Science.gov

Sample records for retardation protein paralogs

  1. Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins.

    PubMed

    Lustig, Arthur J

    2016-01-01

    Through elegant studies in fungal cells and complex organisms, we propose a unifying paradigm for the rapid evolution of telomere binding proteins (TBPs) that associate with either (or both) telomeric DNA and telomeric proteins. TBPs protect and regulate telomere structure and function. Four critical factors are involved. First, TBPs that commonly bind to telomeric DNA include the c-Myb binding proteins, OB-fold single-stranded binding proteins, and G-G base paired Hoogsteen structure (G4) binding proteins. Each contributes independently or, in some cases, cooperatively, to provide a minimum level of telomere function. As a result of these minimal requirements and the great abundance of homologs of these motifs in the proteome, DNA telomere-binding activity may be generated more easily than expected. Second, telomere dysfunction gives rise to genome instability, through the elevation of recombination rates, genome ploidy, and the frequency of gene mutations. The formation of paralogs that diverge from their progenitor proteins ultimately can form a high frequency of altered TBPs with altered functions. Third, TBPs that assemble into complexes (e.g., mammalian shelterin) derive benefits from the novel emergent functions. Fourth, a limiting factor in the evolution of TBP complexes is the formation of mutually compatible interaction surfaces amongst the TBPs. These factors may have different degrees of importance in the evolution of different phyla, illustrated by the apparently simpler telomeres in complex plants. Selective pressures that can utilize the mechanisms of paralog formation and mutagenesis to drive TBP evolution along routes dependent on the requisite physiologic changes.

  2. Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins

    PubMed Central

    Lustig, Arthur J.

    2016-01-01

    Through elegant studies in fungal cells and complex organisms, we propose a unifying paradigm for the rapid evolution of telomere binding proteins (TBPs) that associate with either (or both) telomeric DNA and telomeric proteins. TBPs protect and regulate telomere structure and function. Four critical factors are involved. First, TBPs that commonly bind to telomeric DNA include the c-Myb binding proteins, OB-fold single-stranded binding proteins, and G-G base paired Hoogsteen structure (G4) binding proteins. Each contributes independently or, in some cases, cooperatively, to provide a minimum level of telomere function. As a result of these minimal requirements and the great abundance of homologs of these motifs in the proteome, DNA telomere-binding activity may be generated more easily than expected. Second, telomere dysfunction gives rise to genome instability, through the elevation of recombination rates, genome ploidy, and the frequency of gene mutations. The formation of paralogs that diverge from their progenitor proteins ultimately can form a high frequency of altered TBPs with altered functions. Third, TBPs that assemble into complexes (e.g., mammalian shelterin) derive benefits from the novel emergent functions. Fourth, a limiting factor in the evolution of TBP complexes is the formation of mutually compatible interaction surfaces amongst the TBPs. These factors may have different degrees of importance in the evolution of different phyla, illustrated by the apparently simpler telomeres in complex plants. Selective pressures that can utilize the mechanisms of paralog formation and mutagenesis to drive TBP evolution along routes dependent on the requisite physiologic changes. PMID:26904098

  3. Functional prediction: identification of protein orthologs and paralogs.

    PubMed Central

    Chen, R.; Jeong, S. S.

    2000-01-01

    Orthologs typically retain the same function in the course of evolution. Using beta-decarboxylating dehydrogenase family as a model, we demonstrate that orthologs can be confidently identified. The strategy is based on our recent findings that substitutions of only a few amino acid residues in these enzymes are sufficient to exchange substrate and coenzyme specificities. Hence, the few major specificity determinants can serve as reliable markers for determining orthologous or paralogous relationships. The power of this approach has been demonstrated by correcting similarity-based functional misassignment and discovering new genes and related pathways, and should be broadly applicable to other enzyme families. PMID:11206056

  4. Parameters of the proteome evolution from the distribution of sequence identities of paralogous proteins

    NASA Astrophysics Data System (ADS)

    Yan, Koon-Kiu; Axelsen, Jacob; Maslov, Sergei

    2006-03-01

    The evolution of the full repertoire of proteins encoded in a given genome is driven by gene duplications, deletions and modifications of amino-acid sequences of already existing proteins. The information about relative rates and other intrinsic parameters of these three basic processes is contained in the distribution of sequence identities of pairs of paralogous proteins. We introduced a simple mathematical framework that allows one to extract some of this hidden information. It was then applied to the proteome-wide set of paralogous proteins in H. pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster and H. sapiens. We estimated the stationary per-gene deletion and duplication rates, the distribution of amino-acid substitution rate of these organisms. The validity of our mathematical framework was further confirmed by numerical simulations of a simple evolutionary model of a fixed-size proteome.

  5. Mapping proteins in the presence of paralogs using units of coevolution

    PubMed Central

    2013-01-01

    Background We study the problem of mapping proteins between two protein families in the presence of paralogs. This problem occurs as a difficult subproblem in coevolution-based computational approaches for protein-protein interaction prediction. Results Similar to prior approaches, our method is based on the idea that coevolution implies equal rates of sequence evolution among the interacting proteins, and we provide a first attempt to quantify this notion in a formal statistical manner. We call the units that are central to this quantification scheme the units of coevolution. A unit consists of two mapped protein pairs and its score quantifies the coevolution of the pairs. This quantification allows us to provide a maximum likelihood formulation of the paralog mapping problem and to cast it into a binary quadratic programming formulation. Conclusion CUPID, our software tool based on a Lagrangian relaxation of this formulation, makes it, for the first time, possible to compute state-of-the-art quality pairings in a few minutes of runtime. In summary, we suggest a novel alternative to the earlier available approaches, which is statistically sound and computationally feasible. PMID:24564758

  6. Parameters of proteome evolution from histograms of amino-acid sequence identities of paralogous proteins

    PubMed Central

    Axelsen, Jacob Bock; Yan, Koon-Kiu; Maslov, Sergei

    2007-01-01

    Background The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins. Results We introduce a simple mathematical framework based on a stochastic birth-and-death model that allows one to extract some of this information and apply it to the set of all pairs of paralogous proteins in H. pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster, and H. sapiens. It was found that the histogram of sequence identities p generated by an all-to-all alignment of all protein sequences encoded in a genome is well fitted with a power-law form ~ p-γ with the value of the exponent γ around 4 for the majority of organisms used in this study. This implies that the intra-protein variability of substitution rates is best described by the Gamma-distribution with the exponent α ≈ 0.33. Different features of the shape of such histograms allow us to quantify the ratio between the genome-wide average deletion/duplication rates and the amino-acid substitution rate. Conclusion We separately measure the short-term ("raw") duplication and deletion rates rdup∗, rdel∗ which include gene copies that will be removed soon after the duplication event and their dramatically reduced long-term counterparts rdup, rdel. High deletion rate among recently duplicated proteins is consistent with a scenario in which they didn't have enough time to significantly change their functional roles and thus are to a large degree disposable. Systematic trends of each of the four duplication/deletion rates with the total number of genes in the genome were analyzed. All but the deletion rate of recent duplicates rdel∗ were shown to systematically increase with Ngenes. Abnormally flat shapes

  7. Adhesive Properties of YapV and Paralogous Autotransporter Proteins of Yersinia pestis

    PubMed Central

    Nair, Manoj K. M.; De Masi, Leon; Yue, Min; Galván, Estela M.; Chen, Huaiqing; Wang, Fang

    2015-01-01

    Yersinia pestis is the causative agent of plague. This bacterium evolved from an ancestral enteroinvasive Yersinia pseudotuberculosis strain by gene loss and acquisition of new genes, allowing it to use fleas as transmission vectors. Infection frequently leads to a rapidly lethal outcome in humans, a variety of rodents, and cats. This study focuses on the Y. pestis KIM yapV gene and its product, recognized as an autotransporter protein by its typical sequence, outer membrane localization, and amino-terminal surface exposure. Comparison of Yersinia genomes revealed that DNA encoding YapV or each of three individual paralogous proteins (YapK, YapJ, and YapX) was present as a gene or pseudogene in a strain-specific manner and only in Y. pestis and Y. pseudotuberculosis. YapV acted as an adhesin for alveolar epithelial cells and specific extracellular matrix (ECM) proteins, as shown with recombinant Escherichia coli, Y. pestis, or purified passenger domains. Like YapV, YapK and YapJ demonstrated adhesive properties, suggesting that their previously related in vivo activity is due to their capacity to modulate binding properties of Y. pestis in its hosts, in conjunction with other adhesins. A differential host-specific type of binding to ECM proteins by YapV, YapK, and YapJ suggested that these proteins participate in broadening the host range of Y. pestis. A phylogenic tree including 36 Y. pestis strains highlighted an association between the gene profile for the four paralogous proteins and the geographic location of the corresponding isolated strains, suggesting an evolutionary adaption of Y. pestis to specific local animal hosts or reservoirs. PMID:25690102

  8. Paralogous radiations of PIN proteins with multiple origins of noncanonical PIN structure.

    PubMed

    Bennett, Tom; Brockington, Samuel F; Rothfels, Carl; Graham, Sean W; Stevenson, Dennis; Kutchan, Toni; Rolf, Megan; Thomas, Philip; Wong, Gane Ka-Shu; Leyser, Ottoline; Glover, Beverley J; Harrison, C Jill

    2014-08-01

    The plant hormone auxin is a conserved regulator of development which has been implicated in the generation of morphological novelty. PIN-FORMED1 (PIN) auxin efflux carriers are central to auxin function by regulating its distribution. PIN family members have divergent structures and cellular localizations, but the origin and evolutionary significance of this variation is unresolved. To characterize PIN family evolution, we have undertaken phylogenetic and structural analyses with a massive increase in taxon sampling over previous studies. Our phylogeny shows that following the divergence of the bryophyte and lycophyte lineages, two deep duplication events gave rise to three distinct lineages of PIN proteins in euphyllophytes. Subsequent independent radiations within each of these lineages were taxonomically asymmetric, giving rise to at least 21 clades of PIN proteins, of which 15 are revealed here for the first time. Although most PIN protein clades share a conserved canonical structure with a modular central loop domain, a small number of noncanonical clades dispersed across the phylogeny have highly divergent protein structure. We propose that PIN proteins underwent sub- and neofunctionalization with substantial modification to protein structure throughout plant evolution. Our results have important implications for plant evolution as they suggest that structurally divergent PIN proteins that arose in paralogous radiations contributed to the convergent evolution of organ systems in different land plant lineages.

  9. Paralogous Radiations of PIN Proteins with Multiple Origins of Noncanonical PIN Structure

    PubMed Central

    Bennett, Tom; Brockington, Samuel F.; Rothfels, Carl; Graham, Sean W.; Stevenson, Dennis; Kutchan, Toni; Rolf, Megan; Thomas, Philip; Wong, Gane Ka-Shu; Leyser, Ottoline; Glover, Beverley J.; Harrison, C. Jill

    2014-01-01

    The plant hormone auxin is a conserved regulator of development which has been implicated in the generation of morphological novelty. PIN-FORMED1 (PIN) auxin efflux carriers are central to auxin function by regulating its distribution. PIN family members have divergent structures and cellular localizations, but the origin and evolutionary significance of this variation is unresolved. To characterize PIN family evolution, we have undertaken phylogenetic and structural analyses with a massive increase in taxon sampling over previous studies. Our phylogeny shows that following the divergence of the bryophyte and lycophyte lineages, two deep duplication events gave rise to three distinct lineages of PIN proteins in euphyllophytes. Subsequent independent radiations within each of these lineages were taxonomically asymmetric, giving rise to at least 21 clades of PIN proteins, of which 15 are revealed here for the first time. Although most PIN protein clades share a conserved canonical structure with a modular central loop domain, a small number of noncanonical clades dispersed across the phylogeny have highly divergent protein structure. We propose that PIN proteins underwent sub- and neofunctionalization with substantial modification to protein structure throughout plant evolution. Our results have important implications for plant evolution as they suggest that structurally divergent PIN proteins that arose in paralogous radiations contributed to the convergent evolution of organ systems in different land plant lineages. PMID:24758777

  10. Properties of Sequence Conservation in Upstream Regulatory and Protein Coding Sequences among Paralogs in Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Richardson, Dale N.; Wiehe, Thomas

    Whole genome duplication (WGD) has catalyzed the formation of new species, genes with novel functions, altered expression patterns, complexified signaling pathways and has provided organisms a level of genetic robustness. We studied the long-term evolution and interrelationships of 5’ upstream regulatory sequences (URSs), protein coding sequences (CDSs) and expression correlations (EC) of duplicated gene pairs in Arabidopsis. Three distinct methods revealed significant evolutionary conservation between paralogous URSs and were highly correlated with microarray-based expression correlation of the respective gene pairs. Positional information on exact matches between sequences unveiled the contribution of micro-chromosomal rearrangements on expression divergence. A three-way rank analysis of URS similarity, CDS divergence and EC uncovered specific gene functional biases. Transcription factor activity was associated with gene pairs exhibiting conserved URSs and divergent CDSs, whereas a broad array of metabolic enzymes was found to be associated with gene pairs showing diverged URSs but conserved CDSs.

  11. Trichomonas vaginalis Repair of Iron Centres Proteins: The Different Role of Two Paralogs.

    PubMed

    Nobre, Lígia S; Meloni, Dionigia; Teixeira, Miguel; Viscogliosi, Eric; Saraiva, Lígia M

    2016-06-01

    Trichomonas vaginalis, the causative parasite of one of the most prevalent sexually transmitted diseases is, so far, the only protozoan encoding two putative Repair of Iron Centres (RIC) proteins. Homologs of these proteins have been shown to protect bacteria from the chemical stress imposed by mammalian immunity. In this work, the biochemical and functional characterisation of the T. vaginalis RICs revealed that the two proteins have different properties. Expression of ric1 is induced by nitrosative stress but not by hydrogen peroxide, while ric2 transcription remained unaltered under similar conditions. T. vaginalis RIC1 contains a di-iron centre, but RIC2 apparently does not. Only RIC1 resembles bacterial RICs on spectroscopic profiling and repairing ability of oxidatively-damaged iron-sulfur clusters. Unexpectedly, RIC2 was found to bind DNA plasmid and T. vaginalis genomic DNA, a function proposed to be related with its leucine zipper domain. The two proteins also differ in their cellular localization: RIC1 is expressed in the cytoplasm only, and RIC2 occurs both in the nucleus and cytoplasm. Therefore, we concluded that the two RIC paralogs have different roles in T. vaginalis, with RIC2 showing an unprecedented DNA binding ability when compared with all other until now studied RICs. PMID:27124376

  12. Identifying Cognate Binding Pairs among a Large Set of Paralogs: The Case of PE/PPE Proteins of Mycobacterium tuberculosis

    PubMed Central

    Riley, Robert; Pellegrini, Matteo; Eisenberg, David

    2008-01-01

    We consider the problem of how to detect cognate pairs of proteins that bind when each belongs to a large family of paralogs. To illustrate the problem, we have undertaken a genomewide analysis of interactions of members of the PE and PPE protein families of Mycobacterium tuberculosis. Our computational method uses structural information, operon organization, and protein coevolution to infer the interaction of PE and PPE proteins. Some 289 PE/PPE complexes were predicted out of a possible 5,590 PE/PPE pairs genomewide. Thirty-five of these predicted complexes were also found to have correlated mRNA expression, providing additional evidence for these interactions. We show that our method is applicable to other protein families, by analyzing interactions of the Esx family of proteins. Our resulting set of predictions is a starting point for genomewide experimental interaction screens of the PE and PPE families, and our method may be generally useful for detecting interactions of proteins within families having many paralogs. PMID:18787688

  13. Targeted Identification of SUMOylation Sites in Human Proteins Using Affinity Enrichment and Paralog-specific Reporter Ions*

    PubMed Central

    Lamoliatte, Frederic; Bonneil, Eric; Durette, Chantal; Caron-Lizotte, Olivier; Wildemann, Dirk; Zerweck, Johannes; Wenshuk, Holger; Thibault, Pierre

    2013-01-01

    Protein modification by small ubiquitin-like modifier (SUMO) modulates the activities of numerous proteins involved in different cellular functions such as gene transcription, cell cycle, and DNA repair. Comprehensive identification of SUMOylated sites is a prerequisite to determine how SUMOylation regulates protein function. However, mapping SUMOylated Lys residues by mass spectrometry (MS) is challenging because of the dynamic nature of this modification, the existence of three functionally distinct human SUMO paralogs, and the large SUMO chain remnant that remains attached to tryptic peptides. To overcome these problems, we created HEK293 cell lines that stably express functional SUMO paralogs with an N-terminal His6-tag and an Arg residue near the C terminus that leave a short five amino acid SUMO remnant upon tryptic digestion. We determined the fragmentation patterns of our short SUMO remnant peptides by collisional activation and electron transfer dissociation using synthetic peptide libraries. Activation using higher energy collisional dissociation on the LTQ-Orbitrap Elite identified SUMO paralog-specific fragment ions and neutral losses of the SUMO remnant with high mass accuracy (< 5 ppm). We exploited these features to detect SUMO modified tryptic peptides in complex cell extracts by correlating mass measurements of precursor and fragment ions using a data independent acquisition method. We also generated bioinformatics tools to retrieve MS/MS spectra containing characteristic fragment ions to the identification of SUMOylated peptide by conventional Mascot database searches. In HEK293 cell extracts, this MS approach uncovered low abundance SUMOylated peptides and 37 SUMO3-modified Lys residues in target proteins, most of which were previously unknown. Interestingly, we identified mixed SUMO-ubiquitin chains with ubiquitylated SUMO proteins (K20 and K32) and SUMOylated ubiquitin (K63), suggesting a complex crosstalk between these two modifications. PMID

  14. Multimodular Penicillin-Binding Proteins: An Enigmatic Family of Orthologs and Paralogs

    PubMed Central

    Goffin, Colette; Ghuysen, Jean-Marie

    1998-01-01

    protein-protein interaction. The full-size class B PBPs are an assortment of orthologs and paralogs, which prescribe traits as complex as wall expansion and septum formation. PBPs of subclass B1 are unique to gram-positive bacteria. They are not essential, but they represent an important mechanism of resistance to penicillin among the enterococci and staphylococci. Natural evolution and PBP- and β-lactamase-mediated resistance show that the ability of the catalytic centers to adapt their properties to new situations is limitless. Studies of the reaction pathways by using the methods of quantum chemistry suggest that resistance to penicillin is a road of no return. PMID:9841666

  15. Different Functions of the Paralogs to the N-Terminal Domain of the Orange Carotenoid Protein in the Cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    López-Igual, Rocío; Wilson, Adjélé; Leverenz, Ryan L; Melnicki, Matthew R; Bourcier de Carbon, Céline; Sutter, Markus; Turmo, Aiko; Perreau, François; Kerfeld, Cheryl A; Kirilovsky, Diana

    2016-07-01

    The photoactive Orange Carotenoid Protein (OCP) is involved in cyanobacterial photoprotection. Its N-terminal domain (NTD) is responsible for interaction with the antenna and induction of excitation energy quenching, while the C-terminal domain is the regulatory domain that senses light and induces photoactivation. In most nitrogen-fixing cyanobacterial strains, there are one to four paralogous genes coding for homologs to the NTD of the OCP. The functions of these proteins are unknown. Here, we study the expression, localization, and function of these genes in Anabaena sp. PCC 7120. We show that the four genes present in the genome are expressed in both vegetative cells and heterocysts but do not seem to have an essential role in heterocyst formation. This study establishes that all four Anabaena NTD-like proteins can bind a carotenoid and the different paralogs have distinct functions. Surprisingly, only one paralog (All4941) was able to interact with the antenna and to induce permanent thermal energy dissipation. Two of the other Anabaena paralogs (All3221 and Alr4783) were shown to be very good singlet oxygen quenchers. The fourth paralog (All1123) does not seem to be involved in photoprotection. Structural homology modeling allowed us to propose specific features responsible for the different functions of these soluble carotenoid-binding proteins. PMID:27208286

  16. Different Functions of the Paralogs to the N-Terminal Domain of the Orange Carotenoid Protein in the Cyanobacterium Anabaena sp. PCC 71201[OPEN

    PubMed Central

    López-Igual, Rocío; Wilson, Adjélé; Bourcier de Carbon, Céline; Sutter, Markus; Turmo, Aiko

    2016-01-01

    The photoactive Orange Carotenoid Protein (OCP) is involved in cyanobacterial photoprotection. Its N-terminal domain (NTD) is responsible for interaction with the antenna and induction of excitation energy quenching, while the C-terminal domain is the regulatory domain that senses light and induces photoactivation. In most nitrogen-fixing cyanobacterial strains, there are one to four paralogous genes coding for homologs to the NTD of the OCP. The functions of these proteins are unknown. Here, we study the expression, localization, and function of these genes in Anabaena sp. PCC 7120. We show that the four genes present in the genome are expressed in both vegetative cells and heterocysts but do not seem to have an essential role in heterocyst formation. This study establishes that all four Anabaena NTD-like proteins can bind a carotenoid and the different paralogs have distinct functions. Surprisingly, only one paralog (All4941) was able to interact with the antenna and to induce permanent thermal energy dissipation. Two of the other Anabaena paralogs (All3221 and Alr4783) were shown to be very good singlet oxygen quenchers. The fourth paralog (All1123) does not seem to be involved in photoprotection. Structural homology modeling allowed us to propose specific features responsible for the different functions of these soluble carotenoid-binding proteins. PMID:27208286

  17. Did Androgen-Binding Protein Paralogs Undergo Neo- and/or Subfunctionalization as the Abp Gene Region Expanded in the Mouse Genome?

    PubMed Central

    Karn, Robert C.; Chung, Amanda G.; Laukaitis, Christina M.

    2014-01-01

    The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution. PMID:25531410

  18. The Plasmodium vivax Merozoite Surface Protein 1 Paralog Is a Novel Erythrocyte-Binding Ligand of P. vivax

    PubMed Central

    Cheng, Yang; Wang, Yue; Ito, Daisuke; Kong, Deok-Hoon; Ha, Kwon-Soo; Chen, Jun-Hu; Lu, Feng; Li, Jian; Wang, Bo; Takashima, Eizo; Sattabongkot, Jetsumon

    2013-01-01

    Merozoite surface protein 1 of Plasmodium vivax (PvMSP1), a glycosylphosphatidylinositol-anchored protein (GPI-AP), is a malaria vaccine candidate for P. vivax. The paralog of PvMSP1, named P. vivax merozoite surface protein 1 paralog (PvMSP1P; PlasmoDB PVX_099975), was recently identified and predicted as a GPI-AP. The similarities in genetic structural characteristics between PvMSP1 and PvMSP1P (e.g., size of open reading frames, two epidermal growth factor-like domains, and GPI anchor motif in the C terminus) led us to study this protein. In the present study, different regions of the PvMSP1P protein, demarcated based on the processed forms of PvMSP1, were expressed successfully as recombinant proteins [i.e., 83 (A, B, and C), 30, 38, 42, 33, and 19 fragments]. We studied the naturally acquired immune response against each fragment of recombinant PvMSP1P and the potential ability of each fragment to bind erythrocytes. The N-terminal fragment (83A) and two C-terminal fragments (33 and 19) reacted strongly with sera from P. vivax-infected patients, with 50 to 68% sensitivity and 95 to 96% specificity, respectively. Due to colocalization of PvMSP1P with PvMSP1, we supposed that PvMSP1P plays a similar role as PvMSP1 during erythrocyte invasion. An in vitro cytoadherence assay showed that PvMSP1P, especially the 19-kDa C-terminal region, could bind to erythrocytes. We also found that human sera from populations naturally exposed to vivax malaria and antisera obtained by immunization using the recombinant molecule PvMSP1P-19 inhibited in vitro binding of human erythrocytes to PvMSP1P-19. These results provide further evidence that the PvMSP1P might be an essential parasite adhesion molecule in the P. vivax merozoite and is a potential vaccine candidate against P. vivax. PMID:23460511

  19. Functional characterization of two paralogs that are novel RNA binding proteins influencing mitochondrial transcripts of Trypanosoma brucei.

    PubMed

    Kafková, Lucie; Ammerman, Michelle L; Faktorová, Drahomíra; Fisk, John C; Zimmer, Sara L; Sobotka, Roman; Read, Laurie K; Lukes, Julius; Hashimi, Hassan

    2012-10-01

    A majority of Trypanosoma brucei proteins have unknown functions, a consequence of its independent evolutionary history within the order Kinetoplastida that allowed for the emergence of several unique biological properties. Among these is RNA editing, needed for expression of mitochondrial-encoded genes. The recently discovered mitochondrial RNA binding complex 1 (MRB1) is composed of proteins with several functions in processing organellar RNA. We characterize two MRB1 subunits, referred to herein as MRB8170 and MRB4160, which are paralogs arisen from a large chromosome duplication occurring only in T. brucei. As with many other MRB1 proteins, both have no recognizable domains, motifs, or orthologs outside the order. We show that they are both novel RNA binding proteins, possibly representing a new class of these proteins. They associate with a similar subset of MRB1 subunits but not directly with each other. We generated cell lines that either individually or simultaneously target the mRNAs encoding both proteins using RNAi. Their dual silencing results in a differential effect on moderately and pan-edited RNAs, suggesting a possible functional separation of the two proteins. Cell growth persists upon RNAi silencing of each protein individually in contrast to the dual knockdown. Yet, their apparent redundancy in terms of cell viability is at odds with the finding that only one of these knockdowns results in the general degradation of pan-edited RNAs. While MRB8170 and MRB4160 share a considerable degree of conservation, our results suggest that their recent sequence divergence has led to them influencing mitochondrial mRNAs to differing degrees.

  20. Case study on the evolution of hetero-oligomer interfaces based on the differences in paralogous proteins

    PubMed Central

    Aoto, Saki; Yura, Kei

    2015-01-01

    We addressed the evolutionary trace of hetero-oligomer interfaces by comparing the structures of paralogous proteins; one of them is a monomer or homo-oligomer and the other is a hetero-oligomer. We found different trends in amino acid conservation pattern and hydrophobicity between homo-oligomer and hetero-oligomer. The degree of amino acid conservation in the interface of homo-oligomer has no obvious difference from that in the surface, whereas the degree of conservation is much higher in the interface of hetero-oligomer. The interface of homo-oligomer has a few very conserved residue positions, whereas the residue conservation in the interface of hetero-oligomer tends to be higher. In addition, the interface of hetero-oligomer has a tendency of being more hydrophobic compared with the one in homo-oligomer. We conjecture that these differences are related to the inherent symmetry in homo-oligomers that cannot exist in hetero-oligomers. Paucity of the structural data precludes statistical tests of these tendencies, yet the trend can be applied to the prediction of the interface of hetero-oligomer. We obtained putative interfaces of the subunits in CPSF (cleavage and polyadenylation specificity factor), one of the human pre-mRNA 3′-processing complexes. The locations of predicted interface residues were consistent with the known experimental data. PMID:27493859

  1. Rho proteins, mental retardation and the neurobiological basis of intelligence.

    PubMed

    van Galen, Elly J M; Ramakers, Ger J A

    2005-01-01

    For several decades it has been known that mental retardation is associated with abnormalities in dendrites and dendritic spines. The recent cloning of eight genes which cause nonspecific mental retardation when mutated, provides an important insight into the cellular mechanisms that result in the dendritic abnormalities underlying mental retardation. Three of the encoded proteins, oligophrenin1, PAK3 and alphaPix, interact directly with Rho GTPases. Rho GTPases are key signaling proteins which integrate extracellular and intracellular signals to orchestrate coordinated changes in the actin cytoskeleton, essential for directed neurite outgrowth and the generation/rearrangement of synaptic connectivity. Although many details of the cell biology of Rho signaling in the CNS are as yet unclear, a picture is unfolding showing how mutations that cause abnormal Rho signaling result in abnormal neuronal connectivity which gives rise to deficient cognitive functioning in humans.

  2. AAN82231 protein from uropathogenic E. coli CFT073 is a close paralog of DsbB enzymes and does not belong to the DsbI family.

    PubMed

    Pawłowski, Marcin; Lasica, Anna M; Jagusztyn-Krynicka, Elzbieta K; Bujnicki, Janusz M

    2009-01-01

    Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of membrane and exported proteins. DsbA is an oxidant that catalyzes formation of disulfide bonds in newly synthesized, and yet unfolded proteins. In order to act catalytically again, it has to be reoxidized by a transmembrane protein DsbB characterized by two pairs of disulfides. DsbB is related to another protein family DsbI, characterized by the presence of only one disulfide, and an additional C-terminal beta-propeller domain. The protein AAN82231 from E. coli strain CFT073 has been recently described as a new member of the DsbI family (Grimshaw et al., 2008). It was found that AAN82231 forms a functional redox pair with DsbL--a newly described DsbA-like protein. Here, we report that AAN82231 shares no characteristic features with the DsbI proteins. Instead, according to phylogenetic analyses AAN82231 clearly belongs to another, previously described subfamily of DsbB paralogs. To facilitate classification of DsbB and DsbI homologs, we propose a new nomenclature system and present an updated phylogenetic analysis of the DsbB superfamily, which comprises the following families: "orthodox" DsbB, its paralogs now named DsbB2 (including AAN82231), DsbI and two groups of so far uncharacterized DsbB paralogs termed DsbB3 and DsbB4. We have also developed a web server dedicated to phylogenetic assignment of DsbB/DsbI candidate proteins that will be identified in the future.

  3. Knockout of the abundant Trichomonas vaginalis hydrogenosomal membrane protein TvHMP23 increases hydrogenosome size but induces no compensatory up-regulation of paralogous copies.

    PubMed

    Brás, Xavier Pereira; Zimorski, Verena; Bolte, Kathrin; Maier, Uwe-G; Martin, William F; Gould, Sven B

    2013-05-01

    The Trichomonas vaginalis genome encodes up to 60000 genes, many of which stem from genome duplication events. Paralogous copies thus accompany most T. vaginalis genes, a phenomenon that limits genetic manipulation. We characterized one of the parasite's most abundant hydrogenosomal membrane proteins, TvHMP23, which is phylogenetically distinct from canonical metabolite carriers, and which localizes to the inner hydrogenosomal membrane as shown through sub-organellar fractionation and protease protection assays. Knockout of Tvhmp23 through insertion of the selectable neomycin marker led to a size increase of hydrogenosomes, the first knockout-induced phenotypes reported for Trichomonas, but no growth impairment. The transcriptional response of its four paralogous copies then analyzed revealed that they are not up-regulated, and hence do not compensate for the Tvhmp23 knockout. PMID:23499435

  4. Structure of TatA paralog, TatE, suggests a structurally homogeneous form of Tat protein translocase that transports folded proteins of differing diameter.

    PubMed

    Baglieri, Jacopo; Beck, Daniel; Vasisht, Nishi; Smith, Corinne J; Robinson, Colin

    2012-03-01

    The twin-arginine translocation (Tat) system transports folded proteins across bacterial and plant thylakoid membranes. Most current models for the translocation mechanism propose the coalescence of a substrate-binding TatABC complex with a separate TatA complex. In Escherichia coli, TatA complexes are widely believed to form the translocation pore, and the size variation of TatA has been linked to the transport of differently sized substrates. Here, we show that the TatA paralog TatE can substitute for TatA and support translocation of Tat substrates including AmiA, AmiC, and TorA. However, TatE is found as much smaller, discrete complexes. Gel filtration and blue native electrophoresis suggest sizes between ∼50 and 110 kDa, and single-particle processing of electron micrographs gives size estimates of 70-90 kDa. Three-dimensional models of the two principal TatE complexes show estimated diameters of 6-8 nm and potential clefts or channels of up to 2.5 nm diameter. The ability of TatE to support translocation of the 90-kDa TorA protein suggests alternative translocation models in which single TatA/E complexes do not contribute the bulk of the translocation channel. The homogeneity of both the TatABC and the TatE complexes further suggests that a discrete Tat translocase can translocate a variety of substrates, presumably through the use of a flexible channel. The presence and possible significance of double- or triple-ring TatE forms is discussed.

  5. Phylogenomics with paralogs

    PubMed Central

    Hellmuth, Marc; Wieseke, Nicolas; Lechner, Marcus; Lenhof, Hans-Peter; Middendorf, Martin; Stadler, Peter F.

    2015-01-01

    Phylogenomics heavily relies on well-curated sequence data sets that comprise, for each gene, exclusively 1:1 orthologos. Paralogs are treated as a dangerous nuisance that has to be detected and removed. We show here that this severe restriction of the data sets is not necessary. Building upon recent advances in mathematical phylogenetics, we demonstrate that gene duplications convey meaningful phylogenetic information and allow the inference of plausible phylogenetic trees, provided orthologs and paralogs can be distinguished with a degree of certainty. Starting from tree-free estimates of orthology, cograph editing can sufficiently reduce the noise to find correct event-annotated gene trees. The information of gene trees can then directly be translated into constraints on the species trees. Although the resolution is very poor for individual gene families, we show that genome-wide data sets are sufficient to generate fully resolved phylogenetic trees, even in the presence of horizontal gene transfer. PMID:25646426

  6. Fragile X Mental Retardation Protein Regulates Heterosynaptic Plasticity in the Hippocampus

    ERIC Educational Resources Information Center

    Connor, Steven A.; Hoeffer, Charles A.; Klann, Eric; Nguyen, Peter V.

    2011-01-01

    Silencing of a single gene, FMR1, is linked to a highly prevalent form of mental retardation, characterized by social and cognitive impairments, known as fragile X syndrome (FXS). The FMR1 gene encodes fragile X mental retardation protein (FMRP), which negatively regulates translation. Knockout of Fmr1 in mice results in enhanced long-term…

  7. Elucidating the evolutionary history and expression patterns of nucleoside phosphorylase paralogs (vegetative storage proteins) in Populus and the plant kingdom

    PubMed Central

    2013-01-01

    Background Nucleoside phosphorylases (NPs) have been extensively investigated in human and bacterial systems for their role in metabolic nucleotide salvaging and links to oncogenesis. In plants, NP-like proteins have not been comprehensively studied, likely because there is no evidence of a metabolic function in nucleoside salvage. However, in the forest trees genus Populus a family of NP-like proteins function as an important ecophysiological adaptation for inter- and intra-seasonal nitrogen storage and cycling. Results We conducted phylogenetic analyses to determine the distribution and evolution of NP-like proteins in plants. These analyses revealed two major clusters of NP-like proteins in plants. Group I proteins were encoded by genes across a wide range of plant taxa while proteins encoded by Group II genes were dominated by species belonging to the order Malpighiales and included the Populus Bark Storage Protein (BSP) and WIN4-like proteins. Additionally, we evaluated the NP-like genes in Populus by examining the transcript abundance of the 13 NP-like genes found in the Populus genome in various tissues of plants exposed to long-day (LD) and short-day (SD) photoperiods. We found that all 13 of the Populus NP-like genes belonging to either Group I or II are expressed in various tissues in both LD and SD conditions. Tests of natural selection and expression evolution analysis of the Populus genes suggests that divergence in gene expression may have occurred recently during the evolution of Populus, which supports the adaptive maintenance models. Lastly, in silico analysis of cis-regulatory elements in the promoters of the 13 NP-like genes in Populus revealed common regulatory elements known to be involved in light regulation, stress/pathogenesis and phytohormone responses. Conclusion In Populus, the evolution of the NP-like protein and gene family has been shaped by duplication events and natural selection. Expression data suggest that previously

  8. Distinct expression, localization and function of two Rab7 proteins encoded by paralogous genes in a free-living model eukaryote.

    PubMed

    Osińska, Magdalena; Wiejak, Jolanta; Wypych, Emilia; Bilski, Henryk; Bartosiewicz, Rafał; Wyroba, Elżbieta

    2011-01-01

    Rab7 GTPases are involved in membrane trafficking in the late endosomal/lysosomal pathway. In Paramecium octaurelia Rab7a and Rab7b are encoded by paralogous genes. Antipeptide antibodies generated against divergent C-termini recognize Rab7a of 22.5 kDa and Rab7b of 25 kDa, respectively. In 2D gel electrophoresis two immunoreactive spots were identified for Rab7b at pI about 6.34 and about 6.18 and only one spot for Rab7a of pI about 6.34 suggesting post-translational modification of Rab7b. Mass spectrometry revealed eight identical phosphorylated residues in the both proteins. ProQ Emerald staining and ConA overlay of immunoprecipitated Rab7b indicated its putative glycosylation that was further supported by a faster electrophoretic mobility of this protein upon deglycosylation. Such a post-translational modification and substitution of Ala(140) in Rab7a for Ser(140) in Rab7b may result in distinct targeting to the oral apparatus where Rab7b associates with the microtubular structures as revealed by STED confocal and electron microscopy. Rab7a was mapped to phagosomal compartment. Absolute qReal-Time PCR analysis revealed that expression of Rab7a was 2.6-fold higher than that of Rab7b. Upon latex internalization it was further 2-fold increased for Rab7a and only slightly for Rab7b. Post-transcriptional gene silencing of rab7a suppressed phagosome formation by 70 % and impaired their acidification. Ultrastructural analysis with double immunogold labeling revealed that this effect was due to the lack of V-ATPase recruitment to phagolysosomes. No significant phenotype changes were noticed in cells upon rab7b silencing. In conclusion, Rab7b acquired a new function, whereas Rab7a can be assigned to the phagolysosomal pathway.

  9. Fast protein evolution and germ line expression of a Drosophila parental gene and its young retroposed paralog.

    PubMed

    Betrán, Esther; Bai, Yongsheng; Motiwale, Mansi

    2006-11-01

    This is the first detailed study of the evolution, phylogenetic distribution, and transcription of one young retroposed gene, CG13732, and its parental gene CG15645, whose functions are unknown. CG13732 is a recognizable retroposed copy of CG15645 retaining the signals of this process. We name the parental gene Cervantes and the retrogene Quijote. To determine when this duplication occurred and the phylogenetic distribution of Quijote, we employed polymerase chain reaction, Southern blotting, and the available information on sequenced Drosophila genomes. Interestingly, these analyses revealed that Quijote is present only in 4 species of Drosophila (Drosophila melanogaster, Drosophila simulans, Drosophila sechellia, and Drosophila mauritiana) and that retroposed copies of Cervantes have also originated in the lineages leading to Drosophila yakuba and Drosophila erecta independently in the 3 instances. We name the new retrogene in the D. yakuba lineage Rocinante and the new retrogene in the D. erecta lineage Sancho. In this work, we present data on Quijote and its parental gene Cervantes. Polymorphism analysis of the derived gene and divergence data for both parental and derived genes were used to determine that both genes likely produce functional proteins and that they are changing at a fast rate (KA/KS approximately 0.38). The negative value of H of Fay and Wu in the non-African sample reveals an excess of derived variants at high frequency. This could be explained either by positive selection in the region or by demographic effects. The comparative expression pattern shows that both genes express in the same adult tissues (male and female germ line) in D. melanogaster. Quijote is also expressed in male and female in D. simulans, D. sechellia, and D. mauritiana. We argue that the fast rate of evolution of these genes could be related to their putative germ line function and are further studying the independent recruitment of Cervantes-derived retrogenes in

  10. Compact structure and proteins of pasta retard in vitro digestive evolution of branched starch molecular structure.

    PubMed

    Zou, Wei; Sissons, Mike; Warren, Frederick J; Gidley, Michael J; Gilbert, Robert G

    2016-11-01

    The roles that the compact structure and proteins in pasta play in retarding evolution of starch molecular structure during in vitro digestion are explored, using four types of cooked samples: whole pasta, pasta powder, semolina (with proteins) and extracted starch without proteins. These were subjected to in vitro digestion with porcine α-amylase, collecting samples at different times and characterizing the weight distribution of branched starch molecules using size-exclusion chromatography. Measurement of α-amylase activity showed that a protein (or proteins) from semolina or pasta powder interacted with α-amylase, causing reduced enzymatic activity and retarding digestion of branched starch molecules with hydrodynamic radius (Rh)<100nm; this protein(s) was susceptible to proteolysis. Thus the compact structure of pasta protects the starch and proteins in the interior of the whole pasta, reducing the enzymatic degradation of starch molecules, especially for molecules with Rh>100nm. PMID:27516291

  11. Super Resolution Fluorescence Microscopy and Tracking of Bacterial Flotillin (Reggie) Paralogs Provide Evidence for Defined-Sized Protein Microdomains within the Bacterial Membrane but Absence of Clusters Containing Detergent-Resistant Proteins

    PubMed Central

    Dempwolff, Felix; Schmidt, Felix K.; Hervás, Ana B.; Stroh, Alex; Rösch, Thomas C.; Riese, Cornelius N.; Dersch, Simon; Heimerl, Thomas; Lucena, Daniella; Hülsbusch, Nikola; Stuermer, Claudia A. O.; Takeshita, Norio; Fischer, Reinhard; Graumann, Peter L.

    2016-01-01

    Biological membranes have been proposed to contain microdomains of a specific lipid composition, in which distinct groups of proteins are clustered. Flotillin-like proteins are conserved between pro—and eukaryotes, play an important function in several eukaryotic and bacterial cells, and define in vertebrates a type of so-called detergent-resistant microdomains. Using STED microscopy, we show that two bacterial flotillins, FloA and FloT, form defined assemblies with an average diameter of 85 to 110 nm in the model bacterium Bacillus subtilis. Interestingly, flotillin microdomains are of similar size in eukaryotic cells. The soluble domains of FloA form higher order oligomers of up to several hundred kDa in vitro, showing that like eukaryotic flotillins, bacterial assemblies are based in part on their ability to self-oligomerize. However, B. subtilis paralogs show significantly different diffusion rates, and consequently do not colocalize into a common microdomain. Dual colour time lapse experiments of flotillins together with other detergent-resistant proteins in bacteria show that proteins colocalize for no longer than a few hundred milliseconds, and do not move together. Our data reveal that the bacterial membrane contains defined-sized protein domains rather than functional microdomains dependent on flotillins. Based on their distinct dynamics, FloA and FloT confer spatially distinguishable activities, but do not serve as molecular scaffolds. PMID:27362352

  12. The Fragile X Mental Retardation Protein, FMRP, Recognizes G-Quartets

    ERIC Educational Resources Information Center

    Darnell, Jennifer C.; Warren, Stephen T.; Darnell, Robert B.

    2004-01-01

    Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling some aspects of memory and behavior. Recent evidence suggests that one of the predominant RNA motifs recognized by the FMRP…

  13. Deletion of PTEN Produces Deficits in Conditioned Fear and Increases Fragile X Mental Retardation Protein

    ERIC Educational Resources Information Center

    Lugo, Joaquin N.; Smith, Gregory D.; Morrison, Jessica B.; White, Jessika

    2013-01-01

    The phosphatase and tensin homolog detected on chromosome 10 (PTEN) gene product modulates activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The PI3K pathway has been found to be involved in the regulation of the fragile X mental retardation protein, which is important for long-term depression and in the formation of new…

  14. Leverage principle of retardation signal in titration of double protein via chip moving reaction boundary electrophoresis.

    PubMed

    Zhang, Liu-Xia; Cao, Yi-Ren; Xiao, Hua; Liu, Xiao-Ping; Liu, Shao-Rong; Meng, Qing-Hua; Fan, Liu-Yin; Cao, Cheng-Xi

    2016-03-15

    In the present work we address a simple, rapid and quantitative analytical method for detection of different proteins present in biological samples. For this, we proposed the model of titration of double protein (TDP) and its relevant leverage theory relied on the retardation signal of chip moving reaction boundary electrophoresis (MRBE). The leverage principle showed that the product of the first protein content and its absolute retardation signal is equal to that of the second protein content and its absolute one. To manifest the model, we achieved theoretical self-evidence for the demonstration of the leverage principle at first. Then relevant experiments were conducted on the TDP-MRBE chip. The results revealed that (i) there was a leverage principle of retardation signal within the TDP of two pure proteins, and (ii) a lever also existed within these two complex protein samples, evidently demonstrating the validity of TDP model and leverage theory in MRBE chip. It was also showed that the proposed technique could provide a rapid and simple quantitative analysis of two protein samples in a mixture. Finally, we successfully applied the developed technique for the quantification of soymilk in adulterated infant formula. The TDP-MRBE opens up a new window for the detection of adulteration ratio of the poor food (milk) in blended high quality one.

  15. Linking the Fragile X mental retardation protein to the lipoxygenase pathway.

    PubMed

    Beaulieu, Marc-Alexandre

    2013-03-01

    Fragile X mental retardation is caused by the absence of the FMRP (fragile X mental retardation protein) a RNA-binding protein encoded by the Fmr1 gene. Despite the large number of studies about this syndrome, it is still unclear how the absence of FMRP affects the physiology of the nervous system. It has been reported however that the brain of the Fmr1-KO mouse shows altered membrane protein and lipid oxidation. There is also indirect evidence that FMRP may be involved in a negative feedback mechanism with metabotropic glutamate receptors (mGluRs). In this article, we will discuss several lines of evidences which tend to prove that the lipoxygenase pathway might be the missing link between FMRP and mGluRs.

  16. Regulation of Heart Rate in Drosophila via Fragile X Mental Retardation Protein

    PubMed Central

    Novak, Stefanie Mares; Joardar, Archi; Gregorio, Carol C.; Zarnescu, Daniela C.

    2015-01-01

    RNA binding proteins play a pivotal role in post-transcriptional gene expression regulation, however little is understood about their role in cardiac function. The Fragile X (FraX) family of RNA binding proteins is most commonly studied in the context of neurological disorders, as mutations in Fragile X Mental Retardation 1 (FMR1) are the leading cause of inherited mental retardation. More recently, alterations in the levels of Fragile X Related 1 protein, FXR1, the predominant FraX member expressed in vertebrate striated muscle, have been linked to structural and functional defects in mice and zebrafish models. FraX proteins are established regulators of translation and are known to regulate specific targets in different tissues. To decipher the direct role of FraX proteins in the heart in vivo, we turned to Drosophila, which harbors a sole, functionally conserved and ubiquitously expressed FraX protein, dFmr1. Using classical loss of function alleles as well as muscle specific RNAi knockdown, we show that Drosophila FMRP, dFmr1, is required for proper heart rate during development. Functional analyses in the context of cardiac-specific dFmr1 knockdown by RNAi demonstrate that dFmr1 is required cell autonomously in cardiac cells for regulating heart rate. Interestingly, these functional defects are not accompanied by any obvious structural abnormalities, suggesting that dFmr1 may regulate a different repertoire of targets in Drosophila than in vertebrates. Taken together, our findings support the hypothesis that dFmr1 protein is essential for proper cardiac function and establish the fly as a new model for studying the role(s) of FraX proteins in the heart. PMID:26571124

  17. Use of gel retardation to analyze protein-nucleic acid interactions.

    PubMed Central

    Lane, D; Prentki, P; Chandler, M

    1992-01-01

    Protein-nucleic acid interactions are crucial in the regulation of many fundamental cellular processes. The nature of these interactions is susceptible to analysis by a variety of methods, but the combination of high analytical power and technical simplicity offered by the gel retardation (band shift) technique has made this perhaps the most widely used such method over the last decade. This procedure is based on the observation that the formation of protein-nucleic complexes generally reduces the electrophoretic mobility of the nucleic acid component in the gel matrix. This review attempts to give a simplified account of the physical basis of the behavior of protein-nucleic acid complexes in gels and an overview of many of the applications in which the technique has proved especially useful. The factors which contribute most to the resolution of the complex from the naked nucleic acid are the gel pore size, the relative mass of protein compared with nucleic acid, and changes in nucleic acid conformation (bending) induced by binding. The consequences of induced bending on the mobility of double-strand DNA fragments are similar to those arising from sequence-directed bends, and the latter can be used to help characterize the angle and direction of protein-induced bends. Whether a complex formed in solution is actually detected as a retarded band on a gel depends not only on resolution but also on complex stability within the gel. This is strongly influenced by the composition and, particularly, the ionic strength of the gel buffer. We discuss the applications of the technique to analyzing complex formation and stability, including characterizing cooperative binding, defining binding sites on nucleic acids, analyzing DNA conformation in complexes, assessing binding to supercoiled DNA, defining protein complexes by using cell extracts, and analyzing biological processes such as transcription and splicing. Images PMID:1480106

  18. Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons.

    PubMed

    Tabet, Ricardos; Moutin, Enora; Becker, Jérôme A J; Heintz, Dimitri; Fouillen, Laetitia; Flatter, Eric; Krężel, Wojciech; Alunni, Violaine; Koebel, Pascale; Dembélé, Doulaye; Tassone, Flora; Bardoni, Barbara; Mandel, Jean-Louis; Vitale, Nicolas; Muller, Dominique; Le Merrer, Julie; Moine, Hervé

    2016-06-28

    Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkκ), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkκ expression. The reduction of Dgkκ in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkκ in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkκ deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkκ, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.

  19. The Drosophila fragile X mental retardation protein participates in the piRNA pathway.

    PubMed

    Bozzetti, Maria Pia; Specchia, Valeria; Cattenoz, Pierre B; Laneve, Pietro; Geusa, Annamaria; Sahin, H Bahar; Di Tommaso, Silvia; Friscini, Antonella; Massari, Serafina; Diebold, Celine; Giangrande, Angela

    2015-06-01

    RNA metabolism controls multiple biological processes, and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation, and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP, also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here, we demonstrate for the first time that germline, as well as somatic expression, of Drosophila Fmr1 (denoted dFmr1), the Drosophila ortholog of FMRP, are necessary in a pathway mediated by piRNAs. Moreover, dFmr1 interacts genetically and biochemically with Aubergine, an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system.

  20. Differential domain evolution and complex RNA processing in a family of paralogous EPB41 (protein 4.1) genes facilitates expression of diverse tissue-specific isoforms

    SciTech Connect

    Parra, Marilyn; Gee, Sherry; Chan, Nadine; Ryaboy, Dmitriy; Dubchak, Inna; Narla, Mohandas; Gascard, Philippe D.; Conboy, John G.

    2004-07-15

    The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian genome to encode a complex proteome from a small number of genes. By utilizing alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of structural adapter proteins. Comparative genomic and transcript analysis of these 140kb-240kb genes indicates several unusual features: differential evolution of highly conserved exons encoding known functional domains, interspersed with unique exons whose size and sequence variations contribute substantially to intergenic diversity: alternative first exons, most of which map far upstream of the coding regions; and complex tissue-specific alternative pre-mRNA splicing that facilitates synthesis of functionally different complements of 4.1 proteins in various cells. Understanding the splicing regulatory networks that control protein 4.1 expression will be critical to a full appreciation of the many roles of 4.1 proteins in normal cell biology and their proposed roles in human cancer.

  1. Zfrp8 forms a complex with fragile-X mental retardation protein and regulates its localization and function.

    PubMed

    Tan, William; Schauder, Curtis; Naryshkina, Tatyana; Minakhina, Svetlana; Steward, Ruth

    2016-02-15

    Fragile-X syndrome is the most commonly inherited cause of autism and mental disabilities. The Fmr1 (Fragile-X Mental Retardation 1) gene is essential in humans and Drosophila for the maintenance of neural stem cells, and Fmr1 loss results in neurological and reproductive developmental defects in humans and flies. FMRP (Fragile-X Mental Retardation Protein) is a nucleo-cytoplasmic shuttling protein, involved in mRNA silencing and translational repression. Both Zfrp8 and Fmr1 have essential functions in the Drosophila ovary. In this study, we identified FMRP, Nufip (Nuclear Fragile-X Mental Retardation Protein-interacting Protein) and Tral (Trailer Hitch) as components of a Zfrp8 protein complex. We show that Zfrp8 is required in the nucleus, and controls localization of FMRP in the cytoplasm. In addition, we demonstrate that Zfrp8 genetically interacts with Fmr1 and tral in an antagonistic manner. Zfrp8 and FMRP both control heterochromatin packaging, also in opposite ways. We propose that Zfrp8 functions as a chaperone, controlling protein complexes involved in RNA processing in the nucleus.

  2. Zfrp8 forms a complex with fragile-X mental retardation protein and regulates its localization and function.

    PubMed

    Tan, William; Schauder, Curtis; Naryshkina, Tatyana; Minakhina, Svetlana; Steward, Ruth

    2016-02-15

    Fragile-X syndrome is the most commonly inherited cause of autism and mental disabilities. The Fmr1 (Fragile-X Mental Retardation 1) gene is essential in humans and Drosophila for the maintenance of neural stem cells, and Fmr1 loss results in neurological and reproductive developmental defects in humans and flies. FMRP (Fragile-X Mental Retardation Protein) is a nucleo-cytoplasmic shuttling protein, involved in mRNA silencing and translational repression. Both Zfrp8 and Fmr1 have essential functions in the Drosophila ovary. In this study, we identified FMRP, Nufip (Nuclear Fragile-X Mental Retardation Protein-interacting Protein) and Tral (Trailer Hitch) as components of a Zfrp8 protein complex. We show that Zfrp8 is required in the nucleus, and controls localization of FMRP in the cytoplasm. In addition, we demonstrate that Zfrp8 genetically interacts with Fmr1 and tral in an antagonistic manner. Zfrp8 and FMRP both control heterochromatin packaging, also in opposite ways. We propose that Zfrp8 functions as a chaperone, controlling protein complexes involved in RNA processing in the nucleus. PMID:26772998

  3. Fragile X Mental Retardation Protein Regulates Olfactory Sensitivity But Not Odorant Discrimination

    PubMed Central

    Schilit Nitenson, Arielle; Stackpole, Emily E.; Truszkowski, Torrey L.S.; Midroit, Maellie; Fallon, Justin R.

    2015-01-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is characterized by cognitive impairments and altered sensory function. It is caused by absence of fragile X mental retardation protein (FMRP), an RNA-binding protein essential for normal synaptic plasticity and function. Animal models have provided important insights into mechanisms through which loss of FMRP impacts cognitive and sensory development and function. While FMRP is highly enriched in the developing and adult olfactory bulb (OB), its role in olfactory sensory function remains poorly understood. Here, we used a mouse model of FXS, the fmr1 −/y mouse, to test whether loss of FMRP impacts olfactory discrimination, habituation, or sensitivity using a spontaneous olfactory cross-habituation task at a range of odorant concentrations. We demonstrated that fmr1 −/y mice have a significant decrease in olfactory sensitivity compared with wild type controls. When we controlled for differences in sensitivity, we found no effect of loss of FMRP on the ability to habituate to or spontaneously discriminate between odorants. These data indicate that loss of FMRP significantly alters olfactory sensitivity, but not other facets of basal olfactory function. These findings have important implications for future studies aimed at understanding the role of FMRP on sensory functioning. PMID:25917509

  4. Sequence variation of alcohol dehydrogenase (Adh) paralogs in cactophilic Drosophila.

    PubMed Central

    Matzkin, Luciano M; Eanes, Walter F

    2003-01-01

    This study focuses on the population genetics of alcohol dehydrogenase (Adh) in cactophilic Drosophila. Drosophila mojavensis and D. arizonae utilize cactus hosts, and each host contains a characteristic mixture of alcohol compounds. In these Drosophila species there are two functional Adh loci, an adult form (Adh-2) and a larval and ovarian form (Adh-1). Overall, the greater level of variation segregating in D. arizonae than in D. mojavensis suggests a larger population size for D. arizonae. There are markedly different patterns of variation between the paralogs across both species. A 16-bp intron haplotype segregates in both species at Adh-2, apparently the product of an ancient gene conversion event between the paralogs, which suggests that there is selection for the maintenance of the intron structure possibly for the maintenance of pre-mRNA structure. We observe a pattern of variation consistent with adaptive protein evolution in the D. mojavensis lineage at Adh-1, suggesting that the cactus host shift that occurred in the divergence of D. mojavensis from D. arizonae had an effect on the evolution of the larval expressed paralog. Contrary to previous work we estimate a recent time for both the divergence of D. mojavensis and D. arizonae (2.4 +/- 0.7 MY) and the age of the gene duplication (3.95 +/- 0.45 MY). PMID:12586706

  5. Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

    PubMed Central

    Ahn, Hyo-Min; Koh, Young Ho

    2016-01-01

    We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved. PMID:27313903

  6. Rapidly evolving Rab GTPase paralogs and reproductive isolation in Drosophila.

    PubMed

    Hutter, Pierre

    2007-01-01

    Alterations at the X-linked Hmr gene of Drosophila melanogaster can fully restore viability and partially restore fertility in hybrid flies from crosses between D. melanogaster and any of its three most closely related species. Although more than one gene is expected to be involved in these barriers to reproduction, a single DNA-binding protein was recently identified as HMR. The Hmr gene was shown to evolve unusually fast, a feature that supports its role in causing genetic incompatibility in a hybrid genotype. The current treatment of hybrid genetics focuses not only on Hmr but also on the Rab9D gene, which lies only 1kb from Hmr. Rab9D is proposed also to influence hybrid viability. This gene has remained tightly linked to Hmr for about 10 million years, but it has diverged even more than Hmr with regard to D. melanogaster and its most closely related species. Furthermore, the 197-amino acid RAB9D protein contains four amino acid substitutions in the D. melanogaster-rescuing mutant Hmr1. Rab9D is shown to have evolved under very strong positive selection and to be the most recent member of a cluster of six paralogs that encode small RAB GTPases. Four of the six paralogs are unique to D. melanogaster in which they have diverged considerably, their encoded proteins sharing less than 50% amino acid identities with proteins from their orthologs in the closest species. Only two Rab orthologs are present in these sibling species and none is present in the genomes of more distantly related Drosophila species. Rapidly evolving Rab paralogs near the Hmr locus probably developed functional specialization of redundant proteins involved in trafficking macromolecules between cytoplasm and nucleus. Positive selection acting on duplicates of these Rab genes appears to participate in reproductive isolation.

  7. Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space.

    PubMed

    Hudson, William H; Kossmann, Bradley R; de Vera, Ian Mitchelle S; Chuo, Shih-Wei; Weikum, Emily R; Eick, Geeta N; Thornton, Joseph W; Ivanov, Ivaylo N; Kojetin, Douglas J; Ortlund, Eric A

    2016-01-12

    Many genomes contain families of paralogs--proteins with divergent function that evolved from a common ancestral gene after a duplication event. To understand how paralogous transcription factors evolve divergent DNA specificities, we examined how the glucocorticoid receptor and its paralogs evolved to bind activating response elements [(+)GREs] and negative glucocorticoid response elements (nGREs). We show that binding to nGREs is a property of the glucocorticoid receptor (GR) DNA-binding domain (DBD) not shared by other members of the steroid receptor family. Using phylogenetic, structural, biochemical, and molecular dynamics techniques, we show that the ancestral DBD from which GR and its paralogs evolved was capable of binding both nGRE and (+)GRE sequences because of the ancestral DBD's ability to assume multiple DNA-bound conformations. Subsequent amino acid substitutions in duplicated daughter genes selectively restricted protein conformational space, causing this dual DNA-binding specificity to be selectively enhanced in the GR lineage and lost in all others. Key substitutions that determined the receptors' response element-binding specificity were far from the proteins' DNA-binding interface and interacted epistatically to change the DBD's function through DNA-induced allosteric mechanisms. These amino acid substitutions subdivided both the conformational and functional space of the ancestral DBD among the present-day receptors, allowing a paralogous family of transcription factors to control disparate transcriptional programs despite high sequence identity.

