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1

Hox genes in evolution: protein surfaces and paralog groups.  

PubMed

The clustered Hox genes, which encode homeodomain transcription factors, control cell fates along the anterior-posterior axis. Differences between Hox proteins cause differences between body parts. Vertebrates have 13 Hox subgroups, called paralog groups, which can be correlated with some of the insect and Amphioxus genes, and have remained distinctive for hundreds of millions of years. We identify characteristic residues that define the different paralog groups. Some paralog groups can be recognized by the homeodomain sequence alone; others only by using characteristic residues outside the homeodomain. Mapping characteristic residues onto the known homeodomain crystal structure reveals that most of the homeodomain amino acids that distinguish paralog groups are oriented away from the DNA, in positions where they might engage in protein-protein interactions. PMID:9097725

Sharkey, M; Graba, Y; Scott, M P

1997-04-01

2

Variable Meis-dependence among paralog group-1 Hox proteins  

Microsoft Academic Search

Optimal function of Hox transcription factors may require Meis and Pbx cofactors. Here we test the in vivo Meis-dependence of two zebrafish paralog group-1 (PG1) Hox proteins. Misexpression of Hoxb1a induces ectopic gene expression throughout the anterior nervous system, while Hoxb1b induces ectopic expression primarily in hindbrain rhombomere 2. These activities are drastically reduced when endogenous Meis function is disrupted,

Seong-Kyu Choe; Charles G. Sagerström

2005-01-01

3

Domain mapping of the Rad51 paralog protein complexes  

Microsoft Academic Search

The five human Rad51 paralogs are suggested to play an important role in the maintenance of genome stability through their function in DNA dou- ble-strand break repair. These proteins have been found to form two distinct complexes in vivo, Rad51B-Rad51C-Rad51D-Xrcc2 (BCDX2) and Rad51C-Xrcc3 (CX3). Based on the recent Pyrococcus furiosus Rad51 structure, we have used homology modeling to design deletion

Kristi A. Miller; Dorota Sawicka; Daniel Barsky; Joanna S. Albala

2004-01-01

4

Using orthologous and paralogous proteins to identify specificity-determining residues in bacterial transcription factors.  

PubMed

Concepts of orthology and paralogy are become increasingly important as whole-genome comparison allows their identification in complete genomes. Functional specificity of proteins is assumed to be conserved among orthologs and is different among paralogs. We used this assumption to identify residues which determine specificity of protein-DNA and protein-ligand recognition. Finding such residues is crucial for understanding mechanisms of molecular recognition and for rational protein and drug design. Assuming conservation of specificity among orthologs and different specificity of paralogs, we identify residues that correlate with this grouping by specificity. The method is taking advantage of complete genomes to find multiple orthologs and paralogs. The central part of this method is a procedure to compute statistical significance of the predictions. The procedure is based on a simple statistical model of protein evolution. When applied to a large family of bacterial transcription factors, our method identified 12 residues that are presumed to determine the protein-DNA and protein-ligand recognition specificity. Structural analysis of the proteins and available experimental results strongly support our predictions. Our results suggest new experiments aimed at rational re-design of specificity in bacterial transcription factors by a minimal number of mutations. PMID:12139929

Mirny, Leonid A; Gelfand, Mikhail S

2002-08-01

5

Multigenic families and proteomics: extended protein characterization as a tool for paralog gene identification.  

PubMed

In classical proteomic studies, the searches in protein databases lead mostly to the identification of protein functions by homology due to the non-exhaustiveness of the protein databases. The quality of the identification depends on the studied organism, its complexity and its representation in the protein databases. Nevertheless, this basic function identification is insufficient for certain applications namely for the development of RNA-based gene-silencing strategies, commonly termed RNA interference (RNAi) in animals and post-transcriptional gene silencing (PTGS) in plants, that require an unambiguous identification of the targeted gene sequence. A PTGS strategy was considered in the study of the infection of Oryza sativa by the Rice Yellow Mottle Virus (RYMV). It is suspected that the RYMV recruits host proteins after its entry into plant cells to form a complex facilitating virus multiplication and spreading. The protein partners of this complex were identified by a classical proteomic approach, nano liquid chromatography tandem mass spectrometry. Among the identified proteins, several were retained for a PTGS strategy. Nevertheless most of the protein candidates appear to be members of multigenic families for which all paralog genes are not present in protein databases. Thus the identification of the real expressed paralog gene with classical protein database searches is impossible. Consequently, as the genome contains all genes and thus all paralog genes, a whole genome search strategy was developed to determine the specific expressed paralog gene. With this approach, the identification of peptides matching only a single gene, called discriminant peptides, allows definitive proof of the expression of this identified gene. This strategy has several requirements: (i) a genome completely sequenced and accessible; (ii) high protein sequence coverage. In the present work, through three examples, we report and validate for the first time a genome database search strategy to specifically identify paralog genes belonging to multigenic families expressed under specific conditions. PMID:15627959

Delalande, François; Carapito, Christine; Brizard, Jean-Paul; Brugidou, Christophe; Van Dorsselaer, Alain

2005-02-01

6

Nutrilyzer: a tool for deciphering atomic stoichiometry of differentially expressed paralogous proteins.  

PubMed

Organisms try to maintain homeostasis by balanced uptake of nutrients from their environment. From an atomic perspective this means that, for example, carbon:nitrogen:sulfur ratios are kept within given limits. Upon limitation of, for example, sulfur, its acquisition is triggered. For yeast it was shown that transporters and enzymes involved in sulfur uptake are encoded as paralogous genes that express different isoforms. Sulfur deprivation leads to up-regulation of isoforms that are poor in sulfur-containing amino acids, that is, methinone and cysteine. Accordingly, sulfur-rich isoforms are down-regulated. We developed a web-based software, doped Nutrilyzer, that extracts paralogous protein coding sequences from an annotated genome sequence and evaluates their atomic composition. When fed with gene-expression data for nutrient limited and normal conditions, Nutrilyzer provides a list of genes that are significantly differently expressed and simultaneously contain significantly different amounts of the limited nutrient in their atomic composition. Its intended use is in the field of ecological stoichiometry. Nutrilyzer is available at http://nutrilyzer.hs-mittweida.de. Here we describe the work flow and results with an example from a whole-genome Arabidopsis thaliana gene-expression analysis upon oxygen deprivation. 43 paralogs distributed over 37 homology clusters were found to be significantly differently expressed while containing significantly different amounts of oxygen. PMID:22796635

Lotz, Katrin; Schreiber, Falk; Wünschiers, Röbbe

2012-07-16

7

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

NASA Astrophysics Data System (ADS)

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.

Richardson, Dale N.; Wiehe, Thomas

8

Rho proteins, mental retardation and the neurobiological basis of intelligence  

Microsoft Academic Search

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 ?Pix, interact directly

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

2005-01-01

9

Structural and Binding Properties of Two Paralogous Fatty Acid Binding Proteins of Taenia solium Metacestode  

PubMed Central

Background Fatty acid (FA) binding proteins (FABPs) of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. Methodology/Principal Findings We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15–95% with other related-members. Homology modeling demonstrated a characteristic ?-barrel composed of 10 anti-parallel ?-strands and two ?-helices. TsMFABP2 harbored two additional loops between ?-strands two and three, and ?-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid, dansyl-DL-?-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions of lipids and retinol. Conclusions/Significance The divergent biochemical properties, physiological roles and cellular distributions of the TsMFABPs might be one of the critical mechanisms compensating for inadequate de novo FA synthesis. These proteins might exert harmonized or independent roles on lipid assimilation and intracellular signaling. The specialized distribution of retinol in the canal region further implies that cells in this region might differentiate into diverse cell types during metamorphosis into an adult worm. Identification of bioactive systems pertinent to parasitic homeostasis may provide a valuable target for function-related drug design.

Yang, Hyun-Jong; Shin, Joo-Ho; Diaz-Camacho, Sylvia Paz; Nawa, Yukifumi; Kang, Insug; Kong, Yoon

2012-01-01

10

Functional divergence among silkworm antimicrobial peptide paralogs by the activities of recombinant proteins and the induced expression profiles.  

PubMed

Antimicrobial peptides are small-molecule proteins that are usually encoded by multiple-gene families. They play crucial roles in the innate immune response, but reports on the functional divergence of antimicrobial peptide gene families are rare. In this study, 14 paralogs of antimicrobial peptides belonging to cecropin, moricin and gloverin families were recombinantly expressed in pET expression systems. By antimicrobial activity tests, peptides representing paralogs in the same family of cecropin and moricin families, displayed remarkable differences against 10 tested bacteria. The evolutionary rates were relatively fast in the two families, which presented obvious functional divergence among paralogs of each family. Four peptides of gloverin family had similar antimicrobial spectrum and activity against tested bacteria. The gloverin family showed similar antimicrobial function and slow evolutionary rates. By induced transcriptional activity, genes encoding active antimicrobial peptides were upregulated at obviously different levels when silkworm pupae were infected by three types of microbes. Association analysis of antimicrobial activities and induced transcriptional activities indicated that the antimicrobial activities might be positively correlated with induced transcriptional activities in the cecropin and moricin families. These results suggest that representative BmcecB6, BmcecD and Bmmor as the major effector genes have broad antimicrobial spectrum, strong antimicrobial activity and high microbe-induced expression among each family and maybe play crucial roles in eliminating microbial infection. PMID:21479226

Yang, Wanying; Cheng, Tingcai; Ye, Mingqiang; Deng, Xiaojuan; Yi, Huiyu; Huang, Yadong; Tan, Xiang; Han, Dong; Wang, Bo; Xiang, Zhonghuai; Cao, Yang; Xia, Qingyou

2011-03-29

11

Functional Divergence among Silkworm Antimicrobial Peptide Paralogs by the Activities of Recombinant Proteins and the Induced Expression Profiles  

PubMed Central

Antimicrobial peptides are small-molecule proteins that are usually encoded by multiple-gene families. They play crucial roles in the innate immune response, but reports on the functional divergence of antimicrobial peptide gene families are rare. In this study, 14 paralogs of antimicrobial peptides belonging to cecropin, moricin and gloverin families were recombinantly expressed in pET expression systems. By antimicrobial activity tests, peptides representing paralogs in the same family of cecropin and moricin families, displayed remarkable differences against 10 tested bacteria. The evolutionary rates were relatively fast in the two families, which presented obvious functional divergence among paralogs of each family. Four peptides of gloverin family had similar antimicrobial spectrum and activity against tested bacteria. The gloverin family showed similar antimicrobial function and slow evolutionary rates. By induced transcriptional activity, genes encoding active antimicrobial peptides were upregulated at obviously different levels when silkworm pupae were infected by three types of microbes. Association analysis of antimicrobial activities and induced transcriptional activities indicated that the antimicrobial activities might be positively correlated with induced transcriptional activities in the cecropin and moricin families. These results suggest that representative BmcecB6, BmcecD and Bmmor as the major effector genes have broad antimicrobial spectrum, strong antimicrobial activity and high microbe-induced expression among each family and maybe play crucial roles in eliminating microbial infection.

Ye, Mingqiang; Deng, Xiaojuan; Yi, Huiyu; Huang, Yadong; Tan, Xiang; Han, Dong; Wang, Bo; Xiang, Zhonghuai; Cao, Yang; Xia, Qingyou

2011-01-01

12

Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage  

Microsoft Academic Search

Metazoan Rad51 plays a central role in homologous DNA recombination, and its activity is controlled by a number of Rad51 cofactors. These include five Rad51 paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized that all five par- alogs participate collaboratively in repair. However, this idea was challenged by the biochemical identi- fication of two independent complexes composed of

Yasukazu Yonetani; Helfrid Hochegger; Eiichiro Sonoda; Sayoko Shiny; Hideki Yoshikawa; Shunichi Takeda; Mistuyoshi Yamazoe

2005-01-01

13

Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells  

Microsoft Academic Search

Genetic studies in rodent and chicken mutant cell lines have suggested that Rad51 paralogs (XRCC2, XRCC3, Rad51B\\/Rad51L1, Rad51C\\/Rad51L2 and Rad51D\\/Rad51L3) play important roles in homologous recombinational repair of DNA double-strand breaks and in maintaining chromosome stability. Previous studies using yeast two- and three-hybrid systems have shown interactions among these proteins, but it is not clear whether these interactions occur simultaneously

Nan Liu; David Schild; Michael P. Thelen; Larry H. Thompson

2002-01-01

14

Paralogous Outer Membrane Proteins Mediate Uptake of Different Forms of Iron and Synergistically Govern Virulence in Francisella tularensis tularensis*  

PubMed Central

Francisella tularensis subsp. tularensis is a highly infectious bacterium causing acute disease in mammalian hosts. Mechanisms for the acquisition of iron within the iron-limiting host environment are likely to be critical for survival of this intracellular pathogen. FslE (FTT0025) and FupA (FTT0918) are paralogous proteins that are predicted to form ?-barrels in the outer membrane of virulent strain Schu S4 and are unique to Francisella species. Previous studies have implicated both FupA, initially identified as a virulence factor and FslE, encoded by the siderophore biosynthetic operon, in iron acquisition. Using single and double mutants, we demonstrated that these paralogs function in concert to promote growth under iron limitation. We used a 55Fe transport assay to demonstrate that FslE is involved in siderophore-mediated ferric iron uptake, whereas FupA facilitates high affinity ferrous iron uptake. Optimal replication within J774A.1 macrophage-like cells required at least one of these uptake systems to be functional. In a mouse model of tularemia, the ?fupA mutant was attenuated, but the ?fslE ?fupA mutant was significantly more attenuated, implying that the two systems of iron acquisition function synergistically to promote virulence. These studies highlight the importance of specific iron acquisition functions, particularly that of ferrous iron, for virulence of F. tularensis in the mammalian host.

Ramakrishnan, Girija; Sen, Bhaswati; Johnson, Richard

2012-01-01

15

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

PubMed Central

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.

Kafkova, Lucie; Ammerman, Michelle L.; Faktorova, Drahomira; Fisk, John C.; Zimmer, Sara L.; Sobotka, Roman; Read, Laurie K.; Lukes, Julius; Hashimi, Hassan

2012-01-01

16

Rho proteins, mental retardation and the cellular basis of cognition  

Microsoft Academic Search

For several decades, it has been known that mental retardation (MR) is associated with abnormalities in dendrites and dendritic spines. The recent cloning of seven genes that cause nonspecific MR when mutated provides important insights in the cellular mechanisms that result in the dendritic abnormalities associated with MR. Three of the encoded proteins, oligophrenin1, PAK3 and ?PIX, interact directly with

Ger J. A. Ramakers

2002-01-01

17

Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and replication forks as visualized by electron microscopy.  

PubMed

In mammals, there are five Rad51 paralogs that form two distinct complexes in vivo. One complex is composed of Rad51B-Rad51C-Rad51D-Xrcc2 (BCDX2) and the other Rad51C-Xrcc3 (CX3). We co-expressed and purified human BCDX2 and CX3 protein complexes from insect cells and investigated their binding preferences and structure using transmission electron microscopy (TEM). We visualized the binding of BCDX2 and CX3 to DNA templates containing replication forks and Holliday junctions, intermediates observed during DNA replication and recombination, respectively. We show that both complexes bind with exceptionally high specificity to the DNA junctions with little binding observed elsewhere on the DNAs. Further analysis of the structure of free or DNA-bound BCDX2 and CX3 complexes revealed a multimeric ring structure whose subunits are arranged into a flat disc around a central channel. This work provides the first EM visualization of BCDX2 and CX3 binding to Holliday junctions and forked DNAs and suggests the complexes form ring-shaped structures. PMID:20207730

Compton, Sarah A; Ozgür, Sezgin; Griffith, Jack D

2010-03-05

18

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

Microsoft Academic Search

Whole genome duplication (WGD) has catalyzed the formation of new species, genes with novel functions, altered expression\\u000a patterns, complexified signaling pathways and has provided organisms a level of genetic robustness. We studied the long-term\\u000a evolution and interrelationships of 5’ upstream regulatory sequences (URSs), protein coding sequences (CDSs) and expression\\u000a correlations (EC) of duplicated gene pairs in Arabidopsis. Three distinct methods

Dale N. Richardson; Thomas Wiehe

2009-01-01

19

Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175  

PubMed Central

A member of a Plasmodium receptor family for erythrocyte invasion was identified on chromosome 13 from the Plasmodium falciparum genome sequence of the Sanger Centre (Cambridge, U.K.). The protein (named BAEBL) has homology to EBA-175, a P. falciparum receptor that binds specifically to sialic acid and the peptide backbone of glycophorin A on erythrocytes. Both EBA-175 and BAEBL localize to the micronemes, organelles at the invasive ends of the parasites that contain other members of the family. Like EBA-175, the erythrocyte receptor for BAEBL is destroyed by neuraminidase and trypsin, indicating that the erythrocyte receptor is a sialoglycoprotein. Its specificity, however, differs from that of EBA-175 in that BAEBL can bind to erythrocytes that lack glycophorin A, the receptor for EBA-175. It has reduced binding to erythrocytes with the Gerbich mutation found in another erythrocyte, sialoglycoprotein (glycophorin C/D). The interest in BAEBL's reduced binding to Gerbich erythrocytes derives from the high frequency of the Gerbich phenotype in some regions of Papua New Guinea where P. falciparum is hyperendemic.

Mayer, D. C. Ghislaine; Kaneko, Osamu; Hudson-Taylor, Diana E.; Reid, Marion E.; Miller, Louis H.

2001-01-01

20

Detection of protein complex interactions via a Blue Native-PAGE retardation assay  

Microsoft Academic Search

We describe the Blue Native (BN)-PAGE retardation assay for the detection of interactions of biomolecules with protein complexes. Potential interactors of proteins are included in the BN gel matrix, resulting in retardation of proteins that interact with the added molecule. After validation using the T-cell antigen receptor, we applied the assay for a general identification of dextran interactors in combination

Mahima Swamy; Eszter Molnar; Thomas Bock; Damaris Bausch-Fluck; Bernd Wollscheid; Wolfgang W. A. Schamel

2009-01-01

21

Regulation of GABAA receptors by fragile X mental retardation protein  

PubMed Central

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABAA receptors (GABAARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABAARs and phosphatase PTEN, and recorded GABAAR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs causes increased protein expression of GABAARs in cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABAAR activity may play a role in inhibiting GABAAR function in FMRP-transfected neurons. We further show that FMRP transfection results in an enhanced protein expression of PTEN, which contributes to the inhibition of GABAAR function in FMRP-transfected neurons. These results indicate that GABAARs are regulated by FMRP through both an up-regulation of GABAAR expression and a PTEN enhancement-induced inhibition of GABAAR function, suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP underlies the pathogenesis of FXS.

Liu, Baosong; Li, Lijun; Chen, Juan; Wang, Zefen; Li, Zhiqiang; Wan, Qi

2013-01-01

22

Regulation of GABAA receptors by fragile X mental retardation protein.  

PubMed

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABAA receptors (GABAARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABAARs and phosphatase PTEN, and recorded GABAAR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs causes increased protein expression of GABAARs in cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABAAR activity may play a role in inhibiting GABAAR function in FMRP-transfected neurons. We further show that FMRP transfection results in an enhanced protein expression of PTEN, which contributes to the inhibition of GABAAR function in FMRP-transfected neurons. These results indicate that GABAARs are regulated by FMRP through both an up-regulation of GABAAR expression and a PTEN enhancement-induced inhibition of GABAAR function, suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP underlies the pathogenesis of FXS. PMID:24044036

Liu, Baosong; Li, Lijun; Chen, Juan; Wang, Zefen; Li, Zhiqiang; Wan, Qi

2013-09-10

23

Structure of TatA Paralog, TatE, Suggests a Structurally Homogeneous Form of Tat Protein Translocase That Transports Folded Proteins of Differing Diameter  

PubMed Central

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.

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

2012-01-01

24

Fragile X Mental Retardation Protein Regulates Heterosynaptic Plasticity in the Hippocampus  

ERIC Educational Resources Information Center

|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…

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

2011-01-01

25

Fragile X Mental Retardation Protein Regulates Heterosynaptic Plasticity in the Hippocampus  

ERIC Educational Resources Information Center

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…

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

2011-01-01

26

Protein profile of aging and its retardation by caloric restriction in neural retina  

Microsoft Academic Search

Aging is a slow, gradual deterioration process of an organism. The only experimental intervention, which can reliably retard aging and age-related degenerative diseases, is dietary caloric restriction (CR). To gain insight into the mechanism of CR intervention, we have investigated the protein profile of aging and its retardation by CR in the neural retina of Brown Norway (BN) rats using

Dayu Li; Fang Sun; Keyang Wang

2004-01-01

27

Fragile X Mental Retardation Protein Targets G Quartet mRNAs Important for Neuronal Function  

Microsoft Academic Search

Loss of fragile X mental retardation protein (FMRP) function causes the fragile X mental retardation syndrome. FMRP harbors three RNA binding domains, associates with polysomes, and is thought to regulate mRNA translation and\\/or localization, but the RNAs to which it binds are unknown. We have used RNA selection to demonstrate that the FMRP RGG box binds intramolecular G quartets. This

Jennifer C. Darnell; Kirk B. Jensen; Peng Jin; Victoria Brown; Stephen T. Warren; Robert B. Darnell

2001-01-01

28

Cell morphogenesis of Trypanosoma brucei requires the paralogous, differentially expressed calpain-related proteins CAP5.5 and CAP5.5V.  

PubMed

Proteins from the calpain super-family are involved in developmentally- and environmentally-regulated re-modelling of the eukaryotic cytoskeleton and the dynamic organisation of signal transduction cascades. In trypanosomatid parasites, calpain-related gene families are unusually large, but we have little insight into the functional roles played by these molecules during trypanosomatid lifecycles. Here we report that CAP5.5, a cytoskeletal calpain-related protein subject to strict stage-specific expression in the sleeping sickness parasite Trypanosoma brucei, is essential and required for correct cell morphogenesis of procyclic (tsetse mid-gut stage) T. brucei. Striking consequences of CAP5.5 RNA interference are the loss of protein from the posterior cell-end, organelle mis-positioning giving rise to aberrant cytokinesis, and disorganisation of the sub-pellicular microtubules that define trypanosome cell shape. We further report that the stage-specificity of CAP5.5 expression can be explained by the presence of a paralogue, CAP5.5V, which is required for cell morphogenesis in bloodstream T. brucei; RNAi against this paralogous protein results in a qualitatively similar phenotype to that described for procyclic CAP5.5 RNAi mutants. By comparison to recently described phenotypes for other procyclic trypanosome RNAi mutants, likely functions for CAP5.5 and CAP5.5V are discussed. PMID:19656721

Olego-Fernandez, Sofia; Vaughan, Sue; Shaw, Michael K; Gull, Keith; Ginger, Michael L

2009-08-04

29

GCPII variants, paralogs and orthologs.  

PubMed

Glutamate carboxypeptidase II (GCPII) and its splice variants, paralogs and human homologs represent a family of proteins with diverse tissue distribution, cellular localization and largely unknown function which have been explored only recently. While GCPII itself has been thoroughly studied from different perspectives, as clearly documented in this series of reviews, very little is known about other members of its family, even though they might be biologically relevant. Differential expression of individual GCPII splice variants is associated with tumor progression and prognosis of prostate cancer. The best studied GCPII homolog, GCPIII or NAALADase II, may be a valid pharmaceutical target for itself since it may compensate for a lack of normal GCPII enzymatic activity. Detailed molecular characterization of this family of proteins is thus very important not only with respect to the potential therapeutic use of GCPII inhibitors, but also for better understanding of the biological role of GCPII within as well as outside the nervous system. PMID:22304710

Hlouchová, K; Navrátil, V; Tykvart, J; Sácha, P; Konvalinka, J

2012-01-01

30

A Novel Function for Fragile X Mental Retardation Protein in Translational Activation  

Microsoft Academic Search

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP\\/RNA interaction, the G-quartet and the ''kissing complex,'' which both induce translational repression in the presence of

Elias G. Bechara; Marie Cecile Didiot; Mireille Melko; Laetitia Davidovic; Mounia Bensaid; Patrick Martin; Marie Castets; Philippe Pognonec; Edouard W. Khandjian; Hervé Moine; Barbara Bardoni

2009-01-01

31

The fragile X mental retardation protein has nucleic acid chaperone properties  

Microsoft Academic Search

The fragile X syndrome is the most common cause of inherited mental retardation resulting from the absence of the fragile X mental retardation protein (FMRP). FMRP contains two K-homology (KH) domains and one RGG box that are landmarks char- acteristic of RNA-binding proteins. In agreement with this, FMRP associates with messenger ribo- nucleoparticles (mRNPs) within actively translating ribosomes, and is

Caroline Gabus; Rachid Mazroui; Sandra Tremblay; Edouard W. Khandjian; Jean-Luc Darlix

2004-01-01

32

Identification of a novel gene family, paralogs of inhibitor of apoptosis proteins present in plants, fungi, and animals  

Microsoft Academic Search

Only few orthologs of animal apoptosis regulators have been found in plants. Recently, the ectopic expression of mammalian inhibitor of apoptosis proteins (IAPs) has been shown to affect plant programmed cell death. Here, we identified two novel proteins homologous to ArabidopsisthalianaIAP-like protein (AtILP) 1 and 2 by applying an improved motif searching method. Furthermore, homologs of AtILP1 were found to

K. Higashi; R. Takasawa; A. Yoshimori; T. Goh; S. Tanuma; K. Kuchitsu

2005-01-01

33

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

PubMed Central

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 uncharacterized NP-like proteins may function in nutrient sensing and/or signaling. These proteins are members of Group I NP-like proteins, which are widely distributed in many plant taxa. We conclude that NP-like proteins may function in plants, although this function is undefined.

2013-01-01

34

h-Goliath, paralog of GRAIL, is a new E3 ligase protein, expressed in human leukocytes  

Microsoft Academic Search

In Drosophila, the RING finger protein d-Goliath was originally identified as a transcription factor involved in the embryo mesoderm formation [Bouchard, M.L., Cote, S., 1993. The Drosophila melanogaster developmental gene g1 encodes a variant zinc-finger-motif protein. Gene 125, 205–209]. In mouse, the m-Goliath mRNA level was shown to be increased in growth factor withdrawal-induced apoptosis of myeloid cells [Baker, S.J.,

Adeline Guais; Sylvie Siegrist; Brigitte Solhonne; Hélène Jouault; Georges Guellaën; Frédérique Bulle

2006-01-01

35

Fragile X mental retardation protein has a unique, evolutionarily conserved neuronal function not shared with FXR1P or FXR2P.  

PubMed

Fragile X syndrome (FXS), resulting solely from the loss of function of the human fragile X mental retardation 1 (hFMR1) gene, is the most common heritable cause of mental retardation and autism disorders, with syndromic defects also in non-neuronal tissues. In addition, the human genome encodes two closely related hFMR1 paralogs: hFXR1 and hFXR2. The Drosophila genome, by contrast, encodes a single dFMR1 gene with close sequence homology to all three human genes. Drosophila that lack the dFMR1 gene (dfmr1 null mutants) recapitulate FXS-associated molecular, cellular and behavioral phenotypes, suggesting that FMR1 function has been conserved, albeit with specific functions possibly sub-served by the expanded human gene family. To test evolutionary conservation, we used tissue-targeted transgenic expression of all three human genes in the Drosophila disease model to investigate function at (1) molecular, (2) neuronal and (3) non-neuronal levels. In neurons, dfmr1 null mutants exhibit elevated protein levels that alter the central brain and neuromuscular junction (NMJ) synaptic architecture, including an increase in synapse area, branching and bouton numbers. Importantly, hFMR1 can, comparably to dFMR1, fully rescue both the molecular and cellular defects in neurons, whereas hFXR1 and hFXR2 provide absolutely no rescue. For non-neuronal requirements, we assayed male fecundity and testes function. dfmr1 null mutants are effectively sterile owing to disruption of the 9+2 microtubule organization in the sperm tail. Importantly, all three human genes fully and equally rescue mutant fecundity and spermatogenesis defects. These results indicate that FMR1 gene function is evolutionarily conserved in neural mechanisms and cannot be compensated by either FXR1 or FXR2, but that all three proteins can substitute for each other in non-neuronal requirements. We conclude that FMR1 has a neural-specific function that is distinct from its paralogs, and that the unique FMR1 function is responsible for regulating neuronal protein expression and synaptic connectivity. PMID:20442204

Coffee, R Lane; Tessier, Charles R; Woodruff, Elvin A; Broadie, Kendal

2010-05-04

36

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

ERIC Educational Resources Information Center

|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…

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

2004-01-01

37

Fragile X mental retardation protein and synaptic plasticity  

PubMed Central

Loss of the translational repressor FMRP causes Fragile X syndrome. In healthy neurons, FMRP modulates the local translation of numerous synaptic proteins. Synthesis of these proteins is required for the maintenance and regulation of long-lasting changes in synaptic strength. In this role as a translational inhibitor, FMRP exerts profound effects on synaptic plasticity.

2013-01-01

38

Recombinant bacterial expression and purification of human fragile X mental retardation protein isoform 1  

Microsoft Academic Search

The loss of expression of the fragile X mental retardation protein (FMRP) leads to fragile X syndrome. FMRP has two types of RNA binding domains, two K-homology domains and an arginine–glycine–glycine box domain, and it is proposed to act as a translation regulator of specific messenger RNA. The interest to produce sufficient quantities of pure recombinant FMRP for biochemical and

Timothy L. Evans; Mihaela-Rita Mihailescu

2010-01-01

39

Fragile Mental Retardation Protein Interacts with the RNA-Binding Protein Caprin1 in Neuronal RiboNucleoProtein Complexes  

PubMed Central

Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein. FMRP is associated with messenger RiboNucleoParticles (mRNPs) present in polyribosomes and its absence in neurons leads to alteration in synaptic plasticity as a result of translation regulation defects. The molecular mechanisms by which FMRP plays a role in translation regulation remain elusive. Using immunoprecipitation approaches with monoclonal Ab7G1-1 and a new generation of chicken antibodies, we identified Caprin1 as a novel FMRP-cellular partner. In vivo and in vitro evidence show that Caprin1 interacts with FMRP at the level of the translation machinery as well as in trafficking neuronal granules. As an RNA-binding protein, Caprin1 has in common with FMRP at least two RNA targets that have been identified as CaMKII? and Map1b mRNAs. In view of the new concept that FMRP species bind to RNA regardless of known structural motifs, we propose that protein interactors might modulate FMRP functions.

El Fatimy, Rachid; Tremblay, Sandra; Dury, Alain Y.; Solomon, Samuel; De Koninck, Paul; Schrader, John W.; Khandjian, Edouard W.

2012-01-01

40

Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2.  

PubMed

Although the Hsp90 chaperone family, comprised in humans of four paralogs, Hsp90?, Hsp90?, Grp94 and Trap-1, has important roles in malignancy, the contribution of each paralog to the cancer phenotype is poorly understood. This is in large part because reagents to study paralog-specific functions in cancer cells have been unavailable. Here we combine compound library screening with structural and computational analyses to identify purine-based chemical tools that are specific for Hsp90 paralogs. We show that Grp94 selectivity is due to the insertion of these compounds into a new allosteric pocket. We use these tools to demonstrate that cancer cells use individual Hsp90 paralogs to regulate a client protein in a tumor-specific manner and in response to proteome alterations. Finally, we provide new mechanistic evidence explaining why selective Grp94 inhibition is particularly efficacious in certain breast cancers. PMID:23995768

Patel, Pallav D; Yan, Pengrong; Seidler, Paul M; Patel, Hardik J; Sun, Weilin; Yang, Chenghua; Que, Nanette S; Taldone, Tony; Finotti, Paola; Stephani, Ralph A; Gewirth, Daniel T; Chiosis, Gabriela

2013-09-01

41

The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals  

Microsoft Academic Search

Fragile X syndrome is a frequent cause of mental retardation resulting from the absence of FMRP, the protein encoded by the FMR1 gene. FMRP is an RNA-binding protein of unknown function which is associated with ribosomes. To gain insight into FMRP function, we performed immunolocalization analysis of FMRP truncation and fusion constructs which revealed a nuclear localization signal (NLS) in

Derek E. Eberhart; Henry E. Malter; Yue Feng; Stephen T. Warren

1996-01-01

42

Vertebrate Paralogous Conserved Noncoding Sequences May Be Related to Gene Expressions in Brain  

PubMed Central

Vertebrate genomes include gene regulatory elements in protein-noncoding regions. A part of gene regulatory elements are expected to be conserved according to their functional importance, so that evolutionarily conserved noncoding sequences (CNSs) might be good candidates for those elements. In addition, paralogous CNSs, which are highly conserved among both orthologous loci and paralogous loci, have the possibility of controlling overlapping expression patterns of their adjacent paralogous protein-coding genes. The two-round whole-genome duplications (2R WGDs), which most probably occurred in the vertebrate common ancestors, generated large numbers of paralogous protein-coding genes and their regulatory elements. These events could contribute to the emergence of vertebrate features. However, the evolutionary history and influences of the 2R WGDs are still unclear, especially in noncoding regions. To address this issue, we identified paralogous CNSs. Region-focused Basic Local Alignment Search Tool (BLAST) search of each synteny block revealed 7,924 orthologous CNSs and 309 paralogous CNSs conserved among eight high-quality vertebrate genomes. Paralogous CNSs we found contained 115 previously reported ones and newly detected 194 ones. Through comparisons with VISTA Enhancer Browser and available ChIP-seq data, one-third (103) of paralogous CNSs detected in this study showed gene regulatory activity in the brain at several developmental stages. Their genomic locations are highly enriched near the transcription factor-coding regions, which are expressed in brain and neural systems. These results suggest that paralogous CNSs are conserved mainly because of maintaining gene expression in the vertebrate brain.

Matsunami, Masatoshi; Saitou, Naruya

2013-01-01

43

Fragile X mental retardation protein regulates heterosynaptic plasticity in the hippocampus.  

PubMed

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 depression (LTD) induced by metabotropic glutamate receptor (mGluR) activation. Despite the evidence implicating FMRP in LTD, the role of FMRP in long-term potentiation (LTP) is less clear. Synaptic strength can be augmented heterosynaptically through the generation and sequestration of plasticity-related proteins, in a cell-wide manner. If heterosynaptic plasticity is altered in Fmr1 knockout (KO) mice, this may explain the cognitive deficits associated with FXS. We induced homosynaptic plasticity using the ?-adrenergic receptor (?-AR) agonist, isoproterenol (ISO), which facilitated heterosynaptic LTP that was enhanced in Fmr1 KO mice relative to wild-type (WT) controls. To determine if enhanced heterosynaptic LTP in Fmr1 KO mouse hippocampus requires protein synthesis, we applied a translation inhibitor, emetine (EME). EME blocked homo- and heterosynaptic LTP in both genotypes. We also probed the roles of mTOR and ERK in boosting heterosynaptic LTP in Fmr1 KO mice. Although heterosynaptic LTP was blocked in both WT and KOs by inhibitors of mTOR and ERK, homosynaptic LTP was still enhanced following mTOR inhibition in slices from Fmr1 KO mice. Because mTOR will normally stimulate translation initiation, our results suggest that ?-AR stimulation paired with derepression of translation results in enhanced heterosynaptic plasticity. PMID:21430043

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

2011-03-23

44

Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles  

PubMed Central

Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). This RNA-binding protein is widely expressed in human and mouse tissues, and it is particularly abundant in the brain because of its high expression in neurons, where it localizes in the cell body and in granules throughout dendrites. Although FMRP is thought to regulate trafficking of repressed mRNA complexes and to influence local protein synthesis in synapses, it is not known whether it has additional functions in the control of translation in the cell body. Here, we have used recently developed approaches to investigate whether FMRP is associated with the translation apparatus. We demonstrate that, in the brain, FMRP is present in actively translating polyribosomes, and we show that this association is acutely sensitive to the type of detergent required to release polyribosomes from membranous structures. In addition, proteomic analyses of purified brain polyribosomes reveal the presence of several RNA-binding proteins that, similarly to FMRP, have been previously localized in neuronal granules. Our findings highlight the complex roles of FMRP both in actively translating polyribosomes and in repressed trafficking ribonucleoparticle granules.

Khandjian, Edouard W.; Huot, Marc-Etienne; Tremblay, Sandra; Davidovic, Laetitia; Mazroui, Rachid; Bardoni, Barbara

2004-01-01

45

Detecting Changes in the Functional Constraints of Paralogous Genes  

Microsoft Academic Search

.   We describe a new procedure to determine whether regional alterations in the evolutionary constraints imposed on paralogous\\u000a proteins have occurred. We used as models the A and B (alternatively called ? and ?) subunits of V\\/F\\/A-ATPases, originated\\u000a by a gene duplication more than 3 billion years ago. Changes associated to three major splits (eubacteria versus Archaea-eukaryotes;\\u000a Archaea versus eukaryotes;

Ignacio Marín; Mario Alí Fares; Fernando González-Candelas; Eladio Barrio; Andrés Moya

2001-01-01

46

Comprehensive computational analysis of Hmd enzymes and paralogs in methanogenic Archaea  

PubMed Central

Background Methanogenesis is the sole means of energy production in methanogenic Archaea. H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd) catalyzes a step in the hydrogenotrophic methanogenesis pathway in class I methanogens. At least one hmd paralog has been identified in nine of the eleven complete genome sequences of class I hydrogenotrophic methanogens. The products of these paralog genes have thus far eluded any detailed functional characterization. Results Here we present a thorough computational analysis of Hmd enzymes and paralogs that includes state of the art phylogenetic inference, structure prediction, and functional site prediction techniques. We determine that the Hmd enzymes are phylogenetically distinct from Hmd paralogs but share a common overall structure. We predict that the active site of the Hmd enzyme is conserved as a functional site in Hmd paralogs and use this observation to propose possible molecular functions of the paralog that are consistent with previous experimental evidence. We also identify an uncharacterized site in the N-terminal domains of both proteins that is predicted by our methods to directly impart function. Conclusion This study contributes to our understanding of the evolutionary history, structural conservation, and functional roles, of the Hmd enzymes and paralogs. The results of our phylogenetic and structural analysis constitute datasets that will aid in the future study of the Hmd protein family. Our functional site predictions generate several testable hypotheses that will guide further experimental characterization of the Hmd paralog. This work also represents a novel approach to protein function prediction in which multiple computational methods are integrated to achieve a detailed characterization of proteins that are not well understood.

Goldman, Aaron D; Leigh, John A; Samudrala, Ram

2009-01-01

47

Species-Specific and Isoform-Specific RNA Binding of Human and Mouse Fragile X Mental Retardation Proteins  

Microsoft Academic Search

The loss of the fragile X RNA binding protein, FMRP, causes macroorchidism and mental retardation in man. The discovery of a mouse ortholog led to the development of several FMRP knockout mouse strains that recapitulate some features of the disease. As mouse and human FMRPs differ in several amino acids in their RNA binding domains, we compared the RNA binding

Robert B. Denman; Ying Ju Sung

2002-01-01

48

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

Microsoft Academic Search

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

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

2012-01-01

49

Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP)  

Microsoft Academic Search

Objective: To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior. Methods: This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was

Doron Gothelf; Joyce A. Furfaro; Fumiko Hoeft; Mark A. Eckert; Scott S. Hall; Ruth O'Hara; Heather W. Erba; Jessica Ringel; Kiralee M. Hayashi; Swetapadma Patnaik; Brenda Golianu; Helena C. Kraemer; Paul M. Thompson; Joseph Piven; Allan L. Reiss

2008-01-01

50

Bicaudal-D Regulates Fragile X Mental Retardation Protein Levels, Motility, and Function during Neuronal Morphogenesis  

PubMed Central

Summary The expression of the RNA-binding factor Fragile X mental retardation protein (FMRP) is disrupted in the most common inherited form of cognitive deficiency in humans. FMRP controls neuronal morphogenesis by mediating the translational regulation and localization of a large number of mRNA targets [1–3], and these functions are closely associated with transport of FMRP complexes within neurites by microtubule-based motors [2–4]. However, the mechanisms that link FMRP to motors and regulate its transport are poorly understood. Here we show that FMRP is complexed with Bicaudal-D (BicD) through a domain in the latter protein that mediates linkage of cargoes with the minus-end-directed motor dynein. We demonstrate in Drosophila that the motility and, surprisingly, levels of FMRP protein are dramatically reduced in BicD mutant neurons, leading to a paucity of FMRP within processes. We also provide functional evidence that BicD and FMRP cooperate to control dendritic morphogenesis in the larval nervous system. Our findings open new perspectives for understanding localized mRNA functions in neurons.

Bianco, Ambra; Dienstbier, Martin; Salter, Hannah K.; Gatto, Graziana; Bullock, Simon L.

2010-01-01

51

Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator  

Microsoft Academic Search

Expansion of the FRAXE CCG repeat to a full mutation is associated with methylation and transcriptional silencing of the\\u000a FMR2 gene, and as a consequence, mild-to-borderline mental retardation. FMR2 is a member of a family of four proteins, AF4, LAF4,\\u000a FMR2, and AF5q31. The proteins associated with this family localize to the cell nucleus. Various regions of FMR2, and each

Marie A. Hillman; Jozef Gecz

2001-01-01

52

Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway  

Microsoft Academic Search

Fragile X syndrome is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein which forms a messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes. Recently, mRNA ligands associated with FMRP have been identified. However, the mechanism by which FMRP regulates the translation of its mRNA ligands remains unclear. MicroRNAs

Peng Jin; Daniela C Zarnescu; Stephanie Ceman; Mika Nakamoto; Julie Mowrey; Thomas A Jongens; David L Nelson; Kevin Moses; Stephen T Warren

2004-01-01

53

Recombinant bacterial expression and purification of human fragile X mental retardation protein isoform 1.  

