Search results

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

Title: Generalized Ensemble Sampling of Enzyme Reaction Free Energy Pathways.
Creator: Wu, D, Fajer, M I, Cao, L, Cheng, X, Yang, W
Abstract/Description: Free energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a...
Show moreFree energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a tutorial-like tour on an emerging topic: generalized ensemble sampling of enzyme reaction free energy path. The discussion is largely focused on our own studies, particularly ones based on the metadynamics free energy sampling method and the on-the-path random walk path sampling method. We hope that this minipresentation will provide interested practitioners some meaningful guidance for future algorithm formulation and application study.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27498634, 10.1016/bs.mie.2016.05.012, PMC4978182, 27498634, 27498634, S0076-6879(16)30047-7
Format: Citation

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

Title: The ties that bond: neurochemistry of attachment in voles..
Creator: Gobrogge, Kyle, Wang, Zuoxin
Abstract/Description: In socially monogamous prairie voles (Microtus ochrogaster), mating induces three primary types of behavior; namely, partner preference, selective aggression toward conspecific strangers, and bi-parental care, making this rodent an ideal model system to study sociality and underlying neurochemical mechanisms associated with monogamous mating strategies. Here, we highlight species differences in neurochemical receptor distributions associated with mating experience leading to the establishment...
Show moreIn socially monogamous prairie voles (Microtus ochrogaster), mating induces three primary types of behavior; namely, partner preference, selective aggression toward conspecific strangers, and bi-parental care, making this rodent an ideal model system to study sociality and underlying neurochemical mechanisms associated with monogamous mating strategies. Here, we highlight species differences in neurochemical receptor distributions associated with mating experience leading to the establishment of stable pair-bonds. Specifically, we illustrate the role of nucleus accumbens dopamine in programming the formation and maintenance of monogamous bonds and describe the role of anterior hypothalamic vasopressin in the regulation of selective aggression. We conclude by discussing recent molecular work in voles and emphasize the importance of this rodent for future research in the behavioral neurobiology field.
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Date Issued: 2016-06-01
Identifier: FSU_pmch_27131991, 10.1016/j.conb.2016.04.011, PMC4921794, 27131991, 27131991, S0959-4388(16)30046-0
Format: Citation

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

Title: Neurochemical Mediation of Affiliation and Aggression Associated With Pair-Bonding.
Creator: Gobrogge, Kyle L, Jia, Xixi, Liu, Yan, Wang, Zuoxin
Abstract/Description: The neuropeptides vasopressin and corticotropin-releasing factor facilitate, while serotonin inhibits, aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, Fluoro-Gold, and tested for affiliation and aggression toward a female partner or novel female subject. Subsequent immunocytochemical...
Show moreThe neuropeptides vasopressin and corticotropin-releasing factor facilitate, while serotonin inhibits, aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, Fluoro-Gold, and tested for affiliation and aggression toward a female partner or novel female subject. Subsequent immunocytochemical experiments examined neuronal activation using Fos and neurochemical/neuroreceptor profiles on brain areas involved in these social behaviors. Finally, a series of behavioral pharmacologic and real-time in vivo brain microdialysis experiments were performed on male prairie voles displaying affiliation or aggression. We localized a subpopulation of excitatory vasopressin neurons in the anterior hypothalamus that may gate corticotropin-releasing factor output from the amygdala to the anterior hypothalamus and then the lateral septum to modulate aggression associated with mate guarding. Conversely, we identified a subset of inhibitory serotonergic projection neurons in the dorsal raphe that project to the anterior hypothalamus and may mediate the spatiotemporal release of neuropeptides and their interactions in modulating aggression and affiliation. Together, this study establishes the medial extended amygdala as a major neural substrate regulating the switch between positive and negative affective states, wherein several neurochemicals converge and interact to coordinate divergent social behaviors.
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Date Issued: 2017-02-01
Identifier: FSU_pmch_27129413, 10.1016/j.biopsych.2016.02.013, PMC4992658, 27129413, 27129413, S0006-3223(16)00100-1
Format: Citation

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

Title: Spatial and Temporal Variation in the Effects of Climatic Variables on Dugong Calf Production.
Creator: Fuentes, Mariana M P B, Delean, Steven, Grayson, Jillian, Lavender, Sally, Logan, Murray, Marsh, Helene
Abstract/Description: Knowledge of the relationships between environmental forcing and demographic parameters is important for predicting responses from climatic changes and to manage populations effectively. We explore the relationships between the proportion of sea cows (Dugong dugon) classified as calves and four climatic drivers (rainfall anomaly, Southern Oscillation El Niño Index [SOI], NINO 3.4 sea surface temperature index, and number of tropical cyclones) at a range of spatially distinct locations in...
Show moreKnowledge of the relationships between environmental forcing and demographic parameters is important for predicting responses from climatic changes and to manage populations effectively. We explore the relationships between the proportion of sea cows (Dugong dugon) classified as calves and four climatic drivers (rainfall anomaly, Southern Oscillation El Niño Index [SOI], NINO 3.4 sea surface temperature index, and number of tropical cyclones) at a range of spatially distinct locations in Queensland, Australia, a region with relatively high dugong density. Dugong and calf data were obtained from standardized aerial surveys conducted along the study region. A range of lagged versions of each of the focal climatic drivers (1 to 4 years) were included in a global model containing the proportion of calves in each population crossed with each of the lagged versions of the climatic drivers to explore relationships. The relative influence of each predictor was estimated via Gibbs variable selection. The relationships between the proportion of dependent calves and the climatic drivers varied spatially and temporally, with climatic drivers influencing calf counts at sub-regional scales. Thus we recommend that the assessment of and management response to indirect climatic threats on dugongs should also occur at sub-regional scales.
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Date Issued: 2016-06-29
Identifier: FSU_pmch_27355367, 10.1371/journal.pone.0155675, PMC4927176, 27355367, 27355367, PONE-D-15-52097
Format: Citation

Title: Historical baselines and the future of shell calcification for a foundation species in a changing ocean.
Creator: Pfister, Catherine A, Roy, Kaustuv, Wootton, J Timothy, McCoy, Sophie J, Paine, Robert T, Suchanek, Thomas H, Sanford, Eric
Abstract/Description: Seawater pH and the availability of carbonate ions are decreasing due to anthropogenic carbon dioxide emissions, posing challenges for calcifying marine species. Marine mussels are of particular concern given their role as foundation species worldwide. Here, we document shell growth and calcification patterns in Mytilus californianus, the California mussel, over millennial and decadal scales. By comparing shell thickness across the largest modern shells, the largest mussels collected in the...
Show moreSeawater pH and the availability of carbonate ions are decreasing due to anthropogenic carbon dioxide emissions, posing challenges for calcifying marine species. Marine mussels are of particular concern given their role as foundation species worldwide. Here, we document shell growth and calcification patterns in Mytilus californianus, the California mussel, over millennial and decadal scales. By comparing shell thickness across the largest modern shells, the largest mussels collected in the 1960s-1970s and shells from two Native American midden sites (∼1000-2420 years BP), we found that modern shells are thinner overall, thinner per age category and thinner per unit length. Thus, the largest individuals of this species are calcifying less now than in the past. Comparisons of shell thickness in smaller individuals over the past 10-40 years, however, do not show significant shell thinning. Given our sampling strategy, these results are unlikely to simply reflect within-site variability or preservation effects. Review of environmental and biotic drivers known to affect shell calcification suggests declining ocean pH as a likely explanation for the observed shell thinning. Further future decreases in shell thickness could have significant negative impacts on M. californianus survival and, in turn, negatively impact the species-rich complex that occupies mussel beds.
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Date Issued: 2016-06-15
Identifier: FSU_pmch_27306049, 10.1098/rspb.2016.0392, PMC4920315, 27306049, 27306049, rspb.2016.0392
Format: Citation

Title: Cocaine-induced neurodevelopmental deficits and underlying mechanisms.
Creator: Martin, Melissa M, Graham, Devon L, McCarthy, Deirdre M, Bhide, Pradeep G, Stanwood, Gregg D
Abstract/Description: Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with...
Show moreExposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. Birth Defects Research (Part C) 108:147-173, 2016. © 2016 Wiley Periodicals, Inc.
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Date Issued: 2016-06-01
Identifier: FSU_pmch_27345015, 10.1002/bdrc.21132, PMC5538582, 27345015, 27345015
Format: Citation

Title: Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
Creator: Duclot, Florian, Perez-Taboada, Iara, Wright, Katherine N, Kabbaj, Mohamed
Abstract/Description: Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear...
Show moreOnly a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory.
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27343386, 10.1016/j.neuropharm.2016.06.022, PMC5017153, 27343386, 27343386, S0028-3908(16)30275-1
Format: Citation