  8. Detection of aneuploidies by paralogous sequence quantification

    PubMed Central

    Deutsch, S; Choudhury, U; Merla, G; Howald, C; Sylvan, A; Antonarakis, S

    2004-01-01

    Background: Chromosomal aneuploidies are a common cause of congenital disorders associated with cognitive impairment and multiple dysmorphic features. Pre-natal diagnosis of aneuploidies is most commonly performed by the karyotyping of fetal cells obtained by amniocentesis or chorionic villus sampling, but this method is labour intensive and requires about 14 days to complete. Methods: We have developed a PCR based method for the detection of targeted chromosome number abnormalities termed paralogous sequence quantification (PSQ), based on the use of paralogous genes. Paralogous sequences have a high degree of sequence identity, but accumulate nucleotide substitutions in a locus specific manner. These sequence differences, which we term paralogous sequence mismatches (PSMs), can be quantified using pyrosequencing technology, to estimate the relative dosage between different chromosomes. We designed 10 assays for the detection of trisomies of chromosomes 13, 18, and 21 and sex chromosome aneuploidies. Results: We evaluated the performance of this method on 175 DNAs, highly enriched for abnormal samples. A correct and unambiguous diagnosis was given for 119 out of 120 aneuploid samples as well as for all the controls. One sample which gave an intermediate value for the chromosome 13 assays could not be diagnosed. Conclusions: Our data suggests that PSQ is a robust, easy to interpret, and easy to set up method for the diagnosis of common aneuploidies, and can be performed in less than 48 h, representing a competitive alternative for widespread use in diagnostic laboratories. PMID:15591276

  9. Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.

    PubMed

    Rozhdestvensky, Timofey S; Robeck, Thomas; Galiveti, Chenna R; Raabe, Carsten A; Seeger, Birte; Wolters, Anna; Gubar, Leonid V; Brosius, Jürgen; Skryabin, Boris V

    2016-01-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. PMID:26848093

  10. A Fluorescent In Vitro Assay to Investigate Paralog-Specific SUMO Conjugation.

    PubMed

    Eisenhardt, Nathalie; Chaugule, Viduth K; Pichler, Andrea

    2016-01-01

    Protein modification with the small ubiquitin-related modifier SUMO is a potent regulatory mechanism implicated in a variety of biological pathways. In vitro sumoylation reactions have emerged as a versatile tool to identify and characterize novel SUMO enzymes as well as their substrates. Here, we present detailed protocols for the purification and fluorescent labeling of mammalian SUMO paralogs for their application in sumoylation assays. These assays provide a fast readout for in vitro SUMO chain formation activity of E3 ligases in a paralog-specific manner. Finally, we critically analyze the application of fluorescent SUMO proteins to study substrate modification in vitro revealing also the drawbacks of the system. PMID:27631798

  11. The C terminus of fragile X mental retardation protein interacts with the multi-domain Ran-binding protein in the microtubule-organising centre.

    PubMed

    Menon, Rajesh P; Gibson, Toby J; Pastore, Annalisa

    2004-10-01

    Absence of the fragile X mental retardation protein (FMRP) causes fragile X syndrome, the most common form of hereditary mental retardation. FMRP is a mainly cytoplasmic protein thought to be involved in repression of translation, through a complex network of protein-protein and protein-RNA interactions. Most of the currently known protein partners of FMRP recognise the conserved N terminus of the protein. No interaction has yet been mapped to the highly charged, poorly conserved C terminus, so far thought to be involved in RNA recognition through an RGG motif. In the present study, we show that a two-hybrid bait containing residues 419-632 of human FMRP fishes out a protein that spans the sequence of the Ran-binding protein in the microtubule-organising centre (RanBPM/RanBP9). Specific interaction of RanBPM with FMRP was confirmed by in vivo and in vitro assays. In brain tissue sections, RanBPM is highly expressed in the neurons of cerebral cortex and the cerebellar purkinje cells, in a pattern similar to that described for FMRP. Sequence analysis shows that RanBPM is a multi-domain protein. The interaction with FMRP was mapped in a newly identified CRA motif present in the RanBPM C terminus. Our results suggest that the functional role of RanBPM binding is modulation of the RNA-binding properties of FMRP.

  12. Orthologs, paralogs and genome comparisons

    NASA Technical Reports Server (NTRS)

    Gogarten, J. P.; Olendzenski, L.

    1999-01-01

    During the past decade, ancient gene duplications were recognized as one of the main forces in the generation of diverse gene families and the creation of new functional capabilities. New tools developed to search data banks for homologous sequences, and an increased availability of reliable three-dimensional structural information led to the recognition that proteins with diverse functions can belong to the same superfamily. Analyses of the evolution of these superfamilies promises to provide insights into early evolution but are complicated by several important evolutionary processes. Horizontal transfer of genes can lead to a vertical spread of innovations among organisms, therefore finding a certain property in some descendants of an ancestor does not guarantee that it was present in that ancestor. Complete or partial gene conversion between duplicated genes can yield phylogenetic trees with several, apparently independent gene duplications, suggesting an often surprising parallelism in the evolution of independent lineages. Additionally, the breakup of domains within a protein and the fusion of domains into multifunctional proteins makes the delineation of superfamilies a task that remains difficult to automate.

  13. Delayed myelination in an intrauterine growth retardation model is mediated by oxidative stress upregulating bone morphogenetic protein 4.

    PubMed

    Reid, Mary V; Murray, Kaitlin A; Marsh, Eric D; Golden, Jeffrey A; Simmons, Rebecca A; Grinspan, Judith B

    2012-07-01

    Intrauterine growth retardation (IUGR) is associated with neurological deficits including cerebral palsy and cognitive and behavioral disabilities. The pathogenesis involves oxidative stress that leads to periventricular white matter injury with a paucity of mature oligodendrocytes and hypomyelination. The molecular mechanisms underlying this damage remain poorly understood. We used a rat model of IUGR created by bilateral ligation of the uterine artery at embryonic Day 19 that results in fetal growth retardation and oxidative stress in the developing brain. The IUGR rat pups showed significant delays in oligodendrocyte differentiation and myelination that resolved by 8 weeks. Bone morphogenetic protein 4 (BMP4), which inhibits oligodendrocyte maturation, was elevated in IUGR brains at postnatal time points and returned to near normal by adulthood. Despite the apparent recovery, behavioral deficiencies were found in 8-week-old female animals, suggesting that the early transient myelination defects have permanent effects. In support of these in vivo data, oligodendrocyte precursor cells cultured from postnatal IUGR rats retained increased BMP4 expression and impaired differentiation that was reversed with the BMP inhibitor noggin. Oxidants in oligodendrocyte cultures increased BMP expression, which decreased differentiation; however, abrogating BMP signaling with noggin in vitro and in BMP-deficient mice prevented these effects. Together, these findings suggest that IUGR results in delayed myelination through the generation of oxidative stress that leads to BMP4 upregulation. PMID:22710965

  14. Boronate Complex Formation with Dopa Containing Mussel Adhesive Protein Retards pH-Induced Oxidation and Enables Adhesion to Mica

    PubMed Central

    Israelachvili, Jacob N.; Chen, Yunfei; Waite, J. Herbert

    2014-01-01

    The biochemistry of mussel adhesion has inspired the design of surface primers, adhesives, coatings and gels for technological applications. These mussel-inspired systems often focus on incorporating the amino acid 3,4-dihydroxyphenyl-L-alanine (Dopa) or a catecholic analog into a polymer. Unfortunately, effective use of Dopa is compromised by its susceptibility to auto-oxidation at neutral pH. Oxidation can lead to loss of adhesive function and undesired covalent cross-linking. Mussel foot protein 5 (Mfp-5), which contains ∼30 mole % Dopa, is a superb adhesive under reducing conditions but becomes nonadhesive after pH-induced oxidation. Here we report that the bidentate complexation of borate by Dopa to form a catecholato-boronate can be exploited to retard oxidation. Although exposure of Mfp-5 to neutral pH typically oxidizes Dopa, resulting in a>95% decrease in adhesion, inclusion of borate retards oxidation at the same pH. Remarkably, this Dopa-boronate complex dissociates upon contact with mica to allow for a reversible Dopa-mediated adhesion. The borate protection strategy allows for Dopa redox stability and maintained adhesive function in an otherwise oxidizing environment. PMID:25303409

  15. Proteins of normal hair and of cystine-deficient hair from mentally retarded siblings.

    PubMed

    Pollitt, R J; Stonier, P D

    1971-05-01

    1. S-Carboxymethylkerateines extracted from normal hair can be fractionated into high-sulphur and low-sulphur proteins similar to those obtained from sheep's wool. Normal human hair gives a major high-sulphur protein of higher molecular weight and S-carboxymethylcysteine content than any isolated from normal sheep's wool. 2. The proteins from cystine-deficient hair can also be divided into high-sulphur and low-sulphur proteins. There is a lower proportion of high-sulphur protein in cystine-deficient hair than in normal hair. 3. The high-sulphur proteins from cystine-deficient hair have an abnormal amino acid composition and in particular are lower in S-carboxymethylcysteine content than the corresponding proteins from normal hair. New components are present and the content of very high-sulphur proteins of high molecular weight is much decreased. The low-sulphur proteins of cystine-deficient hair are probably also deficient in S-carboxymethylcysteine. 4. The proteins of cystine-deficient hair probably resemble those in the normal hair root, except that disulphide-bridge formation has occurred.

  16. Learning and Behavioral Deficits Associated with the Absence of the Fragile X Mental Retardation Protein: What a Fly and Mouse Model Can Teach Us

    ERIC Educational Resources Information Center

    Santos, Ana Rita; Kanellopoulos, Alexandros K.; Bagni, Claudia

    2014-01-01

    The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the "FMR1" gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain…

  17. Mental Retardation.

    ERIC Educational Resources Information Center

    Purpura, Dominick P.; And Others

    Evidence today indicates that the causes of mental retardation are biological, psychological, and social in origin and that a combination of these causes frequently occur in a single individual. Mental retardation is identified clinically by the presence of several signs that include, but are not limited to, a significant impairment of…

  18. Mental Retardation.

    ERIC Educational Resources Information Center

    Baumeister, Alfred A., Ed.

    Thirteen papers by different authors consider the application of research findings and theoretical formulations to the practical appraisal and treatment of mental retardation. All suggest methods for shaping appropriate and adaptive behaviors in retarded individuals. The papers include "Definition, Diagnosis, and Classification" by D.W. Brison,…

  19. Brominated Flame Retardants, Tetrabromobisphenol A and Hexabromocyclododecane, Activate Mitogen-Activated Protein Kinases (MAPKs) in Human Natural Killer Cells

    PubMed Central

    Cato, Anita; Celada, Lindsay; Kibakaya, Esther Caroline; Simmons, Nadia; Whalen, Margaret M.

    2014-01-01

    NK cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10-0.5 µM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA. PMID:25341744

  20. Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure.

    PubMed

    Gatto, Cheryl L; Broadie, Kendal

    2008-08-01

    Fragile X syndrome (FraX), caused by the loss-of-function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is essential to define when and where FMRP loss causes the manifestation of synaptic defects, and whether the reintroduction of FMRP can restore normal synapse properties. In the Drosophila FraX model, dFMRP loss causes neuromuscular junction (NMJ) synapse over-elaboration (overgrowth, overbranching, excess synaptic boutons), accumulation of development-arrested satellite boutons, and altered neurotransmission. We used the Gene-Switch method to conditionally drive dFMRP expression to define the spatiotemporal requirements in synaptic mechanisms. Constitutive induction of targeted neuronal dFMRP at wild-type levels rescues all synaptic architectural defects in Drosophila Fmr1 (dfmr1)-null mutants, demonstrating a presynaptic requirement for synapse structuring. By contrast, presynaptic dFMRP expression does not ameliorate functional neurotransmission defects, indicating a postsynaptic dFMRP requirement. Strikingly, targeted early induction of dFMRP effects nearly complete rescue of synaptic structure defects, showing a primarily early-development role. In addition, acute dFMRP expression at maturity partially alleviates dfmr1-null defects, although rescue is not as complete as either early or constitutive dFMRP expression, showing a modest capacity for late-stage structural plasticity. We conclude that dFMRP predominantly acts early in synaptogenesis to modulate architecture, but that late dFMRP introduction at maturity can weakly compensate for early absence of dFMRP function. PMID:18579676

  1. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    SciTech Connect

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki; Ogawa, Atsushi; Suzuki, Shunji

    2011-02-18

    Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.

  2. Subcellular Fractionation and Localization Studies Reveal a Direct Interaction of the Fragile X Mental Retardation Protein (FMRP) with Nucleolin

    PubMed Central

    Taha, Mohamed S.; Nouri, Kazem; Milroy, Lech G.; Moll, Jens M.; Herrmann, Christian; Brunsveld, Luc; Piekorz, Roland P.; Ahmadian, Mohammad R.

    2014-01-01

    Fragile X mental Retardation Protein (FMRP) is a well-known regulator of local translation of its mRNA targets in neurons. However, despite its ubiquitous expression, the role of FMRP remains ill-defined in other cell types. In this study we investigated the subcellular distribution of FMRP and its protein complexes in HeLa cells using confocal imaging as well as detergent-free fractionation and size exclusion protocols. We found FMRP localized exclusively to solid compartments, including cytosolic heavy and light membranes, mitochondria, nuclear membrane and nucleoli. Interestingly, FMRP was associated with nucleolin in both a high molecular weight ribosomal and translation-associated complex (≥6 MDa) in the cytosol, and a low molecular weight complex (∼200 kDa) in the nucleoli. Consistently, we identified two functional nucleolar localization signals (NoLSs) in FMRP that are responsible for a strong nucleolar colocalization of the C-terminus of FMRP with nucleolin, and a direct interaction of the N-terminus of FMRP with the arginine-glycine-glycine (RGG) domain of nucleolin. Taken together, we propose a novel mechanism by which a transient nucleolar localization of FMRP underlies a strong nucleocytoplasmic translocation, most likely in a complex with nucleolin and possibly ribosomes, in order to regulate translation of its target mRNAs. PMID:24658146

  3. Vertebrate Paralogous MEF2 Genes: Origin, Conservation, and Evolution

    PubMed Central

    Wu, Wenwu; de Folter, Stefan; Shen, Xia; Zhang, Wenqian; Tao, Shiheng

    2011-01-01

    Background The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates. Methodology/Principal Findings By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes. First, among the four MEF2 paralogous branches, MEF2B is clearly distant from the other three branches in vertebrates, mainly because it lacks the HJURP_C (Holliday junction recognition protein C-terminal) region. Second, three duplication events might have occurred to produce the four MEF2 paralogous genes and the latest duplication event occurred near the origin of vertebrates producing MEF2A and MEF2C. Third, the ratio (Ka/Ks) of non-synonymous to synonymous nucleotide substitution rates showed that MEF2B evolves faster than the other three MEF2 proteins despite purifying selection on all of the four MEF2 branches. Moreover, a pair model of M0 versus M3 showed that variable selection exists among MEF2 proteins, and branch-site analysis presented that sites 53 and 64 along the MEF2B branch are under positive selection. Finally, and interestingly, substitution rates showed that type II MADS genes (i.e., MEF2-like genes) evolve as slowly as type I MADS genes (i.e., SRF-like genes) in animals, which is inconsistent with the fact that type II MADS genes evolve much slower than type I MADS genes in plants. Conclusion Our findings shed light on the relationship of MEF2A, B, C, and D with functional conservation and evolution in vertebrates. This study provides a rationale for future experimental design to investigate distinct but overlapping regulatory roles of the four MEF2 genes in various tissues. PMID:21394201

  4. Different Poses for Ligand and Chaperone in Inhibitor Bound Hsp90 and GRP94: Implications for Paralog-specific Drug Design

    PubMed Central

    Immormino, Robert M.; Metzger, Louis E.; Reardon, Patrick N.; Dollins, D. Eric; Blagg, Brian S.J.; Gewirth, Daniel T.

    2009-01-01

    Hsp90 chaperones contain an N-terminal ATP binding site that has been effectively targeted by competitive inhibitors. Despite the myriad of inhibitors, none to date have been designed to bind specifically to just one of the four mammalian hsp90 paralogs, which are cytoplasmic Hsp90α and β, ER GRP94, and mitochondrial Trap-1. Given that each of the hsp90 paralogs is responsible for chaperoning a distinct set of client proteins, specific targeting of one hsp90 paralog may result in higher efficacy and therapeutic control. Specific inhibitors may also help elucidate the biochemical roles of each hsp90 paralog. Here we present side by side comparisons of the structures of yeast Hsp90 and mammalian GRP94, bound to the pan-hsp90 inhibitors Geldanamycin and Radamide. These structures reveal paralog specific differences in the Hsp90 and GRP94 conformations in response to Geldanamycin binding. We also report significant variation in the pose and disparate binding affinities for the Geldanamycin-Radicicol chimera Radamide when bound to the two paralogs, which may be exploited in the design of paralog-specific inhibitors. PMID:19361515

  5. Intrauterine Growth Retarded Progeny of Pregnant Sows Fed High Protein:Low Carbohydrate Diet Is Related to Metabolic Energy Deficit

    PubMed Central

    Metges, Cornelia C.; Lang, Iris S.; Hennig, Ulf; Brüssow, Klaus-Peter; Kanitz, Ellen; Tuchscherer, Margret; Schneider, Falk; Weitzel, Joachim M.; Steinhoff-Ooster, Anika; Sauerwein, Helga; Bellmann, Olaf; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2012-01-01

    High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At −5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein∶low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein∶high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal. PMID:22328932

  6. Characterization and Expression of the Zebrafish qki Paralogs.

    PubMed

    Radomska, Katarzyna J; Sager, Jonathan; Farnsworth, Bryn; Tellgren-Roth, Åsa; Tuveri, Giulia; Peuckert, Christiane; Kettunen, Petronella; Jazin, Elena; Emilsson, Lina S

    2016-01-01

    Quaking (QKI) is an RNA-binding protein involved in post-transcriptional mRNA processing. This gene is found to be associated with several human neurological disorders. Early expression of QKI proteins in the developing mouse neuroepithelium, together with neural tube defects in Qk mouse mutants, suggest the functional requirement of Qk for the establishment of the nervous system. As a knockout of Qk is embryonic lethal in mice, other model systems like the zebrafish could serve as a tool to study the developmental functions of qki. In the present study we sought to characterize the evolutionary relationship and spatiotemporal expression of qkia, qki2, and qkib; zebrafish homologs of human QKI. We found that qkia is an ancestral paralog of the single tetrapod Qk gene that was likely lost during the fin-to-limb transition. Conversely, qkib and qki2 are orthologs, emerging at the root of the vertebrate and teleost lineage, respectively. Both qki2 and qkib, but not qkia, were expressed in the progenitor domains of the central nervous system, similar to expression of the single gene in mice. Despite having partially overlapping expression domains, each gene has a unique expression pattern, suggesting that these genes have undergone subfunctionalization following duplication. Therefore, we suggest the zebrafish could be used to study the separate functions of qki genes during embryonic development.

  7. Characterization and Expression of the Zebrafish qki Paralogs

    PubMed Central

    Radomska, Katarzyna J.; Sager, Jonathan; Farnsworth, Bryn; Tellgren-Roth, Åsa; Tuveri, Giulia; Peuckert, Christiane; Kettunen, Petronella; Jazin, Elena; Emilsson, Lina S.

    2016-01-01

    Quaking (QKI) is an RNA-binding protein involved in post-transcriptional mRNA processing. This gene is found to be associated with several human neurological disorders. Early expression of QKI proteins in the developing mouse neuroepithelium, together with neural tube defects in Qk mouse mutants, suggest the functional requirement of Qk for the establishment of the nervous system. As a knockout of Qk is embryonic lethal in mice, other model systems like the zebrafish could serve as a tool to study the developmental functions of qki. In the present study we sought to characterize the evolutionary relationship and spatiotemporal expression of qkia, qki2, and qkib; zebrafish homologs of human QKI. We found that qkia is an ancestral paralog of the single tetrapod Qk gene that was likely lost during the fin-to-limb transition. Conversely, qkib and qki2 are orthologs, emerging at the root of the vertebrate and teleost lineage, respectively. Both qki2 and qkib, but not qkia, were expressed in the progenitor domains of the central nervous system, similar to expression of the single gene in mice. Despite having partially overlapping expression domains, each gene has a unique expression pattern, suggesting that these genes have undergone subfunctionalization following duplication. Therefore, we suggest the zebrafish could be used to study the separate functions of qki genes during embryonic development. PMID:26727370

  8. Characterization of Zebrafish Cardiac and Slow Skeletal Troponin C Paralogs by MD Simulation and ITC.

    PubMed

    Stevens, Charles M; Rayani, Kaveh; Genge, Christine E; Singh, Gurpreet; Liang, Bo; Roller, Janine M; Li, Cindy; Li, Alison Yueh; Tieleman, D Peter; van Petegem, Filip; Tibbits, Glen F

    2016-07-12

    Zebrafish, as a model for teleost fish, have two paralogous troponin C (TnC) genes that are expressed in the heart differentially in response to temperature acclimation. Upon Ca(2+) binding, TnC changes conformation and exposes a hydrophobic patch that interacts with troponin I and initiates cardiac muscle contraction. Teleost-specific TnC paralogs have not yet been functionally characterized. In this study we have modeled the structures of the paralogs using molecular dynamics simulations at 18°C and 28°C and calculated the different Ca(2+)-binding properties between the teleost cardiac (cTnC or TnC1a) and slow-skeletal (ssTnC or TnC1b) paralogs through potential-of-mean-force calculations. These values are compared with thermodynamic binding properties obtained through isothermal titration calorimetry (ITC). The modeled structures of each of the paralogs are similar at each temperature, with the exception of helix C, which flanks the Ca(2+) binding site; this region is also home to paralog-specific sequence substitutions that we predict have an influence on protein function. The short timescale of the potential-of-mean-force calculation precludes the inclusion of the conformational change on the ΔG of Ca(2+) interaction, whereas the ITC analysis includes the Ca(2+) binding and conformational change of the TnC molecule. ITC analysis has revealed that ssTnC has higher Ca(2+) affinity than cTnC for Ca(2+) overall, whereas each of the paralogs has increased affinity at 28°C compared to 18°C. Microsecond-timescale simulations have calculated that the cTnC paralog transitions from the closed to the open state more readily than the ssTnC paralog, an unfavorable transition that would decrease the ITC-derived Ca(2+) affinity while simultaneously increasing the Ca(2+) sensitivity of the myofilament. We propose that the preferential expression of cTnC at lower temperatures increases myofilament Ca(2+) sensitivity by this mechanism, despite the lower Ca(2+) affinity

  9. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

    PubMed

    Hendriks, Hester S; Koolen, Lucas A E; Dingemans, Milou M L; Viberg, Henrik; Lee, Iwa; Leonards, Pim E G; Ramakers, Geert M J; Westerink, Remco H S

    2015-12-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

  10. Genes and processed paralogs co-exist in plant mitochondria.

    PubMed

    Cuenca, Argelia; Petersen, Gitte; Seberg, Ole; Jahren, Anne Hoppe

    2012-04-01

    RNA-mediated gene duplication has been proposed to create processed paralogs in the plant mitochondrial genome. A processed paralog may retain signatures left by the maturation process of its RNA precursor, such as intron removal and no need of RNA editing. Whereas it is well documented that an RNA intermediary is involved in the transfer of mitochondrial genes to the nucleus, no direct evidence exists for insertion of processed paralogs in the mitochondria (i.e., processed and un-processed genes have never been found simultaneously in the mitochondrial genome). In this study, we sequenced a region of the mitochondrial gene nad1, and identified a number of taxa were two different copies of the region co-occur in the mitochondria. The two nad1 paralogs differed in their (a) presence or absence of a group II intron, and (b) number of edited sites. Thus, this work provides the first evidence of co-existence of processed paralogs and their precursors within the plant mitochondrial genome. In addition, mapping the presence/absence of the paralogs provides indirect evidence of RNA-mediated gene duplication as an essential process shaping the mitochondrial genome in plants.

  11. Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells

    NASA Technical Reports Server (NTRS)

    Wiese, Claudia; Collins, David W.; Albala, Joanna S.; Thompson, Larry H.; Kronenberg, Amy; Schild, David; Chatterjee, A. (Principal Investigator)

    2002-01-01

    Homologous recombinational repair of DNA double-strand breaks and crosslinks in human cells is likely to require Rad51 and the five Rad51 paralogs (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3), as has been shown in chicken and rodent cells. Previously, we reported on the interactions among these proteins using baculovirus and two- and three-hybrid yeast systems. To test for interactions involving XRCC3 and Rad51C, stable human cell lines have been isolated that express (His)6-tagged versions of XRCC3 or Rad51C. Ni2+-binding experiments demonstrate that XRCC3 and Rad51C interact in human cells. In addition, we find that Rad51C, but not XRCC3, interacts directly or indirectly with Rad51B, Rad51D and XRCC2. These results argue that there are at least two complexes of Rad51 paralogs in human cells (Rad51C-XRCC3 and Rad51B-Rad51C-Rad51D-XRCC2), both containing Rad51C. Moreover, Rad51 is not found in these complexes. X-ray treatment did not alter either the level of any Rad51 paralog or the observed interactions between paralogs. However, the endogenous level of Rad51C is moderately elevated in the XRCC3-overexpressing cell line, suggesting that dimerization between these proteins might help stabilize Rad51C.

  12. Flame retardants

    NASA Technical Reports Server (NTRS)

    Troitzsch, J.

    1988-01-01

    The use of flame retardants in plastics has grown only slightly in recent years and will probably grow slowly in the future. The reasons for this are slow economic growth and the absence of fundamentally new requirements for future fire prevention. The trends are toward the increasing use of easily handled, dust-free and well-dispersed flame retardant compounds and master batches; there are no spectacular new developments. In the future, questions of smoke evolution, toxicity and corrosiveness of combustion gases will become increasingly important, especially due to new regulations and rising requirements for environmental protection.

  13. Insulin-like growth factor binding protein (IGFBP-1) involvement in intrauterine growth retardation: study on IGFBP-1 overexpressing transgenic mice.

    PubMed

    Ben Lagha, Nadia; Seurin, Danielle; Le Bouc, Yves; Binoux, Michel; Berdal, Ariane; Menuelle, Pierrette; Babajko, Sylvie

    2006-10-01

    In humans, intrauterine growth retardation is correlated to high levels of serum IGF binding protein-1 (IGFBP-1). This present study analyzes in vivo the impact of circulating IGFBP-1 on body growth associated to bone mineralization and carbohydrate resources. Transgenic mice used in this work overexpressed human IGFBP-1 in liver from embryonic day (E)14.5, concomitantly to the appearance of ossification centers, through to adulthood. Growth retardation was observed as early as E17.5 in homozygous (HM) mice being 20% smaller at birth (postnatal d 1). Anatomical analysis of the skeletons by alizarin red and alcian blue staining showed that the mice exhibited pleiotropic defects of several skeletal units. Some bones were small and dysmorphic. Our results showed reduced mineralization in the posterior area of the skull (delayed suture closure), as well as in the appendicular and axial skeleton. Heterozygous crossings showed a loss of HM animals. Moreover, IGFBP-1 overexpression contributed to decreased fetal hepatic glycogen and neonate blood glucose levels which constitute the main reservoir of carbohydrate resources for neonates. Thus, this reduced carbohydrate pool contributed to perinatal mortality. Maternal IGFBP-1 expression was also clearly associated with neonate growth retardation (newborn weights from HM mothers were 20% smaller than newborns from NT mothers) and reduced fetal carbohydrate resources. In conclusion, antenatal growth retardation and delayed mineralization in transgenic mice are related to overexpressed fetal and maternal circulating human IGFBP-1. Similar perturbations could be observed in human intrauterine growth retardation suggesting the IGF/IGFBP system is involved in fetal growth, biomineralization, and energetic status in humans.

  14. Fragile X Mental Retardation Protein is Required for Programmed Cell Death and Clearance of Developmentally-Transient Peptidergic Neurons

    PubMed Central

    Gatto, Cheryl L.; Broadie, Kendal

    2011-01-01

    Fragile X syndrome (FXS), caused by loss of fragile X mental retardation 1 (FMR1) gene function, is the most common heritable cause of intellectual disability and autism spectrum disorders. The FMR1 product (FMRP) is an RNA-binding protein best established to function in activity-dependent modulation of synaptic connections. In the Drosophila FXS disease model, loss of functionally-conserved dFMRP causes synaptic overgrowth and overelaboration in pigment dispersing factor (PDF) peptidergic neurons in the adult brain. Here, we identify a very different component of PDF neuron misregulation in dfmr1 mutants: the aberrant retention of normally developmentally-transient PDF tritocerebral (PDF-TRI) neurons. In wild-type animals, PDF-TRI neurons in the central brain undergo programmed cell death and complete, processive clearance within days of eclosion. In the absence of dFMRP, a defective apoptotic program leads to constitutive maintenance of these peptidergic neurons. We tested whether this apoptotic defect is circuit-specific by examining crustacean cardioactive peptide (CCAP) and bursicon circuits, which are similarly developmentally-transient and normally eliminated immediately post-eclosion. In dfmr1 null mutants, CCAP/bursicon neurons also exhibit significantly delayed clearance dynamics, but are subsequently eliminated from the nervous system, in contrast to the fully persistent PDF-TRI neurons. Thus, the requirement of dFMRP for the retention of transitory peptidergic neurons shows evident circuit specificity. The novel defect of impaired apoptosis and aberrant neuron persistence in the Drosophila FXS model suggests an entirely new level of “pruning” dysfunction may contribute to the FXS disease state. PMID:21596027

  15. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase δ.

    PubMed

    Yoshida, Tomoyuki; Yasumura, Misato; Uemura, Takeshi; Lee, Sung-Jin; Ra, Moonjin; Taguchi, Ryo; Iwakura, Yoichiro; Mishina, Masayoshi

    2011-09-21

    Mental retardation (MR) and autism are highly heterogeneous neurodevelopmental disorders. IL-1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic MR and is associated with autism. Thus, the elucidation of the functional role of IL1RAPL1 will contribute to our understanding of the pathogenesis of these mental disorders. Here, we showed that knockdown of endogenous IL1RAPL1 in cultured cortical neurons suppressed the accumulation of punctate staining signals for active zone protein Bassoon and decreased the number of dendritic protrusions. Consistently, the expression of IL1RAPL1 in cultured neurons stimulated the accumulation of Bassoon and spinogenesis. The extracellular domain (ECD) of IL1RAPL1 was required and sufficient for the presynaptic differentiation-inducing activity, while both the ECD and cytoplasmic domain were essential for the spinogenic activity. Notably, the synaptogenic activity of IL1RAPL1 was specific for excitatory synapses. Furthermore, we identified presynaptic protein tyrosine phosphatase (PTP) δ as a major IL1RAPL1-ECD interacting protein by affinity chromatography. IL1RAPL1 interacted selectively with certain forms of PTPδ splice variants carrying mini-exon peptides in Ig-like domains. The synaptogenic activity of IL1RAPL1 was abolished in primary neurons from PTPδ knock-out mice. IL1RAPL1 showed robust synaptogenic activity in vivo when transfected into the cortical neurons of wild-type mice but not in PTPδ knock-out mice. These results suggest that IL1RAPL1 mediates synapse formation through trans-synaptic interaction with PTPδ. Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of MR and autism as a common pathogenic pathway shared by these mental disorders.

  16. Role of the Saccharomyces cerevisiae Rad51 paralogs in sister chromatid recombination.

    PubMed

    Mozlin, Amy M; Fung, Cindy W; Symington, Lorraine S

    2008-01-01

    Rad51 requires a number of other proteins, including the Rad51 paralogs, for efficient recombination in vivo. Current evidence suggests that the yeast Rad51 paralogs, Rad55 and Rad57, are important in formation or stabilization of the Rad51 nucleoprotein filament. To gain further insights into the function of the Rad51 paralogs, reporters were designed to measure spontaneous or double-strand break (DSB)-induced sister or nonsister recombination. Spontaneous sister chromatid recombination (SCR) was reduced 6000-fold in the rad57 mutant, significantly more than in the rad51 mutant. Although the DSB-induced recombination defect of rad57 was suppressed by overexpression of Rad51, elevated temperature, or expression of both mating-type alleles, the rad57 defect in spontaneous SCR was not strongly suppressed by these same factors. In addition, the UV sensitivity of the rad57 mutant was not strongly suppressed by MAT heterozygosity, even though Rad51 foci were restored under these conditions. This lack of suppression suggests that Rad55 and Rad57 have different roles in the recombinational repair of stalled replication forks compared with DSB repair. Furthermore, these data suggest that most spontaneous SCR initiates from single-stranded gaps formed at stalled replication forks rather than DSBs.

  17. Functional specialization of chordate CDK1 paralogs during oogenic meiosis

    PubMed Central

    Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina; Thompson, Eric M

    2015-01-01

    Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell cycle progression. In contrast to interphase CDKs, the mitotic phase CDK1 is the only CDK capable of driving the entire cell cycle and it can do so from yeast to mammals. Interestingly, plants and the marine chordate, Oikopleura dioica, possess paralogs of the highly conserved CDK1 regulator. However, whereas in plants the 2 CDK1 paralogs replace interphase CDK functions, O. dioica has a full complement of interphase CDKs in addition to its 5 odCDK1 paralogs. Here we show specific sub-functionalization of odCDK1 paralogs during oogenesis. Differential spatiotemporal dynamics of the odCDK1a, d and e paralogs and the meiotic polo-like kinase 1 (Plk1) and aurora kinase determine the subset of meiotic nuclei in prophase I arrest that will seed growing oocytes and complete meiosis. Whereas we find odCDK1e to be non-essential, knockdown of the odCDK1a paralog resulted in the spawning of non-viable oocytes of reduced size. Knockdown of odCDK1d also resulted in the spawning of non-viable oocytes. In this case, the oocytes were of normal size, but were unable to extrude polar bodies upon exposure to sperm, because they were unable to resume meiosis from prophase I arrest, a classical function of the sole CDK1 during meiosis in other organisms. Thus, we reveal specific sub-functionalization of CDK1 paralogs, during the meiotic oogenic program. PMID:25714331

  18. Functional specialization of chordate CDK1 paralogs during oogenic meiosis.

    PubMed

    Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina; Thompson, Eric M

    2015-01-01

    Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell cycle progression. In contrast to interphase CDKs, the mitotic phase CDK1 is the only CDK capable of driving the entire cell cycle and it can do so from yeast to mammals. Interestingly, plants and the marine chordate, Oikopleura dioica, possess paralogs of the highly conserved CDK1 regulator. However, whereas in plants the 2 CDK1 paralogs replace interphase CDK functions, O. dioica has a full complement of interphase CDKs in addition to its 5 odCDK1 paralogs. Here we show specific sub-functionalization of odCDK1 paralogs during oogenesis. Differential spatiotemporal dynamics of the odCDK1a, d and e paralogs and the meiotic polo-like kinase 1 (Plk1) and aurora kinase determine the subset of meiotic nuclei in prophase I arrest that will seed growing oocytes and complete meiosis. Whereas we find odCDK1e to be non-essential, knockdown of the odCDK1a paralog resulted in the spawning of non-viable oocytes of reduced size. Knockdown of odCDK1d also resulted in the spawning of non-viable oocytes. In this case, the oocytes were of normal size, but were unable to extrude polar bodies upon exposure to sperm, because they were unable to resume meiosis from prophase I arrest, a classical function of the sole CDK1 during meiosis in other organisms. Thus, we reveal specific sub-functionalization of CDK1 paralogs, during the meiotic oogenic program. PMID:25714331

  19. Retardation of Protein Dynamics by Trehalose in Dehydrated Systems of Photosynthetic Reaction Centers. Insights from Electron Transfer and Thermal Denaturation Kinetics.

    PubMed

    Malferrari, Marco; Francia, Francesco; Venturoli, Giovanni

    2015-10-29

    Conformational protein dynamics is known to be hampered in amorphous matrixes upon dehydration, both in the absence and in the presence of glass forming disaccharides, like trehalose, resulting in enhanced protein thermal stability. To shed light on such matrix effects, we have compared the retardation of protein dynamics in photosynthetic bacterial reaction centers (RC) dehydrated at controlled relative humidity in the absence (RC films) or in the presence of trehalose (RC-trehalose glasses). Small scale RC dynamics, associated with the relaxation from the dark-adapted to the light-adapted conformation, have been probed up to the second time scale by analyzing the kinetics of electron transfer from the photoreduced quinone acceptor (QA(-)) to the photoxidized primary donor (P(+)) as a function of the duration of photoexcitation from 7 ns (laser pulse) to 20 s. A more severe inhibition of dynamics is found in RC-trehalose glasses than in RC films: only in the latter system does a complete relaxation to the light-adapted conformation occur even at extreme dehydration, although strongly retarded. To gain insight into the large scale RC dynamics up to the time scale of days, the kinetics of thermal denaturation have been studied at 44 °C by spectral analysis of the Qx and Qy bands of the RC bacteriochlorin cofactors, as a function of the sugar/protein molar ratio, m, varied between 0 and 10(4). Upon increasing m, denaturation is slowed progressively, and above m ∼ 500 the RC is stable at least for several days. The stronger retardation of RC relaxation and dynamics induced by trehalose is discussed in the light of a recent molecular dynamics simulation study performed in matrixes of the model protein lysozyme with and without trehalose. We suggest that the efficiency of trehalose in retarding RC dynamics and preventing thermal denaturation stems mainly from its propensity to form and stabilize extended networks of hydrogen bonds involving sugar, residual water, and

  20. pATsi: Paralogs and Singleton Genes from Arabidopsis thaliana

    PubMed Central

    Ambrosino, Luca; Bostan, Hamed; di Salle, Pasquale; Sangiovanni, Mara; Vigilante, Alessandra; Chiusano, Maria L.

    2016-01-01

    Arabidopsis thaliana is widely accepted as a model species in plant biology. Its genome, due to its small size and diploidy, was the first to be sequenced among plants, making this species also a reference for plant comparative genomics. Nevertheless, the evolutionary mechanisms that shaped the Arabidopsis genome are still controversial. Indeed, duplications, translocations, inversions, and gene loss events that contributed to the current organization are difficult to be traced. A reliable identification of paralogs and single-copy genes is essential to understand these mechanisms. Therefore, we implemented a dedicated pipeline to identify paralog genes and classify single-copy genes into opportune categories. PATsi, a web-accessible database, was organized to allow the straightforward access to the paralogs organized into networks and to the classification of single-copy genes. This permits to efficiently explore the gene collection of Arabidopsis for evolutionary investigations and comparative genomics. PMID:26792975

  1. pATsi: Paralogs and Singleton Genes from Arabidopsis thaliana.

    PubMed

    Ambrosino, Luca; Bostan, Hamed; di Salle, Pasquale; Sangiovanni, Mara; Vigilante, Alessandra; Chiusano, Maria L

    2016-01-01

    Arabidopsis thaliana is widely accepted as a model species in plant biology. Its genome, due to its small size and diploidy, was the first to be sequenced among plants, making this species also a reference for plant comparative genomics. Nevertheless, the evolutionary mechanisms that shaped the Arabidopsis genome are still controversial. Indeed, duplications, translocations, inversions, and gene loss events that contributed to the current organization are difficult to be traced. A reliable identification of paralogs and single-copy genes is essential to understand these mechanisms. Therefore, we implemented a dedicated pipeline to identify paralog genes and classify single-copy genes into opportune categories. PATsi, a web-accessible database, was organized to allow the straightforward access to the paralogs organized into networks and to the classification of single-copy genes. This permits to efficiently explore the gene collection of Arabidopsis for evolutionary investigations and comparative genomics.

  2. The paralogous R3 MYB proteins CAPRICE, TRIPTYCHON and ENHANCER OF TRY AND CPC1 play pleiotropic and partly non-redundant roles in the phosphate starvation response of Arabidopsis roots

    PubMed Central

    Chen, Chun-Ying; Schmidt, Wolfgang

    2015-01-01

    Phosphate (Pi) deficiency alters root hair length and frequency as a means of increasing the absorptive surface area of roots. Three partly redundant single R3 MYB proteins, CAPRICE (CPC), ENHANCER OF TRY AND CPC1 (ETC1) and TRIPTYCHON (TRY), positively regulate the root hair cell fate by participating in a lateral inhibition mechanism. To identify putative targets and processes that are controlled by these three transcription factors (TFs), we conducted transcriptional profiling of roots from Arabidopsis thaliana wild-type plants, and cpc, etc1 and try mutants grown under Pi-replete and Pi-deficient conditions using RNA-seq. The data show that in an intricate interplay between the three MYBs regulate several developmental, physiological and metabolic processes that are putatively located in different tissues. When grown on media with a low Pi concentration, all three TFs acquire additional functions that are related to the Pi starvation response, including transition metal transport, membrane lipid remodelling, and the acquisition, uptake and storage of Pi. Control of gene activity is partly mediated through the regulation of potential antisense transcripts. The current dataset extends the known functions of R3 MYB proteins, provides a suite of novel candidates with critical function in root hair development under both control and Pi-deficient conditions, and challenges the definition of genetic redundancy by demonstrating that environmental perturbations may confer specific functions to orthologous proteins that could have similar roles under control conditions. PMID:26022254

  3. Arabidopsis Small Ubiquitin-Like Modifier Paralogs Have Distinct Functions in Development and Defense[C][W][OA

    PubMed Central

    van den Burg, Harrold A.; Kini, Ramachandra K.; Schuurink, Robert C.; Takken, Frank L.W.

    2010-01-01

    Posttranslational modifications allow dynamic and reversible changes to protein function. In Arabidopsis thaliana, a small gene family encodes paralogs of the small ubiquitin-like posttranslational modifier. We studied the function of these paralogs. Single mutants of the SUM1 and SUM2 paralogs do not exhibit a clear phenotype. However, the corresponding double knockdown mutant revealed that SUM1 and SUM2 are essential for plant development, floral transition, and suppression of salicylic acid (SA)–dependent defense responses. The SUM1 and SUM2 genes are constitutively expressed, but their spatial expression patterns do not overlap. Tight transcriptional regulation of these two SUM genes appears to be important, as overexpression of either wild-type or conjugation-deficient mutants resulted in activation of SA-dependent defense responses, as did the sum1 sum2 knockdown mutant. Interestingly, expression of the paralog SUM3 is strongly and widely induced by SA and by the defense elicitor Flg22, whereas its expression is otherwise low and restricted to a few specific cell types. Loss of SUM3 does not result in an aberrant developmental phenotype except for late flowering, while SUM3 overexpression causes early flowering and activates plant defense. Apparently, SUM3 promotes plant defense downstream of SA, while SUM1 and SUM2 together prevent SA accumulation in noninfected plants. PMID:20525853

  4. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo.

    PubMed

    Cappai, Roberto; Cheng, Fang; Ciccotosto, Giuseppe D; Needham, B Elise; Masters, Colin L; Multhaup, Gerd; Fransson, Lars-Ake; Mani, Katrin

    2005-04-01

    Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1. PMID:15677459

  5. Glucocorticoids retard skeletal muscle development and myoblast protein synthesis through a mechanistic target of rapamycin (mTOR)-signaling pathway in broilers (Gallus gallus domesticus).

    PubMed

    Wang, Xiaojuan; Jia, Qing; Xiao, Jingjing; Jiao, Hongchao; Lin, Hai

    2015-01-01

    Glucocorticoids exert a well-known catabolic protein action on skeletal muscle. The mechanistic target of rapamycin (mTOR) signaling pathway acts as a central regulator of protein metabolism. Whether glucocorticoids regulate protein synthesis through the mTOR pathway in skeletal muscle of chickens remains unknown. This study was performed to characterize the effect of glucocorticoids on the mTOR pathway in skeletal muscle development in chickens, and on protein synthesis in cultured embryonic myoblasts. Male 29-d-old chickens were given a dexamethasone injection (2 mg/kg) twice per day for 4 d (n = 16). Chicken embryonic myoblasts were exposed to dexamethasone for 24 h (100 µmol/L, n = 4 cultures). The interaction between dexamethasone and leucine was also investigated. ANOVA and Duncan's multiple test were used to analyze the effects of the dexamethasone and leucine treatments. The results showed that dexamethasone decreased body weight gain, body weight, and feed efficiency. Protein synthesis was inhibited by in vitro dexamethasone exposure. Phosphorylation of mTOR and ribosomal protein S6 protein kinase (p70S6K) were inhibited by dexamethasone, suggesting the mTOR pathway may be involved in dexamethasone-regulated muscle protein synthesis. Phosphorylation of AMP-activated protein kinase (AMPK) was not altered in vitro but was reduced in vivo by dexamethasone. These results imply that the mTOR and AMPK pathways are both involved in retarding muscle development and protein synthesis by glucocorticoids, but the mTOR pathway is a critical point linking glucocorticoid and protein synthesis. Leucine, at least partially, inhibited the effects of dexamethasone on protein synthesis via the mTOR pathway.

  6. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation

    PubMed Central

    Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

    2016-01-01

    secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway. PMID:26894743

  7. Food restriction retards body growth and prevents end-stage renal pathology in remnant kidneys of rats regardless of protein intake.

    PubMed

    Tapp, D C; Wortham, W G; Addison, J F; Hammonds, D N; Barnes, J L; Venkatachalam, M A

    1989-02-01

    The objectives of this study were to evaluate the effects of food restriction (without protein or phosphorus restriction) and protein restriction (without the restriction of other nutrients or calories) on the outcome of the remnant kidney model of chronic renal failure in rats. After 5/6 nephrectomy, rats were assigned to one of the following dietary groups: group I (control-ad libitum) consumed a 21% casein diet ad libitum; group II (food restriction with protein restriction) consumed 36% less calories, protein and minerals than group I; group III (food restriction without protein restriction) consumed 36% less calories and minerals than group I, but equivalent amounts of protein; group IV (protein restriction) consumed 38% less protein than group I, but equivalent amounts of calories and minerals; group V (NaCl restriction) consumed 40% less sodium chloride than group I, but equivalent amounts of all other nutrients. All groups consumed equivalent amounts of calcium, phosphorus and vitamins. Groups II and III experienced retardation of growth in comparison to groups I, IV and V. The food-restricted groups II and III, but not groups IV and V, had less proteinuria than group I 20 weeks postablation. By 21 weeks postablation, the kidneys from group I showed severe parenchymal damage, characteristic of end-stage renal pathology. These changes were prevented in the food-restricted groups II and III, but not in groups IV and V. The percentage of glomeruli with severe structural damage was less in groups II (27.3 +/- 8.8) and III (26.9 +/- 7.5) compared with group I (72.4 +/- 7.8). In contrast, the corresponding values in groups IV and V were not significantly different from group I. Interstitial volume (the percentage of tubulointerstitium which is interstitium) which was proportional to the severity of tubular damage was significantly lower in groups II (25.1 +/- 4.5) and III (20.4 +/- 2.8) when compared with groups I (48.1 +/- 3.0), IV (44.4 +/- 6.6), or V (41

  8. Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans.

    PubMed

    McClendon, T Brooke; Sullivan, Meghan R; Bernstein, Kara A; Yanowitz, Judith L

    2016-05-01

    Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast. Evolutionary analysis of the SWIM domain identified Caenorhabditis elegans sws-1 as a putative homolog of the yeast Shu complex member Shu2. Using a CRISPR-induced nonsense allele of sws-1, we show that sws-1 promotes HR in mitotic and meiotic nuclei. sws-1 mutants exhibit sensitivity to DSB-inducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. Phenotypic similarities between sws-1 and the two RAD-51 paralogs rfs-1 and rip-1 suggest that they function together. Indeed, we detect direct interaction between SWS-1 and RIP-1 by yeast two-hybrid assay that is mediated by the SWIM domain in SWS-1 and the Walker B motif in RIP-1 Furthermore, RIP-1 bridges an interaction between SWS-1 and RFS-1, suggesting that RIP-1 facilitates complex formation with SWS-1 and RFS-1 We propose that SWS-1, RIP-1, and RFS-1 compose a C. elegans Shu complex. Our work provides a new model for studying Shu complex disruption in the context of a multicellular organism that has important implications as to why mutations in the human RAD51 paralogs are associated with genome instability.

  9. Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans.

    PubMed

    McClendon, T Brooke; Sullivan, Meghan R; Bernstein, Kara A; Yanowitz, Judith L

    2016-05-01

    Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast. Evolutionary analysis of the SWIM domain identified Caenorhabditis elegans sws-1 as a putative homolog of the yeast Shu complex member Shu2. Using a CRISPR-induced nonsense allele of sws-1, we show that sws-1 promotes HR in mitotic and meiotic nuclei. sws-1 mutants exhibit sensitivity to DSB-inducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. Phenotypic similarities between sws-1 and the two RAD-51 paralogs rfs-1 and rip-1 suggest that they function together. Indeed, we detect direct interaction between SWS-1 and RIP-1 by yeast two-hybrid assay that is mediated by the SWIM domain in SWS-1 and the Walker B motif in RIP-1 Furthermore, RIP-1 bridges an interaction between SWS-1 and RFS-1, suggesting that RIP-1 facilitates complex formation with SWS-1 and RFS-1 We propose that SWS-1, RIP-1, and RFS-1 compose a C. elegans Shu complex. Our work provides a new model for studying Shu complex disruption in the context of a multicellular organism that has important implications as to why mutations in the human RAD51 paralogs are associated with genome instability. PMID:26936927

  10. EPGD: a comprehensive web resource for integrating and displaying eukaryotic paralog/paralogon information.

    PubMed

    Ding, Guohui; Sun, Yan; Li, Hong; Wang, Zhen; Fan, Haiwei; Wang, Chuan; Yang, Dan; Li, Yixue

    2008-01-01

    Gene duplication is common in all three domains of life, especially in eukaryotic genomes. The duplicates provide new material for the action of evolutionary forces such as selection or genetic drift. Here we describe a sophisticated procedure to extract duplicated genes (paralogs) from 26 available eukaryotic genomes, to pre-calculate several evolutionary indexes (evolutionary rate, synonymous distance/clock, transition redundant exchange clock, etc.) based on the paralog family, and to identify block or segmental duplications (paralogons). We also constructed an internet-accessible Eukaryotic Paralog Group Database (EPGD; http://epgd.biosino.org/EPGD/). The database is gene-centered and organized by paralog family. It focuses on paralogs and evolutionary duplication events. The paralog families and paralogons can be searched by text or sequence, and are downloadable from the website as plain text files. The database will be very useful for both experimentalists and bioinformaticians interested in the study of duplication events or paralog families.

  11. Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study

    PubMed Central

    2011-01-01

    Background Fragile X syndrome is caused by loss of function of the fragile X mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. Methods In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and γ-aminobutyric acid (GABA) A receptor β3 (GABRβ3), as well as glial fibrillary acidic protein (GFAP). Results We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABRβ3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. Conclusion These changes may be responsible for cognitive deficits and seizure disorder in people with autism. PMID:21548960

  12. Fragile X Mental Retardation Protein Interactions with a G quadruplex structure in the 3′-Untranslated Region of NR2B mRNA

    PubMed Central

    Stefanovic, Snezana; DeMarco, Brett A.; Underwood, Ayana; Williams, Kathryn R.; Bassell, Gary J.; Mihailescu, Mihaela Rita

    2015-01-01

    Fragile X syndrome, the most common cause of inherited intellectual disability, is caused by a trinucleotide CGG expansion in the 5′-untranslated region of the FMR1 gene, which leads to the loss of expression of the fragile X mental retardation protein (FMRP). FMRP, an RNA-binding protein that regulates the translation of specific mRNAs, has been shown to bind a subset of its mRNA targets by recognizing G quadruplex structures. It has been suggested that FMRP controls the local protein synthesis of several protein components of the Post Synaptic Density (PSD) in response to specific cellular needs. We have previously shown that the interactions between FMRP and mRNAs of the PSD scaffold proteins PSD-95 and Shank1 are mediated via stable G-quadruplex structures formed within the 3′-untranslated regions of these mRNAs. In this study we used biophysical methods to show that a comparable G quadruplex structure forms in the 3′-untranslated region of the glutamate receptor subunit NR2B mRNA encoding for a subunit of N-methyl-D-aspartate (NMDA) receptors that is recognized specifically by FMRP, suggesting a common theme for FMRP recognition of its dendritic mRNA targets. PMID:26412477

  13. A paralog of the proteinaceous elicitor SM1 is involved in colonization of maize roots by Trichoderma virens.

    PubMed

    Crutcher, Frankie K; Moran-Diez, Maria E; Ding, Shengli; Liu, Jinggao; Horwitz, Benjamin A; Mukherjee, Prasun K; Kenerley, Charles M

    2015-06-01

    The biocontrol agent, Trichoderma virens, has the ability to protect plants from pathogens by eliciting plant defense responses, involvement in mycoparasitism, or secreting antagonistic secondary metabolites. SM1, an elicitor of induced systemic resistance (ISR), was found to have three paralogs within the T. virens genome. The paralog sm2 is highly expressed in the presence of plant roots. Gene deletion mutants of sm2 were generated and the mutants were found to overproduce SM1. The ability to elicit ISR in maize against Colletotrichum graminicola was not compromised for the mutants compared to that of wild type isolate. However, the deletion strains had a significantly lowered ability to colonize maize roots. This appears to be the first report on the involvement of an effector-like protein in colonization of roots by Trichoderma.

  14. Datasets depicting mobility retardation of NCS proteins observed upon incubation with calcium, but not with magnesium, barium or strontium.

    PubMed

    Viviano, Jeffrey; Krishnan, Anuradha; Scully, Jenna; Wu, Hao; Venkataraman, Venkat

    2016-06-01

    In this data article we show the specificity of the Ca(2+)-induced mobility shift in three proteins that belong to the neuronal calcium sensor (NCS) protein family: Hippocalcin, GCAP1 and GCAP2. These proteins did not display a shift in mobility in native gels when incubated with divalent cations other than Ca(2+) - such as Mg(2+), Ba(2+), and Sr(2+), even at 10× concentrations. The data is similar to that obtained with another NCS protein, neurocalcin delta (Viviano et al., 2016, "Electrophoretic Mobility Shift in Native Gels Indicates Calcium-dependent Structural Changes of Neuronal Calcium Sensor Proteins", [1]). PMID:27222862

  15. Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules.

    PubMed

    El Fatimy, Rachid; Davidovic, Laetitia; Tremblay, Sandra; Jaglin, Xavier; Dury, Alain; Robert, Claude; De Koninck, Paul; Khandjian, Edouard W

    2016-07-01

    Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome.

  16. Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules.

    PubMed

    El Fatimy, Rachid; Davidovic, Laetitia; Tremblay, Sandra; Jaglin, Xavier; Dury, Alain; Robert, Claude; De Koninck, Paul; Khandjian, Edouard W

    2016-07-01

    Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome. PMID:27462983

  17. Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules

    PubMed Central

    Tremblay, Sandra; Jaglin, Xavier; Dury, Alain; Robert, Claude; De Koninck, Paul; Khandjian, Edouard W.

    2016-01-01

    Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome. PMID:27462983

  18. Phylogenetic analysis of kindlins suggests subfunctionalization of an ancestral unduplicated kindlin into three paralogs in vertebrates.

    PubMed

    Khan, Ammad Aslam; Janke, Axel; Shimokawa, Takashi; Zhang, Hongquan

    2011-01-01

    Kindlin proteins represent a newly discovered family of evolutionarily conserved FERM domain-containing proteins. This family includes three highly conserved proteins: Kindlin-1, Kindlin-2 and Kindlin-3. All three Kindlin proteins are associated with focal adhesions and are involved in integrin activation. The FERM domain of each Kindlin is bipartite and plays a key role in integrin activation. We herein explore for the first time the evolutionary history of these proteins. The phylogeny of the Kindlins suggests a single ancestral Kindlin protein present in even the earliest metazoan ie, hydra. This protein then underwent duplication events in insects and also experienced genome duplication in vertebrates, leading to the Kindlin family. A comparative study of the Kindlin paralogs showed that Kindlin-2 is the slowest evolving protein among the three family members. The analysis of synonymous and non-synonymous substitutions in orthologous Kindlin sequences in different species showed that all three Kindlins have been evolving under the influence of purifying selection. The expression pattern of Kindlins along with phylogenetic studies supports the subfunctionalization model of gene duplication.

  19. On the role of AtDMC1, AtRAD51 and its paralogs during Arabidopsis meiosis

    PubMed Central

    Pradillo, Mónica; Varas, Javier; Oliver, Cecilia; Santos, Juan L.

    2014-01-01

    Meiotic recombination plays a critical role in achieving accurate chromosome segregation and increasing genetic diversity. Many studies, mostly in yeast, have provided important insights into the coordination and interplay between the proteins involved in the homologous recombination pathway, especially the recombinase RAD51 and the meiosis-specific DMC1. Here we summarize the current progresses on the function of both recombinases and the CX3 complex encoded by AtRAD51 paralogs, in the plant model species Arabidopsis thaliana. Similarities and differences respect to the function of these proteins in other organisms are also indicated. PMID:24596572

  20. Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us.

    PubMed

    Santos, Ana Rita; Kanellopoulos, Alexandros K; Bagni, Claudia

    2014-10-01

    The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the FMR1 gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain and nonneuronal cells. During brain development, FMRP controls the expression of key molecules involved in receptor signaling, cytoskeleton remodeling, protein synthesis and, ultimately, spine morphology. Symptoms associated with FXS include neurodevelopmental delay, cognitive impairment, anxiety, hyperactivity, and autistic-like behavior. Twenty years ago the first Fmr1 KO mouse to study FXS was generated, and several years later other key models including the mutant Drosophila melanogaster, dFmr1, have further helped the understanding of the cellular and molecular causes behind this complex syndrome. Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities.

