Search results

Title: A Landmark-Free Method for Three-Dimensional Shape Analysis.
Creator: Pomidor, Benjamin J, Makedonska, Jana, Slice, Dennis E
Abstract/Description: The tools and techniques used in morphometrics have always aimed to transform the physical shape of an object into a concise set of numerical data for mathematical analysis. The advent of landmark-based morphometrics opened new avenues of research, but these methods are not without drawbacks. The time investment required of trained individuals to accurately landmark a data set is significant, and the reliance on readily-identifiable physical features can hamper research efforts. This is...
Show moreThe tools and techniques used in morphometrics have always aimed to transform the physical shape of an object into a concise set of numerical data for mathematical analysis. The advent of landmark-based morphometrics opened new avenues of research, but these methods are not without drawbacks. The time investment required of trained individuals to accurately landmark a data set is significant, and the reliance on readily-identifiable physical features can hamper research efforts. This is especially true of those investigating smooth or featureless surfaces. In this paper, we present a new method to perform this transformation for data obtained from high-resolution scanning technology. This method uses surface scans, instead of landmarks, to calculate a shape difference metric analogous to Procrustes distance and perform superimposition. This is accomplished by building upon and extending the Iterative Closest Point algorithm. We also explore some new ways this data can be used; for example, we can calculate an averaged surface directly and visualize point-wise shape information over this surface. Finally, we briefly demonstrate this method on a set of primate skulls and compare the results of the new methodology with traditional geometric morphometric analysis.
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Date Issued: 2016-03-08
Identifier: FSU_pmch_26953573, 10.1371/journal.pone.0150368, PMC4783062, 26953573, 26953573, PONE-D-15-18418
Format: Citation

Title: An Unusual Inverted Saline Microbial Mat Community in an Interdune Sabkha in the Rub' al Khali (the Empty Quarter), United Arab Emirates.
Creator: McKay, Christopher P, Rask, Jon C, Detweiler, Angela M, Bebout, Brad M, Everroad, R Craig, Lee, Jackson Z, Chanton, Jeffrey P, Mayer, Marisa H, Caraballo, Adrian A L, Kapili,...
Show moreMcKay, Christopher P, Rask, Jon C, Detweiler, Angela M, Bebout, Brad M, Everroad, R Craig, Lee, Jackson Z, Chanton, Jeffrey P, Mayer, Marisa H, Caraballo, Adrian A L, Kapili, Bennett, Al-Awar, Meshgan, Al-Farraj, Asma
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Abstract/Description: Salt flats (sabkha) are a recognized habitat for microbial life in desert environments and as analogs of habitats for possible life on Mars. Here we report on the physical setting and microbiology of interdune sabkhas among the large dunes in the Rub' al Khali (the Empty Quarter) in Liwa Oasis, United Arab Emirates. The salt flats, composed of gypsum and halite, are moistened by relatively fresh ground water. The result is a salinity gradient that is inverted compared to most salt flat...
Show moreSalt flats (sabkha) are a recognized habitat for microbial life in desert environments and as analogs of habitats for possible life on Mars. Here we report on the physical setting and microbiology of interdune sabkhas among the large dunes in the Rub' al Khali (the Empty Quarter) in Liwa Oasis, United Arab Emirates. The salt flats, composed of gypsum and halite, are moistened by relatively fresh ground water. The result is a salinity gradient that is inverted compared to most salt flat communities with the hypersaline layer at the top and freshwater layers below. We describe and characterize a rich photosynthetically-based microbial ecosystem that is protected from the arid outside environment by a translucent salt crust. Gases collected from sediments under shallow ponds in the sabkha contain methane in concentrations as high as 3400 ppm. The salt crust could preserve biomarkers and other evidence for life in the salt after it dries out. Chloride-filled depressions have been identified on Mars and although surface flow of water is unlikely on Mars today, ground water is possible. Such a near surface system with modern groundwater flowing under ancient salt deposits could be present on Mars and could be accessed by surface rovers.
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Date Issued: 2016-03-16
Identifier: FSU_pmch_26982497, 10.1371/journal.pone.0150342, PMC4794207, 26982497, 26982497, PONE-D-15-26866
Format: Citation

Title: A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis.
Creator: Baab, Karen L, Brown, Peter, Falk, Dean, Richtsmeier, Joan T, Hildebolt, Charles F, Smith, Kirk, Jungers, William
Abstract/Description: The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently,...
Show moreThe Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots in Plio-Pleistocene Homo taxa.
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Date Issued: 2016-06-08
Identifier: FSU_pmch_27275928, 10.1371/journal.pone.0155731, PMC4898715, 27275928, 27275928, PONE-D-15-42984
Format: Citation