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

Title: GABAergic mechanisms contributing to categorical amygdala responses to chemosensory signals.
Creator: Westberry, Jenne M, Meredith, Michael
Abstract/Description: Chemosensory stimuli from conspecific and heterospecific animals, elicit categorically different immediate-early gene response-patterns in medial amygdala in male hamsters and mice. We previously showed that conspecific signals activate posterior (MeP) as well as anterior medial amygdala (MeA), and especially relevant heterospecific signals such as chemosensory stimuli from potential predators also activate MeP in mice. Other heterospecific chemosignals activate MeA, but not MeP. Here we show...
Show moreChemosensory stimuli from conspecific and heterospecific animals, elicit categorically different immediate-early gene response-patterns in medial amygdala in male hamsters and mice. We previously showed that conspecific signals activate posterior (MeP) as well as anterior medial amygdala (MeA), and especially relevant heterospecific signals such as chemosensory stimuli from potential predators also activate MeP in mice. Other heterospecific chemosignals activate MeA, but not MeP. Here we show that male hamster amygdala responds significantly differentially to different conspecific signals, by activating different proportions of cells of different phenotype, possibly leading to differential activation of downstream circuits. Heterospecific signals that fail to activate MeP do activate GABA-immunoreactive cells in the adjacent caudal main intercalated nucleus (mICNc) and elicit selective suppression of MeP cells bearing GABA-Receptors, suggesting GABA inhibition in MeP by GABAergic cells in mICNc. Overall, work presented here suggests that medial amygdala may discriminate between important conspecific social signals, distinguish them from the social signals of other species and convey that information to brain circuits eliciting appropriate social behavior.
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Date Issued: 2016-09-07
Identifier: FSU_pmch_27329335, 10.1016/j.neuroscience.2016.06.020, PMC4955787, 27329335, 27329335, S0306-4522(16)30250-0
Format: Citation

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

Title: The neurobiology of pair bond formation, bond disruption, and social buffering.
Creator: Lieberwirth, Claudia, Wang, Zuoxin
Abstract/Description: Enduring social bonds play an essential role in human society. These bonds positively affect psychological, physiological, and behavioral functions. Here, we review the recent literature on the neurobiology, particularly the role of oxytocin and dopamine, of pair bond formation, bond disruption, and social buffering effects on stress responses, from studies utilizing the socially monogamous prairie vole (Microtus ochrogaster).
Date Issued: 2016-10-01
Identifier: FSU_pmch_27290660, 10.1016/j.conb.2016.05.006, PMC5072360, 27290660, 27290660, S0959-4388(16)30065-4
Format: Citation

Title: Pre-Clovis occupation 14,550 years ago at the Page-Ladson site, Florida, and the peopling of the Americas.
Creator: Halligan, Jessi J, Waters, Michael R, Perrotti, Angelina, Owens, Ivy J, Feinberg, Joshua M, Bourne, Mark D, Fenerty, Brendan, Winsborough, Barbara, Carlson, David, Fisher,...
Show moreHalligan, Jessi J, Waters, Michael R, Perrotti, Angelina, Owens, Ivy J, Feinberg, Joshua M, Bourne, Mark D, Fenerty, Brendan, Winsborough, Barbara, Carlson, David, Fisher, Daniel C, Stafford, Thomas W, Dunbar, James S
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Abstract/Description: Stone tools and mastodon bones occur in an undisturbed geological context at the Page-Ladson site, Florida. Seventy-one radiocarbon ages show that ~14,550 calendar years ago (cal yr B.P.), people butchered or scavenged a mastodon next to a pond in a bedrock sinkhole within the Aucilla River. This occupation surface was buried by ~4 m of sediment during the late Pleistocene marine transgression, which also left the site submerged. Sporormiella and other proxy evidence from the sediments...
Show moreStone tools and mastodon bones occur in an undisturbed geological context at the Page-Ladson site, Florida. Seventy-one radiocarbon ages show that ~14,550 calendar years ago (cal yr B.P.), people butchered or scavenged a mastodon next to a pond in a bedrock sinkhole within the Aucilla River. This occupation surface was buried by ~4 m of sediment during the late Pleistocene marine transgression, which also left the site submerged. Sporormiella and other proxy evidence from the sediments indicate that hunter-gatherers along the Gulf Coastal Plain coexisted with and utilized megafauna for ~2000 years before these animals became extinct at ~12,600 cal yr B.P. Page-Ladson expands our understanding of the earliest colonizers of the Americas and human-megafauna interaction before extinction.
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Date Issued: 2016-05-13
Identifier: FSU_pmch_27386553, 10.1126/sciadv.1600375, PMC4928949, 27386553, 27386553, 1600375
Format: Citation

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

Title: An insight into the thermodynamic characteristics of human thrombopoietin complexation with TN1 antibody.
Creator: Arai, Shigeki, Shibazaki, Chie, Adachi, Motoyasu, Honjo, Eijiro, Tamada, Taro, Maeda, Yoshitake, Tahara, Tomoyuki, Kato, Takashi, Miyazaki, Hiroshi, Blaber, Michael, Kuroki, Ryota
Abstract/Description: Human thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody-hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen-binding fragment (Fab) derived from the TN1 antibody (TN1-Fab). To clarify the mechanism by which hTPO is recognized by TN1-Fab the conformation of free TN1-Fab was determined to a resolution of 2.0 Å using X-ray...
Show moreHuman thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody-hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen-binding fragment (Fab) derived from the TN1 antibody (TN1-Fab). To clarify the mechanism by which hTPO is recognized by TN1-Fab the conformation of free TN1-Fab was determined to a resolution of 2.0 Å using X-ray crystallography and compared with the hTPO-bound form of TN1-Fab determined by a previous study. This structural comparison revealed that the conformation of TN1-Fab does not substantially change after hTPO binding and a set of 15 water molecules is released from the antigen-binding site (paratope) of TN1-Fab upon hTPO complexation. Interestingly, the heat capacity change (ΔCp) measured by ITC (-1.52 ± 0.05 kJ mol(-1) K(-1) ) differed significantly from calculations based upon the X-ray structure data of the hTPO-bound and unbound forms of TN1-Fab (-1.02 ∼ 0.25 kJ mol(-1) K(-1) ) suggesting that hTPO undergoes an induced-fit conformational change combined with significant desolvation upon TN1-Fab binding. The results shed light on the structural biology associated with neutralizing antibody recognition.
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27419667, 10.1002/pro.2985, PMC5029525, 27419667, 27419667
Format: Citation

Title: The role of ΔfosB in the medial preoptic area: Differential effects of mating and cocaine history..
Creator: McHenry, Jenna A, Robison, Christopher L, Bell, Genevieve A, Vialou, Vincent V, Bolaños-Guzmán, Carlos A, Nestler, Eric J, Hull, Elaine M
Abstract/Description: The transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day...
Show moreThe transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of ΔFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase ΔFosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing ΔFosB, its dominant negative antagonist ΔJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. ΔFosB overexpression impaired copulation and promoted female-directed aggression, compared to ΔJunD and control males. These data suggest that ΔFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. (PsycINFO Database Record
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27657309, 10.1037/bne0000160, PMC5201202, 27657309, 27657309, 2016-45747-001
Format: Citation

Title: Structure of myosin filaments from relaxed flight muscle by cryo-EM at 6 Å resolution.
Creator: Hu, Zhongjun, Taylor, Dianne W, Reedy, Michael K, Edwards, Robert J, Taylor, Kenneth A
Abstract/Description: We describe a cryo-electron microscopy three-dimensional image reconstruction of relaxed myosin II-containing thick filaments from the flight muscle of the giant water bug . The relaxed thick filament structure is a key element of muscle physiology because it facilitates the reextension process following contraction. Conversely, the myosin heads must disrupt their relaxed arrangement to drive contraction. Previous models predicted that myosin was unique in having an intermolecular head-head...
Show moreWe describe a cryo-electron microscopy three-dimensional image reconstruction of relaxed myosin II-containing thick filaments from the flight muscle of the giant water bug . The relaxed thick filament structure is a key element of muscle physiology because it facilitates the reextension process following contraction. Conversely, the myosin heads must disrupt their relaxed arrangement to drive contraction. Previous models predicted that myosin was unique in having an intermolecular head-head interaction, as opposed to the intramolecular head-head interaction observed in all other species. In contrast to the predicted model, we find an intramolecular head-head interaction, which is similar to that of other thick filaments but oriented in a distinctly different way. The arrangement of myosin's long α-helical coiled-coil rod domain has been hypothesized as either curved layers or helical subfilaments. Our reconstruction is the first report having sufficient resolution to track the rod α helices in their native environment at resolutions ~5.5 Å, and it shows that the layer arrangement is correct for . Threading separate paths through the forest of myosin coiled coils are four nonmyosin peptides. We suggest that the unusual position of the heads and the rod arrangement separated by nonmyosin peptides are adaptations for mechanical signal transduction whereby applied tension disrupts the myosin heads as a component of stretch activation.
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Date Issued: 2016-09-30
Identifier: FSU_pmch_27704041, 10.1126/sciadv.1600058, PMC5045269, 27704041, 27704041, 1600058
Format: Citation