  1. Orthologous and Paralogous AmpD Peptidoglycan Amidases from Gram-Negative Bacteria

    PubMed Central

    Rivera, Ivanna; Molina, Rafael; Lee, Mijoon; Mobashery, Shahriar

    2016-01-01

    Cell wall recycling and β-lactam antibiotic resistance are linked in Enterobacteriaceae and in Pseudomonas aeruginosa. This process involves a large number of murolytic enzymes, among them a cytoplasmic peptidoglycan amidase AmpD, which plays an essential role by cleaving the peptide stem from key intermediates en route to the β-lactamase production (a resistance mechanism) and cell wall recycling. Uniquely, P. aeruginosa has two additional paralogues of AmpD, designated AmpDh2 and AmpDh3, which are periplasmic enzymes. Despite the fact that AmpDh2 and AmpDh3 share a common motif for their respective catalytic domains, they are each comprised of multidomain architectures and exhibit distinct oligomerization properties. We review herein the structural and biochemical properties of orthologous and paralogous AmpD proteins and discuss their implication in cell wall recycling and antibiotic resistance processes. PMID:27326855

  2. SPOCS: Software for Predicting and Visualizing Orthology/Paralogy Relationships Among Genomes

    SciTech Connect

    Curtis, Darren S.; Phillips, Aaron R.; Callister, Stephen J.; Conlan, Sean; McCue, Lee Ann

    2013-10-15

    At the rate that prokaryotic genomes can now be generated, comparative genomics studies require a flexible method for quickly and accurately predicting orthologs among the rapidly changing set of genomes available. SPOCS implements a graph-based ortholog prediction method to generate a simple tab-delimited table of orthologs and in addition, html files that provide a visualization of the predicted ortholog/paralog relationships to which gene/protein expression metadata may be overlaid. AVAILABILITY AND IMPLEMENTATION: A SPOCS web application is freely available at http://cbb.pnnl.gov/portal/tools/spocs.html. Source code for Linux systems is also freely available under an open source license at http://cbb.pnnl.gov/portal/software/spocs.html; the Boost C++ libraries and BLAST are required.

  3. Mildly Retarded Adults: Their Attitudes Toward Retardation

    ERIC Educational Resources Information Center

    Gan, Jennifer; And Others

    1977-01-01

    Responses to a 40-item questionnaire distributed to 50 mildly mentally retarded (MR) adults indicate that the majority possess accurate information about MR, hold realistic attitudes toward their own needs and abilities, and advocate community integration of the retarded. (Author/JG)

  4. An HcpR paralog of Desulfovibrio gigas provides protection against nitrosative stress

    PubMed Central

    da Silva, Sofia M.; Amaral, Catarina; Neves, Susana S.; Santos, Cátia; Pimentel, Catarina; Rodrigues-Pousada, Claudina

    2015-01-01

    Desulfovibrio gigas belongs to the group of sulfate reducing bacteria (SRB). These ubiquitous and metabolically versatile microorganisms are often exposed to reactive nitrogen species (RNS). Nonetheless, the mechanisms and regulatory elements involved in nitrosative stress protection are still poorly understood. The transcription factor HcpR has emerged as a putative regulator of nitrosative stress response among anaerobic bacteria. HcpR is known to orchestrate the expression of the hybrid cluster protein gene, hcp, proposed to be involved in cellular defense against RNS. According to phylogenetic analyses, the occurrence of hcpR paralog genes is a common feature among several Desulfovibrio species. Within the D. gigas genome we have identified two HcpR-related sequences. One of these sequences, hcpR1, was found in the close vicinity of the hcp gene and this finding prompted us to proceed with its functional characterization. We observed that the growth of a D. gigas strain lacking hcpR1 is severely impaired under nitrosative stress. An in silico search revealed several putative targets of HcpR1 that were experimentally validated. The fact that HcpR1 regulates several genes encoding proteins involved in nitrite and nitrate metabolism, together with the sensitive growth phenotype to NO displayed by an hcpR1 mutant strain, strongly supports a relevant role of this factor under nitrosative stress. Moreover, the finding that several Desulfovibrio species possess HcpR paralogs, which have been transmitted vertically in the evolution and diversification of the genus, suggests that these sequences may confer adaptive or survival advantage to these organisms, possibly by increasing their tolerance to nitrosative stress. PMID:26273559

  5. Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA

    PubMed Central

    Rosa, Ilaria Dalla; Goffart, Steffi; Wurm, Melanie; Wiek, Constanze; Essmann, Frank; Sobek, Stefan; Schroeder, Peter; Zhang, Hongliang; Krutmann, Jean; Hanenberg, Helmut; Schulze-Osthoff, Klaus; Mielke, Christian; Pommier, Yves; Boege, Fritz; Christensen, Morten O.

    2009-01-01

    Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria. In yeast, a single topoisomerase I gene provides for both organelles. In vertebrates, topoisomerase I is divided into nuclear and mitochondrial paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication, we targeted Top1 to mitochondria or Top1mt to nuclei. Overexpression in the fitting organelle served as control. Targeting of Top1 to mitochondria blocked transcription and depleted mitochondrial DNA. This was also seen with catalytically inactive Top1 mutants, but not with Top1mt overexpressed in mitochondria. Targeting of Top1mt to the nucleus revealed that it was much less able to interact with mitotic chromosomes than Top1 overexpressed in the nucleus. Similar experiments with Top1/Top1mt hybrids assigned these functional differences to structural divergences in the DNA-binding core domains. We propose that adaptation of this domain to different chromatin environments in nuclei and mitochondria has driven evolutional development and conservation of organelle-restricted topoisomerase I paralogs in vertebrates. PMID:19720733

  6. Functional Diversification after Gene Duplication: Paralog Specific Regions of Structural Disorder and Phosphorylation in p53, p63, and p73

    PubMed Central

    Siltberg-Liberles, Jessica

    2016-01-01

    Conformational and functional flexibility promote protein evolvability. High evolvability allows related proteins to functionally diverge and perhaps to neostructuralize. p53 is a multifunctional protein frequently referred to as the Guardian of the Genome–a hub for e.g. incoming and outgoing signals in apoptosis and DNA repair. p53 has been found to be structurally disordered, an extreme form of conformational flexibility. Here, p53, and its paralogs p63 and p73, were studied for further insights into the evolutionary dynamics of structural disorder, secondary structure, and phosphorylation. This study is focused on the post gene duplication phase for the p53 family in vertebrates, but also visits the origin of the protein family and the early domain loss and gain events. Functional divergence, measured by rapid evolutionary dynamics of protein domains, structural properties, and phosphorylation propensity, is inferred across vertebrate p53 proteins, in p63 and p73 from fish, and between the three paralogs. In particular, structurally disordered regions are redistributed among paralogs, but within clades redistribution of structural disorder also appears to be an ongoing process. Despite its deemed importance as the Guardian of the Genome, p53 is indeed a protein with high evolvability as seen not only in rearranged structural disorder, but also in fluctuating domain sequence signatures among lineages. PMID:27003913

  7. PERSPECTIVES IN MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    JORDAN, THOMAS E.

    THIRTY-THREE ARTICLES ILLUSTRATE THE EDITOR'S FORMULATION OF ISSUES CONCERNING THE PROBLEM OF MENTAL RETARDATION--(1) THE TRIPARTITE (ONTOLOGICAL, FUNCTIONAL, AND EDOLOGICAL) NATURE OF RETARDATION, (2) THE NECESSITY TO MOVE BEYOND A SINGLE DISCIPLINE IN DEALING WITH RETARDATION, (3) THE NUMBER OF AGENCIES NOW INVOLVED IN STUDY AND CARE, AND (4)…

  8. Introduction to Mental Retardation

    ERIC Educational Resources Information Center

    Arc of the United States, 2004

    2004-01-01

    The purpose of this document is to define mental retardation and answer questions related to this topic. According to the American Association on Mental Retardation (AAMR), mental retardation is a disability that occurs before age 18. It is characterized by significant limitations in intellectual functioning and adaptive behaviors as expressed in…

  9. Structure–Activity Relationship in a Purine-Scaffold Compound Series with Selectivity for the Endoplasmic Reticulum Hsp90 Paralog Grp94

    PubMed Central

    Patel, Hardik J.; Patel, Pallav D.; Ochiana, Stefan O.; Yan, Pengrong; Sun, Weilin; Patel, Maulik R.; Shah, Smit K.; Tramentozzi, Elisa; Brooks, James; Bolaender, Alexander; Shrestha, Liza; Stephani, Ralph; Finotti, Paola; Leifer, Cynthia; Li, Zihai; Gewirth, Daniel T.; Taldone, Tony; Chiosis, Gabriela

    2015-01-01

    Grp94 is involved in the regulation of a restricted number of proteins and represents a potential target in a host of diseases, including cancer, septic shock, autoimmune diseases, chronic inflammatory conditions, diabetes, coronary thrombosis, and stroke. We have recently identified a novel allosteric pocket located in the Grp94 N-terminal binding site that can be used to design ligands with a 2-log selectivity over the other Hsp90 paralogs. Here we perform extensive SAR investigations in this ligand series and rationalize the affinity and paralog selectivity of choice derivatives by molecular modeling. We then use this to design 18c, a derivative with good potency for Grp94 (IC50 = 0.22 μM) and selectivity over other paralogs (>100- and 33-fold for Hsp90α/β and Trap-1, respectively). The paralog selectivity and target-mediated activity of 18c was confirmed in cells through several functional readouts. Compound 18c was also inert when tested against a large panel of kinases. We show that 18c has biological activity in several cellular models of inflammation and cancer and also present here for the first time the in vivo profile of a Grp94 inhibitor. PMID:25901531

  10. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    PubMed

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  11. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    PubMed

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  12. Orthologs and paralogs of regA, a master cell-type regulatory gene in Volvox carteri.

    PubMed

    Duncan, Leonard; Nishii, Ichiro; Howard, Alicia; Kirk, David; Miller, Stephen M

    2006-07-01

    The multicellular green alga Volvox carteri forma nagariensis has only two cell types: terminally differentiated somatic cells and reproductive cells. The regA gene maintains the terminally differentiated state of the somatic cells, apparently by repressing transcription of genes required for chloroplast biogenesis and thereby preventing cell growth. Because the RegA protein sequence bore no obvious motifs, we are attempting to identify regions of functional importance by searching for strongly conserved domains in RegA orthologs. Here we report the cloning and characterization of regA from the most closely related known taxon, V. carteri f. kawasakiensis. Given the closeness of the relationship between these two formas, their regA genes are surprisingly different: they differ in the number of introns and by several lengthy indels, and they encode proteins that are only 80% identical. We also serendipitously discovered a paralogous gene immediately upstream of each regA locus. The two regA genes, both upstream paralogs and several genes in Chlamydomonas (the closest unicellular relative of Volvox) encode a conserved region (the VARL domain) that contains what appears to be a DNA-binding SAND domain. This discovery has opened up a new avenue for exploring how regA and the terminally differentiated state that it controls evolved. PMID:16622701

  13. Exploiting a Reference Genome in Terms of Duplications: The Network of Paralogs and Single Copy Genes in Arabidopsis thaliana.

    PubMed

    Sangiovanni, Mara; Vigilante, Alessandra; Chiusano, Maria Luisa

    2013-01-01

    Arabidopsis thaliana became the model organism for plant studies because of its small diploid genome, rapid lifecycle and short adult size. Its genome was the first among plants to be sequenced, becoming the reference in plant genomics. However, the Arabidopsis genome is characterized by an inherently complex organization, since it has undergone ancient whole genome duplications, followed by gene reduction, diploidization events and extended rearrangements, which relocated and split up the retained portions. These events, together with probable chromosome reductions, dramatically increased the genome complexity, limiting its role as a reference. The identification of paralogs and single copy genes within a highly duplicated genome is a prerequisite to understand its organization and evolution and to improve its exploitation in comparative genomics. This is still controversial, even in the widely studied Arabidopsis genome. This is also due to the lack of a reference bioinformatics pipeline that could exhaustively identify paralogs and singleton genes. We describe here a complete computational strategy to detect both duplicated and single copy genes in a genome, discussing all the methodological issues that may strongly affect the results, their quality and their reliability. This approach was used to analyze the organization of Arabidopsis nuclear protein coding genes, and besides classifying computationally defined paralogs into networks and single copy genes into different classes, it unraveled further intriguing aspects concerning the genome annotation and the gene relationships in this reference plant species. Since our results may be useful for comparative genomics and genome functional analyses, we organized a dedicated web interface to make them accessible to the scientific community.

  14. Parallel reduction in expression, but no loss of functional constraint, in two opsin paralogs within cave populations of Gammarus minus (Crustacea: Amphipoda)

    PubMed Central

    2013-01-01

    Background Gammarus minus, a freshwater amphipod living in the cave and surface streams in the eastern USA, is a premier candidate for studying the evolution of troglomorphic traits such as pigmentation loss, elongated appendages, and reduced eyes. In G. minus, multiple pairs of genetically related, physically proximate cave and surface populations exist which exhibit a high degree of intraspecific morphological divergence. The morphology, ecology, and genetic structure of these sister populations are well characterized, yet the genetic basis of their morphological divergence remains unknown. Results We used degenerate PCR primers designed to amplify opsin genes within the subphylum Crustacea and discovered two distinct opsin paralogs (average inter-paralog protein divergence ≈ 20%) in the genome of three independently derived pairs of G. minus cave and surface populations. Both opsin paralogs were found to be related to other crustacean middle wavelength sensitive opsins. Low levels of nucleotide sequence variation (< 1% within populations) were detected in both opsin genes, regardless of habitat, and dN/dS ratios did not indicate a relaxation of functional constraint in the cave populations with reduced or absent eyes. Maximum likelihood analyses using codon-based models also did not detect a relaxation of functional constraint in the cave lineages. We quantified expression level of both opsin genes and found that the expression of both paralogs was significantly reduced in all three cave populations relative to their sister surface populations. Conclusions The concordantly lowered expression level of both opsin genes in cave populations of G. minus compared to sister surface populations, combined with evidence for persistent purifying selection in the cave populations, is consistent with an unspecified pleiotropic function of opsin proteins. Our results indicate that phototransduction proteins such as opsins may have retained their function in cave

  15. Paralogous genes involved in juvenile hormone action in Drosophila melanogaster.

    PubMed

    Baumann, Aaron; Barry, Joshua; Wang, Shaoli; Fujiwara, Yoshihiro; Wilson, Thomas G

    2010-08-01

    Juvenile hormone (JH) is critical for multiple aspects of insect development and physiology. Although roles for the hormone have received considerable study, an understanding of the molecules necessary for JH action in insects has been frustratingly slow to evolve. Methoprene-tolerant (Met) in Drosophila melanogaster fulfills many of the requirements for a hormone receptor gene. A paralogous gene, germ-cell expressed (gce), possesses homology and is a candidate as a Met partner in JH action. Expression of gce was found to occur at multiple times and in multiple tissues during development, similar to that previously found for Met. To probe roles of this gene in JH action, we carried out in vivo gce over- and underexpression studies. We show by overexpression studies that gce can substitute in vivo for Met, alleviating preadult but not adult phenotypic characters. We also demonstrate that RNA interference-driven knockdown of gce expression in transgenic flies results in preadult lethality in the absence of MET. These results show that (1) unlike Met, gce is a vital gene and shows functional flexibility and (2) both gene products appear to promote JH action in preadult but not adult development.

  16. Mental Retardation in Perspective.

    ERIC Educational Resources Information Center

    Horvath, Michael; And Others

    This monograph presents a general introduction to the history, classification, and characteristics of mental retardation. It begins with a discussion of the history of mental retardation from ancient Greece and Rome to the present. The beginnings of special education are traced to the early 19th century in Europe. Major influences in treatment of…

  17. Brominated Flame Retardants

    EPA Science Inventory

    Brominated flame retardants (BFRs) belong to a large class of compounds known as organohalogens. BFRs are currently the largest marketed flame retardant group due to their high performance efficiency and low cost. In the commercial market, more than 75 different BFRs are recogniz...

  18. Fire-Retardant, Decorative Inks

    NASA Technical Reports Server (NTRS)

    Kourtides, D.; Nir, Z.; Mikroyannidis, J.

    1987-01-01

    Effectiveness of fire-retardant additives evaluated. Fire retardance of decorative acrylic printing inks for aircraft interiors enhanced by certain commercial and experimental fire-retardant additives, according to study.

  19. Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart.

    PubMed

    Somyajit, Kumar; Saxena, Sneha; Babu, Sharath; Mishra, Anup; Nagaraju, Ganesh

    2015-11-16

    Mammalian RAD51 paralogs are implicated in the repair of collapsed replication forks by homologous recombination. However, their physiological roles in replication fork maintenance prior to fork collapse remain obscure. Here, we report on the role of RAD51 paralogs in short-term replicative stress devoid of DSBs. We show that RAD51 paralogs localize to nascent DNA and common fragile sites upon replication fork stalling. Strikingly, RAD51 paralogs deficient cells exhibit elevated levels of 53BP1 nuclear bodies and increased DSB formation, the latter being attributed to extensive degradation of nascent DNA at stalled forks. RAD51C and XRCC3 promote the restart of stalled replication in an ATP hydrolysis dependent manner by disengaging RAD51 and other RAD51 paralogs from the halted forks. Notably, we find that Fanconi anemia (FA)-like disorder and breast and ovarian cancer patient derived mutations of RAD51C fails to protect replication fork, exhibit under-replicated genomic regions and elevated micro-nucleation. Taken together, RAD51 paralogs prevent degradation of stalled forks and promote the restart of halted replication to avoid replication fork collapse, thereby maintaining genomic integrity and suppressing tumorigenesis.

  20. The cytohesin paralog Sec7 of Dictyostelium discoideum is required for phagocytosis and cell motility

    PubMed Central

    2013-01-01

    Background Dictyostelium harbors several paralogous Sec7 genes that encode members of three subfamilies of the Sec7 superfamily of guanine nucleotide exchange factors. One of them is the cytohesin family represented by three members in D. discoideum, SecG, Sec7 and a further protein distinguished by several transmembrane domains. Cytohesins are characterized by a Sec7-PH tandem domain and have roles in cell adhesion and migration. Results We study here Sec7. In vitro its PH domain bound preferentially to phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). When following the distribution of GFP-Sec7 in vivo we observed the protein in the cytosol and at the plasma membrane. Strikingly, when cells formed pseudopods, macropinosomes or phagosomes, GFP-Sec7 was conspicuously absent from areas of the plasma membrane which were involved in these processes. Mutant cells lacking Sec7 exhibited an impaired phagocytosis and showed significantly reduced speed and less persistence during migration. Cellular properties associated with mammalian cytohesins like cell-cell and cell-substratum adhesion were not altered. Proteins with roles in membrane trafficking and signal transduction have been identified as putative interaction partners consistent with the data obtained from mutant analysis. Conclusions Sec7 is a cytosolic component and is associated with the plasma membrane in a pattern distinctly different from the accumulation of PI(3,4,5)P3. Mutant analysis reveals that loss of the protein affects cellular processes that involve membrane flow and the actin cytoskeleton. PMID:23915312

  1. All-or-(N)One - an epistemological characterization of the human tumorigenic neuronal paralogous FAM72 gene loci.

    PubMed

    Kutzner, Arne; Pramanik, Subrata; Kim, Pok-Son; Heese, Klaus

    2015-11-01

    FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. Accumulating data indicate the potential pivotal tumourigenic effects of FAM72. Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-emerging orthologue in all other species. No species with two or three FAM72/SRGAP2 gene pairs could be identified, and the four exclusively human-defining ohnologues, with different mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under epigenetic control through long non-coding (lnc) RNAs. PMID:26206078

  2. Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner☆

    PubMed Central

    Collette, Nicole M.; Yee, Cristal S.; Murugesh, Deepa; Sebastian, Aimy; Taher, Leila; Gale, Nicholas W.; Economides, Aris N.; Harland, Richard M.; Loots, Gabriela G.

    2013-01-01

    WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1–/– mice lack any obvious limb or skeletal defects, Sost–/– mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost–/–; Sostdc1–/– mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost–/– and Sost–/–; Sostdc1–/– mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling. PMID:23994639

  3. Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.

    PubMed

    Collette, Nicole M; Yee, Cristal S; Murugesh, Deepa; Sebastian, Aimy; Taher, Leila; Gale, Nicholas W; Economides, Aris N; Harland, Richard M; Loots, Gabriela G

    2013-11-01

    WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1(-/-) mice lack any obvious limb or skeletal defects, Sost(-/-) mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost(-/-); Sostdc1(-/-) mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost(-/-) and Sost(-/-); Sostdc1(-/-) mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling.

  4. csrR, a Paralog and Direct Target of CsrA, Promotes Legionella pneumophila Resilience in Water

    PubMed Central

    Abbott, Zachary D.; Yakhnin, Helen; Babitzke, Paul

    2015-01-01

    ABSTRACT Critical to microbial versatility is the capacity to express the cohort of genes that increase fitness in different environments. Legionella pneumophila occupies extensive ecological space that includes diverse protists, pond water, engineered water systems, and mammalian lung macrophages. One mechanism that equips this opportunistic pathogen to adapt to fluctuating conditions is a switch between replicative and transmissive cell types that is controlled by the broadly conserved regulatory protein CsrA. A striking feature of the legionellae surveyed is that each of 14 strains encodes 4 to 7 csrA-like genes, candidate regulators of distinct fitness traits. Here we focus on the one csrA paralog (lpg1593) that, like the canonical csrA, is conserved in all 14 strains surveyed. Phenotypic analysis revealed that long-term survival in tap water is promoted by the lpg1593 locus, which we name csrR (for “CsrA-similar protein for resilience”). As predicted by its GGA motif, csrR mRNA was bound directly by the canonical CsrA protein, as judged by electromobility shift and RNA-footprinting assays. Furthermore, CsrA repressed translation of csrR mRNA in vivo, as determined by analysis of csrR-gfp reporters, csrR mRNA stability in the presence and absence of csrA expression, and mutation of the CsrA binding site identified on the csrR mRNA. Thus, CsrA not only governs the transition from replication to transmission but also represses translation of its paralog csrR when nutrients are available. We propose that, during prolonged starvation, relief of CsrA repression permits CsrR protein to coordinate L. pneumophila’s switch to a cell type that is resilient in water supplies. PMID:26060275

  5. Fire retardant polyisocyanurate foam

    NASA Technical Reports Server (NTRS)

    Riccitiello, S. R.; Parker, J. A.

    1972-01-01

    Fire retardant properties of low density polymer foam are increased. Foam has pendant nitrile groups which form thermally-stable heterocyclic structures at temperature below degradation temperature of urethane linkages.

  6. The Impact of Paralogy on Phylogenomic Studies – A Case Study on Annelid Relationships

    PubMed Central

    Struck, Torsten H.

    2013-01-01

    Phylogenomic studies based on hundreds of genes derived from expressed sequence tags libraries are increasingly used to reveal the phylogeny of taxa. A prerequisite for these studies is the assignment of genes into clusters of orthologous sequences. Sophisticated methods of orthology prediction are used in such analyses, but it is rarely assessed whether paralogous sequences have been erroneously grouped together as orthologous sequences after the prediction, and whether this had an impact on the phylogenetic reconstruction using a super-matrix approach. Herein, I tested the impact of paralogous sequences on the reconstruction of annelid relationships based on phylogenomic datasets. Using single-partition analyses, screening for bootstrap support, blast searches and pruning of sequences in the supermatrix, wrongly assigned paralogous sequences were found in eight partitions and the placement of five taxa (the annelids Owenia, Scoloplos, Sthenelais and Eurythoe and the nemertean Cerebratulus) including the robust bootstrap support could be attributed to the presence of paralogous sequences in two partitions. Excluding these sequences resulted in a different, weaker supported placement for these taxa. Moreover, the analyses revealed that paralogous sequences impacted the reconstruction when only a single taxon represented a previously supported higher taxon such as a polychaete family. One possibility of a priori detection of wrongly assigned paralogous sequences could combine 1) a screening of single-partition analyses based on criteria such as nodal support or internal branch length with 2) blast searches of suspicious cases as presented herein. Also possible are a posteriori approaches in which support for specific clades is investigated by comparing alternative hypotheses based on differences in per-site likelihoods. Increasing the sizes of EST libraries will also decrease the likelihood of wrongly assigned paralogous sequences, and in the case of orthology

  7. The Paralogous Pairs of Genes Involved in Clavulanic Acid and Clavam Metabolite Biosynthesis Are Differently Regulated in Streptomyces clavuligerus

    PubMed Central

    Tahlan, Kapil; Anders, Cecilia; Jensen, Susan E.

    2004-01-01

    Carboxyethylarginine synthase, encoded by the paralogous ceaS1 and ceaS2 genes, catalyzes the first reaction in the shared biosynthetic pathway leading to clavulanic acid and the other clavam metabolites in Streptomyces clavuligerus. The nutritional regulation of ceaS1 and ceaS2 expression was analyzed by reverse transcriptase PCR and by the use of the enhanced green fluorescent protein-encoding gene (egfp) as a reporter. ceaS1 was transcribed in complex soy medium only, whereas ceaS2 was transcribed in both soy and defined starch-asparagine (SA) media. The transcriptional start points of the two genes were also mapped to a C residue 98 bp upstream of ceaS1 and a G residue 51 bp upstream of the ceaS2 start codon by S1 nuclease protection and primer extension analyses. Furthermore, transcriptional mapping of the genes encoding the beta-lactam synthetase (bls1) and proclavaminate amidinohydrolase (pah1) isoenzymes from the paralogue gene cluster indicated that a single polycistronic transcript of ∼4.9 kb includes ceaS1, bls1, and pah1. The expression of ceaS1 and ceaS2 in a mutant strain defective in the regulatory protein CcaR was also examined. ceaS1 transcription was not affected in the ccaR mutant, whereas that of ceaS2 was greatly reduced compared to the wild-type strain. Overall, our results suggest that different mechanisms are involved in regulating the expression of ceaS1 and ceaS2, and presumably also of other paralogous genes that encode proteins involved in the early stages of clavulanic acid and clavam metabolite biosynthesis. PMID:15342599

  8. High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells

    PubMed Central

    Swaroop, Manju; Southall, Noel; Huang, Wenwei; Usdin, Karen

    2015-01-01

    Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development. Significance In this study, a specific and sensitive fluorescence resonance energy transfer-based assay for fragile X mental retardation protein detection was developed and optimized for high-throughput screening (HTS) of compound libraries using fragile X syndrome (FXS) patient-derived neural stem cells. The data suggest that this HTS format will be useful for the identification of better lead compounds for developing new therapeutics for FXS. This assay can also be adapted for FMRP detection in clinical and research settings. PMID:25999519

  9. Learning and memory deficits consequent to reduction of the fragile X mental retardation protein result from metabotropic glutamate receptor-mediated inhibition of cAMP signaling in Drosophila.

    PubMed

    Kanellopoulos, Alexandros K; Semelidou, Ourania; Kotini, Andriana G; Anezaki, Maria; Skoulakis, Efthimios M C

    2012-09-19

    Loss of the RNA-binding fragile X protein [fragile X mental retardation protein (FMRP)] results in a spectrum of cognitive deficits, the fragile X syndrome (FXS), while aging individuals with decreased protein levels present with a subset of these symptoms and tremor. The broad range of behavioral deficits likely reflects the ubiquitous distribution and multiple functions of the protein. FMRP loss is expected to affect multiple neuronal proteins and intracellular signaling pathways, whose identity and interactions are essential in understanding and ameliorating FXS symptoms. We used heterozygous mutants and targeted RNA interference-mediated abrogation in Drosophila to uncover molecular pathways affected by FMRP reduction. We present evidence that FMRP loss results in excess metabotropic glutamate receptor (mGluR) activity, attributable at least in part to elevation of the protein in affected neurons. Using high-resolution behavioral, genetic, and biochemical analyses, we present evidence that excess mGluR upon FMRP attenuation is linked to the cAMP decrement reported in patients and models, and underlies olfactory associative learning and memory deficits. Furthermore, our data indicate positive transcriptional regulation of the fly fmr1 gene by cAMP, via protein kinase A, likely through the transcription factor CREB. Because the human Fmr1 gene also contains CREB binding sites, the interaction of mGluR excess and cAMP signaling defects we present suggests novel combinatorial pharmaceutical approaches to symptom amelioration upon FMRP attenuation.

  10. NLR-Associating Transcription Factor bHLH84 and Its Paralogs Function Redundantly in Plant Immunity

    PubMed Central

    Xu, Fang; Kapos, Paul; Cheng, Yu Ti; Li, Meng; Zhang, Yuelin; Li, Xin

    2014-01-01

    In plants and animals, nucleotide-binding and leucine-rich repeat domain containing (NLR) immune receptors are utilized to detect the presence or activities of pathogen-derived molecules. However, the mechanisms by which NLR proteins induce defense responses remain unclear. Here, we report the characterization of one basic Helix-loop-Helix (bHLH) type transcription factor (TF), bHLH84, identified from a reverse genetic screen. It functions as a transcriptional activator that enhances the autoimmunity of NLR mutant snc1 (suppressor of npr1-1, constitutive 1) and confers enhanced immunity in wild-type backgrounds when overexpressed. Simultaneously knocking out three closely related bHLH paralogs attenuates RPS4-mediated immunity and partially suppresses the autoimmune phenotypes of snc1, while overexpression of the other two close paralogs also renders strong autoimmunity, suggesting functional redundancy in the gene family. Intriguingly, the autoimmunity conferred by bHLH84 overexpression can be largely suppressed by the loss-of-function snc1-r1 mutation, suggesting that SNC1 is required for its proper function. In planta co-immunoprecipitation revealed interactions between not only bHLH84 and SNC1, but also bHLH84 and RPS4, indicating that bHLH84 associates with these NLRs. Together with previous finding that SNC1 associates with repressor TPR1 to repress negative regulators, we hypothesize that nuclear NLR proteins may interact with both transcriptional repressors and activators during immune responses, enabling potentially faster and more robust transcriptional reprogramming upon pathogen recognition. PMID:25144198

  11. Functional Divergence in Teleost Cardiac Troponin Paralogs Guides Variation in the Interaction of TnI Switch Region with TnC

    PubMed Central

    Genge, Christine E.; Stevens, Charles M.; Davidson, William S.; Singh, Gurpreet; Peter Tieleman, D.; Tibbits, Glen F.

    2016-01-01

    Gene duplication results in extra copies of genes that must coevolve with their interacting partners in multimeric protein complexes. The cardiac troponin (Tn) complex, containing TnC, TnI, and TnT, forms a distinct functional unit critical for the regulation of cardiac muscle contraction. In teleost fish, the function of the Tn complex is modified by the consequences of differential expression of paralogs in response to environmental thermal challenges. In this article, we focus on the interaction between TnI and TnC, coded for by genes that have independent evolutionary origins, but the co-operation of their protein products has necessitated coevolution. In this study, we characterize functional divergence of TnC and TnI paralogs, specifically the interrelated roles of regulatory subfunctionalization and structural subfunctionalization. We determined that differential paralog transcript expression in response to temperature acclimation results in three combinations of TnC and TnI in the zebrafish heart: TnC1a/TnI1.1, TnC1b/TnI1.1, and TnC1a/TnI1.5. Phylogenetic analysis of these highly conserved proteins identified functionally divergent residues in TnI and TnC. The structural and functional effect of these Tn combinations was modeled with molecular dynamics simulation to link divergent sites to changes in interaction strength. Functional divergence in TnI and TnC were not limited to the residues involved with TnC/TnI switch interaction, which emphasizes the complex nature of Tn function. Patterns in domain-specific divergent selection and interaction energies suggest that substitutions in the TnI switch region are crucial to modifying TnI/TnC function to maintain cardiac contraction with temperature changes. This integrative approach introduces Tn as a model of functional divergence that guides the coevolution of interacting proteins. PMID:26979795

  12. Functional Divergence in Teleost Cardiac Troponin Paralogs Guides Variation in the Interaction of TnI Switch Region with TnC.

    PubMed

    Genge, Christine E; Stevens, Charles M; Davidson, William S; Singh, Gurpreet; Peter Tieleman, D; Tibbits, Glen F

    2016-01-01

    Gene duplication results in extra copies of genes that must coevolve with their interacting partners in multimeric protein complexes. The cardiac troponin (Tn) complex, containing TnC, TnI, and TnT, forms a distinct functional unit critical for the regulation of cardiac muscle contraction. In teleost fish, the function of the Tn complex is modified by the consequences of differential expression of paralogs in response to environmental thermal challenges. In this article, we focus on the interaction between TnI and TnC, coded for by genes that have independent evolutionary origins, but the co-operation of their protein products has necessitated coevolution. In this study, we characterize functional divergence of TnC and TnI paralogs, specifically the interrelated roles of regulatory subfunctionalization and structural subfunctionalization. We determined that differential paralog transcript expression in response to temperature acclimation results in three combinations of TnC and TnI in the zebrafish heart: TnC1a/TnI1.1, TnC1b/TnI1.1, and TnC1a/TnI1.5. Phylogenetic analysis of these highly conserved proteins identified functionally divergent residues in TnI and TnC. The structural and functional effect of these Tn combinations was modeled with molecular dynamics simulation to link divergent sites to changes in interaction strength. Functional divergence in TnI and TnC were not limited to the residues involved with TnC/TnI switch interaction, which emphasizes the complex nature of Tn function. Patterns in domain-specific divergent selection and interaction energies suggest that substitutions in the TnI switch region are crucial to modifying TnI/TnC function to maintain cardiac contraction with temperature changes. This integrative approach introduces Tn as a model of functional divergence that guides the coevolution of interacting proteins. PMID:26979795

  13. Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function.

    PubMed

    Pollock, R A; Sreenath, T; Ngo, L; Bieberich, C J

    1995-05-01

    To investigate the functions of paralogous Hox genes, we compared the phenotypic consequences of altering the embryonic patterns of expression of Hoxb-8 and Hoxc-8 in transgenic mice. A comparison of the phenotypic consequences of altered expression of the two paralogs in the axial skeletons of newborns revealed an array of common transformations as well as morphological changes unique to each gene. Divergence of function of the two paralogs was clearly evident in costal derivatives, where increased expression of the two genes affected opposite ends of the ribs. Many of the morphological consequences of expanding the mesodermal domain and magnitude of expression of either gene were atavistic, inducing the transformation of axial skeletal structures from a modern to an earlier evolutionary form. We propose that regional specialization of the vertebral column has been driven by regionalization of Hox gene function and that a major aspect of this evolutionary progression may have been restriction of Hox gene expression.

  14. [Nosology of mental retardation].

    PubMed

    González Castañón, Diego; Aznar, Andrea S; Wahlberg, Ernesto

    2006-01-01

    The classificatory systems used through history. The analysis of their criteria for categorization allowed the authors to deduce the nosologic considerations and the paradigms underlying the conceptions of mental retardation sustained in each time period, not always from psychiatric origins. The effects of considering mental retardation as a disorder or a disability are discussed together with the correlation with the type of interventions and instituted social practices (related to mental health, social participation, education). The characteristics of the supports' paradigm and its consequences in the classifications and intervention plans are analyzed with more detail.

  15. Fire retardant polyetherimide nanocomposites

    SciTech Connect

    Lee, J.; Takekoshi, T.; Giannelis, E.P.

    1997-09-01

    Polyetherimide-layered silicates nanocomposites with increased char yield and fire retardancy are described. The use of nanocomposites is a new, environmentally-benign approach to improve fire resistance of polymers. An increase in the aromaticity yields high char residues that normally correlate with higher oxygen index and lower flammability. The often high cost of these materials and the specialized processing techniques required, however, have limited the use of these polymers to certain specialized applications. The effectiveness of fire retardant fillers is also limited since the large amounts required make processing difficult and might inadvertently affect mechanical properties.

  16. NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

    PubMed Central

    Parplys, Ann C.; Zhao, Weixing; Sharma, Neelam; Groesser, Torsten; Liang, Fengshan; Maranon, David G.; Leung, Stanley G.; Grundt, Kirsten; Dray, Eloïse; Idate, Rupa; Østvold, Anne Carine; Schild, David; Sung, Patrick; Wiese, Claudia

    2015-01-01

    NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression. PMID:26323318

  17. NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

    SciTech Connect

    Parplys, Ann C.; Zhao, Weixing; Sharma, Neelam; Groesser, Torsten; Liang, Fengshan; Maranon, David G.; Leung, Stanley G.; Grundt, Kirsten; Dray, Eloïse; Idate, Rupa; Østvold, Anne Carine; Schild, David; Sung, Patrick; Wiese, Claudia

    2015-08-31

    NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Finally, our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.

  18. NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability.

    PubMed

    Parplys, Ann C; Zhao, Weixing; Sharma, Neelam; Groesser, Torsten; Liang, Fengshan; Maranon, David G; Leung, Stanley G; Grundt, Kirsten; Dray, Eloïse; Idate, Rupa; Østvold, Anne Carine; Schild, David; Sung, Patrick; Wiese, Claudia

    2015-11-16

    NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression. PMID:26323318

  19. NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

    DOE PAGESBeta

    Parplys, Ann C.; Zhao, Weixing; Sharma, Neelam; Groesser, Torsten; Liang, Fengshan; Maranon, David G.; Leung, Stanley G.; Grundt, Kirsten; Dray, Eloïse; Idate, Rupa; et al

    2015-08-31

    NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintainingmore » wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Finally, our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.« less

  20. Differential deployment of paralogous Wnt genes in the mouse and chick embryo during development

    PubMed Central

    Martin, Audrey; Maher, Stephanie; Summerhurst, Kristen; Davidson, Duncan; Murphy, Paula

    2012-01-01

    SUMMARY Genes encoding Wnt ligands are crucial in body patterning and are highly conserved among metazoans. Given their conservation at the protein-coding level, it is likely that changes in where and when these genes are active are important in generating evolutionary variations. However, we lack detailed knowledge about how their deployment has diverged. Here, we focus on four Wnt subfamilies (Wnt2, Wnt5, Wnt7, and Wnt8) in mammalian and avian species, consisting of a paralogous gene pair in each, believed to have duplicated in the last common ancestor of vertebrates. We use three-dimensional imaging to capture expression patterns in detail and carry out systematic comparisons. We find evidence of greater divergence between these subgroup paralogues than the respective orthologues, consistent with some level of subfunctionalization/neofunctionalization in the common vertebrate ancestor that has been conserved. However, there were exceptions; in the case of chick Wnt2b, individual sites were shared with both mouse Wnt2 and Wnt2b. We also find greater divergence, between paralogues and orthologues, in some subfamilies (Wnt2 and Wnt8) compared to others (Wnt5 and Wnt7) with the more highly similar expression patterns showing more extensive expression in more structures in the embryo. Wnt8 genes were most restricted and most divergent. Major sites of expression for all subfamilies include CNS, limbs, and facial region, and in general there were more similarities in gene deployment in these territories with divergent patterns featuring more in organs such as heart and gut. A detailed comparison of gene expression patterns in the limb showed similarities in overall combined domains across species with notable differences that may relate to lineage-specific morphogenesis. PMID:23017026

  1. Regulation of gill claudin paralogs by salinity, cortisol and prolactin in Mozambique tilapia (Oreochromis mossambicus).

    PubMed

    Tipsmark, Christian K; Breves, Jason P; Rabeneck, D Brett; Trubitt, Rebecca T; Lerner, Darren T; Grau, E Gordon

    2016-09-01

    In euryhaline teleosts, reorganization of gill tight junctions during salinity acclimation involves dynamic expression of specific claudin (Cldn) paralogs. We identified four transcripts encoding Cldn tight junction proteins in the tilapia gill transcriptome: cldn10c, cldn10e, cldn28a and cldn30. A tissue distribution experiment found cldn10c and cldn10e expression levels in the gill to be 100-fold higher than any other tissues examined. cldn28a and cldn30 levels in the gill were 10-fold greater than levels in other tissues. Expression of these genes in Mozambique tilapia was examined during acclimation to fresh water (FW), seawater (SW), and in response to hormone treatments. Transfer of tilapia from FW to SW elevated cldn10c and cldn10e, while cldn28a and cldn30 were stimulated following transfer from SW to FW. In hypophysectomized tilapia transferred to FW, pituitary extirpation induced reduced expression of cldn10c, cldn10e and cldn28a; these effects were mitigated equally by either prolactin or cortisol replacement. In vitro experiments with gill filaments showed that cortisol stimulated expression of all four cldns examined, suggesting a direct action of cortisol in situ. Our data indicate that elevated cldn10c and cldn10e expression is important during acclimation of tilapia to SW possibly by conferring ion specific paracellular permeability. On the other hand, expression of cldn28a and cldn30 appears to contribute to reorganization of branchial epithelium during FW acclimation. Hormone treatment experiments showed that particular FW- and SW-induced cldns are controlled by cortisol and prolactin. PMID:27210417

  2. Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus.

    PubMed

    Grossoehme, Nicholas; Kehl-Fie, Thomas E; Ma, Zhen; Adams, Keith W; Cowart, Darin M; Scott, Robert A; Skaar, Eric P; Giedroc, David P

    2011-04-15

    All strains of Staphylococcus aureus encode a putative copper-sensitive operon repressor (CsoR) and one other CsoR-like protein of unknown function. We show here that NWMN_1991 encodes a bona fide Cu(I)-inducible CsoR of a genetically unlinked copA-copZ copper resistance operon in S. aureus strain Newman. In contrast, an unannotated open reading frame found between NWMN_0027 and NWMN_0026 (denoted NWMN_0026.5) encodes a CsoR-like regulator that represses expression of adjacent genes by binding specifically to a pair of canonical operator sites positioned in the NWMN_0027-0026.5 intergenic region. Inspection of these regulated genes suggests a role in assimilation of inorganic sulfur from thiosulfate and vectorial sulfur transfer, and we designate NWMN_0026.5 as CstR (CsoR-like sulfur transferase repressor). Expression analysis demonstrates that CsoR and CstR control their respective regulons in response to distinct stimuli with no overlap in vivo. Unlike CsoR, CstR does not form a stable complex with Cu(I); operator binding is instead inhibited by oxidation of the intersubunit cysteine pair to a mixture of disulfide and trisulfide linkages by a likely metabolite of thiosulfate assimilation, sulfite. CsoR is unreactive toward sulfite under the same conditions. We conclude that CsoR and CstR are paralogs in S. aureus that function in the same cytoplasm to control distinct physiological processes. PMID:21339296

  3. Retarded ejaculation - a review.

    PubMed

    Richardson, Daniel; Nalabanda, Ananth; Goldmeier, David

    2006-03-01

    Retarded ejaculation, now termed the male orgasmic disorder is not only difficult to manage, but also the scientific evidence for aetiology, treatment and outcome is poor. This is compounded by incomplete consensus regarding definition from the scientific community. In this review, we intend to collate the available information on this sexual problem including definitions, possible aetiological factors and treatment options.

  4. Monkey Retardate Learning Analysis

    ERIC Educational Resources Information Center

    Chamove, A. S.; Molinaro, T. J.

    1978-01-01

    Seven rhesus monkeys reared on diets high in phenylalanine to induce phenylketonuria (PKU--a metabolic disorder associated with mental retardation if untreated) were compared with normal, pair-fed, and younger controls; frontal brain-lesioned monkeys; and those raised on high-tryptophan diets in three object discrimination tasks. (Author)

  5. Vignettes in Mental Retardation.

    ERIC Educational Resources Information Center

    Crissey, Marie Skodak

    1983-01-01

    Described are turn-of-the-century (1900) efforts of E. Johnstone, Vineland Training School for the mentally retarded; H. Goddard, psychologist (also at Vineland); and C. Davenport, Carnegie Foundation biological laboratory, Coldspring Harbor; to identify the roles of genetic heredity and environmental impact, and thus to eradicate or ameliorate…

  6. An Intronless β-amyrin Synthase Gene is More Efficient in Oleanolic Acid Accumulation than its Paralog in Gentiana straminea.

    PubMed

    Liu, Yanling; Zhao, Zhongjuan; Xue, Zheyong; Wang, Long; Cai, Yunfei; Wang, Peng; Wei, Tiandi; Gong, Jing; Liu, Zhenhua; Li, Juan; Li, Shuo; Xiang, Fengning

    2016-01-01

    Paralogous members of the oxidosqualene cyclase (OSC) family encode a diversity of enzymes that are important in triterpenoid biosynthesis. This report describes the isolation of the Gentiana straminea gene GsAS2 that encodes a β-amyrin synthase (βAS) enzyme. Unlike its previously isolated paralog GsAS1, GsAS2 lacks introns. Its predicted protein product was is a 759 residue polypeptide that shares high homology with other known β-amyrin synthases (βASs). Heterologously expressed GsAS2 generates more β-amyrin in yeast than does GsAS1. Constitutive over-expression of GsAS2 resulted in a 5.7 fold increase in oleanolic acid accumulation, while over-expression of GsAS1 led to a 3 fold increase. Additionally, RNAi-directed suppression of GsAS2 and GsAS1 in G. straminea decreased oleonolic acid levels by 65.9% and 21% respectively, indicating that GsAS2 plays a more important role than GsAS1 in oleanolic acid biosynthesis in G. straminea. We uses a docking model to explore the catalytic mechanism of GsAS1/2 and predicted that GsAS2, with its Y560, have higher efficiency than GsAS1 and mutated versions of GsAS2 in β-amyrin produce. When the key residue in GsAS2 was mutagenized, it produced about 41.29% and 71.15% less β-amyrin than native, while the key residue in GsAS1 was mutagenized to that in GsAS2, the mutant produced 38.02% more β-amyrin than native GsAS1. PMID:27624821

  7. An Intronless β-amyrin Synthase Gene is More Efficient in Oleanolic Acid Accumulation than its Paralog in Gentiana straminea

    PubMed Central

    Liu, Yanling; Zhao, Zhongjuan; Xue, Zheyong; Wang, Long; Cai, Yunfei; Wang, Peng; Wei, Tiandi; Gong, Jing; Liu, Zhenhua; Li, Juan; Li, Shuo; Xiang, Fengning

    2016-01-01

    Paralogous members of the oxidosqualene cyclase (OSC) family encode a diversity of enzymes that are important in triterpenoid biosynthesis. This report describes the isolation of the Gentiana straminea gene GsAS2 that encodes a β-amyrin synthase (βAS) enzyme. Unlike its previously isolated paralog GsAS1, GsAS2 lacks introns. Its predicted protein product was is a 759 residue polypeptide that shares high homology with other known β-amyrin synthases (βASs). Heterologously expressed GsAS2 generates more β-amyrin in yeast than does GsAS1. Constitutive over-expression of GsAS2 resulted in a 5.7 fold increase in oleanolic acid accumulation, while over-expression of GsAS1 led to a 3 fold increase. Additionally, RNAi-directed suppression of GsAS2 and GsAS1 in G. straminea decreased oleonolic acid levels by 65.9% and 21% respectively, indicating that GsAS2 plays a more important role than GsAS1 in oleanolic acid biosynthesis in G. straminea. We uses a docking model to explore the catalytic mechanism of GsAS1/2 and predicted that GsAS2, with its Y560, have higher efficiency than GsAS1 and mutated versions of GsAS2 in β-amyrin produce. When the key residue in GsAS2 was mutagenized, it produced about 41.29% and 71.15% less β-amyrin than native, while the key residue in GsAS1 was mutagenized to that in GsAS2, the mutant produced 38.02% more β-amyrin than native GsAS1. PMID:27624821

  8. Two proprotein convertase subtilisin/kexin type 9 (PCSK9) paralogs from the tropical sea cucumber (Stichopus monotuberculatus): Molecular characterization and inducible expression with immune challenge.

    PubMed

    Ren, Chunhua; Chen, Ting; Jiang, Xiao; Sun, Hongyan; Qian, Jing; Hu, Chaoqun; Wang, Yanhong

    2016-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a multifunctional protein that widely exists in eukaryotic species. In this study, two PCSK9 paralogs, named StmPCSK9-1 and StmPCSK9-2, were identified from the tropical sea cucumber (Stichopus monotuberculatus). The cDNAs of StmPCSK9-1 and StmPCSK9-2 are 1330 kb and 1508 kb in size, respectively. The open reading frames (ORF) for StmPCSK9-1 and StmPCSK9-2 cDNAs are 1128 and 1167 bp in length, encoding the proteins of 375 and 388 amino acids with the deduced molecular weights of 38.76 and 41.07 kDa, respectively. In accord with other members in PCSK9 family, the two StmPCSK9 paralogs possessed the inhibitor_I9 and peptidase_S8 functional domains, seven active sites, a catalytic triad and two calcium binding sites. For the gene structure, the splicing of the two StmPCSK9 paralogs was relatively conserved. In addition, the mRNA expression of StmPCSK9-1 and StmPCSK9-2 was only detected in the sea cucumber intestine and coelomocytes, and the expression levels of both the two StmPCSK9 paralogs were higher in intestine. Moreover, StmPCSK9-2 was found to be a cytoplasm protein without signal peptide, and show no response to the immune challenge. On the contrary, StmPCSK9-1 was a secreted protein and the transcriptional expression of StmPCSK9-1 was significantly up-regulated by lipopolysaccharides (LPS) treatment and slightly down-regulated by polyriboinosinic polyribocytidylic acid [Poly (I:C)] challenge in in vitro experiments performed in the cultural primary coelomocytes, suggesting that the StmPCSK9-1 may play critical roles in the innate immune defense of sea cucumber, S. monotuberculatus, against bacterial and/or viral infections. PMID:27426522

  9. Two proprotein convertase subtilisin/kexin type 9 (PCSK9) paralogs from the tropical sea cucumber (Stichopus monotuberculatus): Molecular characterization and inducible expression with immune challenge.

    PubMed

    Ren, Chunhua; Chen, Ting; Jiang, Xiao; Sun, Hongyan; Qian, Jing; Hu, Chaoqun; Wang, Yanhong

    2016-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a multifunctional protein that widely exists in eukaryotic species. In this study, two PCSK9 paralogs, named StmPCSK9-1 and StmPCSK9-2, were identified from the tropical sea cucumber (Stichopus monotuberculatus). The cDNAs of StmPCSK9-1 and StmPCSK9-2 are 1330 kb and 1508 kb in size, respectively. The open reading frames (ORF) for StmPCSK9-1 and StmPCSK9-2 cDNAs are 1128 and 1167 bp in length, encoding the proteins of 375 and 388 amino acids with the deduced molecular weights of 38.76 and 41.07 kDa, respectively. In accord with other members in PCSK9 family, the two StmPCSK9 paralogs possessed the inhibitor_I9 and peptidase_S8 functional domains, seven active sites, a catalytic triad and two calcium binding sites. For the gene structure, the splicing of the two StmPCSK9 paralogs was relatively conserved. In addition, the mRNA expression of StmPCSK9-1 and StmPCSK9-2 was only detected in the sea cucumber intestine and coelomocytes, and the expression levels of both the two StmPCSK9 paralogs were higher in intestine. Moreover, StmPCSK9-2 was found to be a cytoplasm protein without signal peptide, and show no response to the immune challenge. On the contrary, StmPCSK9-1 was a secreted protein and the transcriptional expression of StmPCSK9-1 was significantly up-regulated by lipopolysaccharides (LPS) treatment and slightly down-regulated by polyriboinosinic polyribocytidylic acid [Poly (I:C)] challenge in in vitro experiments performed in the cultural primary coelomocytes, suggesting that the StmPCSK9-1 may play critical roles in the innate immune defense of sea cucumber, S. monotuberculatus, against bacterial and/or viral infections.

  10. Flame retardant spandex type polyurethanes

    NASA Technical Reports Server (NTRS)

    Howarth, J. T.; Sheth, S.; Sidman, K. R.; Massucco, A. A. (Inventor)

    1978-01-01

    Flame retardant elastomeric compositions were developed, comprised of: (1) spandex type polyurethane having incorporated into the polymer chain, halogen containing polyols; (2) conventional spandex type polyurethanes in physical admixture flame retardant additives; and (3) fluoroelastomeric resins in physical admixture with flame retardant additives. Methods of preparing fibers of the flame retardant elastomeric materials are presented and articles of manufacture comprised of the elastomeric materials are mentioned.

  11. Mental Retardation, Selected Conference Papers.

    ERIC Educational Resources Information Center

    Scheerenberger, R.C., Ed.

    A compilation of selected papers includes the following: comprehensive diagnostic services; pediatric aspects of diagnosis; psychological evaluation of the severely retarded; use of social competency devices; diagnosis of the adult retarded; programing for the severely retarded; nursery school experiences for the trainable; a practical approach to…

  12. Mainstreaming: The Educable Mentally Retarded.

    ERIC Educational Resources Information Center

    Watson, Marjorie

    Designed for teachers, the book discusses characteristics of retardation and suggests teaching strategies for retarded children in regular classes. Statistics and definitions of the levels of retardation are described, environmental influences are summarized, and diagnostic factors are reviewed. Discussed are physical, intellectual, and…

  13. Enzymes Catalyzing the Early Steps of Clavulanic Acid Biosynthesis Are Encoded by Two Sets of Paralogous Genes in Streptomyces clavuligerus

    PubMed Central

    Jensen, Susan E.; Elder, Kenneth J.; Aidoo, Kwamena A.; Paradkar, Ashish S.

    2000-01-01

    Genes encoding the proteins required for clavulanic acid biosynthesis and for cephamycin biosynthesis are grouped into a “supercluster” in Streptomyces clavuligerus. Nine open reading frames (ORFs) associated with clavulanic acid biosynthesis were located in a 15-kb segment of the supercluster, including six ORFs encoding known biosynthetic enzymes or regulatory proteins, two ORFs that have been reported previously but whose involvement in clavulanic acid biosynthesis is unclear, and one ORF not previously reported. Evidence for the involvement of these ORFs in clavulanic acid production was obtained by generating mutants and showing that all were defective for clavulanic acid production when grown on starch asparagine medium. However, when five of the nine mutants, including mutants defective in known clavulanic acid biosynthetic enzymes, were grown in a soy-based medium, clavulanic acid-producing ability was restored. This ability to produce clavulanic acid when seemingly essential biosynthetic enzymes have been mutated suggests that paralogous genes encoding functionally equivalent proteins exist for each of the five genes but that these paralogues are expressed only in the soy-based medium. The five genes that have paralogues encode proteins involved in the early steps of the pathway common to the biosynthesis of both clavulanic acid and the other clavam metabolites produced by this organism. No evidence was seen for paralogues of the four remaining genes involved in late, clavulanic acid-specific steps in the pathway. PMID:10681345

  14. A paralog of the proteinaceous elicitor sm1 affects colonization of maize roots by Trichoderma virens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biocontrol agent, Trichoderma virens, has the ability to protect plants from pathogens by eliciting plant defense responses, involvement in mycoparasitism, or secreting antagonistic secondary metabolites. SM1, an elicitor of induced systemic resistance (ISR), was found to have three paralogs wi...

  15. A Theory of Utility Conditionals: Paralogical Reasoning from Decision-Theoretic Leakage

    ERIC Educational Resources Information Center

    Bonnefon, Jean-Francois

    2009-01-01

    Many "if p, then q" conditionals have decision-theoretic features, such as antecedents or consequents that relate to the utility functions of various agents. These decision-theoretic features leak into reasoning processes, resulting in various paralogical conclusions. The theory of utility conditionals offers a unified account of the various forms…

  16. Flame Retardant Epoxy Resins

    NASA Technical Reports Server (NTRS)

    Thompson, C. M.; Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.; Lyon, R. E.

    2004-01-01

    As part of a program to develop fire resistant exterior composite structures for future subsonic commercial aircraft, flame retardant epoxy resins are under investigation. Epoxies and their curing agents (aromatic diamines) containing phosphorus were synthesized and used to prepare epoxy formulations. Phosphorus was incorporated within the backbone of the epoxy resin and not used as an additive. The resulting cured epoxies were characterized by thermogravimetric analysis, propane torch test, elemental analysis and microscale combustion calorimetry. Several formulations showed excellent flame retardation with phosphorous contents as low as 1.5% by weight. The fracture toughness of plaques of several cured formulations was determined on single-edge notched bend specimens. The chemistry and properties of these new epoxy formulations are discussed.

  17. Fire-retardant foams

    NASA Technical Reports Server (NTRS)

    Gagliani, J.

    1978-01-01

    Family of polyimide resins are being developed as foams with exceptional fire-retardant properties. Foams are potentially useful for seat cushions in aircraft and ground vehicles and for applications such as home furnishings and building-construction materials. Basic formulations can be modified with reinforcing fibers or fillers to produce celular materials for variety of applications. By selecting reactants, polymer structure can be modified to give foams with properties ranging from high resiliency and flexibility to brittleness and rigidity.

  18. Palaeophylogenomics of the vertebrate ancestor--impact of hidden paralogy on hagfish and lamprey gene phylogeny.

    PubMed

    Kuraku, Shigehiro

    2010-07-01

    In dissecting the transition from invertebrates to vertebrates at the molecular level, whole-genome duplications are recognized as a key event. This gave rise to more copies of genes in jawed vertebrates (gnathostomes), such as the four Hox clusters in the human, compared to the single ancestral cluster in invertebrates. To date, as the most early-branching lineages in vertebrates, cyclostomes (hagfishes and lampreys) have been used for comparative analyses of gene regulations and functions. However, assignment of orthology/paralogy for cyclostomes' genes is not unambiguously demonstrated. Thus, there is a high degree of incongruence in tree topologies between gene families, although whole genome duplications postulate uniform patterns in gene phylogeny. In this review, we demonstrate how expansion of an ancient genome before the cyclostome-gnathostome split, followed by reciprocal gene loss, can cause this incongruence. This is sometimes referred to as 'hidden paralogy'. PMID:21558193

  19. Roles of Rad51 paralogs for promoting homologous recombination in Leishmania infantum

    PubMed Central

    Genois, Marie-Michelle; Plourde, Marie; Éthier, Chantal; Roy, Gaétan; Poirier, Guy G.; Ouellette, Marc; Masson, Jean-Yves

    2015-01-01

    To achieve drug resistance Leishmania parasite alters gene copy number by using its repeated sequences widely distributed through the genome. Even though homologous recombination (HR) is ascribed to maintain genome stability, this eukaryote exploits this potent mechanism driven by the Rad51 recombinase to form beneficial extrachromosomal circular amplicons. Here, we provide insights on the formation of these circular amplicons by analyzing the functions of the Rad51 paralogs. We purified three Leishmania infantum Rad51 paralogs homologs (LiRad51-3, LiRad51-4 and LiRad51-6) all of which directly interact with LiRad51. LiRad51-3, LiRad51-4 and LiRad51-6 show differences in DNA binding and annealing capacities. Moreover, it is also noteworthy that LiRad51-3 and LiRad51-4 are able to stimulate Rad51-mediated D-loop formation. In addition, we succeed to inactivate the LiRad51-4 gene and report a decrease of circular amplicons in this mutant. The LiRad51-3 gene was found to be essential for cell viability. Thus, we propose that the LiRad51 paralogs play crucial functions in extrachromosomal circular DNA amplification to circumvent drug actions and preserve survival. PMID:25712090

  20. Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance

    SciTech Connect

    Bozdag, Gonensin Ozan; Uluisik, Irem; Gulculer, Gulce Sila; Karakaya, Huseyin C.; Koc, Ahmet

    2011-06-17

    Highlights: {yields} ATR1 paralog YMR279c plays role in boron detoxification. {yields} YMR279c overexpression lowers cytoplasmic boron levels. {yields} ATR1 paralog YOR378w has no roles in boron stress response. -- Abstract: Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast.