Title: Influence of Repressive Histone and DNA Methylation upon D4Z4 Transcription in Non-Myogenic Cells.
Creator: Das, Sunny, Chadwick, Brian P
Abstract/Description: We looked at a disease-associated macrosatellite array D4Z4 and focused on epigenetic factors influencing its chromatin state outside of the disease-context. We used the HCT116 cell line that contains the non-canonical polyadenylation (poly-A) signal required to stabilize somatic transcripts of the human double homeobox gene DUX4, encoded from D4Z4. In HCT116, D4Z4 is packaged into constitutive heterochromatin, characterized by DNA methylation and histone H3 tri-methylation at lysine 9 ...
Show moreWe looked at a disease-associated macrosatellite array D4Z4 and focused on epigenetic factors influencing its chromatin state outside of the disease-context. We used the HCT116 cell line that contains the non-canonical polyadenylation (poly-A) signal required to stabilize somatic transcripts of the human double homeobox gene DUX4, encoded from D4Z4. In HCT116, D4Z4 is packaged into constitutive heterochromatin, characterized by DNA methylation and histone H3 tri-methylation at lysine 9 (H3K9me3), resulting in low basal levels of D4Z4-derived transcripts. However, a double knockout (DKO) of DNA methyltransferase genes, DNMT1 and DNMT3B, but not either alone, results in significant loss of DNA and H3K9 methylation. This is coupled with upregulation of transcript levels from the array, including DUX4 isoforms (DUX4-fl) that are abnormally expressed in somatic muscle in the disease Facioscapulohumeral muscular dystrophy (FSHD) along with DUX4 protein, as indicated indirectly by upregulation of bondafide targets of DUX4 in DKO but not HCT116 cells. Results from treatment with a chemical inhibitor of histone methylation in HCT116 suggest that in the absence of DNA hypomethylation, H3K9me3 loss alone is sufficient to facilitate DUX4-fl transcription. Additionally, characterization of a cell line from a patient with Immunodeficiency, Centromeric instability and Facial anomalies syndrome 1 (ICF1) possessing a non-canonical poly-A signal and DNA hypomethylation at D4Z4 showed DUX4 target gene upregulation in the patient when compared to controls in spite of retention of H3K9me3. Taken together, these data suggest that both DNA methylation and H3K9me3 are determinants of D4Z4 silencing. Moreover, we show that in addition to testis, there is appreciable expression of spliced and polyadenylated D4Z4 derived transcripts that contain the complete DUX4 open reading frame (ORF) along with DUX4 target gene expression in the thymus, suggesting that DUX4 may provide normal function in this somatic tissue.
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Date Issued: 2016-07-28
Identifier: FSU_pmch_27467759, 10.1371/journal.pone.0160022, PMC4965136, 27467759, 27467759, PONE-D-15-54558
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: In Wrong Anticipation - Miscalibrated Beliefs between Germans, Israelis, and Palestinians.
Creator: Goerg, Sebastian J, Hennig-Schmidt, Heike, Walkowitz, Gari, Winter, Eyal
Abstract/Description: The reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners' behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an...
Show moreThe reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners' behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an investee/allocator. We found a notable constellation of calibrated and un-calibrated beliefs. Within each country, transfer standards exist, which investees correctly anticipate within their country. However, across countries these standards differ. By attributing the standard of their own environment to the other countries investees are remarkably bad in predicting foreign investors' behavior. The tendency to ignore this potential difference can be a source of misinterpreting motives in cross-country interaction. Foreigners might perceive behavior as unfavorable or favorable differentiation, even though-unknown to them-investors actually treat fellow-country people and foreigners alike.
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Date Issued: 2016-06-16
Identifier: FSU_pmch_27311066, 10.1371/journal.pone.0156998, PMC4911115, 27311066, 27311066, PONE-D-15-27349
Format: Citation

