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1

Using orthologous and paralogous proteins to identify specificity determining residues  

PubMed Central

Background 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. Results Assuming conservation of specificity among orthologs and different specificity of paralogs, we identify residues which 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. Conclusions While sets of orthologous and paralogous proteins can be easily derived from complete genomic sequences, our method can identify putative specificity determinants in such proteins.

2002-01-01

2

Paralogous genes encoding transport proteins in microbial genomes  

Microsoft Academic Search

The largest superfamilies of prokaryotic genes encode transport proteins, but many transporters are encoded by orphan genes or those that comprise very small families. We have analyzed eighteen completely sequenced prokaryotic genomes for paralogous transport systems and have thereby identified 76 permease families. In this short review, we present and discuss the paralogues in some of these families and interpret

Milton H Saier; Ian T Paulsen

1999-01-01

3

Domain mapping of the Rad51 paralog protein complexes  

PubMed Central

The five human Rad51 paralogs are suggested to play an important role in the maintenance of genome stability through their function in DNA double-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 mutants of the Rad51 paralogs. The models of the human Rad51B, Rad51C, Xrcc3 and murine Rad51D (mRad51D) proteins reveal distinct N-terminal and C-terminal domains connected by a linker region. Using yeast two-hybrid and co-immunoprecipitation techniques, we have demonstrated that a fragment of Rad51B containing amino acid residues 1–75 interacts with the C-terminus and linker of Rad51C, residues 79–376, and this region of Rad51C also interacts with mRad51D and Xrcc3. We have also determined that the N-terminal domain of mRad51D, residues 4–77, binds to Xrcc2 while the C-terminal domain of mRad51D, residues 77–328, binds Rad51C. By this, we have identified the binding domains of the BCDX2 and CX3 complexes to further characterize the interaction of these proteins and propose a scheme for the three-dimensional architecture of the BCDX2 and CX3 paralog complexes.

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

2004-01-01

4

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

5

Paralogs of Genes Encoding Metal Resistance Proteins in Cupriavidus metallidurans Strain CH34  

Microsoft Academic Search

Cupriavidus (Wautersia, Ralstonia, Alcaligenes) metallidurans strain CH34is a well-studied example of a metal-resistant proteobacterium. Genome sequence analysis revealed the presence of a variety of paralogs of proteins that were previously shown to be involved in heavy metal resistance. Which advantage has C. metallidurans in maintaining all these paralogs during evolution? Paralogs investigated belong to the families RND (resistance nodulation cell

Dietrich H. Nies; Grit Rehbein; Toni Hoffmann; Cindy Baumann; Cornelia Grosse

2006-01-01

6

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

NASA Astrophysics Data System (ADS)

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

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

2006-03-01

7

Differential Expression of Two Paralogous Genes of Bacillus subtilis Encoding Single-Stranded DNA Binding Protein  

Microsoft Academic Search

The Bacillus subtilis genome comprises two paralogous single-stranded DNA binding protein (SSB) genes, ssb and ywpH, which show distinct expression patterns. The main ssb gene is strongly expressed during exponential growth and is coregulated with genes encoding the ribosomal proteins S6 and S18. The gene organization rpsF-ssb-rpsR as observed in B. subtilis is found in many gram-positive as well as

Cordula Lindner; Reindert Nijland; Mariska van Hartskamp; Sierd Bron; Leendert W. Hamoen; Oscar P. Kuipers

2004-01-01

8

Mapping proteins in the presence of paralogs using units of coevolution  

PubMed Central

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

2013-01-01

9

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

PubMed Central

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

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

2014-01-01

10

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

PubMed

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

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

2014-08-01

11

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

12

The BBA01 Protein, a Member of Paralog Family 48 from Borrelia burgdorferi, Is Potentially Interchangeable with the Channel-Forming Protein P13  

Microsoft Academic Search

The Borrelia burgdorferi genome exhibits redundancy, with many plasmid-carried genes belonging to paralo- gous gene families. It has been suggested that certain paralogs may be necessary in various environments and that they are differentially expressed in response to different conditions. The chromosomally located p13 gene which codes for a channel-forming protein belongs to paralog family 48, which consists of eight

Marija Pinne; Katrin Denker; Elin Nilsson; Roland Benz; Sven Bergstrom

2006-01-01

13

Protein signatures that promote operator selectivity among paralog MerR monovalent metal ion regulators.  