  1. Roles of Rad51 paralogs for promoting homologous recombination in Leishmania infantum.

    PubMed

    Genois, Marie-Michelle; Plourde, Marie; Éthier, Chantal; Roy, Gaétan; Poirier, Guy G; Ouellette, Marc; Masson, Jean-Yves

    2015-03-11

    To achieve drug resistance Leishmania parasite alters gene copy number by using its repeated sequences widely distributed through the genome. Even though homologous recombination (HR) is ascribed to maintain genome stability, this eukaryote exploits this potent mechanism driven by the Rad51 recombinase to form beneficial extrachromosomal circular amplicons. Here, we provide insights on the formation of these circular amplicons by analyzing the functions of the Rad51 paralogs. We purified three Leishmania infantum Rad51 paralogs homologs (LiRad51-3, LiRad51-4 and LiRad51-6) all of which directly interact with LiRad51. LiRad51-3, LiRad51-4 and LiRad51-6 show differences in DNA binding and annealing capacities. Moreover, it is also noteworthy that LiRad51-3 and LiRad51-4 are able to stimulate Rad51-mediated D-loop formation. In addition, we succeed to inactivate the LiRad51-4 gene and report a decrease of circular amplicons in this mutant. The LiRad51-3 gene was found to be essential for cell viability. Thus, we propose that the LiRad51 paralogs play crucial functions in extrachromosomal circular DNA amplification to circumvent drug actions and preserve survival.

  2. Nearly Identical Paralogs: Implications for Maize (Zea mays L.) Genome Evolution

    PubMed Central

    Emrich, Scott J.; Li, Li; Wen, Tsui-Jung; Yandeau-Nelson, Marna D.; Fu, Yan; Guo, Ling; Chou, Hui-Hsien; Aluru, Srinivas; Ashlock, Daniel A.; Schnable, Patrick S.

    2007-01-01

    As an ancient segmental tetraploid, the maize (Zea mays L.) genome contains large numbers of paralogs that are expected to have diverged by a minimum of 10% over time. Nearly identical paralogs (NIPs) are defined as paralogous genes that exhibit ≥98% identity. Sequence analyses of the “gene space” of the maize inbred line B73 genome, coupled with wet lab validation, have revealed that, conservatively, at least ∼1% of maize genes have a NIP, a rate substantially higher than that in Arabidopsis. In most instances, both members of maize NIP pairs are expressed and are therefore at least potentially functional. Of evolutionary significance, members of many NIP families also exhibit differential expression. The finding that some families of maize NIPs are closely linked genetically while others are genetically unlinked is consistent with multiple modes of origin. NIPs provide a mechanism for the maize genome to circumvent the inherent limitation that diploid genomes can carry at most two “alleles” per “locus.” As such, NIPs may have played important roles during the evolution and domestication of maize and may contribute to the success of long-term selection experiments in this important crop species. PMID:17110490

  3. Functional Annotations of Paralogs: A Blessing and a Curse

    PubMed Central

    Zallot, Rémi; Harrison, Katherine J.; Kolaczkowski, Bryan; de Crécy-Lagard, Valérie

    2016-01-01

    Gene duplication followed by mutation is a classic mechanism of neofunctionalization, producing gene families with functional diversity. In some cases, a single point mutation is sufficient to change the substrate specificity and/or the chemistry performed by an enzyme, making it difficult to accurately separate enzymes with identical functions from homologs with different functions. Because sequence similarity is often used as a basis for assigning functional annotations to genes, non-isofunctional gene families pose a great challenge for genome annotation pipelines. Here we describe how integrating evolutionary and functional information such as genome context, phylogeny, metabolic reconstruction and signature motifs may be required to correctly annotate multifunctional families. These integrative analyses can also lead to the discovery of novel gene functions, as hints from specific subgroups can guide the functional characterization of other members of the family. We demonstrate how careful manual curation processes using comparative genomics can disambiguate subgroups within large multifunctional families and discover their functions. We present the COG0720 protein family as a case study. We also discuss strategies to automate this process to improve the accuracy of genome functional annotation pipelines. PMID:27618105

  4. Functional Annotations of Paralogs: A Blessing and a Curse.

    PubMed

    Zallot, Rémi; Harrison, Katherine J; Kolaczkowski, Bryan; de Crécy-Lagard, Valérie

    2016-01-01

    Gene duplication followed by mutation is a classic mechanism of neofunctionalization, producing gene families with functional diversity. In some cases, a single point mutation is sufficient to change the substrate specificity and/or the chemistry performed by an enzyme, making it difficult to accurately separate enzymes with identical functions from homologs with different functions. Because sequence similarity is often used as a basis for assigning functional annotations to genes, non-isofunctional gene families pose a great challenge for genome annotation pipelines. Here we describe how integrating evolutionary and functional information such as genome context, phylogeny, metabolic reconstruction and signature motifs may be required to correctly annotate multifunctional families. These integrative analyses can also lead to the discovery of novel gene functions, as hints from specific subgroups can guide the functional characterization of other members of the family. We demonstrate how careful manual curation processes using comparative genomics can disambiguate subgroups within large multifunctional families and discover their functions. We present the COG0720 protein family as a case study. We also discuss strategies to automate this process to improve the accuracy of genome functional annotation pipelines. PMID:27618105

  5. Zinc Finger Domain of the PRDM9 Gene on Chromosome 1 Exhibits High Diversity in Ruminants but Its Paralog PRDM7 Contains Multiple Disruptive Mutations

    PubMed Central

    Ahlawat, Sonika; Sharma, Priyanka; Sharma, Rekha; Arora, Reena; De, Sachinandan

    2016-01-01

    PRDM9 is the sole hybrid sterility gene identified so far in vertebrates. PRDM9 gene encodes a protein with an immensely variable zinc-finger (ZF) domain that determines the site of meiotic recombination hotspots genome-wide. In this study, the terminal ZF domain of PRDM9 on bovine chromosome 1 and its paralog on chromosome 22 were characterized in 225 samples from five ruminant species (cattle, yak, mithun, sheep and goat). We found extraordinary variation in the number of PRDM9 zinc fingers (6 to 12). We sequenced PRDM9 ZF encoding region from 15 individuals (carrying the same ZF number in both copies) and found 43 different ZF domain sequences. Ruminant zinc fingers of PRDM9 were found to be diversifying under positive selection and concerted evolution, specifically at positions involved in defining their DNA-binding specificity, consistent with the reports from other vertebrates such as mice, humans, equids and chimpanzees. ZF-encoding regions of the PRDM7, a paralog of PRDM9 on bovine chromosome 22 and on unknown chromosomes in other studied species were found to contain 84 base repeat units as in PRDM9, but there were multiple disruptive mutations after the first repeat unit. The diversity of the ZFs suggests that PRDM9 may activate recombination hotspots that are largely unique to each ruminant species. PMID:27203728

  6. Structure-function analysis of npr1 alleles in Arabidopsis reveals a role for its paralogs in the perception of salicylic acid.

    PubMed

    Canet, Juan Vicente; Dobón, Albor; Roig, Alejandra; Tornero, Pablo

    2010-11-01

    Salicylic acid (SA) is necessary for plant defence against some pathogens, whereas NPR1 is necessary for SA perception. Plant defence can be induced to an extreme by several applications of benzothiadiazole (BTH), an analogue of SA. Thus, plants that do not perceive BTH grow unaffected, whereas wild-type plants grow stunted. This feature allows us to screen for mutants in Arabidopsis thaliana that show insensitivity to BTH in a high-throughput fashion. Most of the mutants are npr1 alleles, with similar phenotypes in plant weight and pathogen growth. The mutations are clustered in the carboxyl-terminal part of the protein, and no obvious null alleles were recovered. These facts have prompted a search for knockouts in the NPR1 gene. Two of these KO alleles identified are null and have an intermediate phenotype. All the evidence presented lead us to propose a redundancy in SA perception, with the paralogs of NPR1 taking part in this signalling. We show that the mutations recovered in the screening genetically interact with the paralogs preventing their function in SA signalling.

  7. Zinc Finger Domain of the PRDM9 Gene on Chromosome 1 Exhibits High Diversity in Ruminants but Its Paralog PRDM7 Contains Multiple Disruptive Mutations.

    PubMed

    Ahlawat, Sonika; Sharma, Priyanka; Sharma, Rekha; Arora, Reena; De, Sachinandan

    2016-01-01

    PRDM9 is the sole hybrid sterility gene identified so far in vertebrates. PRDM9 gene encodes a protein with an immensely variable zinc-finger (ZF) domain that determines the site of meiotic recombination hotspots genome-wide. In this study, the terminal ZF domain of PRDM9 on bovine chromosome 1 and its paralog on chromosome 22 were characterized in 225 samples from five ruminant species (cattle, yak, mithun, sheep and goat). We found extraordinary variation in the number of PRDM9 zinc fingers (6 to 12). We sequenced PRDM9 ZF encoding region from 15 individuals (carrying the same ZF number in both copies) and found 43 different ZF domain sequences. Ruminant zinc fingers of PRDM9 were found to be diversifying under positive selection and concerted evolution, specifically at positions involved in defining their DNA-binding specificity, consistent with the reports from other vertebrates such as mice, humans, equids and chimpanzees. ZF-encoding regions of the PRDM7, a paralog of PRDM9 on bovine chromosome 22 and on unknown chromosomes in other studied species were found to contain 84 base repeat units as in PRDM9, but there were multiple disruptive mutations after the first repeat unit. The diversity of the ZFs suggests that PRDM9 may activate recombination hotspots that are largely unique to each ruminant species. PMID:27203728

  8. Expression of Hox paralog group 13 genes in adult and developing Megalobrama amblycephala.

    PubMed

    Jakovlić, Ivan; Wang, Wei-Min

    2016-07-01

    Hox genes encode transcription factors that play a key role in specifying the body plan in most metazoans. HoxPG13 genes most probably played an important role in body length variation during the evolution of animals. This is the first report of the mRNA expression patterns of the entire Hox paralog group 13 (HoxA13a, HoxA13b, HoxB13a, HoxC13a, HoxC13b, HoxD13a) in fish. Expression was studied by qPCR in five tissues of adult Megalobrama amblycephala specimens (spleen, liver, kidney, intestine and gills) and during development (17 stages: fertilised egg to 90 days-old juveniles). Expression in tissues (for all six genes) was generally very low in gills (0.0006-0.05), spleen (0.006-0.09) and kidney (0.02-0.39); the highest in intestine (from 2.28 for HoxC13b to 244.29 for HoxC13a). During the development, a peak in expression around the hatching was observed for all six genes. Results suggest a high maternal expression of HoxA13a, and low for HoxA13ab. HoxD13a paralog exhibited the lowest expression: 0.0006-2.63 in tissues and 0.0005-1.7 during development, suggesting the possibility of a gradual loss of functionality. Expression of HoxC13 paralogs corroborates the findings in zebrafish: HoxC13b is maternally expressed and more important during the development. In adults, it was the opposite: expression was low for HoxC13b and very variable for HoxC13a (0.06-244.29). Differences in expression levels between both pairs of paralogs (Aa/Ab and Ca/Cb) indicate the possibility of the existence of some redundancy afforded by maintaining both paralogs. PMID:27476414

  9. Fire-Retardant Epoxy Adhesives

    NASA Technical Reports Server (NTRS)

    Bilow, N.; Giants, T. W.

    1982-01-01

    Phosphorus-containing epoxy is fire-retardant and translucent. Intended as adhesive for laminated plastic sheets, new material bonds well to titanium dioxide-filled plastic film, which ordinarily shows little surface interaction with adhesives. Fire retardancy has been demonstrated, and smoke density is low enough to avoid smoke obscuration.

  10. Flame retarded asphalt blend composition

    SciTech Connect

    Walters, R.B.

    1987-04-21

    This patent describes a flame retarded asphalt composition consisting essentially of a blend of: (a) thermoplastic elastomer modified bitumen; (b) 20-30 wt % inert filler; (c) 1-20 wt % of at least one halogenated flame retardant; and (d) 1-5 wt % of at least one inorganic phosphorus containing compound selected from the group consisting of ammonium phosphate compounds and red phosphorus.

  11. Educable Mentally Retarded, Level I.

    ERIC Educational Resources Information Center

    Suo, Minnie Alice; Willemin, Helen

    Intended for teachers of special classes of educable mentally retarded children aged 6 to 8 (mental age = 3.5 to 4.9), the guide stresses skills necessary to the development of physical, personal and social, and vocational competency. An introduction defines philosophy and goals, outlines the educable mentally retarded program and the readiness…

  12. The Mentally Retarded in Sweden.

    ERIC Educational Resources Information Center

    Grunewald, Karl

    Described are residential and educational services provided for mentally retarded (MC) children and adults in Sweden. Normalization is the focus of the services which make maximum use of mental and physical capacities to reduce the handicap of mental retardation. Described are general principles, and four stages involving development of services…

  13. THE PATHOLOGY OF MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CROME, L.; STERN, J.

    DATA FROM RECENT COMPREHENSIVE STUDIES OF THE PATHOLOGY OF MENTAL RETARDATION ARE ASSEMBLED, INCLUDING MATERIAL ON ETIOLOGY, MORPHOLOGY, BIOCHEMISTRY, AND LABORATORY DIAGNOSIS. AREAS COVERED ARE (1) GENETIC CAUSES OF MENTAL RETARDATION, (2) DISORDERS OF GESTATION, (3) BIRTH INJURY, (4) GENERAL CONSIDERATIONS OF POSTNATAL CAUSES OF MENTAL…

  14. Issues in Defining Mental Retardation.

    ERIC Educational Resources Information Center

    Reiss, Steven

    1994-01-01

    This paper responds to criticisms of the American Association on Mental Retardation's new definition of mental retardation. Emphasis is on the intent to change from a deficiency model to a support model, with more importance given to the role of the environment. Also addressed are IQ score guidelines, cultural bias, assessment, and public policy.…

  15. Social Work and Mental Retardation.

    ERIC Educational Resources Information Center

    Schreiber, Meyer, Ed.

    Of special interest for social work students, teachers, and practitioners, the collection of 94 articles presents a broad survey of the field of mental retardation particularly as it relates to social work. The articles indicate both past work and the current status of social work practice with the mentally retarded. Material includes background…

  16. Highly divergent 18S rRNA gene paralogs in a Cryptosporidium genotype from eastern chipmunks (Tamias striatus)1

    PubMed Central

    Stenger, Brianna L.S.; Clark, Mark E.; Kváč, Martin; Khan, Eakalak; Giddings, Catherine W.; Dyer, Neil W.; Schultz, Jessie L.; McEvoy, John M.

    2015-01-01

    Cryptosporidium is an apicomplexan parasite that causes the disease cryptosporidiosis in humans, livestock, and other vertebrates. Much of the knowledge on Cryptosporidium diversity is derived from 18S rRNA gene (18S rDNA) phylogenies. Eukaryote genomes generally have multiple 18S rDNA copies that evolve in concert, which is necessary for the accurate inference of phylogenetic relationships. However, 18S rDNA copies in some genomes evolve by a birth-and-death process that can result in sequence divergence among copies. Most notably, divergent 18S rDNA paralogs in the apicomplexan Plasmodium share only 89–95% sequence similarity, encode structurally distinct rRNA molecules, and are expressed at different life cycle stages. In the present study, Cryptosporidium 18S rDNA was amplified from 28/72 (38.9%) eastern chipmunks (Tamias striatus). Phylogenetic analyses showed the co-occurrence of two 18S rDNA types, Type A and Type B, in 26 chipmunks, and Type B clustered with a sequence previously identified as Cryptosporidium chipmunk genotype II. Types A and B had a sister group relationship but shared less than 93% sequence similarity. In contrast, actin and heat shock protein 70 gene sequences were homogeneous in samples with both Types A and B present. It was therefore concluded that Types A and B are divergent 18S rDNA paralogs in Cryptosporidium chipmunk genotype II. Substitution patterns in Types A and B were consistent with functionally constrained evolution; however, Type B evolved more rapidly than Type A and had a higher G+C content (46.3% versus 41.0%). Oocysts of Cryptosporidium chipmunk genotype II measured 4.17 μm (3.73–5.04 μm) × 3.94 μm (3.50–4.98 μm) with a length-to-width ratio of 1.06 ± 0.06 μm, and infection occurred naturally in the jejunum, cecum, and colon of eastern chipmunks. The findings of this study have implications for the use of 18S rDNA sequences to infer phylogenetic relationships. PMID:25772204

  17. Highly divergent 18S rRNA gene paralogs in a Cryptosporidium genotype from eastern chipmunks (Tamias striatus).

    PubMed

    Stenger, Brianna L S; Clark, Mark E; Kváč, Martin; Khan, Eakalak; Giddings, Catherine W; Dyer, Neil W; Schultz, Jessie L; McEvoy, John M

    2015-06-01

    Cryptosporidium is an apicomplexan parasite that causes the disease cryptosporidiosis in humans, livestock, and other vertebrates. Much of the knowledge on Cryptosporidium diversity is derived from 18S rRNA gene (18S rDNA) phylogenies. Eukaryote genomes generally have multiple 18S rDNA copies that evolve in concert, which is necessary for the accurate inference of phylogenetic relationships. However, 18S rDNA copies in some genomes evolve by a birth-and-death process that can result in sequence divergence among copies. Most notably, divergent 18S rDNA paralogs in the apicomplexan Plasmodium share only 89-95% sequence similarity, encode structurally distinct rRNA molecules, and are expressed at different life cycle stages. In the present study, Cryptosporidium 18S rDNA was amplified from 28/72 (38.9%) eastern chipmunks (Tamias striatus). Phylogenetic analyses showed the co-occurrence of two 18S rDNA types, Type A and Type B, in 26 chipmunks, and Type B clustered with a sequence previously identified as Cryptosporidium chipmunk genotype II. Types A and B had a sister group relationship but shared less than 93% sequence similarity. In contrast, actin and heat shock protein 70 gene sequences were homogeneous in samples with both Types A and B present. It was therefore concluded that Types A and B are divergent 18S rDNA paralogs in Cryptosporidium chipmunk genotype II. Substitution patterns in Types A and B were consistent with functionally constrained evolution; however, Type B evolved more rapidly than Type A and had a higher G+C content (46.3% versus 41.0%). Oocysts of Cryptosporidium chipmunk genotype II measured 4.17 μm (3.73-5.04 μm) × 3.94 μm (3.50-4.98 μm) with a length-to-width ratio of 1.06 ± 0.06 μm, and infection occurred naturally in the jejunum, cecum, and colon of eastern chipmunks. The findings of this study have implications for the use of 18S rDNA sequences to infer phylogenetic relationships.

  18. Four VirB6 paralogs and VirB9 are expressed and interact in Ehrlichia chaffeensis-containing vacuoles.

    PubMed

    Bao, Weichao; Kumagai, Yumi; Niu, Hua; Yamaguchi, Mamoru; Miura, Koshiro; Rikihisa, Yasuko

    2009-01-01

    The type IV secretion system is an important virulence factor in several host cell-associated pathogens, as it delivers various bacterial macromolecules to target eukaryotic cells. Genes homologous to several virB genes and virD4 of Agrobacterium tumefaciens are found in an intravacuolar pathogen Ehrlichia chaffeensis, the tick-borne causative agent of human monocytic ehrlichiosis. In particular, despite its small genome size, E. chaffeensis has four tandem virB6 paralogs (virB6-1, -2, -3, and -4) that are 3- to 10-fold larger than A. tumefaciens virB6. The present study for the first time illustrates the relevance of the larger quadruple VirB6 paralogs by demonstrating the protein expression and interaction in E. chaffeensis. All four virB6 paralogs were cotranscribed in THP-1 human leukemia and ISE6 tick cell cultures. The four VirB6 proteins and VirB9 were expressed by E. chaffeensis in THP-1 cells, and amounts of these five proteins were similar in isolated E. chaffeensis-containing vacuoles and vacuole-free E. chaffeensis. In addition, an 80-kDa fragment of VirB6-2 was detected, which was strikingly more prevalent in E. chaffeensis-containing vacuoles than in vacuole-free E. chaffeensis. Coimmunoprecipitation analysis revealed VirB9 interaction with VirB6-1 and VirB6-2; VirB6-4 interaction with VirB6-1, VirB6-2, and VirB6-3; and VirB6-2 80-kDa fragment interaction with VirB6-3 and VirB6-4. The interaction of VirB9 and VirB6-2 was confirmed by far-Western blotting. The results suggest that E. chaffeensis VirB9, the quadruple VirB6 proteins, and the VirB6-2 80-kDa fragment form a unique molecular subassembly to cooperate in type IV secretion. PMID:18952796

  19. Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles.

    PubMed

    Baud, Olivia; Yuan, Shuguang; Veya, Luc; Filipek, Slawomir; Vogel, Horst; Pick, Horst

    2015-01-01

    A multi-gene family of ~1000 G protein-coupled olfactory receptors (ORs) constitutes the molecular basis of mammalian olfaction. Due to the lack of structural data its remarkable capacity to detect and discriminate thousands of odorants remains poorly understood on the structural level of the receptor. Using site-directed mutagenesis we transferred ligand specificity between two functionally related ORs and thereby revealed amino acid residues of central importance for odorant recognition and discrimination of the two receptors. By exchanging two of three residues, differing at equivalent positions of the putative odorant binding site between the mouse OR paralogs Olfr73 (mOR-EG) and Olfr74 (mOR-EV), we selectively changed ligand preference but remarkably also signaling activation strength in both ORs. Computer modeling proposed structural details at atomic resolution how the very same odorant molecule might interact with different contact residues to induce different functional responses in two related receptors. Our findings provide a mechanistic explanation of how the olfactory system distinguishes different molecular aspects of a given odorant molecule, and unravel important molecular details of the combinatorial encoding of odorant identity at the OR level.

  20. Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles.

    PubMed

    Baud, Olivia; Yuan, Shuguang; Veya, Luc; Filipek, Slawomir; Vogel, Horst; Pick, Horst

    2015-01-01

    A multi-gene family of ~1000 G protein-coupled olfactory receptors (ORs) constitutes the molecular basis of mammalian olfaction. Due to the lack of structural data its remarkable capacity to detect and discriminate thousands of odorants remains poorly understood on the structural level of the receptor. Using site-directed mutagenesis we transferred ligand specificity between two functionally related ORs and thereby revealed amino acid residues of central importance for odorant recognition and discrimination of the two receptors. By exchanging two of three residues, differing at equivalent positions of the putative odorant binding site between the mouse OR paralogs Olfr73 (mOR-EG) and Olfr74 (mOR-EV), we selectively changed ligand preference but remarkably also signaling activation strength in both ORs. Computer modeling proposed structural details at atomic resolution how the very same odorant molecule might interact with different contact residues to induce different functional responses in two related receptors. Our findings provide a mechanistic explanation of how the olfactory system distinguishes different molecular aspects of a given odorant molecule, and unravel important molecular details of the combinatorial encoding of odorant identity at the OR level. PMID:26449412

  1. Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles

    PubMed Central

    Baud, Olivia; Yuan, Shuguang; Veya, Luc; Filipek, Slawomir; Vogel, Horst; Pick, Horst

    2015-01-01

    A multi-gene family of ~1000 G protein-coupled olfactory receptors (ORs) constitutes the molecular basis of mammalian olfaction. Due to the lack of structural data its remarkable capacity to detect and discriminate thousands of odorants remains poorly understood on the structural level of the receptor. Using site-directed mutagenesis we transferred ligand specificity between two functionally related ORs and thereby revealed amino acid residues of central importance for odorant recognition and discrimination of the two receptors. By exchanging two of three residues, differing at equivalent positions of the putative odorant binding site between the mouse OR paralogs Olfr73 (mOR-EG) and Olfr74 (mOR-EV), we selectively changed ligand preference but remarkably also signaling activation strength in both ORs. Computer modeling proposed structural details at atomic resolution how the very same odorant molecule might interact with different contact residues to induce different functional responses in two related receptors. Our findings provide a mechanistic explanation of how the olfactory system distinguishes different molecular aspects of a given odorant molecule, and unravel important molecular details of the combinatorial encoding of odorant identity at the OR level. PMID:26449412

  2. Mutations in SYNGAP1 in Autosomal Nonsyndromic Mental Retardation

    PubMed Central

    Hamdan, Fadi F.; Gauthier, Julie; Spiegelman, Dan; Noreau, Anne; Yang, Yan; Pellerin, Stéphanie; Dobrzeniecka, Sylvia; Côté, Mélanie; Perreau-Linck, Elizabeth; Carmant, Lionel; D’Anjou, Guy; Fombonne, Éric; Addington, Anjene M.; Rapoport, Judith L.; Delisi, Lynn E.; Krebs, Marie-Odile; Mouaffak, Faycal; Joober, Ridha; Mottron, Laurent; Drapeau, Pierre; Marineau, Claude; Lafrenière, Ronald G.; Lacaille, Jean Claude; Rouleau, Guy A.; Michaud, Jacques L.

    2010-01-01

    Summary Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation. PMID:19196676

  3. Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development.

    PubMed

    Ertl, Iris; Porta-de-la-Riva, Montserrat; Gómez-Orte, Eva; Rubio-Peña, Karinna; Aristizábal-Corrales, David; Cornes, Eric; Fontrodona, Laura; Osteikoetxea, Xabier; Ayuso, Cristina; Askjaer, Peter; Cabello, Juan; Cerón, Julián

    2016-03-01

    SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether ham-3 and swsn-2.2 have different functions during C. elegans development since they encode proteins that are probably mutually exclusive in a given SWI/SNF complex. We found that ham-3 and swsn-2.2 display similar functions in vulva specification, germline development, and intestinal cell proliferation, but have distinct roles in embryonic development. Accordingly, we detected functional redundancy in some developmental processes and demonstrated by RNA sequencing of RNAi-treated L4 animals that ham-3 and swsn-2.2 regulate the expression of a common subset of genes but also have specific targets. Cell lineage analyses in the embryo revealed hyper-proliferation of intestinal cells in ham-3 null mutants whereas swsn-2.2 is required for proper cell divisions. Using a proteomic approach, we identified SWSN-2.2-interacting proteins needed for early cell divisions, such as SAO-1 and ATX-2, and also nuclear envelope proteins such as MEL-28. swsn-2.2 mutants phenocopy mel-28 loss-of-function, and we observed that SWSN-2.2 and MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of MEL-28 to the nuclear periphery.

  4. Neurotoxicity of brominated flame retardants

    EPA Science Inventory

    Polybrominated diphenyl ethers (PBDEs) have been commonly used as commercial flame retardants in a variety of products including plastics and textiles. Despite their decreasing usage worldwide, congeners continue to accumulate in the environment, including soil, dust, food, anima...

  5. Intumescent Coatings as Fire Retardants

    NASA Technical Reports Server (NTRS)

    Fish, R. H.; Fohlen, G. M.; Parker, J. A.; Sawko, P. M.

    1970-01-01

    Fire-retardant paint, when activated by the heat of fire, reacts to form a thick, low-density, polymeric coating or char layer. Water vapor and sulphur dioxide are released during the intumescent reaction.

  6. INTRODUCTION TO BROMINATED FLAME RETARDANTS

    EPA Science Inventory

    Brominated flame retardants (BFRs) are a large and diverse class of major industrial products used to provide fire safety. Tetrabromobisphenol A (TBBPA), Hexabromocylocodecane (HBCD), and Polybrominated Diphenyl Ethers (PBDEs) are the major commercial compounds. TBBPA is a react...

  7. Transcendental meditation and mental retardation.

    PubMed

    Eyerman, J

    1981-01-01

    A 26-year old moderately mentally retarded woman was taught the Transcendental Meditation technique. She experienced spontaneous improvements in her verbal and social behavior and physiological functioning over a period of three years while practicing the technique.

  8. Deinstitutionalization of the Mentally Retarded.

    ERIC Educational Resources Information Center

    Cortez, Patricia

    Literature on deinstitutionalization of mentally retarded persons is reviewed. Cited are studies showing positive aspects, including improved communication abilities, increased adaptive behavior and personal satisfaction. Community adjustment findings focus on effects of involuntary relocation to another facility, age differences, and…

  9. Can earthworms survive fire retardants?

    USGS Publications Warehouse

    Beyer, W.N.; Olson, A.

    1996-01-01

    Most common fire retardants are foams or are similar to common agricultural fertilizers, such as ammonium sulfate and ammonium phosphate. Although fire retardants are widely applied to soils, we lack basic information about their toxicities to soil organisms. We measured the toxicity of five fire retardants (Firetrol LCG-R, Firetrol GTS-R, Silv-Ex Foam Concentrate, Phos-chek D-75, and Phos-chek WD-881) to earthworms using the pesticide toxicity test developed for earthworms by the European Economic Community. None was lethal at 1,000 ppm in the soil, which was suggested as a relatively high exposure under normal applications. We concluded that the fire retardants tested are relatively nontoxic to soil organisms compared with other environmental chemicals and that they probably do not reduce earthworm populations when applied under usual firefighting conditions.

  10. The Mentally Retarded Offender: Annotated Bibliography.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; And Others

    An annotated bibliography of approximately 150 books and articles on the mentally retarded offender as well as 30 nonannotated entries are provided. Topics covered include such areas as characteristics of mentally retarded delinquents, rehabilitation of the retarded offender, community services for retarded persons, rights of the mentally…

  11. Developmental Problems of the Moderately Mentally Retarded.

    ERIC Educational Resources Information Center

    Bepko, Raymond A.; And Others

    Hypothesizing that the dimensions of developmental problems faced by the moderately retarded will be analogous to those faced by the mildly retarded, this study considers the appropriateness of the structure of the Social Learning Curriculum (SLC), originally developed for the mildly retarded, for the moderately retarded. The SLC framework…

  12. A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog

    PubMed Central

    Krahmer, Julia; Leopoldi, Alexandra; Artaker, Matthias; Pusch, Oliver; Zezula, Jürgen; Weissmann, Simon; Xie, Yunli; Schöfer, Christian; Schlederer, Michaela; Brosch, Gerald; Matthias, Patrick; Selfridge, Jim; Lassmann, Hans; Knoblich, Jürgen A.; Seiser, Christian

    2016-01-01

    The histone deacetylases HDAC1 and HDAC2 are crucial regulators of chromatin structure and gene expression, thereby controlling important developmental processes. In the mouse brain, HDAC1 and HDAC2 exhibit different developmental stage- and lineage-specific expression patterns. To examine the individual contribution of these deacetylases during brain development, we deleted different combinations of Hdac1 and Hdac2 alleles in neural cells. Ablation of Hdac1 or Hdac2 by Nestin-Cre had no obvious consequences on brain development and architecture owing to compensation by the paralog. By contrast, combined deletion of Hdac1 and Hdac2 resulted in impaired chromatin structure, DNA damage, apoptosis and embryonic lethality. To dissect the individual roles of HDAC1 and HDAC2, we expressed single alleles of either Hdac1 or Hdac2 in the absence of the respective paralog in neural cells. The DNA-damage phenotype observed in double knockout brains was prevented by expression of a single allele of either Hdac1 or Hdac2. Strikingly, Hdac1−/−Hdac2+/− brains showed normal development and no obvious phenotype, whereas Hdac1+/−Hdac2−/− mice displayed impaired brain development and perinatal lethality. Hdac1+/−Hdac2−/− neural precursor cells showed reduced proliferation and premature differentiation mediated by overexpression of protein kinase C, delta, which is a direct target of HDAC2. Importantly, chemical inhibition or knockdown of protein kinase C delta was sufficient to rescue the phenotype of neural progenitor cells in vitro. Our data indicate that HDAC1 and HDAC2 have a common function in maintaining proper chromatin structures and show that HDAC2 has a unique role by controlling the fate of neural progenitors during normal brain development. PMID:24449838

  13. Conserved transcriptional responses to cyanobacterial stressors are mediated by alternate regulation of paralogous genes in Daphnia.

    PubMed

    Asselman, Jana; Pfrender, Michael E; Lopez, Jacqueline A; De Coninck, Dieter I M; Janssen, Colin R; Shaw, Joseph R; De Schamphelaere, Karel A C

    2015-04-01

    Despite a significant increase in genomic data, our knowledge of gene functions and their transcriptional responses to environmental stimuli remains limited. Here, we use the model keystone species Daphnia pulex to study environmental responses of genes in the context of their gene family history to better understand the relationship between genome structure and gene function in response to environmental stimuli. Daphnia were exposed to five different treatments, each consisting of a diet supplemented with one of five cyanobacterial species, and a control treatment consisting of a diet of only green algae. Differential gene expression profiles of Daphnia exposed to each of these five cyanobacterial species showed that genes with known functions are more likely to be shared by different expression profiles, whereas genes specific to the lineage of Daphnia are more likely to be unique to a given expression profile. Furthermore, while only a small number of nonlineage-specific genes were conserved across treatment type, there was a high degree of overlap in expression profiles at the functional level. The conservation of functional responses across the different cyanobacterial treatments can be attributed to the treatment-specific expression of different paralogous genes within the same gene family. Comparison with available gene expression data in the literature suggests differences in nutritional composition in diets with cyanobacterial species compared to diets of green algae as a primary driver for cyanobacterial effects on Daphnia. We conclude that conserved functional responses in Daphnia across different cyanobacterial treatments are mediated through alternate regulation of paralogous gene families.

  14. A theory of utility conditionals: Paralogical reasoning from decision-theoretic leakage.

    PubMed

    Bonnefon, Jean-François

    2009-10-01

    Many "if p, then q" conditionals have decision-theoretic features, such as antecedents or consequents that relate to the utility functions of various agents. These decision-theoretic features leak into reasoning processes, resulting in various paralogical conclusions. The theory of utility conditionals offers a unified account of the various forms that this phenomenon can take. The theory is built on 2 main components: (1) a representational tool (the utility grid), which summarizes in compact form the decision-theoretic features of a conditional, and (2) a set of folk axioms of decision, which reflect reasoners' beliefs about the way most agents make their decisions. Applying the folk axioms to the utility grid of a conditional allows for the systematic prediction of the paralogical conclusions invited by the utility grid's decision-theoretic features. The theory of utility conditionals significantly extends the scope of current theories of conditional inference and moves reasoning research toward a greater integration with decision-making research. PMID:19839689

  15. IDN2 and Its Paralogs Form a Complex Required for RNA–Directed DNA Methylation

    PubMed Central

    Zhang, Cui-Jun; Ning, Yong-Qiang; Zhang, Su-Wei; Chen, Qing; Shao, Chang-Rong; Guo, Yan-Wu; Zhou, Jin-Xing; Li, Lin; Chen, She; He, Xin-Jian

    2012-01-01

    IDN2/RDM12 has been previously identified as a component of the RNA–directed DNA methylation (RdDM) machinery in Arabidopsis thaliana, but how it functions in RdDM remains unknown. By affinity purification of IDN2, we co-purified two IDN2 paralogs IDP1 and IDP2 (IDN2 PARALOG 1 and 2). The coiled-coil domain between the XS and XH domains of IDN2 is essential for IDN2 homodimerization, whereas the IDN2 C-terminal XH domain but not the coiled-coil domain is required for IDN2 interaction with IDP1 and IDP2. By introducing the wild-type IDN2 sequence and its mutated derivatives into the idn2 mutant for complementation testing, we demonstrated that the previously uncharacterized IDN2 XH domain is required for the IDN2-IDP1/IDP2 complex formation as well as for IDN2 function. IDP1 is required for de novo DNA methylation, siRNA accumulation, and transcriptional gene silencing, whereas IDP2 has partially overlapping roles with IDP1. Unlike IDN2, IDP1 and IDP2 are incapable of binding double-stranded RNA, suggesting that the roles of IDP1 and IDP2 are different from those of IDN2 in the IDN2-IDP1/IDP2 complex and that IDP1 and IDP2 are essential for the functioning of the complex in RdDM. PMID:22570638

  16. Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex

    PubMed Central

    2013-01-01

    Background Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. Methods In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling - homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP) - in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)). Results There were significant increases in RAC1, APP 120 kDa and APP 80 kDa proteins in BA9 of children with autism vs. healthy controls. None of the same proteins were significantly affected in cerebellar vermis of children with autism. In BA9 of adults with autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in homer 1 vs. controls. In the vermis of adult subjects with autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with autism. There was a significant effect of anticonvulsant use on STEP 46 kDa/β-actin and a potential effect on homer 1/NSE, in BA9 of adults with autism. However, no other significant confound effects were observed in this study. Conclusions Our findings provide further evidence of abnormalities in FMRP and

  17. Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery

    PubMed Central

    Pan, Shu-Ting; Xue, Danfeng; Li, Zhi-Ling; Zhou, Zhi-Wei; He, Zhi-Xu; Yang, Yinxue; Yang, Tianxin; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-01-01

    The human cytochrome P450 (CYP) superfamily consisting of 57 functional genes is the most important group of Phase I drug metabolizing enzymes that oxidize a large number of xenobiotics and endogenous compounds, including therapeutic drugs and environmental toxicants. The CYP superfamily has been shown to expand itself through gene duplication, and some of them become pseudogenes due to gene mutations. Orthologs and paralogs are homologous genes resulting from speciation or duplication, respectively. To explore the evolutionary and functional relationships of human CYPs, we conducted this bioinformatic study to identify their corresponding paralogs, homologs, and orthologs. The functional implications and implications in drug discovery and evolutionary biology were then discussed. GeneCards and Ensembl were used to identify the paralogs of human CYPs. We have used a panel of online databases to identify the orthologs of human CYP genes: NCBI, Ensembl Compara, GeneCards, OMA (“Orthologous MAtrix”) Browser, PATHER, TreeFam, EggNOG, and Roundup. The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl. For example, the paralogs of CYP2A6 include CYP2A7, 2A13, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 2R1, 2S1, 2U1, and 2W1; CYP11A1 has 6 paralogs including CYP11B1, 11B2, 24A1, 27A1, 27B1, and 27C1; CYP51A1 has only three paralogs: CYP26A1, 26B1, and 26C1; while CYP20A1 has no paralog. The majority of human CYPs are well conserved from plants, amphibians, fishes, or mammals to humans due to their important functions in physiology and xenobiotic disposition. The data from different approaches are also cross-validated and validated when experimental data are available. These findings facilitate our understanding of the evolutionary relationships and functional implications of the human CYP superfamily in drug discovery. PMID:27367670

  18. Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery.

    PubMed

    Pan, Shu-Ting; Xue, Danfeng; Li, Zhi-Ling; Zhou, Zhi-Wei; He, Zhi-Xu; Yang, Yinxue; Yang, Tianxin; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-01-01

    The human cytochrome P450 (CYP) superfamily consisting of 57 functional genes is the most important group of Phase I drug metabolizing enzymes that oxidize a large number of xenobiotics and endogenous compounds, including therapeutic drugs and environmental toxicants. The CYP superfamily has been shown to expand itself through gene duplication, and some of them become pseudogenes due to gene mutations. Orthologs and paralogs are homologous genes resulting from speciation or duplication, respectively. To explore the evolutionary and functional relationships of human CYPs, we conducted this bioinformatic study to identify their corresponding paralogs, homologs, and orthologs. The functional implications and implications in drug discovery and evolutionary biology were then discussed. GeneCards and Ensembl were used to identify the paralogs of human CYPs. We have used a panel of online databases to identify the orthologs of human CYP genes: NCBI, Ensembl Compara, GeneCards, OMA ("Orthologous MAtrix") Browser, PATHER, TreeFam, EggNOG, and Roundup. The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl. For example, the paralogs of CYP2A6 include CYP2A7, 2A13, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 2R1, 2S1, 2U1, and 2W1; CYP11A1 has 6 paralogs including CYP11B1, 11B2, 24A1, 27A1, 27B1, and 27C1; CYP51A1 has only three paralogs: CYP26A1, 26B1, and 26C1; while CYP20A1 has no paralog. The majority of human CYPs are well conserved from plants, amphibians, fishes, or mammals to humans due to their important functions in physiology and xenobiotic disposition. The data from different approaches are also cross-validated and validated when experimental data are available. These findings facilitate our understanding of the evolutionary relationships and functional implications of the human CYP superfamily in drug discovery. PMID:27367670

  19. Development of novel fire retardants

    NASA Astrophysics Data System (ADS)

    Sigdel Regmi, Bhawani

    Numerous candidate environmentally-friendly, water-soluble, and non-toxic fire retardants and fire-retarding processes were developed and tested according to the ASTM D 3801 flammability test and the NRL 8093 smoldering test. Flame retardants that passed the ASTM D 3801 flammability test with the highest V0 rating were boron esters of guanidinium hydroxycarboxylate (glycolate, salicylate and dihydroxybenzoate), zinc gluconate borate ester, and cyanoacetate salts of organic bases (melaminium, cyanoguanidinium, and ammonium). Several related compounds pass this test with the lower V1 rating. Two new synergistic flame and smolder retarding systems were developed in which the individual components were incapable of preventing flame spread or smoldering but in combination they were highly effective. These systems were mixtures of either guanyl urea phosphate and boric acid or beta-alanine and boric acid. Compositions leading to the maximum solubility of boron oxides in the ammonium borate/sodium borate system were determined at several temperatures and the formation of mixtures exceeding 50% dissolved boric acid equivalents was found possible. These mixtures were applied as flame retardants for wood, paper, and carbon-loaded polyurethane foam both directly and indirectly by in situ precipitation of boric acid or zinc borate by appropriate chemical treatments. These all passed the ASTM flammability test with V0 rating. The performance of the boron-containing fire retardants is likely due to deposition of protective boron oxide coatings at elevated temperatures except where phosphate was present and a protective boron phosphate was deposited instead. In all cases, the oxidation of carbonaceous char was strongly inhibited. The hydroxycarboxylate groups generally formed intumescent chars during thermal decomposition that also contributed to fire retardancy.

  20. Conservation of σ28-Dependent Non-Coding RNA Paralogs and Predicted σ54-Dependent Targets in Thermophilic Campylobacter Species.

    PubMed

    Le, My Thanh; van Veldhuizen, Mart; Porcelli, Ida; Bongaerts, Roy J; Gaskin, Duncan J H; Pearson, Bruce M; van Vliet, Arnoud H M

    2015-01-01

    Assembly of flagella requires strict hierarchical and temporal control via flagellar sigma and anti-sigma factors, regulatory proteins and the assembly complex itself, but to date non-coding RNAs (ncRNAs) have not been described to regulate genes directly involved in flagellar assembly. In this study we have investigated the possible role of two ncRNA paralogs (CjNC1, CjNC4) in flagellar assembly and gene regulation of the diarrhoeal pathogen Campylobacter jejuni. CjNC1 and CjNC4 are 37/44 nt identical and predicted to target the 5' untranslated region (5' UTR) of genes transcribed from the flagellar sigma factor σ54. Orthologs of the σ54-dependent 5' UTRs and ncRNAs are present in the genomes of other thermophilic Campylobacter species, and transcription of CjNC1 and CNC4 is dependent on the flagellar sigma factor σ28. Surprisingly, inactivation and overexpression of CjNC1 and CjNC4 did not affect growth, motility or flagella-associated phenotypes such as autoagglutination. However, CjNC1 and CjNC4 were able to mediate sequence-dependent, but Hfq-independent, partial repression of fluorescence of predicted target 5' UTRs in an Escherichia coli-based GFP reporter gene system. This hints towards a subtle role for the CjNC1 and CjNC4 ncRNAs in post-transcriptional gene regulation in thermophilic Campylobacter species, and suggests that the currently used phenotypic methodologies are insufficiently sensitive to detect such subtle phenotypes. The lack of a role of Hfq in the E. coli GFP-based system indicates that the CjNC1 and CjNC4 ncRNAs may mediate post-transcriptional gene regulation in ways that do not conform to the paradigms obtained from the Enterobacteriaceae. PMID:26512728

  1. Firefighters and flame retardant activism.

    PubMed

    Cordner, Alissa; Rodgers, Kathryn M; Brown, Phil; Morello-Frosch, Rachel

    2015-02-01

    In the past decade, exposure to flame retardant chemicals has become a pressing health concern and widely discussed topic of public safety for firefighters in the United States. Working through local, state, and national unions and independent health and advocacy organizations, firefighters have made important contributions to efforts to restrict the use of certain flame retardants. Firefighters are key members in advocacy coalitions dedicated to developing new environmental health regulations and reforming flammability standards to reflect the best available fire science. Their involvement has been motivated by substantiated health concerns and critiques of deceptive lobbying practices by the chemical industry. Drawing on observations and interviews with firefighters, fire safety experts, and other involved stakeholders, this article describes why firefighters are increasingly concerned about their exposure to flame retardant chemicals in consumer products, and analyzes their involvement in state and national environmental health coalitions. PMID:25816168

  2. Firefighters and flame retardant activism.

    PubMed

    Cordner, Alissa; Rodgers, Kathryn M; Brown, Phil; Morello-Frosch, Rachel

    2015-02-01

    In the past decade, exposure to flame retardant chemicals has become a pressing health concern and widely discussed topic of public safety for firefighters in the United States. Working through local, state, and national unions and independent health and advocacy organizations, firefighters have made important contributions to efforts to restrict the use of certain flame retardants. Firefighters are key members in advocacy coalitions dedicated to developing new environmental health regulations and reforming flammability standards to reflect the best available fire science. Their involvement has been motivated by substantiated health concerns and critiques of deceptive lobbying practices by the chemical industry. Drawing on observations and interviews with firefighters, fire safety experts, and other involved stakeholders, this article describes why firefighters are increasingly concerned about their exposure to flame retardant chemicals in consumer products, and analyzes their involvement in state and national environmental health coalitions.

  3. Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance.

    PubMed

    Bozdag, Gonensin Ozan; Uluisik, Irem; Gulculer, Gulce Sila; Karakaya, Huseyin C; Koc, Ahmet

    2011-06-17

    Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast.

  4. Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: ancient CRF paralogs.

    PubMed

    Fekete, Eva M; Zorrilla, Eric P

    2007-04-01

    Urocortins, three paralogs of the stress-related peptide corticotropin-releasing factor (CRF) found in bony fish, amphibians, birds, and mammals, have unique phylogenies, pharmacologies, and tissue distributions. As a result and despite a structural family resemblance, the natural functions of urocortins and CRF in mammalian homeostatic responses differ substantially. Endogenous urocortins are neither simply counterpoints nor mimics of endogenous CRF action. In their own right, urocortins may be clinically relevant molecules in the pathogenesis or management of many conditions, including congestive heart failure, hypertension, gastrointestinal and inflammatory disorders (irritable bowel syndrome, active gastritis, gastroparesis, and rheumatoid arthritis), atopic/allergic disorders (dermatitis, urticaria, and asthma), pregnancy and parturition (preeclampsia, spontaneous abortion, onset, and maintenance of effective labor), major depression and obesity. Safety trials for intravenous urocortin treatment have already begun for the treatment of congestive heart failure. Further understanding the unique functions of urocortin 1, urocortin 2, and urocortin 3 action may uncover other therapeutic opportunities.

  5. Auto cannibalism in mental retardation.

    PubMed

    Verma, Rohit; Mina, Shaily; Sachdeva, Ankur

    2014-01-01

    Mental retardation (MR) deems an individual more vulnerable to psychopathologies. The individual may develop an array of behavioral disturbances manifesting themselves in the form of aggressive and destructive conduct, violent fits of anger, stereotyped, or self-injuring behavior. Self-injurious behavior is heterogeneous in nature ranging from mild to severe variant. We report a case of a 7-year-old boy with MR with self-inflicted severe oral injuries of cannibalistic nature presenting as cleft lip and palate. A more extensive research is needed on the problem behaviors in mentally retarded patients for early detection and effective and timely intervention leading to a better outcome. PMID:24891909

  6. Evolutionary history and epigenetic regulation of the three paralogous pax7 genes in rainbow trout

    PubMed Central

    Seiliez, Iban; Froehlich, Jacob Michael; Marandel, Lucie; Gabillard, Jean-Charles; Biga, Peggy R.

    2015-01-01

    The extraordinary muscle growth potential of teleost fish, particular those of the Salmoninae clade, elicits questions about how the relatively highly conserved transcription factors of the myogenic program are regulated. In addition, the pseudotetraploid nature of the salmonid genome adds another layer of regulatory complexity, and this must be reconciled with epigenetic data to better understand how these fish achieve lifelong muscle growth. To this end, we identified three paralogous pax7 genes (pax7a1, pax7a2, and pax7b) in the rainbow trout genome. During in vitro myogenesis, pax7a1 transcripts remain stable, while pax7a2 and pax7b mRNAs increase in abundance, similarly to myogenin mRNAs and in contrast to the expression pattern of the mammalian ortholog. In addition, we profiled the distribution of repressive H3K27me3 and H3K9me3 and permissive H3K4me3 marks during in vitro myogenesis across these loci, finding that pax7a2 expression was associated with decreased H3K27 trimethylation, while pax7b expression was correlated with decreased H3K9me3 and −K27me3. Altogether, these data link the highly unique differential expression of pax7 paralogs with epigenetic histone modifications in a vertebrate species displaying growth divergent from that of mammals and highlight an important divergence in the regulatory mechanisms of pax7 expression among vertebrates. The system described here provides a more comprehensive picture of the combinatorial control mechanisms orchestrating skeletal muscle growth in a salmonid, leading to a better understanding of myogenesis in this species and across Vertebrata more generally. PMID:25487404

  7. Interactome Analyses Identify Ties of PrPC and Its Mammalian Paralogs to Oligomannosidic N-Glycans and Endoplasmic Reticulum-Derived Chaperones

    PubMed Central

    Won, Amy Hye; Shi, Tujin; Daude, Nathalie; Lau, Agnes; Young, Rebecca; Xu, Lei; Carlson, George A.; Williams, David; Westaway, David; Schmitt-Ulms, Gerold

    2009-01-01

    The physiological environment which hosts the conformational conversion of the cellular prion protein (PrPC) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrPC interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrPC paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrPC and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrPC with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrPSc. A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrPC organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins. PMID:19798432

  8. Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions

    PubMed Central

    Villarino, Alejandro; Laurence, Arian; Robinson, Gertraud W; Bonelli, Michael; Dema, Barbara; Afzali, Behdad; Shih, Han-Yu; Sun, Hong-Wei; Brooks, Stephen R; Hennighausen, Lothar; Kanno, Yuka; O'Shea, John J

    2016-01-01

    The transcription factor STAT5 is fundamental to the mammalian immune system. However, the relationship between its two paralogs, STAT5A and STAT5B, and the extent to which they are functionally distinct, remain uncertain. Using mouse models of paralog deficiency, we demonstrate that they are not equivalent for CD4+ 'helper' T cells, the principal orchestrators of adaptive immunity. Instead, we find that STAT5B is dominant for both effector and regulatory (Treg) responses and, therefore, uniquely necessary for immunological tolerance. Comparative analysis of genomic distribution and transcriptomic output confirm that STAT5B has fargreater impact but, surprisingly, the data point towards asymmetric expression (i.e. paralog dose), rather than distinct functional properties, as the key distinguishing feature. Thus, we propose a quantitative model of STAT5 paralog activity whereby relative abundance imposes functional specificity (or dominance) in the face of widespread structural homology. DOI: http://dx.doi.org/10.7554/eLife.08384.001 PMID:26999798

  9. Effects of MreB paralogs on poly-γ-glutamic acid synthesis and cell morphology in Bacillus amyloliquefaciens.

    PubMed

    Gao, Weixia; Zhang, Zhongxiong; Feng, Jun; Dang, Yulei; Quan, Yufen; Gu, Yanyan; Wang, Shufang; Song, Cunjiang

    2016-09-01

    Actin-like MreB paralogs play important roles in cell shape maintenance, cell wall synthesis and the regulation of the D,L-endopeptidases, CwlO and LytE. The gram-positive bacteria, Bacillus amyloliquefaciens LL3, is a poly-γ-glutamic acid (γ-PGA) producing strain that contains three MreB paralogs: MreB, Mbl and MreBH. In B. amyloliquefaciens, CwlO and LytE can degrade γ-PGA. In this study, we aimed to test the hypothesis that modulating transcript levels of MreB paralogs would alter the synthesis and degradation of γ-PGA. The results showed that overexpression or inhibition of MreB, Mbl or MreBH had distinct effects on cell morphology and the molecular weight of the γ-PGA products. In fermentation medium, cells of mreB inhibition mutant were 50.2% longer than LL3, and the γ-PGA titer increased by 55.7%. However, changing the expression level of mbl showed only slight effects on the morphology, γ-PGA molecular weight and titer. In the mreBH inhibition mutant, γ-PGA production and its molecular weight increased by 56.7% and 19.4%, respectively. These results confirmed our hypothesis that suppressing the expression of MreB paralogs might reduce γ-PGA degradation, and that improving the cell size could strengthen γ-PGA synthesis. This is the first report of enhanced γ-PGA production via suppression of actin-like MreB paralogs. PMID:27481703

  10. Mental Retardation Law in 1980: A Review.

    ERIC Educational Resources Information Center

    Vitello, Stanley J.

    1981-01-01

    Educational and deinstitutionalization law cases decided during 1980 with relevance for mentally retarded persons are reviewed. Noted is the possibility of a period of legal retrenchment regarding the rights of retarded persons. (CL)

  11. The Supreme Court V. Retarded Children.

    ERIC Educational Resources Information Center

    Biklen, Douglas

    1981-01-01

    The author examines the Supreme Court decisions regarding the rights of retarded children not to be institutionalized and rights of retarded people to have aggressive medical treatment that will help prolong their lives. (SB)

  12. The Mentally Retarded in Sweden.

    ERIC Educational Resources Information Center

    Grunewald, Karl

    The aims and principles of normalization and integration of the mentally retarded in Sweden are discussed in terms of implications for services and programs. The historical background of the present care for the mentally handicapped notes legislative actions, responsibilities of the Board of Provisions and County Councils, the development of the…

  13. Reading Retardation and Antisocial Behaviour.

    ERIC Educational Resources Information Center

    Sturge, Claire

    1982-01-01

    Examines the association between reading retardation and antisocial behavior problems in four groups of boys (a total of 129 subjects). Subjects' current behavior and family backgrounds were compared and contrasted. Results show a strong association between the two disorders. (Author/MP)

  14. Mental Retardation: Diagnosis and Treatment.

    ERIC Educational Resources Information Center

    Poser, Charles M., Ed.

    A collection of writings by 17 authors, the text includes the following discussions: general principles of diagnosis and management of mental retardation, neurologic evaluation of the infant and child, psychological evaluation, educational information, and treatment of pseudoretardation, communicative disorders, and metabolic and endocrine causes.…

  15. Detection of Malingered Mental Retardation

    ERIC Educational Resources Information Center

    Shandera, Anne L.; Berry, David T. R.; Clark, Jessica A.; Schipper, Lindsey J.; Graue, Lili O.; Harp, Jordan P.

    2010-01-01

    In a cross-validation of results from L. O. Graue et al. (2007), standard psychological assessment instruments, as well as tests of neurocognitive and psychiatric feigning, were administered under standard instructions to 24 participants diagnosed with mild mental retardation (MR) and 10 demographically matched community volunteers (CVH). A 2nd…

  16. Toilet Training the Retarded Child.

    ERIC Educational Resources Information Center

    Schwartz, Jeffrey K.

    The booklet offers guidelines in both Spanish and English to parents who are toilet training a mentally retarded child. The toilet training process is broken down into tasks that the child must learn, and the importance of positive reinforcement for each successfully accomplished task is emphasized. It is recommended that parents keep charts…

  17. Transportation and the Mentally Retarded.

    ERIC Educational Resources Information Center

    President's Committee on Mental Retardation, Washington, DC.

    Reported were the results of a contract that involved identification, description, and categorization of the nature of transportation problems for the mentally retarded by means of analysis of existing studies, two surveys, and an inventory of specialized programs and systems operating in the United States. One major problem was found to be…

  18. Genetic Counseling in Mental Retardation.

    ERIC Educational Resources Information Center

    Bowen, Peter

    The task of the genetic counselor who identifies genetic causes of mental retardation and assists families to understand risk of recurrence is described. Considered are chromosomal genetic disorders such as Down's syndrome, inherited disorders such as Tay-Sachs disease, identification by testing the amniotic fluid cells (amniocentresis) in time…

  19. MEDICAL ASPECTS OF MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CARTER, CHARLES H., COMP.

    TO AID PHYSICIANS AND OTHER SPECIALISTS IN DIAGNOSING CASES OF MENTAL RETARDATION AND IN COUNSELING PARENTS, THE BOOK PRESENTS MEDICAL INFORMATION, INCLUDING RECENT ADVANCES. THIRTY-TWO AUTHORITIES CONTRIBUTE CHAPTERS IN SUCH AREAS AS DIAGNOSIS, METABOLISM, NUTRITION, ETIOLOGY, MONGOLISM, CRANIAL ABNORMALITIES, BIRTH INJURIES, INFECTIONS,…

  20. Idiots Savants: Retarded and Gifted.

    ERIC Educational Resources Information Center

    Yewchuk, Carolyn

    The paper reviews the paradoxical nature of idiots savants, persons who, although retarded, have exceptional skills in certain areas. Various explanations for the phenomenon are discussed, such as a specific genetic endowment, a specialized compensatory response to general intellectual deficiency, and possession of an eidetic memory. Various…

  1. Social Facilitation of Retardate Performance.

    ERIC Educational Resources Information Center

    Zucker, Stanley H.

    Investigated were the effects of three different social situations on the performance of 48 mildly mentally retarded individuals (12-17 years old). Ss were randomly assigned to one of six treatment groups and were asked to complete simple and complex mazes in one of three audience conditions: no audience, evaluative audience, and non-evaluative…

  2. HANDBOOK OF MENTAL RETARDATION SYNDROMES.

    ERIC Educational Resources Information Center

    CARTER, CHARLES H.

    THE CLINICAL SYNDROMES WHICH CONTRIBUTE TO THE PRODUCTION OF MENTAL RETARDATION ARE DESCRIBED BY SIGNS, SYMPTOMS, AND ETIOLOGY. SYNDROMES TREATED ARE (1) PRENATAL AND POSTNATAL INFECTIONS, (2) PRENATAL INTOXICATION AND ALLERGIC REACTIONS, (3) PRENATAL TRAUMA, PHYSICAL AGENTS, OR INTOXICATION, (4) BIRTH INJURIES, (5) POSTNATAL POISONS AND ALLERGIC…

  3. Fire-retardant epoxy polymers

    NASA Technical Reports Server (NTRS)

    Akawie, R. I.; Bilow, N.; Giants, T. W.

