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Sample records for regulates developmental progression

  1. Developmental Regulation with Progressive Vision Loss: Use of Control Strategies and Affective Well-Being

    ERIC Educational Resources Information Center

    Schilling, Oliver K.; Wahl, Hans-Werner; Boerner, Kathrin; Horowitz, Amy; Reinhardt, Joann P.; Cimarolli, Verena R.; Brennan-Ing, Mark; Heckhausen, Jutta

    2016-01-01

    The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being,…

  2. Developmental regulation with progressive vision loss: Use of control strategies and affective well-being.

    PubMed

    Schilling, Oliver K; Wahl, Hans-Werner; Boerner, Kathrin; Horowitz, Amy; Reinhardt, Joann P; Cimarolli, Verena R; Brennan-Ing, Mark; Heckhausen, Jutta

    2016-04-01

    The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being, in a sample of 364 older adults diagnosed with age-related macular degeneration. Using longitudinal data from 5 occasions at 6-month intervals, we examined intraindividual change in control strategies, and how it was related to change in affective well-being, in terms of self-rated happiness and depressive symptoms. Mixed model analyses confirmed our hypotheses that (a) intraindividual change, particularly in selective primary control and in compensatory secondary control (CSC), predict change toward higher happiness ratings and lower depression; and (b) as functional abilities (instrumental activities of daily living) declined, CSC became increasingly predictive of better affective well-being. Overall, the findings suggest that CSC strategies are essential for maintaining affective well-being when physical functioning declines. Intensified selective primary control striving may be effective to achieve goals that have become difficult to reach but are not associated with affective well-being, possibly because struggling with difficulties undermines the experience of enjoyable mastery. In contrast, goal adjustments and self-protective thinking may help to find pleasure even from restricted daily activities. (PsycINFO Database Record PMID:26845507

  3. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1

    PubMed Central

    Champhekar, Ameya; Damle, Sagar S.; Freedman, George; Carotta, Sebastian; Nutt, Stephen L.

    2015-01-01

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program. PMID:25846797

  4. Developmental regulators in Aspergillus fumigatus.

    PubMed

    Park, Hee-Soo; Yu, Jae-Hyuk

    2016-03-01

    The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species. PMID:26920882

  5. Progressive Polycomb Assembly on H3K27me3 Compartments Generates Polycomb Bodies with Developmentally Regulated Motion

    PubMed Central

    Cheutin, Thierry; Cavalli, Giacomo

    2012-01-01

    Polycomb group (PcG) proteins are conserved chromatin factors that maintain silencing of key developmental genes outside of their expression domains. Recent genome-wide analyses showed a Polycomb (PC) distribution with binding to discrete PcG response elements (PREs). Within the cell nucleus, PcG proteins localize in structures called PC bodies that contain PcG-silenced genes, and it has been recently shown that PREs form local and long-range spatial networks. Here, we studied the nuclear distribution of two PcG proteins, PC and Polyhomeotic (PH). Thanks to a combination of immunostaining, immuno-FISH, and live imaging of GFP fusion proteins, we could analyze the formation and the mobility of PC bodies during fly embryogenesis as well as compare their behavior to that of the condensed fraction of euchromatin. Immuno-FISH experiments show that PC bodies mainly correspond to 3D structural counterparts of the linear genomic domains identified in genome-wide studies. During early embryogenesis, PC and PH progressively accumulate within PC bodies, which form nuclear structures localized on distinct euchromatin domains containing histone H3 tri-methylated on K27. Time-lapse analysis indicates that two types of motion influence the displacement of PC bodies and chromatin domains containing H2Av-GFP. First, chromatin domains and PC bodies coordinately undergo long-range motions that may correspond to the movement of whole chromosome territories. Second, each PC body and chromatin domain has its own fast and highly constrained motion. In this motion regime, PC bodies move within volumes slightly larger than those of condensed chromatin domains. Moreover, both types of domains move within volumes much smaller than chromosome territories, strongly restricting their possibility of interaction with other nuclear structures. The fast motion of PC bodies and chromatin domains observed during early embryogenesis strongly decreases in late developmental stages, indicating a

  6. Developmental Progress in Institutional and Community Settings.

    ERIC Educational Resources Information Center

    Sokol-Kessler, Leslie E.; And Others

    1983-01-01

    Comparison of developmental growth for 104 matched pairs from mentally retarded residents of a public institution and of community living arrangements (CLA) revealed that CLA Ss showed significant developmental progress in reduction of maladaptive behavior while institutionalized Ss showed no change over 2 years. (Author/CL)

  7. Developmental regulation of embryonic genes in plants

    SciTech Connect

    Borkird, C.; Choi, Jung, H.; Jin, Zhenghua; Franz, G.; Hatzopoulos, P.; Chorneaus, R.; Bonas, U.; Pelegri, F.; Sung, Z.R.

    1988-09-01

    Somatic embryogenesis from cultured carrot cells progresses through successive morphogenetic stages termed globular, heart, and torpedo. To understand the molecular mechanisms underlying plant embryogenesis, the authors isolated two genes differentially expressed during embryo development. The expression of these two genes is associated with heart-stage embryogenesis. By altering the culture conditions and examining their expressions in a developmental variant cell line, they found that these genes were controlled by the developmental program of embryogenesis and were not directly regulated by 2,4-dichlorophenoxyacetic acid, the growth regulator that promotes unorganized growth of cultured cells and suppresses embryo morphogenesis. These genes are also expressed in carrot zygotic embryos but not in seedlings or mature plants.

  8. Cerebral aneurysms: Formation, progression and developmental chronology

    PubMed Central

    Etminan, Nima; Buchholz, Bruce A.; Dreier, Rita; Bruckner, Peter; Torner, James C.; Steiger, Hans-Jakob; Hänggi, Daniel; Macdonald, R. Loch

    2015-01-01

    The prevalence of unruptured intracranial aneurysms (UAIs) in the general population is up to 3%. Existing epidemiological data suggests that only a small fraction of UIAs progress towards rupture over the lifetime of an individual, but the surrogates for subsequent rupture and the natural history of UIAs are discussed very controversially at present. In case of rupture of an UIA, the case-fatality is up to 50%, which therefore continues to stimulate interest in the pathogenesis of cerebral aneurysm formation and progression. Actual data on the chronological development of cerebral aneurysm has been especially difficult to obtain and, until recently, the existing knowledge in this respect is mainly derived from animal or mathematical models or short-term observational studies. Here, we highlight the current data on cerebral aneurysm formation and progression as well as a novel approach to investigate the developmental chronology of cerebral aneurysms. PMID:24323717

  9. Developmental Regulation of the Collagenase-3 Promoter in Osteoblasts

    NASA Technical Reports Server (NTRS)

    Partridge, N. C.; Yang, Y.; DAlonzo, R. C.; Winchester, S. K.

    1999-01-01

    Previously, we have shown that collagenase-3 MRNA is developmentally expressed in normal, differentiating rat osteoblasts. In vivo, the gene is expressed in a tissue-specific fashion in hypertrophic chondrocytes and osteoblasts and developmentally regulated. Our studies aim at determining the promoter elements and proteins binding to the promoter responsible for tissue and developmental regulation of collagenase-3.

  10. Negative regulation and developmental competence in Aspergillus.

    PubMed

    Lee, Mi-Kyung; Kwon, Nak-Jung; Lee, Im-Soon; Jung, Seunho; Kim, Sun-Chang; Yu, Jae-Hyuk

    2016-01-01

    Asexual development (conidiation) in the filamentous fungus Aspergillus nidulans is governed by orchestrated gene expression. The three key negative regulators of conidiation SfgA, VosA, and NsdD act at different control point in the developmental genetic cascade. Here, we have revealed that NsdD is a key repressor affecting the quantity of asexual spores in Aspergillus. Moreover, nullifying both nsdD and vosA results in abundant formation of the development specific structure conidiophores even at 12 h of liquid culture, and near constitutive activation of conidiation, indicating that acquisition of developmental competence involves the removal of negative regulation exerted by both NsdD and VosA. NsdD's role in repressing conidiation is conserved in other aspergilli, as deleting nsdD causes enhanced and precocious activation of conidiation in Aspergillus fumigatus or Aspergillus flavus. In vivo NsdD-DNA interaction analyses identify three NsdD binding regions in the promoter of the essential activator of conidiation brlA, indicating a direct repressive role of NsdD in conidiation. Importantly, loss of flbC or flbD encoding upstream activators of brlA in the absence of nsdD results in delayed activation of brlA, suggesting distinct positive roles of FlbC and FlbD in conidiation. A genetic model depicting regulation of conidiation in A. nidulans is presented. PMID:27364479

  11. Negative regulation and developmental competence in Aspergillus

    PubMed Central

    Lee, Mi-Kyung; Kwon, Nak-Jung; Lee, Im-Soon; Jung, Seunho; Kim, Sun-Chang; Yu, Jae-Hyuk

    2016-01-01

    Asexual development (conidiation) in the filamentous fungus Aspergillus nidulans is governed by orchestrated gene expression. The three key negative regulators of conidiation SfgA, VosA, and NsdD act at different control point in the developmental genetic cascade. Here, we have revealed that NsdD is a key repressor affecting the quantity of asexual spores in Aspergillus. Moreover, nullifying both nsdD and vosA results in abundant formation of the development specific structure conidiophores even at 12 h of liquid culture, and near constitutive activation of conidiation, indicating that acquisition of developmental competence involves the removal of negative regulation exerted by both NsdD and VosA. NsdD’s role in repressing conidiation is conserved in other aspergilli, as deleting nsdD causes enhanced and precocious activation of conidiation in Aspergillus fumigatus or Aspergillus flavus. In vivo NsdD-DNA interaction analyses identify three NsdD binding regions in the promoter of the essential activator of conidiation brlA, indicating a direct repressive role of NsdD in conidiation. Importantly, loss of flbC or flbD encoding upstream activators of brlA in the absence of nsdD results in delayed activation of brlA, suggesting distinct positive roles of FlbC and FlbD in conidiation. A genetic model depicting regulation of conidiation in A. nidulans is presented. PMID:27364479

  12. Developmental pathways during in vitro progression of human islet neogenesis

    PubMed Central

    Dodge, Rikke; Loomans, Cindy; Sharma, Arun; Bonner-Weir, Susan

    2009-01-01

    Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initial Adherent-, Expanded-, and Differentiated- stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using Scatter plots we selected genes with a 2-fold or greater differential expression.. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar–enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated-stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition developmentally important pathways, including Notch/jagged, Wnt/Frizzled, TGFβ superfamily (follistatin, BMPs and SMADs), retinoic acid (COUP-TFI, CRABP1, 2 and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation

  13. Epigenetic and developmental regulation in plant polyploids

    PubMed Central

    Song, Qingxin; Chen, Z. Jeffrey

    2015-01-01

    Polyploidy or whole-genome duplication occurs in some animals and many flowering plants, including many important crops such as wheat, cotton and oilseed rape. The prevalence of polyploidy in the plant kingdom suggests it as an important evolutionary feature for plant speciation and crop domestication. Studies of natural and synthetic polyploids have revealed rapid and dynamic changes in genomic structure and gene expression after polyploid formation. Growing evidence suggests that epigenetic modifications can alter homoeologous gene expression and reprogram gene expression networks, which allows polyploids to establish new cytotypes, grow vigorously and adapt in local environments. Sequence and gene expression changes in polyploids have been well documented and reviewed elsewhere. This review is focused on developmental regulation and epigenetic changes including DNA methylation and histone modifications in polyploids. PMID:25765928

  14. Progressive Education as Continuing Education for the Developmentally Disabled

    ERIC Educational Resources Information Center

    Boedicker, Leslie Kuhn

    2013-01-01

    The need for progressive education is prevalent in one of the most underserved portions of the population: the adult developmentally disabled. Though John Dewey wrote little on the education of the disabled, his philosophy, and that of Mahatma Gandhi's, lend themselves to the further education of this unique segment of society. In this paper,…

  15. Developmental Pathways of Emotion Regulation in Childhood: A Neuropsychological Perspective

    ERIC Educational Resources Information Center

    Woltering, Steven; Lewis, Marc D.

    2009-01-01

    This article presents a model featuring two types of emotion regulation--reactive and deliberate--and discusses the developmental trajectory of both types. We argue that the later-developing capacity for deliberate control builds on and coevolves with earlier-developing reactive control. Findings from the field of developmental neuroscience are…

  16. A size threshold governs Caenorhabditis elegans developmental progression.

    PubMed

    Uppaluri, Sravanti; Brangwynne, Clifford P

    2015-08-22

    The growth of organisms from humans to bacteria is affected by environmental conditions. However, mechanisms governing growth and size control are not well understood, particularly in the context of changes in food availability in developing multicellular organisms. Here, we use a novel microfluidic platform to study the impact of diet on the growth and development of the nematode Caenorhabditis elegans. This device allows us to observe individual worms throughout larval development, quantify their growth as well as pinpoint the moulting transitions marking successive developmental stages. Under conditions of low food availability, worms grow very slowly, but do not moult until they have achieved a threshold size. The time spent in larval stages can be extended by over an order of magnitude, in agreement with a simple threshold size model. Thus, a critical worm size appears to trigger developmental progression, and may contribute to prolonged lifespan under dietary restriction. PMID:26290076

  17. Developmental Regulation across the Life Span: Toward a New Synthesis

    ERIC Educational Resources Information Center

    Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

    2013-01-01

    How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

  18. Zebrafish rest regulates developmental gene expression but not neurogenesis.

    PubMed

    Kok, Fatma O; Taibi, Andrew; Wanner, Sarah J; Xie, Xiayang; Moravec, Cara E; Love, Crystal E; Prince, Victoria E; Mumm, Jeff S; Sirotkin, Howard I

    2012-10-01

    The transcriptional repressor Rest (Nrsf) recruits chromatin-modifying complexes to RE1 'silencer elements', which are associated with hundreds of neural genes. However, the requirement for Rest-mediated transcriptional regulation of embryonic development and cell fate is poorly understood. Conflicting views of the role of Rest in controlling cell fate have emerged from recent studies. To address these controversies, we examined the developmental requirement for Rest in zebrafish using zinc-finger nuclease-mediated gene targeting. We discovered that germ layer specification progresses normally in rest mutants despite derepression of target genes during embryogenesis. This analysis provides the first evidence that maternal rest is essential for repression of target genes during blastula stages. Surprisingly, neurogenesis proceeds largely normally in rest mutants, although abnormalities are observed within the nervous system, including defects in oligodendrocyte precursor cell development and a partial loss of facial branchiomotor neuron migration. Mutants progress normally through embryogenesis but many die as larvae (after 12 days). However, some homozygotes reach adulthood and are viable. We utilized an RE1/NRSE transgenic reporter system to dynamically monitor Rest activity. This analysis revealed that Rest is required to repress gene expression in mesodermal derivatives including muscle and notochord, as well as within the nervous system. Finally, we demonstrated that Rest is required for long-term repression of target genes in non-neural tissues in adult zebrafish. Our results point to a broad role for Rest in fine-tuning neural gene expression, rather than as a widespread regulator of neurogenesis or cell fate. PMID:22951640

  19. Intra- and Interprotein Phosphorylation between Two-hybrid Histidine Kinases Controls Myxococcus xanthus Developmental Progression*

    PubMed Central

    Schramm, Andreas; Lee, Bongsoo; Higgs, Penelope I.

    2012-01-01

    Histidine-aspartate phosphorelay signaling systems are used to couple stimuli to cellular responses. A hallmark feature is the highly modular signal transmission modules that can form both simple “two-component” systems and sophisticated multicomponent systems that integrate stimuli over time and space to generate coordinated and fine-tuned responses. The deltaproteobacterium Myxococcus xanthus contains a large repertoire of signaling proteins, many of which regulate its multicellular developmental program. Here, we assign an orphan hybrid histidine protein kinase, EspC, to the Esp signaling system that negatively regulates progression through the M. xanthus developmental program. The Esp signal system consists of the hybrid histidine protein kinase, EspA, two serine/threonine protein kinases, and a putative transport protein. We demonstrate that EspC is an essential component of this system because ΔespA, ΔespC, and ΔespA ΔespC double mutants share an identical developmental phenotype. Neither substitution of the phosphoaccepting histidine residue nor deletion of the entire catalytic ATPase domain in EspC produces an in vivo mutant developmental phenotype. In contrast, substitution of the receiver phosphoaccepting residue yields the null phenotype. Although the EspC histidine kinase can efficiently autophosphorylate in vitro, it does not act as a phosphodonor to its own receiver domain. Our in vitro and in vivo analyses suggest the phosphodonor is instead the EspA histidine kinase. We propose EspA and EspC participate in a novel hybrid histidine protein kinase signaling mechanism involving both inter- and intraprotein phosphotransfer. The output of this signaling system appears to be the combined phosphorylated state of the EspA and EspC receiver modules. This system regulates the proteolytic turnover of MrpC, an important regulator of the developmental program. PMID:22661709

  20. Prothoracicotropic hormone regulates developmental timing and body size in Drosophila

    PubMed Central

    McBrayer, Zofeyah; Ono, Hajime; Shimell, MaryJane; Parvy, Jean-Philippe; Beckstead, Robert B.; Warren, James T.; Thummel, Carl S.; Dauphin-Villemant, Chantal; Gilbert, Lawrence I.; O’Connor, Michael B.

    2008-01-01

    Summary In insects, control of body size is intimately linked to nutritional quality as well as environmental and genetic cues that regulate the timing of developmental transitions. Prothoracicotropic hormone (PTTH) has been proposed to play an essential role in regulating the production and/or release of ecdysone, a steroid hormone that stimulates molting and metamorphosis. In this report we examine the consequences on Drosophila development of ablating the PTTH-producing neurons. Surprisingly, PTTH production is not essential for molting or metamorphosis. Instead, loss of PTTH results in delayed larval development and eclosion of larger flies with more cells. Prolonged feeding, without changing the rate of growth, causes the developmental delay and is a consequence of low ecdysteroid titers. These results indicate that final body size in insects is determined by a balance between growth rate regulators such as insulin and developmental timing cues such as PTTH that set the duration of the feeding interval. PMID:18061567

  1. Promoter architectures and developmental gene regulation.

    PubMed

    Haberle, Vanja; Lenhard, Boris

    2016-09-01

    Core promoters are minimal regions sufficient to direct accurate initiation of transcription and are crucial for regulation of gene expression. They are highly diverse in terms of associated core promoter motifs, underlying sequence composition and patterns of transcription initiation. Distinctive features of promoters are also seen at the chromatin level, including nucleosome positioning patterns and presence of specific histone modifications. Recent advances in identifying and characterizing promoters using next-generation sequencing-based technologies have provided the basis for their classification into functional groups and have shed light on their modes of regulation, with important implications for transcriptional regulation in development. This review discusses the methodology and the results of genome-wide studies that provided insight into the diversity of RNA polymerase II promoter architectures in vertebrates and other Metazoa, and the association of these architectures with distinct modes of regulation in embryonic development and differentiation. PMID:26783721

  2. Developmental Gene Regulation and Mechanisms of Evolution

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The Marine Biological Laboratory and the National Aeronautics and Space Administration have established a cooperative agreement with the formation of a Center for Advanced Studies 'in the Space Life Sciences (CASSLS) at the MBL. This Center serves as an interface between NASA and the basic science community, addressing issues of mutual interest. The Center for Advanced Studies 'in the Space Life Sciences provides a forum for scientists to think and discuss, often for the first time, the role that gravity and aspects of spaceflight may play 'in fundamental cellular and physiologic processes. In addition the Center will sponsor discussions on evolutionary biology. These interactions will inform the community of research opportunities that are of interest to NASA. This workshop is one of a series of symposia, workshops and seminars that will be held at the MBL to advise NASA on a wide variety of topics in the life sciences, including cell biology, developmental biology, mg evolutionary biology, molecular biology, neurobiology, plant biology and systems biology.

  3. The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium.

    PubMed

    Santhanam, Balaji; Cai, Huaqing; Devreotes, Peter N; Shaulsky, Gad; Katoh-Kurasawa, Mariko

    2015-01-01

    In many systems, including the social amoeba Dictyostelium discoideum, development is often marked by dynamic morphological and transcriptional changes orchestrated by key transcription factors. However, efforts to examine sequential genome-wide changes of gene regulation in developmental processes have been fairly limited. Here we report the developmental regulatory dynamics of GtaC, a GATA-type zinc-finger transcription factor, through the analyses of serial ChIP- and RNA-sequencing data. GtaC is essential for developmental progression, decoding extracellular cAMP pulses during early development and may play a role in mediating cell-type differentiation at later stages. We find that GtaC exhibits temporally distinctive DNA-binding patterns concordant with each developmental stage. We identify direct GtaC targets and observe cotemporaneous GtaC-binding and developmental expression regulation. Our results suggest that GtaC regulates multiple physiological processes as Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism. PMID:26144553

  4. The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium

    PubMed Central

    Santhanam, Balaji; Cai, Huaqing; Devreotes, Peter N.; Shaulsky, Gad; Katoh-Kurasawa, Mariko

    2015-01-01

    In many systems, including the social amoeba Dictyostelium discoideum, development is often marked by dynamic morphological and transcriptional changes orchestrated by key transcription factors. However, efforts to examine sequential genome-wide changes of gene regulation in developmental processes have been fairly limited. Here we report the developmental regulatory dynamics of GtaC, a GATA-type zinc-finger transcription factor, through the analyses of serial ChIP- and RNA-sequencing data. GtaC is essential for developmental progression, decoding extracellular cAMP pulses during early development and may play a role in mediating cell-type differentiation at later stages. We find that GtaC exhibits temporally distinctive DNA-binding patterns concordant with each developmental stage. We identify direct GtaC targets and observe cotemporaneous GtaC-binding and developmental expression regulation. Our results suggest that GtaC regulates multiple physiological processes as Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism. PMID:26144553

  5. Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling

    PubMed Central

    Jerde, Travis J.

    2015-01-01

    Phosphatase and tensin homologue (PTEN) is a critical cell endogenous inhibitor of phosphoinositide signaling in mammalian cells. PTEN dephosphorylates phosphoinositide trisphosphate (PIP3), and by so doing PTEN has the function of negative regulation of Akt, thereby inhibiting this key intracellular signal transduction pathway. In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells. Numerous reports exist regarding mutations in PTEN leading to unregulated Akt and human disease, most notably cancer. However, less is commonly known about nonmutational regulation of PTEN. This review focuses on an emerging literature on the regulation of PTEN at the transcriptional, posttranscriptional, translational, and posttranslational levels. Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling. The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival. Perturbations of PTEN regulation consequently lead to human diseases such as cancer, chronic inflammatory syndromes, developmental abnormalities, diabetes, and neurodegeneration. PMID:26339505

  6. Crim1-, a regulator of developmental organogenesis.

    PubMed

    Iyer, Swati; Pennisi, David J; Piper, Michael

    2016-10-01

    The regulation of growth factor localization, availability and activity is critical during embryogenesis to ensure appropriate organogenesis. This process is regulated through the coordinated expression of growth factors and their cognate receptors, as well as via proteins that can bind, sequester or localize growth factors to distinct locations. One such protein is the transmembrane protein Crim1. This protein has been shown to be expressed broadly within the developing embryo, and to regulate organogenesis within the eye, kidney and placenta. Mechanistically, Crim1 has been revealed to mediate organogenesis via its interaction with growth factors including TGFβs, BMPs, VEGFs and PDFGs. More recently, Crim1 has been shown to influence cardiac development, providing further insights into the function of this protein. This review will provide an overview of the role of Crim1 in organogenesis, largely focusing on how this protein regulates growth factor signaling in the nascent heart. Moreover, we will address the challenges ahead relating to further elucidating how Crim1 functions during development. PMID:27044529

  7. Developmental College Student Self-Regulation: Results from Two Measures

    ERIC Educational Resources Information Center

    Young, Dawn; Ley, Kathryn

    2005-01-01

    This study compared 34 lower-achieving (developmental) first-time college students' self-reported self-regulation strategies from a Likert scale to those they reported in structured interviews. Likert scales have offered convenient administration and evaluation and have been used to identify what and how learners study. The reported study activity…

  8. Self-Regulated Strategy Instruction in College Developmental Writing

    ERIC Educational Resources Information Center

    MacArthur, Charles A.; Philippakos, Zoi A.; Ianetta, Melissa

    2015-01-01

    The purpose of this study was to evaluate the effects of a curriculum for college developmental writing classes, developed in prior design research and based on self-regulated strategy instruction. Students learned strategies for planning, drafting, and revising compositions with an emphasis on using knowledge of genre organization to guide…

  9. Functional consequences of developmentally regulated alternative splicing

    PubMed Central

    Kalsotra, Auinash; Cooper, Thomas A.

    2012-01-01

    Genome-wide analyses of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing. Recently, regulatory networks have been identified through which splicing promotes dynamic remodeling of the transcriptome to promote physiological changes, which involve robust and coordinated alternative splicing transitions. The regulation of splicing in yeast, worms, flies and vertebrates affects a variety of biological processes. The functional classes of genes that are regulated by alternative splicing include both those with widespread homeostatic activities and genes with cell-type-specific functions. Alternative splicing can drive determinative physiological change or can have a permissive role by providing mRNA variability that is utilized by other regulatory mechanisms. PMID:21921927

  10. Developmental checkpoints guarded by regulated necrosis.

    PubMed

    Dillon, Christopher P; Tummers, Bart; Baran, Katherine; Green, Douglas R

    2016-06-01

    The process of embryonic development is highly regulated through the symbiotic control of differentiation and programmed cell death pathways, which together sculpt tissues and organs. The importance of programmed necrotic (RIPK-dependent necroptosis) cell death during development has recently been recognized as important and has largely been characterized using genetically engineered animals. Suppression of necroptosis appears to be essential for murine development and occurs at three distinct checkpoints, E10.5, E16.5, and P1. These distinct time points have helped delineate the molecular pathways and regulation of necroptosis. The embryonic lethality at E10.5 seen in knockouts of caspase-8, FADD, or FLIP (cflar), components of the extrinsic apoptosis pathway, resulted in pallid embryos that did not exhibit the expected cellular expansions. This was the first suggestion that these factors play an important role in the inhibition of necroptotic cell death. The embryonic lethality at E16.5 highlighted the importance of TNF engaging necroptosis in vivo, since elimination of TNFR1 from casp8 (-/-), fadd (-/-), or cflar (-/-), ripk3 (-/-) embryos delayed embryonic lethality from E10.5 until E16.5. The P1 checkpoint demonstrates the dual role of RIPK1 in both the induction and inhibition of necroptosis, depending on the upstream signal. This review summarizes the role of necroptosis in development and the genetic evidence that helped detail the molecular mechanisms of this novel pathway of programmed cell death. PMID:27056574

  11. Developmental Psychology and Public Policy: Progress and Prospects

    ERIC Educational Resources Information Center

    Foster, E. Michael; Kalil, Ariel

    2005-01-01

    This article outlines a framework for developmentally oriented policy research. Drawing from U. Bronfenbrenner's (1995) dynamic developmental systems theory, the authors suggest ways in which the key tenets of process, persons, context, and time can inform policy research in developmental psychology and can be used to support a causal…

  12. Regulation of terpene metabolism. Progress report

    SciTech Connect

    Croteau, R.

    1983-01-01

    Progress is reported in the following research areas: function of monoterpene catabolism; pathways and enzymes of monoterpene catabolism; ultrastructure of oil glands; pathways and enzymes of monoterpene biosynthesis; and regulation of metabolism in peppermints. (ACR)

  13. Progress toward risk informed regulation

    SciTech Connect

    Rogers, K.C.

    1997-01-01

    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  14. School Readiness and Self-Regulation: A Developmental Psychobiological Approach

    PubMed Central

    Blair, Clancy; Raver, C. Cybele

    2015-01-01

    Research on the development of self-regulation in young children provides a unifying framework for the study of school readiness. Self-regulation abilities allow for engagement in learning activities and provide the foundation for adjustment to school. A focus on readiness as self-regulation does not supplant interest in the development of acquired ability, such as early knowledge of letters and numbers; it sets the stage for it. In this article, we review research and theory indicating that self-regulation and consequently school readiness are the product of integrated developmental processes at the biological and behavioral levels that are shaped by the contexts in which development is occurring. In doing so, we illustrate the idea that research on self-regulation powerfully highlights ways in which gaps in school readiness and later achievement are linked to poverty and social and economic inequality and points the way to effective approaches to counteract these conditions. PMID:25148852

  15. Academic Progress of Developmental Students, Fall 1993-Spring 1995.

    ERIC Educational Resources Information Center

    Laramie County Community Coll., Cheyenne, WY.

    A study was conducted at Laramie County Community College to assess the performance of developmental students and evaluate the effectiveness of the college's testing and placement system. The study tracked students entering in fall 1993 whose placement scores identified them as developmental to determine actual enrollment and performance in…

  16. Callose homeostasis at plasmodesmata: molecular regulators and developmental relevance

    PubMed Central

    De Storme, Nico; Geelen, Danny

    2014-01-01

    Plasmodesmata are membrane-lined channels that are located in the plant cell wall and that physically interconnect the cytoplasm and the endoplasmic reticulum (ER) of adjacent cells. Operating as controllable gates, plasmodesmata regulate the symplastic trafficking of micro- and macromolecules, such as endogenous proteins [transcription factors (TFs)] and RNA-based signals (mRNA, siRNA, etc.), hence mediating direct cell-to-cell communication and long distance signaling. Besides this physiological role, plasmodesmata also form gateways through which viral genomes can pass, largely facilitating the pernicious spread of viral infections. Plasmodesmatal trafficking is either passive (e.g., diffusion) or active and responses both to developmental and environmental stimuli. In general, plasmodesmatal conductivity is regulated by the controlled build-up of callose at the plasmodesmatal neck, largely mediated by the antagonistic action of callose synthases (CalSs) and β-1,3-glucanases. Here, in this theory and hypothesis paper, we outline the importance of callose metabolism in PD SEL control, and highlight the main molecular factors involved. In addition, we also review other proteins that regulate symplastic PD transport, both in a developmental and stress-responsive framework, and discuss on their putative role in the modulation of PD callose turn-over. Finally, we hypothesize on the role of structural sterols in the regulation of (PD) callose deposition and outline putative mechanisms by which this regulation may occur. PMID:24795733

  17. Differential Methylation during Maize Leaf Growth Targets Developmentally Regulated Genes1[C][W][OPEN

    PubMed Central

    Candaele, Jasper; Demuynck, Kirin; Mosoti, Douglas; Beemster, Gerrit T.S.; Inzé, Dirk; Nelissen, Hilde

    2014-01-01

    DNA methylation is an important and widespread epigenetic modification in plant genomes, mediated by DNA methyltransferases (DMTs). DNA methylation is known to play a role in genome protection, regulation of gene expression, and splicing and was previously associated with major developmental reprogramming in plants, such as vernalization and transition to flowering. Here, we show that DNA methylation also controls the growth processes of cell division and cell expansion within a growing organ. The maize (Zea mays) leaf offers a great tool to study growth processes, as the cells progressively move through the spatial gradient encompassing the division zone, transition zone, elongation zone, and mature zone. Opposite to de novo DMTs, the maintenance DMTs were transcriptionally regulated throughout the growth zone of the maize leaf, concomitant with differential CCGG methylation levels in the four zones. Surprisingly, the majority of differentially methylated sequences mapped on or close to gene bodies and not to repeat-rich loci. Moreover, especially the 5′ and 3′ regions of genes, which show overall low methylation levels, underwent differential methylation in a developmental context. Genes involved in processes such as chromatin remodeling, cell cycle progression, and growth regulation, were differentially methylated. The presence of differential methylation located upstream of the gene anticorrelated with transcript expression, while gene body differential methylation was unrelated to the expression level. These data indicate that DNA methylation is correlated with the decision to exit mitotic cell division and to enter cell expansion, which adds a new epigenetic level to the regulation of growth processes. PMID:24488968

  18. (Regulation of terpene metabolism. ) Progress report

    SciTech Connect

    Croteau, R.

    1984-01-01

    This research program represents a very broad-based approach to understanding the biochemistry of the monoterpene and sesquiterpene constituents of the essential oils. This program includes basic research on the pathways, enzymes and mechanisms of terpene biosynthesis and catabolism, on the physiology of essential oil production, and on the morphology and development of oil glands, as well as practical approaches to manipulating essential oil composition and yield. As a natural extension of research on monoterpene biosynthesis and catabolism in sage and peppermint we have explored some aspects of possible regulatory mechanisms. Tentative evidence has been obtained for developmental regulation of the levels of biosynthetic and catabolic enzymes. 10 refs., 8 figs.

