses for the underlying biological causes of variation in GxE. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in GxE and suggest some important next steps.
Show less - Date Issued
- 2018-06-01
- Identifier
- FSU_libsubv1_wos_000436799100031, 10.1002/ece3.4128
- Format
- Citation
- Title
- Promoter Capture Hi-c: High-resolution, Genome-wide Profiling Of Promoter Interactions.
- Creator
-
Schoenfelder, Stefan, Javierre, Biola-Maria, Furlan-Magaril, Mayra, Wingett, Steven W., Fraser, Peter
- Abstract/Description
-
The three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to...
Show moreThe three-dimensional organization of the genome is linked to its function. For example, regulatory elements such as transcriptional enhancers control the spatio-temporal expression of their target genes through physical contact, often bridging considerable (in some cases hundreds of kilobases) genomic distances and bypassing nearby genes. The human genome harbors an estimated one million enhancers, the vast majority of which have unknown gene targets. Assigning distal regulatory regions to their target genes is thus crucial to understand gene expression control. We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. In PCHi-C, highly complex Hi-C libraries are specifically enriched for promoter sequences through in-solution hybrid selection with thousands of biotinylated RNA baits complementary to the ends of all promoter-containing restriction fragments. The aim is to then pull-down promoter sequences and their frequent interaction partners such as enhancers and other potential regulatory elements. After high-throughput paired-end sequencing, a statistical test is applied to each promoter-ligated restriction fragment to identify significant PIRs at the restriction fragment level. We have used PCHi-C to generate an atlas of long-range promoter interactions in dozens of human and mouse cell types. These promoter interactome maps have contributed to a greater understanding of mammalian gene expression control by assigning putative regulatory regions to their target genes and revealing preferential spatial promoter-promoter interaction networks. This information also has high relevance to understanding human genetic disease and the identification of potential disease genes, by linking non-coding disease-associated sequence variants in or near control sequences to their target genes.
Show less - Date Issued
- 2018-06-01
- Identifier
- FSU_libsubv1_wos_000444752100043, 10.3791/57320
- Format
- Citation
- Title
- Spindly is required for rapid migration of human cells.
- Creator
-
Conte, Claudia, Baird, Michelle A, Davidson, Michael W, Griffis, Eric R
- Abstract/Description
-
Dynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular...
Show moreDynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular localization. Spindly is a protein that targets dynein/dynactin to kinetochores in mitosis and can activate its motility However, no role for Spindly in interphase dynein/dynactin function has been found. We show that Spindly binds to the cell cortex and microtubule tips and colocalizes with dynein/dynactin at the leading edge of migrating U2OS cells and primary fibroblasts. U2OS cells that lack Spindly migrated slower in 2D than control cells, although centrosome polarization appeared to happen properly in the absence of Spindly. Re-expression of Spindly rescues migration, but the expression of a mutant, which is defective for dynactin binding, failed to rescue this defect. Taken together, these data demonstrate that Spindly plays an important role in mediating a subset of dynein/dynactin's function in cell migration.
Show less - Date Issued
- 2018-05-29
- Identifier
- FSU_pmch_29685992, 10.1242/bio.033233, PMC5992534, 29685992, 29685992, bio.033233
- Format
- Citation
- Title
- Unique maternal and environmental effects on the body morphology of the Least Killifish, .
- Creator
-
Landy, J Alex, Travis, Joseph
- Abstract/Description
-
An important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity....
Show moreAn important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity. Here, we report the results of an experiment with males from two populations of the poeciliid fish, , designed to examine the relative influence of environmental maternal effects and environmental effects experienced during growth and development on body morphology, and, in addition, whether the balance among those effects is unique to each population. We used a factorial design that varied thermal environment and water chemistry experienced by mothers and thermal environment and water chemistry experienced by offspring. We found substantial differences between the two populations in their maternal and offspring norms of reaction of male body morphology to differences in thermal environment and water chemistry. We also found that the balance between maternal effects and postparturition environmental effects differed from one thermal regime to another and among traits. These results indicate that environmental maternal effects can be decidedly population-specific and, as a result, might either contribute to the appearance of or blur evidence for local adaptation. These results also suggest that local adaptation might also occur through the evolution of maternal norms of reaction to important, and varying, environmental factors.
Show less - Date Issued
- 2018-05-24
- Identifier
- FSU_pmch_29988417, 10.1002/ece3.4166, PMC6024122, 29988417, 29988417, ECE34166
- Format
- Citation
- Title
- Why does the magnitude of genotype-by-environment interaction vary?.