PubMed

The loss of expression of the fragile X mental retardation protein (FMRP) leads to fragile X syndrome. FMRP has two types of RNA binding domains, two K-homology domains and an arginine-glycine-glycine box domain, and it is proposed to act as a translation regulator of specific messenger RNA. The interest to produce sufficient quantities of pure recombinant FMRP for biochemical and biophysical studies is high. However, the recombinant bacterial expression of FMRP has had limited success, and subsequent recombinant eukaryotic and in vitro expression has also resulted in limited success. In addition, the in vitro and eukaryotic expression systems may produce FMRP which is posttranslationally modified, as phosphorylation and arginine methylation have been shown to occur on FMRP. In this study, we have successfully isolated the conditions for recombinant expression, purification and long-term storage of FMRP using Escherichia coli, with a high yield. The expression of FMRP using E. coli renders the protein devoid of the posttranslational modifications of phosphorylation and arginine methylation, allowing the study of the direct effects of these modifications individually and simultaneously. In order to assure that FMRP retained activity throughout the process, we used fluorescence spectroscopy to assay the binding activity of the FMRP arginine-glycine-glycine box for the semaphorin 3F mRNA and confirmed that FMRP remained active. PMID:20541608

Evans, Timothy L; Mihailescu, Mihaela-Rita

2010-06-10

54

In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation.  

PubMed

Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wild-type (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated protein 1B) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain-learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior. PMID:22080836

Coffee, R Lane; Williamson, Ashley J; Adkins, Christopher M; Gray, Marisa C; Page, Terry L; Broadie, Kendal

2011-11-11

55

In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation  

PubMed Central

Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wild-type (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated protein 1B) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain-learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior.

Coffee, R. Lane; Williamson, Ashley J.; Adkins, Christopher M.; Gray, Marisa C.; Page, Terry L.; Broadie, Kendal

2012-01-01

56

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

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.

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

2004-07-15

57

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

PubMed Central

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).

Matzkin, Luciano M; Eanes, Walter F

2003-01-01

58

A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P  

Microsoft Academic Search

Aminoacyl-tRNA synthetase (aaRS) paralogs with unknown functions exist in various species. We now report novel 'protein lysylation' by an Escherichia coli lysyl-tRNA synthetase paralog, GenX\\/PoxA\\/YjeA. X-ray crystallographic analysis shows that the structure of the GenX protein resembles that of a class II aaRS. Further in vitro studies reveal that it specifically aminoacylates EF-P with lysine. The shape of the protein

Tatsuo Yanagisawa; Tomomi Sumida; Ryohei Ishii; Chie Takemoto; Shigeyuki Yokoyama

2010-01-01

59

Fragile X Mental Retardation Protein (FMRP) and the Spinal Sensory System  

PubMed Central

The purpose of this chapter is to discuss the role of the fragile X mental retardation protein (FMRP) in the spinal sensory system and the potential for use of the mouse model of fragile X syndrome to better understand some aspects of the human syndrome as well as advance knowledge in other areas of investigation, such as pain amplification, an important aspect of clinical pain disorders. We describe how the Fmr1 knockout mouse can be used to better understand the role of Fmrp in axons using cultures of sensory neurons and using manipulations to these neurons in vivo. We also discuss the established evidence for a role of Fmrp in nociceptive sensitization and how this evidence relates to an emerging role of translation control as a key process in pain amplification. Finally, we explore opportunities centered on the Fmr1 KO mouse for gaining further insight into the role of translation control in pain amplification and how this model may be used to identify novel therapeutic targets. We conclude that the study of the spinal sensory system in the Fmr1 KO mouse presents several unique prospects for gaining better insight into the human disorder and other clinical issues, such as chronic pain disorders, that affect millions of people worldwide.

Melemedjian, Ohannes K.

2011-01-01

60

Urinary S100B Protein Concentrations Are Increased in Intrauterine Growth-Retarded Newborns  

Microsoft Academic Search

BACKGROUND.Intrauterine growth retardation is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect brain damage in these patients. METHODS.We conducted a case-control study in tertiary NICUs from December 2001 to December 2003 with 42 intrauterine growth retardation infants and 84 controls. Routine laboratory variables, neurologic outcome at 7-day follow-up, ultrasound

Pasquale Florio; Emanuela Marinoni; Sabina Ciotti; Renata Sacchi; Matteo Bruschettini; Mario Lituania; Giovanni Serra; Fabrizio Michetti; Felice Petraglia; Diego Gazzolo

2010-01-01

61

Screening with the FMR1 protein test among mentally retarded males  

Microsoft Academic Search

The fragile X syndrome is characterized by X-linked mental retardation with additional features such as a long face with\\u000a large protruding ears, macroorchidism, and eye-gaze avoidance. The disorder is caused by an abnormally expanded CGG repeat\\u000a within the first exon of the fragile X mental retardation (FMR1) gene that is associated with shutdown of transcription and absence of the fragile

Bert B. A. de Vries; Serieta Mohkamsing; Ans M. W. van den Ouweland; Dicky J. J. Halley; Martinus F. Niermeijer; Ben A. Oostra; Rob Willemsen

1998-01-01

62

Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome  

Microsoft Academic Search

Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of

Anas M. Alazami; Amr Al-Saif; Abdulaziz Al-Semari; Saeed Bohlega; Soumaya Zlitni; Fatema Alzahrani; Prashant Bavi; Namik Kaya; Dilek Colak; Hanif Khalak; Andy Baltus; Borut Peterlin; Sumita Danda; Kailash P. Bhatia; Susanne A. Schneider; Nadia Sakati; Christopher A. Walsh; Futwan Al-Mohanna; Brian Meyer; Fowzan S. Alkuraya

2008-01-01

63

Detection of aneuploidies by paralogous sequence quantification  

PubMed Central

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.

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

2004-01-01

64

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P  

Microsoft Academic Search

The absence of fragile-X mental-retardation protein (FMRP) results in\\u000a fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been\\u000a described, FXR1P and FXR2P, which are both very similar in amino acid\\u000a sequence to FMRP. Interaction between the three proteins as well as with\\u000a themselves has been demonstrated. The FXR proteins are believed to play a\\u000a role in RNA metabolism. To characterize

Filippo TAMANINI; Leontine VAN UNEN; Cathy BAKKER; Nicoletta SACCHI; Hans GALJAARD; Ben A. OOSTRA; André T. HOOGEVEEN

1999-01-01

65

Drosophila fragile X mental retardation protein developmentally regulates activity-dependent axon pruning.  

PubMed

Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms ranging from hyperexcitability to mental retardation and autism. Loss of the fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding translational regulator FMRP, causes structural over-elaboration of dendritic and axonal processes, as well as functional alterations in synaptic plasticity at maturity. It is unclear, however, whether FraX is primarily a disease of development, a disease of plasticity or both: a distinction that is vital for engineering intervention strategies. To address this crucial issue, we have used the Drosophila FraX model to investigate the developmental function of Drosophila FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides with a transient window of late brain development. During this time, dFMRP is positively regulated by sensory input activity, and is required to limit axon growth and for efficient activity-dependent pruning of axon branches in the Mushroom Body learning/memory center. These results demonstrate that dFMRP has a primary role in activity-dependent neural circuit refinement during late brain development. PMID:18321984

Tessier, Charles R; Broadie, Kendal

2008-03-05

66

Mental Retardation.  

ERIC Educational Resources Information Center

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…

Purpura, Dominick P.; And Others

67

Short- and long-term memory are modulated by multiple isoforms of the fragile X mental retardation protein.  

PubMed

The diversity of protein isoforms arising from alternative splicing is thought to modulate fine-tuning of synaptic plasticity. Fragile X mental retardation protein (FMRP), a neuronal RNA binding protein, exists in isoforms as a result of alternative splicing, but the contribution of these isoforms to neural plasticity are not well understood. We show that two isoforms of Drosophila melanogaster FMRP (dFMR1) have differential roles in mediating neural development and behavior functions conferred by the dfmr1 gene. These isoforms differ in the presence of a protein interaction module that is related to prion domains and is functionally conserved between FMRPs. Expression of both isoforms is necessary for optimal performance in tests of short- and long-term memory of courtship training. The presence or absence of the protein interaction domain may govern the types of ribonucleoprotein (RNP) complexes dFMR1 assembles into, with different RNPs regulating gene expression in a manner necessary for establishing distinct phases of memory formation. PMID:20463240

Banerjee, Paromita; Schoenfeld, Brian P; Bell, Aaron J; Choi, Catherine H; Bradley, Michael P; Hinchey, Paul; Kollaros, Maria; Park, Jae H; McBride, Sean M J; Dockendorff, Thomas C

2010-05-12

68

Early growth retardation induced by excessive exposure to glucocorticoids in utero selectively increases cardiac GLUT1 protein expression and Akt/protein kinase B activity in adulthood.  

PubMed

In the rat, dexamethasone treatment during late pregnancy leads to intrauterine growth retardation and is used as a model of early programming of adult onset disease. The present study investigated whether pre-natal dexamethasone treatment modifies cardiac glucose transporter (GLUT) protein expression in adulthood and identified signalling pathways involved in the response. Dexamethasone (100 microg/kg body wt per day) administered via an osmotic pump to pregnant rats (day 15 to day 21; term=22 to 23 days) reduced fetal weight at day 21 and caused hypertension, hyperinsulinaemia and elevated corticosterone levels in the adult (24-week-old) male offspring. Cardiac GLUT1 protein expression was selectively up-regulated (2.5-fold; P<0.001), in the absence of altered cardiac GLUT4 protein expression, in adult male offspring of dexamethasone-treated dams. Maternal dexamethasone treatment did not influence cardiac GLUT1 protein expression during fetal or early post-natal life. We examined potential regulatory signalling proteins that might mediate up-regulation of cardiac GLUT1 protein expression in adulthood. We observed marked (2.2-fold; P<0.01) activation of Akt/protein kinase B (PKB), together with modest activation of the anti-apoptotic protein kinase C (PKC) isoforms PKC alpha (88%, P<0.05) and PKC epsilon (56%, P<0.05) in hearts of the early-growth-retarded male offspring. These effects were, however, observed in conjunction with up-regulation of cardiac protein expression of PKC beta(1) (191%, P<0.01), PKC beta(2) (49%, P<0.05) and PKC delta (35%; P<0.01), effects that may have adverse consequences. Maternal dexamethasone treatment was without effect on cardiac extracellular signal-related kinase (ERK) 1 or ERK2 activity in adulthood. In conclusion, our data demonstrate an effect of maternal dexamethasone treatment to up-regulate cardiac GLUT1 protein expression in early-growth-retarded, hypertensive, hyperinsulinaemic adult male offspring, an effect observed in conjunction with activation of Akt/PKB. PMID:11250642

Langdown, M L; Holness, M J; Sugden, M C

2001-04-01

69

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

PubMed

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

Gatto, Cheryl L; Broadie, Kendal

2008-06-25

70

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P.  

PubMed

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of >600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [(35)S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions. PMID:10527928

Tamanini, F; Van Unen, L; Bakker, C; Sacchi, N; Galjaard, H; Oostra, B A; Hoogeveen, A T

1999-11-01

71

Neonatal Exposure to Brominated Flame Retardant BDE-47 Reduces Long-Term Potentiation and Postsynaptic Protein Levels in Mouse Hippocampus  

PubMed Central

Background Increasing environmental levels of brominated flame retardants raise concern about possible adverse effects, particularly through early developmental exposure. Objective The objective of this research was to investigate neurodevelopmental mechanisms underlying previously observed behavioral impairments observed after neonatal exposure to polybrominated diphenyl ethers (PBDEs). Methods C57Bl/6 mice received a single oral dose of 2,2?,4,4?-tetrabromodiphenyl ether (BDE-47) on postnatal day (PND) 10 (i.e., during the brain growth spurt). On PND17–19, effects on synaptic plasticity, levels of postsynaptic proteins involved in long-term potentiation (LTP), and vesicular release mechanisms were studied ex vivo. We investigated possible acute in vitro effects of BDE-47 on vesicular catecholamine release and intracellular Ca2+ in rat pheochromocytoma (PC12) cells. Results Field-excitatory postsynaptic potential (f-EPSP) recordings in the hippocampal CA1 area demonstrated reduced LTP after exposure to 6.8 mg (14 ?mol)/kg body weight (bw) BDE-47, whereas paired-pulse facilitation was not affected. Western blotting of proteins in the postsynaptic, triton-insoluble fraction of hippocampal tissue revealed a reduction of glutamate receptor subunits NR2B and GluR1 and autophosphorylated-active Ca2+/calmodulin-dependent protein kinase II (?CaMKII), whereas other proteins tested appeared unaffected. Amperometric recordings in chromaffin cells from mice exposed to 68 mg (140 ?mol)/kg bw BDE-47 did not reveal changes in catecholamine release parameters. Modest effects on vesicular release and intracellular Ca2+ in PC12 cells were seen following acute exposure to 20 ?M BDE-47. The combined results suggest a post-synaptic mechanism in vivo. Conclusion Early neonatal exposure to a single high dose of BDE-47 causes a reduction of LTP together with changes in postsynaptic proteins involved in synaptic plasticity in the mouse hippocampus.

Dingemans, Milou M.L.; Ramakers, Geert M.J.; Gardoni, Fabrizio; van Kleef, Regina G.D.M.; Bergman, Ake; Di Luca, Monica; van den Berg, Martin; Westerink, Remco H.S.; Vijverberg, Henk P.M.

2007-01-01

72

Metabotropic Glutamate Receptor Activation Regulates Fragile X Mental Retardation Protein and Fmr1 mRNA Localization Differentially in Dendrites and at Synapses  

Microsoft Academic Search

Fragile X syndrome is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), which may play a role in activity-regulated localization and translation of mRNA in dendrites and at synapses. We investigated whether neuronal activity and glutamatergic signals regulate trafficking of FMRP and its encoding Fmr1 mRNA into dendrites or at synapses. Using high-resolution fluorescence

Laura N. Antar; Rownak Afroz; Jason B. Dictenberg; Reed C. Carroll; Gary J. Bassell

2004-01-01

73

A new function for the Fragile X Mental Retardation Protein in the regulation of PSD-95 mRNA stability  

PubMed Central

Fragile X Syndrome results from loss of the Fragile X mental retardation protein (FMRP), an RNA-binding protein regulating a variety of cytoplasmic mRNAs. FMRP regulates mRNA translation and has been suggested to play a role in mRNA localization to dendrites. We report a third cytoplasmic regulatory function for FMRP – control of mRNA stability. We find in mice that FMRP binds, in vivo, the mRNA encoding PSD-95, a key molecule regulating neuronal synaptic signalling and learning. This interaction occurs through the 3? untranslated region of the PSD–95 mRNA, increasing message stability. Moreover, stabilization is further increased by mGluR activation. While we also find that the PSD–95 mRNA is synaptically localized in vivo, localization occurs independently of FMRP. Through our functional analysis of this FMRP target we provide evidence that misregulation of mRNA stability may contribute to the cognitive impairments in Fragile X Syndrome patients.

Zalfa, Francesca; Eleuteri, Boris; Dickson, Kirsten S.; Mercaldo, Valentina; De Rubeis, Silvia; di Penta, Alessandra; Tabolacci, Elisabetta; Chiurazzi, Pietro; Neri, Giovanni; Grant, Seth G.N.; Bagni, Claudia

2009-01-01

74

Mutations in mitochondrial ribosomal protein MRPL12 leads to growth retardation, neurological deterioration and mitochondrial translation deficiency?  

PubMed Central

Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and are associated with a wide range of clinical symptoms. We report a subject, born to consanguineous parents, with growth retardation and neurological deterioration. Multiple respiratory chain deficiency was found in muscle and fibroblasts of the subject as well as abnormal assembly of complexes I and IV. A microsatellite genotyping of the family members detected only one region of homozygosity on chromosome 17q24.2–q25.3 in which we focused our attention to genes involved in mitochondrial translation. We sequenced MRPL12, encoding the mitochondrial ribosomal protein L12 and identified a c.542C>T transition in exon 5 changing a highly conserved alanine into a valine (p.Ala181Val). This mutation resulted in a decreased steady-state level of MRPL12 protein, with altered integration into the large ribosomal subunit. Moreover, an overall mitochondrial translation defect was observed in the subject's fibroblasts with a significant reduction of synthesis of COXI, COXII and COXIII subunits. Modeling of MRPL12 shows Ala181 positioned in a helix potentially involved in an interface of interaction suggesting that the p.Ala181Val change might be predicted to alter interactions with the elongation factors. These results contrast with the eubacterial orthologues of human MRPL12, where L7/L12 proteins do not appear to have a selective effect on translation. Therefore, analysis of the mutated version found in the subject presented here suggests that the mammalian protein does not function in an entirely analogous manner to the eubacterial L7/L12 equivalent.

Serre, Valerie; Rozanska, Agata; Beinat, Marine; Chretien, Dominique; Boddaert, Nathalie; Munnich, Arnold; Rotig, Agnes; Chrzanowska-Lightowlers, Zofia M.

2013-01-01

75

Mutations in mitochondrial ribosomal protein MRPL12 leads to growth retardation, neurological deterioration and mitochondrial translation deficiency.  

PubMed

Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and are associated with a wide range of clinical symptoms. We report a subject, born to consanguineous parents, with growth retardation and neurological deterioration. Multiple respiratory chain deficiency was found in muscle and fibroblasts of the subject as well as abnormal assembly of complexes I and IV. A microsatellite genotyping of the family members detected only one region of homozygosity on chromosome 17q24.2-q25.3 in which we focused our attention to genes involved in mitochondrial translation. We sequenced MRPL12, encoding the mitochondrial ribosomal protein L12 and identified a c.542C>T transition in exon 5 changing a highly conserved alanine into a valine (p.Ala181Val). This mutation resulted in a decreased steady-state level of MRPL12 protein, with altered integration into the large ribosomal subunit. Moreover, an overall mitochondrial translation defect was observed in the subject's fibroblasts with a significant reduction of synthesis of COXI, COXII and COXIII subunits. Modeling of MRPL12 shows Ala181 positioned in a helix potentially involved in an interface of interaction suggesting that the p.Ala181Val change might be predicted to alter interactions with the elongation factors. These results contrast with the eubacterial orthologues of human MRPL12, where L7/L12 proteins do not appear to have a selective effect on translation. Therefore, analysis of the mutated version found in the subject presented here suggests that the mammalian protein does not function in an entirely analogous manner to the eubacterial L7/L12 equivalent. PMID:23603806

Serre, Valérie; Rozanska, Agata; Beinat, Marine; Chretien, Dominique; Boddaert, Nathalie; Munnich, Arnold; Rötig, Agnès; Chrzanowska-Lightowlers, Zofia M

2013-04-18

76

Clinicopathologic significance of immunostaining of ?-thalassemia/mental retardation syndrome X-linked protein and death domain-associated protein in neuroendocrine tumors.  

PubMed

?-Thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) genes are tumor suppressors whose mutations have been identified in sporadic pancreatic neuroendocrine tumors as well as in patients with MEN1. However, it is unknown whether ATRX and DAXX alterations are specific for pancreatic neuroendocrine tumor. In addition, the association of ATRX/DAXX protein loss with tumor cell proliferation has not been examined. We, therefore, immunostained ATRX and DAXX in 10 gastric, 15 duodenal, 20 rectal, 70 pancreatic, and 22 pulmonary neuroendocrine tumors with 15 nonneoplastic pancreases and 27 pancreatic adenocarcinomas to elucidate the site-specific roles of ATRX/DAXX abnormalities. At least 1 loss of ATRX and DAXX immunoreactivity was detected in all neuroendocrine tumor cases but not in any of nonneoplastic pancreatic tissues or pancreatic adenocarcinomas. The loss of DAXX protein was correlated with the Ki-67 index (ATRX, P = .904; DAXX, P = .044). The status of DAXX immunoreactivity correlated positively with World Health Organization histologic grade (P = .026). These results suggest that the status of ATRX or DAXX protein loss in neuroendocrine tumor differed among the organs in which these tumors arose, and these proteins may play site-specific roles in the development of these tumors. PMID:23954140

Chen, Shi-Fan; Kasajima, Atsuko; Yazdani, Samaneh; Chan, Monica S M; Wang, Lin; He, Yang-Yang; Gao, Hong-Wen; Sasano, Hironobu

2013-08-16

77

In silico identification of functional divergence between the multiple groEL gene paralogs in Chlamydiae  

PubMed Central

Background Heat-shock proteins are specialized molecules performing different and essential roles in the cell including protein degradation, folding and trafficking. GroEL is a 60 Kda heat-shock protein ubiquitous in bacteria and has been regarded as an important molecule implicated in chronic inflammatory processes caused by Chlamydiae infections. GroEL in Chlamydiae became duplicated at the origin of the Chlamydiae lineage presenting three distinct molecular chaperones, namely the original protein GroEL1 (Ct110), and its paralogous proteins GroEL2 (Ct604) and GroEL3 (Ct755). These chaperones present differential and independent expressions during the different stages of Chlamydiae infections and have been suggested to present differential physiological and regulatory roles. Results In this comprehensive in silico study we show that GroEL protein paralogs have diverged functionally after the different gene duplication events and that this divergence has occurred mainly between GroEL3 and GroEL1. GroEL2 presents an intermediate functional divergence pattern from GroEL1. Our results point to the different protein-protein interaction patterns between GroEL paralogs and known GroEL protein clients supporting their functional divergence after groEL gene duplication. Analysis of selective constraints identifies periods of adaptive evolution after gene duplication that led to the fixation of amino acid replacements in GroEL protein domains involved in the interaction with GroEL protein clients. Conclusion We demonstrate that GroEL protein copies in Chlamydiae species have diverged functionally after the gene duplication events. We also show that functional divergence has occurred in important functional regions of these GroEL proteins and that very probably have affected the ancestral GroEL regulatory role and protein-protein interaction patterns with GroEL client proteins. Most of the amino acid replacements that have affected interaction with protein clients and that were responsible for the functional divergence between GroEL paralogs were fixed by adaptive evolution after the groEL gene duplication events.

McNally, David; Fares, Mario A

2007-01-01

78

Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein  

PubMed Central

Loss of FMR1 gene function results in fragile X syndrome (FXS), the most common heritable form of intellectual disability. The protein encoded from this locus (FMRP) is an RNA binding protein thought to primarily act as a translational regulator, however recent studies implicate FMRP in other mechanisms of gene regulation. Here, we demonstrate that the Drosophila fragile X homolog (dFMR1) biochemically interacts with the A-to-I RNA editing enzyme, dADAR. We found that dAdar and dfmr1 mutant larvae exhibit distinct morphological neuromuscular junction (NMJ) defects. Epistasis experiments based on these phenotypic differences suggest that dAdar acts downstream of dfmr1 and that dFMR1 modulates dADAR activity. Furthermore, sequence analyses revealed that loss or overexpression of dFMR1 affects editing efficiency on certain dADAR targets with defined roles in synaptic transmission. These results link dFMR1 with the RNA editing pathway and suggest that proper NMJ synaptic architecture requires modulation of dADAR activity by dFMR1.

Bhogal, Balpreet; Jepson, James E.; Savva, Yiannis A.; Pepper, Anita S.-R.; Reenan, Robert A.; Jongens, Thomas A.

2011-01-01

79

Identification of Four SUMO Paralogs in the Medaka Fish, Oryzias latipes , and Their Classification into Two Subfamilies  

Microsoft Academic Search

At least four paralogs of the small ubiquitin-related modifier (SUMO) exist in humans, but there is limited information about\\u000a SUMO paralogs from other vertebrate species. We isolated the four cDNA encoding proteins, similar to human SUMOs, from the\\u000a medaka fish, Oryzias latipes: OlSUMO-1, OlSUMO-2, OlSUMO-3, and OlSUMO-4. The amino acid sequences of OlSUMO-2, -3, and -4 are 89–94% identical, but

Shinpei Obata; Tsuyoshi Shirozu; Takeshi Kitano; Hisato Saitoh

2010-01-01

80

RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis.  

PubMed

Chromosomal double-strand breaks (DSBs) have the potential to permanently arrest cell cycle progression and endanger cell survival. They must therefore be efficiently repaired to preserve genome integrity and functionality. Homologous recombination (HR) provides an important error-free mechanism for DSB repair in mammalian cells. In addition to RAD51, the central recombinase activity in mammalian cells, a family of proteins known as the RAD51 paralogs and consisting of five proteins (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3), play an essential role in the DNA repair reactions through HR. The RAD51 paralogs act to transduce the DNA damage signal to effector kinases and to promote break repair. However, their precise cellular functions are not fully elucidated. Here we discuss recent advances in our understanding of how these factors mediate checkpoint responses and act in the HR repair process. In addition, we highlight potential functional similarities with the BRCA2 tumour suppressor, through the recently reported links between RAD51 paralog deficiencies and tumorigenesis triggered by genome instability. PMID:21821141

Suwaki, Natsuko; Klare, Kerstin; Tarsounas, Madalena

2011-07-28

81

Selective and efficient retardation of cancers expressing cytoskeleton-associated protein 2 by targeted RNA replacement.  

PubMed

Human cytoskeleton-associated protein 2 (hCKAP2) is upregulated and highly expressed in various human malignances. hCKAP2 has microtubule-stabilizing characteristics and potentially regulates the dynamics and assembly of the mitotic spindle and chromosome segregation, indicating that hCKAP2 plays important functions during mitosis. In this study, we evaluated hCKAP2 as a plausible anticancer target through development and validation of a targeted cancer gene therapy strategy based on targeting and replacement of hCKAP2 RNA using a trans-splicing ribozyme. This targeted RNA replacement triggered transgene activity via accurate trans-splicing reaction selectively in human cancer cells expressing the hCKAP2 RNA and simultaneously reduced the expression level of the RNA in the cells. Adenoviral vector encoding the hCKAP2-specific trans-splicing ribozyme selectively induced cytotoxicity in tumor cells expressing hCKAP2. Moreover, intratumoral injection of the virus produced selective and efficient regression of tumor that had been subcutaneously inoculated with hCKAP2-positive colon cancer cells in mice with minimal liver toxicity. Furthermore, orthotopically multifocal hCKAP2-positive hepatocarcinoma established in mice were efficiently regressed by systemic delivery of adenoviral vector encoding the specific ribozyme under the control of a liver-selective phosphoenolpyruvate carboxykinase promoter with least hepatotoxicity. The results indicate that hCKAP2 RNA is a promising target for anticancer approach based on trans-splicing ribozyme-mediated RNA replacement. PMID:21328343

Ban, Guyee; Jeong, Jin-Sook; Kim, Areum; Kim, Sung Jin; Han, Sang-Young; Kim, In-Hoo; Lee, Seong-Wook

2011-04-13

82

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

Microsoft Academic Search

Background  Fragile × syndrome is caused by loss of function of the fragile × 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.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In the current study, we have investigated levels of FMRP in the superior frontal cortex of people

S Hossein Fatemi; Timothy D Folsom

2011-01-01

83

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

PubMed Central

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.

Gatto, Cheryl L.; Broadie, Kendal

2011-01-01

84

Differential expression and novel permeability properties of three aquaporin 8 paralogs from seawater-challenged Atlantic salmon smolts.  

PubMed

Aquaporins may facilitate transepithelial water absorption in the intestine of seawater (SW)-acclimated fish. Here we have characterized three full-length aqp8 paralogs from Atlantic salmon (Salmo salar). Bayesian inference revealed that each paralog is a representative of the three major classes of aqp8aa, aqp8ab and aqp8b genes found in other teleosts. The permeability properties were studied by heterologous expression in Xenopus laevis oocytes, and the expression levels examined by qPCR, immunofluorescence and immunoelectron microscopy, and immunoblotting of membrane fractions from intestines of SW-challenged smolts. All three Aqp8 paralogs were permeable to water and urea, whereas Aqp8ab and -8b were, surprisingly, also permeable to glycerol. The mRNA tissue distribution of each paralog was distinct, although some tissues such as the intestine showed redundant expression of more than one paralog. Immunofluorescence microscopy localized Aqp8aa(1+2) to intracellular compartments of the liver and intestine, and Aqp8ab and Aqp8b to apical plasma membrane domains of the intestinal epithelium, with Aqp8b also in goblet cells. In a control experiment with rainbow trout, immunoelectron microscopy confirmed abundant labeling of Aqp8ab and -8b at apical plasma membranes of enterocytes in the middle intestine and also in subapical vesicular structures. During SW challenge, Aqp8ab showed significantly increased levels of protein expression in plasma-membrane-enriched fractions of the intestine. These data indicate that the Atlantic salmon Aqp8 paralogs have neofunctionalized on a transcriptional as well as a functional level, and that Aqp8ab may play a central role in the intestinal transcellular uptake of water during SW acclimation. PMID:23868847

Engelund, Morten B; Chauvigné, François; Christensen, Birgitte Mønster; Finn, Roderick Nigel; Cerdà, Joan; Madsen, Steffen S

2013-07-18

85

A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation  

Microsoft Academic Search

We have identified a novel splice site mutation (IVS6-1G?>?A) in the disc-large homolog 3 (DLG3) gene, encoding the synapse-associated protein 102 (SAP102) in one out of 300 families with moderate to severe non-syndromic\\u000a mental retardation. SAP102 is a member of the neuronal membrane-associated guanylate kinase protein subfamily comprising SAP97,\\u000a postsynaptic density (PSD)95, and PSD93, which interacts with methyl-d-aspartate receptor and

Ginevra Zanni; Hilde van Esch; Anissa Bensalem; Yoann Saillour; Karine Poirier; Laetitia Castelnau; Hans Hilger Ropers; Arjan P. M. de Brouwer; Fréderic Laumonnier; Jean-Pierre Fryns; Jamel Chelly

2010-01-01

86

Transcriptomic and phenotypic analysis of paralogous spx gene function in Bacillus anthracis Sterne.  

PubMed

Spx of Bacillus subtilis is a redox-sensitive protein, which, under disulfide stress, interacts with RNA polymerase to activate genes required for maintaining thiol homeostasis. Spx orthologs are highly conserved among low %GC Gram-positive bacteria, and often exist in multiple paralogous forms. In this study, we used B. anthracis Sterne, which harbors two paralogous spx genes, spxA1 and spxA2, to examine the phenotypes of spx null mutations and to identify the genes regulated by each Spx paralog. Cells devoid of spxA1 were sensitive to diamide and hydrogen peroxide, while the spxA1 spoxA2 double mutant was hypersensitive to the thiol-specific oxidant, diamide. Bacillus anthracis Sterne strains expressing spxA1DD or spxA2DD alleles encoding protease-resistant products were used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses in order to uncover genes under SpxA1, SpxA2, or SpxA1/SpxA2 control. Comparison of transcriptomes identified many genes that were upregulated when either SpxA1DD or SpxA2DD was produced, but several genes were uncovered whose transcript levels increased in only one of the two SpxADD-expression strains, suggesting that each Spx paralog governs a unique regulon. Among genes that were upregulated were those encoding orthologs of proteins that are specifically involved in maintaining intracellular thiol homeostasis or alleviating oxidative stress. Some of these genes have important roles in B. anthracis pathogenesis, and a large number of upregulated hypothetical genes have no homology outside of the B. cereus/thuringiensis group. Microarray and RT-qPCR analyses also unveiled a regulatory link that exists between the two spx paralogous genes. The data indicate that spxA1 and spxA2 are transcriptional regulators involved in relieving disulfide stress but also control a set of genes whose products function in other cellular processes. PMID:23873705

Barendt, Skye; Lee, Hyunwoo; Birch, Cierra; Nakano, Michiko M; Jones, Marcus; Zuber, Peter

2013-07-22

87

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

PubMed Central

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.

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

2010-01-01

88

Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells  

Microsoft Academic Search

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 inter- actions among these proteins using baculovirus and two- and three-hybrid yeast systems. To test for inter-

Claudia Wiese; David W. Collins; Joanna S. Albala; Larry H. Thompson; Amy Kronenberg; David Schild

2002-01-01

89

Cell phenotypes of a mutant in the gene encoding a Rad51 paralog in fission yeast  

Microsoft Academic Search

The discovery of three Rad51 paralogs in Saccharomyces cerevisiae (Rad55, Rad57, and Dmc1), four in Schizosaccharomyces pombe (Rhp55, Rhp57, Rlp1, and Dmc1), and six in human (Rad51B, Rad51C, Rad51D, Xrcc2, Xrcc3, and Dmc1) indicate the functional\\u000a diversity and specialization of RecA-like proteins in the line from the lower to higher organisms. This paper reports characterization\\u000a of a number of mitotic

A. N. Sultanova; A. F. Salakhova; V. I. Bashkirov; F. K. Khasanov

2007-01-01

90

Splign: algorithms for computing spliced alignments with identification of paralogs  

Microsoft Academic Search

BACKGROUND: The computation of accurate alignments of cDNA sequences against a genome is at the foundation of modern genome annotation pipelines. Several factors such as presence of paralogs, small exons, non-consensus splice signals, sequencing errors and polymorphic sites pose recognized difficulties to existing spliced alignment algorithms. RESULTS: We describe a set of algorithms behind a tool called Splign for computing

Yuri Kapustin; Alexander Souvorov; Tatiana Tatusova; David Lipman

2008-01-01

91

Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein  

PubMed Central

Parathyroid hormone (PTH) plays a central role in the regulation of serum calcium and phosphorus homeostasis, while parathyroid hormone-related protein (PTHrP) has important developmental roles. Both peptides signal through the same G protein-coupled receptor, the PTH/PTHrP or PTH type 1 receptor (PTH1R). PTHrP, normally a secreted protein, also contains a nuclear localization signal (NLS) that in vitro imparts functionality to the protein at the level of the nucleus. We investigated this functionality in vivo by introducing a premature termination codon in Pthrp in ES cells and generating mice that express PTHrP (1–84), a truncated form of the protein that is missing the NLS and the C-terminal region of the protein but can still signal through its cell surface receptor. Mice homozygous for the knock-in mutation (Pthrp KI) displayed retarded growth, early senescence, and malnutrition leading postnatally to their rapid demise. Decreased cellular proliferative capacity and increased apoptosis in multiple tissues including bone and bone marrow cells were associated with altered expression and subcellular distribution of the senescence-associated tumor suppressor proteins p16INK4a and p21 and the oncogenes Cyclin D, pRb, and Bmi-1. These findings provide in vivo experimental proof that substantiates the biologic relevance of the NLS and C-terminal portion of PTHrP, a polypeptide ligand that signals mainly via a cell surface G protein-coupled receptor.

Miao, Dengshun; Su, Hanyi; He, Bin; Gao, Jianjun; Xia, Qingwen; Zhu, Min; Gu, Zhen; Goltzman, David; Karaplis, Andrew C.

2008-01-01

92

Identification of pathways, gene networks and paralogous gene families in Daphnia pulex responding to exposure to the toxic cyanobacterium Microcystis aeruginosa  

PubMed Central

Although cyanobacteria produce a wide range of natural toxins that impact aquatic organisms, food webs and water quality, the mechanisms of toxicity are still insufficiently understood. Here, we implemented a whole-genome expression microarray to identify pathways, gene networks and paralogous gene families responsive to Microcystis stress in Daphnia pulex. Therefore, neonates of a sensitive isolate were given a diet contaminated with Microcystis to contrast with those given a control diet for sixteen days. The microarray revealed 2247 differentially expressed (DE) genes (7.6% of the array) in response to Microcystis, of which 17% are lineage specific( i.e., these genes have no detectable homology to any other gene in currently available databases) and 49% are gene duplicates (paralogs). We identified four pathways/gene networks and eight paralogous gene families affected by Microcystis. Differential regulation of the ribosome, including 3 paralogous gene families encoding 40S, 60S and mitochondrial ribosomal proteins, suggests an impact of Microcystis on protein synthesis of D. pulex. In addition, differential regulation of the oxidative phosphorylation pathway (including the NADH ubquinone oxidoreductase gene family) and the trypsin paralogous gene family (a major component of the digestive system in D. pulex) could explain why fitness is reduced based on energy budget considerations.

Asselman, Jana; De Coninck, Dieter IM; Glaholt, Stephen; Colbourne, John K; Janssen, Colin R; Shaw, Joseph R; De Schamphelaere, Karel AC

2013-01-01

93

Sulfolobus tokodaii RadA paralog, stRadC2, is involved in DNA recombination via interaction with RadA and Hjc.  

PubMed

Rad51/RadA paralogs found in eukaryotes and euryarchaea play important roles during recombination and repair, and mutations in one of the human Rad51 paralogs, Rad51C, are associated with breast and ovarian cancers. The hyperthermophilic crenarchaeon Sulfolobus tokodaii encodes four putative RadA paralogs and studies on these proteins may assist in understanding the functions of human Rad51 paralogs. Here, we report the biochemical characterization of stRadC2, a S. tokodaii RadA paralog. Pull-down assays revealed that the protein was able to interact with the recombinase, RadA, and the Holliday junction endonuclease, Hjc. stRadC2 inhibited the strand exchange activity of RadA and facilitated Hjc-mediated Holliday junction DNA cleavage in vitro. RT-PCR analysis revealed that stRadC2 transcription was immediately reduced after UV irradiation, but was restored to normal levels at the late stages of DNA repair. Our results suggest that stRadC2 may act as an anti-recombination factor in DNA recombinational repair in S. tokodaii. PMID:22437993

Wang, Lei; Sheng, DuoHong; Han, WenYuan; Huang, Bin; Zhu, ShanShan; Ni, JinFeng; Li, Jia; Shen, YuLong

2012-03-21

94

A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P.  

PubMed

Aminoacyl-tRNA synthetase (aaRS) paralogs with unknown functions exist in various species. We now report novel 'protein lysylation' by an Escherichia coli lysyl-tRNA synthetase paralog, GenX/PoxA/YjeA. X-ray crystallographic analysis shows that the structure of the GenX protein resembles that of a class II aaRS. Further in vitro studies reveal that it specifically aminoacylates EF-P with lysine. The shape of the protein substrate mimics that of the L-shaped tRNA, and its lysylation site corresponds to the tRNA 3' end. Thus, we show how the aaRS architecture can be adapted to achieve aminoacylation of a specific protein. Moreover, in vivo analyses reveal that the translation elongation factor P (EF-P) lysylation by GenX is enhanced by YjeK (lysine 2,3-aminomutase paralog), which is encoded next to the EF-P gene, and might convert alpha-lysyl-EF-P to beta-lysyl-EF-P. In vivo analyses indicate that the EF-P modification by GenX and YjeK is essential for cell survival. PMID:20729861

Yanagisawa, Tatsuo; Sumida, Tomomi; Ishii, Ryohei; Takemoto, Chie; Yokoyama, Shigeyuki

2010-08-22

95

Microtubule perturbation retards both the direct and the indirect apical pathway but does not affect sorting of plasma membrane proteins in intestinal epithelial cells (Caco-2).  

PubMed Central

Endogenous plasma membrane proteins are sorted from two sites in the human intestinal epithelial cell line Caco-2. Apical proteins are transported from the Golgi apparatus to the apical domain along a direct pathway and an indirect pathway via the basolateral membrane. In contrast, basolateral proteins never appear in the apical plasma membrane. Here we report on the effect of the microtubule-active drug nocodazole on the post-synthetic transport and sorting of plasma membrane proteins. Pulse-chase radiolabeling was combined with domain-specific cell surface assays to monitor the appearance of three apical and one basolateral protein in plasma membrane domains. Nocodazole was found to drastically retard both the direct transport of apical proteins from the Golgi apparatus and the indirect transport (transcytosis) from the basolateral membrane to the apical cell surface. In contrast, neither the transport rates of the basolateral membrane nor the sorting itself were significantly affected by the nocodazole treatment. We conclude that an intact microtubular network facilitates, but is not necessarily required for, the transport of apical membrane proteins along the two post-Golgi pathways to the brush border. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7.

Matter, K; Bucher, K; Hauri, H P

1990-01-01

96

Differential Regulation by Magnesium of the Two MsbB Paralogs of Shigella flexneri?  

PubMed Central

Shigella flexneri, a gram-negative enteric pathogen, is unusual in that it contains two nonredundant paralogous genes that encode the myristoyl transferase MsbB (LpxM) that catalyzes the final step in the synthesis of the lipid A moiety of lipopolysaccharide. MsbB1 is encoded on the chromosome, and MsbB2 is encoded on the large virulence plasmid present in all pathogenic shigellae. We demonstrate that myristoyl transferase activity due to MsbB2 is detected in limited magnesium medium, but not in replete magnesium medium, whereas that due to MsbB1 is detected under both conditions. MsbB2 increases overall hexa-acylation of lipid A under limited magnesium conditions. Regulation of MsbB2 by magnesium occurs at the level of transcription and is dependent on the conserved magnesium-inducible PhoPQ two-component regulatory pathway. Direct hexanucleotide repeats within the promoter upstream of msbB2 were identified as a putative PhoP binding site, and mutations within the repeats led to diminished PhoP-dependent expression of a transcriptional fusion of lacZ to this promoter. Thus, the virulence plasmid-encoded paralog of msbB is induced under limited magnesium in a PhoPQ-dependent manner. PhoPQ regulates the response of many Enterobacteriaceae to environmental signals, which include modifications of lipid A that confer increased resistance of the organism to stressful environments and antimicrobial peptides. The findings reported here are the first example of gene duplication in which one paralog has selectively acquired the mechanism for differential regulation by PhoPQ. Our findings provide molecular insight into the mechanisms by which each of the two MsbB proteins of S. flexneri likely contributes to pathogenesis.