  19. Regulation of priority carcinogens and reproductive or developmental toxicants

    SciTech Connect

    Hooper, K.; LaDou, J.; Rosenbaum, J.S.; Book, S.A. )

    1992-01-01

    In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.

  20. DNA Methylation is Developmentally Regulated for Genes Essential for Cardiogenesis

    PubMed Central

    Chamberlain, Alyssa A.; Lin, Mingyan; Lister, Rolanda L.; Maslov, Alex A.; Wang, Yidong; Suzuki, Masako; Wu, Bingruo; Greally, John M.; Zheng, Deyou; Zhou, Bin

    2014-01-01

    Background DNA methylation is a major epigenetic mechanism altering gene expression in development and disease. However, its role in the regulation of gene expression during heart development is incompletely understood. The aim of this study is to reveal DNA methylation in mouse embryonic hearts and its role in regulating gene expression during heart development. Methods and Results We performed the genome‐wide DNA methylation profiling of mouse embryonic hearts using methyl‐sensitive, tiny fragment enrichment/massively parallel sequencing to determine methylation levels at ACGT sites. The results showed that while global methylation of 1.64 million ACGT sites in developing hearts remains stable between embryonic day (E) 11.5 and E14.5, a small fraction (2901) of them exhibit differential methylation. Gene Ontology analysis revealed that these sites are enriched at genes involved in heart development. Quantitative real‐time PCR analysis of 350 genes with differential DNA methylation showed that the expression of 181 genes is developmentally regulated, and 79 genes have correlative changes between methylation and expression, including hyaluronan synthase 2 (Has2). Required for heart valve formation, Has2 expression in the developing heart valves is downregulated at E14.5, accompanied with increased DNA methylation in its enhancer. Genetic knockout further showed that the downregulation of Has2 expression is dependent on DNA methyltransferase 3b, which is co‐expressed with Has2 in the forming heart valve region, indicating that the DNA methylation change may contribute to the Has2 enhancer's regulating function. Conclusions DNA methylation is developmentally regulated for genes essential to heart development, and abnormal DNA methylation may contribute to congenital heart disease. PMID:24947998

  1. Developmental Studies at Nunez Community College: A Work in Progress

    ERIC Educational Resources Information Center

    Accomando, Annette

    2004-01-01

    This paper chronicles the process undertaken by one community college to analyze its Developmental Studies Program. A participant/observer faculty member involved in the college's assessment activities contemplated the institution's complex past, the challenging present, and the unfolding future. An interesting account explicating committee…

  2. Chronic Disease and Perceived Developmental Progression in Adolescence.

    ERIC Educational Resources Information Center

    Seiffge-Krenke, Inge

    1998-01-01

    Examined whether chronic illness causes delays in adolescents' perceived developmental status, using annually-completed questionnaires from insulin-dependent and healthy adolescents. Found that, in first year of study, diabetic adolescents reported delays in physical maturity and an independent lifestyle compared with healthy peers. Overall…

  3. CAI for the Developmentally Handicapped: Nine Years of Progress.

    ERIC Educational Resources Information Center

    Hallworth, H. J.; Brebner, Ann

    Initiated nine years ago by the University of Calgary Faculty of Education Computer Applications Unit in cooperation with the nearby Vocational and Rehabilitation Research Institute (VRRI), this project uses computer assisted instruction (CAI) to teach social and vocational skills to developmentally handicapped young adults, many of whom also have…

  4. Positive Parenting Practices, Health Disparities, and Developmental Progress

    PubMed Central

    Sobotka, Sarah A.; Chen, Yi-Fan; Msall, Michael E.

    2015-01-01

    OBJECTIVE: To describe interactive activities between parents and young children in a nationally representative sample. We hypothesized that the frequency of participation in interactive activities would be different across economic strata and would be associated with developmental delay. METHODS: Children 4 to 36 months of age were identified by using The National Survey of Children’s Health 2011–2012. Interactive caregiving practices were reported by poverty status. Developmental concerns were derived from caregiver responses and scoring of the Parents Evaluation of Developmental Status. Multivariable logistic regressions with weighting were used to explore the effect of interactive practices on risk for developmental delay across poverty levels. Covariates including age, gender, insurance type, maternal education, parenting stress, and ethnicity were adjusted in the models. RESULTS: In our sample (n = 12 642), caregivers with the lowest income versus highest income reported lower participation in reading (33% vs 64%; P < .0001), singing or telling stories (52% vs 77%, P < .0001), and taking their child on an outing (13% vs 22%, P < .0001). Less frequent participation in interactive activities during the week were associated with increased risk of developmental delay among low-income families (Reading odds ratio [OR] 1.57, 95% confidence interval [CI] 1.15–2.13; Singing songs/Telling Stories OR 1.66, 95% CI 1.15–2.40; Outings OR 1.48, 95% CI 1.11–1.97). CONCLUSIONS: Despite evidence emphasizing the protective effects of supportive parenting practices on early child development, our work demonstrates significant disparities in parenting practices that promote early child development between economically advantaged and disadvantaged parents. Innovative population-level strategies that enrich parenting practices for vulnerable children in early childhood are needed. PMID:26216325

  5. Developmental regulation of Tbx5 in zebrafish embryogenesis.

    PubMed

    Begemann, G; Ingham, P W

    2000-02-01

    T-box (tbx) genes constitute a large family of transcriptional regulators involved in developmental patterning processes. In tetrapods, tbx5 has been implicated in specifying forelimb type identity. Here, we report the cloning of the zebrafish tbx5.1 gene and characterise its expression during zebrafish embryogenesis and early larval development of wild type and mutant embryos that affect pectoral fin patterning. tbx5.1 is expressed during development of the heart, the pectoral fins and the eye. Notably, its expression in the lateral plate mesoderm defines a single and continuous region of heart and pectoral fin precursor cells, and constitutes the earliest specific marker for pectoral fin development in the zebrafish. PMID:10640716

  6. Developmental and nutritional regulation of isoflavone secretion from soybean roots.

    PubMed

    Sugiyama, Akifumi; Yamazaki, Yumi; Yamashita, Kazuaki; Takahashi, Seiji; Nakayama, Toru; Yazaki, Kazufumi

    2015-01-01

    Isoflavones play important roles in plant-microbe interactions in rhizospheres. Soybean roots secrete daidzein and genistein to attract rhizobia. Despite the importance of isoflavones in plant-microbe interactions, little is known about the developmental and nutritional regulation of isoflavone secretion from soybean roots. In this study, soybeans were grown in hydroponic culture, and isoflavone contents in tissues, isoflavone secretion from the roots, and the expression of isoflavone conjugates hydrolyzing beta-glucosidase (ICHG) were investigated. Isoflavone contents did not show strong growth-dependent changes, while secretion of daidzein from the roots dramatically changed, with higher secretion during vegetative stages. Coordinately, the expression of ICHG also peaked at vegetative stages. Nitrogen deficiency resulted in 8- and 15-fold increases in secretion of daidzein and genistein, respectively, with no induction of ICHG. Taken together, these results suggest that large amounts of isoflavones were secreted during vegetative stages via the hydrolysis of (malonyl)glucosides with ICHG. PMID:26168358

  7. Cellular manganese content is developmentally regulated in human dopaminergic neurons

    NASA Astrophysics Data System (ADS)

    Kumar, Kevin K.; Lowe, Edward W., Jr.; Aboud, Asad A.; Neely, M. Diana; Redha, Rey; Bauer, Joshua A.; Odak, Mihir; Weaver, C. David; Meiler, Jens; Aschner, Michael; Bowman, Aaron B.

    2014-10-01

    Manganese (Mn) is both an essential biological cofactor and neurotoxicant. Disruption of Mn biology in the basal ganglia has been implicated in the pathogenesis of neurodegenerative disorders, such as parkinsonism and Huntington's disease. Handling of other essential metals (e.g. iron and zinc) occurs via complex intracellular signaling networks that link metal detection and transport systems. However, beyond several non-selective transporters, little is known about the intracellular processes regulating neuronal Mn homeostasis. We hypothesized that small molecules that modulate intracellular Mn could provide insight into cell-level Mn regulatory mechanisms. We performed a high throughput screen of 40,167 small molecules for modifiers of cellular Mn content in a mouse striatal neuron cell line. Following stringent validation assays and chemical informatics, we obtained a chemical `toolbox' of 41 small molecules with diverse structure-activity relationships that can alter intracellular Mn levels under biologically relevant Mn exposures. We utilized this toolbox to test for differential regulation of Mn handling in human floor-plate lineage dopaminergic neurons, a lineage especially vulnerable to environmental Mn exposure. We report differential Mn accumulation between developmental stages and stage-specific differences in the Mn-altering activity of individual small molecules. This work demonstrates cell-level regulation of Mn content across neuronal differentiation.

  8. Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks

    PubMed Central

    Reyes-Bermudez, Alejandro; Villar-Briones, Alejandro; Ramirez-Portilla, Catalina; Hidaka, Michio; Mikheyev, Alexander S.

    2016-01-01

    Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis during Acropora digitifera’s development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression in A. digitifera is regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages. PMID:26941230

  9. Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks.

    PubMed

    Reyes-Bermudez, Alejandro; Villar-Briones, Alejandro; Ramirez-Portilla, Catalina; Hidaka, Michio; Mikheyev, Alexander S

    2016-03-01

    Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis duringAcropora digitifera's development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression inA. digitiferais regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages. PMID:26941230

  10. Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs.

    PubMed

    Tsichlaki, Elina; FitzHarris, Greg

    2016-01-01

    Maintaining appropriate nucleus size is important for cell health, but the mechanisms by which this is achieved are poorly understood. Controlling nucleus size is a particular challenge in early development, where the nucleus must downscale in size with progressive reductive cell divisions. Here we use live and fixed imaging, micromanipulation approaches, and small molecule analyses during preimplantation mouse development to probe the mechanisms by which nucleus size is determined. We find a close correlation between cell and nuclear size at any given developmental stage, and show that experimental cytoplasmic reduction can alter nuclear size, together indicating that cell size helps dictate nuclear proportions. Additionally, however, by creating embryos with over-sized blastomeres we present evidence of a developmental program that drives nuclear downscaling independently of cell size. We show that this developmental program does not correspond with nuclear import rates, but provide evidence that PKC activity may contribute to this mechanism. We propose a model in which nuclear size regulation during early development is a multi-mode process wherein nucleus size is set by cytoplasmic factors, and fine-tuned on a cell-by-cell basis according to cell size. PMID:27320842

  11. Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs

    PubMed Central

    Tsichlaki, Elina; FitzHarris, Greg

    2016-01-01

    Maintaining appropriate nucleus size is important for cell health, but the mechanisms by which this is achieved are poorly understood. Controlling nucleus size is a particular challenge in early development, where the nucleus must downscale in size with progressive reductive cell divisions. Here we use live and fixed imaging, micromanipulation approaches, and small molecule analyses during preimplantation mouse development to probe the mechanisms by which nucleus size is determined. We find a close correlation between cell and nuclear size at any given developmental stage, and show that experimental cytoplasmic reduction can alter nuclear size, together indicating that cell size helps dictate nuclear proportions. Additionally, however, by creating embryos with over-sized blastomeres we present evidence of a developmental program that drives nuclear downscaling independently of cell size. We show that this developmental program does not correspond with nuclear import rates, but provide evidence that PKC activity may contribute to this mechanism. We propose a model in which nuclear size regulation during early development is a multi-mode process wherein nucleus size is set by cytoplasmic factors, and fine-tuned on a cell-by-cell basis according to cell size. PMID:27320842

  12. Core Mechanisms Regulating Developmentally Timed and Environmentally Triggered Abscission.

    PubMed

    Patharkar, O Rahul; Walker, John C

    2016-09-01

    Drought-triggered abscission is a strategy used by plants to avoid the full consequences of drought; however, it is poorly understood at the molecular genetic level. Here, we show that Arabidopsis (Arabidopsis thaliana) can be used to elucidate the pathway controlling drought-triggered leaf shedding. We further show that much of the pathway regulating developmentally timed floral organ abscission is conserved in regulating drought-triggered leaf abscission. Gene expression of HAESA (HAE) and INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) is induced in cauline leaf abscission zones when the leaves become wilted in response to limited water and HAE continues to accumulate in the leaf abscission zones through the abscission process. The genes that encode HAE/HAESA-LIKE2, IDA, NEVERSHED, and MAPK KINASE4 and 5 are all necessary for drought-induced leaf abscission. Our findings offer a molecular mechanism explaining drought-triggered leaf abscission. Furthermore, the ability to study leaf abscission in Arabidopsis opens up a new avenue to tease apart mechanisms involved in abscission that have been difficult to separate from flower development as well as for understanding the mechanistic role of water and turgor pressure in abscission. PMID:27468996

  13. Aphid polyphenisms: trans-generational developmental regulation through viviparity

    PubMed Central

    Ogawa, Kota; Miura, Toru

    2013-01-01

    Polyphenism, in which multiple discrete phenotypes develop from a single genotype, is considered to have contributed to the evolutionary success of aphids. Of the various polyphenisms observed in the complex life cycle of aphids, the reproductive and wing polyphenisms seen in most aphid species are conspicuous. In reproductive polyphenism, the reproductive modes can change between viviparous parthenogenesis and sexual reproduction in response to the photoperiod. Under short-day conditions in autumn, sexual morphs (males and oviparous females) are produced parthenogenetically. Winged polyphenism is observed in viviparous generations during summer, when winged or wingless (flightless) aphids are produced depending on a variety of environmental conditions (e.g., density, predators). Here, we review the physiological mechanisms underlying reproductive and wing polyphenism in aphids. In reproductive polyphenism, morph determination (male, oviparous or viviparous female) within mother aphids is regulated by juvenile hormone (JH) titers in the mothers. In wing polyphenism, although JH is considered to play an important role in phenotype determination (winged or wingless), the role is still controversial. In both cases, the acquisition of viviparity in Aphididae is considered to be the basis for maternal regulation of these polyphenisms, and through which environmental cues can be transferred to developing embryos through the physiological state of the mother. Although the mechanisms by which mothers alter the developmental programs of their progeny have not yet been clarified, continued developments in molecular biology will likely unravel these questions. PMID:24478714

  14. Developmental Regulation of the Tetrahymena thermophila Origin Recognition Complex

    PubMed Central

    Lee, Po-Hsuen; Meng, Xiangzhou; Kapler, Geoffrey M.

    2015-01-01

    The Tetrahymena thermophila DNA replication machinery faces unique demands due to the compartmentalization of two functionally distinct nuclei within a single cytoplasm, and complex developmental program. Here we present evidence for programmed changes in ORC and MCM abundance that are not consistent with conventional models for DNA replication. As a starting point, we show that ORC dosage is critical during the vegetative cell cycle and development. A moderate reduction in Orc1p induces genome instability in the diploid micronucleus, aberrant division of the polyploid macronucleus, and failure to generate a robust intra-S phase checkpoint response. In contrast to yeast ORC2 mutants, replication initiation is unaffected; instead, replication forks elongation is perturbed, as Mcm6p levels decline in parallel with Orc1p. Experimentally induced down-regulation of ORC and MCMs also impairs endoreplication and gene amplification, consistent with essential roles during development. Unexpectedly Orc1p and Mcm6p levels fluctuate dramatically in developing wild type conjugants, increasing for early cycles of conventional micronuclear DNA replication and macronuclear anlagen replication (endoreplication phase I, rDNA gene amplification). This increase does not reflect the DNA replication load, as much less DNA is synthesized during this developmental window compared to vegetative S phase. Furthermore, although Orc1p levels transiently increase prior to endoreplication phase II, Orc1p and Mcm6p levels decline when the replication load increases and unconventional DNA replication intermediates are produced. We propose that replication initiation is re-programmed to meet different requirements or challenges during the successive stages of Tetrahymena development. PMID:25569357

  15. Embryonic developmental progression in lake trout (Salvelinus namaycush) (Walbaum, 1792) and its relation to lake temperature

    USGS Publications Warehouse

    Allen, Jeffrey D.; Walker, Glenn K.; Adams, Jean V.; Nichols, S. Jerrine; Edsall, Carol C.

    2005-01-01

    Developmental progression of lake trout (Salvelinus namaycush) embryos was examined with light and scanning electron microscopy. From this examination, key developmental stages were described in detail. The key developmental stages were then applied to individual lake trout egg lots incubated in constant temperatures of 2, 4, 6, 8, and 10°C. We used Belehradek's, Thermodynamic, and Power models, and also developed the Zero model to determine stage specific developmental rates of lake trout eggs for each background temperature. From the models, hatch dates and staging were predicted for temperature regimes from Lake Superior (1990–91) and Lake Huron (1996–97). Based on the existing lake temperature data and the observed spawning dates, the Zero and the Power models predict that post peak spawning may contribute significantly to overall recruitment success for these years.

  16. Developmental progress and current status of the Animal QTLdb

    PubMed Central

    Hu, Zhi-Liang; Park, Carissa A.; Reecy, James M.

    2016-01-01

    The Animal QTL Database (QTLdb; http://www.animalgenome.org/QTLdb) has undergone dramatic growth in recent years in terms of new data curated, data downloads and new functions and tools. We have focused our development efforts to cope with challenges arising from rapid growth of newly published data and end users’ data demands, and to optimize data retrieval and analysis to facilitate users’ research. Evidenced by the 27 releases in the past 11 years, the growth of the QTLdb has been phenomenal. Here we report our recent progress which is highlighted by addition of one new species, four new data types, four new user tools, a new API tool set, numerous new functions and capabilities added to the curator tool set, expansion of our data alliance partners and more than 20 other improvements. In this paper we present a summary of our progress to date and an outlook regarding future directions. PMID:26602686

  17. Developmental Progression of Looking and Reaching Performance on the A-Not-B Task

    ERIC Educational Resources Information Center

    Cuevas, Kimberly; Bell, Martha Ann

    2010-01-01

    From a neuropsychological perspective, the cognitive skills of working memory, inhibition, and attention and the maturation of the frontal lobe are requisites for successful A-not-B performance on both the looking and reaching versions of the task. This study used a longitudinal design to examine the developmental progression of infants'…

  18. Progress in outdoor navigation by the SAIL developmental robot

    NASA Astrophysics Data System (ADS)

    Zhang, Nan; Weng, John J.; Huang, Xiao

    2002-02-01

    A sensory mapping method, called Staggered Hierarchical Mapping (SHM), and its developmental algorithm are described in this paper. SHM is a model motivated by human early visual pathways including processing performed by the retina, Lateral Geniculate Nucleus (LGN) and the primary visual cortex. The work reported here concerns not only the design of such a series of processors but also their autonomous development. The primary goal is to address a long standing open problem of visual information processing in that processing elements that are dedicated to receptive fields of different retinal positions and different scales (sizes) must be concurrently functioning, in robotic and other applications in unstructured environments. A new Incremental Principal Component Analysis (IPCA) method is used to automatically develop orientation sensitive and other needed filters. For a fast convergence, the lateral inhibition of sensory neurons is modelled by what is called residual images. A set of staggered receptive fields models the pattern of positioning of processing cells. From sequentially sensed video frames, the proposed developing algorithm develops a hierarchy of filters, whose outputs are uncorrelated within each layer, but with increasing scale of receptive fields from low to higher layers. To study the completeness of the representation generated by the SHM, we experimentally show that the response produced at any layer is sufficient to corresponding retinal image. As an application domain, we describe out preliminary experiments of autonomous navigation by the SAIL robot, and why a mapping like the SHM is needed in our next phase of work of vision guided autonomous navigation in outdoor environments.

  19. Self-Regulation Behaviors in Underprepared (Developmental) and Regular Admission College Students

    PubMed

    Ley; Young

    1998-01-01

    Although there is evidence that self-regulated learning processes, such as self-efficacy and goal setting, are significantly related to academic success most studies have not included participants from the one third of the entering college students who must take remedial college courses. The purpose of our research was to examine the differences between the self regulation reported by regular admission students and by underprepared students. We hypothesized that self regulating behaviors could predict developmental, that is underprepared, status or regular admission status among postsecondary students. Self regulation processes in randomly selected developmental and regular admission college students were identified using a structured interview. A discriminant function analysis tested the predictive ability of three measures of self regulating behavior. Developmental and regular admission students differed significantly in their self regulatory strategy deployment. The results suggest that self regulation may be a distinguishing characteristic between some developmental and regular admission students. Copyright 1998 Academic Press. PMID:9514688

  20. Planning an Action: A Developmental Progression in Tool Use

    PubMed Central

    Keen, Rachel; Lee, Mei-Hua; Adolph, Karen

    2014-01-01

    How children pick up a tool reveals their ability to plan an action with the end goal in mind. When presented with a spoon whose handle points away from their dominant hand, children between infancy and 8 years of age progress from using an awkward ulnar grip that causes food to spill from the spoon to consistently using a radial grip. At 4 years of age children’s grip strategies are highly variable, including the awkward grips of infancy and use of the non-dominant hand, but they also employ adult-like grips never seen in infancy. By 8 years of age the infantile ulnar grip has completely disappeared and is replaced by more mature and effective grips that indicates better planning for the end goal. PMID:24954996

  1. Src Kinase Regulation in Progressively Invasive Cancer

    PubMed Central

    Xu, Weichen; Allbritton, Nancy; Lawrence, David S.

    2012-01-01

    Metastatic progression is a multistep process that involves tumor growth and survival, motility and invasion, and subsequent proliferation in an inappropriate environment. The Src protein tyrosine kinase has been implicated in many of the biochemical pathways that drive these behaviors. Although Src itself is only rarely mutated in human tumors, its aberrant activity has been noted in various cancers and suggested to serve as a barometer of metastatic potential. With these features in mind, we examined Src kinase regulation at the structural, enzymatic, and expression levels as a function of progressively invasive prostate cancer cell lines. Surprisingly, both total Src content and kinase activity decrease with increasing cell line aggressiveness, an observation that appears to be inconsistent with the well-documented role of Src in the signaling pathways that drive growth and invasion. However, we do observe a direct correlation between Src kinase specific activity (total Src kinase activity/total Src content) and metastatic aggressiveness, possibly suggesting that in highly aggressive cell lines, key signaling enzymes are globally recruited to drive the cancerous phenotype. In addition, although the expected enhanced phosphorylation of Src at Tyr-416 (activation site) is present in the most aggressive prostate cancer cell lines, unexpectedly high phosphorylation levels at the Tyr-527 inhibitory site are observed as well. The latter, rather than representative of inhibited enzyme, is more indicative of primed Src responsive to local phosphorylated binding partners. PMID:23145001

  2. Regulated lysosomal exocytosis mediates cancer progression

    PubMed Central

    Machado, Eda; White-Gilbertson, Shai; van de Vlekkert, Diantha; Janke, Laura; Moshiach, Simon; Campos, Yvan; Finkelstein, David; Gomero, Elida; Mosca, Rosario; Qiu, Xiaohui; Morton, Christopher L.; Annunziata, Ida; d’Azzo, Alessandra

    2015-01-01

    Understanding how tumor cells transition to an invasive and drug-resistant phenotype is central to cancer biology, but the mechanisms underlying this transition remain unclear. We show that sarcomas gain these malignant traits by inducing lysosomal exocytosis, a ubiquitous physiological process. During lysosomal exocytosis, the movement of exocytic lysosomes along the cytoskeleton and their docking at the plasma membrane involve LAMP1, a sialylated membrane glycoprotein and target of the sialidase NEU1. Cleavage of LAMP1 sialic acids by NEU1 limits the extent of lysosomal exocytosis. We found that by down-regulation of NEU1 and accumulation of oversialylated LAMP1, tumor cells exacerbate lysosomal exocytosis of soluble hydrolases and exosomes. This facilitates matrix invasion and propagation of invasive signals, and purging of lysosomotropic chemotherapeutics. In Arf−⁄− mice, Neu1 haploinsufficiency fostered the development of invasive, pleomorphic sarcomas, expressing epithelial and mesenchymal markers, and lysosomal exocytosis effectors, LAMP1 and Myosin-11. These features are analogous to those of metastatic, pleomorphic human sarcomas, where low NEU1 levels correlate with high expression of lysosomal exocytosis markers. In a therapeutic proof of principle, we demonstrate that inhibiting lysosomal exocytosis reversed invasiveness and chemoresistance in aggressive sarcoma cells. Thus, we reveal that this unconventional, lysosome-regulated pathway plays a primary role in tumor progression and chemoresistance. PMID:26824057

  3. Inflammatory and Immune Activation in Intestinal Myofibroblasts Is Developmentally Regulated.

    PubMed

    Zawahir, Sharmila; Li, Guanghui; Banerjee, Aditi; Shiu, Jessica; Blanchard, Thomas G; Okogbule-Wonodi, Adora C

    2015-08-01

    We previously demonstrated that intestinal myofibroblasts from immature tissue produce excessive IL-8 in response to Escherichia coli lipopolysaccharide (LPS) compared to cells from mature tissue. However, it is unknown whether other cytokines and TLR agonists contribute to this developmentally regulated response. The aim of this study was to further characterize differences in inflammatory signaling in human primary intestinal fibroblasts from fetal (FIF) and infant (IIF) tissue and examine their potential to activate the adaptive immune response in vitro. Cytokine profiles of LPS-stimulated FIF and IIF were assessed by cytokine profile array. IL-8, IL-6, and IL-10 production in response to TLR2, TLR2/6, TLR4, and TLR5 agonists was determined by quantitative ELISA. The potential of activated myofibroblasts to activate adaptive immunity was determined by measuring surface class II MHC expression using flow cytometry. LPS-stimulated FIF produced a distinct proinflammatory cytokine profile consisting of MCP-1, GRO-alpha, IL-6, and IL-8 expression. FIF produced significant IL-8 and IL-6 in response to TLR4 agonist. IIF produced significant levels of IL-8 and IL-6 in the presence of TLR5 and TLR2 agonists. IFN-γ-treated FIF expressed greater HLA-DR levels compared to unstimulated controls and IFN-γ- and LPS-treated IIF. Activated FIF produce a more diverse inflammatory cytokine profile and greater levels of IL-8 and IL-6 in response to TLR4 stimulation compared to IIF. FIF express class II MHC proteins associated with activation of the adaptive immune response. These data suggest that FIF may contribute to bacterial-associated gut inflammation in the immature intestine. PMID:26101946

  4. Inflammatory and Immune Activation in Intestinal Myofibroblasts Is Developmentally Regulated

    PubMed Central

    Zawahir, Sharmila; Li, Guanghui; Banerjee, Aditi; Shiu, Jessica; Blanchard, Thomas G.

    2015-01-01

    We previously demonstrated that intestinal myofibroblasts from immature tissue produce excessive IL-8 in response to Escherichia coli lipopolysaccharide (LPS) compared to cells from mature tissue. However, it is unknown whether other cytokines and TLR agonists contribute to this developmentally regulated response. The aim of this study was to further characterize differences in inflammatory signaling in human primary intestinal fibroblasts from fetal (FIF) and infant (IIF) tissue and examine their potential to activate the adaptive immune response in vitro. Cytokine profiles of LPS-stimulated FIF and IIF were assessed by cytokine profile array. IL-8, IL-6, and IL-10 production in response to TLR2, TLR2/6, TLR4, and TLR5 agonists was determined by quantitative ELISA. The potential of activated myofibroblasts to activate adaptive immunity was determined by measuring surface class II MHC expression using flow cytometry. LPS-stimulated FIF produced a distinct proinflammatory cytokine profile consisting of MCP-1, GRO-alpha, IL-6, and IL-8 expression. FIF produced significant IL-8 and IL-6 in response to TLR4 agonist. IIF produced significant levels of IL-8 and IL-6 in the presence of TLR5 and TLR2 agonists. IFN-γ-treated FIF expressed greater HLA-DR levels compared to unstimulated controls and IFN-γ- and LPS-treated IIF. Activated FIF produce a more diverse inflammatory cytokine profile and greater levels of IL-8 and IL-6 in response to TLR4 stimulation compared to IIF. FIF express class II MHC proteins associated with activation of the adaptive immune response. These data suggest that FIF may contribute to bacterial-associated gut inflammation in the immature intestine. PMID:26101946

  5. The Role of Emotion Regulation in the Social Problems of Boys with Developmental Delays

    ERIC Educational Resources Information Center

    Wilson, Beverly J.; Fernandes-Richards, Siobhan; Aarskog, Cyrena; Osborn, Teresa; Capetillo, Darla

    2007-01-01

    Parents and teachers reported that 6- to 8-year-old boys with developmental delays were less able to regulate their emotions than nondelayed boys matched on chronological age. Compared to nondelayed boys, boys with developmental delays had more social problems, which persisted and increased over a 3-year period. Children's ability to regulate…

  6. Unliganded Thyroid Hormone Receptor α Regulates Developmental Timing via Gene Repression in Xenopus tropicalis

    PubMed Central

    Choi, Jinyoung; Suzuki, Ken-ichi T.; Sakuma, Tetsushi; Shewade, Leena; Yamamoto, Takashi

    2015-01-01

    Thyroid hormone (TH) receptor (TR) expression begins early in development in all vertebrates when circulating TH levels are absent or minimal, yet few developmental roles for unliganded TRs have been established. Unliganded TRs are expected to repress TH-response genes, increase tissue responsivity to TH, and regulate the timing of developmental events. Here we examined the role of unliganded TRα in gene repression and development in Xenopus tropicalis. We used transcription activator-like effector nuclease gene disruption technology to generate founder animals with mutations in the TRα gene and bred them to produce F1 offspring with a normal phenotype and a mutant phenotype, characterized by precocious hind limb development. Offspring with a normal phenotype had zero or one disrupted TRα alleles, and tadpoles with the mutant hind limb phenotype had two truncated TRα alleles with frame shift mutations between the two zinc fingers followed by 40–50 mutant amino acids and then an out-of-frame stop codon. We examined TH-response gene expression and early larval development with and without exogenous TH in F1 offspring. As hypothesized, mutant phenotype tadpoles had increased expression of TH-response genes in the absence of TH and impaired induction of these same genes after exogenous TH treatment, compared with normal phenotype animals. Also, mutant hind limb phenotype animals had reduced hind limb and gill responsivity to exogenous TH. Similar results in methimazole-treated tadpoles showed that increased TH-response gene expression and precocious development were not due to early production of TH. These results indicate that unliganded TRα delays developmental progression by repressing TH-response genes. PMID:25456067

  7. In Vitro Developmental Toxicology Screens: A Report on the Progress of the Methodology and Future Applications.

    PubMed

    Zhang, Cindy; Ball, Jonathan; Panzica-Kelly, Julie; Augustine-Rauch, Karen

    2016-04-18

    There has been increasing focus on generation and assessment of in vitro developmental toxicology models for assessing teratogenic liability of chemicals. The driver for this focus has been to find reliable in vitro assays that will reduce or replace the use of in vivo tests for assessing teratogenicity. Such efforts may be eventually applied in testing pharmaceutical agents where a developmental toxicology assay or battery of assays may be incorporated into regulatory testing to replace one of the two species currently used in teratogenic assessment. Such assays may be eventually applied in testing a broader spectrum of chemicals, supporting efforts aligned with Tox21 strategies and responding to REACH legislation. This review describes the developmental toxicology assays that are of focus in these assessments: rodent whole embryo culture, zebrafish embryo assays, and embryonic stem cell assays. Progress on assay development as well as future directions of how these assays are envisioned to be applied for broader safety testing of chemicals are discussed. Altogether, the developmental model systems described in this review provide rich biological systems that can be utilized in better understanding teratogenic mechanisms of action of chemotypes and are promising in providing proactive safety assessment related to developmental toxicity. Continual advancements in refining/optimizing these in vitro assays are anticipated to provide a robust data set to provide thoughtful assessment of how whole animal teratogenicity evaluations can be reduced/refined in the future. PMID:26766213

  8. Revisiting a Progressive Pedagogy. The Developmental-Interaction Approach. SUNY Series, Early Childhood Education: Inquiries and Insights.

    ERIC Educational Resources Information Center

    Nager, Nancy, Ed.; Shapiro, Edna K., Ed.