Title: Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer.
Creator: Vallega, Karin A, Liu, NingNing, Myers, Jennifer S, Yu, Kaixian, Sang, Qing-Xiang Amy
Abstract/Description: African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels...
Show moreAfrican American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.
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Date Issued: 2016-06-17
Identifier: FSU_pmch_27314854, 10.1371/journal.pone.0157741, PMC4912107, 27314854, 27314854, PONE-D-16-17121
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: Mining Twitter to Assess the Public Perception of the "Internet of Things".
Creator: Bian, Jiang, Yoshigoe, Kenji, Hicks, Amanda, Yuan, Jiawei, He, Zhe, Xie, Mengjun, Guo, Yi, Prosperi, Mattia, Salloum, Ramzi, Modave, François
Abstract/Description: Social media analysis has shown tremendous potential to understand public's opinion on a wide variety of topics. In this paper, we have mined Twitter to understand the public's perception of the Internet of Things (IoT). We first generated the discussion trends of the IoT from multiple Twitter data sources and validated these trends with Google Trends. We then performed sentiment analysis to gain insights of the public's attitude towards the IoT. As anticipated, our analysis indicates that...
Show moreSocial media analysis has shown tremendous potential to understand public's opinion on a wide variety of topics. In this paper, we have mined Twitter to understand the public's perception of the Internet of Things (IoT). We first generated the discussion trends of the IoT from multiple Twitter data sources and validated these trends with Google Trends. We then performed sentiment analysis to gain insights of the public's attitude towards the IoT. As anticipated, our analysis indicates that the public's perception of the IoT is predominantly positive. Further, through topic modeling, we learned that public tweets discussing the IoT were often focused on business and technology. However, the public has great concerns about privacy and security issues toward the IoT based on the frequent appearance of related terms. Nevertheless, no unexpected perceptions were identified through our analysis. Our analysis was challenged by the limited fraction of tweets relevant to our study. Also, the user demographics of Twitter users may not be strongly representative of the population of the general public.
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Date Issued: 2016-07-08
Identifier: FSU_pmch_27391760, 10.1371/journal.pone.0158450, PMC4938510, 27391760, 27391760, PONE-D-15-54733
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: Impact of age-associated cyclopurine lesions on DNA repair helicases.
Creator: Khan, Irfan, Suhasini, Avvaru N, Banerjee, Taraswi, Sommers, Joshua A, Kaplan, Daniel L, Kuper, Jochen, Kisker, Caroline, Brosh, Robert M
Abstract/Description: 8,5' cyclopurine deoxynucleosides (cPu) are locally distorting DNA base lesions corrected by nucleotide excision repair (NER) and proposed to play a role in neurodegeneration prevalent in genetically defined Xeroderma pigmentosum (XP) patients. In the current study, purified recombinant helicases from different classifications based on sequence homology were examined for their ability to unwind partial duplex DNA substrates harboring a single site-specific cPu adduct. Superfamily (SF) 2 RecQ...
Show more8,5' cyclopurine deoxynucleosides (cPu) are locally distorting DNA base lesions corrected by nucleotide excision repair (NER) and proposed to play a role in neurodegeneration prevalent in genetically defined Xeroderma pigmentosum (XP) patients. In the current study, purified recombinant helicases from different classifications based on sequence homology were examined for their ability to unwind partial duplex DNA substrates harboring a single site-specific cPu adduct. Superfamily (SF) 2 RecQ helicases (RECQ1, BLM, WRN, RecQ) were inhibited by cPu in the helicase translocating strand, whereas helicases from SF1 (UvrD) and SF4 (DnaB) tolerated cPu in either strand. SF2 Fe-S helicases (FANCJ, DDX11 (ChlR1), DinG, XPD) displayed marked differences in their ability to unwind the cPu DNA substrates. Archaeal Thermoplasma acidophilum XPD (taXPD), homologue to the human XPD helicase involved in NER DNA damage verification, was impeded by cPu in the non-translocating strand, while FANCJ was uniquely inhibited by the cPu in the translocating strand. Sequestration experiments demonstrated that FANCJ became trapped by the translocating strand cPu whereas RECQ1 was not, suggesting the two SF2 helicases interact with the cPu lesion by distinct mechanisms despite strand-specific inhibition for both. Using a protein trap to simulate single-turnover conditions, the rate of FANCJ or RECQ1 helicase activity was reduced 10-fold and 4.5-fold, respectively, by cPu in the translocating strand. In contrast, single-turnover rates of DNA unwinding by DDX11 and UvrD helicases were only modestly affected by the cPu lesion in the translocating strand. The marked difference in effect of the translocating strand cPu on rate of DNA unwinding between DDX11 and FANCJ helicase suggests the two Fe-S cluster helicases unwind damaged DNA by distinct mechanisms. The apparent complexity of helicase encounters with an unusual form of oxidative damage is likely to have important consequences in the cellular response to DNA damage and DNA repair.
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Date Issued: 2014-11-19
Identifier: FSU_pmch_25409515, 10.1371/journal.pone.0113293, PMC4237422, 25409515, 25409515, PONE-D-14-42316
Format: Citation

Title: Identification of G1-regulated genes in normally cycling human cells.
Creator: Beyrouthy, Maroun J, Alexander, Karen E, Baldwin, Amy, Whitfield, Michael L, Bass, Hank W, McGee, Dan, Hurt, Myra M
Abstract/Description: Obtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were...
Show moreObtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were conducted, one which involved isolation of RNA hourly for several hours from synchronous cell populations, and one experiment which examined gene activity every 15 minutes from late telophase of mitosis into G1 phase. To verify synchrony of the cell populations under study, we utilized methods including BrdU uptake, FACS, and microarray analyses of histone gene activity. We also examined stress response gene activity. Our analysis enabled identification of 200 early G1-regulated genes, many of which currently have unknown functions. We also confirmed the expression of a set of genes candidates (fos, atf3 and tceb) by qPCR to further validate the newly identified genes. Genome-scale expression analyses of the first two hours of G1 in naturally cycling cells enabled the discovery of a unique set of G1-regulated genes, many of which currently have unknown functions, in cells progressing normally through the cell division cycle. This group of genes may contain future targets for drug development and treatment of human disease.
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Date Issued: 2008-01-01
Identifier: FSU_pmch_19079774, 10.1371/journal.pone.0003943, PMC2600614, 19079774, 19079774
Format: Citation

Title: Myelin basic protein induces neuron-specific toxicity by directly damaging the neuronal plasma membrane.
Creator: Zhang, Jie, Sun, Xin, Zheng, Sixin, Liu, Xiao, Jin, Jinghua, Ren, Yi, Luo, Jianhong
Abstract/Description: The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was...
Show moreThe central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.
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Date Issued: 2014-09-25
Identifier: FSU_pmch_25255088, 10.1371/journal.pone.0108646, PMC4177931, 25255088, 25255088, PONE-D-14-18395
Format: Citation