- Creator
-
Saltz, Julia B, Bell, Alison M, Flint, Jonathan, Gomulkiewicz, Richard, Hughes, Kimberly A, Keagy, Jason
- Abstract/Description
-
Genotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and...
Show moreGenotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and populations, but minimal or absent in others. To encourage synthetic research in this area, we review diverse hypotheses for the underlying biological causes of variation in G × E. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in G × E and suggest some important next steps.
Show less - Date Issued
- 2018-05-08
- Identifier
- FSU_pmch_29988442, 10.1002/ece3.4128, PMC6024136, 29988442, 29988442, ECE34128
- Format
- Citation
- Title
- Spindly Is Required For Rapid Migration Of Human Cells.
- Creator
-
Conte, Claudia, Baird, Michelle A., Davidson, Michael W., Griffis, Eric R.
- Abstract/Description
-
Dynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular...
Show moreDynein is the sole processive minus-end-directed microtubule motor found in animals. It has roles in cell division, membrane trafficking, and cell migration. Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular localization. Spindly is a protein that targets dynein/dynactin to kinetochores in mitosis and can activate its motility in vitro. However, no role for Spindly in interphase dynein/dynactin function has been found. We show that Spindly binds to the cell cortex and microtubule tips and colocalizes with dynein/dynactin at the leading edge of migrating U2OS cells and primary fibroblasts. U2OS cells that lack Spindly migrated slower in 2D than control cells, although centrosome polarization appeared to happen properly in the absence of Spindly. Re-expression of Spindly rescues migration, but the expression of a mutant, which is defective for dynactin binding, failed to rescue this defect. Taken together, these data demonstrate that Spindly plays an important role in mediating a subset of dynein/dynactin's function in cell migration.
Show less - Date Issued
- 2018-05-01
- Identifier
- FSU_libsubv1_wos_000434210800009, 10.1242/bio.033233
- Format
- Citation
- Title
- Genome-wide Analysis Of Replication Timing By Next-generation Sequencing With E/l Repli-seq.
- Creator
-
Marchal, Claire, Sasaki, Takayo, Vera, Daniel, Wilson, Korey, Sima, Jiao, Rivera-Mulia, Juan Carlos, Trevilla-Garcia, Claudia, Nogues, Coralin, Nafie, Ebtesam, Gilbert, David M.
- Abstract/Description
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Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early-and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next...
Show moreCycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early-and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.
Show less - Date Issued
- 2018-05-01
- Identifier
- FSU_libsubv1_wos_000431191400002, 10.1038/nprot.2017.148
- Format
- Citation
- Title
- Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.
- Creator
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Marchal, Claire, Sasaki, Takayo, Vera, Daniel, Wilson, Korey, Sima, Jiao, Rivera-Mulia, Juan Carlos, Trevilla-García, Claudia, Nogues, Coralin, Nafie, Ebtesam, Gilbert, David M
- Abstract/Description
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This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension...
Show moreThis protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.
Show less - Date Issued
- 2018-05-01
- Identifier
- FSU_pmch_29599440, 10.1038/nprot.2017.148, PMC6044726, 29599440, 29599440, nprot.2017.148
- Format
- Citation
- Title
- A Second Specimen Of Citipati Osmolskae Associated With A Nest Of Eggs From Ukhaa Tolgod, Omnogov Aimag, Mongolia.
- Creator
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Norell, Mark A., Balanoff, Amy M., Barta, Daniel E., Erickson, Gregory M.
- Abstract/Description
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Adult dinosaurs preserved attending their nests in brooding positions are among the rarest vertebrate fossils. By far the most common occurrences are members of the dinosaur group Oviraptorosauria. The first finds of these were specimens recovered from the Djadokhta Formation at the Mongolian locality of Ukhaa Tolgod and the Chinese locality of Bayan Mandahu. Since the initial discovery of these specimens, a few more occurrences of nesting oviraptors have been found at other Asian localities....