    This book reviews the history of the developmental-interactive approach, a formulation rooted in developmental psychology and educational practice, progressively informing educational thinking since the early 20th century. The book describes and analyzes key assumptions and assesses the compatibility of new theoretical approaches, focuses on…

  9. NUTRIENT REGULATION OF CELL CYCLE PROGRESSION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cell replication is tightly controlled in normal tissues and aberrant during disease progression, such as in tumorigenesis. The replication of cells can be divided into four distinct phases: Gap 1 (G1), synthesis (S), gap 2 (G2), and mitosis (M). The progression from one phase to the next is intrica...

  10. Suspensor Length Determines Developmental Progression of the Embryo in Arabidopsis1[W][OA

    PubMed Central

    Babu, Yashodar; Musielak, Thomas; Henschen, Agnes; Bayer, Martin

    2013-01-01

    The first structure that differentiates during plant embryogenesis is the extra-embryonic suspensor that positions the embryo in the lumen of the seed. A central role in nutrient transport has been ascribed to the suspensor in species with prominent suspensor structures. Little is known, however, about what impact the size of the rather simple Arabidopsis (Arabidopsis thaliana) suspensor has on embryogenesis. Here, we describe mutations in the predicted exo-polygalacturonase gene NIMNA (NMA) that lead to cell elongation defects in the early embryo and markedly reduced suspensor length. Mutant nma embryos develop slower than wild-type embryos, and we could observe a similar developmental delay in another mutant with shorter suspensors. Interestingly, for both genes, the paternal allele has a stronger influence on the embryonic phenotype. We conclude that the length of the suspensor is crucial for fast developmental progression of the embryo in Arabidopsis. PMID:23709666

  11. Driving Skills of Young Adults with Developmental Coordination Disorder: Regulating Speed and Coping with Distraction

    ERIC Educational Resources Information Center

    de Oliveira, Rita F.; Wann, John P.

    2011-01-01

    In two experiments, we used an automatic car simulator to examine the steering control, speed regulation and response to hazards of young adults with developmental coordination disorder (DCD) and limited driving experience. In Experiment 1 participants either used the accelerator pedal to regulate their speed, or used the brake pedal when they…

  12. A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing.

    PubMed

    Danielsen, E Thomas; Moeller, Morten E; Yamanaka, Naoki; Ou, Qiuxiang; Laursen, Janne M; Soenderholm, Caecilie; Zhuo, Ran; Phelps, Brian; Tang, Kevin; Zeng, Jie; Kondo, Shu; Nielsen, Christian H; Harvald, Eva B; Faergeman, Nils J; Haley, Macy J; O'Connor, Kyle A; King-Jones, Kirst; O'Connor, Michael B; Rewitz, Kim F

    2016-06-20

    Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. PMID:27326933

  13. Novel role of p73 as a regulator of developmental angiogenesis: Implication for cancer therapy

    PubMed Central

    Marin, Maria C; Marques, Margarita M

    2016-01-01

    Information regarding the role of p73 in the regulation of angiogenesis has been incomplete and quite controversial. Remarkably, several groups, including ours, have recently demonstrated that TP73 plays a fundamental role in angiogenesis regulation and that differential expression of TP73 could have important consequences in tumor angiogenesis. Here, we discuss a possible model for p73 function in the regulation of developmental angiogenesis and tumor angiogenesis. PMID:27308533

  14. Resilience as Regulation of Developmental and Family Processes

    PubMed Central

    MacPhee, David; Lunkenheimer, Erika; Riggs, Nathaniel

    2015-01-01

    Resilience can be defined as establishing equilibrium subsequent to disturbances to a system caused by significant adversity. When families experience adversity or transitions, multiple regulatory processes may be involved in establishing equilibrium, including adaptability, regulation of negative affect, and effective problem-solving skills. The authors’ resilience-as-regulation perspective integrates insights about the regulation of individual development with processes that regulate family systems. This middle-range theory of family resilience focuses on regulatory processes across levels that are involved in adaptation: whole-family systems such as routines and sense of coherence; coregulation of dyads involving emotion regulation, structuring, and reciprocal influences between social partners; and individual self-regulation. Insights about resilience-as-regulation are then applied to family-strengthening interventions that are designed to promote adaptation to adversity. Unresolved issues are discussed in relation to resilience-as-regulation in families, in particular how risk exposure is assessed, interrelations among family regulatory mechanisms, and how families scaffold the development of children’s resilience. PMID:26568647

  15. (Regulation of teopene metabolism). Progress report. [Mentha piperita

    SciTech Connect

    Croteau, R.

    1985-01-01

    Progress in elucidating the biosynthesis of several monoterpenes in the peppermint is described. Tracer studies were performed to clarify metabolic pathways involved. Several growth regulators were screened for their influence on monoterpene composition and yield in peppermint and sage. (DT)

  16. Gravid Spot Predicts Developmental Progress and Reproductive Output in a Livebearing Fish, Gambusia holbrooki.

    PubMed

    Norazmi-Lokman, Nor Hakim; Purser, G J; Patil, Jawahar G

    2016-01-01

    In most livebearing fish, the gravid spot is an excellent marker to identify brooding females, however its use to predict progress of embryonic development, brood size, timing of parturition and overall reproductive potential of populations remain unexplored. Therefore, to understand these relationships, this study quantified visual attributes (intensity and size) of the gravid spot in relation to key internal development in Gambusia holbrooki. Observations show that the colour of the gravid spot arises from progressive melanisation on the surface of the ovarian sac at its hind margin, rather than melanisation of the developing embryos or the skin of the brooding mother. More importantly, the gravid spot intensity and size were closely linked with both developmental stages and clutch size, suggesting their reliable use as external surrogates of key internal developmental in the species. Using predictive consistency of the gravid spot, we also determined the effect of rearing temperature (23 °C and 25 °C) on gestation period and parturition behaviour. The results show that gestation period was significantly reduced (F = 364.58; df = 1,48; P ˃ 0.05) at 25 °C. However there was no significant difference in average number of fry parturated in the two temperature groups (P<0.05), reaffirming that gravid spot intensity is a reliable predictor of reproductive output. The parturition in the species occurred predominantly in the morning and in contrast to earlier reports, tails of the fry emerged first with a few exceptions of head-first, twin and premature births. This study demonstrates utility of the gravid spot for downstream reproductive investigations in a live-bearing fish both in the field and laboratory. The reproducibility of the relationships (intensity with both developmental stage and clutch size), imply that they are also relevant to wild populations that experience varying temperature climes and stressors, significant deviations of which may serve as

  17. Gravid Spot Predicts Developmental Progress and Reproductive Output in a Livebearing Fish, Gambusia holbrooki

    PubMed Central

    Norazmi-Lokman, Nor Hakim; Purser, G. J.; Patil, Jawahar G.

    2016-01-01

    In most livebearing fish, the gravid spot is an excellent marker to identify brooding females, however its use to predict progress of embryonic development, brood size, timing of parturition and overall reproductive potential of populations remain unexplored. Therefore, to understand these relationships, this study quantified visual attributes (intensity and size) of the gravid spot in relation to key internal development in Gambusia holbrooki. Observations show that the colour of the gravid spot arises from progressive melanisation on the surface of the ovarian sac at its hind margin, rather than melanisation of the developing embryos or the skin of the brooding mother. More importantly, the gravid spot intensity and size were closely linked with both developmental stages and clutch size, suggesting their reliable use as external surrogates of key internal developmental in the species. Using predictive consistency of the gravid spot, we also determined the effect of rearing temperature (23°C and 25°C) on gestation period and parturition behaviour. The results show that gestation period was significantly reduced (F = 364.58; df = 1,48; P˃0.05) at 25°C. However there was no significant difference in average number of fry parturated in the two temperature groups (P<0.05), reaffirming that gravid spot intensity is a reliable predictor of reproductive output. The parturition in the species occurred predominantly in the morning and in contrast to earlier reports, tails of the fry emerged first with a few exceptions of head-first, twin and premature births. This study demonstrates utility of the gravid spot for downstream reproductive investigations in a live-bearing fish both in the field and laboratory. The reproducibility of the relationships (intensity with both developmental stage and clutch size), imply that they are also relevant to wild populations that experience varying temperature climes and stressors, significant deviations of which may serve as

  18. Developmental regulation of. beta. -conglycinin in soybean axes and cotyledons

    SciTech Connect

    Ladin, B.F.; Tierney, M.L.; Meinke, D.W.; Hosangadi, P.; Veith, M.; Beachy, R.N.

    1987-05-01

    Analysis of the expression of genes encoding the ..beta..-conglycinin seed storage proteins in soybean has been used to extend the authors understanding of developmental gene expression in plants. The ..cap alpha..,..cap alpha..', and ..beta.. subunits of ..beta..-conglycinin are encoded by a multigene family which is organ-specific in its expression. In this study the authors report the differentially programmed accumulation of the ..cap alpha..,..cap alpha..', and ..beta.. subunits of ..beta..-conglycinin. Multiple isomeric forms of each subunit are present in the dry seed, but the timing of their accumulation is unique for each subunit. The previously reported variation in amount of ..cap alpha..' and ..cap alpha.. subunits in axis and cotyledons is also reflected in the amount of subunit specific mRNA which is present in each tissue. The ..beta.. subunit, previously undetected in soybean axes, is found to be synthesized but rapidly degraded. These differences in ..beta..-conglycinin protein accumulation may be reflected by the morphological differences observed in protein bodies between these two tissues.

  19. Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

    PubMed Central

    Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

    2014-01-01

    Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

  20. Absence of canonical active chromatin marks in developmentally regulated genes

    PubMed Central

    Ruiz-Romero, Marina; Corominas, Montserrat; Guigó, Roderic

    2015-01-01

    The interplay of active and repressive histone modifications is assumed to play a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated to stable production of RNA, while unmarked chromatin would permit rapid gene activation and de-activation during development. In this case, regulation by transcription factors would play a comparatively more important regulatory role. PMID:26280901

  1. 76 FR 81942 - Federal Acquisition Regulation; Information Collection; Progress Payments (SF-1443)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... Regulation; Information Collection; Progress Payments (SF-1443) AGENCIES: Department of Defense (DOD... previously information collection requirement concerning progress payments. Public comments are particularly..., Progress Payments, by any of the following methods: Regulations.gov : http://www.regulations.gov ....

  2. Developmental regulation of aromatase activity in the rat hypothalamus

    SciTech Connect

    Lephart, E.D.

    1989-01-01

    The brain of all mammalian species studied thus far contain an enzymatic activity (aromatase) that catalyzes the conversion of androgens to estrogens. The activity is highest during prenatal development and contributes to the establishment of sex differences which determine adult gonadotropin secretion patterns and reproductive behavior. The studies presented in this dissertation represent a systematic effort to elucidate the mechanism(s) that control the initiation of and contribute to maintaining rat hypothalamic aromatase activity during pre- and postnatal development. Aromatase enzyme activity was measured by the {sup 3}H{sub 2}O release assay or by traditional estrogen product isolation. Brain aromatase mRNA was detected by hybridization to a cDNA encoding rat aromatase cytochrome P-450. In both males and females the time of puberty was associated with a decline in hypothalamic aromatase activity. This decline may represent a factor underlying the peri-pubertal decrease in the sensitivity to gonadal steroid feedback that accompanies completion of puberty. The results also indicate that androgens regulate brain aromatase levels during both the prepubertal and peri-pubertal stages of sexual development and that this regulation is transiently lost in young adults. Utilizing a hypothalamic organotypic culture system, aromatase activity in vitro was maintained for as long as two days. The results of studies of a variety of hormonal and metabolic regulators suggest that prenatal aromatase activity is regulated by factor(s) that function independently from the classical cyclic AMP and protein kinase C trans-membrane signaling pathways.

  3. SUMOylation-mediated regulation of cell cycle progression and cancer

    PubMed Central

    Eifler, Karolin; Vertegaal, Alfred C.O.

    2016-01-01

    SUMOylation plays critical roles during cell cycle progression. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate cell cycle progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. Different types of cancers were recently shown to be dependent on a functioning SUMOylation system, a finding that could potentially be exploited in anti-cancer therapies. PMID:26601932

  4. Microenvironmental regulation of tumor progression and metastasis

    PubMed Central

    Quail, DF; Joyce, JA

    2014-01-01

    Cancers develop in complex tissue environments, which they depend upon for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable, and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that reeducation of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here, we will discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, and recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects. PMID:24202395

  5. Self-Regulated Strategy Instruction in Developmental Writing: A Design Research Project

    ERIC Educational Resources Information Center

    MacArthur, Charles A.; Philippakos, Zoi A.

    2013-01-01

    This design research project developed and evaluated curriculum for developmental writing classes in community colleges. The core of the curriculum was self-regulated strategy instruction, which has been shown to be effective with adolescents who are struggling as writers. In the curriculum, students learned strategies for planning, drafting, and…

  6. GLUCOCORTICOID RECEPTOR REGULATION IN THE RAT EMBRYO: A POTENTIAL SITE FOR DEVELOPMENTAL TOXICITY?

    EPA Science Inventory

    Glucocorticoid receptor regulation in the rat embryo: a potential site for developmental toxicity?

    Ghosh B, Wood CR, Held GA, Abbott BD, Lau C.

    National Research Council, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

  7. SNAT2 and LAT1 transporter abundance is developmentally regulated in skeletal muscle of neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, we demonstrated that the insulin and amino acid–induced activation of the mammalian target of rapamycin complex 1 (mTORC1), is developmentally regulated in neonatal pigs. Recent studies have indicated an important role of the System A transporters (SNAT2 and SLC1A5) and the L transporter...

  8. New Directions in Developmental Emotion Regulation Research across the Life Span: Introduction to the Special Section

    ERIC Educational Resources Information Center

    Zimmermann, Peter; Thompson, Ross A.

    2014-01-01

    Research on the development of emotion regulation has become a prominent topic in developmental science covering a broad age range from infancy to old age because of its theoretical importance and practical implications. This introductory essay of this special section includes reflections on some of the conceptual themes of this research field and…

  9. A Developmental Psychopathology Perspective on ADHD and Comorbid Conditions: The Role of Emotion Regulation.

    PubMed

    Steinberg, Elizabeth A; Drabick, Deborah A G

    2015-12-01

    Research investigating attention-deficit/hyperactivity disorder (ADHD) and co-occurring disorders such as oppositional defiant disorder, conduct disorder, anxiety, and depression has surged in popularity; however, the developmental relations between ADHD and these comorbid conditions remain poorly understood. The current paper uses a developmental psychopathology perspective to examine conditions commonly comorbid with ADHD during late childhood through adolescence. First, we present evidence for ADHD and comorbid disorders. Next, we discuss emotion regulation and its associations with ADHD. The role of parenting behaviors in the development and maintenance of emotion regulation difficulties and comorbid disorders among children with ADHD is explored. An illustrative example of emotion regulation and parenting over the course of development is provided to demonstrate bidirectional relations among these constructs. We then present an integrated conceptual model of emotion regulation as a shared risk process that may lead to different comorbid conditions among children with ADHD. Implications and directions for future research are presented. PMID:25662998

  10. Dietary and developmental regulation of intestinal sugar transport.

    PubMed Central

    Ferraris, R P

    2001-01-01

    The Na(+)-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na(+) and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar

  11. Developmental methylation pattern regulates porcine GPR120 expression.

    PubMed

    Wang, H M; Ma, J D; Jin, L; Liu, Y H; Che, T D; Li, M Z; Li, X W

    2016-01-01

    DNA methylation is an important component of the epigenetic machinery and plays a critical role in transcriptional regulation. It mostly occurs in CpG abundant regions, known as CpG islands (CGIs). G protein-coupled receptor 120 (GPR120) functions as an omega-3 fatty acid receptor and is involved in multiple-biological processes, including lipogenesis. Herein, we show that GPR120 is highly expressed in porcine mature adipose tissue and is positively associated with adipose tissue development (r = 0.86, P < 0.01). We also predicted 5 CGIs across the GPR120 genomic sequence and investigated their methylation status using the MassArray approach. Our results show that these CGIs exhibit significantly different methylation states (PCGI < 0.01), and that the DNA methylation of GPR120 5ꞌ-untranslated and first exon regions can negatively regulate its expression levels. This study will aid further investigations on the epigenetic mechanism regulating GPR120 expression. PMID:26909944

  12. Early development of Moniliophthora perniciosa basidiomata and developmentally regulated genes

    PubMed Central

    2009-01-01

    Background The hemibiotrophic fungus Moniliophthora perniciosa is the causal agent of Witches' broom, a disease of Theobroma cacao. The pathogen life cycle ends with the production of basidiocarps in dead tissues of the infected host. This structure generates millions of basidiospores that reinfect young tissues of the same or other plants. A deeper understanding of the mechanisms underlying the sexual phase of this fungus may help develop chemical, biological or genetic strategies to control the disease. Results Mycelium was morphologically analyzed prior to emergence of basidiomata by stereomicroscopy, light microscopy and scanning electron microscopy. The morphological changes in the mycelium before fructification show a pattern similar to other members of the order Agaricales. Changes and appearance of hyphae forming a surface layer by fusion were correlated with primordia emergence. The stages of hyphal nodules, aggregation, initial primordium and differentiated primordium were detected. The morphological analysis also allowed conclusions on morphogenetic aspects. To analyze the genes involved in basidiomata development, the expression of some selected EST genes from a non-normalized cDNA library, representative of the fruiting stage of M. perniciosa, was evaluated. A macroarray analysis was performed with 192 selected clones and hybridized with two distinct RNA pools extracted from mycelium in different phases of basidiomata formation. This analysis showed two groups of up and down-regulated genes in primordial phases of mycelia. Hydrophobin coding, glucose transporter, Rho-GEF, Rheb, extensin precursor and cytochrome p450 monooxygenase genes were grouped among the up-regulated. In the down-regulated group relevant genes clustered coding calmodulin, lanosterol 14 alpha demethylase and PIM1. In addition, 12 genes with more detailed expression profiles were analyzed by RT-qPCR. One aegerolysin gene had a peak of expression in mycelium with primordia and a

  13. The PIKE Homolog Centaurin gamma Regulates Developmental Timing in Drosophila

    PubMed Central

    Sendscheid, Oliver; Aberle, Hermann; Hoch, Michael

    2014-01-01

    Phosphoinositide-3-kinase enhancer (PIKE) proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH) domain, a GTPase-activating (GAP) domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK) and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to third instar

  14. Progranulin: a novel regulator of gastrointestinal cancer progression

    PubMed Central

    DeMorrow, Sharon

    2013-01-01

    Progranulin (PGRN) is a soluble factor that regulates cell proliferation, motility and inflammation. A role for PGRN in the progression of ovarian and breast cancers is well established. However, the expression and subsequent consequences of PGRN on the progression of gastrointestinal tumors is not well recognized. This review briefly summarizes our current knowledge of the mechanisms of action of PGRN and highlights the role of this signaling molecule in various gastrointestinal cancers. PMID:24040621

  15. Developmental trajectories of regulating attentional selection over time.

    PubMed

    Heim, Sabine; Keil, Andreas

    2012-01-01

    Adaptive behavior in learning environments requires both the maintenance of an attentional focus on a task-set and suppression of distracting stimuli. This may be especially difficult when the competing information is more appealing than the target event. The aptitude to "pay attention" and resist distraction has often been noted as an important prerequisite of successful acquisition of intellectual abilities in children. This focused review draws on research that highlights interindividual differences in the temporal dynamics of attentional engagement and disengagement under competition, and their relation with age and cognitive/academic skills. Although basic strategies of attention control are present in very young children, the more refined ability to manage attentional resources over time in an economic and adaptive fashion appears during early school years, dramatically improves until the early teen years, and continues to develop into late adolescence. Across studies, parameters of attention control over time predict specific aspects of academic performance, rather than general intellectual ability. We conclude that the ability to strategically regulate the dynamic allocation of attention at rapid rates may represent an important element of cognitive and academic development. PMID:22905028

  16. Developmental Trajectories of Regulating Attentional Selection Over Time

    PubMed Central

    Heim, Sabine; Keil, Andreas

    2012-01-01

    Adaptive behavior in learning environments requires both the maintenance of an attentional focus on a task-set and suppression of distracting stimuli. This may be especially difficult when the competing information is more appealing than the target event. The aptitude to “pay attention” and resist distraction has often been noted as an important prerequisite of successful acquisition of intellectual abilities in children. This focused review draws on research that highlights interindividual differences in the temporal dynamics of attentional engagement and disengagement under competition, and their relation with age and cognitive/academic skills. Although basic strategies of attention control are present in very young children, the more refined ability to manage attentional resources over time in an economic and adaptive fashion appears during early school years, dramatically improves until the early teen years, and continues to develop into late adolescence. Across studies, parameters of attention control over time predict specific aspects of academic performance, rather than general intellectual ability. We conclude that the ability to strategically regulate the dynamic allocation of attention at rapid rates may represent an important element of cognitive and academic development. PMID:22905028

  17. Developmental mechanisms that regulate retinal ganglion cell dendritic morphology

    PubMed Central

    Tian, Ning

    2011-01-01

    One of the fundamental features of retinal ganglion cells (RGCs) is that dendrites of individual RGCs are confined to one or a few narrow strata within the inner plexiform layer (IPL), and each RGC synapses only with a small group of presynaptic bipolar and amacrine cells with axons/dendrites ramified in the same strata to process distinct visual features. The underlying mechanisms which control the development of this laminar-restricted distribution pattern of RGC dendrites have been extensively studied, and it is still an open question whether the dendritic pattern of RGCs is determined by molecular cues or by activity-dependent refinement. Accumulating evidence suggests that both molecular cues and activity-dependent refinement might regulate RGC dendrites in a cell subtype-specific manner. However, identification of morphological subtypes of RGCs before they have achieved their mature dendritic pattern is a major challenge in the study of RGC dendritic development. This problem is now being circumvented through the use of molecular markers in genetically engineered mouse lines to identify RGC subsets early during development. Another unanswered fundamental question in the study of activity-dependent refinement of RGC dendrites is how changes in synaptic activity lead to the changes in dendritic morphology. Recent studies have started to shed light on the molecular basis of activity-dependent dendritic refinement of RGCs by showing that some molecular cascades control the cytoskeleton reorganization of RGCs. PMID:21542137

  18. Assessing the Phonological Skills of Bilingual Children from Preschool through Kindergarten: Developmental Progression and Cross-Language Transfer

    ERIC Educational Resources Information Center

    Lopez, Lisa M.

    2012-01-01

    The developmental progression hypothesis for phonological awareness states that children perform better on lower level tasks and has been addressed mainly in the literature with children beginning at age 5. In addition, there has been a limited amount of research done regarding the performance of dual-language learners younger than age 5 on…

  19. Progressive and Regressive Developmental Changes in Neural Substrates for Face Processing: Testing Specific Predictions of the Interactive Specialization Account

    ERIC Educational Resources Information Center

    Joseph, Jane E.; Gathers, Ann D.; Bhatt, Ramesh S.

    2011-01-01

    Face processing undergoes a fairly protracted developmental time course but the neural underpinnings are not well understood. Prior fMRI studies have only examined progressive changes (i.e. increases in specialization in certain regions with age), which would be predicted by both the Interactive Specialization (IS) and maturational theories of…

  20. Light-independent developmental regulation of cab gene expression in Arabidopsis thaliana seedlings.

    PubMed Central

    Brusslan, J A; Tobin, E M

    1992-01-01

    We found a transient increase in the amount of mRNA for four nuclear genes encoding chloroplast proteins during early development of Arabidopsis thaliana. This increase began soon after germination as cotyledons emerged from the seed coat; it occurred in total darkness and was not affected by external factors, such as gibberellins or light treatments used to stimulate germination. Three members of the cab gene family and the rbcS-1A gene exhibited this expression pattern. Because timing of the increase coincided with cotyledon emergence and because it occurred independently of external stimuli, we suggest that this increase represents developmental regulation of these genes. Further, 1.34 kilobases of the cab1 promoter was sufficient to confer this expression pattern on a reporter gene in transgenic Arabidopsis seedlings. The ability of the cab genes to respond to phytochrome preceded this developmental increase, showing that these two types of regulation are independent. Images PMID:1380166

  1. Developmental Stability and Change in Self-Regulation from Childhood to Adolescence

    ERIC Educational Resources Information Center

    Raffaelli, Marcela; Crockett, Lisa J.; Shen, Yuh-Ling

    2005-01-01

    The authors examined the developmental course of self-regulation in a cohort of children from the National Longitudinal Survey of Youth. The longitudinal sample included 646 children (48% girls; 52% boys; 36.2% Black, 23.4% Hispanic, 40.4% White) who were 4 to 5 years old in 1986 and who were followed up at ages 8 to 9 and ages 12 to 13. Levels of…

  2. INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila.

    PubMed

    Neuman, Sarah D; Ihry, Robert J; Gruetzmacher, Kelly M; Bashirullah, Arash

    2014-03-15

    Sequential pulses of the steroid hormone ecdysone regulate the major developmental transitions in Drosophila, and the duration of each developmental stage is determined by the length of time between ecdysone pulses. Ecdysone regulates biological responses by directly initiating target gene transcription. In turn, these transcriptional responses are known to be self-limiting, with mechanisms in place to ensure regression of hormone-dependent transcription. However, the biological significance of these transcriptional repression mechanisms remains unclear. Here we show that the chromatin remodeling protein INO80 facilitates transcriptional repression of ecdysone-regulated genes during prepupal development. In ino80 mutant animals, inefficient repression of transcriptional responses to the late larval ecdysone pulse delays the onset of the subsequent prepupal ecdysone pulse, resulting in a significantly longer prepupal stage. Conversely, increased expression of ino80 is sufficient to shorten the prepupal stage by increasing the rate of transcriptional repression. Furthermore, we demonstrate that enhancing the rate of regression of the mid-prepupal competence factor βFTZ-F1 is sufficient to determine the timing of head eversion and thus the duration of prepupal development. Although ino80 is conserved from yeast to humans, this study represents the first characterization of a bona fide ino80 mutation in any metazoan, raising the possibility that the functions of ino80 in transcriptional repression and developmental timing are evolutionarily conserved. PMID:24468295

  3. Developmental regulation of the estrogen receptor and the estrogen responsiveness of five yolk protein genes in the avian liver.

    PubMed Central

    Evans, M I; O'Malley, P J; Krust, A; Burch, J B

    1987-01-01

    The magnitude of the expression of five yolk protein genes in the avian liver in response to exogenous estradiol is shown to be developmentally regulated. Though each of these yolk protein genes gains the capacity to respond to estradiol during embryonic development, we demonstrate that maximal responses for the different genes are achieved at distinct ages between 1 and 6 weeks after hatching. This observation prompted us to look for possible correlations between yolk protein gene expression and changes in the expression of estrogen receptors that might also occur after hatching. We discovered that indeed the maximal level of nuclear estrogen receptors (assayed following the administration of estradiol) increases progressively over this same period of development from approximately 1000 receptors per cell at 1 week after hatching to approximately 3500 receptors per cell at 6 weeks after hatching. The latter number represents the fully mature state, as comparable levels of receptors are present in the livers of egg-laying hens. Thus, though increases in the expression of estrogen receptors during embryonic liver development have previously been reported, our results indicate that the changes that occur after hatching are quantitatively far more significant to the developmental program for this transcription factor. PMID:3479803

  4. Developmental and Endocrine Regulation of Kisspeptin Expression in Mouse Leydig Cells

    PubMed Central

    Adeshina, Ikeoluwa; Chen, Haolin; Zirkin, Barry R.; Hussain, Mehboob A.; Wondisford, Fredric; Wolfe, Andrew

    2015-01-01

    Kisspeptin, encoded by the Kiss1 gene, binds to a specific G protein-coupled receptor (kisspeptin1 receptor) to regulate the central reproductive axis. Kisspeptin has also been reported to be expressed in peripheral tissues, including the testes. However, factors regulating testicular kisspeptin and its role in reproduction are unknown. Our objective herein was to begin to address kisspeptin function in the testis. In particular, we sought to determine the level of kisspeptin in the testis in comparison with the brain and other tissues, how these levels change from the prepubertal period through sexual maturation, and the factors involved in kisspeptin regulation in the testis. Immunohistochemical analysis of testis sections using a validated kisspeptin antibody localized kisspeptin to the Leydig cells. Kisspeptin was not detected in germ cells or Sertoli cells within the seminiferous tubules at any developmental time period studied, from prepuberty to sexual maturation. A developmental time course of testicular kisspeptin revealed that its mRNA and protein levels increased during development, reaching robust levels at postnatal day 28, correlating with pubertal onset. In vitro studies of primary mouse Leydig cells, as well as in vivo studies, indicated clearly that LH is involved in regulating levels of Leydig cell kisspeptin. Interestingly, gonadectomy resulted in elevated LH but reduced serum kisspeptin levels, suggesting that testicular kisspeptin may be secreted. These data document kisspeptin expression in mouse Leydig cells, its secretion into peripheral serum, and its regulation by changes in reproductive neuroendocrine function. PMID:25635620

  5. Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling

    PubMed Central

    Neal, Scott J; Takeishi, Asuka; O'Donnell, Michael P; Park, JiSoo; Hong, Myeongjin; Butcher, Rebecca A; Kim, Kyuhyung; Sengupta, Piali

    2015-01-01

    Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF-β and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity. DOI: http://dx.doi.org/10.7554/eLife.10110.001 PMID:26335407

  6. GABAergic synaptic plasticity during a developmentally-regulated sleep-like state in C. elegans

    PubMed Central

    Dabbish, Nooreen S.; Raizen, David M.