    1978-01-01

    Phosphorus atoms in molecular structure of epoxies make them fire-retardant without degrading their adhesive strength. Moreover, polymers are transparent, unlike compounds that contain arsenic or other inorganics. They have been used to bond polyvinylfluoride and polyether sulfone films onto polyimide glass laminates.

  4. MENTAL RETARDATION--THE PRESENT PROBLEM.

    ERIC Educational Resources Information Center

    SHAFTER, ALBERT J.

    MENTAL RETARDATION IS DEFINED AS A MENTAL DEFECT, NOT A DISEASE. LEVELS OF SEVERITY IN MENTAL RETARDATION ARE CAUSED BY AN INTERRELATIONSHIP BETWEEN HEREDITY AND ENVIRONMENT. ONE OF THE MAJOR PROBLEMS CONCERNS THE LONGER LIFE EXPECTANCY OF THE RETARDATE DUE TO IMPROVEMENTS IN MODERN MEDICINE. THIS IS CREATING A SITUATION WHERE RESIDENTIAL…

  5. Mental Retardation: Prevention Strategies That Work.

    ERIC Educational Resources Information Center

    President's Committee on Mental Retardation, Washington, DC.

    The report by the President's Committee on Mental Retardation reviews the current state of knowledge in the area of biological and environmental prevention of mental retardation and describes programs on the frontiers of research or service delivery. Section I examines programs that are effectively preventing mental retardation through biomedical…

  6. THE TEACHER OF THE MENTALLY RETARDED.

    ERIC Educational Resources Information Center

    CHARNEY, LEON; LACROSSE, EDWARD

    BASIC INFORMATION IS PROVIDED FOR PROSPECTIVE TEACHERS OF MENTALLY RETARDED CHILDREN. THE FIRST FOUR CHAPTERS ARE DEVOTED TO CLASSROOM CONDITIONS, PARENTAL ATTITUDES, AND TEACHER-PUPIL INTERACTION IN THE SPECIAL CLASS FOR RETARDATES. CHAPTER ONE GIVES A GENERAL DESCRIPTION OF THE MENTALLY RETARDED CHILD AS HE APPEARS TO THE TEACHER. CHAPTER TWO…

  7. People with Mental Retardation Are Dying, Legally.

    ERIC Educational Resources Information Center

    Keyes, Denis; And Others

    1997-01-01

    Criticizes the institution of the death penalty for convicted criminals with mental retardation. Examples are given of cases in which juries were not told of the defendant's mental retardation before sentencing, and a list of defendants with mental retardation that have been executed since 1976 is provided. (CR)

  8. Low Elevated Lead Levels and Mental Retardation.

    ERIC Educational Resources Information Center

    Marlowe, Mike; And Others

    The relationship between low elevated lead absorption and mild mental retardation was investigated in 40 rural children (preschool to grade 12) without demonstrable cause for their retardation. Trace mineral analysis of hair samples from Ss and a control group (N=20) indicated the mean hair lead concentrations for the retarded Ss were considerably…

  9. Practitioner review: physical investigations in mental retardation.

    PubMed

    Gillberg, C

    1997-11-01

    Mental retardation occurs in more than 1% of the child population. A cause can be found in almost 80% of individuals with severe mental retardation, but in fewer than 40% of those with mild mental retardation. A work-up is indicated in all cases of mental retardation. A medical doctor with specific training in the field is needed to make "decision-tree diagnosis" and to suggest the most appropriate physical investigations in each case. This paper provides practical guidelines for diagnosis and work-up both in severe and mild mental retardation. PMID:9413789

  10. Methylotrophic Bacillus methanolicus Encodes Two Chromosomal and One Plasmid Born NAD+ Dependent Methanol Dehydrogenase Paralogs with Different Catalytic and Biochemical Properties

    PubMed Central

    Müller, Jonas E. N.; Kupper, Christiane E.; Schneider, Olha; Vorholt, Julia A.; Ellingsen, Trond E.; Brautaset, Trygve

    2013-01-01

    Bacillus methanolicus can utilize methanol as the sole carbon source for growth and it encodes an NAD+-dependent methanol dehydrogenase (Mdh), catalyzing the oxidation of methanol to formaldehyde. Recently, the genomes of the B. methanolicus strains MGA3 (ATCC53907) and PB1 (NCIMB13113) were sequenced and found to harbor three different putative Mdh encoding genes, each belonging to the type III Fe-NAD+-dependent alcohol dehydrogenases. In each strain, two of these genes are encoded on the chromosome and one on a plasmid; only one chromosomal act gene encoding the previously described activator protein ACT was found. The six Mdhs and the ACT proteins were produced recombinantly in Escherichia coli, purified, and characterized. All Mdhs required NAD+ as cosubstrate, were catalytically stimulated by ACT, exhibited a broad and different substrate specificity range and displayed both dehydrogenase and reductase activities. All Mdhs catalyzed the oxidation of methanol; however the catalytic activity for methanol was considerably lower than for most other alcohols tested, suggesting that these enzymes represent a novel class of alcohol dehydrogenases. The kinetic constants for the Mdhs were comparable when acting as pure enzymes, but together with ACT the differences were more pronounced. Quantitative PCR experiments revealed major differences with respect to transcriptional regulation of the paralogous genes. Taken together our data indicate that the repertoire of methanol oxidizing enzymes in thermotolerant bacilli is larger than expected with complex mechanisms involved in their regulation. PMID:23527128

  11. No Distinction of Orthology/Paralogy between Human and Chimpanzee Rh Blood Group Genes

    PubMed Central

    Kitano, Takashi; Kim, Choong-Gon; Blancher, Antoine; Saitou, Naruya

    2016-01-01

    On human (Homo sapiens) chromosome 1, there is a tandem duplication encompassing Rh blood group genes (Hosa_RHD and Hosa_RHCE). This duplication occurred in the common ancestor of humans, chimpanzees (Pan troglodytes), and gorillas, after splitting from their common ancestor with orangutans. Although several studies have been conducted on ape Rh blood group genes, the clear genome structures of the gene clusters remain unknown. Here, we determined the genome structure of the gene cluster of chimpanzee Rh genes by sequencing five BAC (Bacterial Artificial Chromosome) clones derived from chimpanzees. We characterized three complete loci (Patr_RHα, Patr_RHβ, and Patr_RHγ). In the Patr_RHβ locus, a short version of the gene, which lacked the middle part containing exons 4–8, was observed. The Patr_RHα and Patr_RHβ genes were located on the locations corresponding to Hosa_RHD and Hosa_RHCE, respectively, and Patr_RHγ was in the immediate vicinity of Patr_RHβ. Sequence comparisons revealed high sequence similarity between Patr_RHβ and Hosa_RHCE, while the chimpanzee Rh gene closest to Hosa_RHD was not Patr_RHα but rather Patr_RHγ. The results suggest that rearrangements and gene conversions frequently occurred between these genes and that the classic orthology/paralogy dichotomy no longer holds between human and chimpanzee Rh blood group genes. PMID:26872772

  12. Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways.

    PubMed

    Tian, Shi; Zandawala, Meet; Beets, Isabel; Baytemur, Esra; Slade, Susan E; Scrivens, James H; Elphick, Maurice R

    2016-01-01

    Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive maturation in humans and other vertebrates. Homologs of GnRH and its cognate receptor have been identified in invertebrates-for example, the adipokinetic hormone (AKH) and corazonin (CRZ) neuropeptide pathways in arthropods. However, the precise evolutionary relationships and origins of these signalling systems remain unknown. Here we have addressed this issue with the first identification of both GnRH-type and CRZ-type signalling systems in a deuterostome-the echinoderm (starfish) Asterias rubens. We have identified a GnRH-like neuropeptide (pQIHYKNPGWGPG-NH2) that specifically activates an A. rubens GnRH-type receptor and a novel neuropeptide (HNTFTMGGQNRWKAG-NH2) that specifically activates an A. rubens CRZ-type receptor. With the discovery of these ligand-receptor pairs, we demonstrate that the vertebrate/deuterostomian GnRH-type and the protostomian AKH systems are orthologous and the origin of a paralogous CRZ-type signalling system can be traced to the common ancestor of the Bilateria (Urbilateria). PMID:27350121

  13. Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways

    PubMed Central

    Tian, Shi; Zandawala, Meet; Beets, Isabel; Baytemur, Esra; Slade, Susan E.; Scrivens, James H.; Elphick, Maurice R.

    2016-01-01

    Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive maturation in humans and other vertebrates. Homologs of GnRH and its cognate receptor have been identified in invertebrates–for example, the adipokinetic hormone (AKH) and corazonin (CRZ) neuropeptide pathways in arthropods. However, the precise evolutionary relationships and origins of these signalling systems remain unknown. Here we have addressed this issue with the first identification of both GnRH-type and CRZ-type signalling systems in a deuterostome–the echinoderm (starfish) Asterias rubens. We have identified a GnRH-like neuropeptide (pQIHYKNPGWGPG-NH2) that specifically activates an A. rubens GnRH-type receptor and a novel neuropeptide (HNTFTMGGQNRWKAG-NH2) that specifically activates an A. rubens CRZ-type receptor. With the discovery of these ligand-receptor pairs, we demonstrate that the vertebrate/deuterostomian GnRH-type and the protostomian AKH systems are orthologous and the origin of a paralogous CRZ-type signalling system can be traced to the common ancestor of the Bilateria (Urbilateria). PMID:27350121

  14. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts.

    PubMed

    Raines, Anna M; Adam, Mike; Magella, Bliss; Meyer, Sara E; Grimes, H Leighton; Dey, Sudhansu K; Potter, S Steven

    2013-07-01

    Hox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions and interspersed shared enhancers. Here, we describe the use of a novel recombineering strategy to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10 and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting Hoxa9,10,11 mutant mice displayed dramatic synergistic homeotic transformations of the reproductive tracts, with the uterus anteriorized towards oviduct and the vas deferens anteriorized towards epididymis. The Hoxa9,10,11 mutant mice also provided a genetic setting that allowed the discovery of Hoxd9,10,11 redundant reproductive tract patterning function. Both shared and distinct Hox functions were defined. Hoxd9,10,11 play a crucial role in the regulation of uterine immune function. Non-coding non-polyadenylated RNAs were among the key Hox targets, with dramatic downregulation in mutants. We observed Hox cross-regulation of transcription and splicing. In addition, we observed a surprising anti-dogmatic apparent posteriorization of the uterine epithelium. In caudal regions of the uterus, the normal simple columnar epithelium flanking the lumen was replaced by a pseudostratified transitional epithelium, normally found near the more posterior cervix. These results identify novel molecular functions of Hox genes in the development of the male and female reproductive tracts.

  15. Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance.

    PubMed

    Hawkins, Nichola J; Cools, Hans J; Sierotzki, Helge; Shaw, Michael W; Knogge, Wolfgang; Kelly, Steven L; Kelly, Diane E; Fraaije, Bart A

    2014-07-01

    Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

  16. Fire-Retardant Polymeric Additives

    NASA Technical Reports Server (NTRS)

    Williams, Martha K.; Smith, Trent M.

    2011-01-01

    Polyhydroxyamide (PHA) and polymethoxyamide (PMeOA) are fire-retardant (FR) thermoplastic polymers and have been found to be useful as an additive for imparting fire retardant properties to other compatible, thermoplastic polymers (including some elastomers). Examples of compatible flammable polymers include nylons, polyesters, and acrylics. Unlike most prior additives, PHA and PMeOA do not appreciably degrade the mechanical properties of the matrix polymer; indeed, in some cases, mechanical properties are enhanced. Also, unlike some prior additives, PHA and PMeOA do not decompose into large amounts of corrosive or toxic compounds during combustion and can be processed at elevated temperatures. PMeOA derivative formulations were synthesized and used as an FR additive in the fabrication of polyamide (PA) and polystyrene (PS) composites with notable reduction (>30 percent for PS) in peak heat release rates compared to the neat polymer as measured by a Cone Calorimeter (ASTM E1354). Synergistic effects were noted with nanosilica composites. These nanosilica composites had more than 50-percent reduction in peak heat release rates. In a typical application, a flammable thermoplastic, thermoplastic blend, or elastomer that one seeks to render flame-retardant is first dry-mixed with PHA or PMeOA or derivative thereof. The proportion of PHA or PMeOA or derivative in the mixture is typically chosen to lie between 1 and 20 weight percent. The dry blend can then be melt-extruded. The extruded polymer blend can further be extruded and/or molded into fibers, pipes, or any other of a variety of objects that may be required to be fire-retardant. The physical and chemical mechanisms which impart flame retardancy of the additive include inhibiting free-radical oxidation in the vapor phase, preventing vaporization of fuel (the polymer), and cooling through the formation of chemical bonds in either the vapor or the condensed phase. Under thermal stress, the cyclic hydroxyl/ methoxy

  17. Expression of POTE protein in human testis detected by novel monoclonal antibodies

    SciTech Connect

    Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Anver, Miriam R.; Pastan, Ira

    2008-01-25

    The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis, and placenta. We produced 10 monoclonal antibodies (MAbs) against three representative POTE paralogs: POTE-21, POTE-2{gamma}C, and POTE-22. One reacted with all three paralogs, six MAbs reacted with POTE-2{gamma}C and POTE-22, and three MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis.

  18. Nuclear Ribosomal ITS Functional Paralogs Resolve the Phylogenetic Relationships of a Late-Miocene Radiation Cycad Cycas (Cycadaceae)

    PubMed Central

    Xiao, Long-Qian; Möller, Michael

    2015-01-01

    Cycas is the most widespread and diverse genus among the ancient cycads, but the extant species could be the product of late Miocene rapid radiations. Taxonomic treatments to date for this genus are quite controversial, which makes it difficult to elucidate its evolutionary history. We cloned 161 genomic ITS sequences from 31 species representing all sections of Cycas. The divergent ITS paralogs were examined within each species and identified as putative pseudogenes, recombinants and functional paralogs. Functional paralogs were used to reconstruct phylogenetic relationships with pseudogene sequences as molecular outgroups, since an unambiguous ITS sequence alignment with their closest relatives, the Zamiaceae, is unachievable. A fully resolved and highly supported tree topology was obtained at the section level, with two major clades including six minor clades. The results fully supported the classification scheme proposed by Hill (2004) at the section level, with the minor clades representing his six sections. The two major clades could be recognised as two subgenera. The obtained pattern of phylogenetic relationships, combined with the different seed dispersal capabilities and paleogeography, allowed us to propose a late Miocene rapid radiation of Cycas that might have been promoted by vicariant events associated with the complex topography and orogeny of South China and adjacent regions. In contrast, transoceanic dispersals might have played an important role in the rapid diversification of sect. Cycas, whose members have evolved a spongy layer in their seeds aiding water dispersals. PMID:25635842

  19. Trypanosoma brucei harbors a divergent XPB helicase paralog that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms

    PubMed Central

    Badjatia, Nitika; Nguyen, Tu N; Lee, Ju Huck; Günzl, Arthur

    2013-01-01

    Summary Conserved from yeast to humans, TFIIH is essential for RNA polymerase II transcription and nucleotide excision repair (NER). TFIIH consists of a core that includes the DNA helicase Xeroderma pigmentosum B (XPB) and a kinase subcomplex. Trypanosoma brucei TFIIH harbors all core complex components and is indispensable for RNA polymerase II transcription of spliced leader RNA genes (SLRNAs). Kinetoplastid organisms, however, possess two highly divergent XPB paralogs with only the larger being identified as a TFIIH subunit in T. brucei. Here we show that a knockout of the gene for the smaller paralog, termed XPB-R (R for repair) resulted in viable cultured trypanosomes that grew slower than normal. XPB-R depletion did not affect transcription in vivo or in vitro and XPB-R was not found to occupy the SLRNA promoter which assembles a RNA polymerase II transcription pre-initiation complex including TFIIH. However, XPB-R−/− cells were much less tolerant than wild-type cells to UV light- and cisplatin-induced DNAdamage, which require NER. Since XPB-R−/− cells were not impaired in DNA base excision repair, XPB-R appears to function specifically in NER. Interestingly, several other protists possess highly divergent XPB paralogs suggesting that XPBs specialized in transcription or NER exist beyond the Kinetoplastida. PMID:24134817

  20. Nuclear ribosomal ITS functional paralogs resolve the phylogenetic relationships of a late-Miocene radiation cycad Cycas (Cycadaceae).

    PubMed

    Xiao, Long-Qian; Möller, Michael

    2015-01-01

    Cycas is the most widespread and diverse genus among the ancient cycads, but the extant species could be the product of late Miocene rapid radiations. Taxonomic treatments to date for this genus are quite controversial, which makes it difficult to elucidate its evolutionary history. We cloned 161 genomic ITS sequences from 31 species representing all sections of Cycas. The divergent ITS paralogs were examined within each species and identified as putative pseudogenes, recombinants and functional paralogs. Functional paralogs were used to reconstruct phylogenetic relationships with pseudogene sequences as molecular outgroups, since an unambiguous ITS sequence alignment with their closest relatives, the Zamiaceae, is unachievable. A fully resolved and highly supported tree topology was obtained at the section level, with two major clades including six minor clades. The results fully supported the classification scheme proposed by Hill (2004) at the section level, with the minor clades representing his six sections. The two major clades could be recognised as two subgenera. The obtained pattern of phylogenetic relationships, combined with the different seed dispersal capabilities and paleogeography, allowed us to propose a late Miocene rapid radiation of Cycas that might have been promoted by vicariant events associated with the complex topography and orogeny of South China and adjacent regions. In contrast, transoceanic dispersals might have played an important role in the rapid diversification of sect. Cycas, whose members have evolved a spongy layer in their seeds aiding water dispersals. PMID:25635842

  1. Nuclear ribosomal ITS functional paralogs resolve the phylogenetic relationships of a late-Miocene radiation cycad Cycas (Cycadaceae).

    PubMed

    Xiao, Long-Qian; Möller, Michael

    2015-01-01

    Cycas is the most widespread and diverse genus among the ancient cycads, but the extant species could be the product of late Miocene rapid radiations. Taxonomic treatments to date for this genus are quite controversial, which makes it difficult to elucidate its evolutionary history. We cloned 161 genomic ITS sequences from 31 species representing all sections of Cycas. The divergent ITS paralogs were examined within each species and identified as putative pseudogenes, recombinants and functional paralogs. Functional paralogs were used to reconstruct phylogenetic relationships with pseudogene sequences as molecular outgroups, since an unambiguous ITS sequence alignment with their closest relatives, the Zamiaceae, is unachievable. A fully resolved and highly supported tree topology was obtained at the section level, with two major clades including six minor clades. The results fully supported the classification scheme proposed by Hill (2004) at the section level, with the minor clades representing his six sections. The two major clades could be recognised as two subgenera. The obtained pattern of phylogenetic relationships, combined with the different seed dispersal capabilities and paleogeography, allowed us to propose a late Miocene rapid radiation of Cycas that might have been promoted by vicariant events associated with the complex topography and orogeny of South China and adjacent regions. In contrast, transoceanic dispersals might have played an important role in the rapid diversification of sect. Cycas, whose members have evolved a spongy layer in their seeds aiding water dispersals.

  2. Genome-Wide Analysis of PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) Genes in Plants Reveals the Eudicot-Wide PDAT Gene Expansion and Altered Selective Pressures Acting on the Core Eudicot PDAT Paralogs1[OPEN

    PubMed Central

    Pan, Xue; Peng, Fred Y.; Weselake, Randall J.

    2015-01-01

    PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) is an enzyme that catalyzes the transfer of a fatty acyl moiety from the sn-2 position of a phospholipid to the sn-3-position of sn-1,2-diacylglyerol, thus forming triacylglycerol and a lysophospholipid. Although the importance of PDAT in triacylglycerol biosynthesis has been illustrated in some previous studies, the evolutionary relationship of plant PDATs has not been studied in detail. In this study, we investigated the evolutionary relationship of the PDAT gene family across the green plants using a comparative phylogenetic framework. We found that the PDAT candidate genes are present in all examined green plants, including algae, lowland plants (a moss and a lycophyte), monocots, and eudicots. Phylogenetic analysis revealed the evolutionary division of the PDAT gene family into seven major clades. The separation is supported by the conservation and variation in the gene structure, protein properties, motif patterns, and/or selection constraints. We further demonstrated that there is a eudicot-wide PDAT gene expansion, which appears to have been mainly caused by the eudicot-shared ancient gene duplication and subsequent species-specific segmental duplications. In addition, selection pressure analyses showed that different selection constraints have acted on three core eudicot clades, which might enable paleoduplicated PDAT paralogs to either become nonfunctionalized or develop divergent expression patterns during evolution. Overall, our study provides important insights into the evolution of the plant PDAT gene family and explores the evolutionary mechanism underlying the functional diversification among the core eudicot PDAT paralogs. PMID:25585619

  3. Astigmatism among institutionalized and noninstitutionalized mentally retarded.

    PubMed

    Courtney, G R

    1977-06-01

    Astigmatism was measured retinoscopically for 709 subjects residing in an institution for the mentally retarded and for 56 noninstitutionalized mentally retarded subjects at a community training center. About 60% of the subjects were between 15 and 45 years old. Compared to an intellectually normal sample of young men, astigmatism in the mentally retarded was greater in frequency and degree. For subjects with greater degrees of mental retardation, the prevalence of high astigmastism was significantly greater for whites than for nonwhites. There was no difference in astigmatism between institutionalized retardates and those living in a community setting, a finding that implies that the institutional environment was not the cause of the astigmatic differences between retarded and normal subjects.

  4. Evolution of a new function in an esterase: simple amino acid substitutions enable the activity present in the larger paralog, BioH.

    PubMed

    Flores, Humberto; Lin, Steven; Contreras-Ferrat, Gabriel; Cronan, John E; Morett, Enrique

    2012-08-01

    Gene duplication and divergence are essential processes for the evolution of new activities. Divergence may be gradual, involving simple amino acid residue substitutions, or drastic, such that larger structural elements are inserted, deleted or rearranged. Vast protein sequence comparisons, supported by some experimental evidence, argue that large structural modifications have been necessary for certain catalytic activities to evolve. However, it is not clear whether these activities could not have been attained by gradual changes. Interestingly, catalytic promiscuity could play a fundamental evolutionary role: a preexistent secondary activity could be increased by simple amino acid residue substitutions that do not affect the enzyme's primary activity. The promiscuous profile of the enzyme may be modified gradually by genetic drift, making a pool of potentially useful activities that can be selected before duplication. In this work, we used random mutagenesis and in vivo selection to evolve the Pseudomonas aeruginosa PAO1 carboxylesterase PA3859, a small protein, to attain the function of BioH, a much larger paralog involved in biotin biosynthesis. BioH was chosen as a target activity because it provides a highly sensitive selection for evolved enzymatic activities by auxotrophy complementation. After only two cycles of directed evolution, mutants with the ability to efficiently complement biotin auxotrophy were selected. The in vivo and in vitro characterization showed that the activity of one of our mutant proteins was similar to that of the wild-type BioH enzyme. Our results demonstrate that it is possible to evolve enzymatic activities present in larger proteins by discrete amino acid substitutions.

  5. Fire retardancy using applied materials

    NASA Technical Reports Server (NTRS)

    Feldman, R.

    1971-01-01

    An example of advanced technology transfer from the Little Joe, Surveyor, Comsat, re-entry and Apollo age to everyday fire protection needs is presented. Utilizing the principle of sublimation cooling for thermostatic temperature control, the material meets a wide range of fire retardancy and heat transmission control requirements. Properties vary from flexible tape for conduits and electrical cables to rigid coatings for column protection, with a broad spectrum of sublimation temperatures available. The material can be applied in the field or in the factory, utilizing mass production techniques, yielding a product that is reliable, effective, widely available and low in cost.

  6. Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

    PubMed Central

    Wong, Siew Fen Lisa; Agarwal, Vikram; Mansfield, Jennifer H.; Denans, Nicolas; Schwartz, Matthew G.; Prosser, Haydn M.; Pourquié, Olivier; Bartel, David P.; Tabin, Clifford J.; McGlinn, Edwina

    2015-01-01

    The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3′ UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae. PMID:26283362

  7. Aldehyde Dehydrogenase Gene Superfamily in Populus: Organization and Expression Divergence between Paralogous Gene Pairs

    PubMed Central

    Tian, Feng-Xia; Zang, Jian-Lei; Wang, Tan; Xie, Yu-Li; Zhang, Jin; Hu, Jian-Jun

    2015-01-01

    Aldehyde dehydrogenases (ALDHs) constitute a superfamily of NAD(P)+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants. PMID:25909656

  8. Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs.

    PubMed

    Wong, Siew Fen Lisa; Agarwal, Vikram; Mansfield, Jennifer H; Denans, Nicolas; Schwartz, Matthew G; Prosser, Haydn M; Pourquié, Olivier; Bartel, David P; Tabin, Clifford J; McGlinn, Edwina

    2015-09-01

    The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3' UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae.

  9. Aldehyde Dehydrogenase Gene Superfamily in Populus: Organization and Expression Divergence between Paralogous Gene Pairs.

    PubMed

    Tian, Feng-Xia; Zang, Jian-Lei; Wang, Tan; Xie, Yu-Li; Zhang, Jin; Hu, Jian-Jun

    2015-01-01

    Aldehyde dehydrogenases (ALDHs) constitute a superfamily of NAD(P)+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants.

  10. Orthopaedic Problems of the Mentally Retarded

    ERIC Educational Resources Information Center

    McSweeney, Anthony

    1972-01-01

    Problems encountered by orthopedic surgeons treating the mentally retarded are identified, and cooperation among pediatricians, psychiatrists, psychologists, social workers, physiotherapists, occupational therapists, and orthopedic surgeons is recommended. (GW)

  11. Intumescent Coatings as Fire Retardants

    NASA Technical Reports Server (NTRS)

    Parker, J. A.; Fohlen, G. M.; Sawko, P. M.; Fish, R. H.

    1970-01-01

    The development of fire-retardant coatings to protect surfaces which may be exposed to fire or extreme heat is a subject of intense interest to many industries. A fire-retardant paint has been developed which represents a new chemical approach for preparing intumescent coatings, and potentially, is very important to fire-prevention authorities. The requirements for a superior coating include ease of application, suitability to a wide variety of surfaces and finishes, and stability over an extended period of time within a broad range of ambient temperature and humidity conditions. These innovative coatings, when activated by the heat of a fire, react to form a thick, low-density, polymeric coating or char layer. Water vapor and sulphur dioxide are released during the intumescent reaction. Two fire-protection mechanisms thus become available: (1) the char layer retards the flow of heat, due to the extremely low thermal conductivity; and (2) water vapor and sulfur dioxide are released, providing fire quenching properties. Still another mechanism functions in cases where the char, by virtue of its high oxidation resistance and low thermal conductivity, reaches a sufficiently high temperature to re-radiate much of the incident heat load. The coatings consist of dispersions of selective salts of a nitro-amino-arornatic compound. Specifically, para-nitroaniline bisulfate and the ammonium salt of para-nitroaniline-ortho sulphuric acid (2-amino-5-nitrobenzenesulphuric acid) are used. Suitable vehicles are cellulose nitrate of lacquer grade, a nitrite-phenolic modified rubber, or epoxy-polysulfide copolymer. Three separate formulations have been developed. A solvent is usually employed, such as methylethyl ketone, butyl acetate, or toluene, which renders the coatings suitably thin and which evaporates after the coatings are applied. Generally, the intumescent material is treated as insoluble in the vehicle, and is ground and dispersed in the vehicle and solvent like an

  12. Retarded Children of the Poor: A Casebook.

    ERIC Educational Resources Information Center

    Kirkland, Majorie H.

    Written for welfare and social workers, the publication concerns families which have problems of retardation, usually mild or borderline, and which are heavily represented on welfare rolls. A brief discussion of retardation and family and child welfare services is followed by a list of suggested readings dealing with social and child welfare…

  13. Discrimination Learning in Profoundly Retarded Children.

    ERIC Educational Resources Information Center

    Suib, Michael R.; And Others

    1980-01-01

    A study investigating the discrimination abilities of two crib-bound, cerebral palsied, profoundly retarded females demonstrates the importance of individual differences among such children and suggests that discriminative responding may be demonstrated by at least some profoundly retarded children, particularly if distributed practice is employed…

  14. Hand Function Measurement with Educable Mental Retardates

    ERIC Educational Resources Information Center

    Sand, Patricia L.; And Others

    1973-01-01

    Reports on results of the Developmental Hand Function Test administered to 28 educable mentally retarded and 34 normal 12-and 14-year-old girls to show that manual dexterity and functional had skills are compromised in the mentally retarded. (DS)

  15. Residential Facilities for the Mentally Retarded.

    ERIC Educational Resources Information Center

    Baumeister, Alfred A., Ed.; Butterfield, Earl, Ed.

    The handbook on residential institutions, for professionals and students in the field of mental retardation, attempts to interpret the institution as a part of the culture which it serves, avoiding emotional responses but suggesting formulas for change. Characteristics of contemporary institutions for the mentally retarded are examined and…

  16. Body Awareness in Children with Mental Retardation

    ERIC Educational Resources Information Center

    Simons, Johan; Dedroog, Inge

    2009-01-01

    The body awareness of 124 toddlers with mental retardation and of 124 children developing normally matched to them on age and gender was examined. Twenty-nine of the children with mental retardation were diagnosed as Down syndrome (DS). The "Pointing and Naming" Test of Berges and Lezine [Berges, J., & Lezine, I. (1978). "Test d'imitation de…

  17. Interaction between Family Violence and Mental Retardation.

    ERIC Educational Resources Information Center

    Strickler, Heidi

    2001-01-01

    Characteristics that make individuals with mental retardation more vulnerable to family violence are discussed in the areas of child, adult, and sexual abuse. Common psychological effects of this trauma are then explored followed by implications for practice. A case study of a female with mental retardation is presented. (Contains references.)…

  18. Computational Errors of Mentally Retarded Students.

    ERIC Educational Resources Information Center

    Janke, Robert W.

    1980-01-01

    Examined computational errors made by educable mentally retarded students on the arithmetic subtest of the Wide Range Achievement Test. Retarded students had a lower percent of grouping and inappropriate inversion errors and a higher percent of incorrect operation errors than regular students had in Engelhardt's study. (Author)

  19. Severe Mental Retardation: From Theory to Practice.

    ERIC Educational Resources Information Center

    Bricker, Diane, Ed.; Filler, John, Ed.

    Fourteen papers examine current issues and practices in the education of students with severe mental retardation (SMR). Papers touch upon the broad context of education for SMR students, programs for the SMR population, and critical issues. The following papers are presented: "The Severely Mentally Retarded Individual: Philosophical and…

  20. Arm Tremor, Tardive Dyskinesia, and Mental Retardation.

    ERIC Educational Resources Information Center

    van Emmerik, R. E. A.; And Others

    1993-01-01

    The arm tremor of adults (n=32) diagnosed as having mental retardation and/or tardive dyskinesia was examined through an analysis of the acceleration properties of several arm postures. The degree of arm acceleration was increased in all subjects compared to a control group without mental retardation. Effects of neuroleptic medication were noted.…

  1. Human Sexuality for the Mentally Retarded.

    ERIC Educational Resources Information Center

    Zitzow, Darryl; And Others

    The Human Sexuality for the Mentally Retarded program sought to provide cognitive awareness of human sexuality for mentally retarded trainable residents (5 to 21 years old) as well as inservice staff training regarding attitudes and cognitive awareness changes. Cognitive awareness training focused on body parts, discrimination of the sexes,…

  2. Operant Conditioning of Mental Retardates' Visual Monitoring.

    ERIC Educational Resources Information Center

    Perryman, Roy E.; And Others

    1981-01-01

    To study improvement of visual monitoring of retardates, specialized training methods backed up by incentives were used. The extent to which these training techniques might be expected to produce results which would generalize was explored. Subjects were eight female mental retardates (ages 15-22) with IQs from 38 to 69. (Author/SJL)

  3. Mental Retardation: Update 2002. ERIC Digest.

    ERIC Educational Resources Information Center

    Hourcade, Jack

    This digest provides an overview of mental retardation in children and adults. It begins by discussing the definition of mental retardation and the three components that are required for an accurate diagnosis: an IQ score of approximately 70 or below, a determination of deficits in adaptive behavior, and origins of the disability prior to age 18.…

  4. Political Philosophy and the Mentally Retarded.

    ERIC Educational Resources Information Center

    Stanovich, Keith E.

    The effects of Social Darwinism, eugenics, and contemporary political conservatism on the status of advocacy efforts for the mentally retarded are reviewed. Provided are historical sketches of Social Darwinism, which viewed the retarded as members of an inferior race, and eugenics, which argued for sterilization of the "genetically unfit". The…

  5. Poverty and Mental Retardation: A Causal Relationship.

    ERIC Educational Resources Information Center

    Hurley, Rodger L.

    The incidence of mental retardation among the poor and the reasons for such high prevalence are the focus of the text which is based largely on the state of New Jersey. Mental retardation is viewed as a social pathology which thrives in the ghetto; the effects of poverty and racial prejudice are explored as are the assessment of intelligence and…

  6. A Case of Pseudo-Retardation.

    ERIC Educational Resources Information Center

    Stott, D. H.

    Review of a case study of a 4-year-old girl who assumed the role of a retardate reveals that the girl probably suffered multiple congenital impairments of a minor character that affected the central nervous system and the structures governing social behavior and maturation. The stated basis for pseudo-retardation is the person's ability to…

  7. Social development of children with mental retardation

    PubMed Central

    Kumar, Indrabhushan; Singh, Amool R.; Akhtar, S.

    2009-01-01

    Background: Social development of children with mental retardation has implications for prognosis. The present study evaluated whether the social maturity scale alone can reflect on the social maturity, intellectual level and consequent adjustment in family and society of children with mental retardation. Materials and Methods: Thirty-five mentally retarded children were administered Vineland Social Maturity Scale and Stanford Binet Intelligence Scale. Results: It was found that there was significant relationship between the measures of social maturity scale and the IQ of the subjects. Further it was found that with increasing severity of retardation, social development also decreases and age does not have any effect on social development. Conclusion: Social quotient increases from profound to mild level of retardation. PMID:21234165

  8. Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse

    SciTech Connect

    Lundin, L.G. )

    1993-04-01

    Gene constellations on several human chromosomes are interpreted as indications of large regional duplications that took place during evolution of the vertebrate genome. Four groups of paralogous chromosomal regions in man and the house mouse are suggested and are believed to be conserved remnants of the two or three rounds of tetraploidization that are likely to have occurred during evolution of the vertebrates. The phenomenon of differential silencing of genes is described. The importance of conservation of linkage of particular genes is discussed in relation to genetic regulation and cell differentiation. 120 refs., 5 tabs.

  9. Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase

    PubMed Central

    Sellem, Carole H.; di Rago, Jean-Paul; Lasserre, Jean-Paul; Ackerman, Sharon H.; Sainsard-Chanet, Annie

    2016-01-01

    Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8–15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before. PMID:27442014

  10. Clusters of ancestrally related genes that show paralogy in whole or in part are a major feature of the genomes of humans and other species.

    PubMed

    Walker, Michael B; King, Benjamin L; Paigen, Kenneth

    2012-01-01

    Arrangements of genes along chromosomes are a product of evolutionary processes, and we can expect that preferable arrangements will prevail over the span of evolutionary time, often being reflected in the non-random clustering of structurally and/or functionally related genes. Such non-random arrangements can arise by two distinct evolutionary processes: duplications of DNA sequences that give rise to clusters of genes sharing both sequence similarity and common sequence features and the migration together of genes related by function, but not by common descent. To provide a background for distinguishing between the two, which is important for future efforts to unravel the evolutionary processes involved, we here provide a description of the extent to which ancestrally related genes are found in proximity.Towards this purpose, we combined information from five genomic datasets, InterPro, SCOP, PANTHER, Ensembl protein families, and Ensembl gene paralogs. The results are provided in publicly available datasets (http://cgd.jax.org/datasets/clustering/paraclustering.shtml) describing the extent to which ancestrally related genes are in proximity beyond what is expected by chance (i.e. form paraclusters) in the human and nine other vertebrate genomes, as well as the D. melanogaster, C. elegans, A. thaliana, and S. cerevisiae genomes. With the exception of Saccharomyces, paraclusters are a common feature of the genomes we examined. In the human genome they are estimated to include at least 22% of all protein coding genes. Paraclusters are far more prevalent among some gene families than others, are highly species or clade specific and can evolve rapidly, sometimes in response to environmental cues. Altogether, they account for a large portion of the functional clustering previously reported in several genomes.

  11. Expression of the mouse MHC class Ib H2-T11 gene product, a paralog of H2-T23 (Qa-1) with shared peptide-binding specificity.

    PubMed

    Chen, Lili; Reyes-Vargas, Eduardo; Dai, Hu; Escobar, Hernando; Rudd, Brant; Fairbanks, Jared; Ho, Alexander; Cusick, Mathew F; Kumánovics, Attila; Delgado, Julio; He, Xiao; Jensen, Peter E

    2014-08-01

    The mouse MHC class Ib gene H2-T11 is 95% identical at the DNA level to H2-T23, which encodes Qa-1, one of the most studied MHC class Ib molecules. H2-T11 mRNA was observed to be expressed widely in tissues of C57BL/6 mice, with the highest levels in thymus. To circumvent the availability of a specific mAb, cells were transduced with cDNA encoding T11 with a substituted α3 domain. Hybrid T11D3 protein was expressed at high levels similar to control T23D3 molecules on the surface of both TAP(+) and TAP(-) cells. Soluble T11D3 was generated by folding in vitro with Qa-1 determinant modifier, the dominant peptide presented by Qa-1. The circular dichroism spectrum of this protein was similar to that of other MHC class I molecules, and it was observed to bind labeled Qa-1 determinant modifier peptide with rapid kinetics. By contrast to the Qa-1 control, T11 tetramers did not react with cells expressing CD94/NKG2A, supporting the conclusion that T11 cannot replace Qa-1 as a ligand for NK cell inhibitory receptors. T11 also failed to substitute for Qa-1 in the presentation of insulin to a Qa-1-restricted T cell hybridoma. Despite divergent function, T11 was observed to share peptide-loading specificity with Qa-1. Direct analysis by tandem mass spectrometry of peptides eluted from T11D3 and T23D3 isolated from Hela cells demonstrated a diversity of peptides with a clear motif that was shared between the two molecules. Thus, T11 is a paralog of T23 encoding an MHC class Ib molecule that shares peptide-binding specificity with Qa-1 but differs in function. PMID:24958902

  12. Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase.

    PubMed

    Sellem, Carole H; di Rago, Jean-Paul; Lasserre, Jean-Paul; Ackerman, Sharon H; Sainsard-Chanet, Annie

    2016-07-01

    Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8-15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before.

  13. Inhibition of Complement Retards Ankylosing Spondylitis Progression

    PubMed Central

    Yang, Chaoqun; Ding, Peipei; Wang, Qingkai; Zhang, Long; Zhang, Xin; Zhao, Jianquan; Xu, Enjie; Wang, Na; Chen, Jianfeng; Yang, Guang; Hu, Weiguo; Zhou, Xuhui

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy. PMID:27698377

  14. Three-Dimensional Phylogeny Explorer: Distinguishing paralogs, lateral transfer, and violation of "molecular clock" assumption with 3D visualization

    PubMed Central

    Kim, Namshin; Lee, Christopher

    2007-01-01

    Background Construction and interpretation of phylogenetic trees has been a major research topic for understanding the evolution of genes. Increases in sequence data and complexity are creating a need for more powerful and insightful tree visualization tools. Results We have developed 3D Phylogeny Explorer (3DPE), a novel phylogeny tree viewer that maps trees onto three spatial axes (species on the X-axis; paralogs on Z; evolutionary distance on Y), enabling one to distinguish at a glance evolutionary features such as speciation; gene duplication and paralog evolution; lateral gene transfer; and violation of the "molecular clock" assumption. Users can input any tree on the online 3DPE, then rotate, scroll, rescale, and explore it interactively as "live" 3D views. All objects in 3DPE are clickable to display subtrees, connectivity path highlighting, sequence alignments, and gene summary views, and etc. To illustrate the value of this visualization approach for microbial genomes, we also generated 3D phylogeny analyses for all clusters from the public COG database. We constructed tree views using well-established methods and graph algorithms. We used Scientific Python to generate VRML2 3D views viewable in any web browser. Conclusion 3DPE provides a novel phylogenetic tree projection method into 3D space and its web-based implementation with live 3D features for reconstruction of phylogenetic trees of COG database. PMID:17584922

  15. Public health implications of components of plastics manufacture. Flame retardants.

    PubMed

    Pearce, E M; Liepins, R

    1975-06-01

    The four processes involved in the flammability of materials are described and related to the various flame retardance mechanisms that may operate. Following this the four practical approaches used in improving flame retardance of materials are described. Each approach is illustrated with a number of typical examples of flame retardants or synthetic procedures used. This overview of flammability, flame retardance, and flame retardants used is followed by a more detailed examination of most of the plastics manufactured in the United States during 1973, their consumption patterns, and the primary types of flame retardants used in the flame retardance of the most used plastics. The main types of flame retardants are illustrated with a number of typical commercial examples. Statistical data on flame retardant market size, flame retardant growth in plastics, and price ranges of common flame retardants are presented.

  16. Public health implications of components of plastics manufacture. Flame retardants.

    PubMed Central

    Pearce, E M; Liepins, R

    1975-01-01

    The four processes involved in the flammability of materials are described and related to the various flame retardance mechanisms that may operate. Following this the four practical approaches used in improving flame retardance of materials are described. Each approach is illustrated with a number of typical examples of flame retardants or synthetic procedures used. This overview of flammability, flame retardance, and flame retardants used is followed by a more detailed examination of most of the plastics manufactured in the United States during 1973, their consumption patterns, and the primary types of flame retardants used in the flame retardance of the most used plastics. The main types of flame retardants are illustrated with a number of typical commercial examples. Statistical data on flame retardant market size, flame retardant growth in plastics, and price ranges of common flame retardants are presented. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. PMID:1175568

  17. Biodegradation of brominated and organophosphorus flame retardants.

    PubMed

    Waaijers, Susanne L; Parsons, John R

    2016-04-01

    Brominated flame retardants account for about 21% of the total production of flame retardants and many of these have been identified as persistent, bioaccumulative and toxic. Nevertheless, debromination of these chemicals under anaerobic conditions is well established, although this can increase their toxicity. Consequently, the production and use of these chemicals has been restricted and alternative products have been developed. Many of these are brominated compounds and share some of the disadvantages of the chemicals they are meant to replace. Therefore, other, nonbrominated, flame retardants such as organophosphorus compounds are also being used in increasing quantities, despite the fact that knowledge of their biodegradation and environmental fate is often lacking.

  18. A polymeric flame retardant additive for rubbers

    SciTech Connect

    Ghosh, S.N.; Maiti, S.

    1993-12-31

    Synthesis of a polyphosphonate by the interfacial polymerization of bisphenol-A (BPA) and dichloro-phenyl phosphine oxide (DCPO) using cetyltrimethyl ammonium chloride (TMAC) as phase transfer catalyst (PTC) was reported. The polyphosphonate was characterized by elemental analysis, IR, TGA, DSC and 1H-NMR spectroscopy. The flame retardancy of the polymer was done by OI study. The polymer was used as a fire retardant additive to rubbers such as natural rubber (NR), styrene-butadiene rubber(SBR), nitrile rubber (NBR) and chloroprene rubber (CR). The efficiency of the fire retardant property of this additive was determined by LOI measurements of the various rubber samples.

  19. Engineering Flame Retardant Biodegradable Nanocomposites

    NASA Astrophysics Data System (ADS)

    He, Shan; Yang, Kai; Guo, Yichen; Zhang, Linxi; Pack, Seongchan; Davis, Rachel; Lewin, Menahem; Ade, Harald; Korach, Chad; Kashiwagi, Takashi; Rafailovich, Miriam

    2013-03-01

    Cellulose-based PLA/PBAT polymer blends can potentially be a promising class of biodegradable nanocomposites. Adding cellulose fiber reinforcement can improve mechanical properties of biodegradable plastics, but homogeneously dispersing hydrophilic cellulose in the hydrophobic polymer matrix poses a significant challenge. We here show that resorcinol diphenyl phosphates (RDP) can be used to modify the surface energy, not only reducing phase separation between two polymer kinds but also allowing the cellulose particles and the Halloysite clay to be easily dispersed within polymer matrices to achieve synergy effect using melt blending. Here in this study we describe the use of cellulose fiber and Halloysite clay, coated with RDP surfactant, in producing the flame retardant polymer blends of PBAT(Ecoflex) and PLA which can pass the stringent UL-94 V0 test. We also utilized FTIR, SEM and AFM nanoindentation to elucidate the role RDP plays in improving the compatibility of biodegradable polymers, and to determine structure property of chars that resulted in composites that could have optimized mechanical and thermal properties. Supported by Garcia Polymer Center and NSF Foundation.

  20. Trends in Deinstitutionalization of the Mentally Retarded

    ERIC Educational Resources Information Center

    Conroy, James W.

    1977-01-01

    A review of national trends in deinstitutionalization of the mentally retarded indicated limited progress toward depopulation of institutions and showed that much of the national effort has been directed toward interinstitutional relocation. (Author/CL)

  1. Retardation analytical model to extend service life

    NASA Technical Reports Server (NTRS)

    Matejczyk, J.

    1984-01-01

    A fatigue crack growth model that incorporates crack growth retardation effects and is applicable to the materials characteristics and service environments of high performance LH2/LO2 engine systems is discussed. Future Research plans are outlined.

  2. Retardation analytical model to extend service life

    NASA Technical Reports Server (NTRS)

    Matejczyk, D.

    1984-01-01

    A fatigue crack growth model that incorporates crack growth retardation effects and is applicable to the materials characteristics and service environments of high performance LH2/LO2 engine systems was developed and tested.

  3. Video Tape and the Mentally Retarded

    ERIC Educational Resources Information Center

    Weisbord, H. F.

    1972-01-01

    Three uses of video tape recordings with the mentally retarded; discussed briefly are staff training or teacher education, parental involvement in the child's education, and therapeutic uses by psychiatrists and psychologists. (CB)

  4. PCBs, PBBs and Brominated Flame Retardants

    EPA Science Inventory

    This chapter introduces selected organohalogen chemicals such as polychlorinated biphenyls (PCB5), polychiorinated biphenyls (PBBs), and brominated flame retardants (BFRs) with emphasis on the background, physicochemical properties, environmental levels, health effects and possib...

  5. Brominated Flame Retardants and Perfluorinated Chemicals

    EPA Science Inventory

    Brominated flame retardants (BFRs) and perfluorinated chemicals (PFCs) belong to a large class of chemicals known as organohalogens. It is believed that both BFRs and PFCs saved lives by reducing flammability of materials commonly used and bactericidal (biocidal) properties. Thes...

  6. Sterilization of Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Elkins, Thomas E.; Andersen, H. Frank

    1992-01-01

    This article examines the historical, legal, and ethical concerns regarding sterilization for persons with mental retardation and offers guidelines to help counsel individuals with disabilities or their families regarding decision making about sterilization. (DB)

  7. Case Study--Weight Control and Retardation

    ERIC Educational Resources Information Center

    Schoenwetter, Charles D.

    1978-01-01

    Through positive reinforcement of good eating habits, it is possible to help mentally retarded children lose weight and remain within the normal limits consistent with their age and body structure. (JD)

  8. Retardation Measurements of Infrared PVA Wave plate

    NASA Astrophysics Data System (ADS)

    Sun, Y.; Z, H.; W, D.; D, Y.; Z, Z.; S, J.

    The wave plate made of Polyvinyl Alcohol PVA plastic film has several advantages such as its lower cost and insensitivity to temperature and incidence angle so it has been used in the Solar Multi-Channel Telescope SMCT in China But the important parameter retardations of PVA wave plates in the near infrared wavelength have never been provided In this paper a convenient and high precise instrument to get the retardations of discrete wavelengths or a continuous function of wavelength in near infrared is developed In this method the retardations of wave plates have been determined through calculating the maximum and minimum of light intensity The instrument error has been shown Additionally we can get the continuous direction of wavelength retardations in the ultraviolet visible or infrared spectral in another way

  9. Retarded Children at Camp with Normal Children

    ERIC Educational Resources Information Center

    Flax, Norman; Peters, Edward N.

    1969-01-01

    Statistical analysis of data from written forms and scales (designed to measure children's behavior in groups), observations, and interviews indicated that many educalble mentally retarded children can participate successfully in camp activities with normal children. (DR)

  10. Influence of Retardants to Burning Lignocellulosic Materials

    NASA Astrophysics Data System (ADS)

    Tureková, Ivana; Harangozó, Jozef; Martinka, Jozef

    2011-01-01

    The paper deals with monitoring retardant changes of lignocellulosic materials. Combustion of lignocellulosic materials and fire-technical characteristics are described. In assessing the retarding effect of salt NH4H2PO4, fire-technical characteristics as limiting oxygen index (LOI) were measured, and by using thermoanalytical TG and DSC methods. High-temperature process of cellulose degradation at various flame concentrations was studied.

  11. Defining mental retardation from an instructional perspective.

    PubMed

    Dever, R B

    1990-06-01

    A definition of mental retardation developed under the aegis of the instructional paradigm was presented. Its purpose and use is to (a) clarify the task of personnel who work with persons who have been identified as mentally retarded and (b) provide a concept that unifies apparently discrete instructional constructs. This definition can also help mold the perceptual patterns of young persons entering the field by establishing expectations that focus on the provision of instruction. PMID:2195289

  12. Musical aptitudes, musical interests and mental retardation.

    PubMed

    Miller, L K

    1991-08-01

    A modified version of the Bentley scales of musical aptitude was given to a sample of mild and moderately retarded adults chosen on the basis of alleged musical interest or experience. Several comparison groups were also given the assessment battery. The musical nominees generally performed more accurately than both matched retarded subjects with no particular musical interests and a group of normal children matched on (Wechsler) vocabulary scores. The musical nominees showed especially high performance on the subtest assessing voice analysis in chords.

  13. Trends in Classification Usage in the Mental Retardation Literature.

    ERIC Educational Resources Information Center

    Taylor, Ronald L.; Kaufmann, Steve

    1991-01-01

    A total of 685 articles in "Mental Retardation,""American Journal of Mental Deficiency," and "American Journal on Mental Retardation" from 1980 through 1989 were examined. The mental retardation classification system developed by the American Association on Mental Retardation was used in over 50 percent of the articles, whereas the American…

  14. Realidades Acerca de la Deficiencia Mental = Facts about Mental Retardation.

    ERIC Educational Resources Information Center

    Texas State Dept. of Mental Health and Mental Retardation, Austin.

    This document consists of two booklets, one in Spanish and one in English, both covering the same text: the characteristics of mentally retarded individuals, the prevalence of mentally retarded persons in Texas, causes of mental retardation, prevention possibilities, and services available to mentally retarded persons in Texas. A distinction is…

  15. Similar but not the same: insights into the evolutionary history of paralogous sex-determining genes of the dwarf honey bee Apis florea.

    PubMed

    Biewer, M; Lechner, S; Hasselmann, M

    2016-01-01

    Studying the fate of duplicated genes provides informative insight into the evolutionary plasticity of biological pathways to which they belong. In the paralogous sex-determining genes complementary sex determiner (csd) and feminizer (fem) of honey bee species (genus Apis), only heterozygous csd initiates female development. Here, the full-length coding sequences of the genes csd and fem of the phylogenetically basal dwarf honey bee Apis florea are characterized. Compared with other Apis species, remarkable evolutionary changes in the formation and localization of a protein-interacting (coiled-coil) motif and in the amino acids coding for the csd characteristic hypervariable region (HVR) are observed. Furthermore, functionally different csd alleles were isolated as genomic fragments from a random population sample. In the predicted potential specifying domain (PSD), a high ratio of πN/πS=1.6 indicated positive selection, whereas signs of balancing selection, commonly found in other Apis species, are missing. Low nucleotide diversity on synonymous and genome-wide, non-coding sites as well as site frequency analyses indicated a strong impact of genetic drift in A. florea, likely linked to its biology. Along the evolutionary trajectory of ~30 million years of csd evolution, episodic diversifying selection seems to have acted differently among distinct Apis branches. Consistently low amino-acid differences within the PSD among pairs of functional heterozygous csd alleles indicate that the HVR is the most important region for determining allele specificity. We propose that in the early history of the lineage-specific fem duplication giving rise to csd in Apis, A. florea csd stands as a remarkable example for the plasticity of initial sex-determining signals. PMID:26153222

  16. Molecular and functional characterization of seven Na+/K+-ATPase β subunit paralogs in Senegalese sole (Solea senegalensis Kaup, 1858).

    PubMed

    Armesto, Paula; Infante, Carlos; Cousin, Xavier; Ponce, Marian; Manchado, Manuel

    2015-04-01

    In the present work, seven genes encoding Na(+),K(+)-ATPase (NKA) β-subunits in the teleost Solea senegalensis are described for the first time. Sequence analysis of the predicted polypeptides revealed a high degree of conservation with those of other vertebrate species and maintenance of important motifs involved in structure and function. Phylogenetic analysis clustered the seven genes into four main clades: β1 (atp1b1a and atp1b1b), β2 (atp1b2a and atp1b2b), β3 (atp1b3a and atp1b3b) and β4 (atp1b4). In juveniles, all paralogous transcripts were detected in the nine tissues examined albeit with different expression patterns. The most ubiquitous expressed gene was atp1b1a whereas atp1b1b was mainly detected in osmoregulatory organs (gill, kidney and intestine), and atp1b2a, atp1b2b, atp1b3a, atp1b3b and atp1b4 in brain. An expression analysis in three brain regions and pituitary revealed that β1-type transcripts were more abundant in pituitary than the other β paralogs with slight differences between brain regions. Quantification of mRNA abundance in gills after a salinity challenge showed an activation of atp1b1a and atp1b1b at high salinity water (60 ppt) and atp1b3a and atp1b3b in response to low salinity (5 ppt). Transcriptional analysis during larval development showed specific expression patterns for each paralog. Moreover, no differences in the expression profiles between larvae cultivated at 10 and 35 ppt were observed except for atp1b4 with higher mRNA levels at 10 than 35 ppt at 18 days post hatch. Whole-mount in situ hybridization analysis revealed that atp1b1b was mainly localized in gut, pronephric tubule, gill, otic vesicle, and chordacentrum of newly hatched larvae. All these data suggest distinct roles of NKA β subunits in tissues, during development and osmoregulation with β1 subunits involved in the adaptation to hyperosmotic conditions and β3 subunits to hypoosmotic environments.

  17. Paralogs of Atlantic salmon myoblast determination factor genes are distinctly regulated in proliferating and differentiating myogenic cells.

    PubMed

    Bower, Neil I; Johnston, Ian A

    2010-06-01

    The mRNA expression of myogenic regulatory factors, including myoD1 (myoblast determination factor) gene paralogs, and their regulation by amino acids and insulin-like growth factors were investigated in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The cell cycle and S phase were determined as 28.1 and 13.3 h, respectively, at 18 degrees C. Expression of myoD1b and myoD1c peaked at 8 days of culture in the initial proliferation phase and then declined more than sixfold as cells differentiated and was correlated with PCNA (proliferating cell nuclear antigen) expression (R = 0.88, P < 0.0001; R = 0.70, P < 0.0001). In contrast, myoD1a transcripts increased from 2 to 8 days and remained at elevated levels as myotubes were formed. mRNA levels of myoD1c were, on average, 3.1- and 5.7-fold higher than myoD1a and myoD1b, respectively. Depriving cells of amino acids and serum led to a rapid increase in pax7 and a decrease in myoD1c and PCNA expression, indicating a transition to a quiescent state. In contrast, amino acid replacement in starved cells produced significant increases in myoD1c (at 6 h), PCNA (at 12 h), and myoD1b (at 24 h) and decreases in pax7 expression as cells entered the cell cycle. Our results are consistent with temporally distinct patterns of myoD1c and myoD1b expression at the G(1) and S/G(2) phases of the cell cycle. Treatment of starved cells with insulin-like growth factor I or II did not alter expression of the myoD paralogs. It was concluded that, in vitro, amino acids alone are sufficient to stimulate expression of genes regulating myogenesis in myoblasts involving autocrine/paracrine pathways. The differential responses of myoD paralogs during myotube maturation and amino acid treatments suggest that myoD1b and myoD1c are primarily expressed in proliferating cells and myoD1a in differentiating cells, providing evidence for their subfunctionalization following whole genome and local duplications in

  18. Gains and Losses of Cis-regulatory Elements Led to Divergence of the Arabidopsis APETALA1 and CAULIFLOWER Duplicate Genes in the Time, Space, and Level of Expression and Regulation of One Paralog by the Other.

    PubMed

    Ye, Lingling; Wang, Bin; Zhang, Wengen; Shan, Hongyan; Kong, Hongzhi

    2016-06-01

    How genes change their expression patterns over time is still poorly understood. Here, by conducting expression, functional, bioinformatic, and evolutionary analyses, we demonstrate that the differences between the Arabidopsis (Arabidopsis thaliana) APETALA1 (AP1) and CAULIFLOWER (CAL) duplicate genes in the time, space, and level of expression were determined by the presence or absence of functionally important transcription factor-binding sites (TFBSs) in regulatory regions. In particular, a CArG box, which is the autoregulatory site of AP1 that can also be bound by the CAL protein, is a key determinant of the expression differences. Because of the CArG box, AP1 is both autoregulated and cross-regulated (by AP1 and CAL, respectively), and its relatively high-level expression is maintained till to the late stages of sepal and petal development. The observation that the CArG box was gained recently further suggests that the autoregulation and cross-regulation of AP1, as well as its function in sepal and petal development, are derived features. By comparing the evolutionary histories of this and other TFBSs, we further indicate that the divergence of AP1 and CAL in regulatory regions has been markedly asymmetric and can be divided into several stages. Specifically, shortly after duplication, when AP1 happened to be the paralog that maintained the function of the ancestral gene, CAL experienced certain degrees of degenerate evolution, in which several functionally important TFBSs were lost. Later, when functional divergence allowed the survival of both paralogs, CAL remained largely unchanged in expression, whereas the functions of AP1 were gradually reinforced by gains of the CArG box and other TFBSs.