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

Title: 14-3-3τ promotes surface expression of Cav2.2 (α1B) Ca2+ channels.
Creator: Liu, Feng, Zhou, Qin, Zhou, Jie, Sun, Hao, Wang, Yan, Zou, Xiuqun, Feng, Lingling, Hou, Zhaoyuan, Zhou, Aiwu, Zhou, Yi, Li, Yong
Abstract/Description: Surface expression of voltage-gated Ca(2+) (Cav) channels is important for their function in calcium homeostasis in the physiology of excitable cells, but whether or not and how the α1 pore-forming subunits of Cav channels are trafficked to plasma membrane in the absence of the known Cav auxiliary subunits, β and α2δ, remains mysterious. Here we showed that 14-3-3 proteins promoted functional surface expression of the Cav2.2 α1B channel in transfected tsA-201 cells in the absence of any known...
Show moreSurface expression of voltage-gated Ca(2+) (Cav) channels is important for their function in calcium homeostasis in the physiology of excitable cells, but whether or not and how the α1 pore-forming subunits of Cav channels are trafficked to plasma membrane in the absence of the known Cav auxiliary subunits, β and α2δ, remains mysterious. Here we showed that 14-3-3 proteins promoted functional surface expression of the Cav2.2 α1B channel in transfected tsA-201 cells in the absence of any known Cav auxiliary subunit. Both the surface to total ratio of the expressed α1B protein and the current density of voltage step-evoked Ba(2+) current were markedly suppressed by the coexpression of a 14-3-3 antagonist construct, pSCM138, but not its inactive control, pSCM174, as determined by immunofluorescence assay and whole cell voltage clamp recording, respectively. By contrast, coexpression with 14-3-3τ significantly enhanced the surface expression and current density of the Cav2.2 α1B channel. Importantly, we found that between the two previously identified 14-3-3 binding regions at the α1B C terminus, only the proximal region (amino acids 1706-1940), closer to the end of the last transmembrane domain, was retained by the endoplasmic reticulum and facilitated by 14-3-3 to traffic to plasma membrane. Additionally, we showed that the 14-3-3/Cav β subunit coregulated the surface expression of Cav2.2 channels in transfected tsA-201 cells and neurons. Altogether, our findings reveal a previously unidentified regulatory function of 14-3-3 proteins in promoting the surface expression of Cav2.2 α1B channels.
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Date Issued: 2015-01-30
Identifier: FSU_pmch_25516596, 10.1074/jbc.M114.567800, PMC4317001, 25516596, 25516596, M114.567800
Format: Citation

Title: 14-3-3 proteins are required for hippocampal long-term potentiation and associative learning and memory.
Creator: Qiao, Haifa, Foote, Molly, Graham, Kourtney, Wu, Yuying, Zhou, Yi
Abstract/Description: 14-3-3 is a family of regulatory proteins highly expressed in the brain. Previous invertebrate studies have demonstrated the importance of 14-3-3 in the regulation of synaptic functions and learning and memory. However, the in vivo role of 14-3-3 in these processes has not been determined using mammalian animal models. Here, we report the behavioral and electrophysiological characterization of a new animal model of 14-3-3 proteins. These transgenic mice, considered to be a 14-3-3 functional...
Show more14-3-3 is a family of regulatory proteins highly expressed in the brain. Previous invertebrate studies have demonstrated the importance of 14-3-3 in the regulation of synaptic functions and learning and memory. However, the in vivo role of 14-3-3 in these processes has not been determined using mammalian animal models. Here, we report the behavioral and electrophysiological characterization of a new animal model of 14-3-3 proteins. These transgenic mice, considered to be a 14-3-3 functional knock-out, express a known 14-3-3 inhibitor in various brain regions of different founder lines. We identify a founder-specific impairment in hippocampal-dependent learning and memory tasks, as well as a correlated suppression in long-term synaptic plasticity of the hippocampal synapses. Moreover, hippocampal synaptic NMDA receptor levels are selectively reduced in the transgenic founder line that exhibits both behavioral and synaptic plasticity deficits. Collectively, our findings provide evidence that 14-3-3 is a positive regulator of associative learning and memory at both the behavioral and cellular level.
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Date Issued: 2014-04-02
Identifier: FSU_pmch_24695700, 10.1523/JNEUROSCI.4393-13.2014, PMC3972712, 24695700, 24695700, 34/14/4801
Format: Citation

Title: Semiclosed Conformations of the Ligand-Binding Domains of NMDA Receptors during Stationary Gating.
Creator: Dai, Jian, Zhou, Huan-Xiang
Abstract/Description: NMDA receptors are tetrameric ligand-gated ion channels. In the continuous presence of saturating agonists, NMDA receptors undergo stationary gating, in which the channel stochastically switches between an open state that permits ion conductance and a closed state that prevents permeation. The ligand-binding domains (LBDs) of the four subunits are expected to have closed clefts in the channel-open state. On the other hand, there is little knowledge about the conformational status of the LBDs...
Show moreNMDA receptors are tetrameric ligand-gated ion channels. In the continuous presence of saturating agonists, NMDA receptors undergo stationary gating, in which the channel stochastically switches between an open state that permits ion conductance and a closed state that prevents permeation. The ligand-binding domains (LBDs) of the four subunits are expected to have closed clefts in the channel-open state. On the other hand, there is little knowledge about the conformational status of the LBDs in the channel-closed state during stationary gating. To probe the latter conformational status, Kussius and Popescu engineered interlobe disulfide cross-links in NMDA receptors and found that the cross-linking produced stationary gating kinetics that differed only subtly from that produced by agonist binding. These authors assumed that the cross-linking immobilized the LBDs in cleft-closed conformations, and consequently concluded that throughout stationary gating, agonist-bound LBDs also stayed predominantly in cleft-closed conformations and made only infrequent excursions to cleft-open conformations. Here, by calculating the conformational free energies of cross-linked and agonist-bound LBDs, we assess whether cross-linking actually traps the LBDs in cleft-closed conformations and delineate semiclosed conformations of agonist-bound LBDs that may potentially be thermodynamically and kinetically important during stationary gating. Our free-energy results show that the cross-linked LBDs are not locked in the fully closed form; rather, they sample semiclosed conformations almost as readily as the agonist-bound LBDs. Several lines of reasoning suggest that LBDs are semiclosed in the channel-closed state during stationary gating. Our free-energy simulations suggest possible structural details of such semiclosed LBD conformations, including intra- and intermolecular interactions that serve as alternatives to those in the cleft-closed conformations.
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Date Issued: 2016-10-04
Identifier: FSU_pmch_27705765, 10.1016/j.bpj.2016.08.010, PMC5052434, 27705765, 27705765, S0006-3495(16)30697-X
Format: Citation

Title: Expanding anchored hybrid enrichment to resolve both deep and shallow relationships within the spider tree of life.
Creator: Hamilton, Chris A, Lemmon, Alan R, Lemmon, Emily Moriarty, Bond, Jason E
Abstract/Description: Despite considerable effort, progress in spider molecular systematics has lagged behind many other comparable arthropod groups, thereby hindering family-level resolution, classification, and testing of important macroevolutionary hypotheses. Recently, alternative targeted sequence capture techniques have provided molecular systematics a powerful tool for resolving relationships across the Tree of Life. One of these approaches, Anchored Hybrid Enrichment (AHE), is designed to recover hundreds...
Show moreDespite considerable effort, progress in spider molecular systematics has lagged behind many other comparable arthropod groups, thereby hindering family-level resolution, classification, and testing of important macroevolutionary hypotheses. Recently, alternative targeted sequence capture techniques have provided molecular systematics a powerful tool for resolving relationships across the Tree of Life. One of these approaches, Anchored Hybrid Enrichment (AHE), is designed to recover hundreds of unique orthologous loci from across the genome, for resolving both shallow and deep-scale evolutionary relationships within non-model systems. Herein we present a modification of the AHE approach that expands its use for application in spiders, with a particular emphasis on the infraorder Mygalomorphae. Our aim was to design a set of probes that effectively capture loci informative at a diversity of phylogenetic timescales. Following identification of putative arthropod-wide loci, we utilized homologous transcriptome sequences from 17 species across all spiders to identify exon boundaries. Conserved regions with variable flanking regions were then sought across the tick genome, three published araneomorph spider genomes, and raw genomic reads of two mygalomorph taxa. Following development of the 585 target loci in the Spider Probe Kit, we applied AHE across three taxonomic depths to evaluate performance: deep-level spider family relationships (33 taxa, 327 loci); family and generic relationships within the mygalomorph family Euctenizidae (25 taxa, 403 loci); and species relationships in the North American tarantula genus Aphonopelma (83 taxa, 581 loci). At the deepest level, all three major spider lineages (the Mesothelae, Mygalomorphae, and Araneomorphae) were supported with high bootstrap support. Strong support was also found throughout the Euctenizidae, including generic relationships within the family and species relationships within the genus Aptostichus. As in the Euctenizidae, virtually identical topologies were inferred with high support throughout Aphonopelma. The Spider Probe Kit, the first implementation of AHE methodology in Class Arachnida, holds great promise for gathering the types and quantities of molecular data needed to accelerate an understanding of the spider Tree of Life by providing a mechanism whereby different researchers can confidently and effectively use the same loci for independent projects, yet allowing synthesis of data across independent research groups.
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Date Issued: 2016-10-13
Identifier: FSU_pmch_27733110, 10.1186/s12862-016-0769-y, PMC5062932, 27733110, 27733110, 10.1186/s12862-016-0769-y
Format: Citation