    2011-01-01

    Approximately one fourth of the neurons in C. elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA-A receptor agonists, indicating that post-synaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species. PMID:22049436

  7. GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans.

    PubMed

    Dabbish, Nooreen S; Raizen, David M

    2011-11-01

    Approximately one-fourth of the neurons in Caenorhabditis elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA(A) receptor agonists, indicating that postsynaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species. PMID:22049436

  8. Analysis of developmentally regulated chorion gene promoter architecture via electroporation of silk moth follicles.

    PubMed

    Tsatsarounos, S P; Rodakis, G C; Lecanidou, R

    2015-02-01

    In the silk moth Bombyx mori, chorion genes of the same developmental specificity are organized in divergently transcribed α/β gene pairs, sharing a common 5' flanking promoter region. This bidirectional promoter contains a complete set of cis-elements responsible for developmentally accurate gene expression. In the present paper, based on the observation that Bombyx chorion gene promoters contain cis-elements for the same transcription factors without concrete evidence on which of them are essential, we address the question as to how promoter architecture (number, orientation and position of common factor binding sites) facilitates developmentally accurate chorion gene regulation. To this end, we constructed several mutated promoter regions of an early-middle gene pair and cloned them upstream of a reporter gene to introduce these plasmid constructs into silk moth follicle epithelial cells via electroporation as an efficient and quick method for transient expression. This is the first time that an ex vivo method had been applied to test the impact of systematic cis-element mutations on a chorion gene promoter. Our results confirmed the importance of the HMGA factor and the role of the GATA factor as an early repressor, and led to a more detailed understanding of which C/EBP sites participate in the regulation of early-middle chorion gene expression. PMID:25256090

  9. Butterfly wing pattern mutants: developmental heterochrony and co-ordinately regulated phenotypes.

    PubMed

    Koch, P B; Lorenz, U; Brakefield, P M; ffrench-Constant, R H

    2000-11-01

    Butterfly wings are colored late in development, when pigments are synthesized in specialized wing scale cells in a fixed developmental succession. In this succession, colored pigments are deposited first and the remaining areas are later melanized black or brown. Here we studied the developmental changes underlying two wing pattern mutants, firstly melanic mutants of the swallowtail Papilio glaucus, in which the yellow background is turned black, and secondly a Spotty mutant of the satyrid Bicyclus anynana, which carries two additional eyespots. Despite the very different pattern changes in these two mutants, they are both associated with changes in rates of scale development and correspondingly, the final color pattern. In the melanic swallowtail, background scales originally destined to become yellow (normally developing early and synthesizing papiliochrome) show delayed development, fail to make papiliochrome, and subsequently melanize at the same time as scales in the wild-type black pattern. In the B. anynana eyespot, scale maturation begins with the central white focus, then progresses to the surrounding gold ring and later finishes with melanization of the black center. Mutants showing additional eyespots display accelerated rates of scale development (corresponding to new eyespots) in wing cells not normally occupied by eyespots. Thus by either delaying or accelerating rates of scale development, the final color, or position, of a wing pattern element can be changed. We propose that this heterochrony of scale development is a basic mechanism of color pattern formation on which developmental mutants act to change lepidopteran color patterns. PMID:11180804

  10. VGluT1+ Neuronal Glutamatergic Signaling Regulates Postnatal Developmental Maturation of Cortical Protoplasmic Astroglia

    PubMed Central

    Morel, Lydie; Higashimori, Haruki; Tolman, Michaela

    2014-01-01

    Functional maturation of astroglia is characterized by the development of a unique, ramified morphology and the induction of important functional proteins, such as glutamate transporter GLT1. Although pathways regulating the early fate specification of astroglia have been characterized, mechanisms regulating postnatal maturation of astroglia remain essentially unknown. Here we used a new in vivo approach to illustrate and quantitatively analyze developmental arborization of astroglial processes. Our analysis found a particularly high increase in the number of VGluT1+ neuronal glutamatergic synapses that are ensheathed by processes from individual developing astroglia from postnatal day (P) 14 to P26, when astroglia undergo dramatic postnatal maturation. Subsequent silencing of VGluT1+ synaptic activity in VGluT1 KO mice significantly reduces astroglial domain growth and the induction of GLT1 in the cortex, but has no effect on astroglia in the hypothalamus, where non-VGluT1+ synaptic signaling predominates. In particular, electron microscopy analysis showed that the loss of VGluT1+ synaptic signaling significantly decreases perisynaptic enshealthing of astroglial processes on synapses. To further determine whether synaptically released glutamate mediates VGluT1+ synaptic signaling, we pharmacologically inhibited and genetically ablated metabotropic glutamate receptors (mGluRs, especially mGluR5) in developing cortical astroglia and found that developmental arborization of astroglial processes and expression of functional proteins, such as GLT1, is significantly decreased. In summary, our genetic analysis provides new in vivo evidence that VGluT1+ glutamatergic signaling, mediated by the astroglial mGluR5 receptor, regulates the functional maturation of cortical astroglia during development. These results elucidate a new mechanism for regulating the developmental formation of functional neuron-glia synaptic units. PMID:25122895

  11. Developmental regulation of hemoglobin synthesis in the green anole lizard Anolis carolinensis

    PubMed Central

    Storz, Jay F.; Hoffmann, Federico G.; Opazo, Juan C.; Sanger, Thomas J.; Moriyama, Hideaki

    2011-01-01

    Tetrapod vertebrates possess multiple α- and β-like globin genes that are ontogenetically regulated, such that functionally distinct hemoglobin (Hb) isoforms are synthesized during different stages of development. The α- and β-like globin genes of amphibians, birds and mammals are differentially expressed during embryonic development and postnatal life, but little is known about the developmental regulation of globin gene expression in non-avian reptiles. Here we report an investigation into the developmental regulation of Hb synthesis in the green anole lizard Anolis carolinensis. We tested two hypotheses derived from comparative genomic studies of the globin gene clusters in tetrapod vertebrates. First, we tested whether the product of the Anolis αD-globin gene is incorporated into embryonic Hb, thereby performing the role that would normally be performed by the embyronic αE-globin gene (which has been deleted from the green anole genome). Second, we tested whether two ‘lizard-specific’ β-globin paralogs have independently evolved a division of labor between an early-expressed embryonic gene and a later-expressed adult gene. Results of a proteomic analysis revealed that α- and β-like globin genes of the anole are differentially expressed during embryonic development. However, the same repertoire of α- and β-chain Hb isoforms was expressed during all stages of development and postnatal life, and the ontogenetic shifts in isoform composition were relatively subtle. In contrast to the pattern that has been documented in other tetrapod vertebrates, it appears that the developmental regulation of Hb synthesis in the green anole lizard does not involve discrete, stage-specific switches in gene activation and gene silencing. PMID:21270305

  12. Atrial Natriuretic Peptide Regulates Ca2+ Channel in Early Developmental Cardiomyocytes

    PubMed Central

    Miao, Lin; Wang, Min; Yin, Wen-Xuan; Yuan, Qi; Chen, Ying-Xiao; Fleischmann, Bernd; Hescheler, Jürgen; Ji, Guangju

    2010-01-01

    Background Cardiomyocytes derived from murine embryonic stem (ES) cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP) in regulation of membrane potentials and Ca2+ currents has not been investigated in developmental cardiomyocytes. Methodology/Principal Findings We investigated the role of ANP in regulating L-type Ca2+ channel current (ICaL) in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials (APs) in early developmental stage (EDS) cardiomyocytes, embryonic bodies (EB) as well as whole embryo hearts. ANP exerted an inhibitory effect on basal ICaL in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage (LDS) cells. However, after stimulation of ICaL by isoproterenol (ISO) in LDS cells, ANP inhibited the response in about 70% cells. The depression of ICaL induced by ANP was not affected by either Nω, Nitro-L-Arginine methyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, or KT5823, a cGMP-dependent protein kinase (PKG) selective inhibitor, in either EDS and LDS cells; whereas depression of ICaL by ANP was entirely abolished by erythro-9-(2-Hydroxy-3-nonyl) adenine (EHNA), a selective inhibitor of type 2 phosphodiesterase(PDE2) in most cells tested. Conclusion/Significances Taken together, these results indicate that ANP induced depression of action potentials and ICaL is due to activation of particulate guanylyl cyclase (GC), cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3′, 5′–cyclic monophophate (cAMP)–cAMP-dependent protein kinase (PKA) in early cardiomyogenesis. PMID:20107504

  13. FSH Regulates mRNA Translation in Mouse Oocytes and Promotes Developmental Competence.

    PubMed

    Franciosi, Federica; Manandhar, Shila; Conti, Marco

    2016-02-01

    A major challenge in assisted reproductive technology is to develop conditions for in vitro oocyte maturation yielding high-quality eggs. Efforts are underway to assess whether known hormonal and local factors play a role in oocyte developmental competence and to identify the molecular mechanism involved. Here we have tested the hypothesis that FSH improves oocyte developmental competence by regulating the translational program in the oocyte. Accumulation of oocyte proteins (targeting protein for the Xenopus kinesin xklp2 and IL-7) associated with improved oocyte quality is increased when cumulus-oocyte complexes are incubated with FSH. This increase is due to enhanced translation of the corresponding mRNAs, as indicated by microinjection of constructs in which the 3' untranslated region of the Tpx2 or Il7 transcripts is fused to the luciferase reporter. A transient activation of the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte preceded the increase in translation. When the epidermal growth factor (EGF) receptor is down-regulated in follicular cells, the FSH-induced rate of maternal mRNA translation and AKT activation were lost, demonstrating that the effects of FSH are indirect and require EGF receptor signaling in the somatic compartment. Using Pten(fl/fl):Zp3cre oocytes in which the AKT is constitutively activated, translation of reporters was increased and was no longer sensitive to FSH stimulation. More importantly, the oocytes lacking the phosphate and tensin homolog gene showed increased developmental competence, even when cultured in the absence of FSH or growth factors. Thus, we demonstrate that FSH intersects with the follicular EGF network to activate the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte to control translation and developmental competence. These findings provide a molecular rationale for the use of FSH to improve egg quality. PMID:26653334

  14. Enhancer of zeste acts as a major developmental regulator of Ciona intestinalis embryogenesis

    PubMed Central

    Le Goff, Emilie; Martinand-Mari, Camille; Martin, Marianne; Feuillard, Jérôme; Boublik, Yvan; Godefroy, Nelly; Mangeat, Paul; Baghdiguian, Stephen; Cavalli, Giacomo

    2015-01-01

    ABSTRACT The paradigm of developmental regulation by Polycomb group (PcG) proteins posits that they maintain silencing outside the spatial expression domains of their target genes, particularly of Hox genes, starting from mid embryogenesis. The Enhancer of zeste [E(z)] PcG protein is the catalytic subunit of the PRC2 complex, which silences its targets via deposition of the H3K27me3 mark. Here, we studied the ascidian Ciona intestinalis counterpart of E(z). Ci-E(z) is detected by immunohistochemistry as soon as the 2- and 4-cell stages as a cytoplasmic form and becomes exclusively nuclear thereafter, whereas the H3K27me3 mark is detected starting from the gastrula stage and later. Morpholino invalidation of Ci-E(z) leads to the total disappearance of both Ci-E(z) protein and its H3K27me3 mark. Ci-E(z) morphants display a severe phenotype. Strikingly, the earliest defects occur at the 4-cell stage with the dysregulation of cell positioning and mitotic impairment. At later stages, Ci-E(z)-deficient embryos are affected by terminal differentiation defects of neural, epidermal and muscle tissues, by the failure to form a notochord and by the absence of caudal nerve. These major phenotypic defects are specifically rescued by injection of a morpholino-resistant Ci-E(z) mRNA, which restores expression of Ci-E(z) protein and re-deposition of the H3K27me3 mark. As observed by qPCR analyses, Ci-E(z) invalidation leads to the early derepression of tissue-specific developmental genes, whereas late-acting developmental genes are generally down-regulated. Altogether, our results suggest that Ci-E(z) plays a major role during embryonic development in Ciona intestinalis by silencing early-acting developmental genes in a Hox-independent manner. PMID:26276097

  15. Regulation of cell division in higher plants. Progress report

    SciTech Connect

    Jacobs, T.W.

    1992-07-01

    Cell division is arguably the most fundamental of all developmental processes. In higher plants, mitotic activity is largely confined to foci of patterned cell divisions called meristems. From these perpetually embryonic tissues arise the plant`s essential organs of light capture, support, protection and reproduction. Once an adequate understanding of plant cell mitotic regulation is attained, unprecedented opportunities will ensue for analyzing and genetically controlling diverse aspects of development, including plant architecture, leaf shape, plant height, and root depth. The mitotic cycle in a variety of model eukaryotic systems in under the control of a regulatory network of striking evolutionary conservation. Homologues of the yeast cdc2 gene, its catalytic product, p34, and the cyclin regulatory subunits of the MPF complex have emerged as ubiquitous mitotic regulators. We have cloned cdc2-like and cyclin genes from pea. As in other eukaryotic model systems, p34 of Pisum sativum is a subunit of a high molecular weight complex which binds the fission yeast p13 protein and displays histone H1 kinase activity in vitro. Our primary objective in this study is to gain baseline information about the regulation of this higher plant cell division control complex in non-dividing, differentiated cells as well as in synchronous and asynchronous mitotic cells. We are investigating cdc2 and cyclin expression at the levels of protein abundance, protein phosphorylation and quaternary associations.

  16. An Examination of the Impact of Accelerating Community College Students' Progression through Developmental Education

    ERIC Educational Resources Information Center

    Hodara, Michelle; Jaggars, Shanna Smith

    2014-01-01

    In an effort to improve developmental education students' outcomes, community colleges have been experimenting with acceleration strategies. Models of acceleration allow students to complete their developmental requirements in a shorter amount of time. However, there has been limited empirical research on the effects of accelerating students'…

  17. An Examination of the Impact of Accelerating Community College Students' Progression through Developmental Education

    ERIC Educational Resources Information Center

    Hodara, Michelle; Jaggars, Shanna Smith

    2014-01-01

    In an effort to improve developmental education students' outcomes, community colleges have been experimenting with acceleration strategies. Models of acceleration allow students to complete their developmental requirements in a shorter amount of time. However, there has been limited empirical research on the effects of accelerating…

  18. Genetic analysis of developmentally regulated resistance to downy mildew (Hyaloperonospora parasitica) in Arabidopsis thaliana.

    PubMed

    McDowell, John M; Williams, Scott G; Funderburg, Nicholas T; Eulgem, Thomas; Dangl, Jeffery L

    2005-11-01

    Although developmentally regulated disease resistance has been observed in a variety of plant-pathogen interactions, the molecular basis of this phenomenon is not well understood. Arabidopsis thaliana ecotype Columbia-0 (Col-0) expresses a developmentally regulated resistance to Hyaloperonospora parasitica isolate Emco5. Col-0 seedlings support profuse mycelial growth and asexual spore formation in the cotyledons. In contrast, Emco5 growth and reproduction is dramatically (but not completely) restricted in the first set of true leaves. Subsequent leaves exhibit progresssively increased resistance. This adult resistance is strongly suppressed by expression of the salicylic acid-degrading transgene NahG and by loss-of-function mutations in the defense-response regulators PAD4, NDR1, RAR1, PBS3, and NPR1. In contrast to Col-0, the Wassilewskija-0 (Ws-0) ecotype supports profuse growth of Emco5 at all stages of development. Gene-dosage experiments and segregation patterns indicate that adult susceptibility in Ws-0 is incomepletely dominant to adult resistance in Col-0. Genetic mapping in a Col x Ws F2 population revealed a major locus on the bottom arm of chromosome 5, which we named RPP31. Analysis of T-DNA insertion lines indicated that the Columbia allele of RPP8, though tightly linked to RPP31, is not necessary for adult resistance. PMID:16353557

  19. CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila

    PubMed Central

    Xie, Xiao-Jun; Hsu, Fu-Ning; Gao, Xinsheng; Xu, Wu; Ni, Jian-Quan; Xing, Yue; Huang, Liying; Hsiao, Hao-Ching; Zheng, Haiyan; Wang, Chenguang; Zheng, Yani; Xiaoli, Alus M.; Yang, Fajun; Bondos, Sarah E.; Ji, Jun-Yuan

    2015-01-01

    The steroid hormone ecdysone and its receptor (EcR) play critical roles in orchestrating developmental transitions in arthropods. However, the mechanism by which EcR integrates nutritional and developmental cues to correctly activate transcription remains poorly understood. Here, we show that EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability. We observed that cdk8 and cycC mutants resemble EcR mutants and EcR-target genes are systematically down-regulated in both mutants. Indeed, the ability of the EcR-Ultraspiracle (USP) heterodimer to bind to polytene chromosomes and the promoters of EcR target genes is also diminished. Mass spectrometry analysis of proteins that co-immunoprecipitate with EcR and USP identified multiple Mediator subunits, including CDK8 and CycC. Consistently, CDK8-CycC interacts with EcR-USP in vivo; in particular, CDK8 and Med14 can directly interact with the AF1 domain of EcR. These results suggest that CDK8-CycC may serve as transcriptional cofactors for EcR-dependent transcription. During the larval–pupal transition, the levels of CDK8 protein positively correlate with EcR and USP levels, but inversely correlate with the activity of sterol regulatory element binding protein (SREBP), the master regulator of intracellular lipid homeostasis. Likewise, starvation of early third instar larvae precociously increases the levels of CDK8, EcR and USP, yet down-regulates SREBP activity. Conversely, refeeding the starved larvae strongly reduces CDK8 levels but increases SREBP activity. Importantly, these changes correlate with the timing for the larval–pupal transition. Taken together, these results suggest that CDK8-CycC links nutrient intake to developmental transitions (EcR activity) and fat metabolism (SREBP activity) during the larval–pupal transition. PMID:26222308

  20. CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila.

    PubMed

    Xie, Xiao-Jun; Hsu, Fu-Ning; Gao, Xinsheng; Xu, Wu; Ni, Jian-Quan; Xing, Yue; Huang, Liying; Hsiao, Hao-Ching; Zheng, Haiyan; Wang, Chenguang; Zheng, Yani; Xiaoli, Alus M; Yang, Fajun; Bondos, Sarah E; Ji, Jun-Yuan

    2015-07-01

    The steroid hormone ecdysone and its receptor (EcR) play critical roles in orchestrating developmental transitions in arthropods. However, the mechanism by which EcR integrates nutritional and developmental cues to correctly activate transcription remains poorly understood. Here, we show that EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability. We observed that cdk8 and cycC mutants resemble EcR mutants and EcR-target genes are systematically down-regulated in both mutants. Indeed, the ability of the EcR-Ultraspiracle (USP) heterodimer to bind to polytene chromosomes and the promoters of EcR target genes is also diminished. Mass spectrometry analysis of proteins that co-immunoprecipitate with EcR and USP identified multiple Mediator subunits, including CDK8 and CycC. Consistently, CDK8-CycC interacts with EcR-USP in vivo; in particular, CDK8 and Med14 can directly interact with the AF1 domain of EcR. These results suggest that CDK8-CycC may serve as transcriptional cofactors for EcR-dependent transcription. During the larval-pupal transition, the levels of CDK8 protein positively correlate with EcR and USP levels, but inversely correlate with the activity of sterol regulatory element binding protein (SREBP), the master regulator of intracellular lipid homeostasis. Likewise, starvation of early third instar larvae precociously increases the levels of CDK8, EcR and USP, yet down-regulates SREBP activity. Conversely, refeeding the starved larvae strongly reduces CDK8 levels but increases SREBP activity. Importantly, these changes correlate with the timing for the larval-pupal transition. Taken together, these results suggest that CDK8-CycC links nutrient intake to developmental transitions (EcR activity) and fat metabolism (SREBP activity) during the larval-pupal transition. PMID:26222308

  1. Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

    PubMed Central

    Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

  2. CYLD regulates keratinocyte differentiation and skin cancer progression in humans

    PubMed Central

    Alameda, J P; Fernández-Aceñero, M J; Moreno-Maldonado, R; Navarro, M; Quintana, R; Page, A; Ramírez, A; Bravo, A; Casanova, M L

    2011-01-01

    CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies. PMID:21900959

  3. Tumor suppressor Lzap regulates cell cycle progression, doming and zebrafish epiboly

    PubMed Central

    Liu, Dan; Wang, Wen-Der; Melville, David B.; Cha, Yong I.; Yin, Zhirong; Issaeva, Natalia; Knapik, Ela W.; Yarbrough, Wendell G.

    2012-01-01

    Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly – the earliest morphogenetic movement in animal development – which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation. PMID:21523853

  4. Ripening-associated ethylene biosynthesis in tomato fruit is autocatalytically and developmentally regulated

    PubMed Central

    Yokotani, Naoki; Nakano, Ryohei; Imanishi, Shunsuke; Nagata, Masayasu; Inaba, Akitsugu; Kubo, Yasutaka

    2009-01-01

    To investigate the regulatory mechanism(s) of ethylene biosynthesis in fruit, transgenic tomatoes with all known LeEIL genes suppressed were produced by RNA interference engineering. The transgenic tomato exhibited ethylene insensitivity phenotypes such as non-ripening and the lack of the triple response and petiole epinasty of seedlings even in the presence of exogenous ethylene. Transgenic fruit exhibited a low but consistent increase in ethylene production beyond 40 days after anthesis (DAA), with limited LeACS2 and LeACS4 expression. 1-Methylcyclopropene (1-MCP), a potent inhibitor of ethylene perception, failed to inhibit the limited increase in ethylene production and expression of the two 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) genes in the transgenic fruit. These results suggest that ripening-associated ethylene (system 2) in wild-type tomato fruit consists of two parts: a small part regulated by a developmental factor through the ethylene-independent expression of LeACS2 and LeACS4 and a large part regulated by an autocatalytic system due to the ethylene-dependent expression of the same genes. The results further suggest that basal ethylene (system 1) is less likely to be involved in the transition to system 2. Even if the effect of system 1 ethylene is eliminated, fruit can show a small increase in ethylene production due to unknown developmental factors. This increase would be enough for the stimulation of autocatalytic ethylene production, leading to fruit ripening. PMID:19605457

  5. Self-Regulation and Math Attitudes: Effects on Academic Performance in Developmental Math Courses at a Community College

    ERIC Educational Resources Information Center

    Otts, Cynthia D.

    2010-01-01

    The purpose of the study was to investigate the relationship among math attitudes, self-regulated learning, and course outcomes in developmental math. Math attitudes involved perceived usefulness of math and math anxiety. Self-regulated learning represented the ability of students to control cognitive, metacognitive, and behavioral aspects of…

  6. The GATA Factor elt-1 Regulates C. elegans Developmental Timing by Promoting Expression of the let-7 Family MicroRNAs

    PubMed Central

    Cohen, Max L.; Kim, Sunhong; Morita, Kiyokazu; Kim, Seong Heon; Han, Min

    2015-01-01

    Postembryonic development in Caenorhabditis elegans is a powerful model for the study of the temporal regulation of development and for the roles of microRNAs in controlling gene expression. Stable switch-like changes in gene expression occur during development as stage-specific microRNAs are expressed and subsequently down-regulate other stage-specific factors, driving developmental progression. Key genes in this regulatory network are phylogenetically conserved and include the post-transcriptional microRNA repressor LIN-28; the nuclear hormone receptor DAF-12; and the microRNAs LIN-4, LET-7, and the three LET-7 family miRNAs (miR-48, miR-84, and miR-241). DAF-12 is known to regulate transcription of miR-48, miR-84 and miR-241, but its contribution is insufficient to account for all of the transcriptional regulation implied by the mutant phenotypes. In this work, the GATA-family transcription factor ELT-1 is identified from a genetic enhancer screen as a regulator of developmental timing in parallel to DAF-12, and is shown to do so by promoting the expression of the LET-7, miR-48, miR-84, and miR-241 microRNAs. The role of ELT-1 in developmental timing is shown to be separate from its role in cell-fate maintenance during post-embryonic development. In addition, analysis of Chromatin Immnoprecipitation (ChIP) data from the modENCODE project and this work suggest that the contribution of ELT-1 to the control of let-7 family microRNA expression is likely through direct transcription regulation. PMID:25816370

  7. Developmental effects of antiepileptic drugs and the need for improved regulations.

    PubMed

    Meador, Kimford J; Loring, David W

    2016-01-19

    Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis. PMID:26519545

  8. Subcellular Profiling Reveals Distinct and Developmentally Regulated Repertoire of Growth Cone mRNAs

    PubMed Central

    Zivraj, Krishna H.; Tung, Yi Chun Loraine; Piper, Michael; Gumy, Laura; Fawcett, James W.; Yeo, Giles S. H.; Holt, Christine E.

    2013-01-01

    Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons, yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones. Here laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An unexpectedly large pool of mRNAs defined predominant pathways in protein synthesis, oxidative phosphorylation, cancer, neurological disease, and signaling. Comparative profiling of “young” (pathfinding) versus “old” (target-arriving) Xenopus growth cones revealed that the number and complexity of transcripts increases dramatically with age. Many presynaptic protein mRNAs are present exclusively in old growth cones, suggesting that functionally related sets of mRNAs are targeted to growth cones in a developmentally regulated way. Remarkably, a subset of mRNAs was significantly enriched in the growth cone compared with the axon compartment, indicating that mechanisms exist to localize mRNAs selectively to the growth cone. Furthermore, some receptor transcripts (e.g., EphB4), present exclusively in old growth cones, were equally abundant in young and old cell bodies, indicating that RNA trafficking from the soma is developmentally regulated. Our findings show that the mRNA repertoire in growth cones is regulated dynamically with age and suggest that mRNA localization is tailored to match the functional demands of the growing axon tip as it transforms into the presynaptic terminal. PMID:21084603

  9. Loss of MBNL Leads to Disruption of Developmentally Regulated Alternative Polyadenylation in RNA-Mediated Disease

    PubMed Central

    Batra, Ranjan; Charizanis, Konstantinos; Manchanda, Mini; Mohan, Apoorva; Li, Moyi; Finn, Dustin J.; Goodwin, Marianne; Zhang, Chaolin; Sobczak, Krzysztof; Thornton, Charles A.; Swanson, Maurice S.

    2014-01-01

    SUMMARY Inhibition of muscleblind-like (MBNL) activity due to sequestration by microsatellite expansion RNAs is a major pathogenic event in the RNA-mediated disease myotonic dystrophy (DM). Although MBNL1 and MBNL2 bind to nascent transcripts to regulate alternative splicing during muscle and brain development, another major binding site for the MBNL protein family is the 3′ untranslated region of target RNAs. Here, we report that depletion of Mbnl proteins in mouse embryo fibroblasts leads to mis-regulation of thousands of alternative polyadenylation events. HITS-CLIP and minigene reporter analyses indicate that these polyadenylation switches are a direct consequence of MBNL binding to target RNAs. Mis-regulated alternative polyadenylation also occurs in skeletal muscle in a mouse polyCUG model and human DM resulting in the persistence of neonatal polyadenylation patterns. These findings reveal a novel developmental function for MBNL proteins and demonstrate that DM is characterized by mis-regulation of pre-mRNA processing at multiple levels. PMID:25263597

  10. E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila.

    PubMed

    Asano, M; Wharton, R P

    1999-05-01

    Throughout the cell cycle of Saccharomyces cerevisiae, the level of origin recognition complex (ORC) is constant and ORCs are bound constitutively to replication origins. Replication is regulated by the recruitment of additional factors such as CDC6. ORC components are widely conserved, and it generally has been assumed that they are also stable factors bound to origins throughout the cell cycle. In this report, we show that the level of the ORC1 subunit changes dramatically throughout Drosophila development. The accumulation of ORC1 is regulated by E2F-dependent transcription. In embryos, ORC1 accumulates preferentially in proliferating cells. In the eye imaginal disc, ORC1 accumulation is cell cycle regulated, with high levels in late G1 and S phase. In the ovary, the sub-nuclear distribution of ORC1 shifts during a developmentally regulated switch from endoreplication of the entire genome to amplification of the chorion gene clusters. Furthermore, we find that overexpression of ORC1 alters the pattern of DNA synthesis in the eye disc and the ovary. Thus, replication origin activity appears to be governed in part by the level of ORC1 in Drosophila. PMID:10228158

  11. INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION.

    PubMed

    Wang, Yiwen; da Cruz, Tina Correia; Pulfemuller, Alicia; Grégoire, Stéphane; Ferveur, Jean-François; Moussian, Bernard

    2016-05-01

    Fatty acid desaturases are metabolic setscrews. To study their systemic impact on growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in larvae fed with CAY10566. These animals cease feeding soon after hatching, and their growth is strongly attenuated. A starvation program is not launched, but the expression of distinct metabolic genes is activated, possibly to mobilize storage material. Without attaining the normal size, inhibitor-fed larvae molt to the next stage indicating that the steroid hormone ecdysone triggers molting correctly. Nevertheless, after molting, expression of ecdysone-dependent regulators is not induced. While control larvae molt a second time, these larvae fail to do so and die after few days of straying. These effects are similar to those observed in experiments using larvae deficient for the fatty acid desaturase1 gene. Based on these data, we propose that the ratio of saturated to unsaturated fatty acids adjusts a sensor system that directs feeding behavior. We also hypothesize that loss of fatty acid desaturase activity leads to a block of the genetic program of development progression indirectly by switching on a metabolic compensation program. PMID:27037621

  12. Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases

    SciTech Connect

    Yang, Pei-Ming; Olee, Tsaiwei; Kozin, F.; Carson, D.A.; Chen, P.P. ); Olsen, N.J. ); Siminovitch, K.A. )

    1990-10-01

    Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. The authors have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, they studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (V{sub H}) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important V{sub H} genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.

  13. Regulation of developmental and environmental signaling by interaction between microtubules and membranes in plant cells.

    PubMed

    Zhang, Qun; Zhang, Wenhua

    2016-02-01

    Cell division and expansion require the ordered arrangement of microtubules, which are subject to spatial and temporal modifications by developmental and environmental factors. Understanding how signals translate to changes in cortical microtubule organization is of fundamental importance. A defining feature of the cortical microtubule array is its association with the plasma membrane; modules of the plasma membrane are thought to play important roles in the mediation of microtubule organization. In this review, we highlight advances in research on the regulation of cortical microtubule organization by membrane-associated and membrane-tethered proteins and lipids in response to phytohormones and stress. The transmembrane kinase receptor Rho-like guanosine triphosphatase, phospholipase D, phosphatidic acid, and phosphoinositides are discussed with a focus on their roles in microtubule organization. PMID:26687389

  14. Developmental Regulation of Enzymes of Indole Alkaloid Biosynthesis in Catharanthus roseus1

    PubMed Central

    De Luca, Vincenzo; Fernandez, Jesus Alvarez; Campbell, Douglas; Kurz, Wolfgang G. W.

    1988-01-01

    Developing seedlings of Catharanthus roseus were analyzed for appearance of tryptophan decarboxylase (TDC), strictosidine synthase (SS), N-methyltransferase (NMT) and O-acetyltransferase (DAT) enzyme activities. SS enzyme activity appeared early after germination and was present throughout most of the developmental study. TDC activity was highly regulated and peaked over a 48 hour period achieving a maximum by day of 5 of seedling development. Both TDC and SS were present in all tissues of the seedling. NMT and DAT enzyme activities were induced after TDC and SS had peaked and these activities could only be found in hypocotyls and cotyledons. TDC, SS, and NMT did not require light for induction whereas DAT enzyme activity was increased approximately 10-fold after light treatment of dark grown seedlings. PMID:16665928

  15. Antimicrobial peptide expression is developmentally regulated in the ovine gastrointestinal tract.

    PubMed

    Huttner, K M; Brezinski-Caliguri, D J; Mahoney, M M; Diamond, G

    1998-02-01

    Antimicrobial peptides are abundant components of the innate immune system present in species throughout the plant and animal kingdoms. In mammals, these immune peptides have been localized to epithelial tissues of the pig, mouse, rat, cow and human gastrointestinal tracts. We have identified in sheep two members of the beta-defensin antimicrobial peptide gene family that are expressed in a unique pattern throughout the gastrointestinal tract. Sheep beta-defensin 1 mRNA is the most prevalent from tongue to colon with the exception of the distal ileum, where beta-defensin 2 mRNA predominates. Sheep beta-defensin expression varies significantly between animals and is developmentally regulated both pre- and postnatally. These changes in antimicrobial peptide expression may correlate with anatomical differentiation as well as physiologic adaptations to extra-uterine life. PMID:9478010

  16. Transferrin receptor and ferritin-H are developmentally regulated in oligodendrocyte lineage cells.

    PubMed

    Li, Yunxia; Guan, Qiang; Chen, Yuhui; Han, Hongjie; Liu, Wuchao; Nie, Zhiyu

    2013-01-01

    Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin. Multiple iron metabolism proteins are expressed in the brain including transferrin receptor and ferritin-H. However, it is still unknown whether they are developmentally regulated in oligodendrocyte lineage cells for myelination. Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes. Additional different doses of Fe(3+) in the cultured medium did not affect oligodendrocyte precursor cell maturation or ferritin-H expression but decreased the expression of the transferrin receptor. These results indicate that upregulation of both transferrin receptor and ferritin-H contributes to maturation and myelination of oligodendrocyte precursor cells. PMID:25206366

  17. From Premack to PECS: 25 Years of Progress in Communication Intervention for Individuals with Developmental Disabilities

    ERIC Educational Resources Information Center

    Sigafoos, Jeff

    2005-01-01

    Educational and behavioural psychologists have made major contributions to the field of communication intervention for individuals with developmental and physical disabilities. A brief personal perspective is provided on some of the major works and contributors that have shaped the field over the past 25 years. Major contributions and personal…

  18. Investigation of developmentally regulated membrane proteins in muscle and nerve cells

    SciTech Connect

    Rosenberg, J.M.

    1985-01-01

    The developmental regulation of membrane glycoproteins in muscle and nerve cells has been studied. One of these glycoproteins, designated 5B4 antigen, is recognized by a monoclonal antibody (5B4) in rat brain neurons. On immunoblots of fetal rat brain membranes, 5B4 stains a diffuse band with an M/sub r/ of 180-250 kilodalton (kd). Prior digestion of such membranes with a bacteriophage-encoded endoneuraminidase specific for ..cap alpha..-2,8-linked poly(sialic acid) results in a shift in the form of the antigen to two sharp bands of 140 and 180 kd. In adult brain, 5B4 recognizes a pair of sharp bands of M/sub r/ 140 and 180 kd, which are neither sensitive to endo-neuraminidase digestion nor recognized by H.46. V8 peptide maps of the enzymatically iodinated 140 kd adult antigen and the 140 kd endo-neuraminidase digested fetal antigen are identical. These results demonstrate that the polypeptide backbone of the adult and fetal forms of the 5B4 antigen are similar, and that the observed microheterogeneity in the native fetal antigen is due to polysialation. Membrane glycoproteins are through to play an essential role in myoblast fusion during muscle development. In order to identify such glycoproteins, L/sub 6/ myoblasts were labeled with /sup 3/H-N-acetylglucosamine and /sup 3/H-mannose during several stages of differentiation. The effects of various inhibitors of fusion of protein expression were also studied. After identifying membrane glycoproteins whose developmental regulation coincides with myoblast fusion, it is important to establish their role in the fusion process, possibly through reconstitution into phospholipid membrane vesicles (liposomes).

  19. Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor.