Title: Pharmacokinetic properties of 2nd-generation fibroblast growth factor-1 mutants for therapeutic application.
Creator: Xia, Xue, Babcock, Joseph P, Blaber, Sachiko I, Harper, Kathleen M, Blaber, Michael
Abstract/Description: Fibroblast growth factor-1 (FGF-1) is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for...
Show moreFibroblast growth factor-1 (FGF-1) is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK) study in rabbits of human FGF-1 in the presence and absence of heparin, as well as three mutant forms having differential effects upon thermostability, buried reactive thiols, and heparin affinity. The results support the hypothesis that heparan sulfate proteoglycan (HSPG) in the vasculature of liver, kidney and spleen serves as the principle peripheral compartment in the distribution kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like properties of distribution. Mutant forms of FGF-1 that enhance thermostability or eliminate buried reactive thiols demonstrate a shorter distribution half-life, a longer elimination half-life, and a longer mean residence time (MRT) in comparison to wild-type FGF-1. The results show how such mutations can produce useful 2nd-generation forms with tailored PK profiles for specific therapeutic application.
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Date Issued: 2012-01-01
Identifier: FSU_pmch_23133616, 10.1371/journal.pone.0048210, PMC3486806, 23133616, 23133616, PONE-D-12-24821
Format: Citation

Title: Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.
Creator: Singh, Rakesh Kumar, Gonzalez, Melanie, Kabbaj, Marie-Helene Miquel, Gunjan, Akash
Abstract/Description: Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be...
Show moreCore histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus) domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene) finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs) YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases) respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3 ubiquitin ligases to ensure excess histone degradation and thus contribute to the maintenance of genomic stability.
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Date Issued: 2012-01-01
Identifier: FSU_pmch_22570702, 10.1371/journal.pone.0036295, PMC3343073, 22570702, 22570702, PONE-D-11-24652
Format: Citation

Title: Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes..
Creator: Brown, Amber N, Vied, Cynthia, Dennis, Jonathan H, Bhide, Pradeep G
Abstract/Description: Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or...
Show moreDrugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.
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Date Issued: 2015-09-28
Identifier: FSU_pmch_26414157, 10.1371/journal.pone.0139103, PMC4586372, 26414157, 26414157, PONE-D-14-52968
Format: Citation

Title: Dpb11 may function with RPA and DNA to initiate DNA replication.
Creator: Bruck, Irina, Dhingra, Nalini, Martinez, Matthew P, Kaplan, Daniel L
Abstract/Description: Dpb11 is required for the initiation of DNA replication in budding yeast. We found that Dpb11 binds tightly to single-stranded DNA (ssDNA) or branched DNA structures, while its human homolog, TopBP1, binds tightly to branched-DNA structures. We also found that Dpb11 binds stably to CDK-phosphorylated RPA, the eukaryotic ssDNA binding protein, in the presence of branched DNA. A Dpb11 mutant specifically defective for DNA binding did not exhibit tight binding to RPA in the presence of DNA,...
Show moreDpb11 is required for the initiation of DNA replication in budding yeast. We found that Dpb11 binds tightly to single-stranded DNA (ssDNA) or branched DNA structures, while its human homolog, TopBP1, binds tightly to branched-DNA structures. We also found that Dpb11 binds stably to CDK-phosphorylated RPA, the eukaryotic ssDNA binding protein, in the presence of branched DNA. A Dpb11 mutant specifically defective for DNA binding did not exhibit tight binding to RPA in the presence of DNA, suggesting that Dpb11-interaction with DNA may promote the recruitment of RPA to melted DNA. We then characterized a mutant of Dpb11 that is specifically defective in DNA binding in budding yeast cells. Expression of dpb11-m1,2,3,5,ΔC results in a substantial decrease in RPA recruitment to origins, suggesting that Dpb11 interaction with DNA may be required for RPA recruitment to origins. Expression of dpb11-m1,2,3,5,ΔC also results in diminished GINS interaction with Mcm2-7 during S phase, while Cdc45 interaction with Mcm2-7 is like wild-type. The reduced GINS interaction with Mcm2-7 may be an indirect consequence of diminished origin melting. We propose that the tight interaction between Dpb11, CDK-phosphorylated RPA, and branched-DNA may be required for the essential function of stabilizing melted origin DNA in vivo. We also propose an alternative model, wherein Dpb11-DNA interaction is required for some other function in DNA replication initiation, such as helicase activation.
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Date Issued: 2017-05-03
Identifier: FSU_pmch_28467467, 10.1371/journal.pone.0177147, PMC5415106, 28467467, 28467467, PONE-D-17-03239
Format: Citation

Title: Dopamine receptor and Gα(olf) expression in DYT1 dystonia mouse models during postnatal development.
Creator: Zhang, Lin, McCarthy, Deirdre M, Sharma, Nutan, Bhide, Pradeep G
Abstract/Description: DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or...
Show moreDYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or human ΔGAG mutant allele (DYT1 hMT). D1R, D2R, and Gα(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice. We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology.
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Date Issued: 2015-04-10
Identifier: FSU_pmch_25860259, 10.1371/journal.pone.0123104, PMC4393110, 25860259, 25860259, PONE-D-14-28479
Format: Citation

Title: The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.
Creator: Jasińska, Kaja K, Molfese, Peter J, Kornilov, Sergey A, Mencl, W Einar, Frost, Stephen J, Lee, Maria, Pugh, Kenneth R, Grigorenko, Elena L, Landi, Nicole
Abstract/Description: Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans...
Show moreUnderstanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.
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Date Issued: 2016-08-23
Identifier: FSU_pmch_27551971, 10.1371/journal.pone.0157449, PMC4995017, 27551971, 27551971, PONE-D-15-48171
Format: Citation