Title: Acute BDNF treatment upregulates GluR1-SAP97 and GluR2-GRIP1 interactions: implications for sustained AMPA receptor expression..
Creator: Jourdi, Hussam, Kabbaj, Mohamed
Abstract/Description: Brain-derived neurotrophic factor (BDNF) plays several prominent roles in synaptic plasticity and in learning and memory formation. Reduced BDNF levels and altered BDNF signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of AMPAr subunits. BDNF treatment acutely regulates AMPA receptor expression and function, including synaptic AMPAr subunit trafficking, and implicates several well defined signaling molecules that are required to...
Show moreBrain-derived neurotrophic factor (BDNF) plays several prominent roles in synaptic plasticity and in learning and memory formation. Reduced BDNF levels and altered BDNF signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of AMPAr subunits. BDNF treatment acutely regulates AMPA receptor expression and function, including synaptic AMPAr subunit trafficking, and implicates several well defined signaling molecules that are required to elicit long term potentiation and depression (LTP and LTD, respectively). Long term encoding of synaptic events, as in long term memory formation, requires AMPAr stabilization and maintenance. However, factors regulating AMPAr stabilization in neuronal cell membranes and synaptic sites are not well characterized. In this study, we examine the effects of acute BDNF treatment on levels of AMPAr-associated scaffolding proteins and on AMPAr subunit-scaffolding protein interactions. We also examine the effects of BDNF-dependent enhanced interactions between AMPAr subunits with their specific scaffolding proteins on the accumulation of both types of proteins. Our results show that acute BDNF treatment upregulates the interactions between AMPAr subunits (GluR1 and GluR2) with their scaffold proteins SAP97 and GRIP1, respectively, leading to prolonged increased accumulation of both categories of proteins, albeit with distinct mechanisms for GluR1 and GluR2. Our findings reveal a new role for BDNF in the long term maintenance of AMPA receptor subunits and associated scaffolding proteins at synapses and further support the role of BDNF as a key regulator of synaptic consolidation. These results have potential implications for recent findings implicating BDNF and AMPAr subunits in various brain diseases and behavioral disorders.
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Date Issued: 2013-01-01
Identifier: FSU_pmch_23460828, 10.1371/journal.pone.0057124, PMC3584105, 23460828, 23460828, PONE-D-12-38051
Format: Citation

Title: Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination.
Creator: Pulivarthy, Sandhya R, Lion, Mattia, Kuzu, Guray, Matthews, Adam G W, Borowsky, Mark L, Morris, John, Kingston, Robert E, Dennis, Jonathan H, Tolstorukov, Michael Y, Oettinger,...
Show morePulivarthy, Sandhya R, Lion, Mattia, Kuzu, Guray, Matthews, Adam G W, Borowsky, Mark L, Morris, John, Kingston, Robert E, Dennis, Jonathan H, Tolstorukov, Michael Y, Oettinger, Marjorie A
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Abstract/Description: We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination...
Show moreWe show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase. These changes result in establishment of a specific chromatin organization at the RSS that facilitates accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse embryonic fibroblasts the coding segment is depleted of nucleosomes, which instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also find large-scale variations of nucleosome density over hundreds of kilobases, delineating chromosomal domains within IgH, in a cell type-dependent manner. These findings suggest that developmentally regulated changes in nucleosome location and occupancy, in addition to the known chromatin modifications, play a fundamental role in regulating V(D)J recombination. Nucleosome positioning-which has previously been observed to vary locally at individual enhancers and promoters-may be a more general mechanism by which cells can regulate the accessibility of the genome during development, at scales ranging from several hundred base pairs to many kilobases.
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Date Issued: 2016-10-18
Identifier: FSU_pmch_27698124, 10.1073/pnas.1605543113, PMC5081657, 27698124, 27698124, 1605543113
Format: Citation

Title: Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent Markers and Cellular Secretion.
Creator: Yi, Lian, Bandak, Basel, Wang, Xue, Bertram, Richard, Roper, Michael G
Abstract/Description: Glucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with...
Show moreGlucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with high-speed automated insulin immunoassays. As a demonstration of the system, intracellular [Ca] ([Ca]) was measured by imaging Fura-2 fluorescence simultaneously with insulin secretion from islets exposed to elevated glucose levels. Both [Ca] and insulin were oscillatory during application of 10 mM glucose with temporal and quantitative profiles similar to what has been observed elsewhere. In previous work, sinusoidal glucose levels have been used to test the entrainment of islets while monitoring either [Ca] or insulin levels; using this newly developed system, we show unambiguously that oscillations of both [Ca] and insulin release are entrained to oscillatory glucose levels and that the temporal correlation of these are maintained throughout the experiment. It is expected that the developed analytical system can be expanded to investigate a number of other intracellular messengers in islets or other stimulus-secretion pathways in different cells.
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Date Issued: 2016-11-01
Identifier: FSU_pmch_27712062, 10.1021/acs.analchem.6b02404, PMC5089909, 27712062, 27712062
Format: Citation

Title: An S116R Phosphorylation Site Mutation in Human Fibroblast Growth Factor-1 Differentially Affects Mitogenic and Glucose-Lowering Activities.
Creator: Xia, Xue, Kumru, Ozan S, Blaber, Sachiko I, Middaugh, C Russell, Li, Ling, Ornitz, David M, Suh, Jae Myoung, Atkins, Annette R, Downes, Michael, Evans, Ronald M, Tenorio, Connie...
Show moreXia, Xue, Kumru, Ozan S, Blaber, Sachiko I, Middaugh, C Russell, Li, Ling, Ornitz, David M, Suh, Jae Myoung, Atkins, Annette R, Downes, Michael, Evans, Ronald M, Tenorio, Connie A, Bienkiewicz, Ewa, Blaber, Michael
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Abstract/Description: Fibroblast growth factor-1 (FGF-1), a potent human mitogen and insulin sensitizer, signals through both tyrosine kinase receptor-mediated autocrine/paracrine pathways as well as a nuclear intracrine pathway. Phosphorylation of FGF-1 at serine 116 (S116) has been proposed to regulate intracrine signaling. Position S116 is located within a ∼17 amino acid C-terminal loop that contains a rich set of functional determinants including heparin∖heparan sulfate affinity, thiol reactivity, nuclear...
Show moreFibroblast growth factor-1 (FGF-1), a potent human mitogen and insulin sensitizer, signals through both tyrosine kinase receptor-mediated autocrine/paracrine pathways as well as a nuclear intracrine pathway. Phosphorylation of FGF-1 at serine 116 (S116) has been proposed to regulate intracrine signaling. Position S116 is located within a ∼17 amino acid C-terminal loop that contains a rich set of functional determinants including heparin∖heparan sulfate affinity, thiol reactivity, nuclear localization, pharmacokinetics, functional half-life, nuclear ligand affinity, stability, and structural dynamics. Mutational targeting of specific functionality in this region without perturbing other functional determinants is a design challenge. S116R is a non-phosphorylatable variant present in bovine FGF-1 and other members of the human FGF family. We show that the S116R mutation in human FGF-1 is accommodated with no perturbation of biophysical or structural properties, and is therefore an attractive mutation with which to elucidate the functional role of phosphorylation. Characterization of S116R shows reduction in NIH 3T3 fibroblast mitogenic stimulation, increase in fibroblast growth factor receptor-1c activation, and prolonged duration of glucose lowering in ob/ob hyperglycemic mice. A novel FGF-1/fibroblast growth factor receptor-1c dimerization interaction combined with non-phosphorylatable intracrine signaling is hypothesized to be responsible for these observed functional effects.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27773526, 10.1016/j.xphs.2016.09.005, PMC5310217, 27773526, 27773526, S0022-3549(16)41698-9
Format: Citation

Title: Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.
Creator: McKenna, Joseph P, Dhumpa, Raghuram, Mukhitov, Nikita, Roper, Michael G, Bertram, Richard
Abstract/Description: Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with...
Show morePancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.
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Date Issued: 2016-10-27
Identifier: FSU_pmch_27788129, 10.1371/journal.pcbi.1005143, PMC5082885, 27788129, 27788129, PCOMPBIOL-D-16-00306
Format: Citation

Title: Parasite stress and pathogen avoidance relate to distinct dimensions of political ideology across 30 nations.
Creator: Tybur, Joshua M, Inbar, Yoel, Aarøe, Lene, Barclay, Pat, Barlow, Fiona Kate, de Barra, Mícheál, Becker, D Vaughn, Borovoi, Leah, Choi, Incheol, Choi, Jong An, Consedine, Nathan...
Show moreTybur, Joshua M, Inbar, Yoel, Aarøe, Lene, Barclay, Pat, Barlow, Fiona Kate, de Barra, Mícheál, Becker, D Vaughn, Borovoi, Leah, Choi, Incheol, Choi, Jong An, Consedine, Nathan S, Conway, Alan, Conway, Jane Rebecca, Conway, Paul, Adoric, Vera Cubela, Demirci, Dilara Ekin, Fernández, Ana María, Ferreira, Diogo Conque Seco, Ishii, Keiko, Jakšić, Ivana, Ji, Tingting, van Leeuwen, Florian, Lewis, David M G, Li, Norman P, McIntyre, Jason C, Mukherjee, Sumitava, Park, Justin H, Pawlowski, Boguslaw, Petersen, Michael Bang, Pizarro, David, Prodromitis, Gerasimos, Prokop, Pavol, Rantala, Markus J, Reynolds, Lisa M, Sandin, Bonifacio, Sevi, Bariş, De Smet, Delphine, Srinivasan, Narayanan, Tewari, Shruti, Wilson, Cameron, Yong, Jose C, Žeželj, Iris
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Abstract/Description: People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The...
Show morePeople who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The second, which is an intergroup account, holds that these same relationships are based on motivations to avoid contact with outgroups, who might pose greater infectious disease threats than ingroup members. Results from a study surveying 11,501 participants across 30 nations are more consistent with the intragroup account than with the intergroup account. National parasite stress relates to traditionalism (an aspect of conservatism especially related to adherence to group norms) but not to social dominance orientation (SDO; an aspect of conservatism especially related to endorsements of intergroup barriers and negativity toward ethnic and racial outgroups). Further, individual differences in pathogen-avoidance motives (i.e., disgust sensitivity) relate more strongly to traditionalism than to SDO within the 30 nations.
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Date Issued: 2016-11-01
Identifier: FSU_pmch_27791090, 10.1073/pnas.1607398113, PMC5098626, 27791090, 27791090, 1607398113
Format: Citation