    PubMed

    Yoo, B C; Aoki, K; Xiang, Y; Campbell, L R; Hull, R J; Xoconostle-Cázares, B; Monzer, J; Lee, J Y; Ullman, D E; Lucas, W J

    2000-11-10

    We report on the molecular, biochemical, and functional characterization of Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase inhibitor that is developmentally regulated and has anti-elastase properties. CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(-)(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated at 79%. CmPS-1 displayed no detectable inhibitory properties against chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with the piercing-sucking aphid, Myzus persicae, established a close correlation between the developmentally regulated increase in CmPS-1 within the phloem sap and the reduced ability of these insects to survive and reproduce on C. maxima. However, in vitro feeding experiments, using purified phloem CmPS-1, failed to demonstrate a direct effect on aphid survival. Likely roles of this novel phloem serpin in defense against insects/pathogens are discussed. PMID:10960478

  20. Two small heat shock protein genes in Apis cerana cerana: characterization, regulation, and developmental expression.

    PubMed

    Liu, Zhaohua; Yao, Pengbo; Guo, Xingqi; Xu, Baohua

    2014-07-25

    In the present study, we identified and characterized two small heat shock protein genes from Apis cerana cerana, named AccHsp24.2 and AccHsp23.0. An alignment analysis showed that AccHsp24.2 and AccHsp23.0 share high similarity with other members of the α-crystallin/sHSP family, all of which contain the conserved α-crystallin domain. The recombinant AccHsp24.2 and AccHsp23.0 proteins were shown to have molecular chaperone activity by the malate dehydrogenase thermal aggregation assay. Three heat shock elements were detected in the 5'-flanking region of AccHsp24.2 and eleven in AccHsp23.0, and two Drosophila Broad-Complex genes for ecdysone steroid response sites were found in each of the genes. The presence of these elements suggests that the expression of these genes might be regulated by heat shock and ecdysone, which was confirmed by quantitative RT-PCR (RT-qPCR). The results revealed that the expression of the two genes could be induced by cold shock (4°C) and heat shock (37°C and 43°C) in an analogous manner, and AccHsp24.2 was more susceptible than AccHsp23.0. In addition, the expression of the two genes was induced by high concentrations of ecdysone in vitro and in vivo. The accumulation of AccHsp24.2 and AccHsp23.0 mRNA was also detected in different developmental stages and tissues. In spite of the differential expression at the same stage, these genes shared similar developmental patterns, suggesting that they are regulated by similar mechanisms. PMID:24835315

  1. Down regulation by p60v-src of genes specifically expressed and developmentally regulated in postmitotic quail neuroretina cells.

    PubMed Central

    Guermah, M; Gillet, G; Michel, D; Laugier, D; Brun, G; Calothy, G

    1990-01-01

    The avian neuroretina (NR) is composed of photoreceptors and different neurons that are derived from proliferating precursor cells. Neuronal differentiation takes place after terminal mitosis. We have previously shown that differentiating NR cells can be induced to proliferate by infection with Rous sarcoma virus (RSV) and that cell multiplication requires expression of a functional v-src gene. We speculated that the quiescence of NR cells could be determined by specific genes. Cell proliferation could then result from the negative regulation of these genes by the v-src protein. By differential hybridization of a cDNA library, we isolated eight clones corresponding to genes expressed in postmitotic NR cells from 13-day-old quail embryos, transcriptional levels of which are significantly reduced in NR cells induced to proliferate by tsNY68, an RSV mutant with temperature-sensitive mitogenic activity. Partial sequencing analysis indicated that one RNA encoded the calmodulin gene, whereas the other seven showed no similarity to known sequences. By using v-src mutants that induce NR cell proliferation in the absence of transformation, we showed that transcription of six genes was negatively regulated by the v-src protein and that of four genes was correlated with NR cell quiescence. We also report that a subset of genes are specifically transcribed in neural cells and developmentally regulated in the NR. These results indicate that the v-src protein regulates expression of genes likely to play a role in the control of neural cell growth or differentiation. Images PMID:2162475

  2. Apoplastic and intracellular plant sugars regulate developmental transitions in witches’ broom disease of cacao

    PubMed Central

    Barau, Joan; Grandis, Adriana; Carvalho, Vinicius Miessler de Andrade; Teixeira, Gleidson Silva; Zaparoli, Gustavo Henrique Alcalá; do Rio, Maria Carolina Scatolin; Rincones, Johana; Buckeridge, Marcos Silveira; Pereira, Gonçalo Amarante Guimarães

    2015-01-01

    Witches’ broom disease (WBD) of cacao differs from other typical hemibiotrophic plant diseases by its unusually long biotrophic phase. Plant carbon sources have been proposed to regulate WBD developmental transitions; however, nothing is known about their availability at the plant–fungus interface, the apoplastic fluid of cacao. Data are provided supporting a role for the dynamics of soluble carbon in the apoplastic fluid in prompting the end of the biotrophic phase of infection. Carbon depletion and the consequent fungal sensing of starvation were identified as key signalling factors at the apoplast. MpNEP2, a fungal effector of host necrosis, was found to be up-regulated in an autophagic-like response to carbon starvation in vitro. In addition, the in vivo artificial manipulation of carbon availability in the apoplastic fluid considerably modulated both its expression and plant necrosis rate. Strikingly, infected cacao tissues accumulated intracellular hexoses, and showed stunted photosynthesis and the up-regulation of senescence markers immediately prior to the transition to the necrotrophic phase. These opposite findings of carbon depletion and accumulation in different host cell compartments are discussed within the frame of WBD development. A model is suggested to explain phase transition as a synergic outcome of fungal-related factors released upon sensing of extracellular carbon starvation, and an early senescence of infected tissues probably triggered by intracellular sugar accumulation. PMID:25540440

  3. An Organizational Hub of Developmentally Regulated Chromatin Loops in the Drosophila Antennapedia Complex.

    PubMed

    Li, Mo; Ma, Zhibo; Liu, Jiayang K; Roy, Sharmila; Patel, Sapna K; Lane, Derrick C; Cai, Haini N

    2015-12-01

    Chromatin boundary elements (CBEs) are widely distributed in the genome and mediate formation of chromatin loops, but their roles in gene regulation remain poorly understood. The complex expression pattern of the Drosophila homeotic gene Sex combs reduced (Scr) is directed by an unusually long regulatory sequence harboring diverse cis elements and an intervening neighbor gene fushi tarazu (ftz). Here we report the presence of a multitude of CBEs in the Scr regulatory region. Selective and dynamic pairing among these CBEs mediates developmentally regulated chromatin loops. In particular, the SF1 boundary plays a central role in organizing two subsets of chromatin loops: one subset encloses ftz, limiting its access by the surrounding Scr enhancers and compartmentalizing distinct histone modifications, and the other subset subdivides the Scr regulatory sequences into independent enhancer access domains. We show that these CBEs exhibit diverse enhancer-blocking activities that vary in strength and tissue distribution. Tandem pairing of SF1 and SF2, two strong CBEs that flank the ftz domain, allows the distal enhancers to bypass their block in transgenic Drosophila, providing a mechanism for the endogenous Scr enhancer to circumvent the ftz domain. Our study demonstrates how an endogenous CBE network, centrally orchestrated by SF1, could remodel the genomic environment to facilitate gene regulation during development. PMID:26391952

  4. REN: a novel, developmentally regulated gene that promotes neural cell differentiation.

    PubMed

    Gallo, Rita; Zazzeroni, Francesca; Alesse, Edoardo; Mincione, Claudia; Borello, Ugo; Buanne, Pasquale; D'Eugenio, Roberta; Mackay, Andrew R; Argenti, Beatrice; Gradini, Roberto; Russo, Matteo A; Maroder, Marella; Cossu, Giulio; Frati, Luigi; Screpanti, Isabella; Gulino, Alberto

    2002-08-19

    Expansion and fate choice of pluripotent stem cells along the neuroectodermal lineage is regulated by a number of signals, including EGF, retinoic acid, and NGF, which also control the proliferation and differentiation of central nervous system (CNS) and peripheral nervous system (PNS) neural progenitor cells. We report here the identification of a novel gene, REN, upregulated by neurogenic signals (retinoic acid, EGF, and NGF) in pluripotent embryonal stem (ES) cells and neural progenitor cell lines in association with neurotypic differentiation. Consistent with a role in neural promotion, REN overexpression induced neuronal differentiation as well as growth arrest and p27Kip1 expression in CNS and PNS neural progenitor cell lines, and its inhibition impaired retinoic acid induction of neurogenin-1 and NeuroD expression. REN expression is developmentally regulated, initially detected in the neural fold epithelium of the mouse embryo during gastrulation, and subsequently throughout the ventral neural tube, the outer layer of the ventricular encephalic neuroepithelium and in neural crest derivatives including dorsal root ganglia. We propose that REN represents a novel component of the neurogenic signaling cascade induced by retinoic acid, EGF, and NGF, and is both a marker and a regulator of neuronal differentiation. PMID:12186855

  5. Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling

    PubMed Central

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Kim, Hyo Jeong; Ko, Myoung Seok; Seol, Wongi; Joe, Yeonsoo; Chung, Hun Taeg; Lee, Byung Ju; Moon, Chang Hoon; Cho, Wha Ja; Park, Jeong Woo

    2016-01-01

    The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling. DRG2 was associated with phosphatidylinositol 3-phosphate–containing endosomes. It colocalized and interacted with EEA1 and Rab5 on endosomes in a phosphatidylinositol 3-kinase–dependent manner. DRG2 depletion did not affect Tfn uptake and recruitment of RabGAP5 and Rac1 to Rab5 endosomes. However, it resulted in impairment of interaction between Rab5 and RabGAP5, Rab5 deactivation on endosomes, and Tfn recycling. Ectopic expression of shRNA-resistant DRG2 rescued Tfn recycling in DRG2-depleted cells. Our results demonstrate that DRG2 is an endosomal protein and a key regulator of Rab5 deactivation and Tfn recycling. PMID:26582392

  6. Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress.

    PubMed

    Olsovska, Katarina; Kovar, Marek; Brestic, Marian; Zivcak, Marek; Slamka, Pavol; Shao, Hong Bo

    2016-01-01

    Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID:27551283

  7. Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress

    PubMed Central

    Olsovska, Katarina; Kovar, Marek; Brestic, Marian; Zivcak, Marek; Slamka, Pavol; Shao, Hong Bo

    2016-01-01

    Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID:27551283

  8. Med1 regulates meiotic progression during spermatogenesis in mice

    PubMed Central

    Huszar, Jessica M.; Jia, Yuzhi; Reddy, Janardan K.; Payne, Christopher J.

    2015-01-01

    Spermatogenesis is a highly coordinated process. Signaling from nuclear hormone receptors, like those for retinoic acid, is important for normal spermatogenesis. However, the mechanisms regulating these signals are poorly understood. Mediator complex subunit 1 (MED1) is a transcriptional enhancer that directly modulates transcription from nuclear hormone receptors. MED1 is present in male germ cells throughout mammalian development, but its function during spermatogenesis is unknown. To determine its role, we generated mice lacking Med1 specifically in their germ cells beginning just before birth. Conditional Med1 knockout males are fertile, exhibiting normal testis weights and siring ordinary numbers of offspring. Retinoic acid-responsive gene products Stimulated by retinoic acid gene 8 (STRA8) and Synaptonemal complex protein 3 (SYCP3) are first detected in knockout spermatogonia at the expected time points during the first wave of spermatogenesis and persist with normal patterns of cellular distribution in adult knockout testes. Meiotic progression, however, is altered in the absence of Med1. At postnatal day 7 (P7), zygotene-stage knockout spermatocytes are already detected, unlike in control testes, with fewer pre-leptotene-stage cells and more leptotene spermatocytes observed in the knockouts. At P9, Med1 knockout spermatocytes prematurely enter pachynema. Once formed, greater numbers of knockout spermatocytes remain in pachynema relative to the other stages of meiosis throughout testis development and its maintenance in the adult. Meiotic exit is not inhibited. We conclude that MED1 regulates the temporal progression of primary spermatocytes through meiosis, with its absence resulting in abbreviated pre-leptotene, leptotene and zygotene stages, and a prolonged pachytene stage. PMID:25778538

  9. Drosophila melanogaster lipins are tissue-regulated and developmentally regulated and present specific subcellular distributions.

    PubMed

    Valente, Valeria; Maia, Rafaela Martins; Vianna, Murilo Carlos Bizam; Paçó-Larson, Maria Luisa

    2010-11-01

    Lipins constitute a novel family of Mg(2+)-dependent phosphatidate phosphatases that catalyze the dephosphorylation of phosphatidic acid to yield diacylglycerol, an important intermediate in lipid metabolism and cell signaling. Whereas a single lipin is detected in less complex organisms, in mammals there are distinct lipin isoforms and paralogs that are differentially expressed among tissues. Compatible with organism tissue complexity, we show that the single Drosophila Lpin1 ortholog (CG8709, here named DmLpin) expresses at least three isoforms (DmLpinA, DmLpinK and DmLpinJ) in a temporal and spatially regulated manner. The highest levels of lipin in the fat body, where DmLpinA and DmLpinK are expressed, correlate with the highest levels of triacylglycerol (TAG) measured in this tissue. DmLpinK is the most abundant isoform in the central nervous system, where TAG levels are significantly lower than in the fat body. In the testis, where TAG levels are even lower, DmLpinJ is the predominant isoform. Together, these data suggest that DmLpinA might be the isoform that is mainly involved in TAG production, and that DmLpinK and DmLpinJ could perform other cellular functions. In addition, we demonstrate by immunofluorescence that lipins are most strongly labeled in the perinuclear region of the fat body and ventral ganglion cells. In visceral muscles of the larval midgut and adult testis, lipins present a sarcomeric distribution. In the ovary chamber, the lipin signal is concentrated in the internal rim of the ring canal. These specific subcellular localizations of the Drosophila lipins provide the basis for future investigations on putative novel cellular functions of this protein family. PMID:20977671

  10. The Progression of Severe Behavior Disorder in Young Children with Intellectual and Developmental Disabilities

    PubMed Central

    Medeiros, Kristen; Curby, Timothy W.; Bernstein, Alec; Rojahn, Johannes; Schroeder, Stephen R.

    2015-01-01

    Behavior disorders, such as self-injurious, stereotypic, and aggressive behavior are common among individuals with intellectual or developmental disabilities. While we have learned much about those behaviors over the past few decades, longitudinal research that looks at developmental trajectory has been rare. This study was designed to examine the trajectory of these three forms of severe behavior disorders over a one year time period. The behaviors were measured on two dimensions: frequency of occurrence and severity. Participants were 160 infants and toddlers at risk for developmental delays in Lima, Peru. Using structural equation modeling, we found that the frequency of self-injury and stereotypic behavior and the severity of aggressive behavior remained stable over the 12 month period. Uni-directional structural models fit the data best for self-injurious and aggressive behavior (with frequency being a leading indicator of future severity of self-injury and severity being a leading indicator of future frequency for aggression). For stereotypic behavior, a cross-lagged autoregressive model fit the data best, with both dimensions of frequency and severity involved as leading indicators of each other. These models did not vary significantly across diagnostic groups, suggesting that toddlers exhibiting behavior disorders may be assisted with interventions that target the specific frequencies or severities of behaviors, regardless of diagnostic category. PMID:24012587

  11. The progression of severe behavior disorder in young children with intellectual and developmental disabilities.

    PubMed

    Medeiros, Kristen; Curby, Timothy W; Bernstein, Alec; Rojahn, Johannes; Schroeder, Stephen R

    2013-11-01

    Behavior disorders, such as self-injurious, stereotypic, and aggressive behavior are common among individuals with intellectual or developmental disabilities. While we have learned much about those behaviors over the past few decades, longitudinal research that looks at developmental trajectory has been rare. This study was designed to examine the trajectory of these three forms of severe behavior disorders over a one year time period. The behaviors were measured on two dimensions: frequency of occurrence and severity. Participants were 160 infants and toddlers at risk for developmental delays in Lima, Peru. Using structural equation modeling, we found that the frequency of self-injury and stereotypic behavior and the severity of aggressive behavior remained stable over the 12-month period. Uni-directional structural models fit the data best for self-injurious and aggressive behavior (with frequency being a leading indicator of future severity of self-injury and severity being a leading indicator of future frequency for aggression). For stereotypic behavior, a cross-lagged autoregressive model fit the data best, with both dimensions of frequency and severity involved as leading indicators of each other. These models did not vary significantly across diagnostic groups, suggesting that toddlers exhibiting behavior disorders may be assisted with interventions that target the specific frequencies or severities of behaviors, regardless of diagnostic category. PMID:24012587

  12. Using Formative Assessment and Self-Regulated Learning to Help Developmental Mathematics Students Achieve: A Multi-Campus Program

    ERIC Educational Resources Information Center

    Hudesman, John; Crosby, Sara; Ziehmke, Niesha; Everson, Howard; Issac, Sharlene; Flugman, Bert; Zimmerman, Barry; Moylan, Adam

    2014-01-01

    The authors describe an Enhanced Formative Assessment and Self-Regulated Learning (EFA-SRL) program designed to improve the achievement of community college students enrolled in developmental mathematics courses. Their model includes the use of specially formatted quizzes designed to assess both the students' mathematics and metacognitive…

  13. Peer Relations and Emotion Regulation of Children with Emotional and Behavioural Difficulties with and without a Developmental Disorder

    ERIC Educational Resources Information Center

    Lynn, Sasha; Carroll, Annemaree; Houghton, Stephen; Cobham, Vanessa

    2013-01-01

    Children with emotional and behavioural difficulties (EBD) and those who also have developmental disorders, such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), can experience the same adverse consequences in their peer interactions and relationships. This present study compared the emotion regulation and peer…

  14. The Effects of Self-Regulated Learning Training on Community College Students' Metacognition and Achievement in Developmental Math Courses

    ERIC Educational Resources Information Center

    Bol, Linda; Campbell, Karen D. Y.; Perez, Tony; Yen, Cherng-Jyh

    2016-01-01

    The effects of training in self-regulation on metacognition and math achievement were investigated. The participants were 116 community college students enrolled in developmental math courses. Students enrolled in 16 classrooms were randomly assigned to the treatment and control groups. Participants in the treatment group completed four…

  15. Positive Effects of Methylphenidate on Social Communication and Self-Regulation in Children with Pervasive Developmental Disorders and Hyperactivity

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Kasari, Connie L.; McCracken, James T.; Lee, Lisa S-Y.; Aman, Michael G.; McDougle, Christopher J.; Scahill, Lawrence; Tierney, Elaine; Arnold, L. Eugene; Vitiello, Benedetto; Ritz, Louise; Witwer, Andrea; Kustan, Erin; Ghuman, Jaswinder; Posey, David J.

    2009-01-01

    This report examined the effect of methylphenidate on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity in a secondary analysis of RUPP Autism Network data. Participants were 33 children (29 boys) between the ages of 5 and 13 years who participated in a four-week crossover trial of…

  16. Roles of the Developmental Regulator unc-62/Homothorax in Limiting Longevity in Caenorhabditis elegans

    PubMed Central

    Van Nostrand, Eric L.; Sánchez-Blanco, Adolfo; Wu, Beijing; Nguyen, Andy; Kim, Stuart K.

    2013-01-01

    The normal aging process is associated with stereotyped changes in gene expression, but the regulators responsible for these age-dependent changes are poorly understood. Using a novel genomics approach, we identified HOX co-factor unc-62 (Homothorax) as a developmental regulator that binds proximal to age-regulated genes and modulates lifespan. Although unc-62 is expressed in diverse tissues, its functions in the intestine play a particularly important role in modulating lifespan, as intestine-specific knockdown of unc-62 by RNAi increases lifespan. An alternatively-spliced, tissue-specific isoform of unc-62 is expressed exclusively in the intestine and declines with age. Through analysis of the downstream consequences of unc-62 knockdown, we identify multiple effects linked to aging. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Finally, in old age, the intestine shows increased expression of several aberrant genes; these UNC-62 targets are expressed predominantly in neuronal cells in developing animals, but surprisingly show increased expression in the intestine of old animals. Intestinal expression of some of these genes during aging is detrimental for longevity; notably, increased expression of insulin ins-7 limits lifespan by repressing activity of insulin pathway response factor DAF-16/FOXO in aged animals. These results illustrate how unc-62 regulation of intestinal gene expression is responsible for limiting lifespan during the normal aging process. PMID:23468654

  17. Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation.

    PubMed

    Huang, Tao; Ma, Liqun; Krimm, Robin F

    2015-09-15

    The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in Bdnf(lacZ/+) mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development. PMID:26164656

  18. On the Developmental and Environmental Regulation of Secondary Metabolism in Vaccinium spp. Berries

    PubMed Central

    Karppinen, Katja; Zoratti, Laura; Nguyenquynh, Nga; Häggman, Hely; Jaakola, Laura

    2016-01-01

    Secondary metabolites have important defense and signaling roles, and they contribute to the overall quality of developing and ripening fruits. Blueberries, bilberries, cranberries, and other Vaccinium berries are fleshy berry fruits recognized for the high levels of bioactive compounds, especially anthocyanin pigments. Besides anthocyanins and other products of the phenylpropanoid and flavonoid pathways, these berries also contain other metabolites of interest, such as carotenoid derivatives, vitamins and flavor compounds. Recently, new information has been achieved on the mechanisms related with developmental, environmental, and genetic factors involved in the regulation of secondary metabolism in Vaccinium fruits. Especially light conditions and temperature are demonstrated to have a prominent role on the composition of phenolic compounds. The present review focuses on the studies on mechanisms associated with the regulation of key secondary metabolites, mainly phenolic compounds, in Vaccinium berries. The advances in the research concerning biosynthesis of phenolic compounds in Vaccinium species, including specific studies with mutant genotypes in addition to controlled and field experiments on the genotype × environment (G×E) interaction, are discussed. The recently published Vaccinium transcriptome and genome databases provide new tools for the studies on the metabolic routes. PMID:27242856

  19. Developmental and stress regulation of gene expression for plastid and cytosolic isoprenoid pathways in pepper fruits.

    PubMed Central

    Hugueney, P; Bouvier, F; Badillo, A; Quennemet, J; d'Harlingue, A; Camara, B

    1996-01-01

    Plant cells synthesize a myriad of isoprenoid compounds in different subcellular compartments, which include the plastid, the mitochondria, and the endoplasmic reticulum cytosol. To start the study of the regulation of these parallel pathways, we used pepper (Capsicum annuum) fruit as a model. Using different isoprenoid biosynthetic gene probes from cloned cDNAs, we showed that only genes encoding the plastid enzymes (geranylgeranyl pyrophosphate synthase, phytoene synthase, phytoene desaturase, and capasanthin-capsorubin synthase) are specifically triggered during the normal period of development, at the ripening stage. This pattern of expression can be mimicked and precociously induced by a simple wounding stress. Concerning the cytosol-located enzymes, we observed that the expression of the gene encoding farnesyl pyrophosphate synthase is constitutive, whereas that of farnesyl pyrophosphate cyclase (5-epi-aristolochene synthase) is undetectable during the normal development of the fruit. The expression of these later genes are, however, only selectively triggered after elicitor treatment. The results provide evidence for developmental control of isoprenoid biosynthesis occurring in plastids and that cytoplasmic isoprenoid biosynthesis is regulated, in part, by environmental signals. PMID:8787029

  20. On the Developmental and Environmental Regulation of Secondary Metabolism in Vaccinium spp. Berries.

    PubMed

    Karppinen, Katja; Zoratti, Laura; Nguyenquynh, Nga; Häggman, Hely; Jaakola, Laura

    2016-01-01

    Secondary metabolites have important defense and signaling roles, and they contribute to the overall quality of developing and ripening fruits. Blueberries, bilberries, cranberries, and other Vaccinium berries are fleshy berry fruits recognized for the high levels of bioactive compounds, especially anthocyanin pigments. Besides anthocyanins and other products of the phenylpropanoid and flavonoid pathways, these berries also contain other metabolites of interest, such as carotenoid derivatives, vitamins and flavor compounds. Recently, new information has been achieved on the mechanisms related with developmental, environmental, and genetic factors involved in the regulation of secondary metabolism in Vaccinium fruits. Especially light conditions and temperature are demonstrated to have a prominent role on the composition of phenolic compounds. The present review focuses on the studies on mechanisms associated with the regulation of key secondary metabolites, mainly phenolic compounds, in Vaccinium berries. The advances in the research concerning biosynthesis of phenolic compounds in Vaccinium species, including specific studies with mutant genotypes in addition to controlled and field experiments on the genotype × environment (G×E) interaction, are discussed. The recently published Vaccinium transcriptome and genome databases provide new tools for the studies on the metabolic routes. PMID:27242856

  1. Arabidopsis ribosomal proteins control vacuole trafficking and developmental programs through the regulation of lipid metabolism

    PubMed Central

    Li, Ruixi; Sun, Ruobai; Hicks, Glenn R.; Raikhel, Natasha V.

    2015-01-01

    The vacuole is the most prominent compartment in plant cells and is important for ion and protein storage. In our effort to search for key regulators in the plant vacuole sorting pathway, ribosomal large subunit 4 (rpl4d) was identified as a translational mutant defective in both vacuole trafficking and normal development. Polysome profiling of the rpl4d mutant showed reduction in polysome-bound mRNA compared with wild-type, but no significant change in the general mRNA distribution pattern. Ribsomal profiling data indicated that genes in the lipid metabolism pathways were translationally down-regulated in the rpl4d mutant. Live imaging studies by Nile red staining suggested that both polar and nonpolar lipid accumulation was reduced in meristem tissues of rpl4d mutants. Pharmacological evidence showed that sterol and sphingolipid biosynthetic inhibitors can phenocopy the defects of the rpl4d mutant, including an altered vacuole trafficking pattern. Genetic evidence from lipid biosynthetic mutants indicates that alteration in the metabolism of either sterol or sphingolipid biosynthesis resulted in vacuole trafficking defects, similar to the rpl4d mutant. Tissue-specific complementation with key enzymes from lipid biosynthesis pathways can partially rescue both vacuole trafficking and auxin-related developmental defects in the rpl4d mutant. These results indicate that lipid metabolism modulates auxin-mediated tissue differentiation and endomembrane trafficking pathways downstream of ribosomal protein function. PMID:25535344

  2. Developmentally Regulated Expression of the Nerve Growth Factor Receptor Gene in the Periphery and Brain

    NASA Astrophysics Data System (ADS)

    Buck, C. R.; Martinez, Humberto J.; Black, Ira B.; Chao, Moses V.

    1987-05-01

    Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.

  3. Abscisic Acid Induction of Vacuolar H+-ATPase Activity in Mesembryanthemum crystallinum Is Developmentally Regulated1

    PubMed Central

    Barkla, Bronwyn J.; Vera-Estrella, Rosario; Maldonado-Gama, Minerva; Pantoja, Omar

    1999-01-01

    Abscisic acid (ABA) has been implicated as a key component in water-deficit-induced responses, including those triggered by drought, NaCl, and low- temperature stress. In this study a role for ABA in mediating the NaCl-stress-induced increases in tonoplast H+-translocating ATPase (V-ATPase) and Na+/H+ antiport activity in Mesembryanthemum crystallinum, leading to vacuolar Na+ sequestration, were investigated. NaCl or ABA treatment of adult M. crystallinum plants induced V-ATPase H+ transport activity, and when applied in combination, an additive effect on V-ATPase stimulation was observed. In contrast, treatment of juvenile plants with ABA did not induce V-ATPase activity, whereas NaCl treatment resulted in a similar response to that observed in adult plants. Na+/H+ antiport activity was induced in both juvenile and adult plants by NaCl, but ABA had no effect at either developmental stage. Results indicate that ABA-induced changes in V-ATPase activity are dependent on the plant reaching its adult phase, whereas NaCl-induced increases in V-ATPase and Na+/H+ antiport activity are independent of plant age. This suggests that ABA-induced V-ATPase activity may be linked to the stress-induced, developmentally programmed switch from C3 metabolism to Crassulacean acid metabolism in adult plants, whereas, vacuolar Na+ sequestration, mediated by the V-ATPase and Na+/H+ antiport, is regulated through ABA-independent pathways. PMID:10398716

  4. Developmental and Light Regulation of Desacetoxyvindoline 4-Hydroxylase in Catharanthus roseus (L.) G. Don.1

    PubMed Central

    Vazquez-Flota, Felipe A.; De Luca, Vincenzo

    1998-01-01

    The expression of desacetoxyvindoline 4-hydroxylase (D4H), which catalyzes the second to the last reaction in vindoline biosynthesis in Catharanthus roseus, appears to be under complex, multilevel developmental and light regulation. Developmental studies with etiolated and light-treated seedlings suggested that although light had variable effects on the levels of d4h transcripts, those of D4H protein and enzyme activity could be increased, depending on seedling development, up to 9- and 8-fold, respectively, compared with etiolated seedlings. However, light treatment of etiolated seedlings could stop and reverse the decline of d4h transcripts at later stages of seedling development. Repeated exposure of seedlings to light was also required to maintain the full spectrum of enzyme activity observed during seedling development. Further studies showed that a photoreversible phytochrome appeared to be involved in the activation of D4H, since red-light treatment of etiolated seedlings increased the detectable levels of d4h transcripts, D4H protein, and D4H enzyme activity, whereas far-red-light treatment completely reversed this process. Additional studies also confirmed that different major isoforms of D4H protein exist in etiolated (isoelectric point, 4.7) and light-grown (isoelectric point, 4.6) seedlings, suggesting that a component of the light-mediated activation of D4H may involve an undetermined posttranslational modification. The biological reasons for this complex control of vindoline biosynthesis may be related to the need to produce structures that could sequester away from cellular activities the cytotoxic vinblastine and vincristine dimers that are derived partially from vindoline. PMID:9701591

  5. Identification of domains required for developmentally regulated SNARE function in Saccharomyces cerevisiae.

    PubMed Central

    Neiman, A M; Katz, L; Brennwald, P J

    2000-01-01

    Saccharomyces cerevisiae cells contain two homologues of the mammalian t-SNARE protein SNAP-25, encoded by the SEC9 and SPO20 genes. Although both gene products participate in post-Golgi vesicle fusion events, they cannot substitute for one another; Sec9p is active primarily in vegetative cells while Spo20p functions only during sporulation. We have investigated the basis for the developmental stage-specific differences in the function of these two proteins. Localization of the other plasma membrane SNARE subunits, Ssop and Sncp, in sporulating cells suggests that these proteins act in conjunction with Spo20p in the formation of the prospore membrane. In vitro binding studies demonstrate that, like Sec9p, Spo20p binds specifically to the t-SNARE Sso1p and, once bound to Sso1p, can complex with the v-SNARE Snc2p. Therefore, Sec9p and Spo20p interact with the same binding partners, but developmental conditions appear to favor the assembly of complexes with Spo20p in sporulating cells. Analysis of chimeric Sec9p/Spo20p molecules indicates that regions in both the SNAP-25 domain and the unique N terminus of Spo20p are required for activity during sporulation. Additionally, the N terminus of Spo20p is inhibitory in vegetative cells. Deletion studies indicate that activation and inhibition are separable functions of the Spo20p N terminus. Our results reveal an additional layer of regulation of the SNARE complex, which is necessary only in sporulating cells. PMID:10924463

  6. Developmental expression of chicken antithrombin III is regulated by increased RNA abundance and intracellular processing.

    PubMed

    Amrani, D L; Rosenberg, J; Samad, F; Bergtrom, G; Banfield, D K

    1993-01-23

    We isolated and sequenced a 432 bp cDNA to cAT-III, that encoded 115 nucleotides of 5' untranslated sequence, a 17 amino acid long signal peptide and residues 1-88 of the mature protein, and used it to prepare a probe for measuring and correlating the developmental changes of steady-state cAT-III mRNA levels with known changes in antigen levels. Densitometric analysis of nuclease protection (n = 2), Northern blot (n = 4), and slot blots (n = 3) of total RNA from chick livers of 16-day-old embryos to 6-day-old chicks showed a 2.6 +/- 0.5-fold increase in steady-state cAT-III mRNA levels. Assay of functional mRNA levels by in vitro translation of poly(A)+ RNA and specific immunoprecipitation of 35S-Met-labelled cAT-III was comparable to RNA analysis (16-day-old embryos vs. 10-day-old hatchlings). We evaluated whether there were developmental differences in post-translational secretion which may also contribute to the regulation of the circulating level of this protein. Pulse-chase studies of freshly-isolated hepatocytes from 16-day-old embryos and 10-day-old hatchlings maintained in suspension demonstrated a approx. 5.0-5.5-fold increase in cAT-III levels at steady-state secretion. The above findings indicate that changes in circulating cAT-III levels during late embryonic development are primarily due to increased abundance of cAT-III mRNA. In addition, we postulate that post-translational intracellular processing may account for further differences in circulating protein levels. PMID:8424948

  7. Reciprocity in the Developmental Regulation of Aquaporins 1, 3 and 5 during Pregnancy and Lactation in the Rat

    PubMed Central

    Nazemi, Sasan; Rahbek, Mette; Parhamifar, Ladan; Moghimi, Seyed Moein; Babamoradi, Hamid; Mehrdana, Foojan; Klærke, Dan Arne; Knight, Christopher H.