PubMed

Two paralog transcriptional regulators of the MerR family, CueR and GolS, are responsible for monovalent metal ion sensing and resistance in Salmonella enterica. Although similar in sequence and also in their target binding sites, these proteins differ in signal detection and in the set of target genes they control. Recently, we demonstrated that selective promoter recognition depends on the presence of specific bases located at positions 3' and 3 within the operators they interact with. Here, we identify the amino acid residues within the N-terminal DNA-binding domain of these sensor proteins that are directly involved in operator discrimination. We demonstrate that a methionine residue at position 16 of GolS, absolutely conserved among GolS-like proteins but absent in all CueR-like xenologs, is the key to selectively recognize operators that harbor the distinctive GolS-operator signature, whereas the residue at position 19 finely tunes the regulator/operator interaction. Furthermore, swapping these residues switches the set of genes recognized by these transcription factors. These results indicate that co-evolution of a regulator and its cognate operators within the bacterial cell provides the conditions to avoid cross-recognition and guarantees the proper response to metal injury. PMID:23733186

Humbert, María V; Rasia, Rodolfo M; Checa, Susana K; Soncini, Fernando C

2013-07-12

14

Protein Phosphatase 1 ? Paralogs Encode the Zebrafish Myosin Phosphatase Catalytic Subunit  

PubMed Central

Background The myosin phosphatase is a highly conserved regulator of actomyosin contractility. Zebrafish has emerged as an ideal model system to study the in vivo role of myosin phosphatase in controlling cell contractility, cell movement and epithelial biology. Most work in zebrafish has focused on the regulatory subunit of the myosin phosphatase called Mypt1. In this work, we examined the critical role of Protein Phosphatase 1, PP1, the catalytic subunit of the myosin phosphatase. Methodology/Principal Findings We observed that in zebrafish two paralogous genes encoding PP1?, called ppp1cba and ppp1cbb, are both broadly expressed during early development. Furthermore, we found that both gene products interact with Mypt1 and assemble an active myosin phosphatase complex. In addition, expression of this complex results in dephosphorylation of the myosin regulatory light chain and large scale rearrangements of the actin cytoskeleton. Morpholino knock-down of ppp1cba and ppp1cbb results in severe defects in morphogenetic cell movements during gastrulation through loss of myosin phosphatase function. Conclusions/Significance Our work demonstrates that zebrafish have two genes encoding PP1?, both of which can interact with Mypt1 and assemble an active myosin phosphatase. In addition, both genes are required for convergence and extension during gastrulation and correct dosage of the protein products is required.

Jayashankar, Vaishali; Nguyen, Michael J.; Carr, Brandon W.; Zheng, Dale C.; Rosales, Joseph B.; Rosales, Joshua B.; Weiser, Douglas C.

2013-01-01

15

Characterization of Fragile X Mental Retardation Protein Recruitment and Dynamics in Drosophila Stress Granules  

PubMed Central

The RNA-binding protein Fragile X Mental Retardation (FMRP) is an evolutionarily conserved protein that is particularly abundant in the brain due to its high expression in neurons. FMRP deficiency causes fragile X mental retardation syndrome. In neurons, FMRP controls the translation of target mRNAs in part by promoting dynamic transport in and out neuronal RNA granules. We and others have previously shown that upon stress, mammalian FMRP dissociates from translating polysomes to localize into neuronal-like granules termed stress granules (SG). This localization of FMRP in SG is conserved in Drosophila. Whether FMRP plays a key role in SG formation, how FMRP is recruited into SG, and whether its association with SG is dynamic are currently unknown. In contrast with mammalian FMRP, which has two paralog proteins, Drosophila FMR1 (dFMRP) is encoded by a single gene that has no paralog. Using this genetically simple model, we assessed the role of dFMRP in SG formation and defined the determinants required for its recruitment in SG as well as its dynamics in SG. We show that dFMRP is dispensable for SG formation in vitro and ex vivo. FRAP experiments showed that dFMRP shuttles in and out SG. The shuttling activity of dFMRP is mediated by a protein-protein interaction domain located at the N-terminus of the protein. This domain is, however, dispensable for the localization of dFMRP in SG. This localization of dFMRP in SG requires the KH and RGG motifs which are known to mediate RNA binding, as well as the C-terminal glutamine/asparagine rich domain. Our studies thus suggest that the mechanisms controlling the recruitment of FMRP into SG and those that promote its shuttling between granules and the cytosol are uncoupled. To our knowledge, this is the first demonstration of the regulated shuttling activity of a SG component between RNA granules and the cytosol.