Title: Fluoxetine exposure during adolescence increases preference for cocaine in adulthood.
Creator: Iñiguez, Sergio D, Riggs, Lace M, Nieto, Steven J, Wright, Katherine N, Zamora, Norma N, Cruz, Bryan, Zavala, Arturo R, Robison, Alfred J, Mazei-Robison, Michelle S
Abstract/Description: Currently, there is a high prevalence of antidepressant prescription rates within juvenile populations, yet little is known about the potential long-lasting consequences of such treatments, particularly on subsequent responses to drugs of abuse. To address this issue at the preclinical level, we examined whether adolescent exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, results in changes to the sensitivity of the rewarding properties of cocaine in adulthood. Separate...
Show moreCurrently, there is a high prevalence of antidepressant prescription rates within juvenile populations, yet little is known about the potential long-lasting consequences of such treatments, particularly on subsequent responses to drugs of abuse. To address this issue at the preclinical level, we examined whether adolescent exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, results in changes to the sensitivity of the rewarding properties of cocaine in adulthood. Separate groups of male c57bl/6 mice were exposed to FLX (0 or 20 mg/kg) for 15 consecutive days either during adolescence (postnatal days [PD] 35-49) or adulthood (PD 65-79). Twenty-one days after FLX treatment, behavioral responsivity to cocaine (0, 2.5, 5, 10, or 20 mg/kg) conditioned place preference was assessed. Our data shows that mice pretreated with FLX during adolescence, but not during adulthood, display an enhanced dose-dependent preference to the environment paired with cocaine (5 or 10 mg/kg) when compared to age-matched saline pretreated controls. Taken together, our findings suggest that adolescent exposure to FLX increases sensitivity to the rewarding properties of cocaine, later in life.
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Date Issued: 2015-10-09
Identifier: FSU_pmch_26449406, 10.1038/srep15009, PMC4598853, 26449406, 26449406, srep15009
Format: Citation

Title: Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy.
Creator: Witte, Michelina Messina, Resuehr, David, Chandler, Ashley R, Mehle, Ashlee K, Overton, J Michael
Abstract/Description: Ovariectomy (OVX) leads to hyperphagia and weight gain in rats, which can be prevented by estradiol (E2) replacement; however, the role of endogenous E2 on feeding and energy homeostasis in female mice has not been well characterized. The primary goal of this study was to assess the relative contribution of increased energy intake and decreased energy expenditure to OVX-induced weight gain in female rats and mice. OVX led to hyperphagia in rats, but did not produce daily, nor cumulative,...
Show moreOvariectomy (OVX) leads to hyperphagia and weight gain in rats, which can be prevented by estradiol (E2) replacement; however, the role of endogenous E2 on feeding and energy homeostasis in female mice has not been well characterized. The primary goal of this study was to assess the relative contribution of increased energy intake and decreased energy expenditure to OVX-induced weight gain in female rats and mice. OVX led to hyperphagia in rats, but did not produce daily, nor cumulative, hyperphagia in mice. OVX decreased mass-specific metabolic rate in mice, but not in rats. OVX decreased home cage locomotor activity in both species. Pair-feeding attenuated OVX-induced weight gain in rats and produced both short- and long-term changes in expression of key hypothalamic genes involved in food intake and energy homeostasis, i.e., the anorexigenic neuropeptide pro-opiomelanocortin (POMC) and the orexigenic neuropeptides: melanin-concentrating hormone (MCH) and agouti-related peptide (AgRP). No differences in hypothalamic gene expression were observed between OVX'd and sham mice. The results suggest that OVX-induced weight gain is mediated by hyperphagia and reduced locomotor activity in rats, but that in mice, it is primarily mediated by reduced locomotor activity and metabolic rate.
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Date Issued: 2010-05-01
Identifier: FSU_pmch_20067798, 10.1016/j.ygcen.2010.01.006, PMC2856744, 20067798, 20067798, S0016-6480(10)00009-2
Format: Citation

Title: Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone.
Creator: Carrier, Nicole, Kabbaj, Mohamed
Abstract/Description: Human and animal studies suggest that testosterone may have antidepressant effects. In this study, we sought to investigate the molecular mechanisms underlying the antidepressant effects of testosterone within the hippocampus, an area that is fundamental in the etiology of depression. The effects of testosterone replacements in gonadectomized adult male rats were investigated using the sucrose preference and forced swim tests. We explored possible effects of testosterone on hippocampal...
Show moreHuman and animal studies suggest that testosterone may have antidepressant effects. In this study, we sought to investigate the molecular mechanisms underlying the antidepressant effects of testosterone within the hippocampus, an area that is fundamental in the etiology of depression. The effects of testosterone replacements in gonadectomized adult male rats were investigated using the sucrose preference and forced swim tests. We explored possible effects of testosterone on hippocampal neurogenesis and gene expression of stress-related molecules. Through the use of viral vectors, we pursued the antidepressant molecular mechanism(s) of testosterone in mediating anhedonia and manipulated extracellular signal-regulated kinase 2 (ERK2) expression in the dentate gyrus in gonadectomized rats with testosterone replacements. Testosterone had antidepressant effects, likely mediated by aromatization to estrogen metabolites, in the sucrose preference and forced swim tests despite having no effects on hippocampal cell proliferation or survival. We found a testosterone-dependent regulation of hippocampal ERK2 expression. Functionally, reducing ERK2 activity within the dentate gyrus induced anhedonia in gonadectomized rats receiving testosterone supplementation, whereas the overexpression of ERK2 rescued this behavior in gonadectomized rats. These results implicate a role for ERK2 signaling within the dentate gyrus area of the hippocampus as a key mediator of the antidepressant effects of testosterone.
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Date Issued: 2012-04-01
Identifier: FSU_pmch_22265242, 10.1016/j.biopsych.2011.11.028, PMC3307821, 22265242, 22265242, S0006-3223(11)01201-7
Format: Citation

Title: Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock.
Creator: Lee, Hyeongmin, Chen, Rongmin, Lee, Yongjin, Yoo, Seunghee, Lee, Choogon
Abstract/Description: Circadian rhythms in mammals are generated by a negative transcriptional feedback loop in which PERIOD (PER) is rate-limiting for feedback inhibition. Casein kinases Idelta and Iepsilon (CKIdelta/epsilon) can regulate temporal abundance/activity of PER by phosphorylation-mediated degradation and cellular localization. Despite their potentially crucial effects on PER, it has not been demonstrated in a mammalian system that these kinases play essential roles in circadian rhythm generation as...
Show moreCircadian rhythms in mammals are generated by a negative transcriptional feedback loop in which PERIOD (PER) is rate-limiting for feedback inhibition. Casein kinases Idelta and Iepsilon (CKIdelta/epsilon) can regulate temporal abundance/activity of PER by phosphorylation-mediated degradation and cellular localization. Despite their potentially crucial effects on PER, it has not been demonstrated in a mammalian system that these kinases play essential roles in circadian rhythm generation as does their homolog in Drosophila. To disrupt both CKIdelta/epsilon while avoiding the embryonic lethality of CKIdelta disruption in mice, we used CKIdelta-deficient Per2(Luc) mouse embryonic fibroblasts (MEFs) and overexpressed a dominant-negative mutant CKIepsilon (DN-CKIepsilon) in the mutant MEFs. CKIdelta-deficient MEFs exhibited a robust circadian rhythm, albeit with a longer period, suggesting that the cells possess a way to compensate for CKIdelta loss. When CKIepsilon activity was disrupted by the DN-CKIepsilon in the mutant MEFs, circadian bioluminescence rhythms were eliminated and rhythms in endogenous PER abundance and phosphorylation were severely compromised, demonstrating that CKIdelta/epsilon are indeed essential kinases for the clockwork. This is further supported by abolition of circadian rhythms when physical interaction between PER and CKIdelta/epsilon was disrupted by overexpressing the CKIdelta/epsilon binding domain of PER2 (CKBD-P2). Interestingly, CKBD-P2 overexpression led to dramatically low levels of endogenous PER, while PER-binding, kinase-inactive DN-CKIepsilon did not, suggesting that CKIdelta/epsilon may have a non-catalytic role in stabilizing PER. Our results show that an essential role of CKIdelta/epsilon is conserved between Drosophila and mammals, but CKIdelta/epsilon and DBT may have divergent non-catalytic functions in the clockwork as well.
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Date Issued: 2009-12-15
Identifier: FSU_pmch_19948962, 10.1073/pnas.0906651106, PMC2795500, 19948962, 19948962, 0906651106
Format: Citation