    2014-01-01

    Milk secretion involves significant flux of water, driven largely by synthesis of lactose within the Golgi apparatus. It has not been determined whether this flux is simply a passive consequence of the osmotic potential between cytosol and Golgi, or whether it involves regulated flow. Aquaporins (AQPs) are membrane water channels that regulate water flux. AQP1, AQP3 and AQP5 have previously been detected in mammary tissue, but evidence of developmental regulation (altered expression according to the developmental and physiological state of the mammary gland) is lacking and their cellular/subcellular location is not well understood. In this paper we present evidence of developmental regulation of all three of these AQPs. Further, there was evidence of reciprocity since expression of the rather abundant AQP3 and less abundant AQP1 increased significantly from pregnancy into lactation, whereas expression of the least abundant AQP5 decreased. It would be tempting to suggest that AQP3 and AQP1 are involved in the secretion of water into milk. Paradoxically, however, it was AQP5 that demonstrated most evidence of expression located at the apical (secretory) membrane. The possibility is discussed that AQP5 is synthesized during pregnancy as a stable protein that functions to regulate water secretion during lactation. AQP3 was identified primarily at the basal and lateral membranes of the secretory cells, suggesting a possible involvement in regulated uptake of water and glycerol. AQP1 was identified primarily at the capillary and secretory cell cytoplasmic level and may again be more concerned with uptake and hence milk synthesis, rather than secretion. The fact that expression was developmentally regulated supports, but does not prove, a regulatory involvement of AQPs in water flux through the milk secretory cell. PMID:25184686

  8. EST analysis in Ginkgo biloba: an assessment of conserved developmental regulators and gymnosperm specific genes

    PubMed Central

    Brenner, Eric D; Katari, Manpreet S; Stevenson, Dennis W; Rudd, Stephen A; Douglas, Andrew W; Moss, Walter N; Twigg, Richard W; Runko, Suzan J; Stellari, Giulia M; McCombie, WR; Coruzzi, Gloria M

    2005-01-01

    Background Ginkgo biloba L. is the only surviving member of one of the oldest living seed plant groups with medicinal, spiritual and horticultural importance worldwide. As an evolutionary relic, it displays many characters found in the early, extinct seed plants and extant cycads. To establish a molecular base to understand the evolution of seeds and pollen, we created a cDNA library and EST dataset from the reproductive structures of male (microsporangiate), female (megasporangiate), and vegetative organs (leaves) of Ginkgo biloba. Results RNA from newly emerged male and female reproductive organs and immature leaves was used to create three distinct cDNA libraries from which 6,434 ESTs were generated. These 6,434 ESTs from Ginkgo biloba were clustered into 3,830 unigenes. A comparison of our Ginkgo unigene set against the fully annotated genomes of rice and Arabidopsis, and all available ESTs in Genbank revealed that 256 Ginkgo unigenes match only genes among the gymnosperms and non-seed plants – many with multiple matches to genes in non-angiosperm plants. Conversely, another group of unigenes in Gingko had highly significant homology to transcription factors in angiosperms involved in development, including MADS box genes as well as post-transcriptional regulators. Several of the conserved developmental genes found in Ginkgo had top BLAST homology to cycad genes. We also note here the presence of ESTs in G. biloba similar to genes that to date have only been found in gymnosperms and an additional 22 Ginkgo genes common only to genes from cycads. Conclusion Our analysis of an EST dataset from G. biloba revealed genes potentially unique to gymnosperms. Many of these genes showed homology to fully sequenced clones from our cycad EST dataset found in common only with gymnosperms. Other Ginkgo ESTs are similar to developmental regulators in higher plants. This work sets the stage for future studies on Ginkgo to better understand seed and pollen evolution, and to

  9. Functional and developmental identification of a molecular subtype of brain serotonergic neuron specialized to regulate breathing dynamics

    PubMed Central

    Brust, Rachael D.; Corcoran, Andrea E.; Richerson, George B.; Nattie, Eugene; Dymecki, Susan M.

    2015-01-01

    Summary Serotonergic neurons modulate behavioral and physiological responses from aggression and anxiety to breathing and thermoregulation. Disorders involving serotonin (5HT) dysregulation are commensurately heterogeneous and numerous. We hypothesized that this breadth in functionality derives in part from a developmentally determined substructure of distinct subtypes of 5HT neurons each specialized to modulate specific behaviors. We find, by manipulating developmentally defined subgroups one-by-one chemogenetically, that the Egr2-Pet1 subgroup is specialized to drive increased ventilation in response to carbon dioxide elevation and acidosis. Further, this subtype exhibits intrinsic chemosensitivity and modality-specific projections – increasing firing during hypercapnic acidosis and selectively projecting to respiratory chemosensory but not motor centers, respectively. These findings show that serotonergic regulation of the respiratory chemoreflex is mediated by a specialized molecular subtype of 5HT neuron harboring unique physiological, biophysical, and hodological properties specified developmentally, and demonstrate that the serotonergic system contains specialized modules contributing to its collective functional breadth. PMID:25497093

  10. Synaptic commitment: developmentally regulated reciprocal changes in hippocampal granule cell NMDA and AMPA receptors over the lifespan.

    PubMed

    Yang, Zhiyong; Krause, Michael; Rao, Geeta; McNaughton, Bruce L; Barnes, C A

    2008-06-01

    Synaptic transmission in hippocampal field CA1 is largely N-methyl-d-aspartate receptor (NMDA(R)) dependent during the early postnatal period. It becomes increasingly mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptors until an adult ratio of AMPA to NMDA receptors is achieved. It is shown here that increases in the AMPA receptor (AMPA(R))-mediated field potential response continue over the life span of the F-344 rat at the perforant path-granule cell synapse in the dentate gyrus. In contrast, the NMDA(R)-dependent component of the response decreases with age between 1 and 27 mo, leading to an increase of AMPA(R)/NMDA(R) ratio with age. One possible explanation of this age difference is that the AMPA(R)/NMDA(R) ratio can be modified by experience. To test the idea that the changed ratio is caused by the old rats' longer lives, an intensive 10-mo period of enrichment treatment was given to a group of animals, beginning at 3 mo of age. Compared with animals housed in standard cages, the enrichment treatment did not alter the glutamatergic response ratio measured with field potential recording methods. These data provide support for the conclusion that the observed change with age is developmentally regulated rather than experience dependent. Given the role of the NMDA(R) in synaptic plasticity, these changes suggest a progressive commitment of perforant path synapses to particular weights over the life span. One possible implication of this effect includes preservation of selected memories, ultimately at the expense of a reduced capacity to store new information. PMID:18417629

  11. The developmental regulation and biosynthesis of GPI-related structures in Leishmania parasites.

    PubMed

    McConville, M J; Schneider, P; Proudfoot, L; Masterson, C; Ferguson, M A

    1994-02-01

    Most macromolecules on the surface of Leishmania parasites, including the major surface proteins and a complex lipophosphoglycan (LPG) are anchored to the plasma membrane via GPI glycolipids. Free glycoinositol-phospholipids (GIPLs) which are not linked to protein or phosphoglycan are also abundant in the plasma membrane. From structural and metabolic labeling studies it is proposed that most Leishmania species express three distinct pathways of GPI biosynthesis. Some of these pathways (i.e. those involved in the protein and LPG anchor biosynthesis) are down-regulated during the differentiation of the insect (promastigote) stage to the mammalian (amastigote) stage. In contrast, the GIPLs are expressed in high copy number in both developmental stages. Based on analysis of the lipid moieties of the different GPI species it is possible that the pathways of GPI anchor and GIPL biosynthesis are located in different subcellular compartments. The relative flux through the GIPL and LPG biosynthetic pathways has been examined in L. major promastigotes. These studies showed that while the rate of synthesis of the GIPLs and LPG is similar, LPG is shed more rapidly from the plasma membrane and has a higher turnover. The possible metabolic relationship between the GIPL and LPG biosynthetic pathways is discussed. PMID:8081222

  12. New Tools for the Identification of Developmentally Regulated Enhancer Regions in Embryonic and Adult Zebrafish

    PubMed Central

    Krauss, Jana; Koehler, Carla; Boden, Cindy; Harris, Matthew P.

    2013-01-01

    Abstract We have conducted a screen to identify developmentally regulated enhancers that drive tissue-specific Gal4 expression in zebrafish. We obtained 63 stable transgenic lines with expression patterns in embryonic or adult zebrafish. The use of a newly identified minimal promoter from the medaka edar locus resulted in a relatively unbiased set of expression patterns representing many tissue types derived from all germ layers. Subsequent detailed characterization of selected lines showed strong and reproducible Gal4-driven GFP expression in diverse tissues, including neurons from the central and peripheral nervous systems, pigment cells, erythrocytes, and peridermal cells. By screening adults for GFP expression, we also isolated lines expressed in tissues of the adult zebrafish, including scales, fin rays, and joints. The new and efficient minimal promoter and large number of transactivating driver-lines we identified will provide the zebrafish community with a useful resource for further enhancer trap screening, as well as precise investigation of tissue-specific processes in vivo. PMID:23461416

  13. Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats.

    PubMed

    Roepke, Troy A; Yang, Jennifer A; Yasrebi, Ali; Mamounis, Kyle J; Oruc, Elif; Zama, Aparna Mahakali; Uzumcu, Mehmet

    2016-07-01

    Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females. PMID:27103539

  14. Developmentally regulated sesquiterpene production confers resistance to Colletotrichum gloeosporioides in ripe pepper fruits.

    PubMed

    Park, Sangkyu; Park, Ae Ran; Im, Soonduk; Han, Yun-Jeong; Lee, Sungbeom; Back, Kyoungwhan; Kim, Jeong-Il; Kim, Young Soon

    2014-01-01

    Sesquiterpenoid capsidiol, exhibiting antifungal activity against pathogenic fungus, is accumulated in infected ripe pepper fruits. In this study, we found a negative relation between the capsidiol level and lesion size in fruits infected with Colletotrichum gloeosporioides, depending on the stage of ripening. To understand the developmental regulation of capsidiol biosynthesis, fungal-induced gene expressions in the isoprenoid biosynthetic pathways were examined in unripe and ripe pepper fruits. The sterol biosynthetic pathway was almost shut down in healthy ripe fruits, showing very low expression of hydroxymethyl glutaryl CoA reductase (HMGR) and squalene synthase (SS) genes. In contrast, genes in the carotenoid pathway were highly expressed in ripe fruits. In the sesquiterpene pathway, 5-epi-aristolochene synthase (EAS), belonging to a sesquiterpene cyclase (STC) family, was significantly induced in the ripe fruits upon fungal infection. Immunoblot and enzyme activity analyses showed that the STCs were induced both in the infected unripe and ripe fruits, while capsidiol was synthesized discriminatively in the ripe fruits, implying diverse enzymatic specificity of multiple STCs. Thereby, to divert sterol biosynthesis into sesquiterpene production, infected fruits were pretreated with an SS inhibitor, zaragozic acid (ZA), resulting in increased levels of capsidiol by more than 2-fold in the ripe fruits, with concurrent reduction of phytosterols. Taken together, the present results suggest that the enhanced expression and activity of EAS in the ripe fruits play an important role in capsidiol production, contributing to the incompatibility between the anthracnose fungus and the ripe pepper fruits. PMID:25286411

  15. Developmentally Regulated Sesquiterpene Production Confers Resistance to Colletotrichum gloeosporioides in Ripe Pepper Fruits

    PubMed Central

    Im, Soonduk; Han, Yun-Jeong; Lee, Sungbeom; Back, Kyoungwhan; Kim, Jeong-Il; Kim, Young Soon

    2014-01-01

    Sesquiterpenoid capsidiol, exhibiting antifungal activity against pathogenic fungus, is accumulated in infected ripe pepper fruits. In this study, we found a negative relation between the capsidiol level and lesion size in fruits infected with Colletotrichum gloeosporioides, depending on the stage of ripening. To understand the developmental regulation of capsidiol biosynthesis, fungal-induced gene expressions in the isoprenoid biosynthetic pathways were examined in unripe and ripe pepper fruits. The sterol biosynthetic pathway was almost shut down in healthy ripe fruits, showing very low expression of hydroxymethyl glutaryl CoA reductase (HMGR) and squalene synthase (SS) genes. In contrast, genes in the carotenoid pathway were highly expressed in ripe fruits. In the sesquiterpene pathway, 5-epi-aristolochene synthase (EAS), belonging to a sesquiterpene cyclase (STC) family, was significantly induced in the ripe fruits upon fungal infection. Immunoblot and enzyme activity analyses showed that the STCs were induced both in the infected unripe and ripe fruits, while capsidiol was synthesized discriminatively in the ripe fruits, implying diverse enzymatic specificity of multiple STCs. Thereby, to divert sterol biosynthesis into sesquiterpene production, infected fruits were pretreated with an SS inhibitor, zaragozic acid (ZA), resulting in increased levels of capsidiol by more than 2-fold in the ripe fruits, with concurrent reduction of phytosterols. Taken together, the present results suggest that the enhanced expression and activity of EAS in the ripe fruits play an important role in capsidiol production, contributing to the incompatibility between the anthracnose fungus and the ripe pepper fruits. PMID:25286411

  16. Sequential evolution of bacterial morphology by co-option of a developmental regulator

    NASA Astrophysics Data System (ADS)

    Jiang, Chao; Brown, Pamela J. B.; Ducret, Adrien; Brun, Yves V.

    2014-02-01

    What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.

  17. Developmental regulation of the gene for formate dehydrogenase in Neurospora crassa.

    PubMed Central

    Chow, C M; RajBhandary, U L

    1993-01-01

    We have isolated and characterized a gene, fdh, from Neurospora crassa which is developmentally regulated and which produces formate dehydrogenase activity when expressed in Escherichia coli. The gene is closely linked (less than 0.6 kb apart) to the leu-5 gene encoding mitochondrial leucyl-tRNA synthetase; the two genes are transcribed convergently from opposite strands. The expression patterns of these genes differ: fdh mRNA is found only during conidiation and early germination and is not detectable during mycelial growth, while leu-5 mRNA appears during germination and mycelial growth. The structure of the fdh gene was determined from the sequence of cDNA and genomic DNA clones and from mRNA mapping studies. The gene encodes a 375-amino-acid-long protein with sequence similarity to NAD-dependent dehydrogenases of the E. coli 3-phosphoglycerate dehydrogenase (serA gene product) subfamily. In particular, there is striking sequence similarity (52% identity) to formate dehydrogenase from Pseudomonas sp. strain 101. All of the residues thought to interact with NAD in the crystal structure of the Pseudomonas enzyme are conserved in the N. crassa enzyme. We have further shown that expression of the N. crassa gene in E. coli leads to the production of formate dehydrogenase activity, indicating that the N. crassa gene specifies a functional polypeptide. Images PMID:8509325

  18. Developmental regulation of hexosamine biosynthesis by protein phosphatases 2A and 2C in Blastocladiella emersonii.

    PubMed

    Etchebehere, L C; Simon, M N; Campanhã, R B; Zapella, P D; Véron, M; Maia, J C

    1993-08-01

    Extracts of the aquatic fungus Blastocladiella emersonii were found to contain protein phosphatases type 1, type 2A, and type 2C with properties analogous to those found in mammalian tissues. The activities of all three protein phosphatases are developmentally regulated, increasing during sporulation, with maximum level in zoospores. Protein phosphatases 2A and 2C, present in zoospore extracts, catalyze the dephosphorylation of L-glutamine:fructose-6-phosphate amidotransferase (EC 2.6.1.16, amidotransferase), a key regulatory enzyme in hexosamine biosynthesis. The protein phosphatase inhibitor okadaic acid induces encystment and inhibits germ tube formation but does not affect the synthesis of the chitinous cell wall. These results strongly suggest that phosphatase 2C is responsible for the dephosphorylation of amidotransferase in vivo. This dephosphorylation is inhibited by uridine-5'-diphospho-N-acetylglucosamine, the end product of hexosamine synthesis and the substrate for chitin synthesis. This result demonstrates a dual role of uridine-5'-diphospho-N-acetylglucosamine by inhibiting the activity of the phosphorylated form of amidotransferase and by preventing its dephosphorylation by protein phosphatases. PMID:8394312

  19. RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.

    PubMed Central

    Hanrahan, C J; Palladino, M J; Ganetzky, B; Reenan, R A

    2000-01-01

    Post-transcriptional editing of pre-mRNAs through the action of dsRNA adenosine deaminases results in the modification of particular adenosine (A) residues to inosine (I), which can alter the coding potential of the modified transcripts. We describe here three sites in the para transcript, which encodes the major voltage-activated Na(+) channel polypeptide in Drosophila, where RNA editing occurs. The occurrence of RNA editing at the three sites was found to be developmentally regulated. Editing at two of these sites was also conserved across species between the D. melanogaster and D. virilis. In each case, a highly conserved region was found in the intron downstream of the editing site and this region was shown to be complementary to the region of the exonic editing site. Thus, editing at these sites would appear to involve a mechanism whereby the edited exon forms a base-paired secondary structure with the distant conserved noncoding sequences located in adjacent downstream introns, similar to the mechanism shown for A-to-I RNA editing of mammalian glutamate receptor subunits (GluRs). For the third site, neither RNA editing nor the predicted RNA secondary structures were evolutionarily conserved. Transcripts from transgenic Drosophila expressing a minimal editing site construct for this site were shown to faithfully undergo RNA editing. These results demonstrate that Na(+) channel diversity in Drosophila is increased by RNA editing via a mechanism analogous to that described for transcripts encoding mammalian GluRs. PMID:10880477

  20. Clique of functional hubs orchestrates population bursts in developmentally regulated neural networks

    NASA Astrophysics Data System (ADS)

    Torcini, Alessandro; Luccioli, Stefano; Bonifazi, Paolo; Ben-Jacob, Eshel; Barzilai, Ari

    2015-03-01

    It has recently been discovered that single neuron stimulation can impact network dynamics in immature and adult neuronal circuits. Here we report a novel mechanism which can explain in developing neuronal circuits, typically composed of only excitatory cells, the peculiar role played by a few specific neurons in promoting/arresting the population activity. For this purpose, we consider a standard neuronal network model, with short-term synaptic plasticity, whose population activity is characterized by bursting behavior. The addition of developmentally regulated constraints on single neuron excitability and connectivity leads to the emergence of functional hub neurons, whose stimulation/deletion is critical for the network activity. Functional hubs form a clique, where a precise sequential activation of the neurons is essential to ignite collective events without any need for a specific topological architecture. Unsupervised time-lagged firings of supra-threshold cells, in connection with coordinated entrainments of near-threshold neurons, are the key ingredients to orchestrate population activity. This work is part of the activity of the Joint Italian-Israeli Laboratory on Integrative Network Neuroscience supported by the Italian Ministry of Foreign Affairs.

  1. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells.

    PubMed

    Wang, Yang; Li, Yue; Toth, Julia I; Petroski, Matthew D; Zhang, Zhaolei; Zhao, Jing Crystal

    2014-02-01

    N(6)-methyladenosine (m(6)A) has been identified as the most abundant internal modification of messenger RNA in eukaryotes. m(6)A modification is involved in cell fate determination in yeast and embryo development in plants. Its mammalian function remains unknown but thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs) show m(6)A modification and m(6)A demethylases are required for mammalian energy homeostasis and fertility. We identify two proteins, the putative m(6)A MTase, methyltransferase-like 3 (Mettl3; ref. ), and a related but uncharacterized protein Mettl14, that function synergistically to control m(6)A formation in mammalian cells. Knockdown of Mettl3 and Mettl14 in mouse embryonic stem cells (mESCs) led to similar phenotypes, characterized by lack of m(6)A RNA methylation and lost self-renewal capability. A large number of transcripts, including many encoding developmental regulators, exhibit m(6)A methylation inversely correlated with mRNA stability and gene expression. The human antigen R (HuR) and microRNA pathways were linked to these effects. This gene regulatory mechanism operating in mESCs through m(6)A methylation is required to keep mESCs at their ground state and may be relevant to thousands of mRNAs and lncRNAs in various cell types. PMID:24394384

  2. The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea

    PubMed Central

    Golden, Erin J.; Benito-Gonzalez, Ana; Doetzlhofer, Angelika

    2015-01-01

    Proper tissue development requires strict coordination of proliferation, growth, and differentiation. Strict coordination is particularly important for the auditory sensory epithelium, where deviations from the normal spatial and temporal pattern of auditory progenitor cell (prosensory cell) proliferation and differentiation result in abnormal cellular organization and, thus, auditory dysfunction. The molecular mechanisms involved in the timing and coordination of auditory prosensory proliferation and differentiation are poorly understood. Here we identify the RNA-binding protein LIN28B as a critical regulator of developmental timing in the murine cochlea. We show that Lin28b and its opposing let-7 miRNAs are differentially expressed in the auditory sensory lineage, with Lin28b being highly expressed in undifferentiated prosensory cells and let-7 miRNAs being highly expressed in their progeny—hair cells (HCs) and supporting cells (SCs). Using recently developed transgenic mouse models for LIN28B and let-7g, we demonstrate that prolonged LIN28B expression delays prosensory cell cycle withdrawal and differentiation, resulting in HC and SC patterning and maturation defects. Surprisingly, let-7g overexpression, although capable of inducing premature prosensory cell cycle exit, failed to induce premature HC differentiation, suggesting that LIN28B’s functional role in the timing of differentiation uses let-7 independent mechanisms. Finally, we demonstrate that overexpression of LIN28B or let-7g can significantly alter the postnatal production of HCs in response to Notch inhibition; LIN28B has a positive effect on HC production, whereas let-7 antagonizes this process. Together, these results implicate a key role for the LIN28B/let-7 axis in regulating postnatal SC plasticity. PMID:26139524

  3. The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea.

    PubMed

    Golden, Erin J; Benito-Gonzalez, Ana; Doetzlhofer, Angelika

    2015-07-21

    Proper tissue development requires strict coordination of proliferation, growth, and differentiation. Strict coordination is particularly important for the auditory sensory epithelium, where deviations from the normal spatial and temporal pattern of auditory progenitor cell (prosensory cell) proliferation and differentiation result in abnormal cellular organization and, thus, auditory dysfunction. The molecular mechanisms involved in the timing and coordination of auditory prosensory proliferation and differentiation are poorly understood. Here we identify the RNA-binding protein LIN28B as a critical regulator of developmental timing in the murine cochlea. We show that Lin28b and its opposing let-7 miRNAs are differentially expressed in the auditory sensory lineage, with Lin28b being highly expressed in undifferentiated prosensory cells and let-7 miRNAs being highly expressed in their progeny-hair cells (HCs) and supporting cells (SCs). Using recently developed transgenic mouse models for LIN28B and let-7g, we demonstrate that prolonged LIN28B expression delays prosensory cell cycle withdrawal and differentiation, resulting in HC and SC patterning and maturation defects. Surprisingly, let-7g overexpression, although capable of inducing premature prosensory cell cycle exit, failed to induce premature HC differentiation, suggesting that LIN28B's functional role in the timing of differentiation uses let-7 independent mechanisms. Finally, we demonstrate that overexpression of LIN28B or let-7g can significantly alter the postnatal production of HCs in response to Notch inhibition; LIN28B has a positive effect on HC production, whereas let-7 antagonizes this process. Together, these results implicate a key role for the LIN28B/let-7 axis in regulating postnatal SC plasticity. PMID:26139524

  4. FKBPL Is a Critical Antiangiogenic Regulator of Developmental and Pathological Angiogenesis

    PubMed Central

    Yakkundi, Anita; Bennett, Rachel; Hernández-Negrete, Ivette; Delalande, Jean-Marie; Hanna, Mary; Lyubomska, Oksana; Arthur, Kenneth; Short, Amy; McKeen, Hayley; Nelson, Laura; McCrudden, Cian M.; McNally, Ross; McClements, Lana; McCarthy, Helen O.; Burns, Alan J.; Bicknell, Roy; Kissenpfennig, Adrien

    2015-01-01

    Objective— The antitumor effects of FK506-binding protein like (FKBPL) and its extracellular role in angiogenesis are well characterized; however, its role in physiological/developmental angiogenesis and the effect of FKBPL ablation has not been evaluated. This is important as effects of some angiogenic proteins are dosage dependent. Here we evaluate the regulation of FKBPL secretion under angiogenic stimuli, as well as the effect of FKBPL ablation in angiogenesis using mouse and zebrafish models. Approach and Results— FKBPL is secreted maximally by human microvascular endothelial cells and fibroblasts, and this was specifically downregulated by proangiogenic hypoxic signals, but not by the angiogenic cytokines, VEGF or IL8. FKBPL’s critical role in angiogenesis was supported by our inability to generate an Fkbpl knockout mouse, with embryonic lethality occurring before E8.5. However, whilst Fkbpl heterozygotic embryos showed some vasculature irregularities, the mice developed normally. In murine angiogenesis models, including the ex vivo aortic ring assay, in vivo sponge assay, and tumor growth assay, Fkbpl+/− mice exhibited increased sprouting, enhanced vessel recruitment, and faster tumor growth, respectively, supporting the antiangiogenic function of FKBPL. In zebrafish, knockdown of zFkbpl using morpholinos disrupted the vasculature, and the phenotype was rescued with hFKBPL. Interestingly, this vessel disruption was ineffective when zcd44 was knocked-down, supporting the dependency of zFkbpl on zCd44 in zebrafish. Conclusions— FKBPL is an important regulator of angiogenesis, having an essential role in murine and zebrafish blood vessel development. Mouse models of angiogenesis demonstrated a proangiogenic phenotype in Fkbpl heterozygotes. PMID:25767277

  5. Measuring Developmental Progress of Children with Autism Spectrum Disorder on School Entry Using Parent Report

    ERIC Educational Resources Information Center

    Charman, Tony; Howlin, Patricia; Berry, Bryony; Prince, Emily

    2004-01-01

    Increasing numbers of children with autism spectrum disorder (ASD) are diagnosed in the preschool years, and their educational progress must be monitored. Parent questionnaire data can augment psychometric assessments and individual planning at low cost. One hundred and twenty-five parents of UK children who entered dedicated autism primary…

  6. Developmental regulation of molecular signalling in fetal and neonatal diaphragm protein metabolism.

    PubMed

    Song, Yong; Pillow, J Jane

    2013-08-01

    -κB signal transduction. The finding provides new insights into developmental regulation of protein metabolism within development. The implication of these postnatal events for diaphragm adaptation to the ex utero environment needs further investigation. PMID:23828585

  7. Developmentally regulated expression and complex processing of barley pri-microRNAs

    PubMed Central

    2013-01-01

    Background MicroRNAs (miRNAs) regulate gene expression via mRNA cleavage or translation inhibition. In spite of barley being a cereal of great economic importance, very little data is available concerning its miRNA biogenesis. There are 69 barley miRNA and 67 pre-miRNA sequences available in the miRBase (release 19). However, no barley pri-miRNA and MIR gene structures have been shown experimentally. In the present paper, we examine the biogenesis of selected barley miRNAs and the developmental regulation of their pri-miRNA processing to learn more about miRNA maturation in barely. Results To investigate the organization of barley microRNA genes, nine microRNAs - 156g, 159b, 166n, 168a-5p/168a-3p, 171e, 397b-3p, 1120, and 1126 - were selected. Two of the studied miRNAs originate from one MIR168a-5p/168a-3p gene. The presence of all miRNAs was confirmed using a Northern blot approach. The miRNAs are encoded by genes with diverse organizations, representing mostly independent transcription units with or without introns. The intron-containing miRNA transcripts undergo complex splicing events to generate various spliced isoforms. We identified miRNAs that were encoded within introns of the noncoding genes MIR156g and MIR1126. Interestingly, the intron that encodes miR156g is spliced less efficiently than the intron encoding miR1126 from their specific precursors. miR397b-3p was detected in barley as a most probable functional miRNA, in contrast to rice where it has been identified as a complementary partner miRNA*. In the case of miR168a-5p/168a-3p, we found the generation of stable, mature molecules from both pre-miRNA arms, confirming evolutionary conservation of the stability of both species, as shown in rice and maize. We suggest that miR1120, located within the 3′ UTR of a protein-coding gene and described as a functional miRNA in wheat, may represent a siRNA generated from a mariner-like transposable element. Conclusions Seven of the eight barley miRNA genes

  8. Genetical Toxicogenomics in Drosophila Identifies Master Modulatory Loci that are Regulated by Developmental Exposure to Lead

    PubMed Central

    Ruden, Douglas M.; Chen, Lang; Possidente, Debra; Possidente, Bernard; Rasouli, Parsa; Wang, Luan; Lu, Xiangyi; Garfinkel, Mark D.; Hirsch, Helmut V. B.; Page, Grier P.

    2009-01-01

    The genetics of gene expression in recombinant inbred lines (RILs) can be mapped as expression quantitative trait loci (eQTLs). So-called “genetical genomics” studies have identified locally-acting eQTLs (cis-eQTLs) for genes that show differences in steady state RNA levels. These studies have also identified distantly-acting master-modulatory trans-eQTLs that regulate tens or hundreds of transcripts (hotspots or transbands). We expand on these studies by performing genetical genomics experiments in two environments in order to identify trans-eQTL that might be regulated by developmental exposure to the neurotoxin lead. Flies from each of 75 RIL were raised from eggs to adults on either control food (made with 250 µM sodium acetate), or lead-treated food (made with 250 µM lead acetate, PbAc). RNA expression analyses of whole adult male flies (5–10 days old) were performed with Affymetrix DrosII whole genome arrays (18,952 probesets). Among the 1,389 genes with cis-eQTL, there were 405 genes unique to control flies and 544 genes unique to lead-treated ones (440 genes had the same cis-eQTLs in both samples). There are 2,396 genes with trans-eQTL which mapped to 12 major transbands with greater than 95 genes. Permutation analyses of the strain labels but not the expression data suggests that the total number of eQTL and the number of transbands are more important criteria for validation than the size of the transband. Two transbands, one located on the 2nd chromosome and one on the 3rd chromosome, co-regulate 33 lead-induced genes, many of which are involved in neurodevelopmental processes. For these 33 genes, rather than allelic variation at one locus exerting differential effects in two environments, we found that variation at two different loci are required for optimal effects on lead-induced expression. PMID:19737576

  9. Developmental Regulation of Diacylglycerol Acyltransferase Family Gene Expression in Tung Tree Tissues

    PubMed Central

    Cao, Heping; Shockey, Jay M.; Klasson, K. Thomas; Chapital, Dorselyn C.; Mason, Catherine B.; Scheffler, Brian E.