Gareau, Cristina; Houssin, Elise; Martel, David; Coudert, Laetitia; Mellaoui, Samia; Huot, Marc-Etienne; Laprise, Patrick; Mazroui, Rachid

2013-01-01

16

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

17

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

18

Paralogous outer membrane proteins mediate uptake of different forms of iron and synergistically govern virulence in Francisella tularensis tularensis.  

PubMed

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 (55)Fe 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. PMID:22661710

Ramakrishnan, Girija; Sen, Bhaswati; Johnson, Richard

2012-07-20

19

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

20

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

PubMed

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 Arabidopsis thaliana IAP-like protein (AtILP) 1 and 2 by applying an improved motif searching method. Furthermore, homologs of AtILP1 were found to occur as a novel gene family in other organisms such as fungi and animals including Homo sapiens (HsILP1). Like baculovirus IAP repeats (BIRs) in IAPs, ILPs contain two highly conserved BIR-like domains (BLDs) with a putative C2HC-type zinc finger. Phylogenetic analyses indicated that ILPs are putative paralogs of IAPs. Homology modeling revealed that the three-dimensional structure of BLD in HsILP1 is similar to that of BIR. Transient expression of HsILP1 resulted in inhibition of etoposide-induced apoptosis in HEK293 and HeLaS3 cells. These findings suggest that ILPs are conserved in a wide range of eukaryotes including plants, and that their functions are closely related to those of IAPs. PMID:15909109

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

2005-05-01

21

Unfolding stabilities of two paralogous proteins from Naja naja naja (Indian cobra) as probed by molecular dynamics simulations.  

PubMed

Structurally similar but functionally different two paralogous proteins, CTX1 (a cardiotoxin) and LNTX2 (an alpha-neurotoxin), from venom of Naja naja naja have been homology modeled and subjected to molecular dynamics (MD) simulations at four different temperatures (298 K, 310 K, 373 K & 473 K) under close quarters of physiological conditions. Each MD simulation was performed for 25 ns and trajectory structures stored at every 25 ps were used to probe various structural events occurring in the temperature-induced unfolding of the proteins. Notwithstanding their similar scaffolds, the two proteins are drastically differing in their unfolding stabilities from each other. The structural orders of flexibilities for the CTX1 and LNTX2 were found to be loop II > loop III > loop I > C-terminal and C-terminal > loop I > loop III > loop II, respectively. Based on the comprehensive analyses of the simulation data and studies on the various structural interactions of all cardiotoxins (CTXs) and alpha-neurotoxins (NTXs) for which three-dimensional structures determined by experimental techniques are available to date, we have herein proposed a hypothesis ('CN network') rationalizing the differential stabilities of the CTXs and NTXs belonging to a three-finger toxin superfamily of snake venoms. PMID:23791667

Gorai, Biswajit; Sivaraman, Thirunavukkarasu

2013-09-01

22

Genetic polymorphism of Plasmodium vivax msp1p, a paralog of merozoite surface protein 1, from worldwide isolates.  

PubMed

Plasmodium vivax msp1p, a paralog of the candidate vaccine antigen P. vivax merozoite surface protein 1, possesses a signal peptide at its N-terminus and two epidermal growth factor-like domains at its C-terminus with a glycosylphosphatidylinositol attachment site. The msp1p gene locus may have originated by a duplication of the msp1 gene locus in a common ancestor of the analyzed Plasmodium species and lost from P. yoelii, P. berghei, and P. falciparum during their evolutionary history. Full-length sequences of the msp1p gene were generally highly conserved; they had a few amino acid substitutions, one highly polymorphic E/Q-rich region, and a single-to-triple hepta-peptide repeat motif. Twenty-one distinguishable allelic types (A1-A21) of the E/Q-rich region were identified from worldwide isolates. Among them, four types were detected in isolates from South Korea. The length polymorphism of the E/Q-rich region might be useful as a genetic marker for population structure studies in malaria-endemic areas. PMID:21292901

Wang, Yue; Kaneko, Osamu; Sattabongkot, Jetsumon; Chen, Jun-Hu; Lu, Feng; Chai, Jong-Yil; Takeo, Satoru; Tsuboi, Takafumi; Ayala, Francisco J; Chen, Yong; Lim, Chae Seung; Han, Eun-Taek

2011-02-01

23

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

2010-04-30

24

Conformational-Dependent and Independent RNA Binding to the Fragile X Mental Retardation Protein  