  19. X-linked mental retardation and epigenetics

    PubMed Central

    Froyen, Guy; Bauters, Marijke; Voet, Thierry; Marynen, Peter

    2006-01-01

    The search for the genetic defects in constitutional diseases has so far been restricted to direct methods for the identification of genetic mutations in the patients’ genome. Traditional methods such as karyotyping, FISH, mutation screening, positional cloning and CGH, have been complemented with newer methods including array-CGH and PCR-based approaches (MLPA, qPCR). These methods have revealed a high number of genetic or genomic aberrations that result in an altered expression or reduced functional activity of key proteins. For a significant percentage of patients with congenital disease however, the underlying cause has not been resolved strongly suggesting that yet other mechanisms could play important roles in their etiology. Alterations of the ‘native’ epigenetic imprint might constitute such a novel mechanism. Epigenetics, heritable changes that do not rely on the nucleotide sequence, has already been shown to play a determining role in embryonic development, X-inactivation, and cell differentiation in mammals. Recent progress in the development of techniques to study these processes on full genome scale has stimulated researchers to investigate the role of epigenetic modifications in cancer as well as in constitutional diseases. We will focus on mental impairment because of the growing evidence for the contribution of epigenetics in memory formation and cognition. Disturbance of the epigenetic profile due to direct alterations at genomic regions, or failure of the epigenetic machinery due to genetic mutations in one of its components, has been demonstrated in cognitive derangements in a number of neurological disorders now. It is therefore tempting to speculate that the cognitive deficit in a significant percentage of patients with unexplained mental retardation results from epigenetic modifications. PMID:17125586

  20. X-linked mental retardation and epigenetics.

    PubMed

    Froyen, Guy; Bauters, Marijke; Voet, Thierry; Marynen, Peter

    2006-01-01

    The search for the genetic defects in constitutional diseases has so far been restricted to direct methods for the identification of genetic mutations in the patients' genome. Traditional methods such as karyotyping, FISH, mutation screening, positional cloning and CGH, have been complemented with newer methods including array-CGH and PCR-based approaches (MLPA, qPCR). These methods have revealed a high number of genetic or genomic aberrations that result in an altered expression or reduced functional activity of key proteins. For a significant percentage of patients with congenital disease however, the underlying cause has not been resolved strongly suggesting that yet other mechanisms could play important roles in their etiology. Alterations of the 'native' epigenetic imprint might constitute such a novel mechanism. Epigenetics, heritable changes that do not rely on the nucleotide sequence, has already been shown to play a determining role in embryonic development, X-inactivation, and cell differentiation in mammals. Recent progress in the development of techniques to study these processes on full genome scale has stimulated researchers to investigate the role of epigenetic modifications in cancer as well as in constitutional diseases. We will focus on mental impairment because of the growing evidence for the contribution of epigenetics in memory formation and cognition. Disturbance of the epigenetic profile due to direct alterations at genomic regions, or failure of the epigenetic machinery due to genetic mutations in one of its components, has been demonstrated in cognitive derangements in a number of neurological disorders now. It is therefore tempting to speculate that the cognitive deficit in a significant percentage of patients with unexplained mental retardation results from epigenetic modifications.

  1. Molecular and comparative genetics of mental retardation.

    PubMed Central

    Inlow, Jennifer K; Restifo, Linda L

    2004-01-01

    Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the approximately 700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR. PMID:15020472

  2. Binding specificities of the GYF domains from two Saccharomyces cerevisiae paralogs.

    PubMed

    Georgiev, Alexander; Sjöström, Michael; Wieslander, Ake

    2007-09-01

    We have used multivariate statistics and z-scales to represent peptide sequences in a PLS-QSAR model of previously studied binding affinities [Kofler,M., Motzny,K. and Freund,C. (2005b) Mol. Cell. Proteomics, 4, 1797-1811.] of two GYF domains to an array of immobilized synthetic peptides. As a result, we established structural determinants of the binding specificities of the two proteins. Our model was used to define new sets of yeast proteins potentially interacting with Syh1 (YPL105C) and Smy2 (YBR172C). These sets were subsequently examined for co-occurrence of Gene Ontology terms, leading to suggest a group of likely interacting proteins with a common function in mRNA catabolism. Finally, subcellular localization of a GFP-fused Syh1 and Smy2 reinforced the possibility that these proteins reside in cytoplasmic sites of mRNA degradation, thereby providing experimental confirmation to the predictions from the model.

  3. Intrauterine radiation exposures and mental retardation.

    PubMed

    Miller, R W

    1988-08-01

    Small head size and mental retardation have been known as effects of intrauterine exposure to ionizing radiation since the 1920s. In the 1950s, studies of Japanese atomic-bomb survivors revealed that at 4-17 wk of gestation, the greater the dose, the smaller the brain (and head size), and that beginning at 0.5 Gy (50 rad) in Hiroshima, mental retardation increased in frequency with increasing dose. No other excess of birth defects was observed. Otake and Schull (1984) pointed out that the period of susceptibility to mental retardation coincided with that for proliferation and migration of neuronal elements from near the cerebral ventricles to the cortex. Mental retardation could be the result of interference with this process. Their analysis indicated that exposures at 8-15 wk to 0.01-0.02 Gy (1-2 rad) doubled the frequency of severe mental retardation. This estimate was based on small numbers of mentally retarded atomic-bomb survivors. Although nuclear accidents have occurred recently, new cases will hopefully be too rare to provide further information about the risk of mental retardation. It may be possible, however, to learn about lesser impairment. New psychometric tests may be helpful in detecting subtle deficits in intelligence or neurodevelopmental function. One such test is PEERAMID, which is being used in schools to identify learning disabilities due, for example, to deficits in attention, short- or long-term memory, or in sequencing information. This and other tests could be applied in evaluating survivors of intrauterine exposure to various doses of ionizing radiation. The results could change our understanding of the safety of low-dose exposures.

  4. Intrauterine radiation exposures and mental retardation

    SciTech Connect

    Miller, R.W.

    1988-08-01

    Small head size and mental retardation have been known as effects of intrauterine exposure to ionizing radiation since the 1920s. In the 1950s, studies of Japanese atomic-bomb survivors revealed that at 4-17 wk of gestation, the greater the dose, the smaller the brain (and head size), and that beginning at 0.5 Gy (50 rad) in Hiroshima, mental retardation increased in frequency with increasing dose. No other excess of birth defects was observed. Otake and Schull (1984) pointed out that the period of susceptibility to mental retardation coincided with that for proliferation and migration of neuronal elements from near the cerebral ventricles to the cortex. Mental retardation could be the result of interference with this process. Their analysis indicated that exposures at 8-15 wk to 0.01-0.02 Gy (1-2 rad) doubled the frequency of severe mental retardation. This estimate was based on small numbers of mentally retarded atomic-bomb survivors. Although nuclear accidents have occurred recently, new cases will hopefully be too rare to provide further information about the risk of mental retardation. It may be possible, however, to learn about lesser impairment. New psychometric tests may be helpful in detecting subtle deficits in intelligence or neurodevelopmental function. One such test is PEERAMID, which is being used in schools to identify learning disabilities due, for example, to deficits in attention, short- or long-term memory, or in sequencing information. This and other tests could be applied in evaluating survivors of intrauterine exposure to various doses of ionizing radiation. The results could change our understanding of the safety of low-dose exposures.

  5. A naturally chimeric type IIA topoisomerase in Aquifex aeolicus highlights an evolutionary path for the emergence of functional paralogs.

    PubMed

    Tretter, Elsa M; Lerman, Jeffrey C; Berger, James M

    2010-12-21

    Bacteria frequently possess two type IIA DNA topoisomerases, gyrase and topo IV, which maintain chromosome topology by variously supercoiling, relaxing, and disentangling DNA. DNA recognition and functional output is thought to be controlled by the C-terminal domain (CTD) of the topoisomerase DNA binding subunit (GyrA/ParC). The deeply rooted organism Aquifex aeolicus encodes one type IIA topoisomerase conflictingly categorized as either DNA gyrase or topo IV. To resolve this enzyme's catalytic properties and heritage, we conducted a series of structural and biochemical studies on the isolated GyrA/ParC CTD and the holoenzyme. Whereas the CTD displays a global structure similar to that seen in bone fide GyrA and ParC paralogs, it lacks a key functional motif (the "GyrA-box") and fails to wrap DNA. Biochemical assays show that the A. aeolicus topoisomerase cannot supercoil DNA, but robustly removes supercoils and decatenates DNA, two hallmark activities of topo IV. Despite these properties, phylogenetic analyses place all functional domains except the CTD squarely within a gyrase lineage, and the A. aeolicus GyrB subunit is capable of supporting supercoiling with Escherichia coli GyrA, but not DNA relaxation with E. coli ParC. Moreover, swapping the A. aeolicus GyrA/ParC CTD with the GyrA CTD from Thermotoga maritima creates an enzyme that negatively supercoils DNA. These findings identify A. aeolicus as the first bacterial species yet found to exist without a functional gyrase, and suggest an evolutionary path for generation of bacterial type IIA paralogs.

  6. The discovery of Foxl2 paralogs in chondrichthyan, coelacanth and tetrapod genomes reveals an ancient duplication in vertebrates.

    PubMed

    Geraldo, M T; Valente, G T; Braz, A S K; Martins, C

    2013-07-01

    The Foxl2 (forkhead box L2) gene is an important member of the forkhead domain family, primarily responsible for the development of ovaries during female sex differentiation. The evolutionary studies conducted previously considered the presence of paralog Foxl2 copies only in teleosts. However, to search for possible paralog copies in other groups of vertebrates and ensure that all predicted copies were homolog to the Foxl2 gene, a broad evolutionary analysis was performed, based on the forkhead domain family. A total of 2464 sequences for the forkhead domain were recovered, and subsequently, 64 representative sequences for Foxl2 were used in the evolutionary analysis of this gene. The most important contribution of this study was the discovery of a new subgroup of Foxl2 copies (ortholog to Foxl2B) present in the chondrichthyan Callorhinchus milii, in the coelacanth Latimeria chalumnae, in the avian Taeniopygia guttata and in the marsupial Monodelphis domestica. This new scenario indicates a gene duplication event in an ancestor of gnathostomes. Furthermore, based on the analysis of the syntenic regions of both Foxl2 copies, the duplication event was not exclusive to Foxl2. Moreover, the duplicated copy distribution was shown to be complex across vertebrates, especially in tetrapods, and the results strongly support a loss of this copy in eutherian species. Finally, the scenario observed in this study suggests an update for Foxl2 gene nomenclature, extending the actual suggested teleost naming of Foxl2A and Foxl2B to all vertebrate sequences and contributing to the establishment of a new evolutionary context for the Foxl2 gene.

  7. Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice

    PubMed Central

    Ruff, James S.; Saffarini, Raed B.; Ramoz, Leda L.; Morrison, Linda C.; Baker, Shambralyn; Laverty, Sean M.; Tvrdik, Petr; Potts, Wayne K.

    2015-01-01

    Gene targeting techniques have led to the phenotypic characterization of numerous genes; however, many genes show minimal to no phenotypic consequences when disrupted, despite many having highly conserved sequences. The standard explanation for these findings is functional redundancy. A competing hypothesis is that these genes have important ecological functions in natural environments that are not needed under laboratory settings. Here we discriminate between these hypotheses by competing mice (Mus musculus) whose Hoxb1 gene has been replaced by Hoxa1, its highly conserved paralog, against matched wild-type controls in seminatural enclosures. This Hoxb1A1 swap was reported as a genetic manipulation resulting in no discernible embryonic or physiological phenotype under standard laboratory tests. We observed a transient decline in first litter size for Hoxb1A1 homozygous mice in breeding cages, but their fitness was consistently and more dramatically reduced when competing against controls within seminatural populations. Specifically, males homozygous for the Hoxb1A1 swap acquired 10.6% fewer territories and the frequency of the Hoxb1A1 allele decreased from 0.500 in population founders to 0.419 in their offspring. The decrease in Hoxb1A1 frequency corresponded with a deficiency of both Hoxb1A1 homozygous and heterozygous offspring. These data suggest that Hoxb1 and Hoxa1 are more phenotypically divergent than previously reported and support that sub- and/or neofunctionalization has occurred in these paralogous genes leading to a divergence of gene function and incomplete redundancy. Furthermore, this study highlights the importance of obtaining fitness measures of mutants in ecologically relevant conditions to better understand gene function and evolution. PMID:26447130

  8. Functional modeling identifies paralogous solanesyl-diphosphate synthases that assemble the side chain of plastoquinone-9 in plastids.

    PubMed

    Block, Anna; Fristedt, Rikard; Rogers, Sara; Kumar, Jyothi; Barnes, Brian; Barnes, Joshua; Elowsky, Christian G; Wamboldt, Yashitola; Mackenzie, Sally A; Redding, Kevin; Merchant, Sabeeha S; Basset, Gilles J

    2013-09-20

    It is a little known fact that plastoquinone-9, a vital redox cofactor of photosynthesis, doubles as a precursor for the biosynthesis of a vitamin E analog called plastochromanol-8, the physiological significance of which has remained elusive. Gene network reconstruction, GFP fusion experiments, and targeted metabolite profiling of insertion mutants indicated that Arabidopsis possesses two paralogous solanesyl-diphosphate synthases, AtSPS1 (At1g78510) and AtSPS2 (At1g17050), that assemble the side chain of plastoquinone-9 in plastids. Similar paralogous pairs were detected throughout terrestrial plant lineages but were not distinguished in the literature and genomic databases from mitochondrial homologs involved in the biosynthesis of ubiquinone. The leaves of the atsps2 knock-out were devoid of plastochromanol-8 and displayed severe losses of both non-photoactive and photoactive plastoquinone-9, resulting in near complete photoinhibition at high light intensity. Such a photoinhibition was paralleled by significant damage to photosystem II but not to photosystem I. In contrast, in the atsps1 knock-out, a small loss of plastoquinone-9, restricted to the non-photoactive pool, was sufficient to eliminate half of the plastochromanol-8 content of the leaves. Taken together, these results demonstrate that plastochromanol-8 originates from a subfraction of the non-photoactive pool of plastoquinone-9. In contrast to other plastochromanol-8 biosynthetic mutants, neither the single atsps knock-outs nor the atsps1 atsps2 double knock-out displayed any defects in tocopherols accumulation or germination.

  9. Pseudomonas savastanoi pv. savastanoi Contains Two iaaL Paralogs, One of Which Exhibits a Variable Number of a Trinucleotide (TAC) Tandem Repeat▿ †

    PubMed Central

    Matas, Isabel M.; Pérez-Martínez, Isabel; Quesada, José M.; Rodríguez-Herva, José J.; Penyalver, Ramón; Ramos, Cayo

    2009-01-01

    In this study, Pseudomonas savastanoi pv. savastanoi isolates were demonstrated to contain two iaaL paralogs, which are both chromosomally located in most strains. Comparative analysis of iaaL nucleotide sequences amplified from these two paralogs revealed that one paralog, iaaLPsn, is 100% identical to iaaL from P. savastanoi pv. nerii, while the other paralog, iaaLPsv, exhibited 93% identity to iaaL from Pseudomonas syringae pv. tomato (iaaLPto). A 3-nucleotide motif (TAC) comprised of 3 to 15 repeats, which remained stable after propagation of the strains in olive plants, was found in iaaLPsv. Based on the observed nucleotide sequence variations, a restriction fragment length polymorphism assay was developed that allowed differentiation among iaaLPsn, iaaLPsv, and iaaLPto. In addition, reverse transcriptase PCR on total RNA from P. savastanoi pv. savastanoi strains demonstrated that both iaaLPsv and iaaLPsn containing 14 or fewer TAC repeats are transcribed. Capillary electrophoresis analysis of PCR-amplified DNA fragments containing the TAC repeats from iaaLPsv allowed the differentiation of P. savastanoi pv. savastanoi isolates. PMID:19098222

  10. Cooperative and Competitive Behavior of Retarded and Non-Retarded Children at Two Ages.

    ERIC Educational Resources Information Center

    Madsen, Millard C.; Connor, Catherine

    Cooperative and competitive interaction (interpersonal relationship) between pairs of retarded and nonretarded children of ages 6 to 7 and 11 to 12 were assessed in a situation involving a marble pull apparatus in which competitive interaction was nonadaptive in terms of reward attainment. The retarded group was significantly more cooperative than…

  11. Reactions to the Labels "Institutionalized" and "Mentally Retarded" by Retarded and Nonretarded Persons.

    ERIC Educational Resources Information Center

    Gibbons, Frederick X.; Gibbons, Barbara N.

    The effects of labels, "mentally retarded" and "institutionalized" on the evaluations and causal attributions of nonretarded persons, and on the social distance preferences of EMR persons, were assessed. In addition, each group was asked to predict the likelihood of a labeled (mentally retarded) or a nonlabeled target person achieving success at a…

  12. Interplay of the Serine/Threonine-Kinase StkP and the Paralogs DivIVA and GpsB in Pneumococcal Cell Elongation and Division

    PubMed Central

    Campo, Nathalie; Cluzel, Caroline; Lavergne, Jean-Pierre; Freton, Céline; Combet, Christophe; Guiral, Sébastien; Soufi, Boumediene; Macek, Boris; Kuru, Erkin; VanNieuwenhze, Michael S.; Brun, Yves V.; Di Guilmi, Anne-Marie; Claverys, Jean-Pierre; Galinier, Anne; Grangeasse, Christophe

    2014-01-01

    Despite years of intensive research, much remains to be discovered to understand the regulatory networks coordinating bacterial cell growth and division. The mechanisms by which Streptococcus pneumoniae achieves its characteristic ellipsoid-cell shape remain largely unknown. In this study, we analyzed the interplay of the cell division paralogs DivIVA and GpsB with the ser/thr kinase StkP. We observed that the deletion of divIVA hindered cell elongation and resulted in cell shortening and rounding. By contrast, the absence of GpsB resulted in hampered cell division and triggered cell elongation. Remarkably, ΔgpsB elongated cells exhibited a helical FtsZ pattern instead of a Z-ring, accompanied by helical patterns for DivIVA and peptidoglycan synthesis. Strikingly, divIVA deletion suppressed the elongated phenotype of ΔgpsB cells. These data suggest that DivIVA promotes cell elongation and that GpsB counteracts it. Analysis of protein-protein interactions revealed that GpsB and DivIVA do not interact with FtsZ but with the cell division protein EzrA, which itself interacts with FtsZ. In addition, GpsB interacts directly with DivIVA. These results are consistent with DivIVA and GpsB acting as a molecular switch to orchestrate peripheral and septal PG synthesis and connecting them with the Z-ring via EzrA. The cellular co-localization of the transpeptidases PBP2x and PBP2b as well as the lipid-flippases FtsW and RodA in ΔgpsB cells further suggest the existence of a single large PG assembly complex. Finally, we show that GpsB is required for septal localization and kinase activity of StkP, and therefore for StkP-dependent phosphorylation of DivIVA. Altogether, we propose that the StkP/DivIVA/GpsB triad finely tunes the two modes of peptidoglycan (peripheral and septal) synthesis responsible for the pneumococcal ellipsoid cell shape. PMID:24722178

  13. Mutations in single FT- and TFL1-paralogs of rapeseed (Brassica napus L.) and their impact on flowering time and yield components.

    PubMed

    Guo, Yuan; Hans, Harloff; Christian, Jung; Molina, Carlos

    2014-01-01

    Rapeseed (Brassica napus L.) is grown in different geographical regions of the world. It is adapted to different environments by modification of flowering time and requirement for cold. A broad variation exists from very early-flowering spring-type to late-flowering winter cultivars which only flower after exposure to an extended cold period. B. napus is an allopolyploid species which resulted from the hybridization between B. rapa and B. oleracea. In Arabidopsis thaliana, the PEBP-domain genes FLOWERING LOCUS-T (FT) and TERMINAL FLOWER-1 (TFL1) are important integrators of different flowering pathways. Six FT and four TFL1 paralogs have been identified in B. napus. However, their role in flowering time control is unknown. We identified EMS mutants of the B. napus winter-type inbreed line Express 617. In total, 103 mutant alleles have been determined for BnC6FTb, BnC6FTa, and BnTFL1-2 paralogs. We chose three non-sense and 15 missense mutant lines (M3) which were grown in the greenhouse. Although only two out of 6 FT paralogs were mutated, 6 out of 8 BnC6FTb mutant lines flowered later as the control, whereas all five BnC6FTa mutant lines started flowering as the non-mutated parent. Mutations within the BnTFL1-2 paralog had no large effects on flowering time but on yield components. F1 hybrids between BnTFL1-2 mutants and non-mutated parents had increased seed number per pod and total seeds per plant suggesting that heterozygous mutations in a TFL1 paralog may impact heterosis in rapeseed. We demonstrate that single point-mutations in BnFT and BnTFL1 paralogs have effects on flowering time despite the redundancy of the rapeseed genome. Moreover, our results suggest pleiotropic effects of BnTFL1 paralogs beyond the regulation of flowering time.

  14. Evolution of plant RNA polymerase IV/V genes: evidence of subneofunctionalization of duplicated NRPD2/NRPE2-like paralogs in Viola (Violaceae)

    PubMed Central

    2010-01-01

    Background DNA-dependent RNA polymerase IV and V (Pol IV and V) are multi-subunit enzymes occurring in plants. The origin of Pol V, specific to angiosperms, from Pol IV, which is present in all land plants, is linked to the duplication of the gene encoding the largest subunit and the subsequent subneofunctionalization of the two paralogs (NRPD1 and NRPE1). Additional duplication of the second-largest subunit, NRPD2/NRPE2, has happened independently in at least some eudicot lineages, but its paralogs are often subject to concerted evolution and gene death and little is known about their evolution nor their affinity with Pol IV and Pol V. Results We sequenced a ~1500 bp NRPD2/E2-like fragment from 18 Viola species, mostly paleopolyploids, and 6 non-Viola Violaceae species. Incongruence between the NRPD2/E2-like gene phylogeny and species phylogeny indicates a first duplication of NRPD2 relatively basally in Violaceae, with subsequent sorting of paralogs in the descendants, followed by a second duplication in the common ancestor of Viola and Allexis. In Viola, the mutation pattern suggested (sub-) neofunctionalization of the two NRPD2/E2-like paralogs, NRPD2/E2-a and NRPD2/E2-b. The dN/dS ratios indicated that a 54 bp region exerted strong positive selection for both paralogs immediately following duplication. This 54 bp region encodes a domain that is involved in the binding of the Nrpd2 subunit with other Pol IV/V subunits, and may be important for correct recognition of subunits specific to Pol IV and Pol V. Across all Viola taxa 73 NRPD2/E2-like sequences were obtained, of which 23 (32%) were putative pseudogenes - all occurring in polyploids. The NRPD2 duplication was conserved in all lineages except the diploid MELVIO clade, in which NRPD2/E2-b was lost, and its allopolyploid derivates from hybridization with the CHAM clade, section Viola and section Melanium, in which NRPD2/E2-a occurred in multiple copies while NRPD2/E2-b paralogs were either absent or

  15. Mutations in single FT- and TFL1-paralogs of rapeseed (Brassica napus L.) and their impact on flowering time and yield components.

    PubMed

    Guo, Yuan; Hans, Harloff; Christian, Jung; Molina, Carlos

    2014-01-01

    Rapeseed (Brassica napus L.) is grown in different geographical regions of the world. It is adapted to different environments by modification of flowering time and requirement for cold. A broad variation exists from very early-flowering spring-type to late-flowering winter cultivars which only flower after exposure to an extended cold period. B. napus is an allopolyploid species which resulted from the hybridization between B. rapa and B. oleracea. In Arabidopsis thaliana, the PEBP-domain genes FLOWERING LOCUS-T (FT) and TERMINAL FLOWER-1 (TFL1) are important integrators of different flowering pathways. Six FT and four TFL1 paralogs have been identified in B. napus. However, their role in flowering time control is unknown. We identified EMS mutants of the B. napus winter-type inbreed line Express 617. In total, 103 mutant alleles have been determined for BnC6FTb, BnC6FTa, and BnTFL1-2 paralogs. We chose three non-sense and 15 missense mutant lines (M3) which were grown in the greenhouse. Although only two out of 6 FT paralogs were mutated, 6 out of 8 BnC6FTb mutant lines flowered later as the control, whereas all five BnC6FTa mutant lines started flowering as the non-mutated parent. Mutations within the BnTFL1-2 paralog had no large effects on flowering time but on yield components. F1 hybrids between BnTFL1-2 mutants and non-mutated parents had increased seed number per pod and total seeds per plant suggesting that heterozygous mutations in a TFL1 paralog may impact heterosis in rapeseed. We demonstrate that single point-mutations in BnFT and BnTFL1 paralogs have effects on flowering time despite the redundancy of the rapeseed genome. Moreover, our results suggest pleiotropic effects of BnTFL1 paralogs beyond the regulation of flowering time. PMID:24987398

  16. Plasma impregnation of wood with fire retardants

    NASA Astrophysics Data System (ADS)

    Pabeliña, Karel G.; Lumban, Carmencita O.; Ramos, Henry J.

    2012-02-01

    The efficacy of chemical and plasma treatments with phosphate and boric compounds, and nitrogen as flame retardants on wood are compared in this study. The chemical treatment involved the conventional method of spraying the solution over the wood surface at atmospheric condition and chemical vapor deposition in a vacuum chamber. The plasma treatment utilized a dielectric barrier discharge ionizing and decomposing the flame retardants into innocuous simple compounds. Wood samples are immersed in either phosphoric acid, boric acid, hydrogen or nitrogen plasmas or a plasma admixture of two or three compounds at various concentrations and impregnated by the ionized chemical reactants. Chemical changes on the wood samples were analyzed by Fourier transform infrared spectroscopy (FTIR) while the thermal changes through thermo gravimetric analysis (TGA). Plasma-treated samples exhibit superior thermal stability and fire retardant properties in terms of highest onset temperature, temperature of maximum pyrolysis, highest residual char percentage and comparably low total percentage weight loss.

  17. "Idiopathic" mental retardation and new chromosomal abnormalities

    PubMed Central

    2010-01-01

    Mental retardation is a heterogeneous condition, affecting 1-3% of general population. In the last few years, several emerging clinical entities have been described, due to the advent of newest genetic techniques, such as array Comparative Genomic Hybridization. The detection of cryptic microdeletion/microduplication abnormalities has allowed genotype-phenotype correlations, delineating recognizable syndromic conditions that are herein reviewed. With the aim to provide to Paediatricians a combined clinical and genetic approach to the child with cognitive impairment, a practical diagnostic algorithm is also illustrated. The use of microarray platforms has further reduced the percentage of "idiopathic" forms of mental retardation, previously accounted for about half of total cases. We discussed the putative pathways at the basis of remaining "pure idiopathic" forms of mental retardation, highlighting possible environmental and epigenetic mechanisms as causes of altered cognition. PMID:20152051

  18. Employee satisfactions in agencies serving retarded persons.

    PubMed

    Sarata, B P

    1975-01-01

    The work satisfactions of individuals employed by three agencies serving retarded persons were examined. The results contradicted the view held by most administrators that the individual's level of overall satisfaction is determined principally by his attitudes concerning employment in the field of mental retardation. Rather, the data suggest that satisfaction with the specific agency is the chief determinant of overall satisfaction. Extensive contact with clients and the perceived lack of client progress were found to be important sources of staff dissatisfaction. Finally, client-related dissatisfactions were often attributed to agency or staff deficiences. Implications for altering administrative practices were discussed. PMID:1115102

  19. [Considerations of psychopathology in mental retardation].

    PubMed

    Masi, G

    1994-06-01

    There is a high incidence of psychiatric disorders in mentally retarded subjects: one third to two thirds of mentally retarded subjects exhibit psychiatric disorders, a proportion which is much higher than that found in subjects with normal intelligence. The issue is to clarify the nature of the relationship between cognitive and psychiatric disorders (generally analyzed in a dichotomous approach). A way to analyze the phenomenon is to consider a psychopathological approach, which can define the underlying mechanisms responsible for this incidence. The aim of this paper is to analyze the explicatory value of deficient cognitive development, as the main factor determining a specific personality organization. Direct and indirect effects of cognitive impairment on the development of personality disorders are described: the first, in terms of how cognitive deficit (i.e. severity, homogeneity in several cognitive domains, pattern of development) disorganizes personality; the second, in terms of impact that cognitive deficit could have on the child's relationship with the external world, especially with the mother. In order to illustrate these viewpoint, the paper discusses the role of cognitive functions in the development of personality. Specifically, the way the normal child processes his perceptual and motor experiences is analyzed, that is pursuit of new causal links in his knowledge seeking activity of mastering the world. The child's primitive relationship with the world is then aimed at learning, exploring and searching for new causal links. In the light of these considerations, what the child with Mental Retardation experiences is discussed. A series of psychopathological mechanisms in Mental Retardation are postulated. The organization of the Mentally Retarded child's internal world is described, as reflected in Rorschach protocols, which outline a chaotic and primitive internal world, but with a specificity of its own. Finally, the paper discusses the

  20. ORO-DENTAL PATTERN IN MENTALLY RETARDED

    PubMed Central

    Tandon, Pradeep; Jha, Sanjeev; Tandon, Ragini; Sondhi, Deepak; Chandra, Mahesh; Trivedi, J.K.

    1990-01-01

    SUMMARY The study was carried out in 25 mentally retarded children and compared with equal number of normal children. They were subjected to detailed psychiatric evaluation and dental examination. The dental anomalies were corroborated with cephalometric analysis of lateral cephalograms. It was concluded that all mentally retarded children had some dental abnormality in them in form of dental malocclusion, wide inter dental spaces, absence of teeth etc. We suggest early dental management for such patients for reinforcing their neuromuscular coordination modifying the mastication power, swallowing, speech, stomatognathic function and above all their facial profile for better social acceptance. PMID:21927451

  1. Evolution, diversification, and expression of KNOX proteins in plants

    PubMed Central

    Gao, Jie; Yang, Xue; Zhao, Wei; Lang, Tiange; Samuelsson, Tore

    2015-01-01

    The KNOX (KNOTTED1-like homeobox) transcription factors play a pivotal role in leaf and meristem development. The majority of these proteins are characterized by the KNOX1, KNOX2, ELK, and homeobox domains whereas the proteins of the KNATM family contain only the KNOX domains. We carried out an extensive inventory of these proteins and here report on a total of 394 KNOX proteins from 48 species. The land plant proteins fall into two classes (I and II) as previously shown where the class I family seems to be most closely related to the green algae homologs. The KNATM proteins are restricted to Eudicots and some species have multiple paralogs of this protein. Certain plants are characterized by a significant increase in the number of KNOX paralogs; one example is Glycine max. Through the analysis of public gene expression data we show that the class II proteins of this plant have a relatively broad expression specificity as compared to class I proteins, consistent with previous studies of other plants. In G. max, class I protein are mainly distributed in axis tissues and KNATM paralogs are overall poorly expressed; highest expression is in the early plumular axis. Overall, analysis of gene expression in G. max demonstrates clearly that the expansion in gene number is associated with functional diversification. PMID:26557129

  2. Regulation of Plant Morphology by Growth Retardants

    PubMed Central

    Grossmann, Klaus; Kwiatkowski, Jacek; Siebecker, Heinrich; Jung, Johannes

    1987-01-01

    The effects of the growth retardants tetcyclacis, a norbornenodiazetine, and LAB 150 978, a dioxanylalkenyl triazole, on seedling growth and endogenous levels of phytohormone-like substances in Glycine max L. cv Maple Arrow were studied. The levels of phytohormone-like substances in the root and in the various shoot tissues were analyzed by immunoassay. After seed treatment with both compounds, shoot growth was reduced more intensively than root growth. Both compounds decreased, on a fresh weight basis, the amount of various immunoreactive gibberellins when compared with the levels in control plants, especially in the shoot tip. Likewise, the growth retardants lowered the levels of abscisic acid-like material, particularly in the primary leaf, the epicotyl and the root. In contrast, the levels of trans-zeatin-riboside and dihydrozeatin-riboside-type cytokinins were considerably elevated by the growth retardants, mainly in the primary leaf, epicotyl, and hypocotyl. On the other hand the level of isopentenyladenosine-like material was less influenced. In general, the immunoreactive 3-indoleacetic acid content in the different plant parts was changed only slightly. It is assumed that besides their effect on gibberellin content both compounds interfere directly or indirectly with the regulation of the endogenous levels of abscisic acid and cytokinins. This might be seen as an additional mode of action of growth retardants explaining some side effects on developmental processes of treated plants, e.g. delayed senescence and enhanced chlorophyll concentration in the leaves. PMID:16665554

  3. Puberty in the Girl Who is Retarded.

    ERIC Educational Resources Information Center

    Pattullo, Ann

    Designed to help mothers of mentally retarded girls deal with the problems and concerns of puberty, the booklet provides information on physical and emotional changes, menstruation, masturbation, heterosexual behavior, contraception, protection against sexual aggression, the possibilities of marriage, and additional sources of information.…

  4. Improving Outcomes for Workers with Mental Retardation

    ERIC Educational Resources Information Center

    Fornes, Sandra; Rocco, Tonette S.; Rosenberg, Howard

    2008-01-01

    This research presents an analysis of factors predicting job retention, job satisfaction, and job performance of workers with mental retardation. The findings highlight self-determination as a critical skill in predicting the three important employee outcomes. The study examined a hypothesized job retention model and the outcome of the three…

  5. Alpha Biofeedback Conditioning and Retarded Subjects.

    ERIC Educational Resources Information Center

    Martin, Walter; And Others

    1981-01-01

    An experimental group of three institutionalized severely retarded adult males received binary tone feedback for alpha production while a control group (3) followed identical procedures without feedback. Analysis revealed significant difference between groups in alpha percentage increase over baseline, encouraging research on applications for…

  6. Halfway Houses for the Mildly Retarded.

    ERIC Educational Resources Information Center

    Gia, Gilbert P.

    Investigated were number and location of community residences or halfway houses (of fewer than 61 persons) for the mildly retarded and their programing practices. Form letters and questionnaires uncovered 68 programs meeting internal delimitations of the study. Programs were categorized for analysis purposes into California Programs, New Programs…

  7. New fire retardant foams and intumescents

    NASA Technical Reports Server (NTRS)

    Parker, J. A.

    1972-01-01

    The development of fire retardant foams and intumescent paints for protection of commercial aircraft passengers in the event of fire is discussed. Recommended materials and methods for evaluating the effectiveness of the materials are presented. Typical problems resulting from aircraft fires and the basic protective mechanisms to cope with these problems are examined.

  8. BROMINATED FLAME RETARDANTS: CAUSE FOR CONCERN?

    EPA Science Inventory

    Brominated flame retardants (BFRs) have routinely been added to consumer products for several decades in a successful effort to reduce fire-related injury and property damage. Recently, concern for this emerging class of chemicals has risen due to the occurrence of several class...

  9. Perception of Contingency and Mental Retardation.

    ERIC Educational Resources Information Center

    DeVellis, Robert F.; McCauley, Charley

    1979-01-01

    It is argued that the general learning difficulties exhibited by mentally retarded persons are similar in many respects to the learning difficulties of nonretarded persons who are in a state of learned helplessness (M. Seligman, 1975) or who are external in locus of control orientation. (Author)

  10. Vocational Horticulture for Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Kern, William H.; And Others

    The study explored methods and techniques for training mentally retarded adults to perform gardening tasks. A total of 31 subjects ages 21 to 48 (IQ range 32-89) participated in the study, which consisted of three phases. In an initial pilot study, experimentation without subjects resulted in the development of modified tools (e.g., notched…

  11. HEALTH EFFECTS OF BROMINATED FLAME RETARDANTS (BFRS)

    EPA Science Inventory

    Abstract Brominated flame retardant use has increased dramatically in order to provide fire safety to consumers. However, there is growing concern about widespread environmental contamination and potential health risks from some of these products. The most used products...

  12. Aging, Mental Retardation and Physical Fitness.

    ERIC Educational Resources Information Center

    Rimmer, James H.

    This fact sheet uses a question-and-answer format to provide an overview of what physical fitness is and how it relates to people with mental retardation. Questions address the following topics: the fitness movement; a definition of physical fitness; the different components of physical fitness (muscle strength and endurance, flexibility, body…

  13. Euthanasia and Mental Retardation: Suggesting the Unthinkable.

    ERIC Educational Resources Information Center

    Hollander, Russell

    1989-01-01

    The article examines current opinions toward euthanasia of persons with mental retardation in light of the history of public and professional attitudes. It also discusses the rejection of euthanasia on moral and religious grounds, and notes the use of lifelong incarceration, based on eugenics principles, to accomplish similar ends. (DB)

  14. BROMINATED FLAME RETARDANTS: WHY DO WE CARE?

    EPA Science Inventory

    Brominated flame retardants (BFRs) save lives and property by preventing the spread of fires or delaying the time of flashover, enhancing the time people have to escape. The worldwide production of BFRs exceeded 200,000 metric tons in 2003 placing them in the high production vol...

  15. CURRICULUM GUIDE FOR TRAINABLE RETARDED CHILDREN.

    ERIC Educational Resources Information Center

    Webster County Superintendent of Schools Office, Ft. Dodge, IA.

    ELIGIBILITY FOR ADMISSION, ADMINISTRATIVE PRACTICES, AND EDUCATIONAL OBJECTIVES ARE DISCUSSED. CHARACTERISTICS OF THESE TRAINABLE MENTALLY RETARDED CHILDREN ARE DESCRIBED, AND DAILY SCHEDULES FOR YOUNGER AND OLDER GROUPS ARE LISTED. TEACHING SUGGESTIONS ARE PRESENTED FOR SOCIAL ADJUSTMENT (INCLUDING SELF-CARE), ECONOMIC USEFULNESS, ACADEMIC…

  16. HEALTH ASPECTS OF BROMINATED FLAME RETARDANTS (BFRS)

    EPA Science Inventory

    In order to reduce the societal costs of fires, flammability standards have been set for consumer products and equipment. Flame retardants containing bromine have constituted the largest share of this market due both to their efficiency and cost. While there are at least 75 dif...

  17. READINESS AND READING FOR THE RETARDED CHILD.

    ERIC Educational Resources Information Center

    BERNSTEIN, BEBE

    THIS TEACHER'S BOOK AND MANUAL, DESIGNED TO ACCOMPANY TWO WORKBOOKS, PRESENTS A FUNCTIONAL APPROACH TO READINESS AND READING FOR YOUNG EDUCABLE RETARDED CHILDREN. THE WORKBOOKS THEMSELVES OFFER PREPARATORY ACTIVITIES FOR CHILDREN AT THE READINESS LEVEL AND SEQUENTIAL ACTIVITIES AND MATERIALS FOR THOSE AT THE BEGINNING READING STAGE. THE TEACHER'S…

  18. Bibliographic Instruction for Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Norlin, Dennis A.

    Conducted as part of a practicum to be completed at the Champaign (Illinois) Public Library and Information Center, this study was designed to view the availability of appropriate bibliographic instruction for adults who are mentally retarded that will enhance both their ability to use library resources and equipment, and their desire to do so.…

  19. Novel additives to retard permeable flow

    SciTech Connect

    Golombok, Michael; Crane, Carel; Ineke, Erik; Welling, Marco; Harris, Jon

    2008-09-15

    Low concentrations of surfactant and cosolute in water, can selectively retard permeable flow in high permeability rocks compared to low permeability ones. This represents a way forward for more efficient areal sweep efficiency when water flooding a reservoir during improved oil recovery. (author)

  20. Language Transference by Mentally Retarded Spanish Speakers.

    ERIC Educational Resources Information Center

    Flaherty, Carol

    In an investigation of language transference vs. language interference, 12 trainable mentally retarded Spanish speakers (5 to 9 years old) were trained to name in English objects previously identified receptively and objects not previously identified receptively in Spanish. Results indicated no significant difference in the number of words learned…

  1. Operant conditioning of mental retardates' visual monitoring.

    PubMed

    Perryman, R E; Halcomb, C R; Landers, W F

    1981-10-01

    To study improvement of visual monitoring of retardates, specialized training methods backed up by incentives were used. The extent to which these training techniques might be expected to produce results which would generalize to those situations in which the retardate was required to monitor without the increased signal rate and knowledge of results was explored. Subjects were 8 female mental retardates with IQs from 38 to 69. Detection of an aperiodic pattern change during pre-training was compared with final performance after 4 training sessions. During training, the task difficulty was increased until during the final training session it approximated the test conditions. Immediate knowledge of results was given for correct detections and false positive responses. Tokens were given to the subjects, based on the scores at the end of the session. After the final session these tokens were exchanged for prizes. As predicted, training under these conditions significantly enhanced the retardates' performance and transferred to the condition with no knowledge of results.

  2. Mental Retardation: Past, Present and Future

    ERIC Educational Resources Information Center

    Crissey, Marie Skodak

    1975-01-01

    Notes that two developments had major impacts on policies towards the mentally retarded between the 1880s and the 1920s: (1) the swing toward the eugenics-heredity-genetics movement, and (2) the development of individual intelligence testing. (Author/JM)

  3. Abandoning the Myth of Mental Retardation

    ERIC Educational Resources Information Center

    Smith, J. David

    2003-01-01

    In this article, the author talks about the concept underlying the term metal retardation and the effort to define it in a way that is scientifically accurate and in a way that promotes greater sensitivity to the needs of people described by the term which has been continuous for centuries. The author states that a scientifically sound and…

  4. Brominated flame retardants as food contaminants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter reviews analytical methods for the three major brominated flame retardant (BFR) classes in use today, tetrabromobisphenol-A (TBBP-A), hexabromocyclododecanes (HBCDs), and polybrominated diphenyl ethers (PBDEs), a "legacy" BFR no longer in use, polybrominated biphenyls (PBBs), and a...

  5. Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs.

    PubMed

    Tanabe, Lauren M; Liang, Chun-Chi; Dauer, William T

    2016-09-20

    DYT1 dystonia is a neurodevelopmental disease that manifests during a discrete period of childhood. The disease is caused by impaired function of torsinA, a protein linked to nuclear membrane budding. The relationship of NE budding to neural development and CNS function is unclear, however, obscuring its potential role in dystonia pathogenesis. We find NE budding begins and resolves during a discrete neurodevelopmental window in torsinA null neurons in vivo. The developmental resolution of NE budding corresponds to increased torsinB protein, while ablating torsinB from torsinA null neurons prevents budding resolution and causes lethal neural dysfunction. Developmental changes in torsinB also correlate with NE bud formation in differentiating DYT1 embryonic stem cells, and overexpression of torsinA or torsinB rescues NE bud formation in this system. These findings identify a torsinA neurodevelopmental window that is essential for normal CNS function and have important implications for dystonia pathogenesis and therapeutics. PMID:27653693

  6. Expression of paralogous SEP-, FUL-, AG- and STK-like MADS-box genes in wild-type and peloric Phalaenopsis flowers.

    PubMed

    Acri-Nunes-Miranda, Roberta; Mondragón-Palomino, Mariana

    2014-01-01

    The diverse flowers of Orchidaceae are the result of several major morphological transitions, among them the most studied is the differentiation of the inner median tepal into the labellum, a perianth organ key in pollinator attraction. Type A peloria lacking stamens and with ectopic labella in place of inner lateral tepals are useful for testing models on the genes specifying these organs by comparing their patterns of expression between wild-type and peloric flowers. Previous studies focused on DEFICIENS- and GLOBOSA-like MADS-box genes because of their conserved role in perianth and stamen development. The "orchid code" model summarizes this work and shows in Orchidaceae there are four paralogous lineages of DEFICIENS/AP3-like genes differentially expressed in each floral whorl. Experimental tests of this model showed the conserved, higher expression of genes from two specific DEF-like gene lineages is associated with labellum development. The present study tests whether eight MADS-box candidate SEP-, FUL-, AG-, and STK-like genes have been specifically duplicated in the Orchidaceae and are also differentially expressed in association with the distinct flower organs of Phalaenopsis hyb. "Athens." The gene trees indicate orchid-specific duplications. In a way analogous to what is observed in labellum-specific DEF-like genes, a two-fold increase in the expression of SEP3-like gene PhaMADS7 was measured in the labellum-like inner lateral tepals of peloric flowers. The overlap between SEP3-like and DEF-like genes suggests both are associated with labellum specification and similar positional cues determine their domains of expression. In contrast, the uniform messenger levels of FUL-like genes suggest they are involved in the development of all organs and their expression in the ovary suggests cell differentiation starts before pollination. As previously reported AG-like and STK-like genes are exclusively expressed in gynostemium and ovary, however no evidence for

  7. Expression of paralogous SEP-, FUL-, AG- and STK-like MADS-box genes in wild-type and peloric Phalaenopsis flowers

    PubMed Central

    Acri-Nunes-Miranda, Roberta; Mondragón-Palomino, Mariana

    2014-01-01

    The diverse flowers of Orchidaceae are the result of several major morphological transitions, among them the most studied is the differentiation of the inner median tepal into the labellum, a perianth organ key in pollinator attraction. Type A peloria lacking stamens and with ectopic labella in place of inner lateral tepals are useful for testing models on the genes specifying these organs by comparing their patterns of expression between wild-type and peloric flowers. Previous studies focused on DEFICIENS- and GLOBOSA-like MADS-box genes because of their conserved role in perianth and stamen development. The “orchid code” model summarizes this work and shows in Orchidaceae there are four paralogous lineages of DEFICIENS/AP3-like genes differentially expressed in each floral whorl. Experimental tests of this model showed the conserved, higher expression of genes from two specific DEF-like gene lineages is associated with labellum development. The present study tests whether eight MADS-box candidate SEP-, FUL-, AG-, and STK-like genes have been specifically duplicated in the Orchidaceae and are also differentially expressed in association with the distinct flower organs of Phalaenopsis hyb. “Athens.” The gene trees indicate orchid-specific duplications. In a way analogous to what is observed in labellum-specific DEF-like genes, a two-fold increase in the expression of SEP3-like gene PhaMADS7 was measured in the labellum-like inner lateral tepals of peloric flowers. The overlap between SEP3-like and DEF-like genes suggests both are associated with labellum specification and similar positional cues determine their domains of expression. In contrast, the uniform messenger levels of FUL-like genes suggest they are involved in the development of all organs and their expression in the ovary suggests cell differentiation starts before pollination. As previously reported AG-like and STK-like genes are exclusively expressed in gynostemium and ovary, however no

  8. Guidelines for Library Services for People with Mental Retardation.

    ERIC Educational Resources Information Center

    Association of Specialized and Cooperative Library Agencies, Chicago, IL.

    This guide is designed to assist all libraries, including school, public, academic, and specialized libraries such as prison and institutional libraries, to better serve the needs of people of all ages who are mentally retarded. An overview provides a definition of mental retardation, places services for people with mental retardation in…

  9. 40 CFR 201.14 - Standard for retarders.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Standard for retarders. 201.14 Section... Operations Standards § 201.14 Standard for retarders. Effective January 15, 1984, no carrier subject to this regulation shall operate retarders that exceed an adjusted average maximum A-weighted sound level of 83 dB...

  10. Neuropsychological Profiles of Persons with Mental Retardation and Dementia

    ERIC Educational Resources Information Center

    Palmer, Glen A.

    2006-01-01

    This study examined the use of neuropsychological tests to assist in the differential diagnosis of dementia among persons with mental retardation. The author compared performances of persons with mental retardation and dementia ("n" = 10) to persons with mental retardation without dementia ("n" = 12). Participants were matched by IQ (mild or…

  11. Mental Retardation: The Search for Cures. Research Monograph Number 7.

    ERIC Educational Resources Information Center

    Menolascino, Frank J.; Neman, Ronald

    The booklet describes the Association for Retarded Citizens' (ARC's) goal of coordinating efforts to seek a cure for mental retardation. Cures are defined as any intervention that would significantly increase intellectual functioning and adaptive behavior beyond the upper level of retardation. It is explained that because of the variety of causes…

  12. Low Elevated Lead Levels and Mild Mental Retardation.

    ERIC Educational Resources Information Center

    Marlowe, Mike; And Others

    To investigate the relation between low level lead absorption and mild mental retardation, hair lead concentrations were compared in a group of 40 mildly retarded children "etiology unknown" with a control group of 20 children. Children with probable cause for retardation were excluded from the sample as were children with a history of lead…

  13. Cardiovascular Risk Factor Levels in Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Rimmer, James H.; And Others

    1994-01-01

    Comparison of cardiovascular risk factors (blood lipids, obesity, and smoking) in 329 adults with mental retardation residing in various settings with subjects in the Framingham Offspring Study found that adults with mental retardation had cardiovascular risk profiles similar to those of individuals without mental retardation. (Author/DB)

  14. Conjunctive Visual Search in Individuals with and without Mental Retardation

    ERIC Educational Resources Information Center

    Carlin, Michael; Chrysler, Christina; Sullivan, Kate

    2007-01-01

    A comprehensive understanding of the basic visual and cognitive abilities of individuals with mental retardation is critical for understanding the basis of mental retardation and for the design of remediation programs. We assessed visual search abilities in individuals with mild mental retardation and in MA- and CA-matched comparison groups. Our…

  15. Characterization of a generalized elliptical phase retarder by using equivalent theorem of a linear phase retarder and a polarization rotator

    NASA Astrophysics Data System (ADS)

    Yu, Chih-Jen; Chou, Chien

    2011-03-01

    An equivalence theory based on a unitary optical system of a generalized elliptical phase retarder was derived. Whereas the elliptical phase retarder can be treated as the combination of a linear phase retarder and a polarization rotator equivalently. Three fundamental parameters, including the elliptical phase retardation, the azimuth angle and the ellipticity angle of the fast elliptical eigen-polarization state were derived. All parameters of a generalized elliptical phase retarder can be determined from the analytical solution of the characteristic parameters of the optical components: linear phase retardation and fast axis angle of the equivalently linear phase retarder respectively, and polarization rotation angle of an equivalent polarization rotator. In this study, the experimental verification was demonstrated by testing a twisted nematic liquid crystal device (TNLCD) treated as a generalized elliptical phase retarder. A dual-frequency heterodyne ellipsometer was setup and the experimental result demonstrates the capability of the equivalent theory on elliptical birefringence measurement at high sensitivity by using heterodyne technique.

  16. Comprehensive Genetic Analysis of Paralogous Terminal Septin Subunits Shs1 and Cdc11 in Saccharomyces cerevisiae

    PubMed Central

    Finnigan, Gregory C.; Takagi, Julie; Cho, Christina; Thorner, Jeremy

    2015-01-01

    Septins are a family of GTP-binding proteins considered to be cytoskeletal elements because they self-assemble into filaments and other higher-order structures in vivo. In budding yeast, septins establish a diffusion barrier at the bud neck between a mother and daughter cell, promote membrane curvature there, and serve as a scaffold to recruit other proteins to the site of cytokinesis. However, the mechanism by which any septin engages a partner protein has been unclear. The two most related and recently evolved subunits appear to be Cdc11 and Shs1, and the basic building blocks for assembling septin structures are hetero-octameric rods (Cdc11–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11 and Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Shs1). Loss of Cdc11 is not normally tolerated, whereas cells lacking Shs1 do not appear grossly abnormal. We established several different sensitized genetic backgrounds wherein Shs1 is indispensable, which allowed us to carry out the first comprehensive and detailed genetic analysis of Shs1 in vivo. Our analysis revealed several novel insights, including: (i) the sole portion of Shs1 essential for its function is a predicted coiled-coil-forming segment in its C-terminal extension (CTE); (ii) the CTE of Cdc11 shares this function; (iii) this role for the CTEs of Cdc11 and Shs1 is quite distinct from that of the CTEs of Cdc3 and Cdc12; and (iv) heterotypic Cdc11 and Shs1 junctions likely occur in vivo. Related article in GENETICS: Finnigan, G. C. et al., 2015 The Carboxy-Terminal Tails of Septins Cdc11 and Shs1 Recruit Myosin-II Binding Factor Bni5 to the Bud Neck in Saccharomyces cerevisiae. Genetics 200: 843–862. PMID:25971665

  17. Divergent evolutionary and expression patterns between lineage specific new duplicate genes and their parental paralogs in Arabidopsis thaliana.

    PubMed

    Wang, Jun; Marowsky, Nicholas C; Fan, Chuanzhu

    2013-01-01

    Gene duplication is an important mechanism for the origination of functional novelties in organisms. We performed a comparative genome analysis to systematically estimate recent lineage specific gene duplication events in Arabidopsis thaliana and further investigate whether and how these new duplicate genes (NDGs) play a functional role in the evolution and adaption of A. thaliana. We accomplished this using syntenic relationship among four closely related species, A. thaliana, A. lyrata, Capsella rubella and Brassica rapa. We identified 100 NDGs, showing clear origination patterns, whose parental genes are located in syntenic regions and/or have clear orthologs in at least one of three outgroup species. All 100 NDGs were transcribed and under functional constraints, while 24% of the NDGs have differential expression patterns compared to their parental genes. We explored the underlying evolutionary forces of these paralogous pairs through conducting neutrality tests with sequence divergence and polymorphism data. Evolution of about 15% of NDGs appeared to be driven by natural selection. Moreover, we found that 3 NDGs not only altered their expression patterns when compared with parental genes, but also evolved under positive selection. We investigated the underlying mechanisms driving the differential expression of NDGs and their parents, and found a number of NDGs had different cis-elements and methylation patterns from their parental genes. Overall, we demonstrated that NDGs acquired divergent cis-elements and methylation patterns and may experience sub-functionalization or neo-functionalization influencing the evolution and adaption of A. thaliana.

  18. Functional Studies of Heading Date-Related Gene TaPRR73, a Paralog of Ppd1 in Common Wheat.

    PubMed

    Zhang, Wenping; Zhao, Guangyao; Gao, Lifeng; Kong, Xiuying; Guo, Zhiai; Wu, Bihua; Jia, Jizeng

    2016-01-01

    Photoperiod response-related genes play a crucial role in duration of the plant growth. In this study, we focused on TaPRR73, a paralog of "Green Revolution" gene Ppd1 (TaPRR37). We found that overexpression of the truncated TaPRR73 form lacking part of the N-terminal PR domain in transgenic rice promoted heading under long day conditions. Association analysis in common wheat verified that TaPRR73 was an important agronomic photoperiod response gene that significantly affected heading date and plant height; expression analysis proved that specific alleles of TaPRR73-A1 had highly expressed levels in earlier heading lines; the distribution of haplotypes indicated that one of these alleles had been selected in breeding programs. Our results demonstrated that TaPRR73 contributed to regulation of heading date in wheat and could be useful in wheat breeding and in broadening adaptation of the crop to new regions. PMID:27313595

  19. Functional Studies of Heading Date-Related Gene TaPRR73, a Paralog of Ppd1 in Common Wheat

    PubMed Central

    Zhang, Wenping; Zhao, Guangyao; Gao, Lifeng; Kong, Xiuying; Guo, Zhiai; Wu, Bihua; Jia, Jizeng

    2016-01-01

    Photoperiod response-related genes play a crucial role in duration of the plant growth. In this study, we focused on TaPRR73, a paralog of “Green Revolution” gene Ppd1 (TaPRR37). We found that overexpression of the truncated TaPRR73 form lacking part of the N-terminal PR domain in transgenic rice promoted heading under long day conditions. Association analysis in common wheat verified that TaPRR73 was an important agronomic photoperiod response gene that significantly affected heading date and plant height; expression analysis proved that specific alleles of TaPRR73-A1 had highly expressed levels in earlier heading lines; the distribution of haplotypes indicated that one of these alleles had been selected in breeding programs. Our results demonstrated that TaPRR73 contributed to regulation of heading date in wheat and could be useful in wheat breeding and in broadening adaptation of the crop to new regions. PMID:27313595

  20. Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein in murine breast cancer induces distinct vascular patterning adjacent to tumors and retarded tumor growth.

    PubMed

    Zhang, Hui-Yong; Fan, Bing-Lin; Wu, Xin-Sheng; Mu, Ling-Min; Wang, Wen-Feng; Zhu, Wu-Ling

    2015-02-01

    A chimeric plasmin‑resistant vascular endothelial growth factor (VEGF)165/VEGF183 (132-158) protein, named as VEGF183 (according to the nomenclature of VEGF), designed by a previous study, was demonstrated to have an enhanced affinity for the extracellular matrix (ECM) amongst other bioactivities. However, it is now accepted that mutant VEGFs frequently demonstrate different angiogenic activities and produce different vascular patterning from the parental molecule. The present study hypothesized that VEGF183, due to its enhanced binding affinity to the ECM, would exhibit a different angiogenic activity and produce a different vascular patterning compared to those of VEGF165. Murine breast cancer EMT‑6 cells were manipulated to stably overexpress VEGF165 or VEGF183. These cells were then inoculated intradermally into BALB/c mice in order to monitor the formation of vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments revealed that overexpression of VEGF183 in murine breast cancer cells resulted in irregular, disorganized and dense vascular patterning as well as induced a significant inhibition of tumor growth compared with that of VEGF165. In addition, allograft tumor immunochemical assays of VEGF183‑overexpressing tumors demonstrated significantly lower vascular densities than those of VEGF165‑overexpressing tumors; however, VEGF183 tumors had a significantly enlarged vascular caliber. Conversely, cell wound healing experiments revealed that VEGF183‑overexpressing EMT‑6 cells had significantly decreased migration rates compared with those of VEGF165‑overexpressing EMT‑6 cells. In conclusion, the results of the present study supported the hypothesis that the altered ECM affinity of VEGF induced structural alterations to vasculature. In addition, these results provided a novel insight into VEGF design and indirect evidence for the function of exon 8 in VEGF. [Corrected] PMID:25373557

  1. Difference in larval type explains patterns of nonsynonymous substitutions in two ancient paralogs of the histone H3 gene in sea stars.

    PubMed

    Foltz, David W; Mah, Christopher L

    2010-01-01

    Paralogous genes frequently show differences in patterns and rates of substitution that are typically attributed to different selection regimes, mutation rates, or local recombination rates. Here, two anciently diverged paralogous copies of the histone H3 gene in sea stars, the tandem-repetitive early-stage gene and a newly isolated gene with lower copy number that was termed the "putative late-stage histone H3 gene" were analyzed in 69 species with varying mode of larval development. The two genes showed differences in relative copy number, overall substitution rates, nucleotide composition, and codon usage, but similar patterns of relative nonsynonymous substitution rates, when analyzed by the d(N)/d(S) ratio. Sea stars with a nonpelagic and nonfeeding larval type (i.e., brooding lineages) were observed to have d(N)/d(S) ratios that were larger than for nonbrooders but equal between the two paralogs. This finding suggested that demographic differences between brooding and nonbrooding lineages were responsible for the elevated d(N)/d(S) ratios observed for brooders and refuted a suggestion from a previous analysis of the early-stage gene that the excess nonsynonymous substitutions were due to either (1) gene expression differences at the larval stage between brooders and nonbrooders or (2) the highly repetitive structure of the early-stage histone H3 gene.