Goldman, Seth R.; Tu, Yupeng; Goldberg, Marcia B.

2008-01-01

97

HasB, the Serratia marcescens TonB paralog, is specific to HasR.  

PubMed

Serratia marcescens possesses two functional TonB paralogs, TonB(Sm) and HasB, for energizing TonB-dependent transport receptors (TBDT). Previous work had shown that HasB is specific to heme uptake in the natural host and in Escherichia coli expressing the S. marcescens TBDT receptor HasR, whereas the S. marcescens TonB and E. coli TonB proteins function equally well with various TBDT receptors for heme and siderophores. This has raised the question of the target of this specificity. HasB could be specific either to heme TBDT receptors or only to HasR. To resolve this question, we have cloned in E. coli another S. marcescens heme receptor, HemR, and we show here that this receptor is TonB dependent and does not work with HasB. This demonstrates that HasB is not dedicated to heme TBDT receptors but rather forms a specific pair with HasR. This is the first reported case of a specific TonB protein working with only one TBDT receptor in one given species. We discuss the occurrence, possible molecular mechanisms, and selective advantages of such dedicated TonB paralogs. PMID:17951376

Benevides-Matos, Najla; Wandersman, Cécile; Biville, Francis

2007-10-19

98

Dynamic protein composition of Arabidopsis thaliana cytosolic ribosomes in response to sucrose feeding as revealed by label free MSE proteomics  

Microsoft Academic Search

Cytosolic ribosomes are among the largest multisubunit cellular complexes. Arabidopsis thaliana ribosomes consist of 79 different ribosomal proteins (r-proteins) that each are encoded by two to six (paralogous) genes. It is unknown whether the paralogs are incorporated into the ribosome and whether the relative incorporation of r-protein paralogs varies in response to environmental cues. Immunopurified ribosomes were isolated from A.

M. Hummel; J. H. G. C. Cordewener; Groot de J. C. M; S. Smeekens; A. H. P. America; J. Hanson

2012-01-01

99

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

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 ?-aminobutyric acid (GABA) A receptor ?3 (GABR?3), 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 GABR?3. 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.

2011-01-01

100

Neurodegeneration-associated TDP-43 Interacts with Fragile X Mental Retardation Protein (FMRP)/Staufen (STAU1) and Regulates SIRT1 Expression in Neuronal Cells*  

PubMed Central

Despite the identification of the 43 kDa transactive response DNA-binding protein (TDP-43) as a major pathological signatory protein in a wide range of neurodegenerative diseases, the mechanistic role of TDP-43 in neurodegenerative disorders is still poorly understood. Here, we report that TDP-43 is physically associated with fragile X mental retardation protein (FMRP) and Staufen (STAU1) to form a functional complex. Differential microarray analysis revealed that the expression of a collection of functionally important genes including Sirtuin (SIRT1) is regulated by this complex. RNA-immunoprecipitation (RIP) and RNA pull-down assays demonstrated that TDP-43/FMRP/STAU1 specifically binds to the 3?-UTR of SIRT1 mRNA, and that knockdown the expression of any one of these three proteins resulted in the reduction of SIRT1 mRNA and protein. SIRT1 is implicated in double-stranded DNA break repair and is required for cell survival. Indeed, depletion of TDP-43/FMRP/STAU1 sensitizes cells to apoptosis and DNA damages. Collectively, our results revealed a molecular mechanism for the cellular function of TDP-43 and might shed new light on the understanding of the mechanistic role of TDP-43 in neurodegenerative diseases.

Yu, Zhipeng; Fan, Dongsheng; Gui, Bin; Shi, Lei; Xuan, Chenghao; Shan, Lin; Wang, Qian; Shang, Yongfeng; Wang, Yan

2012-01-01

101

Crystal structure of the C-terminal globular domain of the third paralog of the Archaeoglobus fulgidus oligosaccharyltransferases  

PubMed Central

Background Protein N-glycosylation occurs in the three domains of life. Oligosaccharyltransferase (OST) transfers an oligosaccharide chain to the asparagine residue in the N-glycosylation sequons. The catalytic subunits of the OST enzyme are STT3 in eukaryotes, AglB in archaea and PglB in eubacteria. The genome of a hyperthermophilic archaeon, Archaeoglobus fulgidus, encodes three paralogous AglB proteins. We previously solved the crystal structures of the C-terminal globular domains of two paralogs, AglB-Short 1 and AglB-Short 2. Results We determined the crystal structure of the C-terminal globular domain of the third AglB paralog, AglB-Long, at 1.9 Å resolutions. The crystallization of the fusion protein with maltose binding protein (MBP) afforded high quality protein crystals. Two MBP-AglB-L molecules formed a swapped dimer in the crystal. Since the fusion protein behaved as a monomer upon gel filtration, we reconstituted the monomer structure from the swapped dimer by exchanging the swapped segments. The C-terminal domain of A. fulgidus AglB-L includes a structural unit common to AglB-S1 and AglB-S2. This structural unit contains the evolutionally conserved WWDYG and DK motifs. The present structure revealed that A. fulgidus AglB-L contained a variant type of the DK motif with a short insertion, and confirmed that the second signature residue, Lys, of the DK motif participates in the formation of a pocket that binds to the serine and threonine residues at the +2 position of the N-glycosylation sequon. Conclusions The structure of A. fulgidus AglB-L, together with the two previously solved structures of AglB-S1 and AglB-S2, provides a complete overview of the three AglB paralogs encoded in the A. fulgidus genome. All three AglBs contain a variant type of the DK motif. This finding supports a previously proposed rule: The STT3/AglB/PglB paralogs in one organism always contain the same type of Ser/Thr-binding pocket. The present structure will be useful as a search model for molecular replacement in the structural determination of the full-length A. fulgidus AglB-L.

2013-01-01

102

Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA  

Microsoft Academic Search

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

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

2009-01-01

103

The role of recently derived FT paralogs in sunflower domestication.  

PubMed

Gene duplication provides an important source of genetic raw material for phenotypic diversification, but few studies have detailed the mechanisms through which duplications produce evolutionary novelty within species. Here, we investigate how a set of recently duplicated homologs of the floral inducer FLOWERING LOCUS T (FT) has contributed to sunflower domestication. We find that changes in expression of these duplicates are associated with differences in flowering behavior between wild and domesticated sunflower. In addition, we present genetic and functional evidence demonstrating that a frameshift mutation in one paralog, Helianthus annuus FT 1 (HaFT1), underlies a major QTL for flowering time and experienced a selective sweep during early domestication. Notably, this dominant-negative allele delays flowering through interference with action of another paralog, HaFT4. Together, these data reveal that changes affecting the expression, sequence, and gene interactions of HaFT paralogs have played key roles during sunflower domestication. Our findings also illustrate the important role that evolving interactions between new gene family members may play in fostering phenotypic change. PMID:20303265

Blackman, Benjamin K; Strasburg, Jared L; Raduski, Andrew R; Michaels, Scott D; Rieseberg, Loren H

2010-03-18

104

Eukaryotic GPN-loop GTPases paralogs use a dimeric assembly reminiscent of archeal GPN.  

PubMed

GTPases are molecular switches that regulate a wide-range of cellular processes. The GPN-loop GTPase (GPN) is a sub-family of P-loop NTPase that evolved from a single gene copy in archaea to triplicate paralog genes in eukaryotes, each having a non-redundant essential function in cell. In Saccharomyces cerevisiae, yGPN1 and yGPN2 are involved in sister chromatid cohesion mechanism, whereas nothing is known regarding yGPN3 function. Previous high-throughput experiments suggested that GPN paralogs interaction may occur. In this work, GPN|GPN contact was analyzed in details using TAP-Tag approach, yeast two-hybrid assay, in silico energy computation and site-directed mutagenesis of a conserved Glu residue located at the center of the interaction interface. It is demonstrated that this residue is essential for cell viability. A chromatid cohesion assay revealed that, like yGPN1 and yGPN2, yGPN3 also plays a role in sister chromatid cohesion. These results suggest that all three GPN proteins act at the molecular level in sister chromatid cohesion mechanism as a GPN|GPN complex reminiscent of the homodimeric structure of PAB0955, an archaeal member of GPN-loop GTPase. PMID:23324351

Alonso, Béatrice; Beraud, Carole; Meguellati, Sarra; Chen, Shu W; Pellequer, Jean Luc; Armengaud, Jean; Godon, Christian

2013-01-16

105

Genome Reduction by Deletion of Paralogs in the Marine Cyanobacterium Prochlorococcus  

PubMed Central

Several isolates of the marine cyanobacterial genus Prochlorococcus have smaller genome sizes than those of the closely related genus Synechococcus. In order to test whether loss of protein-coding genes has contributed to genome size reduction in Prochlorococcus, we reconstructed events of gene family evolution over a strongly supported phylogeny of 12 Prochlorococcus genomes and 9 Synechococcus genomes. Significantly, more events both of loss of paralogs within gene families and of loss of entire gene families occurred in Prochlorococcus than in Synechococcus. The number of nonancestral gene families in genomes of both genera was positively correlated with the extent of genomic islands (GIs), consistent with the hypothesis that horizontal gene transfer (HGT) is associated with GIs. However, even when only isolates with comparable extents of GIs were compared, significantly more events of gene family loss and of paralog loss were seen in Prochlorococcus than in Synechococcus, implying that HGT is not the primary reason for the genome size difference between the two genera.

Luo, Haiwei; Friedman, Robert; Tang, Jijun; Hughes, Austin L.

2011-01-01

106

Eukaryotic GPN-loop GTPases paralogs use a dimeric assembly reminiscent of archeal GPN  

PubMed Central

GTPases are molecular switches that regulate a wide-range of cellular processes. The GPN-loop GTPase (GPN) is a sub-family of P-loop NTPase that evolved from a single gene copy in archaea to triplicate paralog genes in eukaryotes, each having a non-redundant essential function in cell. In Saccharomyces cerevisiae, yGPN1 and yGPN2 are involved in sister chromatid cohesion mechanism, whereas nothing is known regarding yGPN3 function. Previous high-throughput experiments suggested that GPN paralogs interaction may occur. In this work, GPN|GPN contact was analyzed in details using TAP-Tag approach, yeast two-hybrid assay, in silico energy computation and site-directed mutagenesis of a conserved Glu residue located at the center of the interaction interface. It is demonstrated that this residue is essential for cell viability. A chromatid cohesion assay revealed that, like yGPN1 and yGPN2, yGPN3 also plays a role in sister chromatid cohesion. These results suggest that all three GPN proteins act at the molecular level in sister chromatid cohesion mechanism as a GPN|GPN complex reminiscent of the homodimeric structure of PAB0955, an archaeal member of GPN-loop GTPase.

Alonso, Beatrice; Beraud, Carole; Meguellati, Sarra; Chen, Shu W.; Pellequer, Jean Luc; Armengaud, Jean; Godon, Christian

2013-01-01

107

Analysis of the Fragile X mental retardation protein isoforms 1, 2 and 3 interactions with the G-quadruplex forming semaphorin 3F mRNA.  

PubMed

Fragile X syndrome, the most prevalent inheritable mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP) expression. FMRP is an RNA-binding protein with nucleo-cytoplasmic shuttle activity, proposed to act as a translation regulator of specific mRNAs in the brain. It has been shown that FMRP uses its arginine-glycine-glycine (RGG) box domain to bind a subset of mRNA targets that form a G-quadruplex structure. FMRP has also been shown to undergo the post-translational modifications of arginine methylation and phosphorylation, as well as alternative splicing, resulting in multiple isoforms. The alternative splice isoforms investigated in this study, isoform 1 (ISO1), isoform 2 (ISO2), and isoform 3 (ISO3), are created by the alternative splicing acceptor site at exon 15. FMRP ISO2 and ISO3 are truncated by 12 and 13 residues, respectively, relative to the longest FMRP isoform ISO1. These truncations, which are in the close proximity of the RGG box domain, preserve the integrity of the RGG box in all three isoforms, but eliminate the in vivo phosphorylation sites, present only on FMRP ISO1. We have expressed and purified recombinant FMRP ISO1, ISO2 and ISO3 in Escherichia coli, free of post-translational modifications, and by using fluorescence spectroscopy, we show that each FMRP isoform binds G-quadruplex RNA, albeit with different binding affinities, suggesting that naturally occurring sequence modifications in the proximity of the RGG box modulate its G-quadruplex RNA binding ability. PMID:22134704

Evans, Timothy L; Blice-Baum, Anna C; Mihailescu, Mihaela-Rita

2011-12-01

108

Fire retarded polymer nanocomposites  

Microsoft Academic Search

Nanocomposite structure of polymer intercalated montmorillonites was formed in ethylene vinyl acetate copolymer\\/magnesium hydroxide flame retarded polymer system. Generally the presence of magnesium hydroxide flame retardant particles disturbs the structural analysis of such systems. Raman microscopic method was successfully applied for evaluating the distribution of components in presence of high concentration of flame retardant additives. The interphase formed around the

B. Marosfoi; Sz. Matko; P. Anna Gy. Marosi

2006-01-01

109

Expression of Saccharomyces cerevisiae Sdh3p and Sdh4p Paralogs Results in Catalytically Active Succinate Dehydrogenase Isoenzymes*  

PubMed Central

Succinate dehydrogenase (SDH), also known as complex II, is required for respiratory growth; it couples the oxidation of succinate to the reduction of ubiquinone. The enzyme is composed of two domains. A membrane-extrinsic catalytic domain composed of the Sdh1p and Sdh2p subunits harbors the flavin and iron-sulfur cluster cofactors. A membrane-intrinsic domain composed of the Sdh3p and Sdh4p subunits interacts with ubiquinone and may coordinate a b-type heme. In many organisms, including Saccharomyces cerevisiae, possible alternative SDH subunits have been identified in the genome. S. cerevisiae contains one paralog of the Sdh3p subunit, Shh3p (YMR118c), and two paralogs of the Sdh4p subunit, Shh4p (YLR164w) and Tim18p (YOR297c). We cloned and expressed these alternative subunits. Shh3p and Shh4p were able to complement ?sdh3 and ?sdh4 deletion mutants, respectively, and support respiratory growth. Tim18p was unable to do so. Microarray and proteomics data indicate that the paralogs are expressed under respiratory and other more restrictive growth conditions. Strains expressing hybrid SDH enzymes have distinct metabolic profiles that we distinguished by 1H NMR analysis of metabolites. Surprisingly, the Sdh3p subunit can form SDH isoenzymes with Sdh4p or with Shh4p as well as be a subunit of the TIM22 mitochondrial protein import complex.

Szeto, Samuel S. W.; Reinke, Stacey N.; Oyedotun, Kayode S.; Sykes, Brian D.; Lemire, Bernard D.

2012-01-01

110

Sublethal effects of the flame retardant intermediate hexachlorocyclopentadiene (HCCPD) on the gene transcription and protein activity of Daphnia magna.  

PubMed

Hexachlorocyclopentadiene (HCCPD) is a chlorinated chemical of high production volume used as an intermediate in the production of flame retardants. HCCPD may be released to the environment during production, use, and as a result of product degradation. The objectives of this study were to evaluate sublethal effects of HCCPD exposure to Daphnia magna at environmentally relevant concentrations (0.0138-13.8?g/L) using genomic tools (microarray and qPCR), enzyme activities, and life-history endpoints (survival, reproduction, and growth). In chronic exposures, no differences were observed in life-history endpoints (survival, time of first brood, time of first molt, molt frequency, number of neonates, and body length) between exposed organisms and controls. Microarray analyses indicated significant differential genomic transcription for 46 genes (p-value?0.05 and fold-change>2). Five identified genes were related to metabolic functions. Enzyme activities of ?-amylase and trypsin, selected based on transcriptional responses, were evaluated in D. magna. Although trypsin activity was similar between treatments and controls, the activity of ?-amylase significantly decreased with increasing HCCPD concentrations. On the chemical level, instability of HCCPD was observed in spiked culture media, most probably due to photolysis and biodegradation. HCCPD was not detected in surface water samples collected upstream and at the point of discharge of a major wastewater treatment plant effluent. Environmentally, rapid degradation of HCCPD could be outdone by its continuous release into aquatic ecosystems in specific areas of concern (e.g., vicinity of industries and hazardous sites). Toxicity results from this study highlight the use of genomics in the identification of biomarkers and help advance the science, and potential use, of multi-level biological approaches for environmental risk assessment. PMID:23820075

Houde, Magali; Carter, Barbara; Douville, Mélanie

2013-06-15

111

The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes  

Microsoft Academic Search

The fragile X syndrome results from a transcriptional silencing of the FMR1 gene and the absence of its encoded protein. FMRP is a cytoplasmic RNA-binding protein, whose specific cellular function is still unknown. We present evidence that virtually all detectable cytoplasmic FMRP in mouse NIH 3T3 and human HeLa cells is found strictly in association with mRNA in actively translating

François Corbin; Marlène Bouillon; Anny Fortin; Stanislas Morin; François Rousseau; Edouard W. Khandjian

1997-01-01

112

Fragile X mental retardation protein is required for rapid experience-dependent regulation of the potassium channel Kv3.1b.  

PubMed

Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates synaptic plasticity by repressing translation of specific mRNAs. We found that FMRP binds mRNA encoding the voltage-gated potassium channel Kv3.1b in brainstem synaptosomes. To explore the regulation of Kv3.1b by FMRP, we investigated Kv3.1b immunoreactivity and potassium currents in the auditory brainstem sound localization circuit of male mice. The unique features of this circuit allowed us to control neuronal activity in vivo by exposing animals to high-frequency, amplitude-modulated stimuli, which elicit predictable and stereotyped patterns of input to the anterior ventral cochlear nucleus (AVCN) and medial nucleus of the trapezoid body (MNTB). In wild-type (WT) animals, Kv3.1b is expressed along a tonotopic gradient in the MNTB, with highest levels in neurons at the medial, high-frequency end. At baseline, Fmr1(-/-) mice, which lack FMRP, displayed dramatically flattened tonotopicity in Kv3.1b immunoreactivity and K(+) currents relative to WT controls. Moreover, after 30 min of acoustic stimulation, levels of Kv3.1b immunoreactivity were significantly elevated in both the MNTB and AVCN of WT, but not Fmr1(-/-), mice. These results suggest that FMRP is necessary for maintenance of the gradient in Kv3.1b protein levels across the tonotopic axis of the MNTB, and are consistent with a role for FMRP as a repressor of protein translation. Using numerical simulations, we demonstrate that Kv3.1b tonotopicity may be required for accurate encoding of stimulus features such as modulation rate, and that disruption of this gradient, as occurs in Fmr1(-/-) animals, degrades processing of this information. PMID:20685971

Strumbos, John G; Brown, Maile R; Kronengold, Jack; Polley, Daniel B; Kaczmarek, Leonard K

2010-08-01

113

CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila.  

PubMed

Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental language disorders, autism spectrum disorders, epilepsy, and schizophrenia. We now identified homozygous and compound-heterozygous deletions and mutations via molecular karyotyping and mutational screening in CNTNAP2 and NRXN1 in four patients with severe mental retardation (MR) and variable features, such as autistic behavior, epilepsy, and breathing anomalies, phenotypically overlapping with Pitt-Hopkins syndrome. With a frequency of at least 1% in our cohort of 179 patients, recessive defects in CNTNAP2 appear to significantly contribute to severe MR. Whereas the established synaptic role of NRXN1 suggests that synaptic defects contribute to the associated neuropsychiatric disorders and to severe MR as reported here, evidence for a synaptic role of the CNTNAP2-encoded protein CASPR2 has so far been lacking. Using Drosophila as a model, we now show that, as known for fly Nrx-I, the CASPR2 ortholog Nrx-IV might also localize to synapses. Overexpression of either protein can reorganize synaptic morphology and induce increased density of active zones, the synaptic domains of neurotransmitter release. Moreover, both Nrx-I and Nrx-IV determine the level of the presynaptic active-zone protein bruchpilot, indicating a possible common molecular mechanism in Nrx-I and Nrx-IV mutant conditions. We therefore propose that an analogous shared synaptic mechanism contributes to the similar clinical phenotypes resulting from defects in human NRXN1 and CNTNAP2. PMID:19896112

Zweier, Christiane; de Jong, Eiko K; Zweier, Markus; Orrico, Alfredo; Ousager, Lilian B; Collins, Amanda L; Bijlsma, Emilia K; Oortveld, Merel A W; Ekici, Arif B; Reis, André; Schenck, Annette; Rauch, Anita

2009-11-05

114

CNTNAP2 and NRXN1 Are Mutated in Autosomal-Recessive Pitt-Hopkins-like Mental Retardation and Determine the Level of a Common Synaptic Protein in Drosophila  

PubMed Central

Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental language disorders, autism spectrum disorders, epilepsy, and schizophrenia. We now identified homozygous and compound-heterozygous deletions and mutations via molecular karyotyping and mutational screening in CNTNAP2 and NRXN1 in four patients with severe mental retardation (MR) and variable features, such as autistic behavior, epilepsy, and breathing anomalies, phenotypically overlapping with Pitt-Hopkins syndrome. With a frequency of at least 1% in our cohort of 179 patients, recessive defects in CNTNAP2 appear to significantly contribute to severe MR. Whereas the established synaptic role of NRXN1 suggests that synaptic defects contribute to the associated neuropsychiatric disorders and to severe MR as reported here, evidence for a synaptic role of the CNTNAP2-encoded protein CASPR2 has so far been lacking. Using Drosophila as a model, we now show that, as known for fly Nrx-I, the CASPR2 ortholog Nrx-IV might also localize to synapses. Overexpression of either protein can reorganize synaptic morphology and induce increased density of active zones, the synaptic domains of neurotransmitter release. Moreover, both Nrx-I and Nrx-IV determine the level of the presynaptic active-zone protein bruchpilot, indicating a possible common molecular mechanism in Nrx-I and Nrx-IV mutant conditions. We therefore propose that an analogous shared synaptic mechanism contributes to the similar clinical phenotypes resulting from defects in human NRXN1 and CNTNAP2.

Zweier, Christiane; de Jong, Eiko K.; Zweier, Markus; Orrico, Alfredo; Ousager, Lilian B.; Collins, Amanda L.; Bijlsma, Emilia K.; Oortveld, Merel A.W.; Ekici, Arif B.; Reis, Andre; Schenck, Annette; Rauch, Anita

2009-01-01

115

Metabotropic glutamate receptor-mediated use-dependent down-regulation of synaptic excitability involves the fragile X mental retardation protein.  

PubMed

Loss of the mRNA-binding protein FMRP results in the most common inherited form of both mental retardation and autism spectrum disorders: fragile X syndrome (FXS). The leading FXS hypothesis proposes that metabotropic glutamate receptor (mGluR) signaling at the synapse controls FMRP function in the regulation of local protein translation to modulate synaptic transmission strength. In this study, we use the Drosophila FXS disease model to test the relationship between Drosophila FMRP (dFMRP) and the sole Drosophila mGluR (dmGluRA) in regulation of synaptic function, using two-electrode voltage-clamp recording at the glutamatergic neuromuscular junction (NMJ). Null dmGluRA mutants show minimal changes in basal synapse properties but pronounced defects during sustained high-frequency stimulation (HFS). The double null dfmr1;dmGluRA mutant shows repression of enhanced augmentation and delayed onset of premature long-term facilitation (LTF) and strongly reduces grossly elevated post-tetanic potentiation (PTP) phenotypes present in dmGluRA-null animals. Null dfmr1 mutants show features of synaptic hyperexcitability, including multiple transmission events in response to a single stimulus and cyclic modulation of transmission amplitude during prolonged HFS. The double null dfmr1;dmGluRA mutant shows amelioration of these defects but does not fully restore wildtype properties in dfmr1-null animals. These data suggest that dmGluRA functions in a negative feedback loop in which excess glutamate released during high-frequency transmission binds the glutamate receptor to dampen synaptic excitability, and dFMRP functions to suppress the translation of proteins regulating this synaptic excitability. Removal of the translational regulator partially compensates for loss of the receptor and, similarly, loss of the receptor weakly compensates for loss of the translational regulator. PMID:19036865

Repicky, Sarah; Broadie, Kendal

2008-11-26

116

Comprehensive computational analysis of Hmd enzymes and paralogs in methanogenic Archaea  

Microsoft Academic Search

BACKGROUND: Methanogenesis is the sole means of energy production in methanogenic Archaea. H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd) catalyzes a step in the hydrogenotrophic methanogenesis pathway in class I methanogens. At least one hmd paralog has been identified in nine of the eleven complete genome sequences of class I hydrogenotrophic methanogens. The products of these paralog genes have thus far eluded any

Aaron D Goldman; John A Leigh; Ram Samudrala

2009-01-01

117

Gain of Function Mutations for Paralogous Hox Genes: Implications for the Evolution of Hox Gene Function  

Microsoft Academic Search

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

Robert A. Pollock; Taduru Sreenath; Lien Ngo; Charles J. Bieberich

1995-01-01

118

Cc2d1a, a C2 domain containing protein linked to nonsyndromic mental retardation, controls functional maturation of central synapses  

PubMed Central

Cc2d1a is an evolutionarily conserved protein composed of NH2-terminal Drosophila melanogaster 14 domain (DM14) domains and a COOH-terminal C2 domain. Human patients with homozygotic mutation in the gene suffer from nonsyndromic mental retardation, implying that Cc2d1a functions in the central nervous system. To examine the physiological role of the Cc2d1a, we generated and analyzed Cc2d1a knockout (KO) mice. Cc2d1a KO mice die soon after birth, apparently because of their inability to breathe. Histological analysis of Cc2d1a KO animals did not identify any structural defects in the peripheral respiratory apparatus. However, functional analysis of synapses formed between Cc2d1a-deficient cortical neurons revealed a robust increase in the pace of maturation of evoked synaptic responses as well as synaptic vesicle trafficking. This synaptic anomaly was rescued by reintroducing full-length Cc2d1a but not C2-domain-deletion mutant, underscoring the functional importance of C2 domain. Our data suggest that Cc2d1a is required for mouse survival and performs essential function in controlling functional maturation of synapses.

Zhao, Meng; Raingo, Jesica

2011-01-01

119

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...

120

Training the Difficult Retardate.  

ERIC Educational Resources Information Center

|Described is a 1972 workshop designed to train Pennsylvania personnel in assessing and programing for low functioning or difficult retardates. State legislation dealing with education of the retarded is reviewed. Considered are assessment techniques in the following areas: motor, communication, cognitive, and social-emotional development and…

Stephens, Beth, Ed.; And Others

121

THE MENTALLY RETARDED CHILD.  

ERIC Educational Resources Information Center

THIS IS A REVISION BY THE LEVINSON FOUNDATION STAFF OF A BOOK WRITTEN BY DR. ABRAHAM LEVINSON IN 1952. WRITTEN FOR PARENTS OF MENTALLY RETARDED CHILDREN, THE BOOK REVIEWS TYPICAL PARENTAL REACTIONS TO THE BIRTH OF A RETARDED CHILD AND OFFERS ADVICE ON HOME CARE, SIBLING ACCEPTANCE, AND DISCIPLINE. ITS CONTENTS INCLUDE SUCH MATTERS AS HISTORICAL…

LEVINSON, ABRAHAM

122

Neuroimaging in mental retardation  

Microsoft Academic Search

Objective : To determine the diagnostic yield of neuroimaging ina cohort of children with mental retardation of unknown origin.Methods: Neuroimaging was performed in a total of 47 patients with developmental delay\\/mental retardation, where no etiologic diagnosis\\u000a could be made following clinical examination and preliminary investigations.Results : Thirty (63.82%) children had abnormal neuroimaging findings of which 19 (42.42%) were specific abnormalities

Amita Pandey; Shubha R. Phadke; Neerja Gupta; R. V. Phadke

2004-01-01

123

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

PubMed Central

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-adapted organisms because they may play a pleiotropic role in other important processes that are unrelated to vision.

2013-01-01

124

Splign: algorithms for computing spliced alignments with identification of paralogs  

PubMed Central

Background The computation of accurate alignments of cDNA sequences against a genome is at the foundation of modern genome annotation pipelines. Several factors such as presence of paralogs, small exons, non-consensus splice signals, sequencing errors and polymorphic sites pose recognized difficulties to existing spliced alignment algorithms. Results We describe a set of algorithms behind a tool called Splign for computing cDNA-to-Genome alignments. The algorithms include a high-performance preliminary alignment, a compartment identification based on a formally defined model of adjacent duplicated regions, and a refined sequence alignment. In a series of tests, Splign has produced more accurate results than other tools commonly used to compute spliced alignments, in a reasonable amount of time. Conclusion Splign's ability to deal with various issues complicating the spliced alignment problem makes it a helpful tool in eukaryotic genome annotation processes and alternative splicing studies. Its performance is enough to align the largest currently available pools of cDNA data such as the human EST set on a moderate-sized computing cluster in a matter of hours. The duplications identification (compartmentization) algorithm can be used independently in other areas such as the study of pseudogenes. Reviewers This article was reviewed by: Steven Salzberg, Arcady Mushegian and Andrey Mironov (nominated by Mikhail Gelfand).

Kapustin, Yuri; Souvorov, Alexander; Tatusova, Tatiana; Lipman, David

2008-01-01

125

Paralogous Genes Involved in Juvenile Hormone Action in Drosophila melanogaster  

PubMed Central

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.

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

2010-01-01

126

Elongation factor-1?, a putative single-copy nuclear gene, has divergent sets of paralogs in an arachnid.  

PubMed

Identification of paralogy in candidate nuclear loci is an important prerequisite in phylogenetics and statistical phylogeography, but one that is often overlooked. One marker commonly assumed to be a single-copy gene and claimed to harbor great utility for inferring recent divergences is elongation factor-1? (EF-1?). To test this hypothesis, we systematically cloned EF-1? in three disjunct populations of the harvestman Metasiro americanus. Here we show that EF-1? has a large number of paralogs in this species. The paralogs do not evolve in a concerted manner, and the paralogs diverged prior to the population divergence. Moreover, the paralogs of M. americanus are not comparable to the highly divergent EF-1? paralogs found in bees and spiders, which are easily recognized and separated through the use of specific primers. We demonstrate statistically that our detection of paralogs cannot be attributed to amplification error. The presence of EF-1? paralogs in M. americanus prevents its use in statistical phylogeography, and the presence of out-paralogs argues against its use in phylogenetic inference among recently diverged clades. These data contradict the common assumption that EF-1? is for most or all taxa a single-copy gene, or that it has a small number of paralogs that are homogenized through gene conversion, unequal crossing over, or other processes. PMID:23669012

Clouse, Ronald M; Sharma, Prashant P; Giribet, Gonzalo; Wheeler, Ward C

2013-05-10

127

Monogenic causes of X-linked mental retardation  

Microsoft Academic Search

Mutations in X-linked genes are likely to account for the observation that more males than females are affected by mental retardation. Causative mutations have recently been identified in both syndromic X-linked mental retardation (XLMR) and in the genetically heterogeneous 'nonspecific' forms of XLMR, for which cognitive impairment is the only defining clinical feature. Proteins that function in chromatin remodelling are

Jamel Chelly; Jean-Louis Mandel

2001-01-01

128

The zebrafish genome encodes the largest vertebrate repertoire of functional aquaporins with dual paralogy and substrate specificities similar to mammals  

PubMed Central

Background Aquaporins are integral membrane proteins that facilitate the transport of water and small solutes across cell membranes. These proteins are vital for maintaining water homeostasis in living organisms. In mammals, thirteen aquaporins (AQP0-12) have been characterized, but in lower vertebrates, such as fish, the diversity, structure and substrate specificity of these membrane channel proteins are largely unknown. Results The screening and isolation of transcripts from the zebrafish (Danio rerio) genome revealed eighteen sequences structurally related to the four subfamilies of tetrapod aquaporins, i.e., aquaporins (AQP0, -1 and -4), water and glycerol transporters or aquaglyceroporins (Glps; AQP3 and AQP7-10), a water and urea transporter (AQP8), and two unorthodox aquaporins (AQP11 and -12). Phylogenetic analyses of nucleotide and deduced amino acid sequences demonstrated dual paralogy between teleost and human aquaporins. Three of the duplicated zebrafish isoforms have unlinked loci, two have linked loci, while DrAqp8 was found in triplicate across two chromosomes. Genomic sequencing, structural analysis, and maximum likelihood reconstruction, further revealed the presence of a putative pseudogene that displays hybrid exons similar to tetrapod AQP5 and -1. Ectopic expression of the cloned transcripts in Xenopus laevis oocytes demonstrated that zebrafish aquaporins and Glps transport water or water, glycerol and urea, respectively, whereas DrAqp11b and -12 were not functional in oocytes. Contrary to humans and some rodents, intrachromosomal duplicates of zebrafish AQP8 were water and urea permeable, while the genomic duplicate only transported water. All aquaporin transcripts were expressed in adult tissues and found to have divergent expression patterns. In some tissues, however, redundant expression of transcripts encoding two duplicated paralogs seems to occur. Conclusion The zebrafish genome encodes the largest repertoire of functional vertebrate aquaporins with dual paralogy to human isoforms. Our data reveal an early and specific diversification of these integral membrane proteins at the root of the crown-clade of Teleostei. Despite the increase in gene copy number, zebrafish aquaporins mostly retain the substrate specificity characteristic of the tetrapod counterparts. Based upon the integration of phylogenetic, genomic and functional data we propose a new classification for the piscine aquaporin superfamily.

2010-01-01

129

Close association between paralogous multiple isomiRs and paralogous/orthologues miRNA sequences implicates dominant sequence selection across various animal species.  

PubMed

MicroRNAs (miRNAs) are crucial negative regulators of gene expression at the post-transcriptional level. Next-generation sequencing technologies have identified a series of miRNA variants (named isomiRs). In this study, paralogous isomiR assemblies (from the miRNA locus) were systematically analyzed based on data acquired from deep sequencing data sets. Evolutionary analysis of paralogous (members in miRNA gene family in a specific species) and orthologues (across different animal species) miRNAs was also performed. The sequence diversity of paralogous isomiRs was found to be similar to the diversity of paralogous and orthologues miRNAs. Additionally, both isomiRs and paralogous/orthologues miRNAs were implicated in 5' and 3' ends (especially 3' ends), nucleotide substitutions, and insertions and deletions. Generally, multiple isomiRs can be produced from a single miRNA locus, but most of them had lower enrichment levels, and only several dominant isomiR sequences were detected. These dominant isomiR groups were always stable, and one of them would be selected as the most abundant miRNA sequence in specific animal species. Some isomiRs might be consistent to miRNA sequences in some species but not the other. Homologous miRNAs were often detected in similar isomiR repertoires, and showed similar expression patterns, while dominant isomiRs showed complex evolutionary patterns from miRNA sequences across the animal kingdom. These results indicate that the phenomenon of multiple isomiRs is not a random event, but rather the result of evolutionary pressures. The existence of multiple isomiRs enables different species to express advantageous sequences in different environments. Thus, dominant sequences emerge in response to functional and evolutionary pressures, allowing an organism to adapt to complex intra- and extra-cellular events. PMID:23856130

Guo, Li; Zhao, Yang; Zhang, Hui; Yang, Sheng; Chen, Feng

2013-07-13

130

The impact of paralogy on phylogenomic studies - a case study on annelid relationships.  

PubMed

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 prediction methods like HaMStR it is likewise decreased by using more than one reference taxon. PMID:23667537

Struck, Torsten H

2013-05-07

131

The Impact of Paralogy on Phylogenomic Studies - A Case Study on Annelid Relationships  

PubMed Central

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 prediction methods like HaMStR it is likewise decreased by using more than one reference taxon.

Struck, Torsten H.

2013-01-01

132

BIBLIOGRAPHY ON MENTAL RETARDATION.  

ERIC Educational Resources Information Center

|REFERENCES FROM 1940 TO 1964 ARE ORGANIZED IN FOUR CATEGORIES. THE SECTION ON PROFESSIONAL LITERATURE IS CONCERNED WITH THE ETIOLOGY AND THE PSYCHOLOGICAL, SOCIOLOGICAL, AND MEDICAL ASPECTS OF MENTAL RETARDATION. THE PROFESSIONAL CURRICULUM SECTION IS DEVOTED TO CURRICULUM DEVELOPMENT AND PROGRAM CONTENT FOR TEACHERS. THE GENERAL LITERATURE…

BLESSING, KENNETH R.; PFAEFFLE, HEINZ

133

Flame retardant polymeric materials  

SciTech Connect

The flame retardation of polyolefins is the focus of this volume. Methods for reduction of smoke and experimental evaluation of flammability parameters for polymeric materials are discussed. The flammability evaluation methods for textiles and the use of mass spectrometry for analysis of polymers and their degradation products are also presented.

Lewin, M.; Atlas, S.M.; Pearce, E.M.

1982-01-01

134

Flame Retardation of Polymers.  

National Technical Information Service (NTIS)

The central purpose of this study is to understand the chemical events that may be occurring in the decomposition of a polymer and how a potential flame retardant would in general suppress, alter or modify certain chemical reactions. jg p11.

J. K. Kiang

1979-01-01

135

Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52.  

PubMed

Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response. PMID:15914205

van Veelen, Lieneke R; Essers, Jeroen; van de Rakt, Mandy W M M; Odijk, Hanny; Pastink, Albert; Zdzienicka, Ma?gorzata Z; Paulusma, Coen C; Kanaar, Roland

2005-04-09

136

Evidence of gene conversion events between paralogous sequences produced by tetraploidization in Salmoninae fish.  

PubMed

We investigated the occurrence of gene conversions between paralogous sequences of Salmoninae derived from ancestral tetraploidization and their effect on the evolutionary history of DNA sequences. A microsatellite with long flanking regions (750 bp) including both coding and noncoding sequences was analyzed. Microsatellite size polymorphism was used to detect the alleles of both paralogous counterparts and infer linkage arrangement between loci. DNA sequencing of seven Salmoninae species revealed that paralogous sequences were highly differentiated within species, especially for noncoding regions. Ten gene conversion events between paralogous sequences were inferred. While these events appears to have homogenized regions of otherwise highly differential paralogous sequences, they amplified the differentiation among orthologous sequences. Their effects were larger on coding than on noncoding regions. As a consequence, noncoding sequences grouped by orthologous lineages in phylogenetic trees, whereas coding regions grouped by taxa. Based upon these results, we present a model showing how gene conversion events may also result in the PCR amplification of nonorthologous sequences in different taxa, with obvious complications for phylogenetic inferences, comparative mapping, and population genetic studies. PMID:11956688

Angers, Bernard; Gharbi, Karim; Estoup, Arnaud

2002-04-01

137

Phyletic profiling with cliques of orthologs is enhanced by signatures of paralogy relationships.  

PubMed

New microbial genomes are sequenced at a high pace, allowing insight into the genetics of not only cultured microbes, but a wide range of metagenomic collections such as the human microbiome. To understand the deluge of genomic data we face, computational approaches for gene functional annotation are invaluable. We introduce a novel model for computational annotation that refines two established concepts: annotation based on homology and annotation based on phyletic profiling. The phyletic profiling-based model that includes both inferred orthologs and paralogs-homologs separated by a speciation and a duplication event, respectively-provides more annotations at the same average Precision than the model that includes only inferred orthologs. For experimental validation, we selected 38 poorly annotated Escherichia coli genes for which the model assigned one of three GO terms with high confidence: involvement in DNA repair, protein translation, or cell wall synthesis. Results of antibiotic stress survival assays on E. coli knockout mutants showed high agreement with our model's estimates of accuracy: out of 38 predictions obtained at the reported Precision of 60%, we confirmed 25 predictions, indicating that our confidence estimates can be used to make informed decisions on experimental validation. Our work will contribute to making experimental validation of computational predictions more approachable, both in cost and time. Our predictions for 998 prokaryotic genomes include ~400000 specific annotations with the estimated Precision of 90%, ~19000 of which are highly specific-e.g. "penicillin binding," "tRNA aminoacylation for protein translation," or "pathogenesis"-and are freely available at http://gorbi.irb.hr/. PMID:23308060

Skunca, Nives; Bošnjak, Matko; Kriško, Anita; Panov, Pan?e; Džeroski, Sašo; Smuc, Tomislav; Supek, Fran

2013-01-03

138

Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting.  