Title: Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.
Creator: Wang, Hao, Stefanovic, Branko
Abstract/Description: Type I collagen is extracellular matrix protein composed of two α1(I) and one α2(I) polypeptides that fold into triple helix. Collagen polypeptides are translated in coordination to synchronize the rate of triple helix folding to the rate of posttranslational modifications of individual polypeptides. This is especially important in conditions of high collagen production, like fibrosis. It has been assumed that collagen mRNAs are targeted to the membrane of the endoplasmic reticulum (ER) after...
Show moreType I collagen is extracellular matrix protein composed of two α1(I) and one α2(I) polypeptides that fold into triple helix. Collagen polypeptides are translated in coordination to synchronize the rate of triple helix folding to the rate of posttranslational modifications of individual polypeptides. This is especially important in conditions of high collagen production, like fibrosis. It has been assumed that collagen mRNAs are targeted to the membrane of the endoplasmic reticulum (ER) after translation of the signal peptide and by signal peptide recognition particle (SRP). Here we show that collagen mRNAs associate with the ER membrane even when translation is inhibited. Knock down of LARP6, an RNA binding protein which binds 5' stem-loop of collagen mRNAs, releases a small amount of collagen mRNAs from the membrane. Depolimerization of nonmuscle myosin filaments has a similar, but stronger effect. In the absence of LARP6 or nonmuscle myosin filaments collagen polypeptides become hypermodified, are poorly secreted and accumulate in the cytosol. This indicates lack of coordination of their synthesis and retro-translocation due to hypermodifications and misfolding. Depolimerization of nonmuscle myosin does not alter the secretory pathway through ER and Golgi, suggesting that the role of nonmuscle myosin is primarily to partition collagen mRNAs to the ER membrane. We postulate that collagen mRNAs directly partition to the ER membrane prior to synthesis of the signal peptide and that LARP6 and nonmuscle myosin filaments mediate this process. This allows coordinated initiation of translation on the membrane bound collagen α1(I) and α2(I) mRNAs, a necessary step for proper synthesis of type I collagen.
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Date Issued: 2014-10-01
Identifier: FSU_pmch_25271881, 10.1371/journal.pone.0108870, PMC4182744, 25271881, 25271881, PONE-D-14-22936
Format: Citation

Title: Tacrolimus (FK506) prevents early stages of ethanol induced hepatic fibrosis by targeting LARP6 dependent mechanism of collagen synthesis.
Creator: Manojlovic, Zarko, Blackmon, John, Stefanovic, Branko
Abstract/Description: Tacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the...
Show moreTacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the FK506 treated livers and expression of collagen α2(I) mRNA was at normal levels. Collagen α1(I) mRNA was increased in the FK506 treated livers, but this mRNA was not translated into α1(I) polypeptide. No significant inflammation was associated with the fibrosis model used. FK506 binding protein 3 (FKBP3) is one of cellular proteins which binds FK506 with high affinity. We discovered that FKBP3 interacts with LARP6 and LARP6 is the major regulator of translation and stability of collagen mRNAs. In the presence of FK506 the interaction between FKBP3 and LARP6 is weakened and so is the pull down of collagen mRNAs with FKBP3. We postulate that FK506 inactivates FKBP3 and that lack of interaction of LARP6 and FKBP3 results in aberrant translation of collagen mRNAs and prevention of fibrosis. This is the first report of such activity of FK506 and may renew the interest in using this drug to alleviate hepatic fibrosis.
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Date Issued: 2013-06-03
Identifier: FSU_pmch_23755290, 10.1371/journal.pone.0065897, PMC3670911, 23755290, 23755290, PONE-D-13-06089
Format: Citation

Title: Spermitin: a novel mitochondrial protein in Drosophila spermatids..
Creator: Chen, Jieyan V, Megraw, Timothy L
Abstract/Description: Mitochondria, important energy centers in the cell, also control sperm cell morphogenesis. Drosophila spermatids have a remarkably large mitochondrial formation called the nebenkern. Immediately following meiosis during sperm development, the mitochondria in the spermatid fuse together into two large aggregates which then wrap around one another to produce the spherical nebenkern: a giant mitochondrion about 6 micrometers in diameter. The fused mitochondria play an important role in sperm...
Show moreMitochondria, important energy centers in the cell, also control sperm cell morphogenesis. Drosophila spermatids have a remarkably large mitochondrial formation called the nebenkern. Immediately following meiosis during sperm development, the mitochondria in the spermatid fuse together into two large aggregates which then wrap around one another to produce the spherical nebenkern: a giant mitochondrion about 6 micrometers in diameter. The fused mitochondria play an important role in sperm tail elongation by providing a structural platform to support the elongation of sperm cells. We have identified a novel testis-specific protein, Spermitin (Sprn), a protein with a Pleckstrin homology-like (PH) domain related to Ran-binding protein 1 at its C-terminus. Fluorescence microscopy showed that Sprn localizes at mitochondria in transfected Kc167 cells, and in the nebenkern throughout spermatid morphogenesis. The role of Sprn is unclear, as sprn mutant males are fertile, and have sperm tail length comparable to the wild-type.
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Date Issued: 2014-09-29
Identifier: FSU_pmch_25265054, 10.1371/journal.pone.0108802, PMC4181656, 25265054, 25265054, PONE-D-14-12211
Format: Citation