  2. Functions of Ceramide Synthase Paralogs YPR114w and YJR116w of Saccharomyces cerevisiae

    PubMed Central

    Mallela, Shamroop K.; Almeida, Reinaldo; Ejsing, Christer S.; Conzelmann, Andreas

    2016-01-01

    Ceramide is synthesized in yeast by two redundant acyl-CoA dependent synthases, Lag1 and Lac1. In lag1∆ lac1∆ cells, free fatty acids and sphingoid bases are elevated, and ceramides are produced through the redundant alkaline ceramidases Ypc1 and Ydc1, working backwards. Even with all four of these genes deleted, cells are surviving and continue to contain small amounts of complex sphingolipids. Here we show that these residual sphingolipids are not synthesized by YPR114w or YJR116w, proteins of unknown function showing a high degree of homology to Lag1 and Lac1. Indeed, the hextuple lag1∆ lac1∆ ypc1∆ ydc1∆ ypr114w∆ yjr116w∆ mutant still contains ceramides and complex sphingolipids. Yjr116w∆ exhibit an oxygen-dependent hypersensitivity to Cu2+ due to an increased mitochondrial production of reactive oxygen species (ROS) and a mitochondrially orchestrated programmed cell death in presence of copper, but also a general copper hypersensitivity that cannot be counteracted by the antioxidant N-acetyl-cysteine (NAC). Myriocin efficiently represses the synthesis of sphingoid bases of ypr114w∆, but not its growth. Both yjr116w∆ and ypr114w∆ have fragmented vacuoles and produce less ROS than wild type, before and after diauxic shift. Ypr114w∆/ypr114w∆ have an increased chronological life span. Thus, Yjr116w and Ypr114w are related, but not functionally redundant. PMID:26752183

  3. Functions of Ceramide Synthase Paralogs YPR114w and YJR116w of Saccharomyces cerevisiae.

    PubMed

    Mallela, Shamroop K; Almeida, Reinaldo; Ejsing, Christer S; Conzelmann, Andreas

    2016-01-01

    Ceramide is synthesized in yeast by two redundant acyl-CoA dependent synthases, Lag1 and Lac1. In lag1∆ lac1∆ cells, free fatty acids and sphingoid bases are elevated, and ceramides are produced through the redundant alkaline ceramidases Ypc1 and Ydc1, working backwards. Even with all four of these genes deleted, cells are surviving and continue to contain small amounts of complex sphingolipids. Here we show that these residual sphingolipids are not synthesized by YPR114w or YJR116w, proteins of unknown function showing a high degree of homology to Lag1 and Lac1. Indeed, the hextuple lag1∆ lac1∆ ypc1∆ ydc1∆ ypr114w∆ yjr116w∆ mutant still contains ceramides and complex sphingolipids. Yjr116w∆ exhibit an oxygen-dependent hypersensitivity to Cu2+ due to an increased mitochondrial production of reactive oxygen species (ROS) and a mitochondrially orchestrated programmed cell death in presence of copper, but also a general copper hypersensitivity that cannot be counteracted by the antioxidant N-acetyl-cysteine (NAC). Myriocin efficiently represses the synthesis of sphingoid bases of ypr114w∆, but not its growth. Both yjr116w∆ and ypr114w∆ have fragmented vacuoles and produce less ROS than wild type, before and after diauxic shift. Ypr114w∆/ypr114w∆ have an increased chronological life span. Thus, Yjr116w and Ypr114w are related, but not functionally redundant. PMID:26752183

  4. Functions of Ceramide Synthase Paralogs YPR114w and YJR116w of Saccharomyces cerevisiae.

    PubMed

    Mallela, Shamroop K; Almeida, Reinaldo; Ejsing, Christer S; Conzelmann, Andreas

    2016-01-01

    Ceramide is synthesized in yeast by two redundant acyl-CoA dependent synthases, Lag1 and Lac1. In lag1∆ lac1∆ cells, free fatty acids and sphingoid bases are elevated, and ceramides are produced through the redundant alkaline ceramidases Ypc1 and Ydc1, working backwards. Even with all four of these genes deleted, cells are surviving and continue to contain small amounts of complex sphingolipids. Here we show that these residual sphingolipids are not synthesized by YPR114w or YJR116w, proteins of unknown function showing a high degree of homology to Lag1 and Lac1. Indeed, the hextuple lag1∆ lac1∆ ypc1∆ ydc1∆ ypr114w∆ yjr116w∆ mutant still contains ceramides and complex sphingolipids. Yjr116w∆ exhibit an oxygen-dependent hypersensitivity to Cu2+ due to an increased mitochondrial production of reactive oxygen species (ROS) and a mitochondrially orchestrated programmed cell death in presence of copper, but also a general copper hypersensitivity that cannot be counteracted by the antioxidant N-acetyl-cysteine (NAC). Myriocin efficiently represses the synthesis of sphingoid bases of ypr114w∆, but not its growth. Both yjr116w∆ and ypr114w∆ have fragmented vacuoles and produce less ROS than wild type, before and after diauxic shift. Ypr114w∆/ypr114w∆ have an increased chronological life span. Thus, Yjr116w and Ypr114w are related, but not functionally redundant.

  5. Identification of target genes for a prolactin family paralog in mouse decidua.

    PubMed

    Alam, S M Khorshed; Konno, Toshihiro; Soares, Michael J

    2015-06-01

    Prolactin family 8, subfamily a, member 2 (PRL8A2; also called decidual prolactin-related protein; dPRP) is a member of the expanded prolactin family. PRL8A2 is expressed in the uterine decidua and contributes to pregnancy-dependent adaptations to hypoxia. The purpose of this study was to identify gene targets for PRL8A2 action within the uteroplacental compartment. Affymetrix DNA microarray analysis was performed for RNA samples from WT and Prl8a2 null tissues. Validation of the DNA microarray was performed using quantitative RT-PCR. Nine genes were confirmed with decreased expression in Prl8a2 null tissues (e.g., Klk7, Rimklb, Arhgef6, Calm4, Sprr2h, Prl4a1, Ccl27, Lipg, and Htra3). These include potential decidual, endothelial and trophoblast cell targets positively regulated by PRL8A2. A significant upregulation of Derl3, Herpud1, Creld2, Hsp90b1, Ddit3 and Hspa5 was identified in Prl8a2 null tissues, reflecting an increased endoplasmic reticulum (ER) stress response. ER stress genes were prominently expressed in the uterine decidua. We propose that PRL8A2 is a mediator of progesterone-dependent modulation of intrauterine responses to physiological stressors.

  6. A Prolactin Family Paralog Regulates Placental Adaptations to a Physiological Stressor.

    PubMed

    Bu, Pengli; Alam, Sheikh M Khorshed; Dhakal, Pramod; Vivian, Jay L; Soares, Michael J

    2016-05-01

    The prolactin (PRL) family of hormones and cytokines participates in the regulation of optimal reproductive performance in the mouse and rat. Members of the PRL family are expressed in the anterior pituitary, uterus, and/or placenta. In the present study, we investigated the ontogeny of PRL family 7, subfamily b, member 1 (PRL7B1; also called PRL-like protein-N, PLP-N) expression in the developing mouse placenta and established a mouse model for investigating the biological function of PRL7B1. Transcripts for Prl7b1 were first detected on Gestation Day (d) 8.5. From gestation d8.5 through d14.5, Prl7b1 was expressed in trophoblast cells residing at the interface between maternal mesometrial decidua and the developing placenta. On gestation d17.5, the predominant cellular source of Prl7b1 mRNA was migratory trophoblast cells invading into the uterine mesometrial decidua. The Prl7b1 null mutant allele was generated via replacement of the endogenous Prl7b1 coding sequence with beta-galactosidase (LacZ) reporter and neomycin cassettes. The mutant Prl7b1 allele was successfully passed through the germline. Homozygous Prl7b1 mutant mice were viable and fertile. Under standard animal housing conditions, Prl7b1 had undetectable effects on placentation and pregnancy. Hypoxia exposure during pregnancy evoked adaptations in the organization of the wild-type placenta that were not observed in Prl7b1 null placentation sites. In summary, PRL7B1 is viewed as a part of a pathway regulating placental adaptations to physiological stressors.

  7. Chemistry and toxicity of flame retardants for plastics.

    PubMed

    Liepins, R; Pearce, E M

    1976-10-01

    An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products.

  8. Chemistry and toxicity of flame retardants for plastics.

    PubMed Central

    Liepins, R; Pearce, E M

    1976-01-01

    An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products. PMID:1026419

  9. A field work experience in mental retardation.

    PubMed

    Beardslee, G R

    1976-01-01

    A graduate student specializing in mental retardation found few pertinent electives as well as little opportunity for field work experience. A special arrangement was made for appropriate field work experiences in three types of settings--a large residential institution, school programs, and nursing care facilities. There was little time to view client changes, and rapport with patients and staff was difficult to develop. The advantages included more time with her supervisor, more exposure to organizational and administrative duties, and more exposure to a variety of settings and to the professional roles of numerous therapists. More such field work experiences should be developed to encourage new therapists to choose mental retardation as a specialty. PMID:984162

  10. Brominated flame retardants: cause for concern?

    PubMed Central

    Birnbaum, Linda S; Staskal, Daniele F

    2004-01-01

    Brominated flame retardants (BFRs) have routinely been added to consumer products for several decades in a successful effort to reduce fire-related injury and property damage. Recently, concern for this emerging class of chemicals has risen because of the occurrence of several classes of BFRs in the environment and in human biota. The widespread production and use of BFRs; strong evidence of increasing contamination of the environment, wildlife, and people; and limited knowledge of potential effects heighten the importance of identifying emerging issues associated with the use of BFRs. In this article, we briefly review scientific issues associated with the use of tetrabromobisphenol A, hexabromocyclododecane, and three commercial mixtures of polybrominated diphenyl ethers and discuss data gaps. Overall, the toxicology database is very limited; the current literature is incomplete and often conflicting. Available data, however, raise concern over the use of certain classes of brominated flame retardants. PMID:14698924

  11. Cloning and characterization of the promoter regions from the parent and paralogous creatine transporter genes.

    PubMed

    Ndika, Joseph D T; Lusink, Vera; Beaubrun, Claudine; Kanhai, Warsha; Martinez-Munoz, Cristina; Jakobs, Cornelis; Salomons, Gajja S

    2014-01-10

    Interconversion between phosphocreatine and creatine, catalyzed by creatine kinase is crucial in the supply of ATP to tissues with high energy demand. Creatine's importance has been established by its use as an ergogenic aid in sport, as well as the development of intellectual disability in patients with congenital creatine deficiency. Creatine biosynthesis is complemented by dietary creatine uptake. Intracellular transport of creatine is carried out by a creatine transporter protein (CT1/CRT/CRTR) encoded by the SLC6A8 gene. Most tissues express this gene, with highest levels detected in skeletal muscle and kidney. There are lower levels of the gene detected in colon, brain, heart, testis and prostate. The mechanism(s) by which this regulation occurs is still poorly understood. A duplicated unprocessed pseudogene of SLC6A8-SLC6A10P has been mapped to chromosome 16p11.2 (contains the entire SLC6A8 gene, plus 2293 bp of 5'flanking sequence and its entire 3'UTR). Expression of SLC6A10P has so far only been shown in human testis and brain. It is still unclear as to what is the function of SLC6A10P. In a patient with autism, a chromosomal breakpoint that intersects the 5'flanking region of SLC6A10P was identified; suggesting that SLC6A10P is a non-coding RNA involved in autism. Our aim was to investigate the presence of cis-acting factor(s) that regulate expression of the creatine transporter, as well as to determine if these factors are functionally conserved upstream of the creatine transporter pseudogene. Via gene-specific PCR, cloning and functional luciferase assays we identified a 1104 bp sequence proximal to the mRNA start site of the SLC6A8 gene with promoter activity in five cell types. The corresponding 5'flanking sequence (1050 bp) on the pseudogene also had promoter activity in all 5 cell lines. Surprisingly the pseudogene promoter was stronger than that of its parent gene in 4 of the cell lines tested. To the best of our knowledge, this is the first

  12. Characterization of two paralogous StAR genes in a teleost, Nile tilapia (Oreochromis niloticus).

    PubMed

    Yu, Xiangguo; Wu, Limin; Xie, Lang; Yang, Shijie; Charkraborty, Tapas; Shi, Hongjuan; Wang, Deshou; Zhou, Linyan

    2014-07-01

    Steroidogenic acute regulatory protein (StAR) transports cholesterol, the substrate for steroid synthesis, to the inner membranes of mitochondria. It is well known that estrogen is essential for female sex determination/differentiation in fish. However, no reports showed that the conventional StAR, which was supposed to be essential for estrogen production, was expressed in female gonads during the critical timing of sex determination/differentiation. In this study, two different StAR isoforms, named as StAR1 and StAR2, were characterized from the gonads of Nile tilapia (Oreochromis niloticus). Phylogenetic and synteny analysis revealed that two StAR genes existed in teleosts, Xenopus and chicken indicating that the duplication event occurred before the divergence of teleosts and tetrapods. Real-time PCR revealed that StAR1 was dominantly expressed in the testis, head kidney and kidney; while StAR2 was expressed exclusively in the gonads. In situ hybridization and immunohistochemistry demonstrated that StAR1 was expressed in the interrenal cells of the head kidney and Leydig cells of the testis; while StAR2 was expressed in the Leydig cells of the testis and the interstitial cells of the ovary. Ontogenic analysis demonstrated that StAR2 was expressed abundantly from 5 days after hatching (dah) in the somatic cells in XX gonads, whereas in XY gonads, both StARs could be detected from 30 dah until adulthood. Intraperitoneal injection of human chorionic gonadotropin experiments showed that expression of StAR1 and 2 was significantly elevated at 8h and persisted until 24h after injection in the testis. Taken together, our data suggested that StAR1 is likely to be required for cortisol production in the head kidney, and StAR2 is probably involved in estrogen production during early sex differentiation in XX gonads. In contrast, both StARs might be required for androgen production in testes. For the first time, our data demonstrated that two fish StARs might be involved

  13. Mutations affecting synaptic levels of neurexin-1β in autism and mental retardation.

    PubMed

    Camacho-Garcia, Rafael J; Planelles, Maria Inmaculada; Margalef, Mar; Pecero, Maria L; Martínez-Leal, Rafael; Aguilera, Francisco; Vilella, Elisabet; Martinez-Mir, Amalia; Scholl, Francisco G

    2012-07-01

    The identification of mutations in genes encoding proteins of the synaptic neurexin-neuroligin pathway in different neurodevelopmental disorders, including autism and mental retardation, has suggested the presence of a shared underlying mechanism. A few mutations have been described so far and for most of them the biological consequences are unknown. To further explore the role of the NRXN1β gene in neurodevelopmental disorders, we have sequenced the coding exons of the gene in 86 cases with autism and mental retardation and 200 controls and performed expression analysis of DNA variants identified in patients. We report the identification of four novel independent mutations that affect nearby positions in two regions of the gene/protein: i) sequences important for protein translation initiation, c.-3G>T within the Kozak sequence, and c.3G>T (p.Met1), at the initiation codon; and ii) the juxtamembrane region of the extracellular domain, p.Arg375Gln and p.Gly378Ser. These mutations cosegregate with different psychiatric disorders other than autism and mental retardation, such as psychosis and attention-deficit/hyperactivity disorder. We provide experimental evidence for the use of an alternative translation initiation codon for c.-3G>T and p.Met1 mutations and reduced synaptic levels of neurexin-1β protein resulting from p.Met1 and p.Arg375Gln. The data reported here support a role for synaptic defects of neurexin-1β in neurodevelopmental disorders.

  14. Proteins.

    ERIC Educational Resources Information Center

    Doolittle, Russell F.

    1985-01-01

    Examines proteins which give rise to structure and, by virtue of selective binding to other molecules, make genes. Binding sites, amino acids, protein evolution, and molecular paleontology are discussed. Work with encoding segments of deoxyribonucleic acid (exons) and noncoding stretches (introns) provides new information for hypotheses. (DH)

  15. Protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proteins are the major structural and functional components of all cells in the body. They are macromolecules that comprise 1 or more chains of amino acids that vary in their sequence and length and are folded into specific 3-dimensional structures. The sizes and conformations of proteins, therefor...

  16. Sensitivities of Two Zebrafish TRPA1 Paralogs to Chemical and Thermal Stimuli Analyzed in Heterologous Expression Systems.

    PubMed

    Oda, Mai; Kurogi, Mako; Kubo, Yoshihiro; Saitoh, Osamu

    2016-03-01

    Transient receptor potential A1 (TRPA1) is the only member of the mouse, chick, and frog TRPA family, whereas 2 paralogs (zTRPA1a and zTRPA1b) are present in zebrafish. We herein investigated functional differences in the 2 zebrafish TRPA1s. HEK293T cells were used as heterologous expression systems, and the sensitivities of these cells to 4 chemical irritants (allyl isothiocyanate [AITC], caffeine, auto-oxidized epigallocatechin gallate [EGCG], and hydrogen peroxide [H2O2]) were compared with Ca(2+) imaging techniques. Sensitivities to the activators for AITC, oxidized EGCG, and H2O2 were higher in cells expressing zTRPA1a than in those expressing zTRPA1b, whereas caffeine appeared to activate both cells equally. We also characterized the thermal sensitivity of Xenopus oocytes expressing each TRPA1 electrophysiologically using a 2-electrode voltage clamp. Although endogenous currents induced by a cold stimulation were observed in control oocytes in some batches, oocytes expressing zTRPA1b showed significantly stronger cold- and heat-induced responses. However, significant thermal activation was not observed in oocytes expressing zTRPA1a. The results obtained using in vitro expression systems suggest that zTRPA1a is specialized for chemical sensing, whereas zTRPA1b responds to thermal stimuli. Furthermore, characterization of the chimeric molecule of TRPA1a and 1b revealed the importance of the N-terminal region in chemical and thermal sensing by zTRPA1s.

  17. Parenting provided by adults with mental retardation.

    PubMed

    Dowdney, L; Skuse, D

    1993-01-01

    Studies assessing the quality of parenting provided by adults with mental retardation present conflicting conclusions. Some consider the majority to be doing reasonably well, whilst others report frequently unsatisfactory caretaking. There are a number of reasons for such different views. First, inconsistent selection criteria make it hard to compare across studies. In particular, sample composition will be influenced by the recruitment source. For example, if parents have been chosen from voluntary educational programmes a rather different picture is likely to be found than if they have been selected from individuals known to, or referred by, statutory agencies. On the whole, authors working with subjects from the former source have been rather more optimistic than those working with parents referred because there were already serious concerns about parenting difficulties or about delayed child development. Secondly, the majority of studies have used poorly defined global measures of parenting, with variable criteria of what constitutes adequate care. Some have concentrated on physical care and hygiene, whilst others have looked for the presence of affection and warmth. A child's reception into care as the sole measure of the quality of parenting is an unsatisfactory criterion because parental retardation has itself occasionally been used as the basis for removal of a child into care, even in the absence of other evidence of neglect or abuse. Thirdly, methodological flaws are found in studies that have used observational assessments of parenting. Such studies have suggested mothers with mental retardation tend to lack interactive skills (such as high levels of praise and imitation, and low restrictiveness) which are known to be associated with optimal child development. Control groups have often not been matched on social and other variables which might be expected to exert a significant influence upon parenting practices. In addition, the generalisability of

  18. Parenting provided by adults with mental retardation.

    PubMed

    Dowdney, L; Skuse, D

    1993-01-01

    Studies assessing the quality of parenting provided by adults with mental retardation present conflicting conclusions. Some consider the majority to be doing reasonably well, whilst others report frequently unsatisfactory caretaking. There are a number of reasons for such different views. First, inconsistent selection criteria make it hard to compare across studies. In particular, sample composition will be influenced by the recruitment source. For example, if parents have been chosen from voluntary educational programmes a rather different picture is likely to be found than if they have been selected from individuals known to, or referred by, statutory agencies. On the whole, authors working with subjects from the former source have been rather more optimistic than those working with parents referred because there were already serious concerns about parenting difficulties or about delayed child development. Secondly, the majority of studies have used poorly defined global measures of parenting, with variable criteria of what constitutes adequate care. Some have concentrated on physical care and hygiene, whilst others have looked for the presence of affection and warmth. A child's reception into care as the sole measure of the quality of parenting is an unsatisfactory criterion because parental retardation has itself occasionally been used as the basis for removal of a child into care, even in the absence of other evidence of neglect or abuse. Thirdly, methodological flaws are found in studies that have used observational assessments of parenting. Such studies have suggested mothers with mental retardation tend to lack interactive skills (such as high levels of praise and imitation, and low restrictiveness) which are known to be associated with optimal child development. Control groups have often not been matched on social and other variables which might be expected to exert a significant influence upon parenting practices. In addition, the generalisability of

  19. Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice

    PubMed Central

    Soderling, Scott H.; Langeberg, Lorene K.; Soderling, Jacquelyn A.; Davee, Stephen M.; Simerly, Richard; Raber, Jacob; Scott, John D.

    2003-01-01

    The Scar/WAVE family of scaffolding proteins organize molecular networks that relay signals from the GTPase Rac to the actin cytoskeleton. The WAVE-1 isoform is a brain-specific protein expressed in variety of areas including the regions of the hippocampus and the Purkinje cells of the cerebellum. Targeted disruption of the WAVE-1 gene generated mice with reduced anxiety, sensorimotor retardation, and deficits in hippocampal-dependent learning and memory. These sensorimotor and cognitive deficits are analogous to the symptoms of patients with 3p-syndrome mental retardation who are haploinsufficient for WRP/MEGAP, a component of the WAVE-1 signaling network. Thus WAVE-1 is required for normal neural functioning. PMID:12578964

  20. A new form of X-linked mental retardation with growth retardation, deafness, and microgenitalism.

    PubMed Central

    Juberg, R C; Marsidi, I

    1980-01-01

    The proband and two maternal uncles were similarly affected by a unique constellation of mental retardation and physical abnormalities. There were severe retardation, growth less than the third percentile, and significantly delayed bone age. They manifested deafness, a flat nasal bridge, several ocular abnormalities, and a rudimentary scrotum with cryptorchidism, and one had a small penis. The proband also had onychodystrophy of his fingers and toes. Their birth weights and lengths were less than expected. No chromosomal or biochemical abnormality was detected. Both uncles died, but the proband is healthy at 4 years. Their phenotype is distinguished from other forms of X-linked mental retardation and appears to be a new syndrome. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6107045

  1. Retarded Embryo Development 1 (RED1) regulates embryo development, seed maturation and plant growth in Arabidopsis.

    PubMed

    Du, Qian; Wang, Huanzhong

    2016-07-20

    Plant seeds accumulate large amounts of protein and carbohydrate as storage reserves during maturation. Thus, understanding the genetic control of embryo and seed development may provide bioengineering tools for yield improvement. In this study, we report the identification of Retarded Embryo Development 1 (RED1) gene in Arabidopsis, whose two independent T-DNA insertion mutant lines, SALK_085642 (red1-1) and SALK_022583 (red1-2), show a retarded embryo development phenotype. The embryogenesis process ceases at the late heart stage in red1-1 and at the bent-cotyledon stage in red1-2, respectively, resulting in seed abortion in both lines. The retarded embryo development and seed abortion phenotypes reverted to normal when RED1 complementation constructs were introduced into mutant plants. Small red1-2 homozygous plants can be successfully rescued by culturing immature seeds, indicating that seed abortion likely results from compromised tolerance to the desiccation process associated with seed maturation. Consistent with this observation, red1-2 seeds accumulate less protein, and the expression of two late embryo development reporter transgenes, LEA::GUS and β-conglycinin::GUS, was significantly weak and started relatively late in the red1-2 mutant lines compared to the wild type. The RED1 gene encodes a plant specific novel protein that is localized in the nucleus. These results indicate that RED1 plays important roles in embryo development, seed maturation and plant growth. PMID:27477025

  2. Factors affecting social integration of noninstitutionalized mentally retarded adults.

    PubMed

    Reiter, S; Levi, A M

    1980-07-01

    The social integration of noninstitutionalized moderately and mildly mentally retarded young adults was investigated. A group of moderately and mildly retarded adults (study group) was compared with a group of borderline retarded (control group) adults on employability, behavior at work, social integration and social skills, personality, and self-concept. Findings indicated that the study group was less well integrated at work and in society than was the control group and showed lack of social skills. The retarded adults who had nonretarded friends showed better social-educational skills than did the other subjects. Findings suggest that even retarded individuals who grow up in the community need help in order to become socially independent. The existence of a special social club for retarded adults was found to fulfill the functions of a sheltered framework. Participants in the club showed more positive self-concepts; however, the club did not seem to prepare them for social integration in the general community.

  3. Fire-retardant decorative inks for aircraft interiors

    NASA Technical Reports Server (NTRS)

    Kourtides, D. A.; Nir, Z.; Mikroyannidis, J. A.

    1985-01-01

    Commercial and experimental fire retardants were screened as potential fire retardants for acrylic printing inks used on aircraft interior sandwich panels. The fire retardants are selected according to their physical properties and their thermostabilities. A criterion for selecting a more stable fire retardant is established. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are used to determine thermostabilities. Results show that the fire retardant formulations are more thermally stable than the acrylic ink control. It is determined that an ink formulation containing a brominated phenol and carboxy-terminated butadiene acrylonitrile which has been modified with a brominated polymeric additive (BPA), yields the highest limiting oxygen index (LOI) of all the compounds tested. All of the fire-retardant formulations have a higher oxygen index than the baseline acrylic ink.

  4. Nanotechnology finding its way into flame retardancy

    NASA Astrophysics Data System (ADS)

    Schartel, Bernhard

    2014-05-01

    Nanotechnology is one of the key technologies of the 21st century. The exploitation of "new" effects that arise from materials structured on the nano-scale has also been proposed successfully for flame retardancy of polymers since the end of the 90s. Of all of the approaches these include, at this time the use of nanocomposites offers the best potential for industrial application, also some other ideas are sketched, such as using electrospun nanofibers mats or layer-by-layer deposits as protection coatings, as well as sub-micrometer multilayer coatings as effective IR-mirrors. The general phenomena, inducing a flow limit in the pyrolysing melt and changing the fire residue, are identified in nanocomposites. Key experiments are performed such as quasi online investigation of the protection layer formation to understand what is going on in detail. The flame retardancy mechanisms are discussed and their impact on fire behaviour quantified. With the latter, the presentation pushes forward the state of the art. For instance, the heat shielding is experimentally quantified for a layered silicate epoxy resin nanocomposite proving that it is the only import mechanism controlling the reduction in peak heat release rate in the investigated system for different irradiations. The flame retardancy performance is assessed comprehensively illuminating not only the strengths but also the weak points of the concepts. Guidelines for materials development are deduced and discussed. Apart from inorganic fillers (layered silicate, boehmite, etc.) not only carbon nanoobjects such as multiwall carbon nanotubes, multilayer graphene and graphene are investigated, but also nanoparticles that are more reactive and harbor the potential for more beneficial interactions with the polymer matrix.

  5. Nanotechnology finding its way into flame retardancy

    SciTech Connect

    Schartel, Bernhard

    2014-05-15

    Nanotechnology is one of the key technologies of the 21{sup st} century. The exploitation of 'new' effects that arise from materials structured on the nano-scale has also been proposed successfully for flame retardancy of polymers since the end of the 90s. Of all of the approaches these include, at this time the use of nanocomposites offers the best potential for industrial application, also some other ideas are sketched, such as using electrospun nanofibers mats or layer-by-layer deposits as protection coatings, as well as sub-micrometer multilayer coatings as effective IR-mirrors. The general phenomena, inducing a flow limit in the pyrolysing melt and changing the fire residue, are identified in nanocomposites. Key experiments are performed such as quasi online investigation of the protection layer formation to understand what is going on in detail. The flame retardancy mechanisms are discussed and their impact on fire behaviour quantified. With the latter, the presentation pushes forward the state of the art. For instance, the heat shielding is experimentally quantified for a layered silicate epoxy resin nanocomposite proving that it is the only import mechanism controlling the reduction in peak heat release rate in the investigated system for different irradiations. The flame retardancy performance is assessed comprehensively illuminating not only the strengths but also the weak points of the concepts. Guidelines for materials development are deduced and discussed. Apart from inorganic fillers (layered silicate, boehmite, etc.) not only carbon nanoobjects such as multiwall carbon nanotubes, multilayer graphene and graphene are investigated, but also nanoparticles that are more reactive and harbor the potential for more beneficial interactions with the polymer matrix.

  6. Early identification and prevention of mental retardation.

    PubMed

    Persha, A J

    1992-01-01

    Early identification and prevention of mental retardation helps in terms of treatment for some conditions, better planning and management of cases, and counseling. Diagnostic procedures are available during pregnancy for early detection: blood tests, amniocentesis, ultrasound, fetoscopy, and urine tests; tests available for the newborn are blood tests for hypothyroidism, PKU; urine tests for metabolic disorders; apgar scores for screening of neurological deficits; neurobehavioral assessments, developmental schedules; neurodevelopmental screening; sensory examination; speech and language assessments; EEG; and imaging techniques. Early identification of mental retardation is beneficial in aiding the child's development and personality and in helping parents adjust mentally and learning to cope with caring for the child. Sometimes, it can help to limit the number and extent of the handicap. Prevention can be primary, secondary, or tertiary. The emphasis is on planned pregnancies, regular prenatal care, regular health checkups for mother and child, immunization, nutrition, prevention of environmental hazards and accidents, early identification and screening, genetic studies and counseling, family planning, and creation of awareness among the general population. Inadequate prenatal care is associated with prematurity and low birth weight, which are linked to mental retardation. Prenatal care for the pregnant woman involves participating in regular prenatal checkups, maintaining good nutrition, having preliminary screening, attending promptly to illnesses and infections, and getting immunized at the appropriate time. Avoidance of the following is recommended: unnecessary and nonprescribed drugs, physical accidents, exposure to radiation and teratogens, alcohol and tobacco consumption, exposure to infections such as measles, rubella, or syphilis, toxins and poisons such as lead, and attempts at abortion. Genetic counseling can provide information on the disorders, the

  7. Electrode contamination effects of retarding potential analyzer

    NASA Astrophysics Data System (ADS)

    Fang, H. K.; Oyama, K.-I.; Cheng, C. Z.

    2014-01-01

    The electrode contamination in electrostatic analyzers such as Langmuir probes and retarding potential analyzers (RPA) is a serious problem for space measurements. The contamination layer acts as extra capacitance and resistance and leads to distortion in the measured I-V curve, which leads to erroneous measurement results. There are two main effects of the contamination layer: one is the impedance effect and the other is the charge attachment and accumulation due to the capacitance. The impedance effect can be reduced or eliminated by choosing the proper sweeping frequency. However, for RPA the charge accumulation effect becomes serious because the capacitance of the contamination layer is much larger than that of the Langmuir probe of similar dimension. The charge accumulation on the retarding potential grid causes the effective potential, that ions experience, to be changed from the applied voltage. Then, the number of ions that can pass through the retarding potential grid to reach the collector and, thus, the measured ion current are changed. This effect causes the measured ion drift velocity and ion temperature to be changed from the actual values. The error caused by the RPA electrode contamination is expected to be significant for sounding rocket measurements with low rocket velocity (1-2 km/s) and low ion temperature of 200-300 K in the height range of 100-300 km. In this paper we discuss the effects associated with the RPA contaminated electrodes based on theoretical analysis and experiments performed in a space plasma operation chamber. Finally, the development of a contamination-free RPA for sounding rocket missions is presented.

  8. Proteins

    NASA Astrophysics Data System (ADS)

    Regnier, Fred E.; Gooding, Karen M.

    Because of the complexity of cellular material and body fluids, it is seldom possible to analyze a natural product directly. Qualitative and quantitative analyses must often be preceded by some purification step that separates the molecular species being examined from interfering materials. In the case of proteins, column liquid chromatography has been used extensively for these fractionations. With the advent of gel permeation, cation exchange, anion exchange, hydrophobic, and affinity chromatography, it became possible to resolve proteins through their fundamental properties of size, charge, hydrophobicity, and biological affinity. The chromatographic separations used in the early isolation and characterization of many proteins later became analytical tools in their routine analysis. Unfortunately, these inherently simple and versatile column chromatographic techniques introduced in the 50s and 60s have a severe limitation in routine analysis-separation time. It is common to encounter 1-24 h separation times with the classical gel-type supports.

  9. Theories of dual diagnosis in mental retardation.

    PubMed

    Matson, J L; Sevin, J A

    1994-02-01

    Dual diagnosis, defined in this instance as the co-occurrence of mental health disorders with mental retardation, has become a major area of clinical practice and research in the past 10 years. Whereas areas such as differential diagnosis, assessment, and prevalence have been major focuses of research, etiologies of dual diagnosis have received less attention. Current etiological theories have practical implications for the treatment and prevention of dual diagnoses and suggest important directions for future research. This article provides a historical review of theory development in the field of dual diagnosis. Current status of etiological theories and future directions are discussed with an aim toward encouraging further study.

  10. Tactile function of educable mentally retarded children.

    PubMed

    McCracken, A

    1975-08-01

    The tactile perception ability of 29 seven-and eight-year-old educable mentally retarded children was evaluated by using the tactile perception portions of the Southern California Sensory Integration Tests. The children were also observed for tactile defensive behavior. Compared to normal children of the same age (as reported in normative data), this sample of children was significantly inferior in manual form, finger identification, graphesthesia, and perception of simultaneous stimuli, but not in the localization of single stimuli. During the testing, 62 percent showed tactile defensive behavior. The role of tactile perception in the development of symbolic communications is reviewed.

  11. Aspects of Verbal Behavior Cited by Listeners in Judging Speakers as Retarded or Not Retarded.

    ERIC Educational Resources Information Center

    Kernan, Keith T.; And Others

    1986-01-01

    Results of asking 30 nonprofessionals for reasons speakers were judged to be retarded or not indicated that quality of speech (articulation, prosody, etc.) and the structure, content, and coherence of discourse are more important than sentence-level grammatical features in forming impressions of cognitive competence. (Author/DB)

  12. Evaluation of Still Picture Telephone for Mentally Retarded Persons. Telematics and Mental Retardation.

    ERIC Educational Resources Information Center

    Brodin, Jane; Bjorck-Akesson, Eva

    This study examined the benefit of using a visual telecommunication system for Sweden's children and adults with mild to moderate mental retardation and speech difficulties. The Panasonic Image Communication Unit connects to standard modular telephones and includes a camera and monitor for the transfer of pictures. Units were placed in eight…

  13. Fire-retardant decorative inks for aircraft interiors

    NASA Technical Reports Server (NTRS)

    Nir, Z.; Mikroyannidis, J. A.; Kourtides, D. A.

    1984-01-01

    Commercial and experimental fire retardants were screened for possible use wiith acrylic printing inks on aircraft interior sandwich panels. The fire retardants were selected according to their physical properties and thermostabilities. Thermostabilities were determined by thermogravimetric analysis and differential scanning calorimetry. A criterion was then established for selecting the more stable agent. Results show that some of the bromine-containing fire retardants are more thermostable than the acrylic ink, alone, used as a control. Also, the bromine-containing fire retardants yield even better limiting oxygen index values when tested after adding carboxy-terminated butadiene acrylonitrile (CTBN) rubber.

  14. Scalable Preparation of Multifunctional Fire-Retardant Ultralight Graphene Foams.

    PubMed

    Hu, Chuangang; Xue, Jiangli; Dong, Liye; Jiang, Yue; Wang, Xiaopeng; Qu, Liangti; Dai, Liming

    2016-01-26

    Traditional flame-retardant materials often show poor tolerance to oxidants, strong acidic/alkaline reagents, organic solvents, along with toxicity problems. Herein, highly fire-retardant ultralight graphene foam has been developed, which possesses not only ultralight and compressible characteristics but also efficient flame-retardant properties, outperforming those traditional polymer, metallic oxide, and metal hydroxide based flame retardant materials and their composites. The newly developed unconventional refractory materials are promising for specific applications as demonstrated by the observed high temperature resistant microwave absorption capability.

  15. TG-FTIR characterization of flame retardant polyurethane foams materials

    NASA Astrophysics Data System (ADS)

    Liu, W.; Tang, Y.; Li, F.; Ge, X. G.; Zhang, Z. J.

    2016-07-01

    Dimethyl methylphosphonate (DMMP) and trichloroethyl phosphtate (TCEP) have been used to enhance the flame retardancy of polyurethane foams materials (PUF). Flame retardancy and thermal degradation of PUF samples have been investigated by the LOI tests and thermal analysis. The results indicate that the excellent flame retardancy can be achieved due to the presence of the flame retardant system containing DMMP and TCEP. TG-FTIR reveals that the addition of DMMP/TCEP can not only improve the thermal stability of PUF samples but can also affect the gaseous phase at high temperature.

  16. Depression in Mentally Retarded Persons: Research Findings and Future Directions.

    ERIC Educational Resources Information Center

    Matson, Johnny L.

    1983-01-01

    Depression in mentally retarded persons is examined in terms of incidence and prevalence, diagnostic issues (including assessment approaches), and treatment procedures (including drug therapy and behavioral approaches). (CL)

  17. Molecular characterization of BrMYB28 and BrMYB29 paralogous transcription factors involved in the regulation of aliphatic glucosinolate profiles in Brassica rapa ssp. pekinensis.

    PubMed

    Baskar, Venkidasamy; Park, Se Won

    2015-07-01

    Glucosinolates (GSL) are one of the major secondary metabolites of the Brassicaceae family. In the present study, we aim at characterizing the multiple paralogs of aliphatic GSL regulators, such as BrMYB28 and BrMYB29 genes in Brassica rapa ssp. pekinensis, by quantitative real-time PCR (qRT-PCR) analysis in different tissues and at various developmental stages. An overlapping gene expression pattern between the BrMYBs as well as their downstream genes (DSGs) was found at different developmental stages. Among the BrMYB28 and BrMYB29 paralogous genes, the BrMYB28.3 and BrMYB29.1 genes were dominantly expressed in most of the developmental stages, compared to the other paralogs of the BrMYB genes. Furthermore, the differential expression pattern of the BrMYBs was observed under various stress treatments. Interestingly, BrMYB28.2 showed the least expression in most developmental stages, while its expression was remarkably high in different stress conditions. More specifically, the BrMYB28.2, BrMYB28.3, and BrMYB29.1 genes were highly responsive to various abiotic and biotic stresses, further indicating their possible role in stress tolerance. Moreover, the in silico cis motif analysis in the upstream regulatory regions of BrMYBs showed the presence of various putative stress-specific motifs, which further indicated their responsiveness to biotic and abiotic stresses. These observations suggest that the dominantly expressed BrMYBs, both in different developmental stages and under various stress treatments (BrMYB28.3 and BrMYB29.1), may be potential candidate genes for altering the GSL level through genetic modification studies in B. rapa ssp. pekinensis.

  18. Molecular characterization of BrMYB28 and BrMYB29 paralogous transcription factors involved in the regulation of aliphatic glucosinolate profiles in Brassica rapa ssp. pekinensis.

    PubMed

    Baskar, Venkidasamy; Park, Se Won

    2015-07-01

    Glucosinolates (GSL) are one of the major secondary metabolites of the Brassicaceae family. In the present study, we aim at characterizing the multiple paralogs of aliphatic GSL regulators, such as BrMYB28 and BrMYB29 genes in Brassica rapa ssp. pekinensis, by quantitative real-time PCR (qRT-PCR) analysis in different tissues and at various developmental stages. An overlapping gene expression pattern between the BrMYBs as well as their downstream genes (DSGs) was found at different developmental stages. Among the BrMYB28 and BrMYB29 paralogous genes, the BrMYB28.3 and BrMYB29.1 genes were dominantly expressed in most of the developmental stages, compared to the other paralogs of the BrMYB genes. Furthermore, the differential expression pattern of the BrMYBs was observed under various stress treatments. Interestingly, BrMYB28.2 showed the least expression in most developmental stages, while its expression was remarkably high in different stress conditions. More specifically, the BrMYB28.2, BrMYB28.3, and BrMYB29.1 genes were highly responsive to various abiotic and biotic stresses, further indicating their possible role in stress tolerance. Moreover, the in silico cis motif analysis in the upstream regulatory regions of BrMYBs showed the presence of various putative stress-specific motifs, which further indicated their responsiveness to biotic and abiotic stresses. These observations suggest that the dominantly expressed BrMYBs, both in different developmental stages and under various stress treatments (BrMYB28.3 and BrMYB29.1), may be potential candidate genes for altering the GSL level through genetic modification studies in B. rapa ssp. pekinensis. PMID:26043798

  19. Polybrominated diphenyl ether (PBDE) flame retardants.

    PubMed

    Rahman, F; Langford, K H; Scrimshaw, M D; Lester, J N

    2001-07-25

    Polybrominated diphenyl ether, PBDE, flame retardants are now a world-wide pollution problem reaching even remote areas. They have been found to bioaccumulate and there are concerns over the health effects of exposure to PBDEs, they also have potential endocrine disrupting properties. They are lipophilic compounds so are easily removed from the aqueous environment and are predicted to sorb onto sediments and particulate matter or to fatty tissue, aiding their distribution throughout the environment. PBDEs are structurally similar to PCBs and DDT and, therefore, their chemical properties, persistence and distribution in the environment follow similar patterns. Concentrations of PBDEs found in environmental samples are now higher than those of PCBs. Evidence to date demonstrates that PBDEs are a growing problem in the environment and concern over their fate and effects is warranted. The manufacture of reactive and additive flame retardants is briefly discussed and their fate and behaviour in the environment is assessed. PBDE toxicology is reviewed and methods of analysis are evaluated.

  20. Mental Retardation. Fact Sheet = El Retraso Mental. Hojas Informativas Sobre Discapacidades.

    ERIC Educational Resources Information Center

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This fact sheet on mental retardation is written in both English and Spanish. It begins with a vignette of a 15-year-old boy with mental retardation. Mental retardation is briefly explained as are some causes of mental retardation. It notes that a diagnosis of mental retardation looks at two things: first, the ability of a person's brain to learn,…

  1. Research on mental retardation in Norway 1970-1980: a review.

    PubMed

    Mellgren, S I; Götestam, K G

    1983-01-01

    The present paper reviews most of the research on mental retardation in Norway, published in 1970-1980. An important part of this work is represented by Hole's reports of experimental phenylketonuria (PKU) in the rat and studies on peptides and protein-associated peptide complexes in mental disturbances, including experimental studies of effects on brain function and behavior of a peptide fraction (factor 3 b 2). Among studies on diseases with mental retardation, are determinations of arylsulphatase A in cultured amniotic fluid cells and in amniotic fluid as measures of prenatal diagnosis of metachromatic leukodystrophy, reports on screening disorders of tyrosine metabolism and the occurrence of positive dye test in blind children and patients with physical and mental handicaps. Further, studies on the effects of antiepileptics on immunoglobulins are reported. In the fields of social medicine, psychology and psychiatry, only few studies have been published in international journals. Brief reports on Norwegian articles comprise studies on work and disability, social and psychological handicaps in special school pupils, psychosis in mental retardation, and some efforts to design psychological treatment programs for the mentally retarded. The majority of research on mental retardation or with relevance to this field in Norway, has either been supported by the Norwegian Council for Research on Mental Retardation, or the Norwegian Research Council for Science and the Humanities. Based on annual reports of these councils, and correspondence to centers involved in such research, we have collected reports published in the period 1970 to 1980. We have also received unpublished reports, but have chosen not to include most of them in this review, because of the difficulties for the readers to obtain these reports. The institutional and noninstitutional services for the mentally retarded in Norway have no formal connection with university or other research institutes

  2. Mutation analysis of the HOX paralogous 4-13 genes in children with acute lymphoid malignancies: identification of a novel germline mutation of HOXD4 leading to a partial loss-of-function.

    PubMed

    van Scherpenzeel Thim, Virginie; Remacle, Sophie; Picard, Jacques; Cornu, Guy; Gofflot, Françoise; Rezsohazy, René; Verellen-Dumoulin, Christine

    2005-04-01

    The molecular basis of susceptibility to childhood malignant hemopathy remains largely unknown. An excess of skeletal congenital anomalies has been reported among children with hematological malignancy and points towards involvement of developmental genes, like those belonging to the HOX gene family. In addition to their role in embryogenesis, HOX transcription factors are known to be regulators of proliferation and differentiation of hematopoietic cells. We aimed to explore the possibility that germline alterations of HOX genes might be involved in childhood acute lymphoid malignancies. A cohort of 86 children diagnosed with acute lymphoid malignancy was studied, 20 of them concurrently presenting a congenital anomaly of the skeleton. First, we screened for nucleotide changes throughout the HOX genes of paralogous groups 4 to 13 in the 20 patients with skeletal defects, following a skeletal phenotype-based strategy. Subsequently, we extended the HOX mutation screening to the other 66 children having a malignant lymphoproliferative disorder, but without skeletal defects. In total, 16 germline mutations were identified. While 13 changes were also observed in healthy controls, three variants were exclusively found in acute lymphoid malignancy cases. These comprised the germline c.242A>T (p.Glu81Val) missense mutation of HOXD4, detected in two children diagnosed with acute lymphoblastic leukemia (ALL). Furthermore, this mutation was found in association with other specific HOX variants of cluster D (2q31-q37), defining a unique haplotype. Functional analysis of the murine Hoxd4 homolog revealed that mutant Hoxd4 protein had lower transcriptional activity than wild-type protein in vitro. The p.Glu81Val mutation of HOXD4 thus results in a partial loss-of-function, which might be involved in childhood ALL.

  3. Elucidating toxicological mechanisms of current flame retardants using a bacterial gene profiling assay.

    PubMed

    Krivoshiev, Boris V; Dardenne, Freddy; Blust, Ronny; Covaci, Adrian; Husson, Steven J

    2015-12-01

    Flame retardants are ubiquitously used chemicals that have been shown to contaminate environments. Toxicological data is largely limited, with little insight into their molecular modes of action that may give rise to their toxic phenotypes. Such insight would aid more effective risk assessments concerning these compounds, while also improving molecular design. We therefore used a bacterial stress-gene profiling assay to screen twelve currently-used flame retardants to obtain mechanistic insights of toxicity. Both brominated and organophosphate flame retardants were tested. All compounds showed statistically significant inductions of several stress genes when compared to control treatments. Triphenyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(butyl)phosphate, and tetrabromobisphenol A elicited (at least) two-fold inductions for any of the stress genes. When looking at absolute induction levels, the promoters induced are indicative of protein perturbation, DNA integrity and membrane integrity. However, normalising for the different induction potentials of the different stress genes and clustering using hierarchical and k-means algorithms indicated that in addition to protein and DNA damage, some compounds also resulted in growth arrest and oxidative damage. This research shows that this assay allows for the determination of toxicological modes-of-action while clustering and accounting for induction potentials of the different genes aids better risk assessment.

  4. Elucidating toxicological mechanisms of current flame retardants using a bacterial gene profiling assay.

    PubMed

    Krivoshiev, Boris V; Dardenne, Freddy; Blust, Ronny; Covaci, Adrian; Husson, Steven J

    2015-12-01

    Flame retardants are ubiquitously used chemicals that have been shown to contaminate environments. Toxicological data is largely limited, with little insight into their molecular modes of action that may give rise to their toxic phenotypes. Such insight would aid more effective risk assessments concerning these compounds, while also improving molecular design. We therefore used a bacterial stress-gene profiling assay to screen twelve currently-used flame retardants to obtain mechanistic insights of toxicity. Both brominated and organophosphate flame retardants were tested. All compounds showed statistically significant inductions of several stress genes when compared to control treatments. Triphenyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(butyl)phosphate, and tetrabromobisphenol A elicited (at least) two-fold inductions for any of the stress genes. When looking at absolute induction levels, the promoters induced are indicative of protein perturbation, DNA integrity and membrane integrity. However, normalising for the different induction potentials of the different stress genes and clustering using hierarchical and k-means algorithms indicated that in addition to protein and DNA damage, some compounds also resulted in growth arrest and oxidative damage. This research shows that this assay allows for the determination of toxicological modes-of-action while clustering and accounting for induction potentials of the different genes aids better risk assessment. PMID:26343755

  5. Growth retardation in sickle-cell disease treated by nutritional support.

    PubMed

    Heyman, M B; Vichinsky, E; Katz, R; Gaffield, B; Hurst, D; Castillo, R; Chiu, D; Kleman, K; Ammann, A J; Thaler, M M

    1985-04-20

    The effect of increased nutritional intake was evaluated in 5 growth-retarded children with sickle-cell disease. Growth on recommended daily calorie and protein intakes had been inadequate in all 5. Fat absorption and intestinal mucosal morphology were normal in all 5. 2 children were given nutritional supplementation by nasogastric intubation, 1 received nightly oral formula supplements, and 2 were supplemented with zinc, iron, folate, and vitamin E only. Nutritional supplementation by the nasogastric route produced a rapid sustained increase in growth rate, associated with striking reductions in pain crises and infections which had previously necessitated many hospital admissions. Oral supplementation improved the clinical course but had no effect on growth rate. Mineral and vitamin supplements influenced neither the growth rate nor the clinical course. The observations indicate that nasogastric nutritional supplementation may accelerate growth and reduce the incidence and severity of complications in growth-retarded children with sickle-cell disease. PMID:2858749

  6. Growth retardation in sickle-cell disease treated by nutritional support.

    PubMed

    Heyman, M B; Vichinsky, E; Katz, R; Gaffield, B; Hurst, D; Castillo, R; Chiu, D; Kleman, K; Ammann, A J; Thaler, M M

    1985-04-20

    The effect of increased nutritional intake was evaluated in 5 growth-retarded children with sickle-cell disease. Growth on recommended daily calorie and protein intakes had been inadequate in all 5. Fat absorption and intestinal mucosal morphology were normal in all 5. 2 children were given nutritional supplementation by nasogastric intubation, 1 received nightly oral formula supplements, and 2 were supplemented with zinc, iron, folate, and vitamin E only. Nutritional supplementation by the nasogastric route produced a rapid sustained increase in growth rate, associated with striking reductions in pain crises and infections which had previously necessitated many hospital admissions. Oral supplementation improved the clinical course but had no effect on growth rate. Mineral and vitamin supplements influenced neither the growth rate nor the clinical course. The observations indicate that nasogastric nutritional supplementation may accelerate growth and reduce the incidence and severity of complications in growth-retarded children with sickle-cell disease.

  7. Defining Mental Retardation: A Matter of Life or Death

    ERIC Educational Resources Information Center

    Lichten, William; Simon, Elliot W.

    2007-01-01

    Because persons with mental retardation cannot be executed for murder, the diagnosis becomes a life and death matter. The American Association on Mental Retardation (now the American Association on Intellectual and Developmental Disabilities) and other associations agree that IQ alone is an insufficient criterion and adaptive functioning also…

  8. Newborn Screening To Prevent Mental Retardation. The Arc Q & A.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This information fact sheet on screening newborns to prevent mental retardation defines newborn screening and outlines how screening is performed. It discusses the six most common disorders resulting in mental retardation for which states most commonly screen. These include phenylketonuria, congenital hypothyroidism, galactosemia, maple syrup…

  9. Crisis Intervention With the Mentally Retarded: The New Treatment Look.

    ERIC Educational Resources Information Center

    Sternlicht, Manny; Deutsch, Martin R.

    The trend toward normalization of the mentally retarded has brought a new dimension to the problem of their adjustment. Within the past several years, large numbers of the mentally retarded have been discharged into the community from residential facilities; the stress and anxiety they experience at being thrust into a strange and alien world…

  10. Mental Retardation in the Caribbean: Needs, Resources, Approaches.

    ERIC Educational Resources Information Center

    Thorburn, Marigold J., Ed.

    Presented are conference reports including an opening address on the economic benefits of programs for the mentally retarded (MR), and eight papers discussing the problem of mental retardation in the Caribbean. Two papers on preschool age children, respectively, consider the identification and assessment of MR children in the Caribbean and present…

  11. Educational Initiatives in Mental Retardation in Nineteenth-Century Holland.

    ERIC Educational Resources Information Center

    Weijers, Ido

    2000-01-01

    Reports on the educational initiatives in the Netherlands during the nineteenth century in relation to mental retardation. States that the optimism towards people with mental retardation that emerged in many countries in the second half of the nineteenth century did not emerge within the Netherlands. (CMK)

  12. Communication Problems in Mental Retardation: Diagnosis and Management.

    ERIC Educational Resources Information Center

    Lillywhite, Herold S.; Bradley, Doris P.

    Discussed are the problems of communication in mental retardation with an introductory background and definition of this problem, including the etiological factors and general characteristics. A presentation of diagnostic methods leads into discussions of the problem of medical-dental management and educational management of the retarded child.…

  13. Theories on Criminality and Mental Retardation Project CAMIO, Volume 2.

    ERIC Educational Resources Information Center

    Haskins, Jimmy R.; Friel, Charles M.

    This historical review of theories on criminality and mental retardation is part of Project CAMIO (Correctional Administration and the Mentally Incompetent Offender), a Texas study to determine the incidence of criminal incarceration of the mentally retarded (MR) and to identify laws, procedures, and practices which affect the prosecution and…

  14. Arizona's Comprehensive Plan to Help the Mentally Retarded.

    ERIC Educational Resources Information Center

    Arizona State Dept. of Health, Phoenix. Mental Retardation Section.

    To help combat mental retardation, 136 recommendations are made for the following: establishment by statute of a division of mental retardation, an advisory council, and a coordinating council of agencies; changes in laws governing the Arizona Children's Colony, additional public school legislation, and a study of civil and criminal law; immediate…

  15. Psychopharmacology and Mental Retardation: A 10 Year Review (1990- 1999).

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Bamburg, Jay W.; Mayville, Erik A.; Pinkston, Jim; Bielecki, Joanne; Kuhn, David; Smalls, Yemonja; Logan, James R.

    2000-01-01

    Review of the literature on psychopharmacology and mental retardation from 1990-1999 found most studies had major methodological flaws. Also, most drug administrations were not based in science, were not evaluated appropriately, and generally did not follow best practices for treatment of persons with mental retardation. A table lists the studies…

  16. Nutrition and Mental Retardation. An Annotated Bibliography, 1964-1970.

    ERIC Educational Resources Information Center

    Springer, Ninfa Saturnino

    This annotated bibliography is primarily organized for nutritionists. It presents selected articles published from 1964 to the present. All aspects of nutrition in mental retardation are covered excepting inborn errors of metabolism. Sections are included on: (1) nutrition, birthweight, and mental retardation; (2) nutrition, growth, and mental…

  17. Flame retardant antibacterial cotton high-loft nonwoven fabrics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flame retardant treated gray cotton fibers were blended with antibacterial treated gray cotton fibers and polyester/polyester sheath/core bicomponent fibers to form high-loft fabrics. The high flame retardancy (FR) and antibacterial property of these high lofts were evaluated by limiting oxygen inde...

  18. Physical Trauma as an Etiological Agent in Mental Retardation.

    ERIC Educational Resources Information Center

    Angle, Carol R., Ed.; Bering, Edgar A., Jr., Ed.

    The conference on Physical Trauma as a Cause of Mental Retardation dealt with two major areas of etiological concern - postnatal and perinatal trauma. Following two introductory statements on the problem of and issues related to mental retardation (MR) after early trauma to the brain, five papers on the epidemiology of head trauma cover…

  19. Cognitive Development Among Retardates: Reanalysis of Inhelder's Data.

    ERIC Educational Resources Information Center

    Jordan, Valerie Barnes

    A reanalysis of B. Inhelder's (1968) data concerning cognitive development among retardates was performed by selecting from the original 159 subjects a sample of 104 educable mentally retarded Ss (7-19 years old) who were diagnosed as fixated or nonfixated at three of the cognitive stages postulated by Jean Piaget. The results indicated that among…

  20. A Practical Guide for Teaching the Mentally Retarded to Swim.

    ERIC Educational Resources Information Center

    American Association for Health, Physical Education, and Recreation, Washington, DC.

    A guide for teaching the retarded to swim begins with a general discussion of retardation, the need for individualization, and staff qualifications. Factors discussed in program organization and administration include community agencies, staff training, examples of records and forms, and first aid procedures. Suggested methods consider perceptual…

  1. Further Evidence for Cognitive Inertia of Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Ellis, Norman R.; Dulaney, Cynthia L.

    1991-01-01

    Forty young adults with mental retardation (MR) were compared to 40 young adults without mental retardation in tests examining postpractice interference effects in naming colors of Stroop words. The study concluded that practice developed automatized reading suppression responses which held greater cognitive inertia for longer periods among MR…

  2. New monomers for fire-retardant radiation curable polymers

    SciTech Connect

    Kang, W.G.; Bush, R.W.; Ketley, A.D.

    1983-01-01

    Novel photosensitive compositions are described which combine excellent UV curability and good flame-retardant properties. These compositions consist of halogenated allyl or methallyl esters, which, in combination with polythiols and photoinitiators and other additives, result in screenable liquids which can be applied to electronic circuit boards and cured with UV light to hard, fire-retardant coatings.

  3. IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS

    EPA Science Inventory

    ABSTRACT
    The use of flame retardant chemicals in furniture fabric could pose a potential health risk to consumers from dermal absorption of these compounds. The objective of this study was to examine the in vitro dermal absorption of two flame retardant chemicals, [14C]-d...

  4. TERMINOLOGY AND CONCEPTS IN APPRAISING THE MENTALLY RETARDED.

    ERIC Educational Resources Information Center

    LORGE, IRVING; AND OTHERS

    THE OBJECTIVE OF THIS STUDY WAS TO MINIMIZE THE VARIABILITY IN LEGAL AND EDUCATIONAL CLASSIFICATION OF THE MENTALLY RETARDED. A SYSTEMATIC REVIEW WAS MADE OF THE SEMANTIC VARIATIONS IN THE DEFINITION OF THE MENTALLY RETARDED IN TERMS OF FUNCTIONAL ADEQUACY FOR EDUCATION, TRAINING, OR CUSTODIAL CARE. THE METHOD INVOLVED THE REVIEW OF STATUTES AND…

  5. Cone calorimeter evaluation of two flame retardant cotton fabrics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unbleached (grey) cotton needle punched nonwoven (NW) fabrics with 12.5% polypropylene scrim were treated with two phosphate-nitrogen based fire-retardant (FR) formulations, SRRC-1 and SRRC-2. The SRRC-1 formulation contains diammonium phosphate as the flame retardant chemical along with urea and d...

  6. COGNITIVE TRAINING WITH RETARDED CHILDREN, I. FINAL REPORT.

    ERIC Educational Resources Information Center

    CORTER, HAROLD M.; MCKINNEY, JAMES D.