PubMed

Evidence suggests that insulin-like growth factors-I and -II (IGF-I and II) play a role in regulating fetal growth and development. In the fetus, IGF-I and -II are complexed with two specific binding proteins (IGFBP-1 and -2), which are thought to modulate the actions of the IGFs in target tissues. We examined regulation of the genes for IGF-I, IGF-II, IGFBP-1, and IGFBP-2 in fetal rat liver in an experimental model for intrauterine growth retardation caused by maternal fasting on days 17-21 of gestation. The mean weight of fetuses from the fasted dams was 27-32% lower than the mean weight of fetuses from the fed dams. The concentration of immunoreactive IGF-I was decreased by 71% in serum of fetuses from the fasting dams. The concentration of immunoreactive IGF-II was slightly decreased (by 12%) in serum of fetuses from the fasting dams, whereas the concentration of immunoreactive pro-IGF-II E-domain peptide was decreased by 31%. The abundance of hepatic IGF-I mRNA was decreased by 55% in fetuses from the fasting dams. In contrast, the abundance of IGF-II mRNA in fetal liver was not significantly decreased by maternal fasting. Maternal fasting caused a 2-fold increase in the abundance of IGFBP-1 mRNA in fetal liver, whereas it did not change the abundance of IGFBP-2 mRNA. The induction of IGFBP-1 mRNA in liver of the growth-retarded fetuses is similar to the induction that occurs in liver of fasting adults, while the lack of regulation of IGFBP-2 mRNA differs from the strong induction of IGFBP-2 mRNA that occurs in liver of fasting adults. In summary, these results indicate that maternal fasting causes a decrease in fetal IGF-I gene expression, a decrease in fetal serum IGF-I, and a slight decrease in fetal serum IGF-II and pro-IGF-II E-domain peptide concentrations. Maternal fasting also causes an increase in fetal IGFBP-1 gene expression. Changes in fetal insulin and glucose may be related to changes in expression of the IGF-I and IGFBP-1 genes in the growth-retarded fetuses. The decreased expression of IGF-I and -II and increased expression of the IGFBP-1 gene may contribute to the fetal growth retardation observed in this model system. PMID:1846108

Straus, D S; Ooi, G T; Orlowski, C C; Rechler, M M

1991-01-01

139

OrthoParaMap: Distinguishing orthologs from paralogs by integrating comparative genome data and gene phylogenies  

PubMed Central

Background In eukaryotic genomes, most genes are members of gene families. When comparing genes from two species, therefore, most genes in one species will be homologous to multiple genes in the second. This often makes it difficult to distinguish orthologs (separated through speciation) from paralogs (separated by other types of gene duplication). Combining phylogenetic relationships and genomic position in both genomes helps to distinguish between these scenarios. This kind of comparison can also help to describe how gene families have evolved within a single genome that has undergone polyploidy or other large-scale duplications, as in the case of Arabidopsis thaliana – and probably most plant genomes. Results We describe a suite of programs called OrthoParaMap (OPM) that makes genomic comparisons, identifies syntenic regions, determines whether sets of genes in a gene family are related through speciation or internal chromosomal duplications, maps this information onto phylogenetic trees, and infers internal nodes within the phylogenetic tree that may represent local – as opposed to speciation or segmental – duplication. We describe the application of the software using three examples: the melanoma-associated antigen (MAGE) gene family on the X chromosomes of mouse and human; the 20S proteasome subunit gene family in Arabidopsis, and the major latex protein gene family in Arabidopsis. Conclusion OPM combines comparative genomic positional information and phylogenetic reconstructions to identify which gene duplications are likely to have arisen through internal genomic duplications (such as polyploidy), through speciation, or through local duplications (such as unequal crossing-over). The software is freely available at .

Cannon, Steven B; Young, Nevin D

2003-01-01

140

AbdB-Like Hox Proteins Stabilize DNA Binding by the Meis1 Homeodomain Proteins  

Microsoft Academic Search

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx

WEI-FANG SHEN; JEFFRY C. MONTGOMERY; SOFIA ROZENFELD; JOHN J. MOSKOW; H. JEFFREY LAWRENCE; ARTHUR M. BUCHBERG; COREY LARGMAN

1997-01-01

141

Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism  

PubMed Central

Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABAA receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism vs. age and postmortem interval (PMI) matched controls. There was also a significant decrease in level of GABAA receptor beta 3 (GABR?3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein (GFAP) in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially leads to altered expression of GABAA receptors.

Fatemi, S. Hossein; Folsom, Timothy D.; Kneeland, Rachel E.; Liesch, Stephanie B.

2011-01-01

142

Differential Contributions of Mammalian Rad54 Paralogs to Recombination, DNA Damage Repair, and Meiosis†  

PubMed Central

Homologous recombination is a versatile DNA damage repair pathway requiring Rad51 and Rad54. Here we show that a mammalian Rad54 paralog, Rad54B, displays physical and functional interactions with Rad51 and DNA that are similar to those of Rad54. While ablation of Rad54 in mouse embryonic stem (ES) cells leads to a mild reduction in homologous recombination efficiency, the absence of Rad54B has little effect. However, the absence of both Rad54 and Rad54B dramatically reduces homologous recombination efficiency. Furthermore, we show that Rad54B protects ES cells from ionizing radiation and the interstrand DNA cross-linking agent mitomycin C. Interestingly, at the ES cell level the paralogs do not display an additive or synergic interaction with respect to mitomycin C sensitivity, yet animals lacking both Rad54 and Rad54B are dramatically sensitized to mitomycin C compared to either single mutant. This suggests that the paralogs possibly function in a tissue-specific manner. Finally, we show that Rad54, but not Rad54B, is needed for a normal distribution of Rad51 on meiotic chromosomes. Thus, even though the paralogs have similar biochemical properties, genetic analysis in mice uncovered their nonoverlapping roles.

Wesoly, Joanna; Agarwal, Sheba; Sigurdsson, Stefan; Bussen, Wendy; Van Komen, Stephen; Qin, Jian; van Steeg, Harry; van Benthem, Jan; Wassenaar, Evelyne; Baarends, Willy M.; Ghazvini, Mehrnaz; Tafel, Agnieszka A.; Heath, Helen; Galjart, Niels; Essers, Jeroen; Grootegoed, J. Anton; Arnheim, Norman; Bezzubova, Olga; Buerstedde, Jean-Marie; Sung, Patrick; Kanaar, Roland

2006-01-01

143

Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis.  

PubMed

Homologous recombination is a versatile DNA damage repair pathway requiring Rad51 and Rad54. Here we show that a mammalian Rad54 paralog, Rad54B, displays physical and functional interactions with Rad51 and DNA that are similar to those of Rad54. While ablation of Rad54 in mouse embryonic stem (ES) cells leads to a mild reduction in homologous recombination efficiency, the absence of Rad54B has little effect. However, the absence of both Rad54 and Rad54B dramatically reduces homologous recombination efficiency. Furthermore, we show that Rad54B protects ES cells from ionizing radiation and the interstrand DNA cross-linking agent mitomycin C. Interestingly, at the ES cell level the paralogs do not display an additive or synergic interaction with respect to mitomycin C sensitivity, yet animals lacking both Rad54 and Rad54B are dramatically sensitized to mitomycin C compared to either single mutant. This suggests that the paralogs possibly function in a tissue-specific manner. Finally, we show that Rad54, but not Rad54B, is needed for a normal distribution of Rad51 on meiotic chromosomes. Thus, even though the paralogs have similar biochemical properties, genetic analysis in mice uncovered their nonoverlapping roles. PMID:16428451

Wesoly, Joanna; Agarwal, Sheba; Sigurdsson, Stefan; Bussen, Wendy; Van Komen, Stephen; Qin, Jian; van Steeg, Harry; van Benthem, Jan; Wassenaar, Evelyne; Baarends, Willy M; Ghazvini, Mehrnaz; Tafel, Agnieszka A; Heath, Helen; Galjart, Niels; Essers, Jeroen; Grootegoed, J Anton; Arnheim, Norman; Bezzubova, Olga; Buerstedde, Jean-Marie; Sung, Patrick; Kanaar, Roland

2006-02-01

144

Contrasting patterns of sequence evolution at the functionally redundant bric à brac paralogs in Drosophila melanogaster.  

PubMed

Genes with overlapping expression and function may gradually diverge despite retaining some common functions. To test whether such genes show distinct patterns of molecular evolution within species, we examined sequence variation at the bric à brac (bab) locus of Drosophila melanogaster. This locus is composed of two anciently duplicated paralogs, bab1 and bab2, which are involved in patterning the adult abdomen, legs, and ovaries. We have sequenced the 148 kb genomic region spanning the bab1 and bab2 genes from 94 inbred lines of D. melanogaster sampled from a single location. Two non-coding regions, one in each paralog, appear to be under selection. The strongest evidence of directional selection is found in a region of bab2 that has no known functional role. The other region is located in the bab1 paralog and is known to contain a cis-regulatory element that controls sex-specific abdominal pigmentation. The coding region of bab1 appears to be under stronger functional constraint than the bab2 coding sequences. Thus, the two paralogs are evolving under different selective regimes in the same natural population, illuminating the different evolutionary trajectories of partially redundant duplicate genes. PMID:19639236

Bickel, Ryan D; Schackwitz, Wendy S; Pennacchio, Len A; Nuzhdin, Sergey V; Kopp, Artyom

2009-07-29

145

Paralogous ALT1 and ALT2 Retention and Diversification Have Generated Catalytically Active and Inactive Aminotransferases in Saccharomyces cerevisiae  

PubMed Central

Background Gene duplication and the subsequent divergence of paralogous pairs play a central role in the evolution of novel gene functions. S. cerevisiae possesses two paralogous genes (ALT1/ALT2) which presumably encode alanine aminotransferases. It has been previously shown that Alt1 encodes an alanine aminotransferase, involved in alanine metabolism; however the physiological role of Alt2 is not known. Here we investigate whether ALT2 encodes an active alanine aminotransferase. Principal Findings Our results show that although ALT1 and ALT2 encode 65% identical proteins, only Alt1 displays alanine aminotransferase activity; in contrast ALT2 encodes a catalytically inert protein. ALT1 and ALT2 expression is modulated by Nrg1 and by the intracellular alanine pool. ALT1 is alanine-induced showing a regulatory profile of a gene encoding an enzyme involved in amino acid catabolism, in agreement with the fact that Alt1 is the sole pathway for alanine catabolism present in S. cerevisiae. Conversely, ALT2 expression is alanine-repressed, indicating a role in alanine biosynthesis, although the encoded-protein has no alanine aminotransferase enzymatic activity. In the ancestral-like yeast L. kluyveri, the alanine aminotransferase activity was higher in the presence of alanine than in the presence of ammonium, suggesting that as for ALT1, LkALT1 expression could be alanine-induced. ALT2 retention poses the questions of whether the encoded protein plays a particular function, and if this function was present in the ancestral gene. It could be hypotesized that ALT2 diverged after duplication, through neo-functionalization or that ALT2 function was present in the ancestral gene, with a yet undiscovered function. Conclusions ALT1 and ALT2 divergence has resulted in delegation of alanine aminotransferase activity to Alt1. These genes display opposed regulatory profiles: ALT1 is alanine-induced, while ALT2 is alanine repressed. Both genes are negatively regulated by the Nrg1 repressor. Presented results indicate that alanine could act as ALT2 Nrg1-co-repressor.

Penalosa-Ruiz, Georgina; Aranda, Cristina; Ongay-Larios, Laura; Colon, Maritrini; Quezada, Hector; Gonzalez, Alicia

2012-01-01

146

Flame retarded asphalt blend composition  

SciTech Connect

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.

Walters, R.B.

1987-04-21

147

Schizophrenia in the Mentally Retarded.  

ERIC Educational Resources Information Center

The relationship between schizophrenia and mental retardation is examined. Historical associations between symptoms of the two disorders are reviewed, and a 3-year study of the incidence (14%) of mental illness in 798 retarded individuals in a community based program is described. Information on the etiological, developmental, and phenomenological…

Menolascino, Frank J.

148

THE PATHOLOGY OF MENTAL RETARDATION.  

ERIC Educational Resources Information Center

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…

CROME, L.; STERN, J.

149

Schizophrenia in the Mentally Retarded.  

ERIC Educational Resources Information Center

|The relationship between schizophrenia and mental retardation is examined. Historical associations between symptoms of the two disorders are reviewed, and a 3-year study of the incidence (14%) of mental illness in 798 retarded individuals in a community based program is described. Information on the etiological, developmental, and…

Menolascino, Frank J.

150

International Definitions of Mental Retardation.  

ERIC Educational Resources Information Center

This study investigates definitions and usage of the term "mental retardation" worldwide, via a review of the literature and a survey of 20 countries. Nineteen of the 20 responding countries reported using some sort of intelligence quotient (IQ) criterion to determine mental retardation, though the criterion varies. In some countries, there are…

Soloff, Leah A.; Wright, Eleanor B.

151

China's Approach to Mental Retardation.  

ERIC Educational Resources Information Center

History, tradition, culture, and superstition have played significant roles in influencing Chinese attitudes toward the mentally retarded. China's overwhelmingly rural, agricultural society has made it dependent upon a huge force of semi-skilled and unskilled labor, to which the retarded are capable of contribution. The stress on self-reliance,…

Hittman, Stephan

152

X-linked mental retardation  

Microsoft Academic Search

Genetic factors have an important role in the aetiology of mental retardation. However, their contribution is often underestimated because in developed countries, severely affected patients are mainly sporadic cases and familial cases are rare. X-chromosomal mental retardation is the exception to this rule, and this is one of the reasons why research into the genetic and molecular causes of mental

H.-Hilger Ropers; Pietro Chiurazzi

1980-01-01

153

Roquin paralogs add a new dimension to ICOS regulation.  

PubMed

Two studies in the current issue of Immunity (Pratama et al., 2013; Vogel et al., 2013) demonstrate that the RNA-binding proteins Roquin-1 and Roquin-2 have redundant function in the posttranscriptional repression of Icos messenger RNA by CD4(+) T cells. PMID:23601678

Bertino, Sarah A; Craft, Joe

2013-04-18

154

Cell polarity: ParA-logs gather around the Hub.  

PubMed

The chromosomal origin, chemotaxis arrays and flagellum of Vibrio cholerae congregate at the same pole of the cell. How? A recent study identifies a new pole-organizing protein, HubP, that recruits members of the ParA family of spatial regulators of subcellular structures to the pole. PMID:23257194

Kirkpatrick, Clare L; Viollier, Patrick H

2012-12-18

155

Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation.  

PubMed

Accumulation of T follicular helper (Tfh) cells and proinflammatory cytokines drive autoantibody-mediated diseases. The RNA-binding protein Roquin-1 (Rc3h1) represses the inducible costimulator ICOS and interferon-? (IFN-?) in T cells to prevent Tfh cell accumulation. Unlike Rc3h1(san) mice with a mutation in the ROQ domain of Roquin-1, mice lacking the protein, paradoxically do not display increased Tfh cells. Here we have analyzed mice with mutations that eliminate the RING domain from Roquin-1 or its paralog, Roquin-2 (Rc3h2). RING or ROQ mutations both disrupted Icos mRNA regulation by Roquin-1, but, unlike the ROQ mutant that still occupied mRNA-regulating stress granules, RING-deficient Roquin-1 failed to localize to stress granules and allowed Roquin-2 to compensate in the repression of ICOS and Tfh cells. These paralogs also targeted tumor necrosis factor (TNF) in nonlymphoid cells, ameliorating autoantibody-induced arthritis. The Roquin family emerges as a posttranscriptional brake in the adaptive and innate phases of antibody responses. PMID:23583642

Pratama, Alvin; Ramiscal, Roybel R; Silva, Diego G; Das, Souvik K; Athanasopoulos, Vicki; Fitch, Jessica; Botelho, Natalia K; Chang, Pheh-Ping; Hu, Xin; Hogan, Jennifer J; Maña, Paula; Bernal, David; Korner, Heinrich; Yu, Di; Goodnow, Christopher C; Cook, Matthew C; Vinuesa, Carola G

2013-04-11

156

Functional specificity among ribosomal proteins regulates gene expression.  

PubMed

Duplicated genes escape gene loss by conferring a dosage benefit or evolving diverged functions. The yeast Saccharomyces cerevisiae contains many duplicated genes encoding ribosomal proteins. Prior studies have suggested that these duplicated proteins are functionally redundant and affect cellular processes in proportion to their expression. In contrast, through studies of ASH1 mRNA in yeast, we demonstrate paralog-specific requirements for the translation of localized mRNAs. Intriguingly, these paralog-specific effects are limited to a distinct subset of duplicated ribosomal proteins. Moreover, transcriptional and phenotypic profiling of cells lacking specific ribosomal proteins reveals differences between the functional roles of ribosomal protein paralogs that extend beyond effects on mRNA localization. Finally, we show that ribosomal protein paralogs exhibit differential requirements for assembly and localization. Together, our data indicate complex specialization of ribosomal proteins for specific cellular processes and support the existence of a ribosomal code. PMID:17981122

Komili, Suzanne; Farny, Natalie G; Roth, Frederick P; Silver, Pamela A

2007-11-01

157

Ancient Origin of Chaperonin Gene Paralogs Involved in Ciliopathies  

PubMed Central

The Bardet-Biedl Syndrome (BBS) is a human developmental disorder that has been associated with fourteen BBS genes affecting the development of cilia. Three BBS genes are distant relatives of chaperonin proteins, a family of chaperones well known for the protein-folding role of their double-ringed complexes. Chaperonin-like BBS genes were originally thought to be vertebrate-specific, but related genes from different metazoan species have been identified as chaperonin-like BBS genes based on sequence similarity. Our phylogenetic analyses confirmed the classification of these genes in the chaperonin-like BBS gene family, and set the origin of the gene family earlier than the time of separation of Bilateria, Cnidaria, and Placozoa. By extensive searches of chaperonin-like genes in complete genomes representing several eukaryotic lineages, we discovered the presence of chaperonin-like BBS genes also in the genomes of Phytophthora and Pythium, belonging to the group of Oomycetes. This finding suggests that the chaperonin-like BBS gene family had already evolved before the origin of Metazoa, as early in eukaryote evolution as before separation of the lineages of Unikonts and Chromalveolates. The analysis of coding sequences indicated that chaperonin-like BBS proteins have evolved in all lineages under constraining selection. Furthermore, analysis of the predicted structural features suggested that, despite their high rate of divergence, chaperonin-like BBS proteins mostly conserve a typical chaperonin-like three-dimensional structure, but question their ability to assemble and function as chaperonin-like double-ringed complexes.

Mukherjee, Krishanu; Brocchieri, Luciano

2013-01-01

158

Discrimination between Paralogs using Microarray Analysis: Application to the Yap1p and Yap2p Transcriptional Networks  

PubMed Central

Ohno [Ohno, S. (1970) in Evolution by Gene Duplication, Springer, New York] proposed that gene duplication with subsequent divergence of paralogs could be a major force in the evolution of new gene functions. In practice the functional differences between closely related homologues produced by duplications can be subtle and difficult to separate experimentally. Here we show that DNA microarrays can distinguish the functions of two closely related homologues from the yeast Saccharomyces cerevisiae, Yap1p and Yap2p. Although Yap1p and Yap2p are both bZIP transcription factors involved in multiple stress responses and are 88% identical in their DNA binding domains, our work shows that these proteins activate nonoverlapping sets of genes. Yap1p controls a set of genes involved in detoxifying the effects of reactive oxygen species, whereas Yap2p controls a set of genes over represented for the function of stabilizing proteins. In addition we show that the binding sites in the promoters of the Yap1p-dependent genes differ from the sites in the promoters of Yap2p-dependent genes and we validate experimentally that these differences are important for regulation by Yap1p. We conclude that while Yap1p and Yap2p may have some overlapping functions they are clearly not redundant and, more generally, that DNA microarray analysis will be an important tool for distinguishing the functions of the large numbers of highly conserved genes found in all eukaryotic genomes.

Cohen, Barak A.; Pilpel, Yitzhak; Mitra, Robi D.; Church, George M.

2002-01-01

159

Toxic effects of two brominated flame retardants BDE-47 and BDE-183 on the survival and protein expression of the tubificid Monopylephorus limosus.  

PubMed

The toxic effects of two brominated diphenyl ethers (BDE), BDE-47, and BDE-183, on a benthic oligochaete tubificid, Monopylephorus limosus were studied under laboratory conditions. Investigated responses included survival, growth, and protein expression profiles, at BDE concentrations of 1, 10, 100, and 700 ng/g on a dry soil weight basis, with isooctane as the carrier solvent. Body weight losses among treatments were insignificant after 8 weeks of exposure. The 8-wk LC(50) of BDE-47 and -183 were 2311 and 169 ng/g, respectively. By applying multivariate analysis techniques, protein expression patterns were compared and correlated with stressful sources of long-term culture, carrier solvent, BDE-47 and -183. The treatment of 8-wk 100 ng/g BDE-47 was most closely clustered to the 10 ng/g BDE-183 treatment, based on the 40 examined protein spots. This indicated that BDE-183 was more potent to M. limosus, than was BDE-47. The 2-wk and 8-wk controls clustered into different groups indicating the occurrence of physiological changes due to long-term laboratory culture. Additionally, solvent effect was shown by grouping the isooctane carrier to different clusters. With further characterization by principle component analysis, it was found that the separation was mainly contributed by the 2nd principal-component. And, the primarily inhibitory variation was at spots 2 (UMP-CMP kinase) and 40 (plasma retinol-binding protein precursor) in the 8-wk groups. On the contrary, protein spots 16 (cell division control protein 2 homolog) and 24 (mitochondrial DNA mismatch repair protein) showed stimulatory variation. In all, the observed proteomic responses suggest that BDEs disrupted metabolic function in M. limosus and multivariate analysis tool offers significant potential for the assessment of various stress sources at biochemical level. PMID:22818847

Chiu, K H; Lin, C-R; Huang, H-W; Shiea, J; Liu, L L

2012-07-20

160

Retardation of leaf senescence by benzyladenine in intact bean plants  

Microsoft Academic Search

Benzyladenine (BA) applied to primary leaves of intact bean plants delayed the senescence of both the leaves and the entire shoot. The retardation of senescence was manifested in higher levels of chlorophyll, protein, RNA and ribonuclease activity at all stages of development. Also, the levels of incorporation of labelled precursors into protein and RNA were enhanced. The effect of BA

R. A. Fletcher

1969-01-01

161

Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance  

Microsoft Academic Search

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

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

2011-01-01

162

Contrasting Patterns of Sequence Evolution at the Functionally Redundant bric à brac Paralogs in Drosophila melanogaster  

Microsoft Academic Search

Genes with overlapping expression and function may gradually diverge despite retaining some common functions. To test whether\\u000a such genes show distinct patterns of molecular evolution within species, we examined sequence variation at the bric à brac (bab) locus of Drosophila melanogaster. This locus is composed of two anciently duplicated paralogs, bab1 and bab2, which are involved in patterning the adult

Ryan D. Bickel; Wendy S. Schackwitz; Len A. Pennacchio; Sergey V. Nuzhdin; Artyom Kopp

2009-01-01

163

Analysis of the Drosophila melanogaster Testes Transcriptome Reveals Coordinate Regulation of Paralogous Genes  

Microsoft Academic Search

Gene duplications have been broadly implicated in the generation of testis-specific genes. To perform a comprehensive analysis of paralogous testis-biased genes, we characterized the testes transcriptome of Drosophila melanogaster by comparing gene expression in testes vs. ovaries, heads, and gonadectomized males. A number of the identified 399 testis-biased genes code for the known components of mature sperm. Among the detected

Lyudmila M. Mikhaylova; Kimberly Nguyen; Dmitry I. Nurminsky

2008-01-01

164

Robustness of Helicobacter pylori infection conferred by context-variable redundancy among cysteine-rich paralogs.  

PubMed

Deletion of single genes from expanded gene families in bacterial genomes often does not elicit a phenotype thus implying redundancy or functional non-essentiality of paralogous genes. The molecular mechanisms that facilitate evolutionary maintenance of such paralogs despite selective pressures against redundancy remain mostly unexplored. Here, we investigate the evolutionary, genetic, and functional interaction between the Helicobacter pylori cysteine-rich paralogs hcpG and hcpC in the context of H. pylori infection of cultured mammalian cells. We find that in natural H. pylori populations both hcpG and hcpC are maintained by positive selection in a dual genetic relationship that switches from complete redundancy during early infection, whereby ?hcpC or ?hcpG mutants themselves show no growth defect but a significant growth defect is seen in the ?hcpC,?hcpG double mutant, to quantitative redundancy during late infection wherein the growth defect of the ?hcpC mutant is exacerbated in the ?hcpC,?hcpG double mutant although the ?hcpG mutant itself shows no defect. Moreover, during early infection both hcpG and hcpC are essential for optimal translocation of the H. pylori HspB/GroEL chaperone, but during middle-to-late infection hcpC alone is necessary and sufficient for HspB/GroEL translocation thereby revealing the lack of functional compensation among paralogs. We propose that evolution of context-dependent differences in the nature of genetic redundancy, and function, between hcpG and hcpC may facilitate their maintenance in H. pylori genomes, and confer robustness to H. pylori growth during infection of cultured mammalian cells. PMID:23555707

Putty, Kalyani; Marcus, Sarah A; Mittl, Peer R E; Bogadi, Lindsey E; Hunter, Allison M; Arur, Swathi; Berg, Douglas E; Sethu, Palaniappan; Kalia, Awdhesh

2013-03-26

165

Mutations in SYNGAP1 in Autosomal Nonsyndromic Mental Retardation  

PubMed Central

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.

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

2010-01-01

166

Counseling Parents of Retarded Children  

PubMed Central

Recently pediatricians have become more interested in the retarded child and his family and have come to realize that they have been ill-prepared to face the many problems that continually arise. A basic understanding of the role of parents and their aspirations, coupled with a knowledge of interviewing, techniques will enable them to face these problems with greater assurance. In addition, a knowledge of the community facilities and resources is necessary. This will entail direct contact with schools, parent groups, state hospitals for the retarded as well as state and local agencies which deal with the retarded.

Valente, Mario

1972-01-01

167

Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans.  

PubMed

A genome wide analysis of the human fungal pathogen Cryptococcus neoformans var. grubii has revealed a number of duplications of highly conserved genes involved in morphogenesis. Previously, we reported that duplicate Cdc42 paralogs provide C. neoformans with niche-specific responses to environmental stresses: Cdc42 is required for thermotolerance, while Cdc420 supports the formation of titan cells. The related Rho-GTPase Rac1 has been shown in C. neoformans var. neoformans to play a major role in filamentation and to share Cdc42/Cdc420 binding partners. Here we report the characterization of a second Rac paralog in C. neoformans, Rac2, and describe its overlapping function with the previously described CnRac, Rac1. Further, we demonstrate that the Rac paralogs play a primary role in polarized growth via the organization of reactive oxygen species and play only a minor role in the organization of actin. Finally, we provide preliminary evidence that pharmacological inhibitors of Rac activity and actin stability have synergistic activity. PMID:23748012

Ballou, Elizabeth Ripley; Selvig, Kyla; Narloch, Jessica L; Nichols, Connie B; Alspaugh, J Andrew

2013-06-05

168

Allosteric activation of trypanosomatid deoxyhypusine synthase by a catalytically dead paralog.  

PubMed

Polyamine biosynthesis is a key drug target in African trypanosomes. The "resurrection drug" eflornithine (difluoromethylornithine), which is used clinically to treat human African trypanosomiasis, inhibits the first step in polyamine (spermidine) biosynthesis, a highly regulated pathway in most eukaryotic cells. Previously, we showed that activity of a key trypanosomatid spermidine biosynthetic enzyme, S-adenosylmethionine decarboxylase, is regulated by heterodimer formation with a catalytically dead paralog (a prozyme). Here, we describe an expansion of this prozyme paradigm to the enzyme deoxyhypusine synthase, which is required for spermidine-dependent hypusine modification of a lysine residue in the essential translation factor eIF5A. Trypanosoma brucei encodes two deoxyhypusine synthase paralogs, one that is catalytically functional but grossly impaired, and the other is inactive. Co-expression in Escherichia coli results in heterotetramer formation with a 3000-fold increase in enzyme activity. This functional complex is also present in T. brucei, and conditional knock-out studies indicate that both DHS genes are essential for in vitro growth and infectivity in mice. The recurrent evolution of paralogous, catalytically dead enzyme-based activating mechanisms may be a consequence of the unusual gene expression in the parasites, which lack transcriptional regulation. Our results suggest that this mechanism may be more widely used by trypanosomatids to control enzyme activity and ultimately influence pathogenesis than currently appreciated. PMID:23525104

Nguyen, Suong; Jones, Deuan C; Wyllie, Susan; Fairlamb, Alan H; Phillips, Margaret A

2013-03-21

169

Are protein-protein interfaces more conserved in sequence than the rest of the protein surface?  

Microsoft Academic Search

Protein interfaces are thought to be distinguishable from the rest of the protein surface by their greater degree of residue conservation. We test the validity of this approach on an expanded set of 64 protein- protein interfaces using conservation scores derived from two multiple sequence alignment types, one of close homologs\\/orthologs and one of diverse homologs\\/paralogs. Overall, we find that

DANIEL R. CAFFREY; SHYAMAL SOMAROO; JASON D. HUGHES; JULIAN MINTSERIS; ENOCH S. HUANG

2004-01-01

170

A novel Giraffidae-specific interspersed repeat with a microsatellite, originally found in an intron of a ruminant paralogous p97bcnt gene.  

PubMed

The ruminant-specific p97bcnt gene (bcntp97) is a paralogous gene that includes a region derived from a retrotransposable element 1 (RTE-1). The region comprises an exon (RTE-1 exon) encoding 325 amino acids in the middle of the p97bcnt protein. To understand how the bcntp97 paralog evolved, we examined its organization in several ruminants. We found a 700-base pair (bp) insert in the 5' intron of the RTE-1 exon in giraffe bcntp97. This insert is missing in the corresponding regions of bovine and sika deer. Furthermore, the sequence of the insert is interspersed in the genome of giraffe but not bovine and also contains a (GA)n microsatellite. A highly homologous insert harboring significantly different (GA)n microsatellite was detected in the corresponding region of okapi bcntp97. Therefore, the interspersed fragments with (GA)n microsatellite might serve as a marker for tracking how duplicated genes evolve in a family-specific manner. PMID:15475170

Hon-Nami, Koyu; Ueno, Sadao; Endo, Hideki; Nishimura, Hiroyuki; Igarashi, Takashi; David, Lior; Iwashita, Shintaro

2004-10-13

171

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...

172

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...

173

Foster Grandparents and Retarded Children.  

National Technical Information Service (NTIS)

The overall conclusion of this evaluation is that the Foster Grandparent Project was beneficial to both the foster grandparents and the mentally retarded children who participated in the project. Because of the short term duration of the project exposure,...

R. M. Gray J. M. Kasteler

1967-01-01

174

Comparative Genomics of Helicobacter pylori: Analysis of the Outer Membrane Protein Families  

Microsoft Academic Search

The two complete genomic sequences of Helicobacter pylori J99 and 26695 were used to compare the paralogous families (related genes within one genome, likely to have related function) of genes predicted to encode outer membrane proteins which were present in each strain. We identified five paralogous gene families ranging in size from 3 to 33 members; two of these families

RICHARD A. ALM; JAMES BINA; BETH M. ANDREWS; PETER DOIG; ROBERT E. W. HANCOCK; TREVOR J. TRUST

2000-01-01

175

The Mental Retardation Report Framework  

Microsoft Academic Search

The Mental Retardation Report Framework (MR Framework) assists in reporting the results of psychological evaluations of patients\\u000a who are either known or suspected to be mentally retarded. The program allows the psychologist to produce the framework of\\u000a a report in a few minutes, accepting keyboard input for free-form text and mouse clicks for selecting from lists of choices.\\u000a Input includes

Barry A. Tanner

1994-01-01

176

Human 14-3-3 paralogs differences uncovered by cross-talk of phosphorylation and lysine acetylation.  

PubMed

The 14-3-3 protein family interacts with more than 700 different proteins in mammals, in part as a result of its specific phospho-serine/phospho-threonine binding activity. Upon binding to 14-3-3, the stability, subcellular localization and/or catalytic activity of the ligands are modified. Seven paralogs are strictly conserved in mammalian species. Although initially thought as redundant, the number of studies showing specialization is growing. We created a protein-protein interaction network for 14-3-3, kinases and their substrates signaling in human cells. We included information of phosphorylation, acetylation and other PTM sites, obtaining a complete representation of the 14-3-3 binding partners and their modifications. Using a computational system approach we found that networks of each 14-3-3 isoform are statistically different. It was remarkable to find that Tyr was the most phosphorylatable amino acid in domains of 14-3-3 epsilon partners. This, together with the over-representation of SH3 and Tyr_Kinase domains, suggest that epsilon could be involved in growth factors receptors signaling pathways particularly. We also found that within zeta's network, the number of acetylated partners (and the number of modify lysines) is significantly higher compared with each of the other isoforms. Our results imply previously unreported hidden differences of the 14-3-3 isoforms interaction networks. The phosphoproteome and lysine acetylome within each network revealed post-transcriptional regulation intertwining phosphorylation and lysine acetylation. A global understanding of these networks will contribute to predict what could occur when regulatory circuits become dysfunctional or are modified in response to external stimuli. PMID:23418452

Uhart, Marina; Bustos, Diego M

2013-02-13

177

Human 14-3-3 Paralogs Differences Uncovered by Cross-Talk of Phosphorylation and Lysine Acetylation  

PubMed Central

The 14-3-3 protein family interacts with more than 700 different proteins in mammals, in part as a result of its specific phospho-serine/phospho-threonine binding activity. Upon binding to 14-3-3, the stability, subcellular localization and/or catalytic activity of the ligands are modified. Seven paralogs are strictly conserved in mammalian species. Although initially thought as redundant, the number of studies showing specialization is growing. We created a protein-protein interaction network for 14-3-3, kinases and their substrates signaling in human cells. We included information of phosphorylation, acetylation and other PTM sites, obtaining a complete representation of the 14-3-3 binding partners and their modifications. Using a computational system approach we found that networks of each 14-3-3 isoform are statistically different. It was remarkable to find that Tyr was the most phosphorylatable amino acid in domains of 14-3-3 epsilon partners. This, together with the over-representation of SH3 and Tyr_Kinase domains, suggest that epsilon could be involved in growth factors receptors signaling pathways particularly. We also found that within zeta’s network, the number of acetylated partners (and the number of modify lysines) is significantly higher compared with each of the other isoforms. Our results imply previously unreported hidden differences of the 14-3-3 isoforms interaction networks. The phosphoproteome and lysine acetylome within each network revealed post-transcriptional regulation intertwining phosphorylation and lysine acetylation. A global understanding of these networks will contribute to predict what could occur when regulatory circuits become dysfunctional or are modified in response to external stimuli.

Uhart, Marina; Bustos, Diego M.

2013-01-01

178

Developmental Problems of the Moderately Mentally Retarded.  

ERIC Educational Resources Information Center

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…

Bepko, Raymond A.; And Others

179

The Mentally Retarded Offender: Annotated Bibliography.  

ERIC Educational Resources Information Center

|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…

Schilit, Jeffrey; And Others

180

The Mentally Retarded Offender: Annotated Bibliography.  

ERIC Educational Resources Information Center

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…

Schilit, Jeffrey; And Others

181

Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2  

PubMed Central

Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution.

Bochkis, Irina M.; Schug, Jonathan; Ye, Diana Z.; Kurinna, Svitlana; Stratton, Sabrina A.; Barton, Michelle C.; Kaestner, Klaus H.

2012-01-01

182

Need-Based Up-Regulation of Protein Levels in Response to Deletion of Their Duplicate Genes  

PubMed Central

Many duplicate genes maintain functional overlap despite divergence over long evolutionary time scales. Deleting one member of a paralogous pair often has no phenotypic effect, unless its paralog is also deleted. It has been suggested that this functional compensation might be mediated by active up-regulation of expression of a gene in response to deletion of its paralog. However, it is not clear how prevalent such paralog responsiveness is, nor whether it is hardwired or dependent on feedback from environmental conditions. Here, we address these questions at the genomic scale using high-throughput flow cytometry of single-cell protein levels in differentially labeled cocultures of wild-type and paralog-knockout Saccharomyces cerevisiae strains. We find that only a modest fraction of proteins (22 out of 202) show significant up-regulation to deletion of their duplicate genes. However, these paralog-responsive proteins match almost exclusively duplicate pairs whose overlapping function is required for growth. Moreover, media conditions that add or remove requirements for the function of a duplicate gene pair specifically eliminate or create paralog responsiveness. Together, our results suggest that paralog responsiveness in yeast is need-based: it appears only in conditions in which the gene function is required. Physiologically, such need-based responsiveness could provide an adaptive mechanism for compensation of genetic, environmental, or stochastic perturbations in protein abundance.

Kirschner, Marc W.; Kishony, Roy

2010-01-01

183

Paralogous mitochondrial control region in the giant tiger shrimp, Penaeus monodon (F.) affects population genetics inference: A cautionary tale.  

PubMed

The mitochondrial control region (mtCR) is a widely used genetic marker for phylogenetic, phylogeographic and population genetic inference. The analysis of mtCR in 115 Indonesian specimens of the giant tiger shrimp, Penaeus monodon, revealed 26 individuals yielding a second - apparently paralogous - sequence in addition to the putatively authentic mitochondrial haplotype. The paralogous haplotypes fell into two major haplogroups that are highly diverged with respect to the authentic mitochondrial haplotypes (average pairwise sequence divergence of 12.5% and 5.0%, respectively). A comparison with published mtCR sequences of P. monodon showed that the paralogous contaminant sequences were inadvertently included in a series of recent population genetic studies, leading to seriously compromised conclusions about genetic diversity and differentiation. The prevalence of the paralogous haplotypes throughout the sampled Indo-Pacific populations is highly skewed: From African and Indian individuals only paralogs have been sequenced, while they are completely absent from Australian individuals. This suggests that geographically unequally distributed allelic variants at binding sites of the primer pair ordinarily used to amplify mtCR in P. monodon suppressed the amplification of authentic mtCR in a wide range of samples. PMID:21145976

Walther, Elisabeth; Schöfl, Gerhard; Mrotzek, Grit; Haryanti; Sugama, Ketut; Saluz, Hans Peter

2010-12-09

184

FMR1 targets distinct mRNA sequence elements to regulate protein expression  

PubMed Central

Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMRP. We report the discovery of distinct RNA recognition elements (RREs) that correspond to the two independent RNA binding domains of FMRP, and the binding sites within the mRNA targets for wild-type and I304N mutant FMRP isoforms and its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP affects their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide a molecular guide towards the pursuit of novel therapeutic targets for these neurological disorders.

Ascano, Manuel; Mukherjee, Neelanjan; Bandaru, Pradeep; Miller, Jason B.; Nusbaum, Jeff; Corcoran, David L.; Langlois, Christine; Munschauer, Mathias; Dewell, Scott; Hafner, Markus; Williams, Zev; Ohler, Uwe; Tuschl, Thomas

2012-01-01

185

Expression studies of two paralogous ppa genes encoding distinct Family I pyrophosphatases in marine unicellular cyanobacteria reveal inactivation of the typical cyanobacterial gene.  

PubMed

Genome sequence analyses revealed the occurrence of two paralogous ppa genes potentially encoding distinct Family I inorganic pyrophosphatases (sPPases, EC3.6.1.1) in the marine unicellular cyanobacteria Prochlorococcus marinus strains MED4 and MIT9313 and Synechococcus sp. WH8102. Protein sequence alignment and phylogenetic analysis indicated that the ppa gene proper of cyanobacteria (ppa1) encodes a presumably inactive mutant enzyme whereas the second gene (ppa2) might encode an active sPPase closely related to those of some proteobacteria. Heterologous expression of the two cloned P. marinus MED4 ppa genes in Escherichia coli confirmed this proposal, only the inactive ppa1 product being immunodetected by anti-cyanobacterial sPPase antibodies. A possible scenario of ppa gene inactivation and replacement in the context of the postulated rapid diversification of marine unicellular cyanobacteria, the most abundant photosynthetic prokaryotes in the oceans, is discussed. PMID:12127978

Gómez-García, María R; Serrano, Aurelio

2002-07-26

186

Sexual behaviors in retarded children and adolescents.  

PubMed

Literature reports on the sexual behaviors of mildly retarded adolescents are reviewed. Retarded adolescents often participate in masturbation and homosexual exploratory behavior. The retarded adolescent's heterosexual interests are of great concern to parents. The retarded adolescent is vulnerable to suggestibility, poor judgment and a failure to foresee the consequences of his actions. Parents are usually acutely distressed by the retarded youth's sexual behaviors, and they may develop an attitude that these behaviors are "bad." There is a need to provide appropriate sex education for retardates and to counsel their families about the management of sexual behaviors which occur during the adolescent years. PMID:7251876

Simonds, J F

1980-12-01

187

The De Novo Cytosine Methyltransferase DRM2 Requires Intact UBA Domains and a Catalytically Mutated Paralog DRM3 during RNA-Directed DNA Methylation in Arabidopsis thaliana  

PubMed Central

Eukaryotic DNA cytosine methylation can be used to transcriptionally silence repetitive sequences, including transposons and retroviruses. This silencing is stable between cell generations as cytosine methylation is maintained epigenetically through DNA replication. The Arabidopsis thaliana Dnmt3 cytosine methyltransferase ortholog DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) is required for establishment of small interfering RNA (siRNA) directed DNA methylation. In mammals PIWI proteins and piRNA act in a convergently evolved RNA–directed DNA methylation system that is required to repress transposon expression in the germ line. De novo methylation may also be independent of RNA interference and small RNAs, as in Neurospora crassa. Here we identify a clade of catalytically mutated DRM2 paralogs in flowering plant genomes, which in A.thaliana we term DOMAINS REARRANGED METHYLTRANSFERASE3 (DRM3). Despite being catalytically mutated, DRM3 is required for normal maintenance of non-CG DNA methylation, establishment of RNA–directed DNA methylation triggered by repeat sequences and accumulation of repeat-associated small RNAs. Although the mammalian catalytically inactive Dnmt3L paralogs act in an analogous manner, phylogenetic analysis indicates that the DRM and Dnmt3 protein families diverged independently in plants and animals. We also show by site-directed mutagenesis that both the DRM2 N-terminal UBA domains and C-terminal methyltransferase domain are required for normal RNA–directed DNA methylation, supporting an essential targeting function for the UBA domains. These results suggest that plant and mammalian RNA–directed DNA methylation systems consist of a combination of ancestral and convergent features.