Title: Statistical Models for Tornado Climatology: Long and Short-Term Views..
Creator: Elsner, James B, Jagger, Thomas H, Fricker, Tyler
Abstract/Description: This paper estimates regional tornado risk from records of past events using statistical models. First, a spatial model is fit to the tornado counts aggregated in counties with terms that control for changes in observational practices over time. Results provide a long-term view of risk that delineates the main tornado corridors in the United States where the expected annual rate exceeds two tornadoes per 10,000 square km. A few counties in the Texas Panhandle and central Kansas have annual...
Show moreThis paper estimates regional tornado risk from records of past events using statistical models. First, a spatial model is fit to the tornado counts aggregated in counties with terms that control for changes in observational practices over time. Results provide a long-term view of risk that delineates the main tornado corridors in the United States where the expected annual rate exceeds two tornadoes per 10,000 square km. A few counties in the Texas Panhandle and central Kansas have annual rates that exceed four tornadoes per 10,000 square km. Refitting the model after removing the least damaging tornadoes from the data (EF0) produces a similar map but with the greatest tornado risk shifted south and eastward. Second, a space-time model is fit to the counts aggregated in raster cells with terms that control for changes in climate factors. Results provide a short-term view of risk. The short-term view identifies a shift of tornado activity away from the Ohio Valley under El Niño conditions and away from the Southeast under positive North Atlantic oscillation conditions. The combined predictor effects on the local rates is quantified by fitting the model after leaving out the year to be predicted from the data. The models provide state-of-the-art views of tornado risk that can be used by government agencies, the insurance industry, and the general public.
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Date Issued: 2016-11-22
Identifier: FSU_pmch_27875581, 10.1371/journal.pone.0166895, PMC5119788, 27875581, 27875581, PONE-D-16-27805
Format: Citation

Title: The Florida Harvester Ant, Pogonomyrmex badius, Relies on Germination to Consume Large Seeds.
Creator: Tschinkel, Walter R, Kwapich, Christina L
Abstract/Description: The Florida harvester ant, Pogonomyrmex badius, is one of many ant species and genera that stores large numbers of seeds in damp, underground chambers for later consumption. A comparison of the sizes of seeds recovered from storage chambers with those of seed husks discarded following consumption revealed that the used seeds are far smaller than stored seeds. This difference in use-rate was confirmed in field and laboratory colonies by offering marked seeds of various sizes and monitoring the...
Show moreThe Florida harvester ant, Pogonomyrmex badius, is one of many ant species and genera that stores large numbers of seeds in damp, underground chambers for later consumption. A comparison of the sizes of seeds recovered from storage chambers with those of seed husks discarded following consumption revealed that the used seeds are far smaller than stored seeds. This difference in use-rate was confirmed in field and laboratory colonies by offering marked seeds of various sizes and monitoring the appearance of size-specific chaff. Because foragers collect a range of seed sizes but only open small seeds, large seeds accumulate, forming 70% or more of the weight of seed stores. Major workers increase the rates at which small and medium seeds are opened, but do not increase the size range of opened seeds. Experiments limiting ant access to portions of natural seed chambers showed that seeds germinate during storage, but that the ants rapidly remove them. When offered alongside non germinating seeds, germinating seeds were preferentially fed to larvae. The rate of germination during the annual cycle was determined by both burial in artificial chambers at various depths and under four laboratory temperatures. The germination rate depends upon the species of seed, the soil/laboratory temperature and/or the elapsed time. The seasonal soil temperature cycle generated germination patterns that vary with the mix of locally-available seeds. Taken together, exploitation of germination greatly increases the resources available to the ants in space and time. While the largest seeds may have the nutritional value of 15 small seeds, the inability of workers to open large seeds at will precludes them from rapid use during catastrophic events. The harvester ant's approach to seed harvesting is therefore two-pronged, with both immediate and delayed payoffs arising from the tendency to forage for a wide variety of seeds sizes.
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Date Issued: 2016-11-28
Identifier: FSU_pmch_27893844, 10.1371/journal.pone.0166907, PMC5125654, 27893844, 27893844, PONE-D-16-33448
Format: Citation