PubMed Central

The interaction between the fragile X mental retardation protein (FMRP) and BC1 RNA has been the subject of controversy. We probed the parameters of RNA binding to FMRP in several ways. Nondenaturing agarose gel analysis showed that BC1 RNA transcripts produced by in vitro transcription contain a population of conformers, which can be modulated by preannealing. Accordingly, FMRP differentially binds to the annealed and unannealed conformer populations. Using partial RNase digestion, we demonstrate that annealed BC1 RNA contains a unique conformer that FMRP likely binds. We further demonstrate that this interaction is 100-fold weaker than that the binding of eEF-1A mRNA and FMRP, and that preannealing is not a general requirement for FMRP's interaction with RNA. In addition, binding does not require the N-terminal 204 amino acids of FMRP, methylated arginine residues and can be recapitulated by both fragile X paralogs. Altogether, our data continue to support a model in which BC1 RNA functions independently of FMRP.

Yan, Xin; Denman, Robert B.

2011-01-01

25

LEC1-LIKE paralog transcription factor: how to survive extinction and fit in NF-Y protein complex.  

PubMed

Transcription factor function is crucial for eukaryotic systems. The presence of transcription factor families in genomes represents a significant technical challenge for functional studies. To understand their function, we must understand how they evolved and maintained by organisms. Based on genome scale searches for homologs of LEAFY COTYLEDON-LIKE (L1L; AtNF-YB6), NF-YB transcription factor, we report the discovery and annotation of a complete repertoire of thirteen novel genes that belong to the L1L paralogous gene family of Solanum lycopersicum. Gene duplication events within the species resulted in the expansion of the L1L family. Sequence and structure-based phylogenetic analyses revealed two distinct groups of L1Ls in tomato. Natural selection appears to have contributed to the asymmetric evolution of paralogs. Our results point to key differences among SlL1L paralogs in the presence of motifs, structural features, cysteine composition and expression patterns during plant and fruit development. Furthermore, differences in the binding domains of L1L members suggest that some of them evolved new binding specificities. These results reveal dramatic functional diversification of L1L paralogs for their maintenance in tomato genome. Our comprehensive insights on tomato L1L family should provide the basis for further functional and genetic experimentation. PMID:24727055

Hilioti, Zoe; Ganopoulos, Ioannis; Bossis, Ioannis; Tsaftaris, Athanasios

2014-06-15

26

Paralogous chemoreceptors mediate chemotaxis towards protein amino acids and the non-protein amino acid gamma-aminobutyrate (GABA).  

PubMed

The paralogous receptors PctA, PctB and PctC of Pseudomonas aeruginosa were reported to mediate chemotaxis to amino acids, intermediates of amino acid metabolism and chlorinated hydrocarbons. We show that the recombinant ligand binding regions (LBRs) of PctA, PctB and PctC bind 17, 5 and 2 l-amino acids respectively. In addition, PctC-LBR recognized GABA but not any other structurally related compound. l-Gln, one of the three amino acids that is not recognized by PctA-LBR, was the most tightly binding ligand to PctB suggesting that PctB has evolved to mediate chemotaxis primarily towards l-Gln. Bacteria were efficiently attracted to l-Gln and GABA, but mutation of pctB and pctC, respectively, abolished chemoattraction. The physiological relevance of taxis towards GABA is proposed to reside in an interaction with plants. LBRs were predicted to adopt double PDC (PhoQ/DcuS/CitA) like structures and site-directed mutagenesis studies showed that ligands bind to the membrane-distal module. Analytical ultracentrifugation studies have shown that PctA-LBR and PctB-LBR are monomeric in the absence and presence of ligands, which is in contrast to the enterobacterial receptors that require sensor domain dimers for ligand recognition. PMID:23650915

Rico-Jiménez, Miriam; Muñoz-Martínez, Francisco; García-Fontana, Cristina; Fernandez, Matilde; Morel, Bertrand; Ortega, Alvaro; Ramos, Juan Luis; Krell, Tino

2013-06-01

27

Ortholog search of proteins involved in copper delivery to cytochrome C oxidase and functional analysis of paralogs and gene neighbors by genomic context.  