Show moreAdult dinosaurs preserved attending their nests in brooding positions are among the rarest vertebrate fossils. By far the most common occurrences are members of the dinosaur group Oviraptorosauria. The first finds of these were specimens recovered from the Djadokhta Formation at the Mongolian locality of Ukhaa Tolgod and the Chinese locality of Bayan Mandahu. Since the initial discovery of these specimens, a few more occurrences of nesting oviraptors have been found at other Asian localities. Here we report on a second nesting oviraptorid specimen (IGM 100/1004) sitting in a brooding position atop a nest of eggs from Ukhaa Tolgod, Omnogov, Mongolia. This is a large specimen of the ubiquitous Ukhaa Tolgod taxon Citipati osmolskae. It is approximately 11% larger based on humeral length than the original Ukhaa Tolgod nesting Citipati osmolskae specimen (IGM 100/979), yet eggshell structure and egg arrangement are identical. No evidence for colonial breeding of these animals has been recovered. Reexamination of another "nesting" oviraptorosaur, the holotype of Oviraptor philoceratops (AMNH FARB 6517) indicates that in addition to the numerous partial eggs associated with the original skeleton that originally led to its referral as a protoceratopsian predator, there are the remains of a tiny theropod. This hind limb can be provisionally assigned to Oviraptoridae. It is thus at least possible that some of the eggs associated with the holotype had hatched and the perinates had not left the nest.
Show less - Date Issued
- 2018-04-26
- Identifier
- FSU_libsubv1_wos_000430953800001
- Format
- Citation
- Title
- Iseg: An Efficient Algorithm For Segmentation Of Genomic And Epigenomic Data.
- Creator
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Girimurugan, Senthil B., Liu, Yuhang, Lung, Pei-Yau, Vera, Daniel L., Dennis, Jonathan H., Bass, Hank W., Zhang, Jinfeng
- Abstract/Description
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Background: Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems. Results: We designed an efficient...
Show moreBackground: Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems. Results: We designed an efficient algorithm, called iSeg, for segmentation of genomic and epigenomic profiles. iSeg first utilizes dynamic programming to identify candidate segments and test for significance. It then uses a novel data structure based on two coupled balanced binary trees to detect overlapping significant segments and update them simultaneously during searching and refinement stages. Refinement and merging of significant segments are performed at the end to generate the final set of segments. By using an objective function based on the p-values of the segments, the algorithm can serve as a general computational framework to be combined with different assumptions on the distributions of the data. As a general segmentation method, it can segment different types of genomic and epigenomic data, such as DNA copy number variation, nucleosome occupancy, nuclease sensitivity, and differential nuclease sensitivity data. Using simple t-tests to compute p-values across multiple datasets of different types, we evaluate iSeg using both simulated and experimental datasets and show that it performs satisfactorily when compared with some other popular methods, which often employ more sophisticated statistical models. Implemented in C++, iSeg is also very computationally efficient, well suited for large numbers of input profiles and data with very long sequences. Conclusions: We have developed an efficient general-purpose segmentation tool and showed that it had comparable or more accurate results than many of the most popular segment-calling algorithms used in contemporary genomic data analysis. iSeg is capable of analyzing datasets that have both positive and negative values. Tunable parameters allow users to readily adjust the statistical stringency to best match the biological nature of individual datasets, including widely or sparsely mapped genomic datasets or those with non-normal distributions.
Show less - Date Issued
- 2018-04-11
- Identifier
- FSU_libsubv1_wos_000431023300006, 10.1186/s12859-018-2140-3
- Format
- Citation
- Title
- Insect Herbivores Increase The Spatial Aggregation Of A Clonal Plant.
- Creator
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Hakes, Alyssa S., Halpern, Stacey, Underwood, Nora
- Abstract/Description
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Premise of research.In a plant population, the pattern of spatial dispersion from uniform to strongly aggregated can influence the intensity of ecological interactions, including those between plants and their consumers, such as herbivorous insects. Whether insect herbivores also contribute to the generation of dispersion patterns within plant populations, however, is not well understood. We investigated how insect herbivory and plant density interact to influence the degree of aggregation of...
Show morePremise of research.In a plant population, the pattern of spatial dispersion from uniform to strongly aggregated can influence the intensity of ecological interactions, including those between plants and their consumers, such as herbivorous insects. Whether insect herbivores also contribute to the generation of dispersion patterns within plant populations, however, is not well understood. We investigated how insect herbivory and plant density interact to influence the degree of aggregation of stems in experimental plots of the clonal perennial herb Solanum carolinense, a noxious weed in the southeastern United States and invasive in other parts of the world.Methodology.We planted S. carolinense in 40 experimental plots at five densities and maintained each plot at one of two herbivory levels. Stems in every plot were initially planted in a uniform dispersion pattern. For 3 yr, we quantified the dispersion of clonal recruits in each plot at six spatial scales.Pivotal results.At larger spatial scales, we found significant interactions between plant density and insect herbivory. In plots with herbivores, spatial aggregation increased as plant density decreased, but this relationship was weak or nonexistent in plots where herbivores were excluded (herbivore-excluded plots exhibited random dispersion of stems across all densities). Solanum carolinense in plots exposed to herbivores were on average twice as aggregated as those that had herbivores excluded.Conclusions.These results suggest that insect herbivores can influence clonal growth or ramet survival in ways that increase population-level aggregation of S. carolinense. Our findings also imply that S. carolinense populations in its invasive range may have increased spatial spread and decreased intraspecific competition when herbivory is low. We discuss the potential for specific types of feedbacks between insect damage and plant dispersion, highlighting important targets for future research.