    THE MAJOR PURPOSE OF THIS RESEARCH WAS TO DETERMINE WHETHER TRAINING IN SPECIFIC COGNITIVE PROCESSES IS EFFECTIVE IN INCREASING THE COGNITIVE FUNCTIONING OF RETARDED CHILDREN. IN PHASE I OF THE PROJECT, 51 EDUCABLE RETARDED AND 18 NORMAL SUBJECTS RECEIVED A 20-DAY PROGRAM IN SIMILARITIES-DIFFERENCES CONCEPT FORMATION AND WERE COMPARED WITH 42…

  7. Novel phosphonates triazine derivative as economic flame retardant for cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphorous-containing flame retardants are widely used in standard and engineering plastics, polyurethane foams, thermosets, coatings, and textiles. Organophosphorous flame retardants have been known to be more effective when used in conjunction with nitrogen-containing systems. Their mixture produ...

  8. Perceptual-Motor Attributes of Mentally Retarded Youth.

    ERIC Educational Resources Information Center

    Cratty, Bryant J.

    To evaluate six perceptual-motor attributes of trainable and educable mentally retarded children, a battery of tests was constructed which included body perception, gross agility, balance, locomotor ability, throwing, and tracking; 83 retarded subjects provided reliability data, and their scores, with those of 120 additional subjects, provided…

  9. Muscle Fatigue during Intermittent Exercise in Individuals with Mental Retardation

    ERIC Educational Resources Information Center

    Zafeiridis, Andreas; Giagazoglou, Paraskevi; Dipla, Konstantina; Salonikidis, Konstantinos; Karra, Chrisanthi; Kellis, Eleftherios

    2010-01-01

    This study examined fatigue profile during intermittent exercise in 10 men with mild to moderate mental retardation (MR) and 10 men without mental retardation (C). They performed 4 x 30 s maximal knee extensions and flexions with 1-min rest on an isokinetic dynamometer. Peak torque of flexors (PTFL) and extensors (PTEX), total work (TW), and…

  10. Behavioral Treatment of Aggression in the Mentally Retarded: A Review.

    ERIC Educational Resources Information Center

    Feldstein, Jerome H.

    The paper reviews 34 behavioral treatment studies (1967-1983) examining reduction of aggressive behavior in mentally retarded people. Research reviewed was limited to treatment of physically aggressive responses such as hits, kicks, bites, chokes, scratches, and throwing objects by persons designated as mentally retarded. Among results reported…

  11. Sexual Abuse Prevention for Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Lumley, Vicki A.; Miltenberger, Raymond G.

    1997-01-01

    Discusses sexual abuse among persons with mental retardation, skills for preventing sexual abuse, and methods for assessing prevention skills. Reviews research on abduction prevention programs for persons with mental retardation and on sexual abuse prevention programs for children, and makes suggestions for future research. (Author/CR)

  12. IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS

    EPA Science Inventory

    IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS. M F Hughes1, B C Edwards1, C T Mitchell1, and B Bhooshan2. 1US EPA, ORD, NHEERL, RTP, NC; 2US CPSC, LSC, Rockville, MD.
    Two flame retardant chemicals that are candidates for treating furniture fabrics were evaluated for ...

  13. Qualitative Differences in the Structure of Intelligence of Retarded Children.

    ERIC Educational Resources Information Center

    Wilson, Sheryl L.; Cleaves, Wallace T.

    To examine whether or not retarded individuals have the same structure of intelligence as normal IQ individuals, test scores from the Wechsler Intelligence Scale for Children-Revised (WISC-R), Reitan's Trail Making Test (TMT), and Beery's Developmental Test of Visual Motor Integration (VMI) for both a mildly retarded and normal IQ population of…

  14. The Elderly Retarded: A Little-known Group

    ERIC Educational Resources Information Center

    DiGiovanni, Louis

    1978-01-01

    Various methodologies place the number of elderly retarded Americans between 50,000 and 315,000 persons. The literature surveyed by the author indicates that the retarded experience the aging process similarly to the nonretarded population, can adapt to the nursing-home environment, and will become a greater social concern in the future. (Author)

  15. Estate Planning for Retarded Persons and Their Families.

    ERIC Educational Resources Information Center

    Fruge, Don L.; Green, Karen O.

    Intended for parents and legal guardians of mentally retarded persons, the manual provides guidelines for estate planning. An overview of definitions, causes, and prevalence factors in retardation is followed by reviews of the major financial assistance governmental programs such as Medicare, and Supplemental Security Income, and of legal…

  16. Building America Top Innovations 2012: Vapor Retarder Classification

    SciTech Connect

    none,

    2013-01-01

    This Building America Top Innovations profile describes research in vapor retarders. Since 2006 the IRC has permitted Class III vapor retarders like latex paint (see list above) in all climate zones under certain conditions thanks to research by Building America teams.

  17. Adaptive Behavior Malingering in Legal Claims of Mental Retardation

    ERIC Educational Resources Information Center

    Kadlubek, Renee Marie

    2012-01-01

    In 2002, the Supreme Court ruled that it is unconstitutional to put people with mental retardation to death for capital crimes ("Atkins v. Virginia," 2002). Justice Scalia dissented, suggesting that mental retardation is a condition easy to feign. The current study examined whether participants provided with the definition of mental…

  18. 38 CFR 4.127 - Mental retardation and personality disorders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... personality disorders. 4.127 Section 4.127 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... and personality disorders. Mental retardation and personality disorders are not diseases or injuries... superimposed upon mental retardation or a personality disorder may be service-connected. (Authority: 38...

  19. 38 CFR 4.127 - Mental retardation and personality disorders.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... personality disorders. 4.127 Section 4.127 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... and personality disorders. Mental retardation and personality disorders are not diseases or injuries... superimposed upon mental retardation or a personality disorder may be service-connected. (Authority: 38...

  20. 38 CFR 4.127 - Mental retardation and personality disorders.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... personality disorders. 4.127 Section 4.127 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... and personality disorders. Mental retardation and personality disorders are not diseases or injuries... superimposed upon mental retardation or a personality disorder may be service-connected. (Authority: 38...

  1. 38 CFR 4.127 - Mental retardation and personality disorders.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... personality disorders. 4.127 Section 4.127 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... and personality disorders. Mental retardation and personality disorders are not diseases or injuries... superimposed upon mental retardation or a personality disorder may be service-connected. (Authority: 38...

  2. 38 CFR 4.127 - Mental retardation and personality disorders.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... personality disorders. 4.127 Section 4.127 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... and personality disorders. Mental retardation and personality disorders are not diseases or injuries... superimposed upon mental retardation or a personality disorder may be service-connected. (Authority: 38...

  3. Psychiatric Illness in Mentally Retarded Adolescents: Clinical Features.

    ERIC Educational Resources Information Center

    Masi, Gabriele

    1998-01-01

    Describes the clinical features of the most important psychiatric disorders in mentally retarded adolescents: mood disorders, psychotic disorders, severe behavioral disorders, personality disorders, anxiety disorders, and attention-deficit The impact of mental retardation on personality development is confirmed by the high psychopathological…

  4. Public Health Approach to the Study of Mental Retardation

    ERIC Educational Resources Information Center

    Chapman, Derek A.; Scott, Keith G.; Stanton-Chapman, Tina L.

    2008-01-01

    We applied a public health approach to the study of mental retardation by providing a basic descriptive epidemiological analysis using a large statewide linked birth and public school record database (N = 327,831). Sociodemographic factors played a key role across all levels of mental retardation. Birthweight less than 1000 g was associated with…

  5. Zebrafish Wnt9a,9b paralog comparisons suggest ancestral roles for Wnt9 in neural, oral-pharyngeal ectoderm and mesendoderm.

    PubMed

    Cox, A A; Jezewski, P A; Fang, P-K; Payne-Ferreira, T L

    2010-09-01

    The Wnts are a highly conserved family of secreted glycoproteins involved in cell-cell signaling and pattern formation during early embryonic development. Teasing out the role of individual Wnt molecules through development is challenging. Gene duplications are one of the most important mechanisms for generating evolutionary variations. The current consensus suggests that most anatomical variation is generated by divergence of regulatory control regions rather than by coding sequence divergence. Thus phylogenetic comparisons of divergent gene expression patterns are essential to understanding ancestral morphogenetic patterns from which subsequent anatomy diversified in modern lineages. We previously demonstrated strongest expression of zebrafish wnt9b within its heart tube, limb bud and ventral/anterior ectoderm during oral and pharyngeal arch patterning. Our goal is to compare and contrast zwnt9b to its closest paralog, zwnt9a. Sequenced, fulllength zebrafish wnt9a and wnt9b cDNA clones were used for phylogenetic analysis, which suggests their derivation from a common pre-vertebrate archeolog by gene duplication and divergence. Here we demonstrate that zwnt9a expression is found within unique (CNS, pronephric ducts, sensory organs) and overlapping (pectoral fin buds) expression domains relative to zwnt9b. Apparently, Wnt9 paralogs differentially parsed common ancestral expression domains during their subsequent rounds of gene duplication, divergence and loss in different vertebrate lineages. This expression data suggests ancestral roles for Wnt9s in early patterning of neural/oral-pharyngeal ectoderm and mesendoderm derivatives.

  6. Positive selection and functional divergence of R2R3-MYB paralogous genes expressed in inflorescence buds of Scutellaria species (Labiatae).

    PubMed

    Huang, Bing-Hong; Pang, Erli; Chen, Yi-Wen; Cao, Huifen; Ruan, Yu; Liao, Pei-Chun

    2015-03-13

    Anthocyanin is the main pigment forming floral diversity. Several transcription factors that regulate the expression of anthocyanin biosynthetic genes belong to the R2R3-MYB family. Here we examined the transcriptomes of inflorescence buds of Scutellaria species (skullcaps), identified the expression R2R3-MYBs, and detected the genetic signatures of positive selection for adaptive divergence across the rapidly evolving skullcaps. In the inflorescence buds, seven R2R3-MYBs were identified. MYB11 and MYB16 were detected to be positively selected. The signature of positive selection on MYB genes indicated that species diversification could be affected by transcriptional regulation, rather than at the translational level. When comparing among the background lineages of Arabidopsis, tomato, rice, and Amborella, heterogeneous evolutionary rates were detected among MYB paralogs, especially between MYB13 and MYB19. Significantly different evolutionary rates were also evidenced by type-I functional divergence between MYB13 and MYB19, and the accelerated evolutionary rates in MYB19, implied the acquisition of novel functions. Another paralogous pair, MYB2/7 and MYB11, revealed significant radical amino acid changes, indicating divergence in the regulation of different anthocyanin-biosynthetic enzymes. Our findings not only showed that Scutellaria R2R3-MYBs are functionally divergent and positively selected, but also indicated the adaptive relevance of regulatory genes in floral diversification.

  7. Optimization of retardance for a complete Stokes polarimeter

    SciTech Connect

    Sabatke, D.S.; Descour, M.R.; Dereniak, E.L.; Sweatt, W.C.; Kemme, S.A.; Phipps, G.S.

    2000-01-13

    The authors present two figures of merit based on singular value decomposition which can be used to assess the noise immunity of a complete Stokes polarimeter. These are used to optimize a polarimeter consisting of a rotatable retarder and fixed polarizer. A retardance of 132{degree} (approximately three eights wave) and retarder orientation angles of {+-}51.7{degree} and {+-}15.1{degree} are found to be optimal when four measurements are used. Use of this retardance affords a factor of 1.5 improvement in signal-to-noise ratio over systems employing a quarter wave plate. A geometric means of visualizing the optimization process is discussed, and the advantages of the use of additional measurements are investigated. No advantage of using retarder orientation angles spaced uniformly through 360{degree} is found over repeated measurements made at the four angles given previously.

  8. Conjunctive visual search in individuals with and without mental retardation.

    PubMed

    Carlin, Michael; Chrysler, Christina; Sullivan, Kate

    2007-01-01

    A comprehensive understanding of the basic visual and cognitive abilities of individuals with mental retardation is critical for understanding the basis of mental retardation and for the design of remediation programs. We assessed visual search abilities in individuals with mild mental retardation and in MA- and CA-matched comparison groups. Our goal was to determine the effect of decreasing target-distracter disparities on visual search efficiency. Results showed that search rates for the group with mental retardation and the MA-matched comparisons were more negatively affected by decreasing disparities than were those of the CA-matched group. The group with mental retardation and the MA-matched group performed similarly on all tasks. Implications for theory and application are discussed. PMID:17181391

  9. FXR1, an autosomal homolog of the fragile X mental retardation gene.

    PubMed Central

    Siomi, M C; Siomi, H; Sauer, W H; Srinivasan, S; Nussbaum, R L; Dreyfuss, G

    1995-01-01

    Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1. Images PMID:7781595

  10. Metakaolin as a radon retardant from concrete.

    PubMed

    Lau, B M F; Balendran, R V; Yu, K N

    2003-01-01

    Granite aggregates are known to be the radon source in concrete. Recently, metakaolin has been introduced as a partial substitution of Portland cement to produce high strength concrete. It can effectively reduce the porosity of both the matrix and the aggregate/paste transition zone, which suggests its ability to retard radon emission from concrete aggregates. In the present work, radon exhalation rates from concrete cubes substituted with metakaolin were measured using charcoal canisters and gamma spectroscopy, and were considerably lower than those from normal concrete, by about 30%. The indoor radon concentration reduction is estimated as approximately 9 Bq m(-3) calculated using a room model, causing a 30% reduction in the indoor radon concentration and the corresponding radon dose. Therefore, metakaolin is a simple material to reduce the indoor radon concentration and the radon dose.

  11. Cytogenetic Findings in Mentally Retarded Iranian Patients

    PubMed Central

    Nasiri, F; Mahjoubi, F; Manouchehry, F; Razazian, F; Mortezapour, F; Rahnama, M

    2012-01-01

    We conducted a cytogenetic study on 865 individuals with idiopathic mental retardation (MR) who were admitted to the Cytogenetics Department of the Iran Blood Transfusion Organisation (IBTO) Research Centre, Tehran, Iran; these were performed on blood samples using conventional staining methods. Chromosome anomalies were identified in 205 of the patients (23.6%). The majority were Down’s syndrome cases (n = 138). In 33 males, a positive fragile X anomaly was found. The remainder (n = 34) had other chromosomal abnormalities including structural chromosome aberrations (n = 23), marker chromosomes with an unknown origin (n = 3), sex chromosome aneuploidy (n = 6) and trisomy 18 (n = 2). The contribution of chromosome aberrations to the cause of MR in this group of patients is discussed. PMID:24052729

  12. The Helmholtz theorem and retarded fields

    NASA Astrophysics Data System (ADS)

    Heras, Ricardo

    2016-11-01

    Textbooks frequently use the Helmholtz theorem to derive expressions for electrostatic and magnetostatic fields but they do not usually apply this theorem to derive expressions for time-dependent electric and magnetic fields, even when there is no formal objection to doing so because the proof of the theorem does not involve time derivatives but only spatial derivatives. Here we address the question as to whether the Helmholtz theorem is useful in deriving expressions for the fields of Maxwell’s equations. We show that when this theorem is applied to Maxwell’s equations we obtain instantaneous expressions of the electric and magnetic fields, which are formally correct but of little practical usefulness. We then discuss two generalizations of the theorem which are shown to be useful in deriving the retarded fields.

  13. A mentally retarded patient with schizophrenia.

    PubMed

    Rabia, K; Khoo, Em

    2008-01-01

    Schizophrenia is one of the most incapacitating forms of mental disorder that runs a chronic and relapsing course. It typically starts in adolescence or early adulthood and can be life-long. It is more common in people with learning disabilities than in the general population. Its prodromal features include depression, anxiety, suspiciousness, social isolation and bizarre behaviour. It may result in significant functional, social and economic impairments. The care of patients with schizophrenia places a considerable burden on all carers including patient's family, health and social services. Treatment includes pharmacotherapy and psychosocial interventions. In this case report we describe a thirteen-year-old patient with schizophrenia who has a background history of mental retardation. PMID:25606140

  14. Highly accurate spectral retardance characterization of a liquid crystal retarder including Fabry-Perot interference effects

    SciTech Connect

    Vargas, Asticio; Mar Sánchez-López, María del; García-Martínez, Pascuala; Arias, Julia; Moreno, Ignacio

    2014-01-21

    Multiple-beam Fabry-Perot (FP) interferences occur in liquid crystal retarders (LCR) devoid of an antireflective coating. In this work, a highly accurate method to obtain the spectral retardance of such devices is presented. On the basis of a simple model of the LCR that includes FP effects and by using a voltage transfer function, we show how the FP features in the transmission spectrum can be used to accurately retrieve the ordinary and extraordinary spectral phase delays, and the voltage dependence of the latter. As a consequence, the modulation characteristics of the device are fully determined with high accuracy by means of a few off-state physical parameters which are wavelength-dependent, and a single voltage transfer function that is valid within the spectral range of characterization.

  15. Environmental monitoring of brominated flame retardants

    NASA Astrophysics Data System (ADS)

    Vagula, Mary C.; Kubeldis, Nathan; Nelatury, Charles F.

    2011-06-01

    Brominated flame retardants (BFRs) are synthetic organobromide compounds which inhibit ignition and combustion processes. Because of their immense ability to retard fire and save life and property, they have been extensively used in many products such as TVs, computers, foam, plastics etc. The five major classes of BFRs are tetrabromobisphenol-A (TBBPA), hexabromocyclododecane (HBCD), pentabromodiphenyl ether, octabromodiphenyl ether, and decabromodiphenyl ether. The last three are also commonly called PBDEs. BDE-85 and BDE-209 are the two prominent congeners of PBDEs and this study reports the adverse effects of these congeners in rodents. Exposure of rat sciatic nerves to 5 μg/mL and 20 μg/mL of BDE-85 and BDE-209 respectively lead to significant, concentration dependent reduction in nerve conduction function. Glucose absorption in the rat intestinal segments exposed to 5 μg/mL of BDE-85 and BDE-209 was significantly reduced for both the compounds tested. Lastly, mice when exposed to 0.25 mg/kg body weight for four days showed a disruption in oxidant and antioxidant equilibrium. The tissues namely liver and brain have shown increase in the levels of lipid hydroperoxides indicating oxidative stress. Moreover, all the protective enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and glutathione S transferase (GST) have shown tissue specific alterations indicating the induction of damaging oxidative stress and setting in of lipid peroxidation in exposed animals. The results indicate monitoring of PBDEs in the environment is essential because levels as low as 5 μg/mL and 0.25 mg/kg body weight were able to cause damage to the functions of rodents.

  16. Residential Programming for Mentally Retarded Persons. Volume I, Prevailing Attitudes and Practices in the Field of Mental Retardation.

    ERIC Educational Resources Information Center

    National Association for Retarded Children, Arlington, TX. South Central Regional Office.

    The first of a series of four booklets on residential programing for the mentally retarded reviews for parents the prevailing definitions, attitudes and practices in the field. Mental retardation is defined as subaverage functioning which originates during the developmental period and is associated with impairment in adaptive behavior. The need…

  17. Genes and proteins of Escherichia coli K-12.

    PubMed

    Riley, M

    1998-01-01

    GenProtEC is a database of Escherichia coli genes and their gene products, classified by type of function and physiological role and with citations to the literature for each. Also present are data on sequence similarities among E.coli proteins, representing groups of paralogous genes, with PAM values, percent identity of amino acids, length of alignment and percent aligned. GenProtEC can be accessed at the URL http://www.mbl.edu/html/ecoli.html PMID:9399799

  18. A New Protein Superfamily: TPPP-Like Proteins

    PubMed Central

    Orosz, Ferenc

    2012-01-01

    The introduction of the term ‘Tubulin Polymerization Promoting Protein (TPPP)-like proteins’ is suggested. They constitute a eukaryotic protein superfamily, characterized by the presence of the p25alpha domain (Pfam05517, IPR008907), and named after the first identified member, TPPP/p25, exhibiting microtubule stabilizing function. TPPP-like proteins can be grouped on the basis of two characteristics: the length of their p25alpha domain, which can be long, short, truncated or partial, and the presence or absence of additional domain(s). TPPPs, in the strict sense, contain no other domains but one long or short p25alpha one (long- and short-type TPPPs, respectively). Proteins possessing truncated p25alpha domain are first described in this paper. They evolved from the long-type TPPPs and can be considered as arthropod-specific paralogs of long-type TPPPs. Phylogenetic analysis shows that the two groups (long-type and truncated TPPPs) split in the common ancestor of arthropods. Incomplete p25alpha domains can be found in multidomain TPPP-like proteins as well. The various subfamilies occur with a characteristic phyletic distribution: e. g., animal genomes/proteomes contain almost without exception long-type TPPPs; the multidomain apicortins occur almost exclusively in apicomplexan parasites. There are no data about the physiological function of these proteins except two human long-type TPPP paralogs which are involved in developmental processes of the brain and the musculoskeletal system, respectively. I predict that the superfamily members containing long or partial p25alpha domain are often intrinsically disordered proteins, while those with short or truncated domain(s) are structurally ordered. Interestingly, members of this superfamily connected or maybe connected to diseases are intrinsically disordered proteins. PMID:23166627

  19. Flame Retardant Applications in Camping Tents and Potential Exposure.

    PubMed

    Keller, Alexander S; Raju, Nikhilesh P; Webster, Thomas F; Stapleton, Heather M

    2014-02-11

    Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met CPAI-84 standards by analyzing 11 samples of tent fabrics for chemical flame retardant additives. Furthermore, we investigated potential exposure by collecting paired samples of tent wipes and hand wipes from 27 individuals after tent setup. Of the 11 fabric samples analyzed, 10 contained flame retardant additives, which included tris(1,3-dichloroisopropyl) phosphate (TDCPP), decabromodiphenyl ether (BDE-209), triphenyl phosphate, and tetrabromobisphenol-A. Flame retardant concentrations were discovered to be as high as 37.5 mg/g (3.8% by weight) in the tent fabric samples, and TDCPP and BDE-209 were the most frequently detected in these samples. We also observed a significant association between TDCPP levels in tent wipes and those in paired hand wipes, suggesting that human contact with the tent fabric material leads to the transfer of the flame retardant to the skin surface and human exposure. These results suggest that direct contact with flame retardant-treated textiles may be a source of exposure. Future studies will be needed to better characterize exposure, including via inhalation and dermal sorption from air. PMID:24804279

  20. Flame Retardant Applications in Camping Tents and Potential Exposure

    PubMed Central

    2015-01-01

    Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met CPAI-84 standards by analyzing 11 samples of tent fabrics for chemical flame retardant additives. Furthermore, we investigated potential exposure by collecting paired samples of tent wipes and hand wipes from 27 individuals after tent setup. Of the 11 fabric samples analyzed, 10 contained flame retardant additives, which included tris(1,3-dichloroisopropyl) phosphate (TDCPP), decabromodiphenyl ether (BDE-209), triphenyl phosphate, and tetrabromobisphenol-A. Flame retardant concentrations were discovered to be as high as 37.5 mg/g (3.8% by weight) in the tent fabric samples, and TDCPP and BDE-209 were the most frequently detected in these samples. We also observed a significant association between TDCPP levels in tent wipes and those in paired hand wipes, suggesting that human contact with the tent fabric material leads to the transfer of the flame retardant to the skin surface and human exposure. These results suggest that direct contact with flame retardant-treated textiles may be a source of exposure. Future studies will be needed to better characterize exposure, including via inhalation and dermal sorption from air. PMID:24804279

  1. Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site

    SciTech Connect

    Grossman, Moran; Born, Benjamin; Heyden, Matthias; Tworowski, Dmitry; Fields, Gregg B.; Sagi, Irit; Havenith, Martina

    2011-09-18

    Solvent dynamics can play a major role in enzyme activity, but obtaining an accurate, quantitative picture of solvent activity during catalysis is quite challenging. Here, we combine terahertz spectroscopy and X-ray absorption analyses to measure changes in the coupled water-protein motions during peptide hydrolysis by a zinc-dependent human metalloprotease. These changes were tightly correlated with rearrangements at the active site during the formation of productive enzyme-substrate intermediates and were different from those in an enzyme–inhibitor complex. Molecular dynamics simulations showed a steep gradient of fast-to-slow coupled protein-water motions around the protein, active site and substrate. Our results show that water retardation occurs before formation of the functional Michaelis complex. We propose that the observed gradient of coupled protein-water motions may assist enzyme-substrate interactions through water-polarizing mechanisms that are remotely mediated by the catalytic metal ion and the enzyme active site.

  2. Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkin's Lymphomas

    PubMed Central

    Thapa, Dharma R.; Li, Xinmin; Jamieson, Beth D.; Martínez-Maza, Otoniel

    2011-01-01

    Background Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined. Methodology/Principal Findings We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis. Conclusion Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs. PMID:21698185

  3. LGR4/GPR48 Inactivation Leads to Aniridia-Genitourinary Anomalies-Mental Retardation Syndrome Defects*

    PubMed Central

    Yi, Tingfang; Weng, Jinsheng; Siwko, Stefan; Luo, Jian; Li, Dali; Liu, Mingyao

    2014-01-01

    AGR syndrome (the clinical triad of aniridia, genitourinary anomalies, and mental retardation, a subgroup of WAGR syndrome for Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation) is a rare syndrome caused by a contiguous gene deletion in the 11p13–14 region. However, the mechanisms of WAGR syndrome pathogenesis are elusive. In this study we provide evidence that LGR4 (also named GPR48), the only G-protein-coupled receptor gene in the human chromosome 11p12–11p14.4 fragment, is the key gene responsible for the diseases of AGR syndrome. Deletion of Lgr4 in mouse led to aniridia, polycystic kidney disease, genitourinary anomalies, and mental retardation, similar to the pathological defects of AGR syndrome. Furthermore, Lgr4 inactivation significantly increased cell apoptosis and decreased the expression of multiple important genes involved in the development of WAGR syndrome related organs. Specifically, deletion of Lgr4 down-regulated the expression of histone demethylases Jmjd2a and Fbxl10 through cAMP-CREB signaling pathways both in mouse embryonic fibroblast cells and in urinary and reproductive system mouse tissues. Our data suggest that Lgr4, which regulates eye, kidney, testis, ovary, and uterine organ development as well as mental development through genetic and epigenetic surveillance, is a novel candidate gene for the pathogenesis of AGR syndrome. PMID:24519938

  4. Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins.

    PubMed

    Panina, Ekaterina M; Mironov, Andrey A; Gelfand, Mikhail S

    2003-08-19

    Zinc is an important component of many proteins, but in large concentrations it is poisonous to the cell. Thus its transport is regulated by zinc repressors ZUR of proteobacteria and Gram-positive bacteria from the Bacillus group and AdcR of bacteria from the Streptococcus group. Comparative computational analysis allowed us to identify binding signals of ZUR repressors GAAATGTTATANTATAACATTTC for gamma-proteobacteria, GTAATGTAATAACATTAC for the Agrobacterium group, GATATGTTATAACATATC for the Rhododoccus group, TAAATCGTAATNATTACGATTTA for Gram-positive bacteria, and TTAACYRGTTAA of the streptococcal AdcR repressor. In addition to known transporters and their paralogs, zinc regulons were predicted to contain a candidate component of the ATP binding cassette, zinT (b1995 in Escherichia coli and yrpE in Bacillus subtilis). Candidate AdcR-binding sites were identified upstream of genes encoding pneumococcal histidine triad (PHT) proteins from a number of pathogenic streptococci. Protein functional analysis of this family suggests that PHT proteins are involved in the invasion process. Finally, repression by zinc was predicted for genes encoding a variety of paralogs of ribosomal proteins. The original copies of all these proteins contain zinc-ribbon motifs and thus likely bind zinc, whereas these motifs are destroyed in zinc-regulated paralogs. We suggest that the induction of these paralogs in conditions of zinc starvation leads to their incorporation in a fraction of ribosomes instead of the original ribosomal proteins; the latter are then degraded with subsequent release of some zinc for the utilization by other proteins. Thus we predict a mechanism for maintaining zinc availability for essential enzymes. PMID:12904577

  5. Stokes polarimetry using analysis of the nonlinear voltage-retardance relationship for liquid-crystal variable retarders

    SciTech Connect

    López-Téllez, J. M. Bruce, N. C.

    2014-03-15

    We present a method for using liquid-crystal variable retarders (LCVR’s) with continually varying voltage to measure the Stokes vector of a light beam. The LCVR's are usually employed with fixed retardance values due to the nonlinear voltage-retardance behavior that they show. The nonlinear voltage-retardance relationship is first measured and then a linear fit of the known retardance terms to the detected signal is performed. We use known waveplates (half-wave and quarter-wave) as devices to provide controlled polarization states to the Stokes polarimeter and we use the measured Stokes parameters as functions of the orientation of the axes of the waveplates as an indication of the quality of the polarimeter. Results are compared to a Fourier analysis method that does not take into account the nonlinear voltage-retardance relationship and also to a Fourier analysis method that uses experimental voltage values to give a linear retardance function with time. Also, we present results of simulations for comparison.

  6. A Database of Plastid Protein Families from Red Algae and Apicomplexa and Expression Regulation of the moeB Gene

    PubMed Central

    2015-01-01

    We report the database of plastid protein families from red algae, secondary and tertiary rhodophyte-derived plastids, and Apicomplexa constructed with the novel method to infer orthology. The families contain proteins with maximal sequence similarity and minimal paralogous content. The database contains 6509 protein entries, 513 families and 278 nonsingletons (from which 230 are paralog-free, and among the remaining 48, 46 contain at maximum two proteins per species, and 2 contain at maximum three proteins per species). The method is compared with other approaches. Expression regulation of the moeB gene is studied using this database and the model of RNA polymerase competition. An analogous database obtained for green algae and their symbiotic descendants, and applications based on it are published earlier. PMID:26114108

  7. A Database of Plastid Protein Families from Red Algae and Apicomplexa and Expression Regulation of the moeB Gene.

    PubMed

    Zverkov, Oleg A; Seliverstov, Alexandr V; Lyubetsky, Vassily A

    2015-01-01

    We report the database of plastid protein families from red algae, secondary and tertiary rhodophyte-derived plastids, and Apicomplexa constructed with the novel method to infer orthology. The families contain proteins with maximal sequence similarity and minimal paralogous content. The database contains 6509 protein entries, 513 families and 278 nonsingletons (from which 230 are paralog-free, and among the remaining 48, 46 contain at maximum two proteins per species, and 2 contain at maximum three proteins per species). The method is compared with other approaches. Expression regulation of the moeB gene is studied using this database and the model of RNA polymerase competition. An analogous database obtained for green algae and their symbiotic descendants, and applications based on it are published earlier.

  8. Fire retardant effects of polymer nanocomposites.

    PubMed

    Hull, T Richard; Stec, Anna A; Nazare, Shonali

    2009-07-01

    Among the many and varied applications of nanotechnology, the dispersion of nanoscopic fillers to form polymer nanocomposites with improved fire behaviour illustrates the potential and diversity of nanoscience. Different polymers decompose in different ways and fire retardants act to inhibit the decomposition or flaming combustion processes. Polymer nanocomposites form barriers between the fuel and air, reducing the rate of burning, but beyond that there is little consistency in their effects. It is shown that the decomposition products of polypropylene are changed by the presence of nanoclay, although there is only a small influence on the mass loss rate. The rheological properties of molten polymer nanocomposites are radically different from those of virgin polymers, and these will profoundly affect the heat transfer through the material, resulting in a shorter time to ignition and lower peak in the heat release rate, typical of polymer nanocomposites. The dispersion of nanofillers within polymers is generally measured in the cold polymer, but since this does not reflect the condition at the time of ignition, it is proposed that temperature ramped rheological measurements are more appropriate indicators of dispersion. The influence of polymer nanocomposite formation on the yields of toxic products from fire is studied using the ISO 19700 steady state tube furnace, and it is found that under early stages of burning more carbon monoxide and organoirritants are formed, but under the more toxic under-ventilated conditions, less toxic products are formed.

  9. Oral rehabilitation and management of mentally retarded.

    PubMed

    Solanki, Jitender; Khetan, Jitendra; Gupta, Sarika; Tomar, Deepak; Singh, Meenakshi

    2015-01-01

    High level of periodontal problems of dental caries are frequently observed in mentally handicapped children. This group of patients presents various problems when they face dental treatments. Identification of such population and providing them affordable oral health care is the new concept. A systematic method for identification and screening of persons with mental retardation has been developed and is being followed. Cost and fear are the most commonly cited barriers to dental care. Physical or mental may lead to deterioration in self-care, and oral care state have a low priority. Risk factors are inter-related and are often barriers to oral health. With advancements in today's world sufficient information and support is available for each and every individual to lead a healthy life which include the access to the oral health care. Factors such as fear, anxiety and dental phobia plays a vital role in acceptance of dental care and also the delaying of dental care. Lack of knowledge of oral and dental disease, awareness or oral need, oral side-effects of medication and organization of dental services are highlighted in the literature. All health personnel should receive training to support the concept of primary oral health care. Training about dealing with such mentally handicapped people should be addressed urgently among the health professionals. PMID:25738098

  10. Oral Rehabilitation and Management of Mentally Retarded

    PubMed Central

    Khetan, Jitendra; Gupta, Sarika; Tomar, Deepak; Singh, Meenakshi

    2015-01-01

    High level of periodontal problems of dental caries are frequently observed in mentally handicapped children. This group of patients presents various problems when they face dental treatments. Identification of such population and providing them affordable oral health care is the new concept. A systematic method for identification and screening of persons with mental retardation has been developed and is being followed. Cost and fear are the most commonly cited barriers to dental care. Physical or mental may lead to deterioration in self-care, and oral care state have a low priority. Risk factors are inter-related and are often barriers to oral health. With advancements in today’s world sufficient information and support is available for each and every individual to lead a healthy life which include the access to the oral health care. Factors such as fear, anxiety and dental phobia plays a vital role in acceptance of dental care and also the delaying of dental care. Lack of knowledge of oral and dental disease, awareness or oral need, oral side-effects of medication and organization of dental services are highlighted in the literature. All health personnel should receive training to support the concept of primary oral health care. Training about dealing with such mentally handicapped people should be addressed urgently among the health professionals. PMID:25738098

  11. Radionuclide transport and retardation in tuff

    SciTech Connect

    Vine, E.N.; Bayhurst, B.P.; Daniels, W.R.; DeVilliers, S.J.; Erdal, B.R.; Lawrence, F.O.; Wolfsberg, K.

    1980-12-31

    Batch measurements provide an understanding of which experimental variables are important. For example, sorption ratios vary little with particle size (and surface area); however, groundwater composition and rock composition are quite important. A general correlation has been identified between mineralogy (major phases) and degree of sorption for strontium, cesium, and barium. Although these are approximate, a more detailed analysis may be possible as more samples are studied and the data base increased. Data from crushed tuff columns indicate that, except in simple cases where sorption coefficients are relatively low, and ion-exchange equilibria not only exist but are the dominant mechanism for removal of radioisotopes from solution, the simple relation between the sorption ratio R/sub d/ (or K/sub d/) and the relative velocity of radionuclides with respect to groundwater velocity may be insufficient to permit accurate modeling of the retardation of radionuclides. Additional work on whole core columns and larger blocks of intact material is required to better understand radionuclide sorption and transport through rock.

  12. Brominated flame retardant exposure of aircraft personnel.

    PubMed

    Strid, Anna; Smedje, Greta; Athanassiadis, Ioannis; Lindgren, Torsten; Lundgren, Håkan; Jakobsson, Kristina; Bergman, Åke

    2014-12-01

    The use of brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) in aircraft is the result of high fire safety demands. Personnel working in or with aircraft might therefore be exposed to several BFRs. Previous studies have reported PBDE exposure in flight attendants and in passengers. One other group that may be subjected to significant BFR exposure via inhalation, are the aircraft maintenance workers. Personnel exposure both during flights and maintenance of aircraft, are investigated in the present study. Several BFRs were present in air and dust sampled during both the exposure scenarios; PBDEs, hexabromocyclododecane (HBCDD), decabromodiphenyl ethane (DBDPE) and 1,2-bis (2,4,6-tribromophenoxy) ethane. PBDEs were also analyzed in serum from pilots/cabin crew, maintenance workers and from a control group of individuals without any occupational aircraft exposure. Significantly higher concentrations of PBDEs were found in maintenance workers compared to pilots/cabin crew and control subjects with median total PBDE concentrations of 19, 6.8 and 6.6 pmol g(-1) lipids, respectively. Pilots and cabin crew had similar concentrations of most PBDEs as the control group, except for BDE-153 and BDE-154 which were significantly higher. Results indicate higher concentrations among some of the pilots compared to the cabin crew. It is however, evident that the cabin personnel have lower BFR exposures compared to maintenance workers that are exposed to such a degree that their blood levels are significantly different from the control group. PMID:24745557

  13. Psychomotor Retardation in Elderly Untreated Depressed Patients

    PubMed Central

    Beheydt, Lieve Lia; Schrijvers, Didier; Docx, Lise; Bouckaert, Filip; Hulstijn, Wouter; Sabbe, Bernard

    2015-01-01

    Background: Psychomotor retardation (PR) is one of the core features in depression according to DSM V (1), but also aging in itself causes cognitive and psychomotor slowing. This is the first study investigating PR in relation to cognitive functioning and to the concomitant effect of depression and aging in a geriatric population ruling out contending effects of psychotropic medication. Methods: A group of 28 non-demented depressed elderly is compared to a matched control group of 20 healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests. Statistical analysis consisted of a General Linear Method multivariate analysis of variance to compare the clinical, cognitive, and psychomotor outcomes of the two groups. Results: Patients performed worse on all clinical, cognitive, and PR measures. Both groups showed an effect of cognitive load on fine motor function but the influence was significantly larger for patients than for healthy elderly except for the initiation time. Limitations: Due to the restrictive inclusion criteria, only a relatively limited sample size could be obtained. Conclusion: With a medication free sample, an additive effect of depression and aging on cognition and PR in geriatric patients was found. As this effect was independent of demand of effort (by varying the cognitive load), it was apparently not a motivational slowing effect of depression. PMID:25674065

  14. Brominated flame retardant exposure of aircraft personnel.

    PubMed

    Strid, Anna; Smedje, Greta; Athanassiadis, Ioannis; Lindgren, Torsten; Lundgren, Håkan; Jakobsson, Kristina; Bergman, Åke

    2014-12-01

    The use of brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) in aircraft is the result of high fire safety demands. Personnel working in or with aircraft might therefore be exposed to several BFRs. Previous studies have reported PBDE exposure in flight attendants and in passengers. One other group that may be subjected to significant BFR exposure via inhalation, are the aircraft maintenance workers. Personnel exposure both during flights and maintenance of aircraft, are investigated in the present study. Several BFRs were present in air and dust sampled during both the exposure scenarios; PBDEs, hexabromocyclododecane (HBCDD), decabromodiphenyl ethane (DBDPE) and 1,2-bis (2,4,6-tribromophenoxy) ethane. PBDEs were also analyzed in serum from pilots/cabin crew, maintenance workers and from a control group of individuals without any occupational aircraft exposure. Significantly higher concentrations of PBDEs were found in maintenance workers compared to pilots/cabin crew and control subjects with median total PBDE concentrations of 19, 6.8 and 6.6 pmol g(-1) lipids, respectively. Pilots and cabin crew had similar concentrations of most PBDEs as the control group, except for BDE-153 and BDE-154 which were significantly higher. Results indicate higher concentrations among some of the pilots compared to the cabin crew. It is however, evident that the cabin personnel have lower BFR exposures compared to maintenance workers that are exposed to such a degree that their blood levels are significantly different from the control group.

  15. Cytochrome P450 and actin genes expressed in Helicoverpa zea and Helicoverpa armigera: paralogy/orthology identification, gene conversion and evolution.

    PubMed

    Li, Xianchun; Berenbaum, May R; Schuler, Mary A

    2002-03-01

    Molecular phylogenetic analysis was conducted using conserved cytoplasmic actin and diversified cytochrome P450 (P450) sequences isolated from Helicoverpa zea and Helicoverpa armigera, two species thought to be closely related based on allozyme analyses. These sequences were compared in turn with published sequences from other insects to gain insight into how different gene families evolve. In Bombyx mori and these Helicoverpa species, cytoplasmic actin genes are present as a pair of tandemly duplicated paralogs with coding sequence identities as high as 95.5% (B. mori), 98.9% (H. zea) and 98.5% (H. armigera) due to recent 5'-polar gene conversions. Phylogeny and interspecies comparisons assign the six actin genes into two orthologous groups: HaA3a/HzA3a/BmA3 and HaA3b/HzA3b/BmA4, which exhibit more similarities between H. zea and H. armigera than between Helicoverpa species and B. mori. Like the actin genes in H. zea, four CYP6B genes exist as two pairs of duplicated paralogs with recent 5'-polar gene conversions. Interspecific comparisons and phylogeny analysis identified three groups of orthologous CYP6B genes: H. zea CYP6B8 or CYP6B28/H. armigera CYP6B7, H. zea CYP6B27/H. armigera CYP6B6, and H. zea CYP6B9/H. armigera CYP6B2/Heliothis virescens CYP6B10. The low degree of divergence in the first two of these groups is comparable to allelic variation within a single species. These orthologous relationships and the high degrees of similarity in both actin and P450 genes strongly indicate that these Helicoverpa species are extremely closely related.

  16. Gene conversion and DNA sequence polymorphism in the sex-determination gene fog-2 and its paralog ftr-1 in Caenorhabditis elegans.

    PubMed

    Rane, Hallie S; Smith, Jessica M; Bergthorsson, Ulfar; Katju, Vaishali

    2010-07-01

    Gene conversion, a form of concerted evolution, bears enormous potential to shape the trajectory of sequence and functional divergence of gene paralogs subsequent to duplication events. fog-2, a sex-determination gene unique to Caenorhabditis elegans and implicated in the origin of hermaphroditism in this species, resulted from the duplication of ftr-1, an upstream gene of unknown function. Synonymous sequence divergence in regions of fog-2 and ftr-1 (excluding recent gene conversion tracts) suggests that the duplication occurred 46 million generations ago. Gene conversion between fog-2 and ftr-1 was previously discovered in experimental fog-2 knockout lines of C. elegans, whereby hermaphroditism was restored in mutant obligately outcrossing male-female populations. We analyzed DNA-sequence variation in fog-2 and ftr-1 within 40 isolates of C. elegans from diverse geographic locations in order to evaluate the contribution of gene conversion to genetic variation in the two gene paralogs. The analysis shows that gene conversion contributes significantly to DNA-sequence diversity in fog-2 and ftr-1 (22% and 34%, respectively) and may have the potential to alter sexual phenotypes in natural populations. A radical amino acid change in a conserved region of the F-box domain of fog-2 was found in natural isolates of C. elegans with significantly lower fecundity. We hypothesize that the lowered fecundity is due to reduced masculinization and less sperm production and that amino acid replacement substitutions and gene conversion in fog-2 may contribute significantly to variation in the degree of inbreeding and outcrossing in natural populations.

  17. Development of Flame Retardants for Engineering Polymers and Polyurethanes

    NASA Astrophysics Data System (ADS)

    Desikan, Anantha

    2013-03-01

    With a broad portfolio of brominated, organophosphorus and inorganic flame retardants, ICL Industrial Products (ICL-IP) is engaged in the development of new flame retardants by exploiting the synergism between bromine based, phosphorus based and other halogen-free flame retardants. ICL-IP is also focusing on the development of polymeric and reactive flame retardants. This presentation will give examples of existing and new polymeric and reactive products for applications in thermoplastics, thermosets and polyurethane foam. This presentation will also show examples of phosphorus-bromine synergism allowing partial or complete elimination of antimony trioxide in many thermoplastics for electronic applications. New synergistic combinations of magnesium hydroxide with phosphorus and other halogen-free FRs will be presented. Work done in collaboration with S. Levchik, ICL-IP America, 430 Saw Mill Rriver Rd., Ardsley, NY, 10502, USA and M. Leifer, ICL-IP, P. O. Box 180, Beer Sheva 84101, Israel.

  18. Reversal and Rotation Errors by Normal and Retarded Readers

    ERIC Educational Resources Information Center

    Black, F. William

    1973-01-01

    Reports an investigation of the incidence of and relationships among word and letter reversals in writing and Bender-Gestalt rotation errors in matched samples of normal and retarded readers. No significant diffenences were found in the two groups. (TO)

  19. Sorption of Organophosphorus Flame-Retardants on Settled Dust

    EPA Science Inventory

    Dust is an important sink for indoor air pollutants, such as organophosphorus flame-retardants (OPFRs) that are used as additives in industrial and consumer products including electrical and electronic products, furniture, plastics, textile, and building/construction materials. T...

  20. Sorption of Organophosphorus Flame Retardants (OPFRs) on Settled Dust

    EPA Science Inventory

    Organophosphorus flame retardants (OPFRs) are widely used as additives in industrial and consumer products such as electrical and electronic products, furniture, plastics, textiles, and building/construction materials. Due to human exposure and potential health effects, OPFRs inc...

  1. Consumer Roulette: The Shopping Patterns of Mentally Retarded Persons.

    ERIC Educational Resources Information Center

    Williams, Randall D.; Ewing, Sheryl

    1981-01-01

    To develop information regarding the commercial product purchasing behavior of mildly mentally retarded adults, 11 participants were included in a mock shopping exercise. The results indicated several serious deficiencies in the purchasing strategies of the participants. (Author/SB)

  2. Fire retardant foams developed to suppress fuel fires

    NASA Technical Reports Server (NTRS)

    Fish, R.; Gilwee, W. J.; Parker, J. A.; Riccitiello, S. R.

    1968-01-01

    Heat insulating polyurethane foam retards and suppresses fuel fires. Uniformly dispersed in the foam is a halogenated polymer capable of splitting off hydrogen halide upon heating and charring of the polyurethane.

  3. Acquired alopecia, mental retardation, short stature, microcephaly, and optic atrophy.

    PubMed Central

    Hennekam, R C; Renckens-Wennen, E G

    1990-01-01

    We report on a female patient who had acquired total alopecia, short stature, microcephaly, optic atrophy, severe myopia, and mental retardation. A survey of published reports failed to show an identical patient, despite various similar cases. Images PMID:2246773

  4. Burning To Learn: An Introduction to Flame Retardants.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 2001

    2001-01-01

    Presents an activity that demonstrates the effectiveness of flame retardants--substances added to combustible materials to slow down or hinder burning--that can be introduced when discussing combustion reactions or during a practical or everyday chemistry unit. (ASK)

  5. Intrauterine growth retardation--small events, big consequences.

    PubMed

    Saleem, Taimur; Sajjad, Nida; Fatima, Sanna; Habib, Nida; Ali, Syed R; Qadir, Maqbool

    2011-01-01

    Intrauterine growth retardation refers to a rate of growth of a fetus that is less than normal for the growth potential of a fetus (for that particular gestational age). As one of the leading causes of perinatal mortality and morbidity, intrauterine growth retardation has immense implications for the short term and long term growth of children. It is an important public health concern in the developing countries. Health statistics encompassing parameters for maternal and child health in the Indian subcontinent have shown improvement in the past few years but they are still far from perfect. Maternal health, education and empowerment bears a strong influence on perinatal outcomes including intrauterine growth retardation and should be the primary focus of any stratagem targeted at reducing the incidence of intrauterine growth retardation. A concerted liaison of various medical and social disciplines is imperative in this regard. PMID:21899747

  6. The Overweight Preschool Retarded Child Can and Should Lose Weight.

    ERIC Educational Resources Information Center

    Fox, Robert; And Others

    1983-01-01

    Describes a weight reduction and control program for obese retarded preschool children involving parent leaders and incorporating social and tangible rewards. Discusses techniques children practice daily for a total of 15 weeks. (RH)

  7. Inferential reading abilities of mildly mentally retarded and nonretarded students.

    PubMed

    Bos, C S; Tierney, R J

    1984-07-01

    The inferential operations of mildly mentally retarded students reading at the intermediate level were investigated using methods based on discourse comprehension theory. We hypothesized that problems encountered in reading by these students are related to difficulties in generating logical inferences. Mildly retarded junior-high students and nonretarded third-grade students of the same reading comprehension level read and recalled a descriptive expository and a narrative passage. On the expository passage mildly retarded students generated the same quantity of inferences as did nonretarded students, but the inferences were qualitatively inferior. On the narrative passage the differences between the two groups were not significant. These findings were discussed in relation to the cognitive functioning of mildly retarded students.

  8. The Effects of Institutionalisation on Retardates Social Independence.

    ERIC Educational Resources Information Center

    Burkhart, G.; Seim, R.

    1979-01-01

    Forty retarded adults were the Ss of a study to evaluate the hypothesis that individuals who have been institutionalized for a greater percentage of their lifetime are more socially immature than those institutionalized for a smaller percentage. (CL)

  9. Penis agenesis associated with mental retardation: a case report.

    PubMed

    Kargi, Eksal; Aköz, Tayfun; Tuncel, Asuman; Erdogan, Bülent; Mungan, Aydin

    2002-01-01

    Penile agenesis is an extremely rare anomaly, with a reported incidence ranging from 1 in 10 million to in 3 million births. There are only about 80 published cases. This report first describe of penile agenesis associated with mental retardation.

  10. EFFECT OF ORGANOPHOSPHORUS FLAME RETARDANTS ON NEURONAL DEVELOPMENT IN VITRO

    EPA Science Inventory

    The increased use of organophosphorus compounds as alternatives to brominated flame retardants (BFRs) has led to widespread human exposure, There is, however, limited information on their potential health effects. This study compared the effects of nii ne organophosphorus flame...

  11. Clinical Comparison of Haloperidol with Chlorpromazine in Mentally Retarded Children

    ERIC Educational Resources Information Center

    LeVann, Leonard J.

    1971-01-01

    In an 8-week double-blind comparison, haloperidol reduced the severity of the target symptoms impulsiveness, hostility, and aggressiveness in significantly more mentally retarded children than did chlorpromazine. (Author)

  12. Cognitive modifiability in adult and older people with mental retardation.

    PubMed

    Lifshitz, H; Rand, Y

    1999-04-01

    Activation of change processes in cognitive capacity of 71 institutionalized adults with mental retardation in four age groups was investigated. The central means of intervention was the Instrumental Enrichment Program. Effects of the intervention were examined in reference to logical thinking, predictive thinking, and insightful thinking. The test series was administered twice before and twice after the intervention. Although all subjects improved significantly, the initial and final scores of adults with Down syndrome were lower than those of adults with other forms of mental retardation. Subjects with moderate retardation achieved greater improvement than did those with mild retardation only in the Children Test. Significant changes were obtained in all age groups. For logical and predictive thinking, a divergency effect was found. Results support structural cognitive modifiability theory.

  13. Halogenated flame retardants in the Great Lakes environment.

    PubMed

    Venier, Marta; Salamova, Amina; Hites, Ronald A

    2015-07-21

    Flame retardants are widely used industrial chemicals that are added to polymers, such as polyurethane foam, to prevent them from rapidly burning if exposed to a small flame or a smoldering cigarette. Flame retardants, especially brominated flame retardants, are added to many polymeric products at percent levels and are present in most upholstered furniture and mattresses. Most of these chemicals are so-called "additive" flame retardants and are not chemically bound to the polymer; thus, they migrate from the polymeric materials into the environment and into people. As a result, some of these chemicals have become widespread pollutants, which is a concern given their possible adverse health effects. Perhaps because of their environmental ubiquity, the most heavily used group of brominated flame retardants, the polybrominated diphenyl ethers (PBDEs), was withdrawn from production and use during the 2004-2013 period. This led to an increasing demand for other flame retardants, including other brominated aromatics and organophosphate esters. Although little is known about the use or production volumes of these newer flame retardants, it is evident that some of these chemicals are also becoming pervasive in the environment and in humans. In this Account, we describe our research on the occurrence of halogenated and organophosphate flame retardants in the environment, with a specific focus on the Great Lakes region. This Account starts with a short introduction to the first generation of brominated flame retardants, the polybrominated biphenyls, and then presents our measurements of their replacement, the PBDEs. We summarize our data on PBDE levels in babies, bald eagles, and in air. Once these compounds came off the market, we began to measure several of the newer flame retardants in air collected on the shores of the Great Lakes once every 12 days. These new measurements focus on a tetrabrominated benzoate, a tetrabrominated phthalate, a hexabrominated diphenoxyethane

  14. Halogenated flame retardants in the Great Lakes environment.

    PubMed

    Venier, Marta; Salamova, Amina; Hites, Ronald A

    2015-07-21

    Flame retardants are widely used industrial chemicals that are added to polymers, such as polyurethane foam, to prevent them from rapidly burning if exposed to a small flame or a smoldering cigarette. Flame retardants, especially brominated flame retardants, are added to many polymeric products at percent levels and are present in most upholstered furniture and mattresses. Most of these chemicals are so-called "additive" flame retardants and are not chemically bound to the polymer; thus, they migrate from the polymeric materials into the environment and into people. As a result, some of these chemicals have become widespread pollutants, which is a concern given their possible adverse health effects. Perhaps because of their environmental ubiquity, the most heavily used group of brominated flame retardants, the polybrominated diphenyl ethers (PBDEs), was withdrawn from production and use during the 2004-2013 period. This led to an increasing demand for other flame retardants, including other brominated aromatics and organophosphate esters. Although little is known about the use or production volumes of these newer flame retardants, it is evident that some of these chemicals are also becoming pervasive in the environment and in humans. In this Account, we describe our research on the occurrence of halogenated and organophosphate flame retardants in the environment, with a specific focus on the Great Lakes region. This Account starts with a short introduction to the first generation of brominated flame retardants, the polybrominated biphenyls, and then presents our measurements of their replacement, the PBDEs. We summarize our data on PBDE levels in babies, bald eagles, and in air. Once these compounds came off the market, we began to measure several of the newer flame retardants in air collected on the shores of the Great Lakes once every 12 days. These new measurements focus on a tetrabrominated benzoate, a tetrabrominated phthalate, a hexabrominated diphenoxyethane

  15. Genetic Causes of Mental Retardation. ARC Q&A #101-50.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This fact sheet uses a question-and-answer format to summarize what is known about the genetic causes of mental retardation. Questions and answers address the following topics: what genetics is; how a person's genes can cause mental retardation; how often mental retardation is inherited (up to 60 percent of severe mental retardation has genetic…

  16. Flame Retardant Exposure among Collegiate U.S. Gymnasts

    PubMed Central

    Carignan, Courtney C.; Heiger-Bernays, Wendy; McClean, Michael D.; Roberts, Simon C.; Stapleton, Heather M.; Sjödin, Andreas; Webster, Thomas F.

    2013-01-01

    Gymnastics training facilities contain large volumes of polyurethane foam, a material that often contains additive flame retardants such as PentaBDE. While investigations of human exposure to flame retardants have focused on the general population, potentially higher than background exposures may occur in gymnasts and certain occupational groups. Our objectives were to compare PentaBDE body burden among gymnasts to the general U.S. population and characterize flame retardants levels in gym equipment, air and dust. We recruited 11 collegiate female gymnasts (ages 18–22) from one gym in the Eastern U.S. The geometric mean (GM) concentration of BDE-153 in gymnast sera (32.5 ng/g lipid) was 4–6.5 times higher than general U.S. population groups. Median concentrations of PentaBDE, TBB and TBPH in paired handwipe samples were 2–3 times higher after practice compared to before, indicating the gymnasts contacted these flame retardants during practice. GM concentrations of PentaBDE, TBB and TBPH were 1-3 orders of magnitude higher in gym air and dust than in residences. Our findings suggest that these collegiate gymnasts experienced higher exposures to PentaBDE flame retardants compared to the general U.S. population and that gymnasts may also have increased exposure to other additive flame retardants used in polyurethane foam such as TBB and TBPH. PMID:24195753

  17. Developing proper mealtime behaviors of the institutionalized retarded1

    PubMed Central

    O'Brien, F.; Azrin, N. H.

    1972-01-01

    The institutionalized mentally retarded display a variety of unsanitary, disruptive, and improper table manners. A program was developed that included (1) acquisition-training of a high standard of proper table manners and (2) maintenance procedures to provide continued motivation to maintain proper mealtime behaviors and decrease improper skills. Twelve retardates received acquisition training, individually, by a combination of verbal instruction, imitation, and manual guidance. The students then ate in their group dining arrangement where the staff supervisor provided continuing approval for proper manners and verbal correction and timeout for improper manners. The results were: (1) the trained retardates showed significant improvement, whereas those untrained did not; (2) the trained retardates ate as well in the institution as non-retarded customers did in a public restaurant; (3) proper eating was maintained in the group dining setting; (4) timeout was rarely needed; (5) the program was easily administered by regular staff in a regular dining setting. The rapidity, feasibility, and effectiveness of the program suggests the program as a solution to improper mealtime behaviors by the institutionalized mentally retarded. PMID:16795363

  18. CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.

    PubMed

    Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L; Precht, Patricia; Mughal, Mohamed R; Wood, William H; Zhang, Yonqing; Becker, Kevin G; Mattson, Mark P; Pazin, Michael J

    2011-01-01

    CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease.

  19. CHD5, a Brain-Specific Paralog of Mi2 Chromatin Remodeling Enzymes, Regulates Expression of Neuronal Genes

    PubMed Central

    Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L.; Precht, Patricia; Mughal, Mohamed R.; Wood, William H.; Zhang, Yonqing; Becker, Kevin G.; Mattson, Mark P.; Pazin, Michael J.

    2011-01-01

    CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease. PMID:21931736

  20. Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway

    PubMed Central

    Sati, Leyla; Zeiss, Caroline; Yekkala, Krishna; Demir, Ramazan

    2015-01-01

    CTCFL, a paralog of CTCF, also known as BORIS (brother of regulator of imprinted sites), is a testis-expressed gene whose function is largely unknown. Its product is a cancer testis antigen (CTA), and it is often expressed in tumor cells and also seen in two benign human vascular malformations, juvenile angiofibromas and infantile hemangiomas. To understand the function of Ctcfl, we created tetracycline-inducible Ctcfl transgenic mice. We show that Ctcfl expression during embryogenesis results in growth retardation, eye malformations, multiorgan pathologies, vascular defects, and neonatal death. This phenotype resembles prior mouse models that perturb the transforming growth factor β (TGFB) pathway. Embryonic stem (ES) cells with the Ctcfl transgene reproduce the phenotype in ES cell-tetraploid chimeras. Transcriptome sequencing of the Ctcfl ES cells revealed 14 genes deregulated by Ctcfl expression. Bioinformatic analysis revealed the TGFB pathway as most affected by embryonic Ctcfl expression. Understanding the consequence of Ctcfl expression in nontesticular cells and elucidating downstream targets of Ctcfl could explain the role of its product as a CTA and its involvement in two, if not more, human vascular malformations. PMID:26169830