Henderson, Ian R.; Deleris, Angelique; Wong, William; Zhong, Xuehua; Chin, Hang Gyeong; Horwitz, Gregory A.; Kelly, Krystyna A.; Pradhan, Sriharsa; Jacobsen, Steven E.

2010-01-01

188

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

PubMed

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

Bonnefon, Jean-François

2009-10-01

189

The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy.  

PubMed

The interplay between homologous DNA recombination and mitotic progression is poorly understood. The five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) are key enzymes for DNA double-strand break repair. In our search for specific functions of the various RAD51 paralogs, we found that inhibition of XRCC3 elicits checkpoint defects, while inhibition of RAD51B or RAD51C induces G2/M cell cycle arrest in HeLa cells. Using live-cell microscopy we show that in XRCC3-knockdown cells the spindle assembly checkpoint persists and there is a higher frequency of chromosome misalignments, anaphase bridges, and aneuploidy. We observed centrosome defects in the absence of XRCC3. While RAD51B and RAD51C act early in homologous recombination, XRCC3 functions jointly with GEN1 later in the pathway at the stage of Holliday junction resolution. Our data demonstrate that Holliday junction resolution has critical functions for preventing aberrant mitosis and aneuploidy in mitotic cells. PMID:23108668

Rodrigue, Amélie; Coulombe, Yan; Jacquet, Karine; Gagné, Jean-Phillipe; Roques, Céline; Gobeil, Stéphane; Poirier, Guy; Masson, Jean-Yves

2012-10-29

190

IDN2 and Its Paralogs Form a Complex Required for RNA-Directed DNA Methylation  

PubMed Central

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.

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

191

in MentallyRetardedPersons  

Microsoft Academic Search

Haptoglobin phenotype frequencies for 887 un- selected mentally retarded patients were within the range reported for normal European popula- tions. Of these sera, 2% initially classified as anhaptoglobinemic by subjective appraisal of starch-gel electropherograms were subsequently shown to be hypohaptoglobinemic. This frequency of hypohaptoglobinemia is similar to that reported for normal populations. Sixteen of the hypohapto- globinemic cases were reinvestigated,

A. T. Rundle; B. Clothier; Barbara Sudell

192

VOCATIONAL PROGRAMMING FOR THE RETARDED.  

ERIC Educational Resources Information Center

A SUCCESSFUL PROGRAM OF VOCATIONAL TRAINING FOR THE MENTALLY RETARDED IS BEING CARRIED ON AT THE MADISON (WISCONSIN) VOCATIONAL, TECHNICAL, AND ADULT SCHOOLS. THE TRAINEES MUST BE 17 YEARS OR OLDER, WITH AN IQ OF APPROXIMATELY 50-75. THE SCHOOL OF QUANTITY FOOD PREPARATION CONTRIBUTES GREATLY TO THIS PROGRAM, FOR WHILE IT MAINLY TEACHES CHEFS AND…

BRICE, CARL R.

193

Dichotic Stimulation and Mental Retardation.  

ERIC Educational Resources Information Center

|This paper reviews literature on the use of dichotic stimulation in individuals with mental retardation, and examines how noninvasive dichotic stimulation relates to hemisphere lateralization. Common findings are discussed concerning direction and magnitude of ear asymmetries, patterns of intrusion errors, and speech lateralization of Down…

Mosley, James L.; Virbancic, Mirna I.

1990-01-01

194

Genetic Counseling in Mental Retardation.  

ERIC Educational Resources Information Center

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…

Bowen, Peter

195

Mental Retardation: Diagnosis and Treatment.  

ERIC Educational Resources Information Center

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.…

Poser, Charles M., Ed.

196

HANDBOOK OF MENTAL RETARDATION SYNDROMES.  

ERIC Educational Resources Information Center

|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…

CARTER, CHARLES H.

197

Detection of Malingered Mental Retardation  

ERIC Educational Resources Information Center

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…

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

2010-01-01

198

VOCATIONAL PROGRAMMING FOR THE RETARDED.  

ERIC Educational Resources Information Center

|A SUCCESSFUL PROGRAM OF VOCATIONAL TRAINING FOR THE MENTALLY RETARDED IS BEING CARRIED ON AT THE MADISON (WISCONSIN) VOCATIONAL, TECHNICAL, AND ADULT SCHOOLS. THE TRAINEES MUST BE 17 YEARS OR OLDER, WITH AN IQ OF APPROXIMATELY 50-75. THE SCHOOL OF QUANTITY FOOD PREPARATION CONTRIBUTES GREATLY TO THIS PROGRAM, FOR WHILE IT MAINLY TEACHES CHEFS AND…

BRICE, CARL R.

199

Psychotherapy With the Institutionalized Retarded  

Microsoft Academic Search

The belief that psychotherapy may be of value with the mentally retarded is of fairly recent origin. One has only to peruse the literature of the last several decades to find much skepticism as regards its worth in the area of mental deficiency. To mention just a few, Huttcfl (1945), Healy and Bronner ( 1939) , Morgan ( 1926), Paster

IRA GOLDBERG

200

Genetic Counseling in Mental Retardation.  

ERIC Educational Resources Information Center

|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…

Bowen, Peter

201

HANDBOOK OF MENTAL RETARDATION SYNDROMES.  

ERIC Educational Resources Information Center

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…

CARTER, CHARLES H.

202

Reformulation of fire retardant coatings  

Microsoft Academic Search

Fire retardant coatings currently in use contain a number of ingredients which are either considered to be ‘toxic’ heavy metals or on the hazardous air pollutants (HAPs) list. In addition, there is concern that the use of halogenated chemicals in these coatings and other products will be banned in the future. This paper contains the details of two reformulations programs.

Donald B. Dahm

1996-01-01

203

Citizen Advocacy in a Mental Retardation Unit  

ERIC Educational Resources Information Center

Described is a program initiated by the social work staff of a hospital mental retardation unit which involved locating and screening citizen advocates to serve as friend, big brother, social worker, and legal counselor to retarded patients. (GW)

Smiley, Charles W.; Craik, Mildred C.

1972-01-01

204

Report on Mental Retardation and Developmental Handicaps.  

National Technical Information Service (NTIS)

Mental retardation and developmental handicaps are discussed in a report prepared by the Comprehensive Health Planning Council of South Florida. The council's planning group for developmental handicaps and retardation was responsible for evaluating commun...

1975-01-01

205

People with Mental Retardation Are Dying, Legally.  

ERIC Educational Resources Information Center

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)

Keyes, Denis; And Others

1997-01-01

206

Non-specific X linked mental retardation  

Microsoft Academic Search

Non-specific X linked mental retardation (MRX) is mental retardation in persons of normal physical appearance who have no recognisable features apart from a characteristic pedigree. Review of published reports shows that there is clinical variability in the degree of mental retardation within families and genetic heterogeneity, based on gene localisation, between families. We propose a classification based on genetic localisation

B Kerr; G Turner; J Mulley; A Gedeon; M Partington

1991-01-01

207

Endocrine Disorders Associated with Mental Retardation  

PubMed Central

Endocrine disorders associated with mental retardation are described in relation to clinical characteristics, pathogenesis, diagnostic procedures, and treatment. Some endocrine disorders, particularly hypothyroidism, nephrogenic-diabetes insipidus, and hypoglycemic conditions, are frequently associated with mental retardation. Early diagnosis and prompt and proper management reduce mortality and the incidence of mental retardation associated with endocrine disorders.

Reddy, Churku Mohan

1980-01-01

208

Low Elevated Lead Levels and Mental Retardation.  

ERIC Educational Resources Information Center

|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…

Marlowe, Mike; And Others

209

MENTAL RETARDATION--THE PRESENT PROBLEM.  

ERIC Educational Resources Information Center

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…

SHAFTER, ALBERT J.

210

Evolutionary dynamics and functional specialization of plant paralogs formed by whole and small-scale genome duplications.  

PubMed

Gene duplicates are a major source of evolutionary novelties in the form of new or specialized functions and play a key role in speciation. Gene duplicates are generated through whole genome duplications (WGD) or small-scale genome duplications (SSD). Although WGD preserves the stoichiometric relationships between duplicates, those arising from SSD are usually unbalanced and are expected to follow different evolutionary dynamics than those formed by WGD. To dissect the role of the mechanism of duplication in these differential dynamics and determine whether this role was shared across species, we performed a genome wide evolutionary analysis of gene duplications arising from the most recent WGD events and contemporary episodes of SSD in four model species representing distinct plant evolutionary lineages. We found an excess of relaxed purifying selection after duplication in SSD paralogs compared with WGD, most of which may have been the result of functional divergence events between gene copies as estimated by measures of genetic distances. These differences were significant in three angiosperm genomes but not in the moss species Physcomitrella patens. Although the comparison of models of evolution does not attribute a relevant role to the mechanism of duplication in the evolution duplicates, distribution of retained genes among Gene Ontology functional categories support the conclusion that evolution of gene duplicates depends on its origin of duplication (WGD and SSD) but, most importantly, on the species. Similar lineage-specific biases were also observed in protein network connectivity, translational efficiency, and selective constraints acting on synonymous codon usage. Although the mechanism of duplication may determine gene retention, our results attribute a dominant role to the species in determining the ultimate pattern of duplicate gene retention and reveal an unanticipated complexity in the evolutionary dynamics and functional specialization of duplicated genes in plants. PMID:22734049

Carretero-Paulet, Lorenzo; Fares, Mario A

2012-06-24

211

Expression Pattern of Two Paralogs Encoding Cinnamyl Alcohol Dehydrogenases in Arabidopsis. Isolation and Characterization of the Corresponding Mutants1  

PubMed Central

Studying Arabidopsis mutants of the phenylpropanoid pathway has unraveled several biosynthetic steps of monolignol synthesis. Most of the genes leading to monolignol synthesis have been characterized recently in this herbaceous plant, except those encoding cinnamyl alcohol dehydrogenase (CAD). We have used the complete sequencing of the Arabidopsis genome to highlight a new view of the complete CAD gene family. Among nine AtCAD genes, we have identified the two distinct paralogs AtCAD-C and AtCAD-D, which share 75% identity and are likely to be involved in lignin biosynthesis in other plants. Northern, semiquantitative restriction fragment-length polymorphism-reverse transcriptase-polymerase chain reaction and western analysis revealed that AtCAD-C and AtCAD-D mRNA and protein ratios were organ dependent. Promoter activities of both genes are high in fibers and in xylem bundles. However, AtCAD-C displayed a larger range of sites of expression than AtCAD-D. Arabidopsis null mutants (Atcad-D and Atcad-C) corresponding to both genes were isolated. CAD activities were drastically reduced in both mutants, with a higher impact on sinapyl alcohol dehydrogenase activity (6% and 38% of residual sinapyl alcohol dehydrogenase activities for Atcad-D and Atcad-C, respectively). Only Atcad-D showed a slight reduction in Klason lignin content and displayed modifications of lignin structure with a significant reduced proportion of conventional S lignin units in both stems and roots, together with the incorporation of sinapaldehyde structures ether linked at C?. These results argue for a substantial role of AtCAD-D in lignification, and more specifically in the biosynthesis of sinapyl alcohol, the precursor of S lignin units.

Sibout, Richard; Eudes, Aymerick; Pollet, Brigitte; Goujon, Thomas; Mila, Isabelle; Granier, Fabienne; Seguin, Armand; Lapierre, Catherine; Jouanin, Lise

2003-01-01

212

ACC oxidase genes expressed in the wood-forming tissues of loblolly pine (Pinus taeda L.) include a pair of nearly identical paralogs (NIPs).  

PubMed

1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final reaction of the ethylene biosynthetic pathway, converting the unusual cyclic amino acid, ACC, into ethylene. Past studies have shown a possible link between ethylene and compression wood formation in conifers, but the relationship has received no more than modest study at the gene expression level. In this study, a cDNA clone encoding a putative ACC oxidase, PtACO1, was isolated from a cDNA library produced using mRNA from lignifying xylem of loblolly pine (Pinus taeda) trunk wood. The cDNA clone comprised an open reading frame of 1461 bp encoding a protein of 333 amino acids. Using PCR amplification techniques, a genomic clone corresponding to PtACO1 was isolated and shown to contain three introns with typical GT/AG boundaries defining the splice junctions. The PtACO1 gene product shared 70% identity with an ACC oxidase from European white birch (Betula pendula), and phylogenetic analyses clearly placed the gene product in the ACC oxidase cluster of the Arabidopsis thaliana 2-oxoglutarate-dependent dioxygenase superfamily tree. The PtACO1 sequence was used to identify additional ACC oxidase clones from loblolly pine root cDNA libraries characterized as part of an expressed sequence tag (EST) discovery project. The PtACO1 sequence was also used to recover additional paralogous sequences from genomic DNA, one of which (PtACO2) turned out to be >98% identical to PtACO1 in the nucleotide coding sequence, leading to its classification as a "nearly identical paralog" (NIP). Quantitative PCR analyses showed that the expression level of PtACO1-like transcripts varied in different tissues, as well as in response to hormonal treatments and bending. Possible roles for PtACO1 in compression wood formation in loblolly pine and the discovery of its NIP are discussed in light of these results. PMID:20053371

Yuan, S; Wang, Y; Dean, J F D

2010-01-04

213

Sequence Motifs in MADS Transcription Factors Responsible for Specificity and Diversification of Protein-Protein Interaction  

Microsoft Academic Search

Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important

Aalt D. J. van Dijk; Giuseppa Morabito; Martijn Fiers; Roeland C. H. J. van Ham; Gerco C. Angenent; Richard G. H. Immink

2010-01-01

214

The theory of retarded potentials  

SciTech Connect

The theory of retarded potentials is formulated in a very general fashion which includes all postulates on the velocity of light, all definitions of the scalar and vector potentials and all forms of the force equation which have so far been mathematically formulated. Two of the four Maxwell equations are the same for all postulates; two may have slightly different forms. If the force field is studied directly, the four Maxwell equations are replaced by two equations which depend on the postulates employed.

Mirchandaney, A.S. (Cornell Univ., Ithaca, NY (USA)); Spencer, D.E.; Uma, S.Y.; Mann, P.J. (Univ. of Connecticut, Storrs (USA))

1988-09-01

215

X-linked mental retardation  

Microsoft Academic Search

A survey of the mentally retarded children with an IQ between 30 and 55 born in a 10-year period (1955-64) and now of school age was carried out in New South Wales. The number of propositi who had a similarly affected sib of the same sex was ascertained; 58 boys had a similarly affected brother(s) and 22 girls had a

Gillian Turner; Brian Turner

1974-01-01

216

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

Microsoft Academic Search

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

L Lundin

1993-01-01

217

Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis.  

PubMed

Hox genes encode transcription factors governing complex developmental processes in several organs. A subset of Hox genes are expressed in the developing lung. Except for Hoxa5, the lack of overt lung phenotype in single mutants suggests that Hox genes may not play a predominant role in lung ontogeny or that functional redundancy may mask anomalies. In the Hox5 paralog group, both Hoxa5 and Hoxb5 genes are expressed in the lung mesenchyme whereas Hoxa5 is also expressed in the tracheal mesenchyme. Herein, we generated Hoxa5;Hoxb5 compound mutant mice to evaluate the relative contribution of each gene to lung development. Hoxa5;Hoxb5 mutants carrying the four mutated alleles displayed an aggravated lung phenotype, resulting in the death of the mutant pups at birth. Characterization of the phenotype highlighted the role of Hoxb5 in lung formation, the latter being involved in branching morphogenesis, goblet cell specification, and postnatal air space structure, revealing partial functional redundancy with Hoxa5. However, the Hoxb5 lung phenotypes were less severe than those seen in Hoxa5 mutants, likely because of Hoxa5 compensation. New specific roles for Hoxa5 were also unveiled, demonstrating the extensive contribution of Hoxa5 to the developing respiratory system. The exclusive expression of Hoxa5 in the trachea and the phrenic motor column likely underlies the Hoxa5-specific trachea and diaphragm phenotypes. Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog genes shared some functions during lung morphogenesis, Hoxa5 playing a predominant role. PMID:23585229

Boucherat, Olivier; Montaron, Séverine; Bérubé-Simard, Félix-Antoine; Aubin, Josée; Philippidou, Polyxeni; Wellik, Deneen M; Dasen, Jeremy S; Jeannotte, Lucie

2013-04-12

218

Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation.  

PubMed

The Roquin-1 protein binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. A single point mutation in Roquin-1, but not gene ablation, increases follicular helper T (Tfh) cell numbers and causes lupus-like autoimmune disease in mice. In T cells, we did not identify a unique role for the much lower expressed paralog Roquin-2. However, combined ablation of both genes induced accumulation of T cells with an effector and follicular helper phenotype. We showed that Roquin-1 and Roquin-2 proteins redundantly repressed the mRNA of inducible costimulator (Icos) and identified the Ox40 costimulatory receptor as another shared mRNA target. Combined acute deletion increased Ox40 signaling, as well as Irf4 expression, and imposed Tfh differentiation on CD4(+) T cells. These data imply that both proteins maintain tolerance by preventing inappropriate T cell activation and Tfh cell differentiation, and that Roquin-2 compensates in the absence of Roquin-1, but not in the presence of its mutated form. PMID:23583643

Vogel, Katharina U; Edelmann, Stephanie L; Jeltsch, Katharina M; Bertossi, Arianna; Heger, Klaus; Heinz, Gitta A; Zöller, Jessica; Warth, Sebastian C; Hoefig, Kai P; Lohs, Claudia; Neff, Frauke; Kremmer, Elisabeth; Schick, Joel; Repsilber, Dirk; Geerlof, Arie; Blum, Helmut; Wurst, Wolfgang; Heikenwälder, Mathias; Schmidt-Supprian, Marc; Heissmeyer, Vigo

2013-04-11

219

[Clinical studies on pramipexol retard].  

PubMed

Pramipexol retard is the newest drug for the treatment of Parkinson's disease. The prolonged release of the agent in this preparation allows a more continuous dopaminergic stimulation than previous preparations, without reducing the agent's already known and proven clinical efficiency. In addition, it has a more favourable adverse effect profile than previous preparations, and patient compliance can also be better as it needs to be taken only once daily. These benefits have been proven in recent clinical studies, of which the most important ones are reviewed here. PMID:20648781

Klivényi, Péter; Vécsei, László

2010-05-30

220

Streptomycin retards the phenotypic maturation of chick myogenic cells  

Microsoft Academic Search

Summary  As part of an effort to optimize conditions required for the complete maturation of muscle cells in vitro, we have investigated\\u000a the effects of the antibiotics penicillin, streptomycin, and Fungizone (amphotericin B) on the development of cultured chick\\u000a embryo skeletal muscle. It is shown that even low dosages of streptomycin, but not penicillin or Fungizone, retard protein\\u000a synthesis and accumulation

Paul S. Moss; Dennis H. Spector; Charles A. Glass; Richard C. Strohman

1984-01-01

221

Orthopaedic Problems of the Mentally Retarded  

ERIC Educational Resources Information Center

|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)|

McSweeney, Anthony

1972-01-01

222

Mental Retardation: The Known and the Unknown. Report of the President's Committee on Mental Retardation.  

National Technical Information Service (NTIS)

Mental Retardation is a condition with which we have been living since civilization began. Although in recent years much has been accomplished to identify, treat, and sometimes eliminate certain causes of mental retardation, we are continually learning th...

1976-01-01

223

Flame retardant mechanism of hyperbranched polyurethane acrylates used for UV curable flame retardant coatings  

Microsoft Academic Search

A hyperbranched polyurethane acrylate containing phosphorus was found to display flame retardance with a limiting oxygen index of 27.0 after being UV cured. The retardant mechanism was investigated by observing the site where retardance take places and the synergistic effect of phosphorus and nitrogen. It is shown that the best synergistic effect happens when the phosphorus content is around 0.7

Sheng-Wu Zhu; Wen-Fang Shi

2002-01-01

224

Newly identified paralogous groups on mouse chromosomes 5 and 11 reveal the age of a T-box cluster duplication  

SciTech Connect

A novel family of ancient transcription factors, the T-box family, involved in embryonic development in metazoans, was described recently. Four members of this family are grouped in two tightly linked pairs within the mouse genome. This arrangement can be explained by an original cluster formation followed by an en masse duplication. Here we demonstrate that this duplication event also included several closely linked genes. Using data obtained from linked paralogous genes, we show that the T-box cluster duplication occurred prior to the divergence between bony fish and tetrapods around 400 million years ago. This work facilitates our understanding of the status of the T-box gene family in different vertebrate lineages and also defines a novel paralogy group within the mouse genome. 15 refs., 2 figs.

Ruvinsky, I.; Silver, L.M. [Princeton Univ., NJ (United States)

1997-03-01

225

The paralogous MarR/DUF24-family repressors YodB and CatR control expression of the catechol dioxygenase CatE in Bacillus subtilis.  

PubMed

The redox-sensing MarR/DUF24-type repressor YodB controls expression of the azoreductase AzoR1 and the nitroreductase YodC that are involved in detoxification of quinones and diamide in Bacillus subtilis. In the present paper, we identified YodB and its paralog YvaP (CatR) as repressors of the yfiDE (catDE) operon encoding a catechol-2,3-dioxygenase that also contributes to quinone resistance. Inactivation of both CatR and YodB is required for full derepression of catDE transcription. DNA-binding assays and promoter mutagenesis studies showed that CatR protects two inverted repeats with the consensus sequence TTAC-N(5)-GTAA overlapping the -35 promoter region (BS1) and the transcriptional start site (TSS) (BS2). The BS1 operator was required for binding of YodB in vitro. CatR and YodB share the conserved N-terminal Cys residue, which is required for redox sensing of CatR in vivo as shown by Cys-to-Ser mutagenesis. Our data suggest that CatR is modified by intermolecular disulfide formation in response to diamide and quinones in vitro and in vivo. Redox regulation of CatR occurs independently of YodB, and no protein interaction was detected between CatR and YodB in vivo using protein cross-linking and mass spectrometry. PMID:20639328

Chi, Bui Khanh; Kobayashi, Kazuo; Albrecht, Dirk; Hecker, Michael; Antelmann, Haike

2010-07-16

226

The Paralogous MarR/DUF24-Family Repressors YodB and CatR Control Expression of the Catechol Dioxygenase CatE in Bacillus subtilis? †  

PubMed Central

The redox-sensing MarR/DUF24-type repressor YodB controls expression of the azoreductase AzoR1 and the nitroreductase YodC that are involved in detoxification of quinones and diamide in Bacillus subtilis. In the present paper, we identified YodB and its paralog YvaP (CatR) as repressors of the yfiDE (catDE) operon encoding a catechol-2,3-dioxygenase that also contributes to quinone resistance. Inactivation of both CatR and YodB is required for full derepression of catDE transcription. DNA-binding assays and promoter mutagenesis studies showed that CatR protects two inverted repeats with the consensus sequence TTAC-N5-GTAA overlapping the ?35 promoter region (BS1) and the transcriptional start site (TSS) (BS2). The BS1 operator was required for binding of YodB in vitro. CatR and YodB share the conserved N-terminal Cys residue, which is required for redox sensing of CatR in vivo as shown by Cys-to-Ser mutagenesis. Our data suggest that CatR is modified by intermolecular disulfide formation in response to diamide and quinones in vitro and in vivo. Redox regulation of CatR occurs independently of YodB, and no protein interaction was detected between CatR and YodB in vivo using protein cross-linking and mass spectrometry.

Chi, Bui Khanh; Kobayashi, Kazuo; Albrecht, Dirk; Hecker, Michael; Antelmann, Haike

2010-01-01

227

Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel  

Microsoft Academic Search

Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were

Lina Basel-Vanagaite; Ellen Taub; Gabrielle J Halpern; Valerie Drasinover; Nurit Magal; Bella Davidov; Joël Zlotogora; Mordechai Shohat

2007-01-01

228

ZINC-INDUCED FACILITATOR-LIKE family in plants: lineage-specific expansion in monocotyledons and conserved genomic and expression features among rice (Oryza sativa) paralogs  

PubMed Central

Background Duplications are very common in the evolution of plant genomes, explaining the high number of members in plant gene families. New genes born after duplication can undergo pseudogenization, neofunctionalization or subfunctionalization. Rice is a model for functional genomics research, an important crop for human nutrition and a target for biofortification. Increased zinc and iron content in the rice grain could be achieved by manipulation of metal transporters. Here, we describe the ZINC-INDUCED FACILITATOR-LIKE (ZIFL) gene family in plants, and characterize the genomic structure and expression of rice paralogs, which are highly affected by segmental duplication. Results Sequences of sixty-eight ZIFL genes, from nine plant species, were comparatively analyzed. Although related to MSF_1 proteins, ZIFL protein sequences consistently grouped separately. Specific ZIFL sequence signatures were identified. Monocots harbor a larger number of ZIFL genes in their genomes than dicots, probably a result of a lineage-specific expansion. The rice ZIFL paralogs were named OsZIFL1 to OsZIFL13 and characterized. The genomic organization of the rice ZIFL genes seems to be highly influenced by segmental and tandem duplications and concerted evolution, as rice genome contains five highly similar ZIFL gene pairs. Most rice ZIFL promoters are enriched for the core sequence of the Fe-deficiency-related box IDE1. Gene expression analyses of different plant organs, growth stages and treatments, both from our qPCR data and from microarray databases, revealed that the duplicated ZIFL gene pairs are mostly co-expressed. Transcripts of OsZIFL4, OsZIFL5, OsZIFL7, and OsZIFL12 accumulate in response to Zn-excess and Fe-deficiency in roots, two stresses with partially overlapping responses. Conclusions We suggest that ZIFL genes have different evolutionary histories in monocot and dicot lineages. In rice, concerted evolution affected ZIFL duplicated genes, possibly maintaining similar expression patterns between pairs. The enrichment for IDE1 boxes in rice ZIFL gene promoters suggests a role in Zn-excess and Fe-deficiency up-regulation of ZIFL transcripts. Moreover, this is the first description of the ZIFL gene family in plants and the basis for functional studies on this family, which may play important roles in Zn and Fe homeostasis in plants.

2011-01-01

229

Clinical outcome in cardiac transplant recipients receiving tacrolimus retard.  

PubMed

Tacrolimus (TAC) retard is a new oral formulation of TAC that is given once instead of twice daily. We investigated the efficacy and safety of TAC retard in heart transplant recipients during a 36-month follow-up period. We included 11 patients receiving TAC retard (once-daily [OD] group) and 11 age- and sex-matched patients receiving TAC (twice-daily [TD] group). The primary endpoint was a composite of death, graft loss, and drug discontinuation (treatment failure). Secondary endpoints were biopsy-proven rejection, malignancy, infection, and safety parameters determined on the basis of laboratory evaluations. In the OD and TD groups, the primary endpoint was reached by 18.2% and 45.54% of patients, respectively (P = .277). In detail, 3-year survivals were 90.0% and 70.0% (P = .291) and freedom from drug discontinuation 90.9% and 77.9% (P = .533), respectively. Freedom from biopsy-proven rejection, malignancy, and infection were similar between the groups. Moreover, biochemical parameters of kidney and liver function, hematologic parameters, and C-reactive protein levels were similar. Despite a remarkably higher prescribed dose, blood trough levels of TAC were below the lower target value in several patients of the OD group at the end of the follow-up period, but in none of the patients in the TD group. In conclusion, this small 3-year follow-up study suggests efficacy and safety in patients receiving TAC retard similar to those in patients receiving TAC. Nevertheless, the required dose of TAC retard for achieving acceptable blood trough levels should be investigated in more detail. PMID:23769094

Fuchs, U; Zittermann, A; Ensminger, S; Schulze, B; Hakim-Meibodi, K; Gummert, J; Schulz, U

2013-06-01

230

Unraveling the function of paralogs of the aldehyde dehydrogenase super family from Sulfolobus solfataricus.  

PubMed

Aldehyde dehydrogenases (ALDHs) have been well established in all three domains of life and were shown to play essential roles, e.g., in intermediary metabolism and detoxification. In the genome of Sulfolobus solfataricus, five paralogs of the aldehyde dehydrogenases superfamily were identified, however, so far only the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) and ?-ketoglutaric semialdehyde dehydrogenase (?-KGSADH) have been characterized. Detailed biochemical analyses of the remaining three ALDHs revealed the presence of two succinic semialdehyde dehydrogenase (SSADH) isoenzymes catalyzing the NAD(P)(+)-dependent oxidation of succinic semialdehyde. Whereas SSO1629 (SSADH-I) is specific for NAD(+), SSO1842 (SSADH-II) exhibits dual cosubstrate specificity (NAD(P)(+)). Physiological significant activity for both SSO-SSADHs was only detected with succinic semialdehyde and ?-ketoglutarate semialdehyde. Bioinformatic reconstructions suggest a major function of both enzymes in ?-aminobutyrate, polyamine as well as nitrogen metabolism and they might additionally also function in pentose metabolism. Phylogenetic studies indicated a close relationship of SSO-SSALDHs to GAPNs and also a convergent evolution with the SSADHs from E. coli. Furthermore, for SSO1218, methylmalonate semialdehyde dehydrogenase (MSDH) activity was demonstrated. The enzyme catalyzes the NAD(+)- and CoA-dependent oxidation of methylmalonate semialdehyde, malonate semialdehyde as well as propionaldehyde (PA). For MSDH, a major function in the degradation of branched chain amino acids is proposed which is supported by the high sequence homology with characterized MSDHs from bacteria. This is the first report of MSDH as well as SSADH isoenzymes in Archaea. PMID:23296511

Esser, D; Kouril, T; Talfournier, F; Polkowska, J; Schrader, T; Bräsen, C; Siebers, B

2013-01-08

231

Characterization of two closely related ?-amylase paralogs in the bark beetle, Ips typographus (L.).  

PubMed

Ips typographus (L.), the eight-spined spruce bark beetle, causes severe damage throughout Eurasian spruce forests and suitable nuclear markers are needed in order to study its population structure on a genetic level. Two closely related genes encoding ?-amylase in I. typographus were characterized and named AmyA and AmyB. Both ?-amylase paralogs consisted of six exons and five introns. AmyA encodes a polypeptide of 483 amino acids, whereas AmyB has two alternative transcripts encoding polypeptides of 483 and 370 amino acids. The expression levels of both genes were high during larval stage and adulthood. The AmyB transcripts were absent in the pupal stage. A modification of the allozyme staining method allowed us to detect two clusters of bands on the electrophoretic gel that may correspond to the two ?-amylase genes. There was a correlation between the lack of AmyB expression in pupa and the absence of the fast migrating isozyme cluster at this stage, suggesting that the faster migrating isoforms are products of the AmyB gene, whereas the slowly migrating bands are derived from the AmyA. PMID:21638308

Viktorinova, Ivana; Kucerova, Lucie; Bohmova, Marta; Henry, Ian; Jindra, Marek; Dolezal, Petr; Zurovcova, Martina; Zurovec, Michal

2011-06-02

232

Regulation of Drosophila Vasa In Vivo through Paralogous Cullin-RING E3 Ligase Specificity Receptors? †  

PubMed Central

In Drosophila species, molecular asymmetries guiding embryonic development are established maternally. Vasa, a DEAD-box RNA helicase, accumulates in the posterior pole plasm, where it is required for embryonic germ cell specification. Maintenance of Vasa at the posterior pole requires the deubiquitinating enzyme Fat facets, which protects Vasa from degradation. Here, we found that Gustavus (Gus) and Fsn, two ubiquitin Cullin-RING E3 ligase specificity receptors, bind to the same motif on Vasa through their paralogous B30.2/SPRY domains. Both Gus and Fsn accumulate in the pole plasm in a Vasa-dependent manner. Posterior Vasa accumulation is precocious in Fsn mutant oocytes; Fsn overexpression reduces ovarian Vasa levels, and embryos from Fsn-overexpressing females form fewer primordial germ cells (PGCs); thus, Fsn destabilizes Vasa. In contrast, endogenous Gus may promote Vasa activity in the pole plasm, as gus females produce embryos with fewer PGCs, and posterior accumulation of Vas is delayed in gus mutant oocytes that also lack one copy of cullin-5. We propose that Fsn- and Gus-containing E3 ligase complexes contribute to establishing a fine-tuned steady state of Vasa ubiquitination that influences the kinetics of posterior Vasa deployment.

Kugler, Jan-Michael; Woo, Jae-Sung; Oh, Byung-Ha; Lasko, Paul

2010-01-01

233

Mental Retardation; Its Social Context and Social Consequences.  

ERIC Educational Resources Information Center

Concerned with mental retardation as a social product, the following topics are discussed: mental retardation as a social phenomenon, the concept of the retarded as surplus population, labeling and incompetence in relation to life chances, mental retardation as deviance and as incompetence, and findings on the prevalence of retardation in the…

Farber, Bernard

234

Differential Expression of sigH Paralogs during Growth and under Different Stress Conditions in Mycobacterium smegmatis  

Microsoft Academic Search

Received 18 December 2008\\/Accepted 6 February 2009 SigH regulates a transcriptional network that responds to heat and oxidative stress in mycobacteria. Seven sigH paralogs are reported to exist in the Mycobacterium smegmatis genome. A comprehensive real-time reverse transcriptase PCR analysis during different stages of growth and upon exposure to various stress conditions and antimycobacterial compounds showed differential expression of sigH

Anirudh K. Singh; Bhupendra N. Singh

2009-01-01

235

Nuclear ribosomal pseudogenes resolve a corroborated monophyly of the eucalypt genus Corymbia despite misleading hypotheses at functional ITS paralogs.  

PubMed

Divergent paralogs can create both obstacles and opportunities for phylogenetic reconstruction. Phylogenetic relationships among eucalypt genera have been incongruent among datasets in previous studies, where morphological characters supported monophyly of the genus Corymbia, while intergenic spacers of the nuclear ribosomes (ITS) and chloroplast loci (trnL, trnH, psbA) showed Corymbia as either equivocal or paraphyletic. Ribosomal DNA occurs in multiple copies in a genome. We cloned and sequenced the nrITS to investigate if gene duplication was the cause of incongruence among trees in the eucalypts. Three ITS riboforms, two of them widespread, were recovered within some genomes. One of the ITS riboforms recovered a robust phylogeny showing Corymbia as a monophyletic genus, corroborating the evidence from morphology, fossil data, a recent ITS/ETS dataset and microsatellites (SSRs). Compelling evidence suggested that this divergent riboform is a pseudogene, i.e., non-functional paralog: comparatively lower GC content suggesting lower structural stability, deamination-like mutations at potential methylation sites, lack of conserved helices and hairpins and conspicuously lower thermodynamic stability in secondary structures. Phylogenies from the apparently functional riboform retained Corymbia as paraphyletic. We show here that pseudogenes can recover a well-corroborated phylogeny whereas their functional paralogs show misleading hypotheses. We explain that phylogenetic signals may be obscured when functional constraints in ITS necessitate compensatory mutations in the secondary structure helices involved in RNA transcription, whereas pseudogenes mutate under neutrality. PMID:17570687

Ochieng, Joel W; Henry, Robert J; Baverstock, Peter R; Steane, Dorothy A; Shepherd, Mervyn

2007-05-06

236

Petal-specific subfunctionalization of an APETALA3 paralog in the Ranunculales and its implications for petal evolution.  

PubMed

• The petals of the lower eudicot family Ranunculaceae are thought to have been derived many times independently from stamens. However, investigation of the genetic basis of their identity has suggested an alternative hypothesis: that they share a commonly inherited petal identity program. This theory is based on the fact that an ancient paralogous lineage of APETALA3 (AP3) in the Ranunculaceae appears to have a conserved, petal-specific expression pattern. • Here, we have used a combination of approaches, including RNAi, comparative gene expression and molecular evolutionary studies, to understand the function of this petal-specific AP3 lineage. • Functional analysis of the Aquilegia locus AqAP3-3 has demonstrated that the paralog is required for petal identity with little contribution to the identity of the other floral organs. Expanded expression studies and analyses of molecular evolutionary patterns provide further evidence that orthologs of AqAP3-3 are primarily expressed in petals and are under higher purifying selection across the family than the other AP3 paralogs. • Taken together, these findings suggest that the AqAP3-3 lineage underwent progressive subfunctionalization within the order Ranunculales, ultimately yielding a specific role in petal identity that has probably been conserved, in stark contrast with the multiple independent origins predicted by botanical theories. PMID:21557746

Sharma, Bharti; Guo, Chunce; Kong, Hongzhi; Kramer, Elena M

2011-05-09

237

Cyclic phosphines as flame retardants  

US Patent & Trademark Office Database

The present invention is related to the use of specific cyclic and/or polymeric aryl-phosphines as flame retardants and to a method for reducing the flammability of organic material by incorporating into the material these specific cyclic and/or polymeric phosphines. Moreover, the invention is related to a polymeric composition containing a polymeric material and at least one of the specific cyclic and/or polymeric phosphines in an amount of from 1 to 15% by weight, based on the weight of the polymeric material. The invention also relates to a composition comprising at least one of the specific cyclic and/or polymeric phosphines and at least one polymerizable monomer.

2013-08-27

238

The Texas Plan to Combat Mental Retardation.  

ERIC Educational Resources Information Center

The Texas state plan of action against mental retardation is presented. Aspects considered include the evolution of the plan, the role of the health services, medical aspects of retardation, education and training, vocational rehabilitation and employment, and social welfare. Also surveyed are the following: residential and day care, manpower,…

Governor's Advisory Committee on Mental Retardation Planning, Austin, TX.

239

Retinal Detachment in the Mentally Retarded  

Microsoft Academic Search

Purpose: To report the clinical features and surgical outcomes of retinal detachment in mentally retarded patients.Methods: Retrospective review of records of mentally retarded patients who had retinal reattachment surgery at the authors' institutions between February 1994 and February 2000. There were 8 patients with 13 surgically treated eyes. Demographic and clinical data were abstracted from the patients' medical records.Results: The

Rika Kuwabara; Atsushi Minamoto; Ken Yamane; Tetsu Kajikawa; Hideaki Mizote; Hiromu K Mishima

2003-01-01

240

Schizophrenia in Mental Retardation: Clinical Features.  

ERIC Educational Resources Information Center

The literature on schizophrenia in individuals with mental retardation is reviewed, and the clinical features, symptomatology, diagnostic parameters, and treatment approaches are briefly discussed. Data are presented about prevalence rates, degree of mental retardation, male/female distribution, and age of onset. (Author/PB)

Reid, Andrew H.

1989-01-01

241

Long Term Memory in Normals and Retardates.  

ERIC Educational Resources Information Center

|The study sought to determine if relationships existed among Piagetian measures of reasoning and memory, and if development of the memory process in normals and retardates is identical. Subjects were 48 normals (IQ 90-110) and 48 retardates (IQ 50-75), all CA 8-20 years. A battery of assessments, including conservation, spatial imagery, and…

McLaughlin, John A.; Stephens, Will Beth

242

Counseling the Mentally Retarded: A Psychoeducational Perspective.  

ERIC Educational Resources Information Center

The paper suggests that a cognitive or psychoeducational perspective is valuable in counseling mentally retarded individuals. Psychoeducational considerations in pretreatment assessment, with an emphasis on process rather than product, are noted; and it is explained that counseling of mentally retarded persons can be enhanced through the use of…

Spragg, Paul A.

243

IQ changes in hospitalized mental retardates  

Microsoft Academic Search

Analyzed changes in ca, ma, and iq in 324 representative patients in a hospital for the mentally retarded. Results indicate that A. Silverstein's (see pa, vol. 43:8600) cross-sectional equation relating iq to hospital age better fits the data than does his semilongitudinal equation. Further analysis shows that decrement in iq in mentally retarded ss is due primarily to increases in

Robert T. Ross

1971-01-01

244

Growth-retarded fetuses and pulmonary maturity.  

PubMed

The amniotic fluid of 250 patients in the third trimester of pregnancy was examined for surfactant content by means of the bubble test and total phospholipid estimation. No evidence was found that intra-uterine growth retardation accelerates pulmonary maturity in the fetus, and the finding of early pulmonary maturity does not indicate intrauterine growth retardation. PMID:581621

Gunston, K D; Davey, D A

1978-09-16

245

Fire Retardant Wood-Fiber Insulating Board  

Microsoft Academic Search

Two types of fire retardant insulating wood-fiber boards have been developed in laboratory and mill scale. Both include treatments which are incorporated in the normal wet process for manufacturing such boards with a concentration of the fire retardant to one side of the board. One type involves addition of a calcium borate mineral, colemanite, to the top fiber layer of

Birgit A. L. Östman

1984-01-01

246

Teaching Arithmetic to Mentally Retarded Children.  