    2013-01-01

    Diacylglycerol acyltransferases (DGAT) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT genes have been identified in numerous organisms. Multiple isoforms of DGAT are present in eukaryotes. We previously cloned DGAT1 and DGAT2 genes of tung tree (Vernicia fordii), whose novel seed TAGs are useful in a wide range of industrial applications. The objective of this study was to understand the developmental regulation of DGAT family gene expression in tung tree. To this end, we first cloned a tung tree gene encoding DGAT3, a putatively soluble form of DGAT that possesses 11 completely conserved amino acid residues shared among 27 DGAT3s from 19 plant species. Unlike DGAT1 and DGAT2 subfamilies, DGAT3 is absent from animals. We then used TaqMan and SYBR Green quantitative real-time PCR, along with northern and western blotting, to study the expression patterns of the three DGAT genes in tung tree tissues. Expression results demonstrate that 1) all three isoforms of DGAT genes are expressed in developing seeds, leaves and flowers; 2) DGAT2 is the major DGAT mRNA in tung seeds, whose expression profile is well-coordinated with the oil profile in developing tung seeds; and 3) DGAT3 is the major form of DGAT mRNA in tung leaves, flowers and immature seeds prior to active tung oil biosynthesis. These results suggest that DGAT2 is probably the major TAG biosynthetic isoform in tung seeds and that DGAT3 gene likely plays a significant role in TAG metabolism in other tissues. Therefore, DGAT2 should be a primary target for tung oil engineering in transgenic organisms. PMID:24146944

  10. S-(-)equol production is developmentally regulated and related to early diet composition.

    PubMed

    Brown, Nadine M; Galandi, Stephanie L; Summer, Suzanne S; Zhao, Xueheng; Heubi, James E; King, Eileen C; Setchell, Kenneth D R

    2014-05-01

    S-(-)7-hydroxy-3-(4'-hydroxyphenyl)-chroman, or S-(-)equol, a biologically active intestinally derived bacterial metabolite of the soy isoflavones daidzin/daidzein, is not produced in neonatal life. Because its synthesis is dependent on equol-producing bacteria, we hypothesized that early nutrition may influence equol production. This prospective 2.5-year study determined the frequency of S-(-)equol production in healthy infants (n = 90) fed breast milk, soy infant formula, or cow's milk formula in their first year. Urinary S-(-)equol and daidzein were quantified by mass spectrometry after a standardized 3.5-day soy isoflavone challenge. Infants were tested at 6, 9, 12, 18, 24, and 36 months of age, and 3-day diet records were obtained at each visit to explore the effect of early and postweaning (>12 months) macronutrient and micronutrient dietary composition and S-(-)equol production. Use of antibiotics was also recorded. At age 6 months, none of the breast-fed infants produced S-(-)equol, whereas 3.8% and 6.0%, respectively, of soy and cow's milk formula-fed infants were equol producers. By age 3 years, 50% of the formula-fed infants were equol producers, compared with 25% of breast-fed infants. Use of antibiotics was prevalent among infants and may have impacted the stability of S-(-)equol production. No significant differences among the groups were observed in postweaning dietary intakes of total energy, carbohydrate, fiber, protein, fat, saturated fatty acids, or polyunsaturated fatty acids and the propensity to make S-(-)equol. In conclusion, S-(-)equol production is developmentally regulated and initially related to diet composition with the proportion of equol producers increasing over the first 3 years of life, with a trend for formula feeding favoring S-(-)equol production. PMID:24916553

  11. Developmental stage-specific regulation of atrial natriuretic factor gene transcription in cardiac cells.

    PubMed Central

    Argentin, S; Ardati, A; Tremblay, S; Lihrmann, I; Robitaille, L; Drouin, J; Nemer, M

    1994-01-01

    Cardiac myocytes undergo a major genetic switch within the first week of postnatal development, when cell division ceases terminally and many cardiac genes are either activated or silenced. We have developed stage-specific cardiocyte cultures to analyze transcriptional control of the rat atrial natriuretic factor (ANF) gene to identify the mechanisms underlying tissue-specific and developmental regulation of this gene in the heart. The first 700 bp of ANF flanking sequences was sufficient for cardiac muscle- and stage-specific expression in both atrial and ventricular myocytes, and a cardiac muscle-specific enhancer was localized between -136 and -700 bp. Deletion of this enhancer markedly reduced promoter activity in cardiac myocytes and derepressed ANF promoter activity in nonexpressing cells. Two distinct domains of the enhancer appeared to contribute differentially to cardiac specificity depending on the differentiation stage of the myocytes. DNase I footprinting of the enhancer domain active in differentiated cells revealed four putative regulatory elements including an A+T-rich region and a CArG element. Deletion mutagenesis and promoter reconstitution assays revealed an important role for the CArG-containing element exclusively in cardiac cells, where its activity was switched on in differentiated myocytes. Transcriptional activity of the ANF-CArG box correlated with the presence of a cardiac- and stage-specific DNA-binding complex which was not recognized by the c-fos serum response element. Thus, the use of this in vitro model system representing stage-specific cardiac development unraveled the presence of different regulatory mechanisms for transcription of the ANF gene during cardiac differentiation and may be useful for studying the regulatory pathways of other genes that undergo switching during cardiac myogenesis. Images PMID:8264645

  12. Developmental regulation of the gene for chimeric calcium/calmodulin-dependent protein kinase in anthers.

    PubMed

    Poovaiah, B W; Xia, M; Liu, Z; Wang, W; Yang, T; Sathyanarayanan, P V; Franceschi, V R

    1999-08-01

    Chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) was cloned from developing anthers of lily (Lilium longiflorum Thumb. cv. Nellie White) and tobacco (Nicotiana tabacum L. cv. Xanthi). Previous biochemical characterization and structure/function studies had revealed that CCaMK has dual modes of regulation by Ca(2+) and Ca(2+)/calmodulin. The unique structural features of CCaMK include a catalytic domain, a calmodulin-binding domain, and a neural visinin-like Ca(2+)-binding domain. The existence of these three features in a single polypeptide distinguishes it from other kinases. Western analysis revealed that CCaMK is expressed in a stage-specific manner in developing anthers. Expression of CCaMK was first detected in pollen mother cells and continued to increase, reaching a peak around the tetrad stage of meiosis. Following microsporogenesis, CCaMK expression rapidly decreased and at later stages of microspore development, no expression was detected. A tobacco genomic clone of CCaMK was isolated and transgenic tobacco plants were produced carrying the CCaMK promoter fused to the beta-glucuronidase reporter gene. Both CCaMK mRNA and protein were detected in the pollen sac and their localizations were restricted to the pollen mother cells and tapetal cells. Consistent results showing a stage-specific expression pattern were obtained by beta-glucuronidase analysis, in-situ hybridization and immunolocalization. The stage- and tissue-specific appearance of CCaMK in anthers suggests that it could play a role in sensing transient changes in free Ca(2+) concentration in target cells, thereby controlling developmental events in the anther. PMID:10436217

  13. Developmental and Environmental Regulation of Aquaporin Gene Expression across Populus Species: Divergence or Redundancy?

    PubMed Central

    Cohen, David; Bogeat-Triboulot, Marie-Béatrice; Vialet-Chabrand, Silvère; Merret, Rémy; Courty, Pierre-Emmanuel; Moretti, Sébastien; Bizet, François; Guilliot, Agnès; Hummel, Irène

    2013-01-01

    Aquaporins (AQPs) are membrane channels belonging to the major intrinsic proteins family and are known for their ability to facilitate water movement. While in Populus trichocarpa, AQP proteins form a large family encompassing fifty-five genes, most of the experimental work focused on a few genes or subfamilies. The current work was undertaken to develop a comprehensive picture of the whole AQP gene family in Populus species by delineating gene expression domain and distinguishing responsiveness to developmental and environmental cues. Since duplication events amplified the poplar AQP family, we addressed the question of expression redundancy between gene duplicates. On these purposes, we carried a meta-analysis of all publicly available Affymetrix experiments. Our in-silico strategy controlled for previously identified biases in cross-species transcriptomics, a necessary step for any comparative transcriptomics based on multispecies design chips. Three poplar AQPs were not supported by any expression data, even in a large collection of situations (abiotic and biotic constraints, temporal oscillations and mutants). The expression of 11 AQPs was never or poorly regulated whatever the wideness of their expression domain and their expression level. Our work highlighted that PtTIP1;4 was the most responsive gene of the AQP family. A high functional divergence between gene duplicates was detected across species and in response to tested cues, except for the root-expressed PtTIP2;3/PtTIP2;4 pair exhibiting 80% convergent responses. Our meta-analysis assessed key features of aquaporin expression which had remained hidden in single experiments, such as expression wideness, response specificity and genotype and environment interactions. By consolidating expression profiles using independent experimental series, we showed that the large expansion of AQP family in poplar was accompanied with a strong divergence of gene expression, even if some cases of functional redundancy

  14. Developmental regulation of the gene for chimeric calcium/calmodulin-dependent protein kinase in anthers

    NASA Technical Reports Server (NTRS)

    Poovaiah, B. W.; Xia, M.; Liu, Z.; Wang, W.; Yang, T.; Sathyanarayanan, P. V.; Franceschi, V. R.

    1999-01-01

    Chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) was cloned from developing anthers of lily (Lilium longiflorum Thumb. cv. Nellie White) and tobacco (Nicotiana tabacum L. cv. Xanthi). Previous biochemical characterization and structure/function studies had revealed that CCaMK has dual modes of regulation by Ca(2+) and Ca(2+)/calmodulin. The unique structural features of CCaMK include a catalytic domain, a calmodulin-binding domain, and a neural visinin-like Ca(2+)-binding domain. The existence of these three features in a single polypeptide distinguishes it from other kinases. Western analysis revealed that CCaMK is expressed in a stage-specific manner in developing anthers. Expression of CCaMK was first detected in pollen mother cells and continued to increase, reaching a peak around the tetrad stage of meiosis. Following microsporogenesis, CCaMK expression rapidly decreased and at later stages of microspore development, no expression was detected. A tobacco genomic clone of CCaMK was isolated and transgenic tobacco plants were produced carrying the CCaMK promoter fused to the beta-glucuronidase reporter gene. Both CCaMK mRNA and protein were detected in the pollen sac and their localizations were restricted to the pollen mother cells and tapetal cells. Consistent results showing a stage-specific expression pattern were obtained by beta-glucuronidase analysis, in-situ hybridization and immunolocalization. The stage- and tissue-specific appearance of CCaMK in anthers suggests that it could play a role in sensing transient changes in free Ca(2+) concentration in target cells, thereby controlling developmental events in the anther.

  15. Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

    PubMed Central

    Hall, F. Scott; Perona, Maria T. G.

    2012-01-01

    This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

  16. Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

    PubMed

    Hall, F Scott; Perona, Maria T G

    2012-12-01

    This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that is determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

  17. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements

    PubMed Central

    Maliszewska-Olejniczak, Kamila; Gruchota, Julita; Gromadka, Robert; Denby Wilkes, Cyril; Arnaiz, Olivier; Mathy, Nathalie; Duharcourt, Sandra; Bétermier, Mireille; Nowak, Jacek K.

    2015-01-01

    Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for

  18. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements.

    PubMed

    Maliszewska-Olejniczak, Kamila; Gruchota, Julita; Gromadka, Robert; Denby Wilkes, Cyril; Arnaiz, Olivier; Mathy, Nathalie; Duharcourt, Sandra; Bétermier, Mireille; Nowak, Jacek K

    2015-07-01

    Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for

  19. Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

    PubMed

    van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

    2014-01-01

    Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family. PMID:24259184

  20. Developmental Progression of the Coronary Vasculature in Human Embryos and Fetuses.

    PubMed

    Tomanek, Robert J

    2016-01-01

    Although considerable advances in our understanding of mammalian and avian embryonic coronary development have occurred during the last decade, our current knowledge of this topic in humans is limited. Accordingly, the aim of this study was to determine if the development of the human coronary vasculature in humans is like that of other mammals and avians. The data document a progression of events involving mesenchymal cell-containing villi from the proepicardium, establishment of blood islands and a capillary network. The major finding of the study is direct evidence that the capillary plexus associated with spindle cells and erythroblasts invades the base of the aorta to form coronary ostia. A role for the dorsal mesocardium is also indicated by the finding that cells from this region are continuous with the aorta and pulmonary artery. The development of the tunica media of the coronary arteries follows the same base-apex progression as in other species, with the development of branches occurring late in the embryonic period. The fetal period is characterized by 1) growth and a numerical increase in the smallest arterial branches, veins, and venules, 2) innervation of arteries, and 3) inclusion of elastic fibers in the tunica media of the coronary arteries and development of the tunica adventitia. In conclusion, the data demonstrate that the development of the coronary system in humans is similar to that of other mammalian and avian species, and for the first time documents that the formation of the ostia and coronary stems in humans occurs by ingrowth of a vascular plexus and associated cells from the epicardium. PMID:26475042

  1. Assessment of Reproductive and Developmental Toxicity of Mixtures of Regulated Drinking Water Chlorination By-Products in a Multigenerational Rat Bioassay

    EPA Science Inventory

    Epidemiological and animal toxicity studies have raised concerns regarding possible adverse reproductive and developmental effects of disinfection by-products (DBPs) in drinking water. To address these concerns, we provided mixtures of the regulated trihalomethanes (THMs; chlorof...

  2. Developmental consequences of early parenting experiences: self-recognition and self-regulation in three cultural communities.

    PubMed

    Keller, Heidi; Yovsi, Relindis; Borke, Joern; Kärtner, Joscha; Jensen, Henning; Papaligoura, Zaira

    2004-01-01

    This study relates parenting of 3-month-old children to children's self-recognition and self-regulation at 18 to 20 months. As hypothesized, observational data revealed differences in the sociocultural orientations of the 3 cultural samples' parenting styles and in toddlers' development of self-recognition and self-regulation. Children of Cameroonian Nso farmers who experience a proximal parenting style develop self-regulation earlier, children of Greek urban middle-class families who experience a distal parenting style develop self-recognition earlier, and children of Costa Rican middle-class families who experience aspects of both distal and proximal parenting styles fall between the other 2 groups on both self-regulation and self-recognition. Results are discussed with respect to their implications for culturally informed developmental pathways. PMID:15566377

  3. Developmental regulation of myeloerythroid progenitor function by the Lin28b-let-7-Hmga2 axis.

    PubMed

    Rowe, R Grant; Wang, Leo D; Coma, Silvia; Han, Areum; Mathieu, Ronald; Pearson, Daniel S; Ross, Samantha; Sousa, Patricia; Nguyen, Phi T; Rodriguez, Antony; Wagers, Amy J; Daley, George Q

    2016-07-25

    For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development. PMID:27401346

  4. Beckwith-Wiedemann and Silver-Russell syndromes: opposite developmental imbalances in imprinted regulators of placental function and embryonic growth.

    PubMed

    Jacob, K J; Robinson, W P; Lefebvre, L

    2013-10-01

    Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two congenital disorders with opposite outcomes on fetal growth, overgrowth and growth restriction, respectively. Although both disorders are heterogeneous, most cases of BWS and SRS are associated with opposite epigenetic or genetic abnormalities on 11p15.5 leading to opposite imbalances in the expression levels of imprinted genes. In this article, we review evidence implicating these genes in the developmental regulation of embryonic growth and placental function in mouse models. The emerging picture suggests that both SRS and BWS can be caused by the simultaneous and opposite deregulation of two groups of imprinted genes on 11p15.5. A detailed description of the phenotypic abnormalities associated with each syndrome must take into consideration the developmental functions of each gene involved. PMID:23495910

  5. Developmentally-regulated sodium channel subunits are differentially sensitive to {alpha}-cyano containing pyrethroids

    SciTech Connect

    Meacham, Connie A.; Brodfuehrer, Peter D.; Watkins, Jennifer A.; Shafer, Timothy J.

    2008-09-15

    Juvenile rats have been reported to be more sensitive to the acute neurotoxic effects of the pyrethroid deltamethrin than adults. While toxicokinetic differences between juveniles and adults are documented, toxicodynamic differences have not been examined. Voltage-gated sodium channels, the primary targets of pyrethroids, are comprised of {alpha} and {beta} subunits, each of which have multiple isoforms that are expressed in a developmentally-regulated manner. To begin to test whether toxicodynamic differences could contribute to age-dependent deltamethrin toxicity, deltamethrin effects were examined on sodium currents in Xenopus laevis oocytes injected with different combinations of rat {alpha} (Na{sub v}1.2 or Na{sub v}1.3) and {beta} ({beta}{sub 1} or {beta}{sub 3}) subunits. Deltamethrin induced tail currents in all isoform combinations and increased the percent of modified channels in a concentration-dependent manner. Effects of deltamethrin were dependent on subunit combination; Na{sub v}1.3-containing channels were modified to a greater extent than were Na{sub v}1.2-containing channels. In the presence of a {beta} subunit, deltamethrin effects were significantly greater, an effect most pronounced for Na{sub v}1.3 channels; Na{sub v}1.3/{beta}{sub 3} channels were more sensitive to deltamethrin than Na{sub v}1.2/{beta}{sub 1} channels. Na{sub v}1.3/{beta}{sub 3} channels are expressed embryonically, while the Na{sub v}1.2 and {beta}{sub 1} subunits predominate in adults, supporting the hypothesis for age-dependent toxicodynamic differences. Structure-activity relationships for sensitivity of these subunit combinations were examined for other pyrethroids. Permethrin and tetramethrin did not modify currents mediated by either subunit combination. Cypermethrin, {beta}-cyfluthrin, esfenvalerate and fenpropathrin all modified sodium channel function; effects were significantly greater on Na{sub v}1.3/{beta}{sub 3} than on Na{sub v}1.2/{beta}{sub 1} channels. These

  6. HEB associates with PRC2 and SMAD2/3 to regulate developmental fates.

    PubMed

    Yoon, Se-Jin; Foley, Joseph W; Baker, Julie C

    2015-01-01

    In embryonic stem cells, extracellular signals are required to derepress developmental promoters to drive lineage specification, but the proteins involved in connecting extrinsic cues to relaxation of chromatin remain unknown. We demonstrate that the helix-loop-helix (HLH) protein, HEB, directly associates with the Polycomb repressive complex 2 (PRC2) at a subset of developmental promoters, including at genes involved in mesoderm and endoderm specification and at the Hox and Fox gene families. While we show that depletion of HEB does not affect mouse ESCs, it does cause premature differentiation after exposure to Activin. Further, we find that HEB deposition at developmental promoters is dependent upon PRC2 and independent of Nodal, whereas HEB association with SMAD2/3 elements is dependent of Nodal, but independent of PRC2. We suggest that HEB is a fundamental link between Nodal signalling, the derepression of a specific class of poised promoters during differentiation, and lineage specification in mouse ESCs. PMID:25775035

  7. Developmental change in the neurophysiological correlates of self-regulation in high- and low-emotion conditions

    PubMed Central

    Lamm, Connie; Lewis, Marc D.

    2010-01-01

    One of the most important tasks of childhood is learning to self-regulate in the presence of negative emotions. Until recently, almost no research has examined the neurophysiological correlates of emotional self-regulation as it develops over childhood and adolescence. We were interested in plotting a fine-grained developmental profile of the neural underpinnings of self-regulation, in the context of negative emotion, for 7- to 14-year-old children. We predicted that children would recruit less cortical activation with age in the service of self-regulation, reflecting increased neural efficiency with development. We also predicted that children would recruit more cortical activation with increased negative emotion, possibly reflecting greater demand on cortical resources. We administered a go/nogo task with an emotion induction block and we measured the amplitude of the N2, an event-related potential associated with inhibitory control, as it varied with block and with age. Furthermore, we estimated activation for a ventral prefrontal region of interest (ROI; suggestive of orbital frontal, ventromedial prefrontal, or rostral anterior cingulate activation) and a dorsomedial prefrontal ROI (suggestive of dorsal anterior cingulate activation) frequently modeled as cortical generators underlying the N2. Results revealed a marginal decrease in mediofrontal scalp activation, but a more pronounced decrease in activation of the ventromedial prefrontal ROI, with age. There were no age-related changes in dorsomedial prefrontal ROI activation. Lastly, as predicted, we found increased ventral prefrontal ROI activation during the negative emotion induction, possibly reflecting greater recruitment of frontocortical resources underlying emotion regulation, but developmental change in this activation was no different than for the other conditions. Thus, both self-regulation in general and emotion regulation in particular recruited less cortical activation with age, suggesting more

  8. Developmental Regulation of a Plasma Membrane Arabinogalactan Protein Epitope in Oilseed Rape Flowers.

    PubMed Central

    Pennell, RI; Janniche, L; Kjellbom, P; Scofield, GN; Peart, JM; Roberts, K

    1991-01-01

    We have identified and characterized the temporal and spatial regulation of a plasma membrane arabinogalactan protein epitope during development of the aerial parts of oilseed rape using the monoclonal antibody JIM8. The JIM8 epitope is expressed by the first cells of the embryo and by certain cells in the sexual organs of flowers. During embryogenesis, the JIM8 epitope ceases to be expressed by the embryo proper but is still found in the suspensor. During differentiation of the stamens and carpels, expression of the JIM8 epitope progresses from one cell type to another, ultimately specifying the endothecium and sperm cells, the nucellar epidermis, synergid cells, and the egg cell. This complex temporal sequence demonstrates rapid turnover of the JIM8 epitope. There is no direct evidence for any cell-inductive process in plant development. However, if cell-cell interactions exist in plants and participate in flower development, the JIM8 epitope may be a marker for one set of them. PMID:12324592

  9. Will new disposal regulations undo decades of progress?

    SciTech Connect

    Ward, J.

    2009-07-01

    In 1980, the Belville Amendments to RCRA instructed EPA to 'conduct a detailed and comprehensive study and submit a report' to Congress on the 'adverse effects on human health and the environment, if any, of the disposal and utilization' of coal ash. In both 1988 and 1999, EPA submitted reports to Congress and recommended coal ash should not be regulated as hazardous waste. After the failure of a Tennesse power plant's coal ash disposal facility, EPA will be proposing new disposal regulations.

  10. Developmental regulation of protein kinase-A and -C activities in the baboon fetal adrenal.

    PubMed

    Davies, W A; Berghorn, K A; Albrecht, E D; Pepe, G J

    1993-06-01

    We have previously demonstrated that the estrogen-regulated change in transuteroplacental metabolism of cortisol (F) and cortisone (E) from preferential reduction (E to F) at midgestation to oxidation (F to E) near term results in activation of the hypothalamic-pituitary-adrenal axis of the baboon and the ontogenesis of rate-limiting steroidogenic enzymes, culminating in de novo F secretion. It is well established that transcription of messages activated by peptide-mediated binding to membrane receptors can occur via cAMP-dependent protein kinase-A (PKA) and/or phospholipid/calcium-dependent protein kinase-C (PKC). The present study was designed to determine whether basal levels of PKA and PKC in the fetal adrenal are developmentally regulated during baboon gestation and, thus, could provide the mechanism(s) by which activation of the fetal adrenal near term is mediated. Fetal adrenal glands were obtained on day 100 (n = 8) and day 165 (n = 6) of gestation (term = day 184) from untreated baboons and on day 100 after treatment of the mother with estradiol benzoate, injected sc between days 70-100 to increase estrogen production. PKA activity (picomoles of 32P incorporated into kemptide per min/mg protein) was determined by incubation of adrenal cytosol (12,000 x g; 0.3-30 micrograms protein) in reaction mixtures containing 0.25 mM ATP, 1 x 10(6) dpm [lambda-32P]ATP, and 3 micrograms kemptide in the presence or absence of 0.02 mM cAMP. PKC activity (picomoles of 32P incorporated into histone IIIS per min/mg protein) was determined in cytosol (105,000 x g) and detergent-solubilized membrane fractions after incubation with 0.02 mM ATP, 50 micrograms histone IIIS, and 1 x 10(6) dpm [lambda-32P]ATP in the presence or absence of calcium and phospholipids. Mean (+/- SE) maternal serum estradiol concentrations (nanograms per ml) were 3-fold greater (P < 0.05) at term (1.9 +/- 0.3) than at midgestation and increased (P < 0.05) after treatment with estradiol. PKA activity was

  11. Emerging roles of long non-coding RNA in root developmental plasticity and regulation of phosphate homeostasis

    PubMed Central

    Bazin, Jeremie; Bailey-Serres, Julia

    2015-01-01

    Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression in a variety of biological process and in multiple species. In plants, they are transcribed by different RNA polymerases and show diverse structural features. With the aid of next-generation sequencing technologies, a large number of lncRNA have been identified in model plants as well as in crops. This review focuses on the demonstration that lncRNAs control root system architecture, notably in response to phosphate availability, through regulation of transcription, alternative splicing, microRNA activity, messenger RNA stability and translation, illustrating remarkable diversity in their roles in regulating developmental plasticity. PMID:26106399

  12. DEVELOPMENTAL REGULATION OF PROTEIN KINASE B ACTIVATION IS ISOFORM SPECIFIC IN SKELETAL MUSCLE OF NEONATAL PIGS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The postprandial activation of the insulin signaling pathway that leads to translation initiation is enhanced in skeletal muscle of the neonate and decreases with development in parallel with the developmental decline in muscle protein synthesis. Our previous study showed that the activity of protei...

  13. Regulation of prostate cancer progression by the tumor microenvironment.

    PubMed

    Shiao, Stephen L; Chu, Gina Chia-Yi; Chung, Leland W K

    2016-09-28

    Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. PMID:26828013

  14. Regulation of polyamine synthesis in plants. Annual progress report

    SciTech Connect

    Malmberg, R.L.

    1993-02-09

    Polyamines are small positively charged compounds that have been hypothesized to be involved in a wide variety of plant physiological and development functions. The regulation of the polyamine synthesis pathway is uniquely interesting because of the existence of two pathways to putrescine synthesis, and the consequent questions of how these two pathways are compartmentalized and how they interact with each other. The specific directions our research is taking are: (1) A characterization of arginine decarboxylase regulation; we have discovered two post-translational mechanisms for regulating arginine decarboxylase activity. One of these is a novel protease that clips the arginine decarboxylase pre-protein to activate it. We would like to understand this activating protease better, determine its mechanism of action, and determine its importance in the overall scheme of arginine decarboxylase regulation. (2) We have begun a similar characterization of ornithine decarboxylase by purifying it from plants. (3) We are characterizing the polyamine mutant collection we have developed. (4) Finally, we have begun to characterize the evolution of arginine decarboxylase, as an additional approach that could shed light on its functions in plants. Our intent is to understand arginine decarboxylase structure and regulation in detail, and then to further explore regulatory differences between ornithine and arginine decarboxylases.

  15. Chromatin remodelling and antisense-mediated up-regulation of the developmental switch gene eud-1 control predatory feeding plasticity.

    PubMed

    Serobyan, Vahan; Xiao, Hua; Namdeo, Suryesh; Rödelsperger, Christian; Sieriebriennikov, Bogdan; Witte, Hanh; Röseler, Waltraud; Sommer, Ralf J

    2016-01-01

    Phenotypic plasticity has been suggested to act through developmental switches, but little is known about associated molecular mechanisms. In the nematode Pristionchus pacificus, the sulfatase eud-1 was identified as part of a developmental switch controlling mouth-form plasticity governing a predatory versus bacteriovorous mouth-form decision. Here we show that mutations in the conserved histone-acetyltransferase Ppa-lsy-12 and the methyl-binding-protein Ppa-mbd-2 mimic the eud-1 phenotype, resulting in the absence of one mouth-form. Mutations in both genes cause histone modification defects and reduced eud-1 expression. Surprisingly, Ppa-lsy-12 mutants also result in the down-regulation of an antisense-eud-1 RNA. eud-1 and antisense-eud-1 are co-expressed and further experiments suggest that antisense-eud-1 acts through eud-1 itself. Indeed, overexpression of the antisense-eud-1 RNA increases the eud-1-sensitive mouth-form and extends eud-1 expression. In contrast, this effect is absent in eud-1 mutants indicating that antisense-eud-1 positively regulates eud-1. Thus, chromatin remodelling and antisense-mediated up-regulation of eud-1 control feeding plasticity in Pristionchus. PMID:27487725

  16. Chromatin remodelling and antisense-mediated up-regulation of the developmental switch gene eud-1 control predatory feeding plasticity

    PubMed Central

    Serobyan, Vahan; Xiao, Hua; Namdeo, Suryesh; Rödelsperger, Christian; Sieriebriennikov, Bogdan; Witte, Hanh; Röseler, Waltraud; Sommer, Ralf J.

    2016-01-01

    Phenotypic plasticity has been suggested to act through developmental switches, but little is known about associated molecular mechanisms. In the nematode Pristionchus pacificus, the sulfatase eud-1 was identified as part of a developmental switch controlling mouth-form plasticity governing a predatory versus bacteriovorous mouth-form decision. Here we show that mutations in the conserved histone-acetyltransferase Ppa-lsy-12 and the methyl-binding-protein Ppa-mbd-2 mimic the eud-1 phenotype, resulting in the absence of one mouth-form. Mutations in both genes cause histone modification defects and reduced eud-1 expression. Surprisingly, Ppa-lsy-12 mutants also result in the down-regulation of an antisense-eud-1 RNA. eud-1 and antisense-eud-1 are co-expressed and further experiments suggest that antisense-eud-1 acts through eud-1 itself. Indeed, overexpression of the antisense-eud-1 RNA increases the eud-1-sensitive mouth-form and extends eud-1 expression. In contrast, this effect is absent in eud-1 mutants indicating that antisense-eud-1 positively regulates eud-1. Thus, chromatin remodelling and antisense-mediated up-regulation of eud-1 control feeding plasticity in Pristionchus. PMID:27487725

  17. Improving child self-regulation and parenting in families of pre-kindergarten children with developmental disabilities and behavioral difficulties.

    PubMed

    Pears, Katherine C; Kim, Hyoun K; Healey, Cynthia V; Yoerger, Karen; Fisher, Philip A

    2015-02-01

    The transition to school may be particularly difficult for children with developmental disabilities and behavioral difficulties. Such children are likely to experience problems with self-regulation skills, which are critical to school adjustment. Additionally, inconsistent discipline practices and low parental involvement in children's schooling may contribute to a poor transition to school. This study employed a randomized clinical trial to examine the effects of a school readiness intervention that focused on children's self-regulation skills as well as parenting and parental involvement in school. Results showed that the intervention had positive effects on children's self-regulation in kindergarten as measured by teacher and observer reports. Additionally, the intervention significantly reduced ineffective parenting prior to school entry, which in turn affected parental involvement. This finding is significant because it demonstrates that parental involvement in school may be increased by efforts to improve parenting skills in general. Overall, the study demonstrated that school adjustment across kindergarten among children with developmental disabilities and behavioral difficulties can be enhanced through an intervention aimed specifically at improving school readiness skills. PMID:24676874

  18. The Role of pH Regulation in Cancer Progression.

    PubMed

    McIntyre, Alan; Harris, Adrian L

    2016-01-01

    Frequently observed phenotypes of tumours include high metabolic activity, hypoxia and poor perfusion; these act to produce an acidic microenvironment. Cellular function depends on pH homoeostasis, and thus, tumours become dependent on pH regulatory mechanisms. Many of the proteins involved in pH regulation are highly expressed in tumours, and their expression is often of prognostic significance. The more acidic tumour microenvironment also has important implications with regard to chemotherapeutic and radiotherapeutic interventions. In addition, we review pH-sensing mechanisms, the role of pH regulation in tumour phenotype and the use of pH regulatory mechanisms as therapeutic targets. PMID:27557536

  19. A role for pectin de-methylesterification in a developmentally regulated growth acceleration in dark-grown Arabidopsis hypocotyls.

    PubMed

    Pelletier, Sandra; Van Orden, Jürgen; Wolf, Sebastian; Vissenberg, Kris; Delacourt, Julien; Ndong, Yves Assoumou; Pelloux, Jérôme; Bischoff, Volker; Urbain, Aurélie; Mouille, Grégory; Lemonnier, Gaëtan; Renou, Jean-Pierre; Höfte, Herman

    2010-11-01

    • We focused on a developmentally regulated growth acceleration in the dark-grown Arabidopsis hypocotyl to study the role of changes in cell wall metabolism in the control of cell elongation. • To this end, precise transcriptome analysis on dissected dark-grown hypocotyls, Fourier transform infrared (FT-IR) microspectroscopy and kinematic analysis were used. • Using a cellulose synthesis inhibitor, we showed that the growth acceleration marks a developmental transition during which growth becomes uncoupled from cellulose synthesis. We next investigated the cellular changes that take place during this transition. FT-IR microspectroscopy revealed significant changes in cell wall composition during, but not after, the growth acceleration. Transcriptome analysis suggested a role for cell wall remodeling, in particular pectin modification, in this growth acceleration. This was confirmed by the overexpression of a pectin methylesterase inhibitor, which caused a delay in the growth acceleration. • This study shows that the acceleration of cell elongation marks a developmental transition in dark-grown hypocotyl cells and supports a role for pectin de-methylesterification in the timing of this event. PMID:20819179

  20. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. PMID:26844865

  1. The Opposing Forces that Shape Developmental Education: Assessment, Placement, and Progression at CUNY Community Colleges. CCRC Working Paper No. 36

    ERIC Educational Resources Information Center

    Jaggars, Shanna Smith; Hodara, Michelle

    2011-01-01

    The developmental education process, as it is typically implemented in colleges across the country, seems straightforward: underprepared students are assessed and placed into an appropriate developmental course sequence designed to prepare them for college-level work; once finished with the sequence, these students presumably then move on to…

  2. The Retention, Success, and Progress Rates of Rural Females in Traditional Lecture and Online Developmental Mathematics Courses

    ERIC Educational Resources Information Center

    Lynch-Newberg, Stacie A.