Title: Exercise training reverses aging-induced impairment of myogenic constriction in skeletal muscle arterioles.
Creator: Ghosh, Payal, Mora Solis, Fredy R, Dominguez, James M, Spier, Scott A, Donato, Anthony J, Delp, Michael D, Muller-Delp, Judy M
Abstract/Description: To investigate whether exercise training can reverse age-related impairment of myogenic vasoconstriction in skeletal muscle arterioles, young (4 mo) and old (22 mo) male Fischer 344 rats were randomly assigned to either sedentary or exercise-trained groups. The roles of the endothelium and Kv1 channels in age- and exercise training-induced adaptations of myogenic responses were assessed through evaluation of pressure-induced constriction in endothelium-intact and denuded soleus muscle...
Show moreTo investigate whether exercise training can reverse age-related impairment of myogenic vasoconstriction in skeletal muscle arterioles, young (4 mo) and old (22 mo) male Fischer 344 rats were randomly assigned to either sedentary or exercise-trained groups. The roles of the endothelium and Kv1 channels in age- and exercise training-induced adaptations of myogenic responses were assessed through evaluation of pressure-induced constriction in endothelium-intact and denuded soleus muscle arterioles in the presence and absence of the Kv1 channel blocker, correolide. Exercise training enhanced myogenic constriction in arterioles from both old and young rats. In arterioles from old rats, exercise training restored myogenic constriction to a level similar to that of arterioles from young sedentary rats. Removal of the endothelium did not alter myogenic constriction of arterioles from young sedentary rats, but reduced myogenic constriction in arterioles from young exercise-trained rats. In contrast, endothelial removal had no effect on myogenic constriction of arterioles from old exercise-trained rats, but increased myogenic vasoconstriction in old sedentary rats. The effect of Kv1 channel blockade was also dependent on age and training status. In arterioles from young sedentary rats, Kv1 blockade had little effect on myogenic constriction, whereas in old sedentary rats Kv1 blockade increased myogenic constriction. After exercise training, Kv1 channel blockade increased myogenic constriction in arterioles from both young and old rats. Thus exercise training restores myogenic constriction of arterioles from old rats and enhances myogenic constriction from young rats through adaptations of the endothelium and smooth muscle Kv1 channels.
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Date Issued: 2015-04-01
Identifier: FSU_pmch_25634999, 10.1152/japplphysiol.00277.2014, PMC4422370, 25634999, 25634999, japplphysiol.00277.2014
Format: Citation

Title: An Examination of Dynamic Gene Expression Changes in the Mouse Brain During Pregnancy and the Postpartum Period.
Creator: Ray, Surjyendu, Tzeng, Ruei-Ying, DiCarlo, Lisa M, Bundy, Joseph L, Vied, Cynthia, Tyson, Gary, Nowakowski, Richard, Arbeitman, Michelle N
Abstract/Description: The developmental transition to motherhood requires gene expression changes that alter the brain to drive the female to perform maternal behaviors. We broadly examined the global transcriptional response in the mouse maternal brain, by examining four brain regions: hypothalamus, hippocampus, neocortex, and cerebellum, in virgin females, two pregnancy time points, and three postpartum time points. We find that overall there are hundreds of differentially expressed genes, but each brain region...
Show moreThe developmental transition to motherhood requires gene expression changes that alter the brain to drive the female to perform maternal behaviors. We broadly examined the global transcriptional response in the mouse maternal brain, by examining four brain regions: hypothalamus, hippocampus, neocortex, and cerebellum, in virgin females, two pregnancy time points, and three postpartum time points. We find that overall there are hundreds of differentially expressed genes, but each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions. Interestingly, a set of "early-response genes" is repressed in all brain regions during pregnancy and postpartum stages. Several genes previously implicated in underlying postpartum depression change expression. This study serves as an atlas of gene expression changes in the maternal brain, with the results demonstrating that pregnancy, parturition, and postpartum maternal experience substantially impact diverse brain regions.
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Date Issued: 2015-11-23
Identifier: FSU_pmch_26596646, 10.1534/g3.115.020982, PMC4704721, 26596646, 26596646, g3.115.020982
Format: Citation

Title: Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains.
Creator: Dalton, Justin E, Fear, Justin M, Knott, Simon, Baker, Bruce S, McIntyre, Lauren M, Arbeitman, Michelle N
Abstract/Description: Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (Fru(M)). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. By over-expressing individual Fru(M) isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional...
Show moreDrosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (Fru(M)). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. By over-expressing individual Fru(M) isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three Fru(M) isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of Fru(M) isoforms, including many annotated with neuronal functions. By determining the binding sites of individual Fru(M) isoforms using SELEX we demonstrate that the distinct zinc finger domain of each Fru(M) isoforms confers different DNA binding specificities. A genome-wide search for these binding site sequences finds that the gene sets identified as induced by over-expression of Fru(M) isoforms in males are enriched for genes that contain the binding sites. An analysis of the chromosomal distribution of genes downstream of Fru(M) shows that those that are induced and repressed in males are highly enriched and depleted on the X chromosome, respectively. This study elucidates the different regulatory and DNA binding activities of three Fru(M) isoforms on a genome-wide scale and identifies genes regulated by these isoforms. These results add to our understanding of sex chromosome biology and further support the hypothesis that in some cell-types genes with male-biased expression are enriched on the X chromosome.
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Date Issued: 2013-09-27
Identifier: FSU_pmch_24074028, 10.1186/1471-2164-14-659, PMC3852243, 24074028, 24074028, 1471-2164-14-659
Format: Citation

Title: Light-regulated translational control of circadian behavior by eIF4E phosphorylation.
Creator: Cao, Ruifeng, Gkogkas, Christos G, de Zavalia, Nuria, Blum, Ian D, Yanagiya, Akiko, Tsukumo, Yoshinori, Xu, Haiyan, Lee, Choogon, Storch, Kai-Florian, Liu, Andrew C, Amir,...
Show moreCao, Ruifeng, Gkogkas, Christos G, de Zavalia, Nuria, Blum, Ian D, Yanagiya, Akiko, Tsukumo, Yoshinori, Xu, Haiyan, Lee, Choogon, Storch, Kai-Florian, Liu, Andrew C, Amir, Shimon, Sonenberg, Nahum
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Abstract/Description: The circadian (∼24 h) clock is continuously entrained (reset) by ambient light so that endogenous rhythms are synchronized with daily changes in the environment. Light-induced gene expression is thought to be the molecular mechanism underlying clock entrainment. mRNA translation is a key step of gene expression, but the manner in which clock entrainment is controlled at the level of mRNA translation is not well understood. We found that a light- and circadian clock-regulated MAPK/MNK pathway...
Show moreThe circadian (∼24 h) clock is continuously entrained (reset) by ambient light so that endogenous rhythms are synchronized with daily changes in the environment. Light-induced gene expression is thought to be the molecular mechanism underlying clock entrainment. mRNA translation is a key step of gene expression, but the manner in which clock entrainment is controlled at the level of mRNA translation is not well understood. We found that a light- and circadian clock-regulated MAPK/MNK pathway led to phosphorylation of the cap-binding protein eIF4E in the mouse suprachiasmatic nucleus of the hypothalamus, the locus of the master circadian clock in mammals. Phosphorylation of eIF4E specifically promoted translation of Period 1 (Per1) and Period 2 (Per2) mRNAs and increased the abundance of basal and inducible PER proteins, which facilitated circadian clock resetting and precise timekeeping. Together, these results highlight a critical role for light-regulated translational control in the physiology of the circadian clock.
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Date Issued: 2015-06-01
Identifier: FSU_pmch_25915475, 10.1038/nn.4010, PMC4446158, 25915475, 25915475, nn.4010
Format: Citation

Title: Long-term caloric restriction reduces metabolic rate and heart rate under cool and thermoneutral conditions in FBNF1 rats.
Creator: Knight, W David, Witte, M M, Parsons, A D, Gierach, M, Overton, J Michael
Abstract/Description: The long-term metabolic and cardiovascular responses to caloric restriction (CR) are poorly understood. We examined the responses to one year of CR in FBNF1 rats housed in cool (COOL; T(a)=15 °C) or thermoneutral (TMN; T(a)=30 °C) conditions. Rats were acclimated to COOL or TMN for 2 months, instrumented for cardiovascular telemetry and studied in calorimeters. Baseline caloric intake, oxygen consumption (VO(2)), mean arterial blood pressure (MAP), and heart rate (HR) were determined prior to...
Show moreThe long-term metabolic and cardiovascular responses to caloric restriction (CR) are poorly understood. We examined the responses to one year of CR in FBNF1 rats housed in cool (COOL; T(a)=15 °C) or thermoneutral (TMN; T(a)=30 °C) conditions. Rats were acclimated to COOL or TMN for 2 months, instrumented for cardiovascular telemetry and studied in calorimeters. Baseline caloric intake, oxygen consumption (VO(2)), mean arterial blood pressure (MAP), and heart rate (HR) were determined prior to assignment to ad lib (AL) or CR groups (30-40% CR) within each T(a) (n = 8). Groups of rats were studied after 10 weeks CR, one year CR, and after 4 days of re-feeding. Both 10 weeks and one year of CR reduced HR and VO(2) irrespective of T(a). Evaluation of the relationship between metabolic organ mass (liver, heart, brain, and kidney mass) and energy expenditure revealed a clear shift induced by CR to reduce expenditure per unit metabolic mass in both COOL and TMN groups. Re-feeding resulted in prompt elevations of HR and VO(2) to levels observed in control rats. These findings are consistent with the hypothesis that long term CR produces sustained reductions in metabolic rate and heart rate in rats.
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Date Issued: 2011-05-01
Identifier: FSU_pmch_21513729, 10.1016/j.mad.2011.04.001, PMC3118456, 21513729, 21513729, S0047-6374(11)00046-7
Format: Citation