ERIC Educational Resources Information Center

The effect of mental retardation on the learning of arithmetic is considered; the school program, beginning instruction, and the instructional method are described. Also discussed are methods of developing interest, using instructional games, teaching left to right, teaching for meaning, adapting arithmetic to the trainable retarded, and planning…

Thomas, Janet K.

247

Problems of Psychology of Mentally Retarded Children.  

ERIC Educational Resources Information Center

|Presented are 18 papers on problems in the psychology of mentally retarded children. Seven of the papers are in English, two in French, and nine in Russian. The English papers are concerned with the following topics: peculiarities of psychic functions in oligophrenic (retarded) children with pronounced underdevelopment of frontal lobes of…

Academy of Pedagogical Sciences of the USSR, Moscow. Inst. of Defectology.

248

The Mentally Retarded Offender and Corrections.  

ERIC Educational Resources Information Center

The booklet provides an overview of the issues involved in correctional rehabilitation for the mentally retarded offender. Reviewed are clinical and legal definitions of criminal behavior and retardation, and discussed are such issues as law enforcement and court proceedings problems, pros and cons of special facilities, labeling, normalization,…

Santamour, Miles; West, Bernadette

249

UNDERSTANDING AND HELPING THE RETARDED READER.  

ERIC Educational Resources Information Center

|THE PROCEEDINGS OF A 1962 STATEWIDE ARIZONA CONFERENCE ON READING DEVELOPMENT AND READING DIFFICULTIES INCLUDE 15 PAPERS. ARTICLES ON THE ABLE RETARDED READER ARE "UNDERSTANDING THE ABLE RETARDED READER" BY HELEN M. ROBINSON, AND "CLASSROOM PROCEDURES" BY ROSEMARY YOAKUM. PAPERS ON EMOTIONALLY DISTURBED CHILDREN ARE "IDENTIFICATION OF EMOTIONAL…

STRANG, RUTH, ED.

250

Semistability of retarded functional differential equations  

Microsoft Academic Search

In this paper, we develop a semistability analy- sis framework for retarded functional differential equations (RFDE) having a continuum of equilibria with time-varying parameters and delays with applications to stability analysis of multiagent dynamic networks with consensus protocols in the presence of unknown heterogeneous time-varying delays and parameters along the communication links. We show that for such a retarded functional

Qing Hui

2011-01-01

251

Teaching Physical Education to Mentally Retarded Children.  

ERIC Educational Resources Information Center

Methods for teaching physical education activities and skills to mentally retarded children are presented. General objectives are listed and the physical education program is outlined. Hints are offered for teaching the retarded child; and basic skills and rhythms are described. The following are then described; rhythm games, a volleyball unit and…

Davis, Patricia A.

252

A Simple Cylindrical Retarding Field Energy Analyzer  

Microsoft Academic Search

A simple cylindrical retarding electron energy analyzer (CREA) with a retarding field was designed on the basis of a calculation of the potential distribution and the electron trajectories. A prototype analyzer was constructed and the performance was examined. The resolution obtained was about 0.3% at the FWHM at the electron energy of 500 eV, which was in fairly good agreement

Yasuo Fujii; Eiji Ishiguro; Tadayoshi Kitada

1990-01-01

253

Political Philosophy and the Mentally Retarded.  

ERIC Educational Resources Information Center

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…

Stanovich, Keith E.

254

Body Awareness in Children with Mental Retardation  

ERIC Educational Resources Information Center

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…

Simons, Johan; Dedroog, Inge

2009-01-01

255

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

SciTech Connect

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.

Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori [Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264 (United States); Anver, Miriam R. [Pathology/Histotechnology Laboratory, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702-1201 (United States); Bera, Tapan K. [Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264 (United States); Pastan, Ira [Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264 (United States)], E-mail: pastani@mail.nih.gov

2008-01-25

256

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 false Mental retardation and personality disorders. 4.127 Section 4.127 Pensions...4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are not diseases or...

2009-07-01

257

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Mental retardation and personality disorders. 4.127 Section 4.127 Pensions...4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are not diseases or...

2010-07-01

258

Fire-Retardant Decorative Inks for Aircraft Interiors.  

National Technical Information Service (NTIS)

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...

D. A. Kourtides Z. Nir J. A. Mikroyannidis

1985-01-01

259

[X-linked alpha-thalassemia/mental retardation syndrome].  

PubMed

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X syndrome, OMIM #301040) is one of the syndromes associated with abnormal epigenetic gene regulation, including ICF(DNMT3B), Rett (MECP2), Rubinstein-Taybi (CBP), Coffin-Lowry (RSK2), and Sotos (NSD1) syndromes. It is a syndromic form of X-linked mental retardation, which affects males and is characterized by profound mental retardation, mild HbH disease (alpha-thalassemia), facial dysmorphism, skeletal abnormalities, and autistic behavior. ATR-X syndrome is caused by a mutation in the ATRX gene on the X chromosome (Xq13), which encodes ATRX protein, belonging to the SNF2 family of chromatin-remodeling proteins. The protein has two functionally important domains: an ADD (ATRX-DNMT3-DNMT3L) domain at the N-terminus, and chromatin-remodeling domain in the C-terminal half, where the ATRX gene mutations of most ATR-X patients reside. Perturbation in DNA methylation in the rDNA genes was repored in ATR-X patients, and ATRX protein is presumed to be involved in the establishment and maintenance of DNA methylation. Based on its various clinical phenotypes, the expressions of many genes, including alpha globin genes, seem to be abnormally regulated in ATR-X patients. However, the precise mechanism involving ATRX protein remains to be elucidated. Epigenetics can link environmental and genetic causes of many pathological conditions. The genes, which are abnormally regulated by a perturbed epigenetic mechanism, are, in themselves, structurally normal, and the elucidation of their mechanism may lead to the development of appropriate therapy. PMID:19489441

Wada, Takahito

2009-04-01

260

Pediatricians' perceptions of mentally retarded individuals.  

PubMed

Three hundred randomly selected members of the American Academy of Pediatrics were surveyed to determine their perceptions of mildly, moderately, and severely mentally retarded individuals. For each of the three categories of mental retardation, pediatricians completed the Prognostic Beliefs Scale which consisted of 27 functional capabilities and choices of residential and vocational placement. Of the 169 (56%) questionnaires returned, 142 (47%) were available for analysis. The pediatricians' perceptions were different for mildly, moderately, and severely retarded individuals. Most pediatricians believed mildly retarded individuals could do all but tasks requiring judgment, could function in unskilled competitive employment, and were likely to live in their own apartments. They believed that those with moderate retardation were limited in their capacity to simple and supervised tasks, could function in sheltered workshops, and were likely to live in group-home settings. They believed that severely retarded individuals were restricted to simple feeding tasks and following one-stage commands, were not capable of any productive employment, and would most likely live in institutions. Pediatric expectations and prognostications for placements were significantly lower than those of other professionals caring for mentally retarded individuals. PMID:3670966

Wolraich, M L; Siperstein, G N; O'Keefe, P

1987-11-01

261

Intrauterine growth retardation leads to a permanent nephron deficit in the rat  

Microsoft Academic Search

Intrauterine growth retardation (IUGR) was induced in Sprague-Dawley rats by partial artery ligation of one uterine horn in the mother on day 17 of gestation or by feeding the mother a 5% protein diet from day 8 of gestation. The controls were pups of the contralateral uterine horn or pups born to mothers fed a normal (22%) protein diet. The

Claudie Merlet-Bénichou; Thierry Gilbert; Martine Muffat-Joly; Martine Lelièvre-Pégorier; Bruno Leroy

1994-01-01

262

Engineering Flame Retardant Biodegradable Nanocomposites  

NASA Astrophysics Data System (ADS)

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.

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

263

Detection of malingered mental retardation.  

PubMed

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 group of 25 community volunteers was instructed to malinger MR (CVM) during testing. CVM participants obtained Wechsler Adult Intelligence Scale (3rd ed.; D. Wechsler, 1997) Full Scale Intelligence Quotient scores that were significantly lower than the demographically similar CVH group but comparable to the MR group, suggesting that CVM subjects feigned cognitive impairment. On the basis of standard cutting scores from test manuals or published articles, of the 11 feigning measures administered, only the Test of Memory Malingering (TOMM; T. N. Tombaugh, 1996) retention trial had a specificity rate >.90 in the MR group. However, the 2nd learning trial of the TOMM, as well as a short form of the Digit Memory Test (T. J. Guilmette, K. J. Hart, A. J. Guiliano, & B. E. Leininger, 1994), approached this level of specificity, with both at .88. These results raise concerns about the specificity rates at recommended cutting scores of commonly used feigning tests in defendants with MR. PMID:20230151

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

2010-03-01

264

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

PubMed Central

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.

Pearce, E M; Liepins, R

1975-01-01

265

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...

266

Mechanistic Studies of Phosphorus Containing Flame Retardants.  

National Technical Information Service (NTIS)

A combination of mass spectrometric and optical spectroscopic studies has been made to establish a mechanism for phosphorus controlled flame retardancy in thermoplastics. It is shown that a vapor phase mode of flame inhibition can account for the known fl...

C. L. McBee J. W. Hastie

1976-01-01

267

Teaching mending skills to mentally retarded adolescents.  

PubMed

This experiment presents a model for analyzing community living skills and teaching them to mentally retarded adolescents. A task analysis of three mending skills was developed and validated, aided by consultation with persons having expertise in home economics and mental retardation. The task analysis was modified to compensate for the constraints imposed by the trainees' disabilities. Five moderately retarded youths received training on sewing hems, buttons, and seams. Sewing skills were acquired rapidly and maintained. The behavior generalized from trained to untrained tasks on their common components for all subjects. A multiple baseline across participants combined with a multiple baseline across responses demonstrated the combined effectiveness of an objectively validated, detailed task analysis; graduated sequence of prompts; and response consequences in training and maintaining community living skills with mentally retarded adolescents. PMID:117004

Cronin, K A; Cuvo, A J

1979-01-01

268

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...

269

Epilepsy, Mental Retardation, and Anticonvulsant Therapy.  

ERIC Educational Resources Information Center

|Inappropriate or inadequately documented medication for patients in mental retardation institutions is a major medical and economic problem. Within a 127-patient ward, 41 patients were treated with anticonvulsants. Of these patients, 24 had no documented indications for usage. (Author)|

Kaufman, Kenneth Roland; Katz-Garris, Lynda

1979-01-01

270

Satellite Sheltered Workshops for Retarded Adults.  

National Technical Information Service (NTIS)

In 1964 the Association for the Help of Retarded Children (AHRC) in New York City initiated a demonstration of extending sheltered employment to satellite branches in Brooklyn and Queens. Clients, referred from the AHRC Training Center in Manhattan were t...

M. Dubrow

1975-01-01

271

Sterilization of Persons with Mental Retardation.  

ERIC Educational Resources Information Center

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)

Elkins, Thomas E.; Andersen, H. Frank

1992-01-01

272

Self-Recognition in Retarded Children.  

ERIC Educational Resources Information Center

Using the objective technique of increased mark-directed responses as evidence of self-recognition, this study investigated the relationship between cognitive and affective development among young retarded children. (Author/MP)

Hill, Suzanne D.; Tomlin, Cynthia

1981-01-01

273

Quality of Learning of Severely Retarded Adolescents.  

ERIC Educational Resources Information Center

A modified discrimination reversal task was employed to assess the quality of learning of severely retarded adolescents. In comparison to earlier findings with nonhuman primates, results were interpreted as indicative of mediational learning processes. (Author)

Meador, Darlene M.; Rumbaugh, Duane M.

1981-01-01

274

Physical Education: Equipment for Teaching the Retarded  

ERIC Educational Resources Information Center

Equipment designed to help mentally retarded students develop flexibility, eye-hand and eye-foot coordination, muscle coordination, body balance and control, and social involvement in their peer group. (Author/MLF)

Chaya, John

1976-01-01

275

X-linked mental retardation 2  

SciTech Connect

This book contains papers on X-linked mental retardation. Chapters include clinical aspects; cytogenetic aspects; DNA and lineage; genetics and segregation; epidemiology and genetics; cytogenetics and fragile site expression.

Opitz, J.M.; Reynolds, J.F.; Spano, L.M. (Shodair Children's Hospital, Helena, MT (US))

1986-01-01

276

Identification of the Polyhydroxyalkanoate (PHA)Specific Acetoacetyl Coenzyme A Reductase among Multiple FabG Paralogs in Haloarcula hispanica and Reconstruction of the PHA Biosynthetic Pathway in Haloferax volcanii  

Microsoft Academic Search

Genome-wide analysis has revealed abundant FabG (-ketoacyl-ACP reductase) paralogs, with uncharac- terized biological functions, in several halophilic archaea. In this study, we identified for the first time that the fabG1 gene, but not the other five fabG paralogs, encodes the polyhydroxyalkanoate (PHA)-specific acetoacetyl coenzyme A (acetoacetyl-CoA) reductase in Haloarcula hispanica. Although all of the paralogous fabG genes were actively transcribed,

Jing Han; Qiuhe Lu; Ligang Zhou; Hailong Liu; Hua Xiang

2009-01-01

277

Influence of Retardants to Burning Lignocellulosic Materials  

NASA Astrophysics Data System (ADS)

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.

Tureková, Ivana; Harangozó, Jozef; Martinka, Jozef

2011-01-01

278

Thermally Stable and Flame Retardant Elastomeric Nanocomposites  

Microsoft Academic Search

\\u000a This chapter is dedicated to thermally stable and flame retardant elastomeric composites. Two approaches are considered: the\\u000a synthesis of elastomeric nanocomposites, where the nanoparticles are dispersed at the nanoscale, and the incorporation of\\u000a nanofillers at high loadings where agglomerate of nanoparticles are observed in the elastomeric matrix. The chapter is mainly\\u000a focused on the key parameter influencing the flame retardancy,

O. Cerin; G. Fontaine; S. Duquesne; S. Bourbigot

279

Diagnosis and Management of Intrauterine Growth Retardation  

Microsoft Academic Search

Intrauterine growth retardation (IUGR) is associated with significant perinatal morbidity and mortality. This condition can be a sign of genetic disorders, fetal infection, uteroplacental insufficiency, or constitutionally small fetuses. Correct determination of gestational age is the first step in prenatal screening of growth-retarded fetuses. The discovery of a small-for-gestational age fetus necessitates fetal assessment for the evaluation of the etiology

J. Lepercq; D. Mahieu-Caputo

1998-01-01

280

Mental retardation and inborn errors of metabolism  

Microsoft Academic Search

Summary  In countries where clinical phenylketonuria is detected by newborn screening inborn errors of metabolism are rare causes of\\u000a isolated mental retardation. There is no international agreement about what type of metabolic tests must be applied in patients\\u000a with unspecific mental retardation. However, and although infrequent, there are a number of inborn errors of metabolism that\\u000a can present in this way.

A. García-Cazorla; N. I. Wolf; M. Serrano; U. Moog; B. Pérez-Dueñas; P. Póo; M. Pineda; J. Campistol; G. F. Hoffmann

2009-01-01

281

High-density linkage mapping and evolution of paralogs and orthologs in Salix and Populus  

PubMed Central

Background Salix (willow) and Populus (poplar) are members of the Salicaceae family and they share many ecological as well as genetic and genomic characteristics. The interest of using willow for biomass production is growing, which has resulted in increased pressure on breeding of high yielding and resistant clones adapted to different environments. The main purpose of this work was to develop dense genetic linkage maps for mapping of traits related to yield and resistance in willow. We used the Populus trichocarpa genome to extract evenly spaced markers and mapped the orthologous loci in the willow genome. The marker positions in the two genomes were used to study genome evolution since the divergence of the two lineages some 45 mya. Results We constructed two linkage maps covering the 19 linkage groups in willow. The most detailed consensus map, S1, contains 495 markers with a total genetic distance of 2477 cM and an average distance of 5.0 cM between the markers. The S3 consensus map contains 221 markers and has a total genetic distance of 1793 cM and an average distance of 8.1 cM between the markers. We found high degree of synteny and gene order conservation between willow and poplar. There is however evidence for two major interchromosomal rearrangements involving poplar LG I and XVI and willow LG Ib, suggesting a fission or a fusion in one of the lineages, as well as five intrachromosomal inversions. The number of silent substitutions were three times lower (median: 0.12) between orthologs than between paralogs (median: 0.37 - 0.41). Conclusions The relatively slow rates of genomic change between willow and poplar mean that the genomic resources in poplar will be most useful in genomic research in willow, such as identifying genes underlying QTLs of important traits. Our data suggest that the whole-genome duplication occurred long before the divergence of the two genera, events which have until now been regarded as contemporary. Estimated silent substitution rates were 1.28 × 10-9 and 1.68 × 10-9 per site and year, which are close to rates found in other perennials but much lower than rates in annuals.

2010-01-01

282

The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-?-lysine.  

PubMed

The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with ?-lysine at low efficiency. Cell-free extracts containing non-?-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of ?-lysine, a substrate also predicted by genomic analyses. EF-P was efficiently functionally modified with (R)-?-lysine but not (S)-?-lysine or genetically encoded ?-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases. PMID:21841797

Roy, Hervé; Zou, S Betty; Bullwinkle, Tammy J; Wolfe, Benjamin S; Gilreath, Marla S; Forsyth, Craig J; Navarre, William W; Ibba, Michael

2011-08-14

283

Including Children with Mental Retardation in the Religious Community.  

ERIC Educational Resources Information Center

|This article describes practical strategies for promoting inclusion in religious programs. Strategies are provided for including children with mental disabilities, mild mental retardation, moderate mental retardation, and severe to profound mental retardation, and older students with mental retardation. Strategies are also provided for preparing…

Collins, Belva C.; Epstein, Ann; Reiss, Toni; Lowe, Verna

2001-01-01

284

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

ERIC Educational Resources Information Center

|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…

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

285

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

ERIC Educational Resources Information Center

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…

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

286

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 Central

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 [1], [2], [3]. 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.

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

2012-01-01

287

Intrauterine radiation exposures and mental retardation  

SciTech Connect

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.

Miller, R.W.

1988-08-01

288

Diversity and Evolution of Coral Fluorescent Proteins  

Microsoft Academic Search

GFP-like fluorescent proteins (FPs) are the key color determinants in reef-building corals (class Anthozoa, order Scleractinia) and are of considerable interest as potential genetically encoded fluorescent labels. Here we report 40 additional members of the GFP family from corals. There are three major paralogous lineages of coral FPs. One of them is retained in all sampled coral families and is

Naila O. Alieva; Karen A. Konzen; Steven F. Field; Ella A. Meleshkevitch; Marguerite E. Hunt; Victor Beltran-Ramirez; David J. Miller; Jörg Wiedenmann; Anya Salih; Mikhail V. Matz; Hany A. El-Shemy

2008-01-01

289

Expression pattern of two paralogs of the PI/GLO-like locus during Orchis italica (Orchidaceae, Orchidinae) flower development.  

PubMed

The class B MADS-box genes belong to two distinct functional groups: the AP3/DEF-like and the PI/GLO-like sub-families. In orchids, AP3/DEF-like genes are present in four copies, each with a different role in floral organ formation, which is described in the "orchid code" model. Interestingly, the orchid PI/GLO-like genes are present in two copies in Orchidinae, whereas they are described as single copy in the other orchid lineages. The two PI/GLO-like paralogs have site-specific different selective constraints; in addition, they show relaxation of purifying selection when compared to the single-copy lineages. In this study, we present a comparative analysis of the expression patterns of the two PI/GLO-like paralogs, OrcPI and OrcPI2, in floral tissues of Orchis italica in different developmental stages using real-time PCR. The two genes show similar expression profiles in the tissue examined, with differences detectable between immature and mature inflorescence. In all cases, OrcPI2 is expressed at a higher level than OrcPI. Real-time PCR results reveal that the co-expression of the two duplicated loci could have a fully or partially redundant function. The possible evolutionary fate of OrcPI and OrcPI2 is discussed as well as their involvement in ovary development. PMID:21892737

Salemme, Marinella; Sica, Maria; Gaudio, Luciano; Aceto, Serena

2011-09-04

290

Recent Research Progress on the Flame-Retardant Mechanism of Halogen-Free Flame Retardant Polypropylene  

Microsoft Academic Search

Polypropylene (PP) is one of the five kinds of universal polymers that have greatly improved our life qualities. While a pestilent limitation of PP is its flammability. Usually, halogen-containing flame retardants (FRs) are used to improve its flame retard ability. However, the halogen-containing FRs are limited more and more strictly because they would produce environment problems, such as the release

Jianjun Wang; Li Wang; Anguo Xiao

2009-01-01

291

The X-linked intellectual disability protein IL1RAPL1 regulates excitatory synapse formation by binding PTP? and RhoGAP2  

PubMed Central

Mutations of the Interleukin-1-receptor accessory protein like 1 (IL1RAPL1) gene are associated with cognitive impairment ranging from non-syndromic X-linked mental retardation to autism. IL1RAPL1 belongs to a novel family of IL1/Toll receptors, which is localized at excitatory synapses and interacts with PSD-95. We previously showed that IL1RAPL1 regulates the synaptic localization of PSD-95 by controlling c-Jun N-terminal kinase activity and PSD-95 phosphorylation. Here, we show that the IgG-like extracellular domains of IL1RAPL1 induce excitatory pre-synapse formation by interacting with protein tyrosine phosphatase delta (PTP?). We also found that IL1RAPL1 TIR domains interact with RhoGAP2, which is localized at the excitatory post-synaptic density. More interestingly, the IL1RAPL1/PTP? complex recruits RhoGAP2 at excitatory synapses to induce dendritic spine formation. We also found that the IL1RAPL1 paralog, IL1RAPL2, interacts with PTP? and induces excitatory synapse and dendritic spine formation. The interaction of the IL1RAPL1 family of proteins with PTP? and RhoGAP2 reveals a pathophysiological mechanism of cognitive impairment associated with a novel type of trans-synaptic signaling that regulates excitatory synapse and dendritic spine formation.

Valnegri, Pamela; Montrasio, Chiara; Brambilla, Dario; Ko, Jaewon; Passafaro, Maria; Sala, Carlo

2011-01-01

292

Plasma impregnation of wood with fire retardants  

NASA Astrophysics Data System (ADS)

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.

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

2012-02-01

293

Depolarization and retardation of a birefringent slab.  

PubMed

Mueller matrices for normal transmission of light through a birefringent slab are formulated to analyze retardation and depolarization. A finite wave band, wedge slab, and microroughness may cause a spread in retardance, which in turn produces depolarization. The spectra of depolarization, cross-polarized transmittance, and retardance by rotating-analyzer ellipsometry are simulated for the quasi-monochromatic effect with a finite bandwidth. These spectra agree excellently with the measured spectra for a sapphire slab. The depolarization spectrum simulated for the wedge effect fits the measured spectrum in the long-wave region but is too small in the short-wave region. The depolarization simulated for incoherent multiple reflections demonstrates the oscillating structure, which is small compared with the measured depolarization. The finite bandwidth effect contributes more than the other effects to the measured depolarization of a sapphire slab. PMID:11059604

Nee, S M

2000-11-01

294

History of mental retardation: an essay review.  

PubMed

The history of mental retardation previously focused on residential institutions and the ideas of professionals. Given that the vast majority of people with mental retardation lived in their family homes or other locations in their communities, this emphasis has been misleading. Recent historical studies by James W. Trent Jr.; Philip M. Ferguson; Steven Noll; and the British scholars in David Wright and Anne Digby's collection, From Idiocy to Mental Deficiency, have opened up the field by describing the complicated relationships between families and the state, by outlining the development of lay concepts of mental disabilities, and by acknowledging the wide diversity of experiences of people with mental disabilities. PMID:11623617

Brockley, J A

1999-02-01

295

Patterned retarder films using reactive mesogen technology  

NASA Astrophysics Data System (ADS)

A range of polymerisable liquid crystals mixtures have been developed (so called, Reactive Mesogen) that are ideally suited for the fabrication of patterned retarder films. Such films, made using a combination of Merck Reactive Mesogen Mixtures coated on a plastic substrate containing a photoalignment layer, are commercially employed to produce 3D displays. Different methods of patterning Reactive Mesogen Mixtures are discussed and the merits of each considered. Although the first commercial products use normal dispersion Reactive Mesogen Materials, the advantages of using the next generation of materials, which have improved wavelength dispersion, are introduced with a focus on their use in 3D patterned retarder films.

Parri, Owain; Smith, Graham; Harding, Richard; Yoon, Hyun-Jin; Gardiner, Iain; Sargent, Joe; Skjonnemand, Karl

2011-02-01

296

Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).  

PubMed

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates. However, frogs are relatively insensitive to TCDD toxicity, especially during early life stages. Toxicity of TCDD and related halogenated aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AhR), and specific differences in properties of the AhR signaling pathway can underlie in TCDD toxicity in different species. This study investigated the role of AhR in frog TCDD insensitivity, using Xenopus laevis as a model system. X. laevis, a pseudotetraploid species, expresses two distinct AhR1 genes, AhR1alpha and AhR1beta. Sharing 86% amino acid identity, these likely represent distinct genes, both orthologous to mammalian AhR and paralogous to the AhR2 gene(s) in most fish. Both AhR1alpha and AhR1beta exhibit TCDD-dependent binding of cognate DNA sequences, but they bind TCDD with at least 20-fold lower affinity than the mouse AhR(b-1) protein, and they are similarly less responsive in TCDD-induced reporter gene induction in conjunction with the mouse CYP1A1 promoter. Furthermore, CYP1A6 and CYP1A7 induction by TCDD in cultured X. laevis A6 cells appears much less responsive than CYP1A induction in cell lines derived from more sensitive animals. Taken together, these data suggest that low affinity binding by X. laevis AhRs plays an important mechanistic role in the insensitivity of frogs to TCDD. An understanding of these molecular mechanisms should aid amphibian ecotoxicology and refine the use of frog embryos as a model [e.g. in FETAX (Frog Embryo Teratogenesis Assay-Xenopus)] for determining developmental toxicity of samples containing dioxin-like compounds. PMID:15958654

Lavine, Jeremy A; Rowatt, Ashley J; Klimova, Tatyana; Whitington, Aric J; Dengler, Emelyne; Beck, Catherine; Powell, Wade H

2005-06-15

297

Nrf2b, Novel Zebrafish Paralog of Oxidant-responsive Transcription Factor NF-E2-related Factor 2 (NRF2)*  

PubMed Central

NF-E2-related factor 2 (NRF2; also called NFE2L2) and related NRF family members regulate antioxidant defenses by activating gene expression via antioxidant response elements (AREs), but their roles in embryonic development are not well understood. We report here that zebrafish (Danio rerio), an important developmental model species, possesses six nrf genes, including duplicated nrf1 and nrf2 genes. We cloned a novel zebrafish nrf2 paralog, nrf2b. The predicted Nrf2b protein sequence shares several domains with the original Nrf2 (now Nrf2a) but lacks the Neh4 transactivation domain. Zebrafish-human comparisons demonstrate conserved synteny involving nrf2 and hox genes, indicating that nrf2a and nrf2b are co-orthologs of human NRF2. nrf2a and nrf2b displayed distinct patterns of expression during embryonic development; nrf2b was more highly expressed at all stages. Embryos in which Nrf2a expression had been knocked down with morpholino oligonucleotides were more sensitive to tert-butylhydroperoxide but not tert-butylhydroquinone, whereas knockdown of Nrf2b did not affect sensitivity of embryos to either chemical. Gene expression profiling by microarray identified a specific role for Nrf2b as a negative regulator of several genes, including p53, cyclin G1, and heme oxygenase 1, in embryos. Nrf2a and Nrf2b exhibited different mechanisms of cross-talk with the Ahr2 signaling pathway. Together, these results demonstrate distinct roles for nrf2a and nrf2b, consistent with subfunction partitioning, and identify a novel negative regulatory role for Nrf2b during development. The identification of zebrafish nrf2 co-orthologs will facilitate new understanding of the multiple roles of NRF2 in protecting vertebrate embryos from oxidative damage.

Timme-Laragy, Alicia R.; Karchner, Sibel I.; Franks, Diana G.; Jenny, Matthew J.; Harbeitner, Rachel C.; Goldstone, Jared V.; McArthur, Andrew G.; Hahn, Mark E.

2012-01-01

298

Aryl Hydrocarbon Receptors in the frog Xenopus laevis: Two AHR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)  

PubMed Central

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates. However, frogs are relatively insensitive to TCDD toxicity, especially during early life stages. Toxicity of TCDD and related halogenated aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AHR), and specific differences in properties of the AHR signaling pathway can underlie differences in TCDD toxicity in different species. This study investigated the role of AHR in frog TCDD insensitivity, using Xenopus laevis as a model system. X. laevis, a pseudotetraploid species, expresses two distinct AHR1 genes, AHR1? and AHR1?. Sharing 86% amino acid identity, these likely represent distinct genes, both orthologous to mammalian AHR and paralogous to the AHR2 gene(s) in most fish. Both AHR1? and AHR1? exhibit TCDD-dependent binding of cognate DNA sequences, but they bind TCDD with at least 20-fold lower affinity than the mouse AHRb-1 protein, and they are similarly less responsive in TCDD-induced reporter gene induction in conjunction with the mouse CYP1A1 promoter. Furthermore, CYP1A6 and CYP1A7 induction by TCDD in cultured X. laevis A6 cells appears much less responsive than CYP1A induction in cell lines derived from more sensitive animals. Taken together, these data suggest that low affinity binding by X. laevis AHRs plays an important mechanistic role in the insensitivity of frogs to TCDD. An understanding of these molecular mechanisms should aid amphibian ecotoxicology and refine the use of frog embryos as a model [e.g. in FETAX (Frog Embryo Teratogenesis Assay-Xenopus)] for determining developmental toxicity of samples containing dioxin-like compounds.

Lavine, Jeremy A.; Rowatt, Ashley J.; Klimova, Tatyana; Whitington, Aric J.; Dengler, Emelyne; Beck, Catherine; Powell, Wade H.

2005-01-01

299

Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21-q22  

PubMed Central

Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under accession nos. AB045357–AB045365.

Shiina, Takashi; Ando, Asako; Suto, Yumiko; Kasai, Fumio; Shigenari, Atsuko; Takishima, Nobusada; Kikkawa, Eri; Iwata, Kyoko; Kuwano, Yuko; Kitamura, Yuka; Matsuzawa, Yumiko; Sano, Kazumi; Nogami, Masahiro; Kawata, Hisako; Li, Suyun; Fukuzumi, Yasuhito; Yamazaki, Masaaki; Tashiro, Hiroyuki; Tamiya, Gen; Kohda, Atsushi; Okumura, Katsuzumi; Ikemura, Toshimichi; Soeda, Eiichi; Mizuki, Nobuhisa; Kimura, Minoru; Bahram, Seiamak; Inoko, Hidetoshi

2001-01-01

300

Thermal and flame retardant properties of novel intumescent flame retardant low-density polyethylene (LDPE) composites  

Microsoft Academic Search

A char-forming agent (CFA) and silica-gel-microencapsulated ammonium polyphosphate (MCAPP) were selected to form novel intumescent\\u000a flame retardant system (IFRs), and then the influence of this novel IFRs on the thermal and flame retardant properties of\\u000a low-density polyethylene (LDPE) were studied. The results of cone calorimetry show that the flame retardant properties of\\u000a LDPE with 30 wt% novel IFR (CFA\\/MCAPP = 1:3) improve remarkably.

Shibin Nie; Mingxu Zhang; Shujie Yuan; Guanglong Dai; Ningning Hong; Lei Song; Yuan Hu; Xueli Liu

301

Organ transplantation, organ donation and mental retardation  

Microsoft Academic Search

We reviewed the literature on accessibility and outcomes of organ transplantation in individuals with mental retardation (MR) and on the prevalence of organ donation in this population. Six centers have published outcome data on renal transplantation in 34 individuals with MR. The one- and three-yr patient survival rates were 100% and 90%, respectively. The studies reported good compliance with post-transplant

Marilee A. Martens; Linda Jones; Steven Reiss

2006-01-01

302

CURRICULUM GUIDE FOR TRAINABLE RETARDED CHILDREN.  

ERIC Educational Resources Information Center

|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…

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

303

Flame Retardancy of Cellular Polymeric Materials  

Microsoft Academic Search

The combustion behavior of cellular polymeric materials is reviewed. The correlations between the structure and thermophysical properties of cellular polymers are discussed. The tests for potential fire hazard of cellular polymeric materials are reviewed. The approaches to flame retardancy of rigid foams based on reactive polyfunctional olygomers (phenolformaldehyde and urea formaldehyde ones, polyurethane) are demonstrated.

R. M. Aseeva; G. E. Zaikov

1996-01-01

304

DEVELOPING GENERATIVE VOCATIONAL BEHAVIORS IN RETARDED STUDENTS  

Microsoft Academic Search

Three mentally retarded women were given four days of training in cleaning the bath area of a standard hotel room and not given training for other aspects of room cleaning. The results of an ABAB single subject design showed that with training on the bath area only, the time needed to clean the entire room decreased during training and increased

M. J. Corley; Everett D. DeHaven; Donald V. Hofeling

1979-01-01

305

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...

306

Flame retarding polymer nanocomposites: Synergism, cooperation, antagonism  

Microsoft Academic Search

Three systems of FR treatments of polyamide 6 with conventional flame retarding additives in the absence and in the presence of nanoparticles are discussed: I. ammonium sulfamate (AS) and dipentaerythritol (Di) II. melamine cyanurate (MC) III. pentabromobenzyl acrylate in the monomeric (PMA) and the polymeric (PPA) form. Depending on the concentration of the nanoparticles; synergism, antagonism, and cooperation in flame

Menachem Lewin

2011-01-01

307

Gravitation is Retarded:Theory and Evidence  

Microsoft Academic Search

Gravitation is Retarded:Theory and Evidence There were more than twenty times of observations about gravity anomalies during the solar eclipses since Maurice Allais's pendulum test during the total solar eclipse of 1954 in Paris. All the theoretical modes are calculated according to Newton's gravitation law. But due to the observation environments and conditions during above observations were not quite well,

K. Tang

2009-01-01

308

Mental Illness in the Elderly Mentally Retarded  

Microsoft Academic Search

The life expectancy of mentally retarded citizens has increased significantly in recent decades. At the same time, we have learned that this special population is nearly twice as likely as the general population to develop severe mental illness. These facts, coupled with the psychological and physiological changes that accompany aging in general, are increasingly challenging the mental health professionals of

Frank J. Menolascino; Jane F. Potter

1989-01-01

309

Polybrominated diphenyl ether (PBDE) flame retardants  

Microsoft Academic Search

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

Frank Rahman; Katherine H Langford; Mark D Scrimshaw; John N Lester

2001-01-01

310

Pharmacotherapy in Mental Retardation and Autism.  

ERIC Educational Resources Information Center

|Reviews studies examining effects of pharmacological interventions for children with mental retardation and autism. Discusses information regarding stimulants, neuroleptics, anticonvulsants, antianxiety drugs, and antidepressant drugs as measured by their effects on laboratory and clinical measures of activity level, self-injurious behavior, and…

Handen, Benjamin L.

1993-01-01

311

Epilepsy and Mental Retardation: An Overview.  

ERIC Educational Resources Information Center

|The comprehensive management of epilepsy in people with mental retardation requires consideration of four aspects of care: diagnosis and classification, anticonvulsant drug treatment, safety and protection from injury, and psychosocial functioning. This paper outlines what is known and unknown in these four areas and introduces articles in this…

Coulter, David L.

1993-01-01

312

Drugs in Mental Retardation: Treatment or Tragedy?  

ERIC Educational Resources Information Center

|Treatment of mentally retarded persons with psychotropic and anticonvulsant drugs is discussed in terms of drug classification, rationale for use, attitudes toward use, and clinical research findings. The literature on neuroleptic, anticonvulsant, anxiolytic, and cerebral stimulant drugs is summarized. Controversial reports that some medications…

Aman, Michael G.

1985-01-01

313

DRIFT RETARDING ADJUVANTS WITH GLYPHOSATE HERBICIDE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The volume of fine, highly driftable spray droplets (<144 um diameter) of glyphosate herbicide (0.56 kg ai in 94 L of water/ha and 276 kPa pressure) was 53% for glyphosate alone and reduced by 11 to 42% with the addition of eight drift retarding compounds. At 2 weeks after treatment in the field, gl...

314

Paraprofessional Staff Teaching Adults with Mental Retardation.  

ERIC Educational Resources Information Center

Paraprofessional staff (n=148) working in group homes, institutions, day care centers, and sheltered workshops for people with mental retardation participated in inservice training on adult education and basic teaching skills. The majority wrote and implemented individual teaching programs for their clients that resulted in positive gains in…

Saloviita, Timo; Lehtinen, Ulla

2001-01-01

315

Brominated flame retardants and endocrine disruption  

Microsoft Academic Search

From an environmental point of view, an increasing important group of organohalogen compounds are the brominated flame retardants (BFRs), which are widely used in polymers and textiles and applied in construction materials, furniture, and electronic equipment. BFRs with the highest production volume are the polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBP-A), and hexabromocyclododecane (HBCD). Because of their persistence and low

Joseph G. Vos; Georg Becher; Martin van den Berg; Jacob de Boer; Pim E. G. Leonards

2003-01-01

316

Information Resources in Mental Retardation: An Overview  

ERIC Educational Resources Information Center

|Proposals are made for a goal oriented approach to coordinate bibliographic control in the multidisciplinary field of mental retardation, establish networks of information service, and provide consultants for setting up services in various institutions and locales. A review of existing efforts for bibliographic control, classification, and…

Weber, Sandra J.

1978-01-01

317

Puberty in the Girl Who is Retarded.  

ERIC Educational Resources Information Center

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.…

Pattullo, Ann

318

Throwing Patterns of the Mentally Retarded.  

ERIC Educational Resources Information Center

|This study explored developmental patterns in the acquisition of the gross motor skill of throwing among 110 educable, mentally retarded 7- to 12-year-olds. Each child was examined through cinematographic procedures to discover: a) variance in throwing patterns, b) elements composing throwing skills, and c) sequential integration of the elements…

Auxter, David

319

Mental Retardation and Developmental Disabilities. Second Edition.  

ERIC Educational Resources Information Center

|This book presents 19 chapters on life span perspectives and service issues for people with mental retardation and developmental disabilities. The book presents best practices and provides a view of the range of services necessary to work with people who have those disabilities. It is intended to provide a core reference for providers in the…

McLaughlin, Phillip J., Ed.; Wehman, Paul, Ed.

320

CURRICULUM GUIDE FOR TRAINABLE RETARDED CHILDREN.  

ERIC Educational Resources Information Center

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…

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

321

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...

322

Mental Illness in Persons with Mental Retardation  

Microsoft Academic Search

What is mental health? Mental health is a goal for all people, including those with mental retardation, not just those having difficulties. Mental health is an essential ingredient in the quality of life. The two main aspects of mental health are emotional well-being and rewarding social and interpersonal relationships. Emotional well-being is an important part of the gift of human

Steven Reiss; Ruth Ryan

323

Fire retardancy of polypropylene\\/flax blends  

Microsoft Academic Search

A comprehensive characterization of the thermal and the fire behaviour is presented for polypropylene (PP) flax compounds containing ammonium polyphosphate (APP) and expandable graphite as fire retardants. Thermogravimetry coupled with an evolved gas analysis (TG-FTIR) was performed to ensure a significant thermal analysis. The fire response under forced flaming conditions was studied using a cone calorimeter. The external heat flux

B. Schartel; U. Braun; U. Schwarz; S. Reinemann

2003-01-01

324

21 Monosomy in a retarded female infant  

Microsoft Academic Search

A 20-month-old female infant with complete monosomy 21 is described. She has marked mental and physical retardation, antimongoloid slant, low set ears, micrognathia, syndactyly of the toes, and cardiac abnormalities. Karyotypes of fibroblasts and lymphocytes, examined with Giemsa banding, quinacrine banding, and reversed banding techniques revealed no evidence of translocation.

Katherine H. Halloran; W. Roy Breg; Maurice J. Mahoney

1974-01-01

325

Jean Piaget Archives Bibliography on Mental Retardation.  

ERIC Educational Resources Information Center

This bibliography lists all entries from the Jean Piaget Archives Catalogues dealing with mental retardation. The list, including almost 200 entries, encompasses four works by Piaget himself, one collaboration, and 189 works by other authors. Entries are arranged in order by their publication in one of the 12 catalogues of the archives, providing…

Bolton, Susie; And Others

326

Novel additives to retard permeable flow  

SciTech Connect

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)

Golombok, Michael [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Department of Mechanical Engineering, Technische Universiteit Eindhoven, 5600 MB Eindhoven (Netherlands); Crane, Carel; Ineke, Erik; Welling, Marco [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Harris, Jon [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Shell UK Ltd., North Anderson Drive, Aberdeen, AB15 6BL (United Kingdom)

2008-09-15

327

Individualized Educational Programming for the Mentally Retarded.  

ERIC Educational Resources Information Center

|The minimal components of a model which utilizes a computer for summarizing individual performance records for teaching educational skills to the mentally retarded are described. The most important components are assessment, individual and group programing, continuous data collection, and program evaluation. (Author)|

Singh, Nirbhay N.; Ahrens, Michael G.

1980-01-01

328

Maleic Hydrazide as a Growth Retardant.  

National Technical Information Service (NTIS)

Application of Maleic Hydrazide (MH) on roadside plots in Minnesota was evaluated during a four-year period ending in 1964 to determine its usefulness as a growth retardant. The chemical was applied at various rates, in different seasons, and with and wit...