Show less - Date Issued
- 2018-04
- Identifier
- FSU_libsubv1_wos_000426758000005, 10.1086/696685
- Format
- Citation
- Title
- Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven by Four Toxin Families.
- Creator
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Strickland, Jason L, Mason, Andrew J, Rokyta, Darin R, Parkinson, Christopher L
- Abstract/Description
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Phenotypic diversity generated through altered gene expression is a primary mechanism facilitating evolutionary response in natural systems. By linking the phenotype to genotype through transcriptomics, it is possible to determine what changes are occurring at the molecular level. High phenotypic diversity has been documented in rattlesnake venom, which is under strong selection due to its role in prey acquisition and defense. Rattlesnake venom can be characterized by the presence (Type A) or...
Show morePhenotypic diversity generated through altered gene expression is a primary mechanism facilitating evolutionary response in natural systems. By linking the phenotype to genotype through transcriptomics, it is possible to determine what changes are occurring at the molecular level. High phenotypic diversity has been documented in rattlesnake venom, which is under strong selection due to its role in prey acquisition and defense. Rattlesnake venom can be characterized by the presence (Type A) or absence (Type B) of a type of neurotoxic phospholipase A 2 (PLA 2 ), such as Mojave toxin, that increases venom toxicity. Mojave rattlesnakes (), represent this diversity as both venom types are found within this species and within a single panmictic population in the Sonoran Desert. We used comparative venom gland transcriptomics of nine specimens of from this region to test whether expression differences explain diversity within and between venom types. Type A individuals expressed significantly fewer toxins than Type B individuals owing to the diversity of C-type lectins (CTLs) and snake venom metalloproteinases (SVMPs) found in Type B animals. As expected, both subunits of Mojave toxin were exclusively found in Type A individuals but we found high diversity in four additional PLA 2 s that was not associated with a venom type. Myotoxin expression and toxin number variation was not associated with venom type, and myotoxin had the highest range of expression of any toxin class. Our study represents the most comprehensive transcriptomic profile of the venom type dichotomy in rattlesnakes and . Even intra-specifically, Mojave rattlesnakes showcase the diversity of snake venoms and illustrate that variation within venom types blurs the distinction of the venom dichotomy.
Show less - Date Issued
- 2018-03-23
- Identifier
- FSU_pmch_29570631, 10.3390/toxins10040135, PMC5923301, 29570631, 29570631, toxins10040135
- Format
- Citation
- Title
- Elevated Anxiety And Impaired Attention In Super-smeller, Kv1.3 Knockout Mice.
- Creator
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Huang, Zhenbo, Hoffman, Carlie A., Chelette, Brandon M., Thiebaud, Nicolas, Fadool, Debra A.
- Abstract/Description
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It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is...
Show moreIt has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3-/-), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3-/- mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3-/- mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3-/- mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3-/- mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3-/- mice may have behaviors associated with inattentiveness.
Show less - Date Issued
- 2018-03-19
- Identifier
- FSU_libsubv1_wos_000427729100001, 10.3389/fnbeh.2018.00049
- Format
- Citation
- Title
- Elevated Anxiety and Impaired Attention in Super-Smeller, Kv1.3 Knockout Mice.
- Creator
-
Huang, Zhenbo, Hoffman, Carlie A, Chelette, Brandon M, Thiebaud, Nicolas, Fadool, Debra A
- Abstract/Description
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It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is...
Show moreIt has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3-/-), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3-/- mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3-/- mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3-/- mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3-/- mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3-/- mice may have behaviors associated with inattentiveness.
Show less - Date Issued
- 2018-03-19
- Identifier
- FSU_pmch_29615878, 10.3389/fnbeh.2018.00049, PMC5867313, 29615878, 29615878
- Format
- Citation