Title: Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy.
Creator: Abbasi, Saad, Kumar, Sanjay S
Abstract/Description: Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is often refractory to antiepileptic medications. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies suggest that inputs from the presubiculum (PrS) contribute to MEA pathophysiology. We assessed electrophysiologically how PrS influences MEA excitability using the rat pilocarpine model of TLE. PrS-MEA...
Show moreTemporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is often refractory to antiepileptic medications. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies suggest that inputs from the presubiculum (PrS) contribute to MEA pathophysiology. We assessed electrophysiologically how PrS influences MEA excitability using the rat pilocarpine model of TLE. PrS-MEA connectivity was confirmed by electrically stimulating PrS afferents while recording from neurons within superficial layers of MEA. Assessment of alterations in PrS-mediated synaptic drive to MEA neurons was made following focal application of either glutamate or NBQX to the PrS in control and epileptic animals. Here, we report that monosynaptic inputs to MEA from PrS neurons are conserved in epileptic rats, and that PrS modulation of MEA excitability is layer-specific. PrS contributes more to synaptic inhibition of LII stellate cells than excitation. Under epileptic conditions, stellate cell inhibition is significantly reduced while excitatory synaptic drive is maintained at levels similar to control. PrS contributes to both synaptic excitation and inhibition of LIII pyramidal cells in control animals. Under epileptic conditions, overall excitatory synaptic drive to these neurons is enhanced while inhibitory synaptic drive is maintained at control levels. Additionally, neither glutamate nor NBQX applied focally to PrS now affected EPSC and IPSC frequency of LIII pyramidal neurons. These layer-specific changes in PrS-MEA interactions are unexpected and of significance in unraveling pathophysiological mechanisms underlying TLE.
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Date Issued: 2015-11-01
Identifier: FSU_pmch_26378210, 10.1152/jn.00823.2015, PMC4737416, 26378210, 26378210, jn.00823.2015
Format: Citation

Title: Long term ablation of protein kinase A (PKA)-mediated cardiac troponin I phosphorylation leads to excitation-contraction uncoupling and diastolic dysfunction in a knock-in mouse model of hypertrophic cardiomyopathy.
Creator: Dweck, David, Sanchez-Gonzalez, Marcos A, Chang, Audrey N, Dulce, Raul A, Badger, Crystal-Dawn, Koutnik, Andrew P, Ruiz, Edda L, Griffin, Brittany, Liang, Jingsheng, Kabbaj,...
Show moreDweck, David, Sanchez-Gonzalez, Marcos A, Chang, Audrey N, Dulce, Raul A, Badger, Crystal-Dawn, Koutnik, Andrew P, Ruiz, Edda L, Griffin, Brittany, Liang, Jingsheng, Kabbaj, Mohamed, Fincham, Frank D, Hare, Joshua M, Overton, J Michael, Pinto, Jose R
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Abstract/Description: The cardiac troponin I (cTnI) R21C (cTnI-R21C) mutation has been linked to hypertrophic cardiomyopathy and renders cTnI incapable of phosphorylation by PKA in vivo. Echocardiographic imaging of homozygous knock-in mice expressing the cTnI-R21C mutation shows that they develop hypertrophy after 12 months of age and have abnormal diastolic function that is characterized by longer filling times and impaired relaxation. Electrocardiographic analyses show that older R21C mice have elevated heart...
Show moreThe cardiac troponin I (cTnI) R21C (cTnI-R21C) mutation has been linked to hypertrophic cardiomyopathy and renders cTnI incapable of phosphorylation by PKA in vivo. Echocardiographic imaging of homozygous knock-in mice expressing the cTnI-R21C mutation shows that they develop hypertrophy after 12 months of age and have abnormal diastolic function that is characterized by longer filling times and impaired relaxation. Electrocardiographic analyses show that older R21C mice have elevated heart rates and reduced cardiovagal tone. Cardiac myocytes isolated from older R21C mice demonstrate that in the presence of isoproterenol, significant delays in Ca(2+) decay and sarcomere relaxation occur that are not present at 6 months of age. Although isoproterenol and stepwise increases in stimulation frequency accelerate Ca(2+)-transient and sarcomere shortening kinetics in R21C myocytes from older mice, they are unable to attain the corresponding WT values. When R21C myocytes from older mice are treated with isoproterenol, evidence of excitation-contraction uncoupling is indicated by an elevation in diastolic calcium that is frequency-dissociated and not coupled to shorter diastolic sarcomere lengths. Myocytes from older mice have smaller Ca(2+) transient amplitudes (2.3-fold) that are associated with reductions (2.9-fold) in sarcoplasmic reticulum Ca(2+) content. This abnormal Ca(2+) handling within the cell may be attributed to a reduction (2.4-fold) in calsequestrin expression in conjunction with an up-regulation (1.5-fold) of Na(+)-Ca(2+) exchanger. Incubation of permeabilized cardiac fibers from R21C mice with PKA confirmed that the mutation prevents facilitation of mechanical relaxation. Altogether, these results indicate that the inability to enhance myofilament relaxation through cTnI phosphorylation predisposes the heart to abnormal diastolic function, reduced accessibility of cardiac reserves, dysautonomia, and hypertrophy.
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Date Issued: 2014-08-15
Identifier: FSU_pmch_24973218, 10.1074/jbc.M114.561472, PMC4132808, 24973218, 24973218, M114.561472
Format: Citation

Title: Juvenile and adult rats differ in cocaine reward and expression of zif268 in the forebrain.
Creator: Hollis, F, Gaval-Cruz, M, Carrier, N, Dietz, D M, Kabbaj, M
Abstract/Description: Adolescents are more likely to experiment with and become addicted to drugs of abuse. A number of studies indicate that the developmental forebrain may be responsible for making adolescents vulnerable to the addictive properties of such drugs. The aim of this study was to first compare behavioral responses to novelty and cocaine between juvenile and adult rats and then compare levels of the immediate-early gene zif268 activation in several forebrain areas via in situ hybridization. We found...
Show moreAdolescents are more likely to experiment with and become addicted to drugs of abuse. A number of studies indicate that the developmental forebrain may be responsible for making adolescents vulnerable to the addictive properties of such drugs. The aim of this study was to first compare behavioral responses to novelty and cocaine between juvenile and adult rats and then compare levels of the immediate-early gene zif268 activation in several forebrain areas via in situ hybridization. We found that juveniles demonstrated higher locomotion scores and required a higher dose of cocaine than adults to establish a conditioned place preference. Additionally, at this higher dose, juvenile rats exhibited higher levels of zif268 mRNA in the prefrontal cortex compared with adults. A developmental effect for increased zif268 mRNA was also observed in the striatum and nucleus accumbens, but there was no interaction with the cocaine dose. These findings hold interesting implications for the study of the molecular mechanisms underlying juvenile drug addiction.
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Date Issued: 2012-01-03
Identifier: FSU_pmch_22056598, 10.1016/j.neuroscience.2011.10.012, PMC3249467, 22056598, 22056598, S0306-4522(11)01186-9
Format: Citation

Title: Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration..
Creator: Radulovic, Maja, Yoon, Hyesook, Larson, Nadya, Wu, Jianmin, Linbo, Rachel, Burda, Joshua E, Diamandis, Eleftherios P, Blaber, Sachiko I, Blaber, Michael, Fehlings, Michael G,...
Show moreRadulovic, Maja, Yoon, Hyesook, Larson, Nadya, Wu, Jianmin, Linbo, Rachel, Burda, Joshua E, Diamandis, Eleftherios P, Blaber, Sachiko I, Blaber, Michael, Fehlings, Michael G, Scarisbrick, Isobel A
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Abstract/Description: Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme...
Show moreKallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in KLK expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. Kallikrein 9 showed the most marked changes and remained chronically elevated. Importantly, a subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI cases examined. Together, these findings demonstrate that elevated levels of a significant subset of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and, therefore, represent new potential targets for the development of neuroprotective strategies.
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Date Issued: 2013-11-01
Identifier: FSU_pmch_24128681, 10.1097/NEN.0000000000000007, PMC4097185, 24128681, 24128681
Format: Citation

Title: Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells.
Creator: Subathra, Marimuthu, Korrapati, Midhun, Howell, Lauren A, Arthur, John M, Shayman, James A, Schnellmann, Rick G, Siskind, Leah J
Abstract/Description: Glycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/m and diabetic db/db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/db mouse kidney cortices, specifically in glomeruli, and also in urine. In our recent paper ...
Show moreGlycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/m and diabetic db/db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/db mouse kidney cortices, specifically in glomeruli, and also in urine. In our recent paper (25), we observed that the kidneys exhibited glomerular hypertrophy and proximal tubular vacuolization and increased fibrosis markers at these time points. Mesangial cells contribute to hyperglycemia-induced glomerular hypertrophy in DN. Hyperglycemic culture conditions, similar to that present in diabetes, were sufficient to elevate mesangial cell HexCers and increase markers of fibrosis, extracellular matrix proteins, and cellular hypertrophy. Inhibition of glucosylceramide synthase or lowering glucose levels decreased markers of fibrosis and extracellular matrix proteins and reversed mesangial cell hypertrophy. Hyperglycemia increased phosphorylated (p)SMAD3 and pAkt levels and reduced phosphatase and tensin homolog levels, which were reversed with glucosylceramide synthase inhibition. These data suggest that inhibition of glucosylceramide synthase reversed mesangial cell hypertrophy through decreased pAkt and pSmad3 and increased pathways responsible for protein degradation. Importantly, urinary GSL levels were higher in patients with DN compared with healthy control subjects, implicating a role for these lipids in human DN. Thus, hyperglycemia in type II diabetes leads to renal dysfunction at least in part by inducing accumulation of HexCers and LacCers in mesangial cells, resulting in fibrosis, extracellular matrix production, and hypertrophy.
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Date Issued: 2015-08-01
Identifier: FSU_pmch_26041445, 10.1152/ajprenal.00150.2015, PMC4525094, 26041445, 26041445, ajprenal.00150.2015
Format: Citation