L. E. Foote B. F. Himmelman

1965-01-01

329

Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway.  

PubMed

The Rad51 paralogs are required for homologous recombination (HR) and the maintenance of genomic stability. The molecular mechanisms by which the five vertebrate Rad51 paralogs regulate HR and genomic integrity remain unclear. The Rad51 paralogs associate with one another in two distinct complexes: Rad51B-Rad51C-Rad51D-XRCC2 (BCDX2) and Rad51C-XRCC3 (CX3). We find that the BCDX2 and CX3 complexes act at different stages of the HR pathway. In response to DNA damage, the BCDX2 complex acts downstream of BRCA2 recruitment but upstream of Rad51 recruitment. In contrast, the CX3 complex acts downstream of Rad51 recruitment but still has a marked impact on the measured frequency of homologous recombination. Both complexes are epistatic with BRCA2 and synthetically lethal with Rad52. We conclude that human Rad51 paralogs facilitate BRCA2-Rad51-dependent homologous recombination at different stages in the pathway and function independently of Rad52. PMID:23149936

Chun, Jarin; Buechelmaier, Erika S; Powell, Simon N

2012-11-12

330

Gravitation is Retarded:Theory and Evidence  

NASA Astrophysics Data System (ADS)

Gravitation is Retarded:Theory and Evidence There were more than twenty times of observations about gravity anomalies during the solar eclipses since Maurice Allais’s pendulum test during the total solar eclipse of 1954 in Paris. All the theoretical modes are calculated according to Newton’s gravitation law. But due to the observation environments and conditions during above observations were not quite well, the platform for mounting the gravimeters were quite simple, so that the environment and human’s disturbance were unavoidable, therefore the data obtained from above observation where questionable. It is very hard to give a conclusion to say the gravity anomalies during the eclipses were really existing or not. The more important issue is that none of the suggested external factors could account for the magnitude and timing of observed anomalies, according to Chris Duif of University of Technology of Netherland. Since the total solar eclipse of Mohe, 1997, I have been working on a theory to explain the gravity anomalies. At Mohe, I was watching the image of the eclipse, and led a scientific term to conduct a comprehensive geophysical observation, including the gravity observation. The two kinds of observations were conducted at same location and same time. We noticed that solar light of the eclipse was emitted 500 seconds before the image reached to our eyes and cameras. It was reasonable to have similar idea that the gravitation emitted from the sun is also 500 seconds before our gravimeter received and recorded it; it means that gravitation is retarded. Based on either the Special Relativity or Leinard-Wiechert retarded potential, I have deduced the expressions for retarded gravitation; it is vector modification on Newton’s universal gravitation law. The retarded gravitation is gRT=-GM(R-R?)(1-?2)/R3(1-?r)3 For common cases, bodies move in a weak gravitation field along a quasi-straight light or with a slow speed, such as planets move around the sun or the moon/satellites moves around the earth, I have deduced a very useful expression gRT=gNT[1+(??2-2?r2)/2c2] where,?=v/c,?r=vr/c,??=v?/c, gNT=-GMr/r3. I would like to stress that the approximate solution from the general relativity is only of a scalar modification, as a comparison. The Great Total Soar Eclipse along Yangzi River of July 22 of 2009 provided us a great opportunity to clean up the doubts for last 50 years. Consider that solar gravitation is retarded and the earth’s response is delayed, moon’s retarded factor is negligible, all the theoretical amplitudes and the frequencies for each components of solar tide and moon tide can be calculated, the amplitudes and delay factor of earth tide, the frequencies for each components of solar tide, moon tide and earth tide can been separated and measured from the observation data: Asin?S(t-tS+tE)+Bsin?M(t+tE)=Csin?tot(t+ttot). Taking t=t1 and t=t2, we can get two equations with only two variables, solve the two equations, we can get the retarded factor of the solar gravitation and the delay factor of earth response for each compoenets. The retarded factor obtained will be strong evidence that gravitation is retarded.

Tang, K.

2009-12-01

331

An evolutionary perspective on Elovl5 fatty acid elongase: comparison of Northern pike and duplicated paralogs from Atlantic salmon  

PubMed Central

Background The ability to produce physiologically critical LC-PUFA from dietary fatty acids differs greatly among teleost species, and is dependent on the possession and expression of fatty acyl desaturase and elongase genes. Atlantic salmon, as a result of a recently duplicated genome, have more of these enzymes than other fish. Recent phylogenetic studies show that Northern pike represents the closest extant relative of the preduplicated ancestral salmonid. Here we characterise a pike fatty acyl elongase, elovl5, and compare it to Atlantic salmon elovl5a and elovl5b duplicates. Results Phylogenetic analyses show that Atlantic salmon paralogs are evolving symmetrically, and they have been retained in the genome by purifying selection. Heterologous expression in yeast showed that Northern pike Elovl5 activity is indistinguishable from that of the salmon paralogs, efficiently elongating C18 and C20 substrates. However, in contrast to salmon, pike elovl5 was predominantly expressed in brain with negligible expression in liver and intestine. Conclusions We suggest that the predominant expression of Elovl5b in salmon liver and Elovl5a in salmon intestine is an adaptation, enabled by genome duplication, to a diet rich in terrestrial invertebrates which are relatively poor in LC-PUFA. Pike have retained an ancestral expression profile which supports the maintenance of PUFA in the brain but, due to a highly piscivorous LC-PUFA-rich diet, is not required in liver and intestine. Thus, the characterisation of elovl5 in Northern pike provides insights into the evolutionary divergence of duplicated genes, and the ecological adaptations of salmonids which have enabled colonisation of nutrient poor freshwaters.

2013-01-01

332

Orthopedia Transcription Factor otpa and otpb Paralogous Genes Function during Dopaminergic and Neuroendocrine Cell Specification in Larval Zebrafish.  

PubMed

The homeodomain transcription factor Orthopedia (Otp) is an important regulator for specification of defined subsets of neuroendocrine cells and dopaminergic neurons in vertebrates. In zebrafish, two paralogous otp genes, otpa and otpb, are present in the genome. Neither complete loss of Otp activity nor differential contributions of Otpa and Otpb to specification of defined neuronal populations have been analyzed in detail. We characterized zebrafish embryos and early larvae mutant for null alleles of otpa, otpb, or both genes to determine their individual contributions to the specification of th expressing dopaminergic neuronal populations as well as of crh, oxt, avp, trh or sst1.1 expressing neuroendocrine cells. otpa mutant larvae show an almost complete reduction of ventral diencephalic dopaminergic neurons, as reported previously. A small reduction in the number of trh cells in the preoptic region is detectable in otpa mutants, but no significant loss of crh, oxt and avp preoptic neuroendocrine cells. otpb single mutant larvae do not display a reduction in dopaminergic neurons or neuroendocrine cells in the otp expressing regions. In contrast, in otpa and otpb double mutant larvae specific groups of dopaminergic neurons as well as of crh, oxt, avp, trh and sst1.1-expressing neuroendocrine cells are completely lost. These observations suggest that the requirement for otpa and otpb function during development of the larval diencephalon is partially redundant. During evolutionary diversification of the paralogous otp genes, otpa maintained the prominent role in ventral diencephalic dopaminergic and neuroendocrine cell specification and is capable of partially compensating otpb loss of function. In addition, we identified a role of Otp in the development of a domain of somatostatin1-expressing cells in the rostral hindbrain, a region with strong otp expression but so far uncharacterized Otp function. Otp may thus be crucial for defined neuronal cell types also in the hindbrain. PMID:24073233

Fernandes, António M; Beddows, Erin; Filippi, Alida; Driever, Wolfgang

2013-09-20

333

Orthopedia Transcription Factor otpa and otpb Paralogous Genes Function during Dopaminergic and Neuroendocrine Cell Specification in Larval Zebrafish  

PubMed Central

The homeodomain transcription factor Orthopedia (Otp) is an important regulator for specification of defined subsets of neuroendocrine cells and dopaminergic neurons in vertebrates. In zebrafish, two paralogous otp genes, otpa and otpb, are present in the genome. Neither complete loss of Otp activity nor differential contributions of Otpa and Otpb to specification of defined neuronal populations have been analyzed in detail. We characterized zebrafish embryos and early larvae mutant for null alleles of otpa, otpb, or both genes to determine their individual contributions to the specification of th expressing dopaminergic neuronal populations as well as of crh, oxt, avp, trh or sst1.1 expressing neuroendocrine cells. otpa mutant larvae show an almost complete reduction of ventral diencephalic dopaminergic neurons, as reported previously. A small reduction in the number of trh cells in the preoptic region is detectable in otpa mutants, but no significant loss of crh, oxt and avp preoptic neuroendocrine cells. otpb single mutant larvae do not display a reduction in dopaminergic neurons or neuroendocrine cells in the otp expressing regions. In contrast, in otpa and otpb double mutant larvae specific groups of dopaminergic neurons as well as of crh, oxt, avp, trh and sst1.1-expressing neuroendocrine cells are completely lost. These observations suggest that the requirement for otpa and otpb function during development of the larval diencephalon is partially redundant. During evolutionary diversification of the paralogous otp genes, otpa maintained the prominent role in ventral diencephalic dopaminergic and neuroendocrine cell specification and is capable of partially compensating otpb loss of function. In addition, we identified a role of Otp in the development of a domain of somatostatin1-expressing cells in the rostral hindbrain, a region with strong otp expression but so far uncharacterized Otp function. Otp may thus be crucial for defined neuronal cell types also in the hindbrain.

Fernandes, Antonio M.; Beddows, Erin; Filippi, Alida; Driever, Wolfgang

2013-01-01

334

Obsessive-compulsive disorder in a mentally retarded woman.  

PubMed

Obsessive-compulsive disorder is extremely rare among mentally retarded people. We report here a case of a mildly mentally retarded woman who exhibits contamination obsessions, compulsive hand-washing rituals, and avoidance. PMID:2605414

McNally, R J; Calamari, J E

1989-07-01

335

The role of boron in flame-retardant treatments  

Treesearch

Forest Products Laboratory ... 39-41 : ill. Description: Flame retardants for wood alter the combustion properties of wood to reduce surface flame spread. Flame ... Two types of fire tests were used to evaluate flame retardancy. Clearwood and ...

336

Fire-Retardant Decorative Inks for Aircraft Interiors.  

National Technical Information Service (NTIS)

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 ...

Z. Nir J. A. Mikroyannidis D. A. Kourtides

1984-01-01

337

Synergistic Effect of Montmorillonite and Intumescent Flame Retardant on Flame Retardance Enhancement of ABS  

Microsoft Academic Search

The synergistic effects of organic montmorillonite (OMMT) and intumescent flame retardant (IFR) based on the ammonium polyphosphate (APP) and pentaerythritol (PER) on flame retardant enhancement of acrylonitrile-butadiene-styrene copolymer (ABS) were investigated by using the limiting oxygen index (LOI), the UL-94 (vertical flame) test, thermogravimetric analysis (TGA), x-ray diffractometry (XRD) and scanning electron microscopy (SEM). The LOI data and vertical flame

Ying Xia; Xi-gao Jian; Jian-feng Li; Xin-hong Wang; Yan-yan Xu

2007-01-01

338

Set-retarding Effects of Sugars in Portland Cement Pastes  

Microsoft Academic Search

DURING an investigation of the retardation of setting in Portland cement pastes by a series of sugars, the disaccharide alphaalpha-trehalose was found to possess only weak retarding properties, while all the other sugars studied were powerful set-retarding agents. The reason for the distinctive behaviour of alphaalpha-trehalose may help to explain the mechanisms by which organic materials retard the setting reactions

G. M. Bruere

1966-01-01

339

Neuropsychological Profiles of Persons with Mental Retardation and Dementia  

ERIC Educational Resources Information Center

|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…

Palmer, Glen A.

2006-01-01

340

WASTE MANAGEMENT OF PLASTICS CONTAINING BROMINATED FLAME RETARDANTS  

Microsoft Academic Search

Bromine is used as the building block for some of the most effective flame retarding agents available to the plastics industry today. They are used to protect against the risk of accidental fires in a wide range of electrical and electronic equipment (EEE). Brominated flame retardants (BFRs), as all flame retardants, act to decrease the risk of fire by increasing

Lein Tange; Dieter Drohmann

2002-01-01

341

Flame-Retarding Plastics and Elastomers with Melamine  

Microsoft Academic Search

Melamine has shown broad utility as a flame retardant in plastics although its commercial use to date as a flame retardant additive has been principally in coatings and flexible urethane foams. Its mode of action appears to involve endothermic sublimation and vapor-phase dissociation, but it also undergoes conversion to non-volatile products and ammonia. Combinations of melamine with other flame retardants

Edward D. Weil; Veena Choudhary

1995-01-01

342

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

ERIC Educational Resources Information Center

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…

Menolascino, Frank J.; Neman, Ronald

343

Psychopharmacology in the mentally retarded individual: New approaches, new directions  

Microsoft Academic Search

This article reviews the latest findings in the psychopharmacologic treatment of mentally retarded individuals. Recognition of the existence of dual diagnosis in the mentally retarded individual makes it necessary to separate behavioral problems commonly associated with mental retardation from psychiatric problems associated with a second diagnosis. A framework for making this distinction is provided. The drugs (by class) available for

Timothy M. Rivinus; Laura M. Grofer; Carl Feinstein; Rowland P. Barrett

1989-01-01

344

Cardiovascular Risk Factor Levels in Adults with Mental Retardation.  

ERIC Educational Resources Information Center

|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)|

Rimmer, James H.; And Others

1994-01-01

345

Recyclable flame retardant nonwoven for sound absorption; RUBA®  

Microsoft Academic Search

A flame retardant nonwoven fabric for sound absorption, using para-aramid fibre and polyester fibre as a substitute for conventional materials (such as glass wool, flame retardant foam and flame retardant polyester fibre) was investigated. A combination of nonwoven fabric and paper was studied, and the resulting sound absorption qualities and sound permeation loss were compared. By attaching para-aramid paper with

Kazuhiko Kosuge; Akira Takayasu; Teruo Hori

2005-01-01

346

Preferential expression of a HLP homolog encoding a mitochondrial L14 ribosomal protein in stamens of common wheat  

Microsoft Academic Search

Interaction between nucleus and cytoplasm has essential roles in plant development, including that of floral organs. We isolated a wheat homolog Whlp of Arabidopsis HUELLENLOS PARALOG (HLP) gene encoding a mitochondrial (mt) ribosomal protein L14. Transient expression analysis using the green fluorescent protein (GFP) fusion protein showed that 50 amino residues located on the N-terminal of the wheat HLP homolog

Kota Mizumoto; Koji Murai; Chiharu Nakamura; Shigeo Takumi

2004-01-01

347

On the mechanism of flame retardancy and characterization of halogen-free, flame-retardant materials for wires and cables  

Microsoft Academic Search

During exploratory on mechanistic pathway of halogen-free, flame-retardant materials, containing metal hydroxide with other ingredients, there were revealed that the char formation at high temperatures should play an important role to enhance flame retardancy of resultant compositions, and some metallic compounds which were capable of increase catalytically the amount of char could further improve flame retardancy. It has also been

H. Kato; T. Futagami; M. Ishida; K. Sengoku; M. Ueda

1986-01-01

348

Flame retardant compositions and method of use  

US Patent & Trademark Office Database

A flame retardant composition comprises at least one cyclic phosphonate ester and at least one phosphono amide. The ester and the amide are present in a ratio by weight of 0.1 to 2:1. A co-curing agent (e.g. urea, ethylene urea or an amino-triazine) may be included. The composition may also contain a non-rewetting agent and/or a softening or conditioning agent. The composition is used for the flame retardant treatment of a fabric by first impregnating the fabric with an aqueous solution of the composition and then heating the impregnated fabric at at least 100.degree. C. and under acid pH conditions.

1992-06-30

349

[Atherosclerosis treatment with etofibrate retard. New perspectives].  

PubMed

In a multicentric general-practice-study 2504 hyperlipoproteinemic patients were treated with etofibrate retard for 4 weeks. The drug was administered once daily in the evening. A highly significant decrease of the mean values of cholesterol around 18.4% and 27.6% resp., and of the mean triglycerides between 31.3% and 16.5% resp. were observed. The atherogenic index was reduced by 28%. The simultaneous, highly significant reduction of blood glucose and of uric acid levels as well as of blood pressure showed the comprising effects of etofibrate retard against the atherosclerosis and its risk factors. The excellent tolerance of the drug was stated by more than 99% of the patients treated. PMID:6618402

Degenring, F H; Schatton, W; Hotz, W

1983-08-11

350

Prepartially crosslinked gel for retarding fluid flow  

SciTech Connect

This patent describes a subterranean formation having channels which have a high permeability to the flow of fluids. A process for retarding fluid flow in the channels comprises: providing a gel-forming composition which when substantially completely gelled in the high permeability channels is operable for retarding fluid flow therein. The gel-forming composition comprises: an aqueous solution comprising a first substance selected from the group consisting of polyvinyl alcohol, a polyvinyl alcohol copolymer, and mixtures thereof, and an effective amount of a second substance selected from the group consisting of aldehydes, aldehyde generating substances, acetals, acetal generating substances, and mixtures thereof capable of crosslinking with the first substance through the formation of acetal crosslinkages. The second substance is operable for forming a gel with the aqueous solution when the gel-forming composition is acidic.

Sandiford, B.B.; Chiou, C.S.

1987-05-19

351

Brominated flame retardants: cause for concern?  

PubMed Central

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.

Birnbaum, Linda S; Staskal, Daniele F

2004-01-01

352

Optimal achromatic wave retarders using two birefringent wave plates.  

PubMed

Two plates of different birefringence material can be combined to obtain an achromatic wave retarder. In this work, we achieve a correction for the overall retardation of the system that extends the relation to any azimuth. Current techniques for the design of achromatic wave retarders do not present a parameter that characterizes its achromatism on a range of wavelengths. Thus, an achromatic degree has been introduced, in order to determine the optimal achromatic design composed with retarder plates for a spectrum of incident light. In particular, we have optimized a quarter retarder using two wave plates for the visible spectrum. Our technique has been compared to previous results, showing significant improvement. PMID:23518734

Vilas, Jose Luis; Sanchez-Brea, Luis Miguel; Bernabeu, Eusebio

2013-03-20

353

Interactions of the G quartet forming semaphorin 3F RNA with the RGG box domain of the fragile X protein family  

PubMed Central

Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the transcriptional silencing of the fmr1 gene due to an unstable expansion of a CGG trinucleotide repeat and its subsequent hypermethylation in its 5? UTR. This gene encodes for the fragile X mental retardation protein (FMRP), an RNA-binding protein that has been shown to use its RGG box domain to bind to G quartet-forming RNA. In this study, we performed a detailed analysis of the interactions between the FMRP RGG box domain and one of its proposed RNA targets, human semaphorin 3F (S3F) RNA by using biophysical methods such as fluorescence, UV and circular dichroism spectroscopy. We show that this RNA forms a G quartet-containing structure, which is recognized with high affinity and specificity by the FMRP RGG box. In addition, we analyzed the interactions of human S3F RNA with the RGG box and RG cluster of the two FMRP autosomal paralogs, the FXR1P and FXR2P. We found that this RNA is bound with high affinity and specificity only by the FXR1P RGG box, but not by the FXR2P RG cluster. Both FMRP and FXR1P RGG box are able to unwind the G quartet structure of S3F RNA, however, the peptide concentrations required in this process are very different: a ratio of 1:6 RNA:FMRP RGG box versus 1:2 RNA:FXR1P RGG box.

Menon, Lakshmi; Mihailescu, Mihaela-Rita

2007-01-01

354

Clock retardation, absolute space, and special relativity  

Microsoft Academic Search

We consider a sequence of absolute-space kinematical theories which differ more or less from the special theory of relativity (STR) in the amount of clock retardation which they predict, but which agree with STR with respect to roundtrip light experiments, such as Michelson-Morley and Kennedy-Thorndike. This sequence of theories is imbedded in the synchrony-free formulation of STR developed by Winnie

Carlo Giannoni

1979-01-01

355

Predicting Fatigue Crack Retardation Following Overload Cycles  

Microsoft Academic Search

Dating back to the beginning of the seventies, a number of models have been proposed to predict fatigue crack growth rate\\u000a under variable amplitude loading. This effort was motivated by earlier observations that the application of an overload is\\u000a followed by crack growth retardation over a crack length increment. The model of Willenborg, which belong to the group of\\u000a yield

Marcos V. Pereira; Fathi A. Darwish; Arnaldo F. Camarao; Sérgio H. Motta

356

Diagnostic Genome Profiling in Mental Retardation  

Microsoft Academic Search

Mental retardation (MR) occurs in 2%-3% of the general population. Conventional karyotyping has a resolution of 5-10 million bases and detects chromosomal alterations in approximately 5% of individuals with unexplained MR. The frequency of smaller submicroscopic chromosomal alterations in these patients is unknown. Novel molecular karyotyping methods, such as array-based comparative genomic hybridization (array CGH), can detect submicroscopic chromosome alterations

Bert B. A. de Vries; Rolph Pfundt; Martijn Leisink; David A. Koolen; Lisenka E. L. M. Vissers; Irene M. Janssen; Simon van Reijmersdal; Willy M. Nillesen; Erik H. L. P. G. Huys; Nicole de Leeuw; Dominique Smeets; Erik A. Sistermans; Ton Feuth; Conny M. A. van Ravenswaaij-Arts; Eric F. P. M. Schoenmakers; Han G. Brunner; Joris A. Veltman

2005-01-01

357

Intrastrain and interstrain genetic variation within a paralogous gene family in Chlamydia pneumoniae  

Microsoft Academic Search

BACKGROUND: Chlamydia pneumoniae causes human respiratory diseases and has recently been associated with atherosclerosis. Analysis of the three recently published C. pneumoniae genomes has led to the identification of a new gene family (the Cpn 1054 family) that consists of 11 predicted genes and gene fragments. Each member encodes a polypeptide with a hydrophobic domain characteristic of proteins localized to

Wasna Viratyosin; Lee Ann Campbell; Cho-Chou Kuo; Daniel D Rockey

2002-01-01

358

Independent expression of the two paralogous CCL4 genes in monocytes and B lymphocytes  

Microsoft Academic Search

The CCL4 chemokine is secreted by a variety of cells following stimulation. CCL4 affects several different types of cells that are important for acute inflammatory responses and are critical for the development of specific immune responses to foreign antigens. The human genome contains two genes for the CCL4 chemokine. Although highly homologous, the two genes encode slightly different proteins. We

Jun Lu; Marek Honczarenko; Steven R. Sloan

2004-01-01

359

Chemistry and toxicity of flame retardants for plastics.  

PubMed Central

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.

Liepins, R; Pearce, E M

1976-01-01

360

Autophagy contributes to retardation of cardiac growth in diabetic rats.  

PubMed

Diabetes mellitus is a major predictor of heart failure, although the mechanisms by which the disease causes cardiomyopathy are not well understood. The purpose of this study was to determine whether prolonged exposure of cardiomyocytes to high glucose concentrations induces autophagy and contributes to cardiomyopathy. Interestingly, there were no differences in the autophagic activation produced by different glucose concentrations. However, cell viability was decreased by high glucose. In the diabetic rats, we found a higher level of microtubule-associated protein light chain 3 (LC3) expression and a reduction in the size of the left ventricle (LV) (P<0.05) caused by growth retardation, suggesting activated autophagy. Our in vitro findings indicate that hyperglycemic oxidative stress induces autophagy, and our in vivo studies reveal that autophagy is involved in the progression of pathophysiological remodeling of the heart. Taken together, the studies suggest that autophagy may play a role in the pathogenesis of juvenile diabetic cardiomyopathy. PMID:22787483

Lee, Youngjeon; Hong, Yunkyung; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2012-06-26

361

Multi-twist retarders: broadband retardation control using self-aligning reactive liquid crystal layers.  

PubMed

We report on a family of complex birefringent elements, called Multi-Twist Retarders (MTRs), which offer remarkably effective control of broadband polarization transformation. MTRs consist of two or more twisted liquid crystal (LC) layers on a single substrate and with a single alignment layer. Importantly, subsequent LC layers are aligned directly by prior layers, allowing simple fabrication, achieving automatic layer registration, and resulting in a monolithic film with a continuously varying optic axis. In this work, we employ a numerical design method and focus on achromatic quarter- and half-wave MTRs. In just two or three layers, these have bandwidths and general behavior that matches or exceeds all traditional approaches using multiple homogenous retarders. We validate the concept by fabricating several quarter-wave retarders using a commercial polymerizeable LC, and show excellent achromaticity across bandwidths of 450-650 nm and 400-800 nm. Due to their simple fabrication and many degrees of freedom, MTRs are especially well suited for patterned achromatic retarders, and can easily achieve large bandwidth and/or low-variation of retardation within visible through infrared wavelengths. PMID:23388933

Komanduri, Ravi K; Lawler, Kristopher F; Escuti, Michael J

2013-01-14

362

RAD51 paralogs: Roles in DNA damage signalling, recombinational repair and tumorigenesis  

Microsoft Academic Search

Chromosomal double-strand breaks (DSBs) have the potential to permanently arrest cell cycle progression and endanger cell survival. They must therefore be efficiently repaired to preserve genome integrity and functionality. Homologous recombination (HR) provides an important error-free mechanism for DSB repair in mammalian cells. In addition to RAD51, the central recombinase activity in mammalian cells, a family of proteins known as

Natsuko Suwaki; Kerstin Klare; Madalena Tarsounas

363

Chromosome Instability and Defective Recombinational Repair in Knockout Mutants of the Five Rad51 Paralogs  

Microsoft Academic Search

The Rad51 protein, a eukaryotic homologue of Escherichia coli RecA, plays a central role in both mitotic and meiotic homologous DNA recombination (HR) in Saccharomyces cerevisiae and is essential for the proliferation of vertebrate cells. Five vertebrate genes, RAD51B ,- C, and -D and XRCC2 and -3, are implicated in HR on the basis of their sequence similarity to Rad51

MINORU TAKATA; MASAO S. SASAKI; SEIJI TACHIIRI; TORU FUKUSHIMA; EIICHIRO SONODA; DAVID SCHILD; LARRY H. THOMPSON; SHUNICHI TAKEDA

2001-01-01

364

Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases  

PubMed Central

Identification of genes regulated by the ferric uptake regulator (Fur) protein has provided insights into the diverse mechanisms of adaptation to iron limitation. In the soil bacterium Bacillus subtilis, Fur senses iron sufficiency and represses genes that enable iron uptake, including biosynthetic and transport genes for the siderophore bacillibactin and uptake systems for siderophores produced by other organisms. We here demonstrate that Fur regulates hmoA (formerly yetG), which encodes a haem monooxygenase. HmoA is the first characterized member of a divergent group of putative monooxygenases that cluster separately from the well-characterized IsdG family. B. subtilis also encodes an IsdG family protein designated HmoB (formerly YhgC). Unlike hmoA, hmoB is constitutively expressed and not under Fur control. HmoA and HmoB both bind haemin in vitro with approximately 1?:?1 stoichiometry and degrade haemin in the presence of an electron donor. Mutational and spectroscopic analyses indicate that HmoA and HmoB have distinct active site architectures and interact differently with haem. We further show that B. subtilis can use haem as an iron source, but that this ability is independent of HmoA and HmoB.

Gaballa, Ahmed

2011-01-01

365

Hox11 paralogous genes are required for formation of wrist and ankle joints and articular surface organization.  

PubMed

Limb skeletal elements are connected by distinct synovial joints, but the mechanisms regulating joint formation, diversity, and organization remain unclear. Previous studies showed that Hox11 mouse mutants have severe developmental defects in radius and ulna and tibia and fibula, but wrist and ankle joint formation and characteristics were not examined in detail. We now find that E11.5 and E12.5 triple Hox11aaccdd mutants exhibit a significant reduction in prospective carpal and tarsal mesenchyme. Although the mesenchyme became segmented into individual carpal and tarsal skeletal elements with further development, the elements were ill defined and the more proximal elements (radiale, ulnare, talus, and calcaneous) actually underwent involution and/or fusion. Wild-type carpal and tarsal elements displayed a thick articulating superficial zone at their outer perimeter that expressed genes typical of developing joint interzones and articulating cells, including Gdf5, Erg, Gli3, collagen IIA, and lubricin, and defined each element anatomically. In mutant wrists and ankles, the superficial zone around each element was thin and ill defined, and expression of several of those genes was low and often interrupted. These and other data provide novel and clear evidence that Hox11 paralogous genes regulate wrist and ankle joint organization and are essential for establishing carpal and tarsal element boundary and maintaining their articulating surface tissue. PMID:20392252

Koyama, Eiki; Yasuda, Tadashi; Wellik, Deneen M; Pacifici, Maurizio

2010-03-01

366

Divergent Evolutionary and Expression Patterns between Lineage Specific New Duplicate Genes and Their Parental Paralogs in Arabidopsis thaliana  

PubMed Central

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.

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

2013-01-01

367

Divergent Evolutionary and Expression Patterns between Lineage Specific New Duplicate Genes and Their Parental Paralogs in Arabidopsis thaliana.  

PubMed

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. PMID:24009676

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

2013-08-29

368

Paralogous Mouse Hox Genes, Hoxa9, Hoxb9, and Hoxd9, Function Together to Control Development of the Mammary Gland in Response to Pregnancy  

Microsoft Academic Search

Although the role of Hox genes in patterning the mammalian body plan has been studied extensively during embryonic and fetal development, relatively little is known concerning Hox gene function in adult animals. Analysis of mice with mutant Hoxa9, Hoxb9, and Hoxd9 genes shows that these paralogous genes are required for mediating the expansion and\\/or differentiation of the mammary epithelium ductal

Feng Chen; Mario R. Capecchi

1999-01-01

369

Interactome analyses of mature ?-secretase complexes reveal distinct molecular environments of presenilin (PS) paralogs and preferential binding of signal peptide peptidase to PS2.  

PubMed

?-Secretase plays a pivotal role in the production of neurotoxic amyloid ?-peptides (A?) in Alzheimer disease (AD) and consists of a heterotetrameric core complex that includes the aspartyl intramembrane protease presenilin (PS). The human genome codes for two presenilin paralogs. To understand the causes for distinct phenotypes of PS paralog-deficient mice and elucidate whether PS mutations associated with early-onset AD affect the molecular environment of mature ?-secretase complexes, quantitative interactome comparisons were undertaken. Brains of mice engineered to express wild-type or mutant PS1, or HEK293 cells stably expressing PS paralogs with N-terminal tandem-affinity purification tags served as biological source materials. The analyses revealed novel interactions of the ?-secretase core complex with a molecular machinery that targets and fuses synaptic vesicles to cellular membranes and with the H(+)-transporting lysosomal ATPase macrocomplex but uncovered no differences in the interactomes of wild-type and mutant PS1. The catenin/cadherin network was almost exclusively found associated with PS1. Another intramembrane protease, signal peptide peptidase, predominantly co-purified with PS2-containing ?-secretase complexes and was observed to influence A? production. PMID:23589300

Jeon, Amy Hye Won; Böhm, Christopher; Chen, Fusheng; Huo, Hairu; Ruan, Xueying; Ren, Carl He; Ho, Keith; Qamar, Seema; Mathews, Paul M; Fraser, Paul E; Mount, Howard T J; St George-Hyslop, Peter; Schmitt-Ulms, Gerold

2013-04-15

370

Polarization holography for vortex retarders recording.  

PubMed

We present an original static recording method for vortex retarders (VRs) made from liquid crystal polymers (LCPs) using the superimposition of several polarized beams. VRs are birefringent plates characterized by a rotation of their fast axis about their center. The new method is based on polarization holography and photo-orientable LCP. Combining several polarized beams induces the polarization patterns required for the recording process of VRs without mechanical action. A mathematical description of the method, the outcomes of the numerical simulations, and the first experimental results are presented. PMID:24085221

Piron, Pierre; Blain, Pascal; Habraken, Serge; Mawet, Dimitri

2013-10-01

371

Long Term Memory in Normals and Retardates. Memory and Mental Imagery in Retardates: A Pilot Study.  

ERIC Educational Resources Information Center

|Two studies are reported. The first is based on Piaget's assertion that the child's representation of his world is dependent on the level of cognitive development at which he is currently functioning. Forty-eight normals and 48 retardates were given a visual memory task. They were asked to recall a configural presentation in a number of ways,…

McLaughlin, John A.; And Others

372

Two recently duplicated maize NAC transcription factor paralogs are induced in response to Colletotrichum graminicola infection  

PubMed Central

Background NAC transcription factors belong to a large family of plant-specific transcription factors with more than 100 family members in monocot and dicot species. To date, the majority of the studied NAC proteins are involved in the response to abiotic stress, to biotic stress and in the regulation of developmental processes. Maize NAC transcription factors involved in the biotic stress response have not yet been identified. Results We have found that two NAC transcription factors, ZmNAC41 and ZmNAC100, are transcriptionally induced both during the initial biotrophic as well as the ensuing necrotrophic colonization of maize leaves by the hemibiotrophic ascomycete fungus C. graminicola. ZmNAC41 transcripts were also induced upon infection with C. graminicola mutants that are defective in host penetration, while the induction of ZmNAC100 did not occur in such interactions. While ZmNAC41 transcripts accumulated specifically in response to jasmonate (JA), ZmNAC100 transcripts were also induced by the salicylic acid analog 2,6-dichloroisonicotinic acid (INA). To assess the phylogenetic relation of ZmNAC41 and ZmNAC100, we studied the family of maize NAC transcription factors based on the recently annotated B73 genome information. We identified 116 maize NAC transcription factor genes that clustered into 12 clades. ZmNAC41 and ZmNAC100 both belong to clade G and appear to have arisen by a recent gene duplication event. Including four other defence-related NAC transcription factors of maize and functionally characterized Arabidopsis and rice NAC transcription factors, we observed an enrichment of NAC transcription factors involved in host defense regulation in clade G. In silico analyses identified putative binding elements for the defence-induced ERF, Myc2, TGA and WRKY transcription factors in the promoters of four out of the six defence-related maize NAC transcription factors, while one of the analysed maize NAC did not contain any of these potential binding sites. Conclusions Our study provides a systematic in silico analysis of maize NAC transcription factors in which we propose a nomenclature for maize genes encoding NAC transcription factors, based on their chromosomal position. We have further identified five pathogen-responsive maize NAC transcription factors that harbour putative binding elements for other defence-associated transcription factors in the proximal promoter region, indicating an involvement of the described NACs in the maize defence network. Our phylogenetic analysis has revealed that the majority of the yet described pathogen responsive NAC proteins from all plant species belong to clade G and suggests that they are phylogenetically related.

2013-01-01

373

Conversational Competence and Peer Response to Mildly Retarded Children  

Microsoft Academic Search

This study investigated the relationship between mildly retarded children’s conversational competence and their acceptance by regular education students. Ninety-four elementary school students watched videotapes in which mildly retarded children displayed either skill or lack of skill at conversational management. Half of the students were told the retarded children’s special education placement; half were not. Students responded more positively when the

Lowry Hemphill; Gary N. Siperstein

1990-01-01

374

Flame retardant property of nanopowder aerosols toward methane  

Microsoft Academic Search

The flame retardant property of aerosols formed from 18 different nanopowders has been studied. The diameter of nanocrystalline\\u000a powders was determined by XRD and TEM. The concentration of combustible gas was determined by gas chromatography. It was found\\u000a that ZrO2 nanocrystalline powdered aerosol can effectively retard the burning of CH4. The flame retardation caused by ZrO2 toward the combustion reaction

Ch. Huang; X. Yang; L. Lu; X. Wang

2006-01-01

375

Detection of L1 CAM mutation in a male child with mental retardation  

Microsoft Academic Search

Recent studies have presented evidence for the involvement of L1CAM gene mutations in various X-linked mental retardation\\u000a syndromes. The neural cell adhesion molecule, L1CAM is a transmembrane protein belonging to the super family of the immunoglobulins\\u000a that play a key role in embryonic development of the nervous system and is involved in memory and learning. No studies were\\u000a carried out

M. Swarna; M. Sujatha; P. Usha Rani; P. P. Reddy

2004-01-01

376

Desalting Milk and Whey by Ion Retardation and Gel Filtration1  

Microsoft Academic Search

Gel filtration on Sephadex G-10 and Bio-Gel P-2 and ion retardation on a Resin AG 11A8 were applied to desalting Cot- tage cheese whey. Gel filtration revealed difficulties when protein and lactose were collected. Lactose was not separated from calcium salts be- cause of their similar elution volumes, and the whey was diluted to a large extent due to differences

S. Nakai; W. A. Blair; A. Helmersen; B. A. Eagles

1968-01-01

377

The mGluR theory of fragile X mental retardation  

Microsoft Academic Search

Many of the diverse functional consequences of activating group 1 metabotropic glutamate receptors require translation of pre-existing mRNA near synapses. One of these consequences is long-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus. This finding is consistent with

Mark F. Bear; Kimberly M. Huber; Stephen T. Warren

2004-01-01

378

Amyrel, a paralogous gene of the amylase gene family in Drosophila melanogaster and the Sophophora subgenus  

PubMed Central

We describe a gene from Drosophila melanogaster related to the alpha-amylase gene Amy. This gene, which exists as a single copy, was named Amyrel. It is strikingly divergent from Amy because the amino acid divergence is 40%. The coding sequence is interrupted by a short intron at position 655, which is unusual in amylase genes. Amyrel has also been cloned in Drosophila ananassae, Drosophila pseudoobscura, and Drosophila subobscura and is likely to be present throughout the Sophophora subgenus, but, to our knowledge, it has not been detected outside. Unexpectedly, there is a strong conservation of 5? and 3? flanking regions between Amyrel genes from different species, which is not the case for Amy and which suggests that selection acts on these regions. In contrast to the Amy genes, Amyrel is transcribed in larvae of D. melanogaster but not in adults. However, the protein has not been detected yet. Amyrel evolves about twice as fast as Amy in the several species studied. We suggest that this gene could result from a duplication of Amy followed by accelerated and selected divergence toward a new adaptation.

Da Lage, Jean-Luc; Renard, Emmanuelle; Chartois, Frederique; Lemeunier, Francoise; Cariou, Marie-Louise

1998-01-01

379

Functional analysis of paralogous thiol-disulfide oxidoreductases in Streptococcus gordonii.  

PubMed

Disulfide bonds are important for the stability of many extracellular proteins, including bacterial virulence factors. Formation of these bonds is catalyzed by thiol-disulfide oxidoreductases (TDORs). Little is known about their formation in Gram-positive bacteria, particularly among facultative anaerobic Firmicutes, such as streptococci. To investigate disulfide bond formation in Streptococcus gordonii, we identified five putative TDORs from the sequenced genome. Each of the putative TDOR genes was insertionally inactivated with an erythromycin resistance cassette, and the mutants were analyzed for autolysis, extracellular DNA release, biofilm formation, bacteriocin production, and genetic competence. This analysis revealed a single TDOR, SdbA, which exhibited a pleiotropic mutant phenotype. Using an in silico analysis approach, we identified the major autolysin AtlS as a natural substrate of SdbA and showed that SdbA is critical to the formation of a disulfide bond that is required for autolytic activity. Analysis by BLAST search revealed homologs to SdbA in other Gram-positive species. This study provides the first in vivo evidence of an oxidoreductase, SdbA, that affects multiple phenotypes in a Gram-positive bacterium. SdbA shows low sequence homology to previously identified oxidoreductases, suggesting that it may belong to a different class of enzymes. Our results demonstrate that SdbA is required for disulfide bond formation in S. gordonii and indicate that this enzyme may represent a novel type of oxidoreductase in Gram-positive bacteria. PMID:23615907

Davey, Lauren; Ng, Crystal K W; Halperin, Scott A; Lee, Song F

2013-04-24

380

Visual problems among people with mental retardation.  

PubMed

Vision impairment can be a debilitating condition, affecting not only the social, emotional, mental and physical functioning of an individual, but also the individual's ability to perform basic and instrumental activities of daily living. Scant knowledge exists about visual impairment among people with mental retardation. The results of this prospective study were based on interviews and eye ophthalmologic screening of 106 adults with a moderate level of mental retardation, ranging in ages from 19 to 62 years. Findings show that only 3% of those interviewed recalled having had an eye examination, yet 24% reported that they had visual problems. In spite of the high probability of visual problems for this group, only 13% reported having glasses and 20% said they needed glasses; 92% reported watching television but 22% stated they had difficulty seeing the TV; 62% of the respondents reported that they cook for themselves but 17% reported that visual problems affected their ability to perform this activity. Medical eye screening of the participants found that 79% had ocular problems - 42% were in need of eyeglasses, 12% had a cataract problem requiring surgery and 25% needed outpatient care at the local hospital. The study findings are discussed in terms of policy implications and service provision, and recommendations are made for additional research. PMID:12799611

Isralowitz, Richard; Madar, Michal; Lifshitz, Tova; Assa, Valentina

2003-06-01

381

Psychomotor retardation in depression: Biological underpinnings, measurement, and treatment  

PubMed Central

Psychomotor retardation is a long established component of depression that can have significant clinical and therapeutic implications for treatment. Due to its negative impact on overall function in depressed patients, we review its biological correlates, optimal methods of measurement, and relevance in the context of therapeutic interventions. The aim of the paper is to provide a synthesis of the literature on psychomotor retardation in depression with the goal of enhanced awareness for clinicians and researchers. Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Manifestations of psychomotor retardation include slowed speech, decreased movement, and impaired cognitive function. It is common in patients with melancholic depression and those with psychotic features. Biological correlates may include abnormalities in the basal ganglia and dopaminergic pathways. Neurophysiologic tools such as neuroimaging and transcranial magnetic stimulation may play a role in the study of this symptom in the future. At present, there are three objective scales to evaluate psychomotor retardation severity. Studies examining the impact of psychomotor retardation on clinical outcome have found differential results. However, available evidence suggests that depressed patients with psychomotor retardation may respond well to electroconvulsive therapy (ECT). Current literature regarding antidepressants is inconclusive, though tricyclic antidepressants may be considered for treatment of patients with psychomotor retardation. Future work examining this objective aspect of major depressive disorder (MDD) is essential. This could further elucidate the biological underpinnings of depression and optimize its treatment.