    2010-01-01

    Currently, 92% of community colleges offer courses online, yet only 13% offer online mathematics developmental courses. Little research has been conducted to verify the effectiveness of such courses. This study attempted to answer: Are online developmental mathematics courses addressing the academic requirements (retention, success, and…

  3. Regulation of cancer progression by β-endorphin neuron.

    PubMed

    Sarkar, Dipak K; Murugan, Sengottuvelan; Zhang, Changqing; Boyadjieva, Nadka

    2012-02-15

    It is becoming increasingly clear that stressful life events can affect cancer growth and metastasis by modulating nervous, endocrine, and immune systems. The purpose of this review is to briefly describe the process by which stress may potentiate carcinogenesis and how reducing body stress may prevent cancer growth and progression. The opioid peptide β-endorphin plays a critical role in bringing the stress axis to a state of homeostasis. We have recently shown that enhancement of endogenous levels of β-endorphin in the hypothalamus via β-endorphin neuron transplantation suppresses stress response, promotes immune function, and reduces the incidence of cancer in rat models of prostate and breast cancers. The cancer-preventive effect of β-endorphin is mediated through the suppression of sympathetic neuronal function, which results in increased peripheral natural killer cell and macrophage activities, elevated levels of anti-inflammatory cytokines, and reduced levels of inflammatory cytokines. β-endorphin inhibition of tumor progression also involves alteration in the tumor microenvironment, possibly because of suppression of catecholamine and inflammatory cytokine production, which are known to alter DNA repair, cell-matrix attachments, angiogenic process, and epithelial-mesenchymal transition. Thus, β-endorphin cell therapy may offer some therapeutic value in cancer prevention. PMID:22287549

  4. Parental Influences on Children's Self-Regulation of Energy Intake: Insights from Developmental Literature on Emotion Regulation

    PubMed Central

    Frankel, Leslie A.; Hughes, Sheryl O.; O'Connor, Teresia M.; Power, Thomas G.; Fisher, Jennifer O.; Hazen, Nancy L.

    2012-01-01

    The following article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to children's behavior, assistance in helping children self-regulate, and motivating children through rewards and punishments. Additionally, sources of variation in parental influences on regulation are examined, including parenting style, child temperament, and child-parent attachment security. Parallels in the nature of parents' role in socializing children's regulation of emotions and energy intake are examined. Implications for future research are discussed. PMID:22545206

  5. TRAIP regulates replication fork recovery and progression via PCNA

    PubMed Central

    Feng, Wanjuan; Guo, Yingying; Huang, Jun; Deng, Yiqun; Zang, Jianye; Huen, Michael Shing-Yan

    2016-01-01

    PCNA is a central scaffold that coordinately assembles replication and repair machineries at DNA replication forks for faithful genome duplication. Here, we describe TRAIP (RNF206) as a novel PCNA-interacting factor that has important roles during mammalian replicative stress responses. We show that TRAIP encodes a nucleolar protein that migrates to stalled replication forks, and that this is accomplished by its targeting of PCNA via an evolutionarily conserved PIP box on its C terminus. Accordingly, inactivation of TRAIP or its interaction with the PCNA clamp compromised replication fork recovery and progression, and leads to chromosome instability. Together, our findings establish TRAIP as a component of the mammalian replicative stress response network, and implicate the TRAIP-PCNA axis in recovery of stalled replication forks. PMID:27462463

  6. Regulation of mitotic progression by the spindle assembly checkpoint

    PubMed Central

    Lischetti, Tiziana; Nilsson, Jakob

    2015-01-01

    Equal segregation of sister chromatids during mitosis requires that pairs of kinetochores establish proper attachment to microtubules emanating from opposite poles of the mitotic spindle. The spindle assembly checkpoint (SAC) protects against errors in segregation by delaying sister separation in response to improper kinetochore–microtubule interactions, and certain checkpoint proteins help to establish proper attachments. Anaphase entry is inhibited by the checkpoint through assembly of the mitotic checkpoint complex (MCC) composed of the 2 checkpoint proteins, Mad2 and BubR1, bound to Cdc20. The outer kinetochore acts as a catalyst for MCC production through the recruitment and proper positioning of checkpoint proteins and recently there has been remarkable progress in understanding how this is achieved. Here, we highlight recent advances in our understanding of kinetochore–checkpoint protein interactions and inhibition of the anaphase promoting complex by the MCC. PMID:27308407

  7. Honey bee (Apis mellifera) transferrin-gene structure and the role of ecdysteroids in the developmental regulation of its expression.

    PubMed

    do Nascimento, Adriana Mendes; Cuvillier-Hot, Virginie; Barchuk, Angel Roberto; Simões, Zilá Luz Paulino; Hartfelder, Klaus

    2004-05-01

    Social life is prone to invasion by microorganisms, and binding of ferric ions by transferrin is an efficient strategy to restrict their access to iron. In this study, we isolated cDNA and genomic clones encoding an Apis mellifera transferrin (AmTRF) gene. It has an open reading frame (ORF) of 2136 bp spread over nine exons. The deduced protein sequence comprises 686 amino acid residues plus a 26 residues signal sequence, giving a predicted molecular mass of 76 kDa. Comparison of the deduced AmTRF amino acid sequence with known insect transferrins revealed significant similarity extending over the entire sequence. It clusters with monoferric transferrins, with which it shares putative iron-binding residues in the N-terminal lobe. In a functional analysis of AmTRF expression in honey bee development, we monitored its expression profile in the larval and pupal stages. The negative regulation of AmTRF by ecdysteroids deduced from the developmental expression profile was confirmed by experimental treatment of spinning-stage honey bee larvae with 20-hydroxyecdysone, and of fourth instar-larvae with juvenile hormone. A juvenile hormone application to spinning-stage larvae, in contrast, had only a minor effect on AmTRF transcript levels. This is the first study implicating ecdysteroids in the developmental regulation of transferrin expression in an insect species. PMID:15110862

  8. Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

    PubMed

    Kaneko, Y; Kimura, T; Nishiyama, H; Noda, Y; Fujita, J

    1997-04-01

    Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells. PMID:9144406

  9. daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans.

    PubMed

    Antebi, A; Yeh, W H; Tait, D; Hedgecock, E M; Riddle, D L

    2000-06-15

    The daf-12 gene acts at the convergence of pathways regulating larval diapause, developmental age, and adult longevity in Caenorhabditis elegans. It encodes a nuclear receptor most closely related to two C. elegans receptors, NHR-8 and NHR-48, Drosophila DHR96, and vertebrate vitamin D and pregnane-X receptors. daf-12 has three predicted protein isoforms, two of which contain DNA- and ligand-binding domains, and one of which contains the ligand-binding domain only. Mutations cluster in DNA- and ligand-binding domains, but correspond to distinct phenotypic classes. DAF-12 is expressed widely in target tissues from embryo to adult, but is upregulated during midlarval stages. In the adult, expression persists in nervous system and somatic gonad, two tissues that regulate adult longevity. We propose that DAF-12 integrates hormonal signals in cellular targets to coordinate major life history traits. PMID:10859169

  10. [Research progress on phosphorus budgets and regulations in reservoirs].

    PubMed

    Shen, Xiao; Li, Xu; Zhang, Wang-shou

    2014-12-01

    Phosphorus is an important limiting factor of water eutrophication. A clear understanding of its budget and regulated method is fundamental for reservoir ecological health. In order to pro- mote systematic research further and improve phosphorus regulation system, the budget balance of reservoir phosphorus and its influencing factors were concluded, as well as conventional regulation and control measures. In general, the main phosphorus sources of reservoirs include upstream input, overland runoff, industrial and domestic wastewater, aquaculture, atmospheric deposition and sediment release. Upstream input is the largest phosphorus source among them. The principal output path of phosphorus is the flood discharge, the emission load of which is mainly influenced by drainage patterns. In addition, biological harvest also can export a fraction of phosphorus. There are some factors affecting the reservoir phosphorus balance, including reservoirs' function, hydrological conditions, physical and chemical properties of water, etc. Therefore, the phosphorus budgets of different reservoirs vary greatly, according to different seasons and regions. In order to reduce the phosphorus loading in reservoirs, some methods are carried out, including constructed wetlands, prefix reservoir, sediment dredging, biomanipulation, etc. Different methods need to be chosen and combined according to different reservoirs' characteristics and water quality management goals. Thus, in the future research, it is reasonable to highlight reservoir ecological characteristics and proceed to a complete and systematic analysis of the inherent complexity of phosphorus budget and its impact factors for the reservoirs' management. Besides, the interaction between phosphorus budget and other nutrients in reservoirs also needs to be conducted. It is fundamental to reduce the reservoirs' phosphorus loading to establish a scientific and improved management system based on those researches. PMID:25876422

  11. MUC1 Regulates PDGFA Expression During Pancreatic Cancer Progression

    PubMed Central

    Sahraei, Mahnaz; Roy, Lopamudra Das; Curry, Jennifer M; Teresa, Tinder L; Nath, Sritama; Besmer, Dahlia; Kidiyoor, Amritha; Dalia, Ritu; Gendler, Sandra J; Mukherjee, Pinku

    2012-01-01

    Pancreatic Ductal Adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility, and metastasis. Its expression is known to be associated with poor prognosis in patients. However, the precise mechanism remains elusive. We report a novel association of MUC1 with Platelet-Derived Growth Factor-A (PDGFA). PDGFA is one of the many drivers of tumor growth, angiogenesis, and metastasis in PDA. Using mouse PDA models as well as human samples, we show clear evidence that MUC1 regulates the expression and secretion of PDGFA. This, in turn, influences proliferation and invasion of pancreatic cancer cells leading to higher tumor burden in vivo. In addition, we reveal that MUC1 over expressing cells are heavily dependent on PDGFA both for proliferation and invasion while MUC1-null cells are not. Moreover, PDGFA and MUC1 are critical for translocation of βcatenin to the nucleus for oncogenesis to ensue. Finally, we elucidate the underlying mechanism by which MUC1 regulates PDGFA expression and secretion in pancreatic cancer cells. We show that MUC1 associates with Hif1-α, a known transcription factor involved in controlling PDGFA expression. Furthermore, MUC1 facilitates Hif1-α translocation to the nucleus. In summary, we have demonstrated that MUC1-induced invasion and proliferation occurs via increased exogenous production of PDGFA. Thus, impeding MUC1 regulation of PDGFA signaling may be therapeutically beneficial for patients with PDA. PMID:22266848

  12. Analysis of splice variants for the C. elegans orthologue of human neuroligin reveals a developmentally regulated transcript.

    PubMed

    Calahorro, Fernando; Holden-Dye, Lindy; O'Connor, Vincent

    2015-03-01

    Neuroligins are synaptic adhesion molecules and important determinants of synaptic function. They are expressed at postsynaptic sites and involved in synaptic organization through key extracellular and intracellular protein interactions. They undergo trans-synaptic interaction with presynaptic neurexins. Distinct neuroligins use differences in their intracellular domains to selectively recruit synaptic scaffolds and this plays an important role in how they encode specialization of synaptic function. Several levels of regulation including gene expression, splicing, protein translation and processing regulate the expression of neuroligin function. We have used in silico and cDNA analyses to investigate the mRNA splicing of the Caenorhabditis elegans orthologue nlg-1. Transcript analysis highlights the potential for gene regulation with respect to both temporal expression and splicing. We found nlg-1 splice variants with all the predicted exons are a minor species relative to major splice variants lacking exons 13 and 14, or 14 alone. These major alternatively spliced variants change the intracellular domain of the gene product NLG-1. Interestingly, exon 14 encodes a cassette with two distinct potential functional domains. One is a polyproline SH3 binding domain and the other has homology to a region encoding the binding site for the scaffolding protein gephyrin in mammalian neuroligins. This suggests differential splicing impacts on NLG-1 competence to recruit intracellular binding partners. This may have developmental relevance as nlg-1 exon 14 containing transcripts are selectively expressed in L2-L3 larvae. These results highlight a developmental regulation of C. elegans nlg-1 that could play a key role in the assembly of synaptic protein complexes during the early stages of nervous system development. PMID:25726726

  13. Challenges to Developmental Regulation across the Life Course: What Are They and Which Individual Differences Matter?

    ERIC Educational Resources Information Center

    Heckhausen, Jutta; Wrosch, Carsten

    2016-01-01

    We discuss the major processes involved in individuals' motivation and self-regulation of goal striving throughout the life course. While much is regulated based on the biological and societal scaffolding of lifespan development, certain challenges for motivation and self-regulation are more substantial and need to be managed by the individual,…

  14. (Regulation of alcohol fermentation by Escherichia coli). Progress report

    SciTech Connect

    Clark, D.P.

    1985-01-01

    Constitutive adhC mutants were used as a starting point for the isolation of further mutants, some of which are defective in alcohol dehydrogenase (ADH) and/or acetaldehyde dehydrogenase (ACDH) activities and some of which are regulatory and express elevated enzyme levels. The structural mutants map close to the adhC gene, suggesting the existence of an anaerobically controlled operon responsible for the conversion of acetyl-CoA to ethanol. Purification of the two enzyme activities indicates that both copurify as a complex of approximately 200,000 daltons. Although confirmation is required, both enzyme activities appear to be functions of a single polypeptide of MW 100,000 daltons. This interpretation is consistent with genetic data which show that most mutants selected directly for loss of either enzyme have also lost the other activity. Temperature sensitive mutants in which both enzymes are thermolabile also support the idea of a single polypeptide for the two activities. Regulatory mutants located away from the adhC locus have been isolated, and result in two to tenfold elevation of both ADH and ACDH. These mutants are in process of further characterization. Study of adh regulation by means of gene fusions has been slowed by technical problems, however we have devised a direct method for the selection of mutants unable to excrete acidic fermentation products and have accumulated a variety of anaerobically regulated gene fusions which have allowed us to estimate that anaerobiosis in E. coli requires the induction of around 50 genes.

  15. Parental influences on children's self-regulation of energy intake: Insights from developmental literature on emotion regulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to childre...

  16. Progression to Impaired Glucose Regulation and Diabetes in the Population-Based Inter99 Study

    PubMed Central

    Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine; Glümer, Charlotte; Jørgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

    2009-01-01

    OBJECTIVE The purpose of this study was to estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population–based Inter99 study and in a high-risk subpopulation, separately. RESEARCH DESIGN AND METHODS From a population-based primary prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity, or impaired glucose tolerance). High-risk individuals (57.1%) were examined with an oral glucose tolerance test at 1 and 3 years, and all of the participants were reexamined at the 5-year follow-up. Person-years at risk were calculated. Progression rates to impaired glucose regulation and diabetes were estimated directly from baseline to the 5-year follow-up for all the participants and from baseline through the 1- and 3- to 5-year follow-up examinations for the high-risk individuals, separately. RESULTS In the combined low- and high-risk group, 2.1 individuals per 100 person-years progressed from normal glucose tolerance (NGT) to impaired glucose regulation or diabetes. Among high-risk individuals, 5.8 per 100 person-years with NGT progressed to impaired glucose regulation or diabetes, and 4.9 per 100 person-years progressed from impaired glucose regulation to diabetes. CONCLUSIONS Progression rates to impaired glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies. PMID:19114617

  17. (Regulation of terpene metabolism). Progress report. [Mentha piperita

    SciTech Connect

    Croteau, R.

    1986-01-01

    Studies on the regulation of monoterpene metabolism in M. piperita were conducted. All of the steps from the acyclic precursor geranyl pyrophosphate to the various menthol isomers have been demonstrated. The first intermediate to accumulate in vivo is d-pulegone. The emphasis has been on the demonstration, partial purification and characterization of the relevant enzymes in the pathway. The studies on the isopiperitenol dehydrogenase and isopiperitenone isomerase have been completed. We are not studying the endocyclic double-bond reductase (NADPH-dependent) and, based on substrate specificity studies and the previously demonstrated isomerization of cis- isopulegone to pulegone, are now virtually convinced that the major pathway to menthol(s) in peppermint involves reduction of isopiperitenone to isopulegone and isomerication of isopulegone to pulegone. 16 refs., 1 fig.

  18. Genome-Wide Ultrabithorax Binding Analysis Reveals Highly Targeted Genomic Loci at Developmental Regulators and a Potential Connection to Polycomb-Mediated Regulation.

    PubMed

    Shlyueva, Daria; Meireles-Filho, Antonio C A; Pagani, Michaela; Stark, Alexander

    2016-01-01

    Hox homeodomain transcription factors are key regulators of animal development. They specify the identity of segments along the anterior-posterior body axis in metazoans by controlling the expression of diverse downstream targets, including transcription factors and signaling pathway components. The Drosophila melanogaster Hox factor Ultrabithorax (Ubx) directs the development of thoracic and abdominal segments and appendages, and loss of Ubx function can lead for example to the transformation of third thoracic segment appendages (e.g. halters) into second thoracic segment appendages (e.g. wings), resulting in a characteristic four-wing phenotype. Here we present a Drosophila melanogaster strain with a V5-epitope tagged Ubx allele, which we employed to obtain a high quality genome-wide map of Ubx binding sites using ChIP-seq. We confirm the sensitivity of the V5 ChIP-seq by recovering 7/8 of well-studied Ubx-dependent cis-regulatory regions. Moreover, we show that Ubx binding is predictive of enhancer activity as suggested by comparison with a genome-scale resource of in vivo tested enhancer candidates. We observed densely clustered Ubx binding sites at 12 extended genomic loci that included ANTP-C, BX-C, Polycomb complex genes, and other regulators and the clustered binding sites were frequently active enhancers. Furthermore, Ubx binding was detected at known Polycomb response elements (PREs) and was associated with significant enrichments of Pc and Pho ChIP signals in contrast to binding sites of other developmental TFs. Together, our results show that Ubx targets developmental regulators via strongly clustered binding sites and allow us to hypothesize that regulation by Ubx might involve Polycomb group proteins to maintain specific regulatory states in cooperative or mutually exclusive fashion, an attractive model that combines two groups of proteins with prominent gene regulatory roles during animal development. PMID:27575958

  19. Genome-Wide Ultrabithorax Binding Analysis Reveals Highly Targeted Genomic Loci at Developmental Regulators and a Potential Connection to Polycomb-Mediated Regulation

    PubMed Central

    Meireles-Filho, Antonio C. A.; Pagani, Michaela; Stark, Alexander

    2016-01-01

    Hox homeodomain transcription factors are key regulators of animal development. They specify the identity of segments along the anterior-posterior body axis in metazoans by controlling the expression of diverse downstream targets, including transcription factors and signaling pathway components. The Drosophila melanogaster Hox factor Ultrabithorax (Ubx) directs the development of thoracic and abdominal segments and appendages, and loss of Ubx function can lead for example to the transformation of third thoracic segment appendages (e.g. halters) into second thoracic segment appendages (e.g. wings), resulting in a characteristic four-wing phenotype. Here we present a Drosophila melanogaster strain with a V5-epitope tagged Ubx allele, which we employed to obtain a high quality genome-wide map of Ubx binding sites using ChIP-seq. We confirm the sensitivity of the V5 ChIP-seq by recovering 7/8 of well-studied Ubx-dependent cis-regulatory regions. Moreover, we show that Ubx binding is predictive of enhancer activity as suggested by comparison with a genome-scale resource of in vivo tested enhancer candidates. We observed densely clustered Ubx binding sites at 12 extended genomic loci that included ANTP-C, BX-C, Polycomb complex genes, and other regulators and the clustered binding sites were frequently active enhancers. Furthermore, Ubx binding was detected at known Polycomb response elements (PREs) and was associated with significant enrichments of Pc and Pho ChIP signals in contrast to binding sites of other developmental TFs. Together, our results show that Ubx targets developmental regulators via strongly clustered binding sites and allow us to hypothesize that regulation by Ubx might involve Polycomb group proteins to maintain specific regulatory states in cooperative or mutually exclusive fashion, an attractive model that combines two groups of proteins with prominent gene regulatory roles during animal development. PMID:27575958

  20. Differential regulation of plastid mRNA stability. Progress report

    SciTech Connect

    Stern, D.B.

    1993-09-01

    Our goal is to identify cis-acting sequences and transacting factors that function in plastid mRNA maturation, stabilization, and/or decay through an in vitro and in vivo analysis of mRNA:protein interactions. Our previous results emphasized the study of 3{prime}end inverted repeat sequences (IRs) that serve both as mRNA processing elements and stability determinants, and associate with plastid proteins that potentially play enzymatic, structural and/or regulatory roles. We seek to define, by single base and internal deletion mutagenesis, the sequence and structural requirements for protein binding to the 3{prime} IRs of petD and psbA mRNAs; to purify RNA-binding proteins that demonstrate gene- or sequence-specific binding, or that are implicated in RNA stabilization or decay; and to investigate the native form of mRNA in the plastid, by attempting to purify ribonucleoprotein (RNP) particles from organelles. Our view of mRNA decay is that it is regulated by three interactive components: RNA structure, ribonucleases and RNA-binding proteins. We have used mutagenesis to study the role of RNA structure in regulating RNA decay rates, and to identify protein binding and endonuclease recognition sites. We have identified at least three endonuclease activities; one that cleaves psbA RNA; and two whose cleavage patterns with petD 3{prime} IR-RNA has been studied (endoC1 and endoC2). Additionally, we have continued to analyze the properties of the major RNA processing exoribonuclease. We have concentrated our efforts on three RNA-binding proteins. A 100 kd protein with properties suggestive of a mammalian RNP component has been purified. A protein of 55 kd that may also be an endonuclease has been partially purified. We have studied the interaction of a 29 kd protein with the petD stem/loop, and its role in RNA processing. Recently, we have used a novel gel shift/SDS-PAGE technique to identify new RNA-binding proteins.

  1. Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission

    PubMed Central

    Akinosoglou, Karolina A; Bushell, Ellen S C; Ukegbu, Chiamaka Valerie; Schlegelmilch, Timm; Cho, Jee-Sun; Redmond, Seth; Sala, Katarzyna; Christophides, George K; Vlachou, Dina

    2015-01-01

    The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midgut of Anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved in developmental processes or in interactions with the mosquito. At least two of these programmes are associated with the ookinete development that is linked to mosquito midgut invasion and establishment of infection. Targeted disruption by homologous recombination of two of these genes resulted in mutant parasites exhibiting notable infection phenotypes. GAMER encodes a short polypeptide with granular localization in the gametocyte cytoplasm and shows a highly penetrant loss-of-function phenotype manifested as greatly reduced ookinete numbers, linked to impaired male gamete release. HADO encodes a putative magnesium phosphatase with distinctive cortical localization along the concave ookinete periphery. Disruption of HADO compromises ookinete development leading to significant reduction of oocyst numbers. Our data provide important insights into the molecular framework underpinning Plasmodium development in the mosquito and identifies two genes with important functions at initial stages of parasite development in the mosquito midgut. PMID:25225164

  2. Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

    PubMed

    Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin; Tellides, George; Simons, Michael

    2016-01-01

    The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2α led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high-fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFβ activity, and increased disease severity. These results identify SMC FGF/TGFβ signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth. PMID:27189169

  3. ERRβ splice variants differentially regulate cell cycle progression

    PubMed Central

    Heckler, Mary Mazzotta; Riggins, Rebecca B

    2015-01-01

    Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERRβ splice variants, short form ERRβ (ERRβsf) and ERRβ2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERRβ), splice-variant selective shRNA, and exogenous ERRβsf and ERRβ2 cDNAs, we demonstrate the role of ERRβsf in mediating the G1 checkpoint through p21. We also show ERRβsf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERRβ2 can mediate a G2/M arrest in response to DY131. In the absence of ERRβ2, the DY131-induced G2/M arrest is reversed, and this is accompanied by p21 induction and a G1 arrest. This study illustrates novel functions for ERRβ splice variants and provides evidence for splice variant interaction. PMID:25496115

  4. Estrogen target gene regulation and coactivator expression in rat uterus after developmental exposure to the ultraviolet filter 4-methylbenzylidene camphor.

    PubMed

    Durrer, Stefan; Maerkel, Kirsten; Schlumpf, Margret; Lichtensteiger, Walter

    2005-05-01

    Because the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of nonclassical ER agonists. UV filters from cosmetics represent new classes of endocrine active chemicals, including the preferential ER beta ligands 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor. We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, and 47 mg/kg x d) administered in feed to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. 4-MBC altered steady-state levels of mRNAs encoding for ER alpha, ER beta, progesterone receptor (PR), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-wk-old offspring. Western-blot analyses of the same tissue homogenates indicated changes in ER alpha and PR but not ER beta proteins. To assess sensitivity to estradiol (E2), offspring were ovariectomized on d 70, injected with E2 (10 or 50 microg/kg sc) on d 84, and killed 6 h later. Acute up-regulation of PR and IGF-I and down-regulation of ER alpha and androgen receptor by E2 were dose-dependently reduced in 4-MBC-exposed rats. The reduced response to E2 was accompanied by reduced coactivator SRC-1 mRNA and protein levels. Our data indicate that developmental exposure to 4-MBC affects the regulation of estrogen target genes and the expression of nuclear receptor coregulators in uterus at mRNA and protein levels. PMID:15705771

  5. TORC1 Regulates Developmental Responses to Nitrogen Stress via Regulation of the GATA Transcription Factor Gaf1

    PubMed Central

    Laor, Dana; Cohen, Adiel; Kupiec, Martin

    2015-01-01

    ABSTRACT The TOR (target of rapamycin [sirolimus]) is a universally conserved kinase that couples nutrient availability to cell growth. TOR complex 1 (TORC1) in Schizosaccharomyces pombe positively regulates growth in response to nitrogen availability while suppressing cellular responses to nitrogen stress. Here we report the identification of the GATA transcription factor Gaf1 as a positive regulator of the nitrogen stress-induced gene isp7+, via three canonical GATA motifs. We show that under nitrogen-rich conditions, TORC1 positively regulates the phosphorylation and cytoplasmic retention of Gaf1 via the PP2A-like phosphatase Ppe1. Under nitrogen stress conditions when TORC1 is inactivated, Gaf1 becomes dephosphorylated and enters the nucleus. Gaf1 was recently shown to negatively regulate the transcription induction of ste11+, a major regulator of sexual development. Our findings support a model of a two-faceted role of Gaf1 during nitrogen stress. Gaf1 positively regulates genes that are induced early in the response to nitrogen stress, while inhibiting later responses, such as sexual development. Taking these results together, we identify Gaf1 as a novel target for TORC1 signaling and a step-like mechanism to modulate the nitrogen stress response. PMID:26152587

  6. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    SciTech Connect

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  7. Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos.

    PubMed

    Lindeman, Leif C; Winata, Cecilia L; Aanes, Hvard; Mathavan, Sinnakaruppan; Alestrom, Peter; Collas, Philippe

    2010-01-01

    Embryo development proceeds from a cascade of gene activation and repression events controlled by epigenetic modifications of DNA and histones. Little is known about epigenetic states in the developing zebrafish, despite its importance as a model organism. We report here DNA methylation and histone modification profiles of promoters of developmentally-regulated genes (pou5f1, sox2, sox3, klf4, nnr, otx1b, nes, vasa), as well as tert and bactin2, in zebrafish embryos at the mid-late blastula transition, shortly after embryonic genome activation. We identify four classes of promoters based on the following profiles: (i) those enriched in marks of active genes (H3K9ac, H4ac, H3K4me3) without transcriptionally repressing H3K9me3 or H3K27me3; (ii) those enriched in H3K9ac, H4ac and H3K27me3, without H3K9me3; one such gene was klf4, shown by in situ hybridization to be mosaically expressed, likely accounting for the detection of both activating and repressive marks on its promoter; (iii) those enriched in H3K4me3 and H3K27me3 without acetylation; and (iv) those enriched in all histone modifications examined. Culture of embryo-derived cells under differentiation conditions leads to H3K9 and H4 deacetylation and H3K9 and H3K27 trimethylation on genes that are inactivated, yielding an epigenetic profile similar to those of fibroblasts or muscle. All promoters however retain H3K4me3, indicating an uncoupling of H3K4me3 occupancy and gene expression. All non-CpG island developmentally-regulated promoters are DNA unmethylated in embryos, but hypermethylated in fibroblasts. Our results suggest that differentially expressed embryonic genes are regulated by various patterns of histone modifications on unmethylated DNA, which create a developmentally permissive chromatin state. PMID:20336603

  8. MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother

    PubMed Central

    Alsaweed, Mohammed; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2015-01-01

    Human milk (HM) is the optimal source of nutrition, protection and developmental programming for infants. It is species-specific and consists of various bioactive components, including microRNAs, small non-coding RNAs regulating gene expression at the post-transcriptional level. microRNAs are both intra- and extra-cellular and are present in body fluids of humans and animals. Of these body fluids, HM appears to be one of the richest sources of microRNA, which are highly conserved in its different fractions, with milk cells containing more microRNAs than milk lipids, followed by skim milk. Potential effects of exogenous food-derived microRNAs on gene expression have been demonstrated, together with the stability of milk-derived microRNAs in the gastrointestinal tract. Taken together, these strongly support the notion that milk microRNAs enter the systemic circulation of the HM fed infant and exert tissue-specific immunoprotective and developmental functions. This has initiated intensive research on the origin, fate and functional significance of milk microRNAs. Importantly, recent studies have provided evidence of endogenous synthesis of HM microRNA within the human lactating mammary epithelium. These findings will now form the basis for investigations of the role of microRNA in the epigenetic control of normal and aberrant mammary development, and particularly lactation performance. PMID:26529003

  9. Environmental and Developmental Regulation of the Wound-Induced Cell Wall Protein WI12 in the Halophyte Ice Plant1

    PubMed Central

    Yen, Shyi-Kae; Chung, Mei-Chu; Chen, Pei-Chung; Yen, Hungchen E.

    2001-01-01

    A wounded gene WI12 was used as a marker to examine the interaction between biotic stress (wounding) and abiotic stress (high salt) in the facultative halophyte ice plant (Mesembryanthemum crystallinum). The deduced WI12 amino acid sequence has 68% similarity to WUN1, a known potato (Solanum tuberosum) wound-induced protein. Wounding, methyl jasmonate, and pathogen infection induced local WI12 expression. Upon wounding, the expression of WI12 reached a maximum level after 3 h in 4-week-old juvenile leaves, whereas the maximum expression was after 24 h in 8-week-old adult leaves. The temporal expression of WI12 in salt-stressed juvenile leaves was similar to that of adult leaves. The result suggests that a salt-induced switch from C3 to Crassulacean acid metabolism has a great influence on the ice plant's response to wounding. The expression of WI12 and the accumulation of WI12 protein were constitutively found in phloem and in wounded mesophyll cells. At the reproductive stage, WI12 was constitutively found in petals and styles, and developmentally regulated in the placenta and developing seeds. The histochemical analysis showed that the appearance of WI12 is controlled by both environmental and developmental factors. Immunogold labeling showed WI12 preferentially accumulates in the cell wall, suggesting its role in the reinforcement of cell wall composition after wounding and during plant development. PMID:11598226

  10. Regulation of Melanoma Progression through the TCF4/miR-125b/NEDD9 Cascade.

    PubMed

    Rambow, Florian; Bechadergue, Audrey; Luciani, Flavie; Gros, Gwendoline; Domingues, Melanie; Bonaventure, Jacky; Meurice, Guillaume; Marine, Jean-Christophe; Larue, Lionel

    2016-06-01

    Melanoma progression from a primary lesion to a distant metastasis is a complex process associated with genetic alterations, epigenetic modifications, and phenotypic switches. Elucidation of these phenomena may indicate how to interfere with this fatal disease. The role of microRNAs as key negative regulators of gene expression, controlling all cellular processes including cell migration and invasion, is now being recognized. Here, we used in silico analysis of microRNA expression profiles of primary and metastatic melanomas and functional experiments to show that microRNA-125b (miR-125b) is a determinant candidate of melanoma progression: (i) miR-125b is more strongly expressed in aggressive metastatic than primary melanomas, (ii) there is an inverse correlation between the amount of miR-125b and overall patient survival, (iii) invasion/migration potentials in vitro are inversely correlated with the amount of miR-125b in a series of human melanoma cell lines, and (iv) inhibition of miR-125b reduces migratory and invasive potentials without affecting cell proliferation in vitro. Furthermore, we show that neural precursor cell expressed developmentally down-regulated protein 9 (i.e., NEDD9) is a direct target of miR-125b and is involved in modulating melanoma cell migration and invasion. Also, transcription factor 4, associated with epithelial-mesenchymal transition and invasion, induces the transcription of miR-125b-1. In conclusion, the transcription factor 4/miR-125b/NEDD9 cascade promotes melanoma cell migration/invasion. PMID:26968260