Title: Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner.
Creator: Saland, Samantha K, Schoepfer, Kristin J, Kabbaj, Mohamed
Abstract/Description: We recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and...
Show moreWe recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response.
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Date Issued: 2016-02-18
Identifier: FSU_pmch_26888470, 10.1038/srep21322, PMC4766854, 26888470, 26888470, srep21322
Format: Citation

Title: LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression..
Creator: Zhang, Yujie, Stefanovic, Branko
Abstract/Description: Type I collagen is the most abundant structural protein in all vertebrates, but its constitutive rate of synthesis is low due to long half-life of the protein (60-70 days). However, several hundred fold increased production of type I collagen is often seen in reparative or reactive fibrosis. The mechanism which is responsible for this dramatic upregulation is complex, including multiple levels of regulation. However, posttranscriptional regulation evidently plays a predominant role....
Show moreType I collagen is the most abundant structural protein in all vertebrates, but its constitutive rate of synthesis is low due to long half-life of the protein (60-70 days). However, several hundred fold increased production of type I collagen is often seen in reparative or reactive fibrosis. The mechanism which is responsible for this dramatic upregulation is complex, including multiple levels of regulation. However, posttranscriptional regulation evidently plays a predominant role. Posttranscriptional regulation comprises processing, transport, stabilization and translation of mRNAs and is executed by RNA binding proteins. There are about 800 RNA binding proteins, but only one, La ribonucleoprotein domain family member 6 (LARP6), is specifically involved in type I collagen regulation. In the 5'untranslated region (5'UTR) of mRNAs encoding for type I and type III collagens there is an evolutionally conserved stem-loop (SL) structure; this structure is not found in any other mRNA, including any other collagen mRNA. LARP6 binds to the 5'SL in sequence specific manner to regulate stability of collagen mRNAs and their translatability. Here, we will review current understanding of how is LARP6 involved in posttranscriptional regulation of collagen mRNAs. We will also discuss how other proteins recruited by LARP6, including nonmuscle myosin, vimentin, serine threonine kinase receptor associated protein (STRAP), 25 kD FK506 binding protein (FKBP25) and RNA helicase A (RHA), contribute to this process.
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Date Issued: 2016-03-22
Identifier: FSU_pmch_27011170, 10.3390/ijms17030419, PMC4813270, 27011170, 27011170, ijms17030419
Format: Citation

Title: Heterogeneous ageing of skeletal muscle microvascular function.
Creator: Muller-Delp, Judy M
Abstract/Description: The distribution of blood flow to skeletal muscle during exercise is altered with advancing age. Changes in arteriolar function that are muscle specific underlie age-induced changes in blood flow distribution. With advancing age, functional adaptations that occur in resistance arterioles from oxidative muscles differ from those that occur in glycolytic muscles. Age-related adaptations of morphology, as well as changes in both endothelial and vascular smooth muscle signalling, differ in muscle...
Show moreThe distribution of blood flow to skeletal muscle during exercise is altered with advancing age. Changes in arteriolar function that are muscle specific underlie age-induced changes in blood flow distribution. With advancing age, functional adaptations that occur in resistance arterioles from oxidative muscles differ from those that occur in glycolytic muscles. Age-related adaptations of morphology, as well as changes in both endothelial and vascular smooth muscle signalling, differ in muscle of diverse fibre type. Age-induced endothelial dysfunction has been reported in most skeletal muscle arterioles; however, unique alterations in signalling contribute to the dysfunction in arterioles from oxidative muscles as compared with those from glycolytic muscles. In resistance arterioles from oxidative muscle, loss of nitric oxide signalling contributes significantly to endothelial dysfunction, whereas in resistance arterioles from glycolytic muscle, alterations in both nitric oxide and prostanoid signalling underlie endothelial dysfunction. Similarly, adaptations of the vascular smooth muscle that occur with advancing age are heterogeneous between arterioles from oxidative and glycolytic muscles. In both oxidative and glycolytic muscle, late-life exercise training reverses age-related microvascular dysfunction, and exercise training appears to be particularly effective in reversing endothelial dysfunction. Patterns of microvascular ageing that develop among muscles of diverse fibre type and function may be attributable to changing patterns of physical activity with ageing. Importantly, aerobic exercise training, initiated even at an advanced age, restores muscle blood flow distribution patterns and vascular function in old animals to those seen in their young counterparts.
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Date Issued: 2016-04-15
Identifier: FSU_pmch_26575597, 10.1113/JP271005, PMC4933125, 26575597, 26575597
Format: Citation

Title: In Vivo Analysis of Troponin C Knock-In (A8V) Mice: Evidence that TNNC1 Is a Hypertrophic Cardiomyopathy Susceptibility Gene..
Creator: Martins, Adriano S, Parvatiyar, Michelle S, Feng, Han-Zhong, Bos, J Martijn, Gonzalez-Martinez, David, Vukmirovic, Milica, Turna, Rajdeep S, Sanchez-Gonzalez, Marcos A, Badger,...
Show moreMartins, Adriano S, Parvatiyar, Michelle S, Feng, Han-Zhong, Bos, J Martijn, Gonzalez-Martinez, David, Vukmirovic, Milica, Turna, Rajdeep S, Sanchez-Gonzalez, Marcos A, Badger, Crystal-Dawn, Zorio, Diego A R, Singh, Rakesh K, Wang, Yingcai, Jin, J-P, Ackerman, Michael J, Pinto, Jose R
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Abstract/Description: Mutations in thin-filament proteins have been linked to hypertrophic cardiomyopathy, but it has never been demonstrated that variants identified in the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in vivo. The goal of this study was to determine whether TNNC1 can be categorized as an hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband. The TNNC1-A8V proband diagnosed with severe obstructive...
Show moreMutations in thin-filament proteins have been linked to hypertrophic cardiomyopathy, but it has never been demonstrated that variants identified in the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in vivo. The goal of this study was to determine whether TNNC1 can be categorized as an hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband. The TNNC1-A8V proband diagnosed with severe obstructive hypertrophic cardiomyopathy at 34 years of age exhibited mild-to-moderate thickening in left and right ventricular walls, decreased left ventricular dimensions, left atrial enlargement, and hyperdynamic left ventricular systolic function. Genetically engineered knock-in (KI) mice containing the A8V mutation (heterozygote=KI-TnC-A8V(+/-); homozygote=KI-TnC-A8V(+/+)) were characterized by echocardiography and pressure-volume studies. Three-month-old KI-TnC-A8V(+/+) mice displayed decreased ventricular dimensions, mild diastolic dysfunction, and enhanced systolic function, whereas KI-TnC-A8V(+/-) mice displayed cardiac restriction at 14 months of age. KI hearts exhibited atrial enlargement, papillary muscle hypertrophy, and fibrosis. Liquid chromatography-mass spectroscopy was used to determine incorporation of mutant cardiac troponin C (≈ 21%) into the KI-TnC-A8V(+/-) cardiac myofilament. Reduced diastolic sarcomeric length, increased shortening, and prolonged Ca(2+) and contractile transients were recorded in intact KI-TnC-A8V(+/-) and KI-TnC-A8V(+/+) cardiomyocytes. Ca(2+) sensitivity of contraction in skinned fibers increased with mutant gene dose: KI-TnC-A8V(+/+)>KI-TnC-A8V(+/-)>wild-type, whereas KI-TnC-A8V(+/+) relaxed more slowly on flash photolysis of diazo-2. The TNNC1-A8V mutant increases the Ca(2+)-binding affinity of the thin filament and elicits changes in Ca(2+) homeostasis and cellular remodeling, which leads to diastolic dysfunction. These in vivo alterations further implicate the role of TNNC1 mutations in the development of cardiomyopathy.
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Date Issued: 2015-10-01
Identifier: FSU_pmch_26304555, 10.1161/CIRCGENETICS.114.000957, PMC4618104, 26304555, 26304555
Format: Citation

Title: Intracellular linkers are involved in Mg2+-dependent modulation of the Eag potassium channel.
Creator: Liu, Xinqiu, Wu, Yuying, Zhou, Yi
Abstract/Description: Modulation of activation kinetics by divalent ions is one of the characteristic features of Eag channels. Here, we report that Mg(2+)-dependent deceleration of Eag channel activation is significantly attenuated by a G297E mutation, which exhibits a gain-of-function phenotype in Drosophila by suppressing the effect of shaker mutation on behavior and neuronal excitability. The G297 residue is located in the intracellular linker of transmembrane segments S2 and S3, and is thus not involved in...
Show moreModulation of activation kinetics by divalent ions is one of the characteristic features of Eag channels. Here, we report that Mg(2+)-dependent deceleration of Eag channel activation is significantly attenuated by a G297E mutation, which exhibits a gain-of-function phenotype in Drosophila by suppressing the effect of shaker mutation on behavior and neuronal excitability. The G297 residue is located in the intracellular linker of transmembrane segments S2 and S3, and is thus not involved in direct binding of Mg(2+) ions. Moreover, mutation of the only positively charged residue in the other intracellular linker between S4 and S5 also results in a dramatic reduction of Mg(2+)-dependent modulation of Eag activation kinetics. Collectively, the two mutations in eag eliminate or even paradoxically reverse the effect of Mg(2+) on channel activation and inactivation kinetics. Together, these results suggest an important role of the intracellular linker regions in gating processes of Eag channels.
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Date Issued: 2010-07-01
Identifier: FSU_pmch_20855938, 10.4161/chan.4.4.12329, PMC3322480, 20855938, 20855938, 12329
Format: Citation

Department of Biomedical Sciences (125)	+ -
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