Buyukdura, Jeylan S.; McClintock, Shawn M.; Croarkin, Paul E.

2013-01-01

382

On the mechanism of flame retardancy and characterization of halogen-free, flame-retardant materials for wires and cables  

NASA Astrophysics Data System (ADS)

During exploratory on mechanistic pathway of halogen-free, flame-retardant materials, containing metal hydroxide with other ingredients, there were revealed that the char formation at high temperatures should play an important role to enhance flame retardancy of resultant compositions, and some metallic compounds which were capable of increase catalytically the amount of char could further improve flame retardancy. It has also been revealed that a certain combination of alpha-polyolefins having peculiar MFR values and densities, or only certain crosslinked alpha-polyolefin copolymers having limited comonomer content gave excellent physical and electrical properties, especially with magnesium hydroxide as an inorganic flame retardant. Based on these results, the authors have developed halogen-free (HF), flame-retardant (FR) cables showing excellent flame retardancy, low smoke generation, physical, electrical and aging properties.

Kato, H.; Futagami, T.; Ishida, M.; Sengoku, K.; Ueda, M.

1986-11-01

383

Effect of Elastomer on Flame Retardancy, Thermal Degradation, and Mechanical Properties of Intumescent Flame-Retardant Polyethylene  

Microsoft Academic Search

Ethylene—acrylic ester—maleic anhydride (EAEM), as a compatibilizer, has been used to modify a new halogen-free flame retardant linear low-density polyethylene (LLDPE) in this article. Intumescent flame retardants (IFRs) consist of a charring—foaming agent (CFA), ammonium polyphosphate (APP), organic montmorillonite (OMMT) and an antidripping agent. Based on limiting oxygen index values and UL-94 ratings, the IFRs show the effective flame retardancy

Sheng Li; Bin Li

2011-01-01

384

Crystal Structure of Thermus Aquaticus Gfh1, a Gre-factor Paralog that Inhibits rather than Stimulates transcript Cleavage  

SciTech Connect

Transcription elongation in bacteria is promoted by Gre-factors, which stimulate an endogenous, endonucleolytic transcript cleavage activity of the RNA polymerase. A GreA paralog, Gfh1, present in Thermus aquaticus and Thermus thermophilus, has the opposite effect on elongation complexes, inhibiting rather than stimulating transcript cleavage. We have determined the 3.3 Angstroms-resolution X-ray crystal structure of T. aquaticus Gfh1. The structure reveals an N-terminal and a C-terminal domain with close structural similarity to the domains of GreA, but with an unexpected conformational change in terms of the orientation of the domains with respect to each other. However, structural and functional analysis suggests that when complexed with RNA polymerase, Gfh1 adopts a conformation similar to that of GreA. These results reveal considerable structural flexibility for Gfh1, and for Gre-factors in general, as suggested by structural modeling, and point to a possible role for the conformational switch in Gre-factor and Gfh1 regulation. The opposite functional effect of Gfh1 compared with GreA may be determined by three structural characteristics. First, Gfh1 lacks the basic patch present in Gre-factors that likely plays a role in anchoring the 3'-fragment of the backtracked RNA. Second, the loop at the tip of the N-terminal coiled-coil is highly flexible and contains extra acidic residues compared with GreA. Third, the N-terminal coiled-coil finger lacks a kink in the first a-helix, resulting in a straight coiled-coil compared with GreA. The latter two characteristics suggest that Gfh1 chelates a magnesium ion in the RNA polymerase active site (like GreA) but in a catalytically inactive configuration.

Lamour,V.; Hogan, B.; Erie, D.; Darst, S.

2006-01-01

385

Cytogenetic Findings in Mentally Retarded Iranian Patients  

PubMed Central

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.

Nasiri, F; Mahjoubi, F; Manouchehry, F; Razazian, F; Mortezapour, F; Rahnama, M

2012-01-01

386

Emerging Brominated Flame Retardants in the Environment  

Microsoft Academic Search

\\u000a \\u000a Abstract  A number of new brominated flame retardants (BFRs) are being found in the environment but the amount of data is still very\\u000a small. The best studied emerging BFRs are 1,2-bis(2,4,6-tribromophenoxy)ethane and decabromodiphenyl ethane, with some data\\u000a for hexabromobenzene, pentabromoethylbenzene, pentabromotoluene, tetrabromobisphenol A derivatives, bis(2-ethylhexyl) tetrabromophthalate,\\u000a 2-ethylhexyltetrabromobenzoate, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, and 2,4,6-tribromophenol. Very little data are\\u000a available for 2,4,6-tribromophenyl allyl ether, 2,3-dibromopropyl-2,4,6-tribromophenyl ether,

Cynthia A. de Wit; Amelie Kierkegaard; Niklas Ricklund; Ulla Sellström

387

Analysis of parallel-plate retarder in electrostatic zoom lens  

Microsoft Academic Search

A simple preretarding lens system is analyzed which involves a parallel-plate retarder B placed between two cylindrical lens systems A and C. The exact transfer matrix elements for the retarder are developed. The system can deliver fixed-energy electrons for any input energy by providing potentials on the upstream lens element which are a fixed fraction of the desired input kinetic

James E. Draper; Cheng-Yi Lee

1977-01-01

388

Insulin Resistance in Short Children with Intrauterine Growth Retardation  

Microsoft Academic Search

Epidemiological studies have demonstrated an association be- tween intrauterine growth retardation and an increased risk of adult diseases that include essential hypertension, noninsulin-dependent diabetes mellitus, and ischemic heart disease. A common feature of these diseases is insulin resistance. To investigate whether abnormal insulin sensitivity was a char- acteristic of subjects with intrauterine growth retardation (IUGR), we compared two groups of

PAUL L. HOFMAN; WAYNE S. CUTFIELD; ELIZABETH M. ROBINSON; RICHARD N. BERGMAN; RAM K. MENON; MARK A. SPERLING; PETER D. GLUCKMAN

389

A Sociological Perspective on Labeling in Mental Retardation.  

ERIC Educational Resources Information Center

The recent literature on labeling in mental retardation is reviewed and a conceptual scheme based on T. Scheff's model is presented for future study of the labeling problem. The issue of the medicalization or demedicalization of mental retardation is discussed in light of P.L. 94-142, the Education for All Handicapped Children Act. (Author)

Rowitz, Louis

1981-01-01

390

Psychopharmacology and Mental Retardation: A 10 Year Review (1990- 1999).  

ERIC Educational Resources Information Center

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…

Matson, Johnny L.; Bamburg, Jay W.; Mayville, Erik A.; Pinkston, Jim; Bielecki, Joanne; Kuhn, David; Smalls, Yemonja; Logan, James R.

2000-01-01

391

Public Health Approach to the Study of Mental Retardation  

ERIC Educational Resources Information Center

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…

Chapman, Derek A.; Scott, Keith G.; Stanton-Chapman, Tina L.

2008-01-01

392

Recognition of Emotion by Mentally Retarded Adolescents and Young Adults.  

ERIC Educational Resources Information Center

|The study found that mildly mentally retarded adolescents and young adults (N=21) were not able to correctly match photographs of faces to emotionally expressive voices. Results suggest that mentally retarded individuals may have specific deficits in recognizing how bodily expressions of emotion are coordinated with each other. (Author/DB)|

Hobson, R. P.; And Others

1989-01-01

393

Iconic Memory Deficit of Mildly Mentally Retarded Individuals.  

ERIC Educational Resources Information Center

Ten mildly retarded young adult males and nonretarded subjects matched for chronological age or mental age were required to recognize both verbal and nonverbal stimuli presented tachistoscopically. Results of a backward visual masking paradigm varying stimulus onset asynchrony (SOA) indicated the retarded subjects performed poorer at the longest…

Hornstein, Henry A.; Mosley, James L.

1987-01-01

394

Effect of Fluorochemicals on Flame-Retardant Fibers  

Microsoft Academic Search

To develop durable flame, water and oil repellent fabrics, a study was undertaken using fluorochemicals as water and oil repellent agents on inherently flame-retardant fibers. The treated samples were leached for 30 and 60 min to evaluate durability of the chemical treatment. The fluorochemical treatments produced durable fabrics that were simultaneously flame retardant and water and oil repellent. The effect

NISHKAM KASTURIYA; PRIYANKA KATIYAR; G. S. BHARGAVA; ANITA NISHKAM

2003-01-01

395

Arizona's Comprehensive Plan to Help the Mentally Retarded.  

ERIC Educational Resources Information Center

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…

Arizona State Dept. of Health, Phoenix. Mental Retardation Section.

396

Thoughts on the Police Interrogation of Individuals with Mental Retardation.  

ERIC Educational Resources Information Center

|This article presents 20 reasons why it is usually easy for police to get confessions from individuals with mental retardation. It urges that police training be seen as everyone's responsibility and that individuals with mental retardation be prepared for possible police interrogation. (DB)|

Perske, Robert

1994-01-01

397

Muscle Fatigue during Intermittent Exercise in Individuals with Mental Retardation  

ERIC Educational Resources Information Center

|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…

Zafeiridis, Andreas; Giagazoglou, Paraskevi; Dipla, Konstantina; Salonikidis, Konstantinos; Karra, Chrisanthi; Kellis, Eleftherios

2010-01-01

398

Development of the Fear Survey for Adults with Mental Retardation  

ERIC Educational Resources Information Center

|This paper describes the development of the fear survey for adults with mental retardation (FSAMR) and provides initial evidence of its psychometric properties. The FSAMR was designed to be sensitive to the assessment needs of individuals with mental retardation. The items were developed through open-ended interviews, a review of existing…

Ramirez, Sylvia Z.; Lukenbill, James F.

2007-01-01

399

Behavioral Treatment of Aggression in the Mentally Retarded: A Review.  

ERIC Educational Resources Information Center

|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…

Feldstein, Jerome H.

400

Carbamazepine-Induced Hyponatremia in Patients with Mental Retardation.  

ERIC Educational Resources Information Center

|This study of 40 patients with mental retardation receiving carbamazepine found hyponatremia in only 5 percent of these patients and found a statistically, but not clinically, significant decrease in serum sodium levels in patients receiving anticonvulsant polytherapy. Results support the use of this drug with patients with mental retardation and…

Kastner, Ted; And Others

1992-01-01

401

Regeneration of the Amputated Amphibian Limb: Retardation by Hemicholinium-3  

Microsoft Academic Search

Doses of hemicholinium-3 which partially paralyze the larval salamander profoundly retarded regeneration of the amputated hind limb. The drug also reduced the vascularity and mitotic index of the regenerating tissue. After withdrawal of the drug the rate of regeneration returned to normal. Atropine, in a daily dose of 40 milligrams per kilogram of body weight, did not retard growth. These

F. Hui; A. Smith

1970-01-01

402

A Note on Mental Retardation in the Cook Islands.  

ERIC Educational Resources Information Center

The results of a survey of mental retardation in the Cook Islands are presented. The need for the establishment of services for the mentally retarded is discussed. The close ties that the Cook Islands have with New Zealand have probably ameliorated some problems encountered elsewhere in Pacific Island Territories while creating others. (Author)

Price, J.

1980-01-01

403

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 ...

404

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...

405

Current Mental Retardation Research in the Soviet Union.  

ERIC Educational Resources Information Center

|The paper consists of a review of 24 studies on mental retardation published in two Soviet journals between 1970 and 1980. An introductory section focuses on the theoretical framework for mental retardation research in the Soviet Union with a differentiation between oligophrenics (who have organic brain damage) and the intellectually backward (or…

Holowinsky, Ivan Z.

406

Qualitative Differences in the Structure of Intelligence of Retarded Children.  

ERIC Educational Resources Information Center

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…

Wilson, Sheryl L.; Cleaves, Wallace T.

407

The Mentally Retarded Inmate: Prison Adjustment and Implications for Treatment.  

ERIC Educational Resources Information Center

|Examined whether or not there were differences in the prison adaptation of mentally retarded and nonretarded inmates. Compared 439 retarded inmates, 439 matched nonretarded inmates, and 439 unmatched nonretarded inmates. Found statistically significant differences between groups in the areas of assaults on correctional officers and other…

Smith, Craig; And Others

1988-01-01

408

Optimization of Halogen Free Flame Retardant Wire and Cable Compounds  

Microsoft Academic Search

Halogen Free Flame Retardant (HFFR) wire and cable compounds use ATH or MDH as the main flame retardant component. Together with this it is necessary to use a maleated coupling agent and other additives such as lubricant, antioxidant, which allow incorporation of high ATH loading. Optim® maleic anhydride grafted resins can be used as coupling agents between polymers and fillers

Vidya Gupta; Devendra Jain

409

Halogen-free flame retardation and silane crosslinking of polyethylenes  

Microsoft Academic Search

Halogen-free flame-retarded and silane crosslinkable polyethylenes have been prepared by a melt process using magnesium hydroxide (MH) as a flame retardant. The effects of silane concentration, peroxide concentration, etc. on the silane grafting on linear low density polyethylenes were investigated. The thermal analysis of the silane crosslinked polyethylenes was performed by thermogravimetry (TG), and its results show that silane crosslinking

Zhengzhou Wang; Yuan Hu; Zhou Gui; Ruowen Zong

2003-01-01

410

Weathering resistance of halogen-free flame retardance in thermoplastics  

Microsoft Academic Search

The influence of weathering on the fire retardancy of polymers is investigated by means of a cone calorimeter test, before and after artificial weathering. The surface degradation was monitored using different techniques (ATR–FTIR, microscopy, colour measurement). Different kinds of polymeric materials were chosen, all as they are used in practice: polycarbonate (PC) blends, polyamide (PA) and polypropylene (PP) flame-retarded with

U. Braun; V. Wachtendorf; A. Geburtig; H. Bahr; B. Schartel

2010-01-01

411

Halogen free flame retardants for Epoxy substrate in electronic applications  

Microsoft Academic Search

Epoxy resins together with glass fibers had been extensively used as the core substrate in electronic applications due to its superior mechanical properties and chemical resistance. Due to its application in high heat environment, flame retardants became a required additive for the epoxy resins to prevent any flame mishaps. In this paper, intumescent and nitrogen based flame retardants, specifically the

W. K. P. Lim; M. Mariatti; W. S. Chow; K. T. Mar

2010-01-01

412

A NEW GENERATION OF FLAME RETARDED POLYAMIDES BASED ON PHOSPHINATES  

Microsoft Academic Search

Polyamide 6 and 66, especially glass fibre reinforced grades, can be effectively fire retarded with a new halogen free product based on an organic phosphinic acid salt. Organic phosphinates are a newly developed class of flame retardants for engineering thermoplastics, and are especially effective for polyamides and polyesters. The chemical registration process in Europe (ELINCS) and US (TSCA) has already

S. Hörold; O. Schacker; W. Wanzke

413

Nutrition and Mental Retardation. An Annotated Bibliography, 1964-1970.  

ERIC Educational Resources Information Center

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…

Springer, Ninfa Saturnino

414

Can Nutritional Supplements Help Mentally Retarded Children? An Exploratory Study  

Microsoft Academic Search

To explore the hypothesis that mental retardations are in part genetotrophic diseases (diseases in which the genetic pattern of the afflicted individual requires an augmented supply of one or more nutrients such that when these nutrients are adequately supplied the disease is ameliorated), we carried out a partially double-blind experiment with 16 retarded children (initial IQs, ≈ 17-70) of school

Ruth F. Harrell; Ruth H. Capp; Donald R. Davis; Julius Peerless; Leonard R. Ravitz

1981-01-01

415

Visual evoked potentials in disproportionately growth-retarded human neonates  

Microsoft Academic Search

To study brain function in the neonatal period, disproportionately growth-retarded (n = 33) and appropriately grown (n = 21) infants were examined using Doppler flow velocities prenatally and visual evoked potentials postnatally. Visual evoked potentials recordings were made at gestation of 40 and 46 weeks. The group of growth-retarded infants had significantly prolonged latencies to both of the two major

C. Magnus Thordstein; Bo L Sultan; Margareta M Wennergren; Eva Törnqvist; Kaj G Lindecrantz; Ingemar Kjellmer

2004-01-01

416

Programs for Preventing the Causes of Mental Retardation.  

ERIC Educational Resources Information Center

|This monograph, which reports findings from the New Jersey Governor's Council on the Prevention of Mental Retardation, discusses the scope of mental retardation (MR), its causes, identification of people at risk, and prevention methods. The Council cites several cost-effective prevention programs, such as vaccination programs and prenatal care…

Oliphant, Peter S.; And Others

417

Fire Retardant-Caused Corrosion: A 1986 Field Reassessment.  

National Technical Information Service (NTIS)

In 1986, selected air attack bases in the Western United States were inspected to reassess the threat of fire retardant-caused corrosion to aircraft and retardant-mixing equipment. Conclusions were that the corrosion problems had not worsened during the p...

C. W. George G. A. Gehring

1988-01-01

418

Automatic and Effortful Processing by Mentally Retarded and Nonretarded Persons.  

ERIC Educational Resources Information Center

Brain-injured (N=24), cultural-familially retarded (N=24), and nonretarded (N=28) adolescents and young adults were compared on a letter priming task requiring recognition of matched pairs. Response time in both retarded groups was considerably slower than in the nonretarded group, and effortful processing was also slower to develop. (JW)

Meador, Darlene M.; Ellis, Norman R.

1987-01-01

419

Physical Trauma as an Etiological Agent in Mental Retardation.  

ERIC Educational Resources Information Center

|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…

Angle, Carol R., Ed.; Bering, Edgar A., Jr., Ed.

420

Communication Problems in Mental Retardation: Diagnosis and Management.  

ERIC Educational Resources Information Center

|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.…

Lillywhite, Herold S.; Bradley, Doris P.

421

A Novel Non-Halogenated Flame Retardant for Composite Materials  

Microsoft Academic Search

Flame retardants, such as inorganic fillers or halogenated resins, are incorporated into composites either as additives or reactive materials. In order to improve processability and mechanical properties, as well as reduce smoke toxicity, a method is being developed to introduce highly effective, inexpen- sive flame retardant materials into thermoset resins. Superabsorbent polymers (SAP) can be loaded with inexpensive inorganic phosphates

Martin Rogers; Lisa Sterner; Thomas Amos; Ayesha Johnson

422

Screening of the ARX gene in 682 retarded males.  

PubMed

The newly identified gene, ARX, when mutated has been shown to cause both syndromic and nonsyndromic forms of mental retardation. It seems that the less severe forms are due to polyalanine expansions and missense mutations in the gene. We screened 682 developmentally retarded males for polyalanine expansions in ARX in order to examine the contribution of ARX mutations to the causes of developmental retardation. We also reinvestigated 11 putative MRX and three MR families where no cause of mental retardation had been found, by mutational analysis of ARX. Mutational analysis was also performed in 11 probands with autism from families with two or more affected males. We find that previously described polyalanine expansions of ARX are not a common cause of mental retardation. PMID:15199382

Grønskov, Karen; Hjalgrim, Helle; Nielsen, Inge-Merete; Brøndum-Nielsen, Karen

2004-09-01

423

Pmp-Like Proteins Pls1 and Pls2 Are Secreted into the Lumen of the Chlamydia trachomatis Inclusion  

Microsoft Academic Search

The obligate intracellular pathogen Chlamydia trachomatis secretes effector proteins across the membrane of the pathogen-containing vacuole (inclusion) to modulate host cellular functions. In an immunological screen for secreted chlamydial proteins, we identified CT049 and CT050 as potential inclusion membrane-associated proteins. These acidic, nonglobular proteins are paralogously related to the passenger domain of the poly- morphic membrane protein PmpC and, like

Ine Jorgensen; Raphael H. Valdivia

2008-01-01

424

Conservation of telomere protein complexes: shuffling through evolution.  

PubMed

The rapid evolution of telomere proteins has hindered identification of orthologs from diverse species and created the impression that certain groups of eukaryotes have largely non-overlapping sets of telomere proteins. However, the recent identification of additional telomere proteins from various model organisms has dispelled this notion by expanding our understanding of the composition, architecture and range of telomere protein complexes present in individual species. It is now apparent that versions of the budding yeast CST complex and mammalian shelterin are present in multiple phyla. While the precise subunit composition and architecture of these complexes vary between species, the general function is often conserved. Despite the overall conservation of telomere protein complexes, there is still considerable species-specific variation, with some organisms having lost a particular subunit or even an entire complex. In some cases, complex components appear to have migrated between the telomere and the telomerase RNP. Finally, gene duplication has created telomere protein paralogs with novel functions. While one paralog may be part of a conserved telomere protein complex and have the expected function, the other paralog may serve in a completely different aspect of telomere biology. PMID:19839711

Linger, Benjamin R; Price, Carolyn M

425

Analysis of the Criminal Justice Personnels' (Police, Lawyers, Judges) Understanding of Mental Retardation and of the Mentally Retarded Offender.  

ERIC Educational Resources Information Center

|The study involving 100 police officers, 75 lawyers, and 35 judges was designed to investigate and analyze the criminal justice system (CJS) personnel's understanding of mental retardation and the mentally retarded (MR) offender. Among findings obtained from responses to questionnaires were the following: 65% of the respondents indicated they…

Schilit, Jeffrey

426

Homology Modeling and Domain Interactions in Fetal Serum Protein  

NSDL National Science Digital Library

This exercise is intended to engage students to design, model, visualize and evaluate the theoretical three dimensional image of a protein whose structure has not yet been determined. The phylogenetic analysis in Biology Workbench of paralogs and orthologs to alphafetoprotein reveals more divergent sequences within active site domains of related proteins without biological activity and greater conservation of the alphafetoprotein active domain between different species.

Steve Festin (Hamilton College;)

2003-10-12

427

Attitudes of Fast Food Restaurant Managers towards Hiring the Mentally Retarded: A Survey.  

ERIC Educational Resources Information Center

The majority of the managers reported some prior experience with mentally retarded persons, believed that the mentally retarded should be employed competitively, but were undecided whether they personally would employ an adequately prepared mentally retarded worker. (SW)

Gruenhagen, Kathleen A.

1982-01-01

428

Cooperative and Competitive Behavior of Retarded and Nonretarded Children at Two Ages  

ERIC Educational Resources Information Center

|Results show that the retarded group was significantly more cooperative than the nonretarded group, and the 6-7 year retarded group was more cooperative than the 11-12-year retarded group. (Authors/CB)|

Madsen, Millard C.; Connor, Catherine

1973-01-01

429

Cooperative and Competitive Behavior of Retarded and Nonretarded Children at Two Ages  

ERIC Educational Resources Information Center

Results show that the retarded group was significantly more cooperative than the nonretarded group, and the 6-7 year retarded group was more cooperative than the 11-12-year retarded group. (Authors/CB)

Madsen, Millard C.; Connor, Catherine

1973-01-01

430

The Retarding-Field Tube as a Detector for Any Carrier Frequency  

Microsoft Academic Search

The rectifying effect of the retarding-field detector even at extremely high frequencies is due to the nonlinear retarding-field characteristic curve. The more detailed discussion of the retarding-field circuit as a \\

H. E. Hollmann

1934-01-01

431

Evolution of developmental roles of Pax2/5/8 paralogs after independent duplication in urochordate and vertebrate lineages  

PubMed Central

Background Gene duplication provides opportunities for lineage diversification and evolution of developmental novelties. Duplicated genes generally either disappear by accumulation of mutations (nonfunctionalization), or are preserved either by the origin of positively selected functions in one or both duplicates (neofunctionalization), or by the partitioning of original gene subfunctions between the duplicates (subfunctionalization). The Pax2/5/8 family of important developmental regulators has undergone parallel expansion among chordate groups. After the divergence of urochordate and vertebrate lineages, two rounds of independent gene duplications resulted in the Pax2, Pax5, and Pax8 genes of most vertebrates (the sister group of the urochordates), and an additional duplication provided the pax2a and pax2b duplicates in teleost fish. Separate from the vertebrate genome expansions, a duplication also created two Pax2/5/8 genes in the common ancestor of ascidian and larvacean urochordates. Results To better understand mechanisms underlying the evolution of duplicated genes, we investigated, in the larvacean urochordate Oikopleura dioica, the embryonic gene expression patterns of Pax2/5/8 paralogs. We compared the larvacean and ascidian expression patterns to infer modular subfunctions present in the single pre-duplication Pax2/5/8 gene of stem urochordates, and we compared vertebrate and urochordate expression to infer the suite of Pax2/5/8 gene subfunctions in the common ancestor of olfactores (vertebrates + urochordates). Expression pattern differences of larvacean and ascidian Pax2/5/8 orthologs in the endostyle, pharynx and hindgut suggest that some ancestral gene functions have been partitioned differently to the duplicates in the two urochordate lineages. Novel expression in the larvacean heart may have resulted from the neofunctionalization of a Pax2/5/8 gene in the urochordates. Expression of larvacean Pax2/5/8 in the endostyle, in sites of epithelial remodeling, and in sensory tissues evokes like functions of Pax2, Pax5 and Pax8 in vertebrate embryos, and may indicate ancient origins for these functions in the chordate common ancestor. Conclusion Comparative analysis of expression patterns of chordate Pax2/5/8 duplicates, rooted on the single-copy Pax2/5/8 gene of amphioxus, whose lineage diverged basally among chordates, provides new insights into the evolution and development of the heart, thyroid, pharynx, stomodeum and placodes in chordates; supports the controversial conclusion that the atrial siphon of ascidians and the otic placode in vertebrates are homologous; and backs the notion that Pax2/5/8 functioned in ancestral chordates to engineer epithelial fusions and perforations, including gill slit openings.

Bassham, Susan; Canestro, Cristian; Postlethwait, John H

2008-01-01

432

Differential responses of the promoters from nearly identical paralogs of loblolly pine ( Pinus taeda L.) ACC oxidase to biotic and abiotic stresses in transgenic Arabidopsis thaliana  

Microsoft Academic Search

Promoters from an ACC oxidase gene (PtACO1) and its nearly identical paralog (NIP) (PtACO2) of loblolly pine (Pinus taeda L.) were recovered from genomic DNA using PCR amplification. Transgenic Arabidopsis plants harboring genetic constructs from which ?-glucuronidase (GUS) expression was driven by the full-length (pACO1:GUS, pACO2:GUS) or truncated (pACO1-1.2:GUS, pACO2-1.2:GUS) loblolly pine ACC oxidase gene promoters displayed distinctive patterns of

Shenghua Yuan; Jeffrey F. D. Dean

2010-01-01

433

An efficiently halogen-free flame-retardant long-glass-fiber-reinforced polypropylene system  

Microsoft Academic Search

In order to solve the “candlewick effect” caused by glass fibers, which results in the decrease of flame retardancy of flame-retardant long-glass-fiber-reinforced polypropylene (LGFPP) systems, and the deterioration of mechanical properties caused by adding an additional amount of flame retardants compared with flame-retardant non-glass-fiber-reinforced polypropylene systems so as to keep a same flame retardancy, a novel intumescent flame retardant (IFR)

Yun Liu; Cheng-Liang Deng; Jing Zhao; Jun-Sheng Wang; Li Chen; Yu-Zhong Wang

2011-01-01

434

FXR1, an autosomal homolog of the fragile X mental retardation gene.  

PubMed Central

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

Siomi, M C; Siomi, H; Sauer, W H; Srinivasan, S; Nussbaum, R L; Dreyfuss, G

1995-01-01

435

Tetradecabromodiphenoxybenzene flame retardant undergoes photolytic debromination.  

PubMed

Highly brominated flame retardant compounds have relatively low bioavailability, but some of these compounds have been shown to be of environmental concern. Tetradecabromodiphenoxybenzene (TDBDPB) contains 14 bromine atoms and is the major component of commercial flame retardant mixtures such as the recently phased out SAYTEX 120. The chemical stability of TDBDPB has not been reported. We demonstrated that TDBDPB can photolytically undergo stepwise reductive debromination that follows first-order kinetic degradation models when exposed to UV or natural sunlight radiation and when dissolved in the solvents tetrahydrofuran, methanol, or n-hexane. Photolytic degradation half-lives of TDBDPB ranged from 98 to 169 min, 0.78 to 0.83 min, 1.0 to 1.8 min, and 4.9 to 7.4 min when exposed to UV-A, -B, and -C, and natural sunlight, respectively. However, the TDBDPB half-lives when exposed to UV-B and especially UV-C are likely underestimated since solutions were in borosilicate glass vials during irradiation resulting from increasingly lower % transmittance of ? < 300 nm. Neat technical TDBDPB powder exposed to UV-B and -C radiation also produced less brominated products, although the rate was much slower as compared to when in solution. Exposure of TDBDPB solutions to natural sunlight generated a number of polybrominated diphenoxybenzene (PBDPB) photolysis products, among which the Br(4)- to Br(7)-PBDPBs were the most frequently observed and estimated to be most concentrated. As evidenced by the TDBDPB half-lives and the degree of debrominated byproduct formation, the findings showed that the fraction of the absorbed irradiation that was of sufficient energy to break C-Br bonds of TDBDPB and lesser brominated PBDPBs increased from UV-B or -C to UV-A. Coincidentally, we recently reported on the presence of several Br(4) to Br(6) methoxylated PBDPBs in the Great Lakes herring gull eggs, which may be linked to a TDBDPB source via photolytic degradation to more bioavailable and persistent debromination products. PMID:23289781

Chen, Da; Letcher, Robert J; Gauthier, Lewis T; Chu, Shaogang

2013-01-16

436

Ras1 Acts through Duplicated Cdc42 and Rac Proteins to Regulate Morphogenesis and Pathogenesis in the Human Fungal Pathogen Cryptococcus neoformans.  

PubMed

Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, and Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies of all three, provides a unique model in which to examine the interactions of these conserved proteins. Previously, we demonstrated that RAS1 mediates C. neoformans virulence by acting as a central regulator of both thermotolerance and mating. We report here that ras1? mutants accumulate defects in polarized growth, cytokinesis, and cell cycle progression. We demonstrate that the ras1? defects in thermotolerance and mating can be largely explained by the compromised activity of four downstream Rho-GTPases: the Cdc42 paralogs, Cdc42 and Cdc420; and the Rac paralogs, Rac1 and Rac2. Further, we demonstrate that the separate GTPase classes play distinct Ras-dependent roles in C. neoformans morphogenesis and pathogenesis. Cdc42 paralogs primarily control septin localization and cytokinesis, while Rac paralogs play a primary role in polarized cell growth. Together, these duplicate, related signaling proteins provide a robust system to allow microbial proliferation in the presence of host-derived cell stresses. PMID:23950731

Ballou, Elizabeth Ripley; Kozubowski, Lukasz; Nichols, Connie B; Alspaugh, J Andrew

2013-08-08

437

40 CFR 201.26 - Procedures for the measurement on receiving property of retarder and car coupling noise.  

Code of Federal Regulations, 2013 CFR

...measurement on receiving property of retarder and car coupling noise. 201.26 Section 201...measurement on receiving property of retarder and car coupling noise. (a) Retarders ...Ladj ave max ) for retarders. (b) Car coupling impact â(1)...

2013-07-01

438

40 CFR 201.26 - Procedures for the measurement on receiving property of retarder and car coupling noise.  

Code of Federal Regulations, 2010 CFR

...receiving property of retarder and car coupling noise. 201.26 Section 201.26...receiving property of retarder and car coupling noise. (a) Retarders â(1) Microphone...ave max ) for retarders. (b) Car coupling impact â(1) Microphone....

2009-07-01

439

40 CFR 201.26 - Procedures for the measurement on receiving property of retarder and car coupling noise.  

Code of Federal Regulations, 2010 CFR

...receiving property of retarder and car coupling noise. 201.26 Section 201.26...receiving property of retarder and car coupling noise. (a) Retarders â(1) Microphone...ave max ) for retarders. (b) Car coupling impact â(1) Microphone....

2010-07-01

440

40 CFR 201.26 - Procedures for the measurement on receiving property of retarder and car coupling noise.  

Code of Federal Regulations, 2011 CFR

...measurement on receiving property of retarder and car coupling noise. 201.26 Section 201...measurement on receiving property of retarder and car coupling noise. (a) Retarders ...Ladj ave max ) for retarders. (b) Car coupling impact â(1)...

2011-07-01

441

Linking energy production and protein synthesis in hydrogenotrophic methanogens.  

PubMed

Hydrogenotrophic methanogens possessing the hydrogen-dependent dehydrogenase Hmd also encode paralogs of this protein whose function is poorly understood. Here we present biochemical evidence that the two inactive Hmd paralogs of Methanocaldococcus jannaschii, HmdII and HmdIII, form binary and ternary complexes with several components of the protein translation apparatus. HmdII and HmdIII, but not the active dehydrogenase Hmd, bind with micromolar binding affinities to a number of tRNAs and form ternary complexes with tRNA(Pro) and prolyl-tRNA synthetase (ProRS). Fluorescence spectroscopy experiments also suggest that binding of HmdII and ProRS involves distinct binding determinants on the tRNA. These biochemical data suggest the possibility of a regulatory link between energy production and protein translation pathways that may allow a rapid cellular response to altered environmental conditions. PMID:22401293

Oza, Javin P; Sowers, Kevin R; Perona, John J

2012-03-13

442

The prevalence of intrauterine growth retardation in Mexican Americans.  

PubMed Central

This study evaluated the prevalence of intrauterine growth retardation in Mexican Americans compared with non-Hispanic Whites in the state of Arizona. Data came from all live birth certificates in 1986 and 1987. Rates of intrauterine growth retardation in Mexican-American and non-Hispanic White infants in Arizona were lower than those in White infants in California. Differences in patterns of the 10th percentile growth distribution curves were observed between infants born in Arizona and those born in California. Compared with non-Hispanic Whites, Mexican Americans had lower adjusted odds ratios for intrauterine growth retardation according to several maternal risk characteristics.

Balcazar, H

1994-01-01

443

Fire retardant effects of polymer nanocomposites.  

PubMed

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. PMID:19916477

Hull, T Richard; Stec, Anna A; Nazare, Shonali

2009-07-01

444

The Overweight Preschool Retarded Child Can and Should Lose Weight.  

ERIC Educational Resources Information Center

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)

Fox, Robert; And Others

1983-01-01

445

Activational Peaking in Educable and Trainable Mentally Retarded Persons  

ERIC Educational Resources Information Center

A study involving 10 educable and 10 trainable mentally retarded adolescents indicated that levels of intellectual functioning influenced patterns of autonomic activation as measured by magnitude of the galvanic skin response. (CL)

Gargiulo, Richard M.; Uno, Tad

1977-01-01

446

Development and Testing of Flame Retardant Additives and Polymers.  

National Technical Information Service (NTIS)

Novel flame-retardant chemical additives and polymers were synthesized and their flammability measured in the Underwriters Laboratory test for flammability of plastics (UL94). Self-extinguishing (V-0) compositions were obtained for poly (acrylonitrile-but...

J. L. Jurs

2007-01-01

447

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2013 CFR

...VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Mental Disorders § 4.127 Mental retardation...not be service-connected. However, disability resulting from a mental disorder that is superimposed upon...

2013-07-01

448

Retardation in Mathematics: A Consideration of Multi-Factorial Determination  

ERIC Educational Resources Information Center

Discusses mathematical retardation as a construct and examines the possible contributions of emotional factors, socioeconomic factors, poor teaching, cognitive factors, and sex difference to low achievement in mathematics. (JB)

Lansdown, Richard

1978-01-01

449

Guide to Establishing an Activity Center for Mentally Retarded Persons.  

National Technical Information Service (NTIS)

The principle of normalization and the developmental model are accepted in the U.S. as key elements in designing programs and service delivery systems for mentally retarded persons. The principle of normalization involves utilizing means to establish beha...

A. Bergman

1977-01-01

450

The effect of etofibrate retard, bezafibrate and procetofen.  

PubMed

The effects and side effects of 500 mg of etofibrate retard were comared with those of 100 mg t.i.d. of procetofene and of 200 mg t.i.d. of bezafibrate in two different studies in 60 and 63 outpatients respectively. In types IIa, IIb and IV hyperlipoproteinaemia cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were affected markedly stronger by procetofene and bezafibrate than by etofibrate retard. This impact was not only superior in its quantity by also in its proportion of responding patients. Side effects were a flush under etofibrate retard and gastric discomfort, headache and nausea in about 5% under all three drugs. Etofibrate retard did not give significant changes in the laboratory parameters while procetofene and bezafibrate slightly increased transaminases and creatinine. Alcaline phosphatase and GT were significantly lowered. Uric acid decreased under procetofene and increased under bezafibrate. PMID:7458677

Luley, C; Schwartzkopff, W; Schilling, A; Calder, D; Scheffler, W

1980-01-01

451

Assessing the Work Personalities of Mentally Retarded Adults.  

National Technical Information Service (NTIS)

A series of studies was conducted to modify administration of the General Aptitude Test Battery (GATB) and the content of the Minnesota Importance Questionnaire (MIQ) for use with mentally retarded individuals. The revised MIQ was a useful tool in assessi...

L. H. Lofquist R. V. Dawis D. J. Weiss

1970-01-01

452

Personal Vulnerability to Victimization of People with Mental Retardation  

Microsoft Academic Search

People with mental retardation are more vulnerable to victimization. This is a con- sequence of cultural, institutional, and other environmental circumstances but may include victim characteristics. To recognize this is not \\

TED NETTELBECK; CARLENE WILSON

2002-01-01

453

Gender Identity in a Group of Retarded Children.  

ERIC Educational Resources Information Center

The Michigan Gender Identity Test (MGIT) was administered to 52 retarded children (three to ten years old) and 36 normal children (two to five years old) to assess the acquisition of gender identity. (Author)

Abelson, Geoffrey; Paluszny, Maria

1978-01-01

454

Regional Plan for Developmental Disabilities: Epileptic, Cerebral Palsy, Mental Retardation.  

National Technical Information Service (NTIS)

The regional plan of the North Central Texas Council of Governments for the developmental disabilities of epilepsy, cerebral palsy, and mental retardation is presented. It is pointed out that the three developmental disabilities share many common needs wh...

1973-01-01

455

Assessing and Increasing Descriptive Communication Skills in Retarded Children  

ERIC Educational Resources Information Center

The purpose of the paper was to review the impact of recent developments in research methodology with specific reference to the assessment and habilitation of communication problems in retarded children. (Author)

Longhurst, Thomas M.

1972-01-01

456

Factors Affecting Production by the Retarded: Base Rate  

ERIC Educational Resources Information Center

Twenty educable or trainable retarded adolescents and adults in three sheltered workshops, who worked either 1 or 3 hours per day for 10 days under a no-external reinforcement condition, assembled a 14-piece bicycle brake. (Author/MC)

Gold, Marc W.

1973-01-01

457

Eye Gaze and Dominance Hierarchy in Profoundly Mentally Retarded Males  

ERIC Educational Resources Information Center

|Examined was the relationship between duration of eye gaze and ranked position in a social group's dominance hierarchy in two groups of 12 institutionalized profoundly mentally retarded adults. (CL)|

Rago, William V., Jr.

1977-01-01

458

X-linked mental retardation associated with macro-orchidism  

Microsoft Academic Search

Two families are described with an X-linked form of mental retardation in whom the affected males were found to have bilateral enlargement of the testes. No conclusive evidence of any endocrinological disturbance was found.

G Turner; C Eastman; J Casey; A McLeay; P Procopis; B Turner

1975-01-01

459

Flame retardant mechanism of organo-bentonite in polypropylene  

Microsoft Academic Search

Effects of organo-bentonite on the flame retardancy, mechanical and rheological properties of intumescent flame retardant (IFR) polypropylene (PP) were investigated. The X-ray diffraction and transmission electron microscopy measurements indicated that the organo-clay particles were partially exfoliated. Thermogravimetric analysis showed that incorporating 1.8 mass% organo-clay into PP\\/IFR considerably enhanced the thermal stability and increased the char residue by ca. 7 mass%

Baoxian Du; Zhenghong Guo; Ping'an Song; Hui Liu; Zhengping Fang; Yu Wu

2009-01-01

460

Ignition inhibitors for cellulosic materials. [Fire retardants; effects of irradiation  

Microsoft Academic Search

By exposing samples to various irradiance levels from a calibrated thermal radiation source, the ignition responses of blackened alpha-cellulose and cotton cloth with and without fire-retardant additives were compared. Samples treated with retardant compounds which showed the most promise were then isothermally pyrolyzed in air for comparisons between the pyrolysis rates. Alpha-cellulose samples containing a mixture of boric acid, borax,

Alvares

1976-01-01