Title: Eastern Mediterranean Economic Exchange during the Iron Age: Portable X-Ray Fluorescence and Neutron Activation Analysis of Cypriot-Style Pottery in the Amuq Valley, Turkey..
Creator: Karacic, Steven, Osborne, James F
Abstract/Description: Two markers of regional exchange in the Eastern Mediterranean during the first millennium BCE are the White Painted and Bichrome Wares from Cyprus's Cypro-Geometric and Cypro-Archaic periods. Although these ceramics are often assumed to be imports from Cyprus, excavations in southern Turkey at sites such as Tarsus-Gözlükule, Kilise Tepe, Sirkeli Höyük, and Kinet Höyük suggest that at least some of this pottery was produced locally, requiring a major revision of our understanding of economic...
Show moreTwo markers of regional exchange in the Eastern Mediterranean during the first millennium BCE are the White Painted and Bichrome Wares from Cyprus's Cypro-Geometric and Cypro-Archaic periods. Although these ceramics are often assumed to be imports from Cyprus, excavations in southern Turkey at sites such as Tarsus-Gözlükule, Kilise Tepe, Sirkeli Höyük, and Kinet Höyük suggest that at least some of this pottery was produced locally, requiring a major revision of our understanding of economic interaction in the Eastern Mediterranean. We employ a combination of portable x-ray fluorescence and neutron activation analysis to investigate the White Painted and Bichrome Wares recovered from Tell Tayinat, Çatal Höyük, and Tell Judaidah, three sites in the Amuq Valley of southeastern Anatolia. Our results demonstrate that a clear geochemical distinction exists between imported and local versions of this pottery. Through comparison with legacy datasets, we locate the likely origin of the imported pottery in the Circum-Troodos sediments of central and southern Cyprus. The secondary and tertiary settlements of Çatal Höyük and Tell Judaidah had access only to this imported material. In contrast, the inhabitants of Tell Tayinat, capital city of the region, consumed both imported and locally produced White Painted and Bichrome Wares. This pattern cannot be explained in purely economic terms whereby the frequency of imports decreases as distance from the point of production increases. Instead, we suggest that elite feasting practices drove demand, resulting in either local potters producing Cypriot-style pottery or Cypriot potters settling in the vicinity of Tell Tayinat. These findings offer new insights into the relationship between historically attested Iron Age kingdoms in southern Turkey and Cyprus and complicate our understanding of exchange in the Eastern Mediterranean during the Iron Age.
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Date Issued: 2016-11-30
Identifier: FSU_pmch_27902729, 10.1371/journal.pone.0166399, PMC5130191, 27902729, 27902729, PONE-D-16-37930
Format: Citation

Title: Understanding the Home Math Environment and Its Role in Predicting Parent Report of Children's Math Skills.
Creator: Hart, Sara A, Ganley, Colleen M, Purpura, David J
Abstract/Description: There is a growing literature concerning the role of the home math environment in children's math development. In this study, we examined the relation between these constructs by specifically addressing three goals. The first goal was to identify the measurement structure of the home math environment through a series of confirmatory factor analyses. The second goal was to examine the role of the home math environment in predicting parent report of children's math skills. The third goal was to...
Show moreThere is a growing literature concerning the role of the home math environment in children's math development. In this study, we examined the relation between these constructs by specifically addressing three goals. The first goal was to identify the measurement structure of the home math environment through a series of confirmatory factor analyses. The second goal was to examine the role of the home math environment in predicting parent report of children's math skills. The third goal was to test a series of potential alternative explanations for the relation between the home math environment and parent report of children's skills, specifically the direct and indirect role of household income, parent math anxiety, and parent math ability as measured by their approximate number system performance. A final sample of 339 parents of children aged 3 through 8 drawn from Mechanical Turk answered a questionnaire online. The best fitting model of the home math environment was a bifactor model with a general factor representing the general home math environment, and three specific factors representing the direct numeracy environment, the indirect numeracy environment, and the spatial environment. When examining the association of the home math environment factors to parent report of child skills, the general home math environment factor and the spatial environment were the only significant predictors. Parents who reported doing more general math activities in the home reported having children with higher math skills, whereas parents who reported doing more spatial activities reported having children with lower math skills.
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Date Issued: 2016-12-22
Identifier: FSU_pmch_28005925, 10.1371/journal.pone.0168227, PMC5179117, 28005925, 28005925, PONE-D-16-10081
Format: Citation

Title: Withaferin-A reduces type I collagen expression in vitro and inhibits development of myocardial fibrosis in vivo.
Creator: Challa, Azariyas A, Vukmirovic, Milica, Blackmon, John, Stefanovic, Branko
Abstract/Description: Type I collagen is the most abundant protein in the human body. Its excessive synthesis results in fibrosis of various organs. Fibrosis is a major medical problem without an existing cure. Excessive synthesis of type I collagen in fibrosis is primarily due to stabilization of collagen mRNAs. We recently reported that intermediate filaments composed of vimentin regulate collagen synthesis by stabilizing collagen mRNAs. Vimentin is a primary target of Withaferin-A (WF-A). Therefore, we...
Show moreType I collagen is the most abundant protein in the human body. Its excessive synthesis results in fibrosis of various organs. Fibrosis is a major medical problem without an existing cure. Excessive synthesis of type I collagen in fibrosis is primarily due to stabilization of collagen mRNAs. We recently reported that intermediate filaments composed of vimentin regulate collagen synthesis by stabilizing collagen mRNAs. Vimentin is a primary target of Withaferin-A (WF-A). Therefore, we hypothesized that WF-A may reduce type I collagen production by disrupting vimentin filaments and decreasing the stability of collagen mRNAs. This study is to determine if WF-A exhibits anti-fibrotic properties in vitro and in vivo and to elucidate the molecular mechanisms of its action. In lung, skin and heart fibroblasts WF-A disrupted vimentin filaments at concentrations of 0.5-1.5 µM and reduced 3 fold the half-lives of collagen α1(I) and α2(I) mRNAs and protein expression. In addition, WF-A inhibited TGF-β1 induced phosphorylation of TGF-β1 receptor I, Smad3 phosphorylation and transcription of collagen genes. WF-A also inhibited in vitro activation of primary hepatic stellate cells and decreased their type I collagen expression. In mice, administration of 4 mg/kg WF-A daily for 2 weeks reduced isoproterenol-induced myocardial fibrosis by 50%. Our findings provide strong evidence that Withaferin-A could act as an anti-fibrotic compound against fibroproliferative diseases, including, but not limited to, cardiac interstitial fibrosis.
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Date Issued: 2012-01-01
Identifier: FSU_pmch_22900077, 10.1371/journal.pone.0042989, PMC3416765, 22900077, 22900077, PONE-D-12-16085
Format: Citation

Title: The transcription factor YY1 is a novel substrate for Aurora B kinase at G2/M transition of the cell cycle.
Creator: Kassardjian, Ari, Rizkallah, Raed, Riman, Sarah, Renfro, Samuel H, Alexander, Karen E, Hurt, Myra M
Abstract/Description: Yin Yang 1 (YY1) is a ubiquitously expressed and highly conserved multifunctional transcription factor that is involved in a variety of cellular processes. Many YY1-regulated genes have crucial roles in cell proliferation, differentiation, apoptosis, and cell cycle regulation. Numerous mechanisms have been shown to regulate the function of YY1, such as DNA binding affinity, subcellular localization, and posttranslational modification including phosphorylation. Polo-like kinase 1(Plk1) and...
Show moreYin Yang 1 (YY1) is a ubiquitously expressed and highly conserved multifunctional transcription factor that is involved in a variety of cellular processes. Many YY1-regulated genes have crucial roles in cell proliferation, differentiation, apoptosis, and cell cycle regulation. Numerous mechanisms have been shown to regulate the function of YY1, such as DNA binding affinity, subcellular localization, and posttranslational modification including phosphorylation. Polo-like kinase 1(Plk1) and Casein kinase 2α (CK2 α) were the first two kinases identified to phosphorylate YY1. In this study, we identify a third kinase. We report that YY1 is a novel substrate of the Aurora B kinase both in vitro and in vivo. Serine 184 phosphorylation of YY1 by Aurora B is cell cycle regulated and peaks at G2/M and is rapidly dephosphorylated, likely by protein phosphatase 1 (PP1) as the cells enter G1. Aurora A and Aurora C can also phosphorylate YY1 in vitro, but at serine/threonine residues other than serine 184. We present evidence that phosphorylation of YY1 in the central glycine/alanine (G/A)-rich region is important for DNA binding activity, with a potential phosphorylation/acetylation interplay regulating YY1 function. Given their importance in mitosis and overexpression in human cancers, Aurora kinases have been identified as promising therapeutic targets. Increasing our understanding of Aurora substrates will add to the understanding of their signaling pathways.
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Date Issued: 2012-01-01
Identifier: FSU_pmch_23226345, 10.1371/journal.pone.0050645, PMC3511337, 23226345, 23226345, PONE-D-12-19550
Format: Citation

Title: δ/ω-Plectoxin-Pt1a: an excitatory spider toxin with actions on both Ca(2+) and Na(+) channels..
Creator: Zhou, Yi, Zhao, Mingli, Fields, Gregg B, Wu, Chun-Fang, Branton, W Dale
Abstract/Description: The venom of spider Plectreurys tristis contains a variety of peptide toxins that selectively target neuronal ion channels. O-palmitoylation of a threonine or serine residue, along with a characteristic and highly constrained disulfide bond structure, are hallmarks of a family of toxins found in this venom. Here, we report the isolation and characterization of a new toxin, δ/ω-plectoxin-Pt1a, from this spider venom. It is a 40 amino acid peptide containing an O-palmitoylated Ser-39. Analysis...
Show moreThe venom of spider Plectreurys tristis contains a variety of peptide toxins that selectively target neuronal ion channels. O-palmitoylation of a threonine or serine residue, along with a characteristic and highly constrained disulfide bond structure, are hallmarks of a family of toxins found in this venom. Here, we report the isolation and characterization of a new toxin, δ/ω-plectoxin-Pt1a, from this spider venom. It is a 40 amino acid peptide containing an O-palmitoylated Ser-39. Analysis of δ/ω-plectoxin-Pt1a cDNA reveals a small precursor containing a secretion signal sequence, a 14 amino acid N-terminal propeptide, and a C-terminal amidation signal. The biological activity of δ/ω-plectoxin-Pt1a is also unique. It preferentially blocks a subset of Ca(2+) channels that is apparently not required for neurotransmitter release; decreases threshold for Na(+) channel activation; and slows Na(+) channel inactivation. As δ/ω-plectoxin-Pt1a enhances synaptic transmission by prolonging presynaptic release of neurotransmitter, its effects on Na(+) and Ca(2+) channels may act synergistically to sustain the terminal excitability.
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Date Issued: 2013-05-14
Identifier: FSU_pmch_23691198, 10.1371/journal.pone.0064324, PMC3653879, 23691198, 23691198, PONE-D-13-04611
Format: Citation

Title: The transcription factor YY1 is a substrate for Polo-like kinase 1 at the G2/M transition of the cell cycle.
Creator: Rizkallah, Raed, Alexander, Karen E, Kassardjian, Ari, Lüscher, Bernhard, Hurt, Myra M
Abstract/Description: Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle...
Show moreYin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate.
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Date Issued: 2011-01-06
Identifier: FSU_pmch_21253604, 10.1371/journal.pone.0015928, PMC3017090, 21253604, 21253604
Format: Citation

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