PubMed

Cytochrome c oxidase (COX) is a multi-subunit enzyme of the mitochondrial respiratory chain. Delivery of metal cofactors to COX is essential for assembly, which represents a long-standing puzzle. The proteins Cox17, Sco1/2, and Cox11 are necessary for copper insertion into CuA and CuB redox centers of COX in eukaryotes. A genome-wide search in all prokaryotic genomes combined with genomic context reveals that only Sco and Cox11 have orthologs in prokaryotes. However, while Cox11 function is confined to COX assembly, Sco acts as a multifunctional linker connecting a variety of biological processes. Multifunctionality is achieved by gene duplication and paralogs. Neighbor genes of Sco paralogs often encode cuproenzymes and cytochrome c domains and, in some cases, Sco is fused to cytochrome c. This led us to suggest that cytochrome c might be relevant to Sco function and the two proteins might jointly be involved in COX assembly. Sco is also related, in terms of gene neighborhood and phylogenetic occurrence, to a newly detected protein involved in copper trafficking in bacteria and archaea, but with no sequence similarity to the mitochondrial copper chaperone Cox17. By linking the assembly system to the copper uptake system, Sco allows COX to face alternative copper trafficking pathways. PMID:15707358

Arnesano, Fabio; Banci, Lucia; Bertini, Ivano; Martinelli, Manuele

2005-01-01

28

Synthetic Motility and Cell Shape Defects Associated with Deletions of Flotillin/Reggie Paralogs in Bacillus subtilis and Interplay of These Proteins with NfeD Proteins  

PubMed Central

Flotillin/reggie proteins are membrane-associated proteins present in all kinds of cells and belong to the family of proteins carrying the SPFH (stomatin, prohibitin, flotillin, and HflK/HflC) domain. In addition to this domain of unknown function, flotillin proteins are characterized by the flotillin domain, which is rich in heptad repeats. Bacterial flotillin orthologs have recently been shown to be part of lipid rafts, like their eukaryotic counterparts, and to be involved in signaling events. Double deletions of floT and the gene encoding the second flotillin-like protein in Bacillus subtilis, floA, show strong synthetic defects in cell morphology, motility, and transformation efficiency. The lack of FloT resulted in a marked defect in motility. Using total internal reflection fluorescence (TIRF) microscopy, we show that both proteins localize in characteristic focal structures within the cell membrane, which move in a highly dynamic and random manner but localize independently of each other. Thus, flotillin paralogs act in a spatially distinct manner. Flotillin domains in both FloA and FloT are essential for focal assemblies and for the proper function of flotillins. Both flotillin genes are situated next to genes encoding NfeD proteins. FloT dramatically affects the localization of NfeD2: FloT apparently recruits NfeD2 into the focal assemblies, documenting a close interaction between flotillins and NfeDs in bacteria. In contrast, the localization of NfeD1b is not affected by FloA, FloT, or NfeD2. FloA does not show a spatial connection with the upstream-encoded NfeD1b (YqeZ). Our work establishes that bacterial flotillin-like proteins have overlapping functions in a variety of membrane-associated processes and that flotillin domain-mediated assembly and NfeD proteins play important roles in setting up the flotillin raft-like structures in vivo.

Dempwolff, Felix; Moller, Heiko M.

2012-01-01

29

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

30

Selective binding of Borrelia burgdorferi OspE paralogs to factor H and serum proteins from diverse animals: possible expansion of the role of OspE in Lyme disease pathogenesis.  

PubMed

The binding of Borrelia burgdorferi OspE, OspF, and family 163 (Elp) proteins to factor H/factor H-like protein 1 (FHL-1) and other serum proteins from different animals was assessed. OspE paralogs bound factor H and unidentified serum proteins from a subset of animals, while OspF and Elp proteins did not. These data advance our understanding of factor H binding, the host range of the Lyme spirochetes, and the expanding role of OspE in pathogenesis. PMID:16495576

Hovis, Kelley M; Tran, Emily; Sundy, Christina M; Buckles, Eric; McDowell, John V; Marconi, Richard T

2006-03-01

31

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

32

The maize heat shock factor-binding protein paralogs EMP2 and HSBP2 interact non-redundantly with specific heat shock factors.  

PubMed

The heat shock response (HSR) is a conserved mechanism by which transcripts of heat shock protein (hsp) genes accumulate following mobilization of heat shock transcription factors (HSFs) in response to thermal stress. Studies in animals identified the heat shock factor-binding protein1 (HSBP1) that interacts with heat shock transcription factor1 (HSF1) during heat shock attenuation; overexpression analyses revealed that the coiled-coil protein HSBP1 functions as a negative regulator of the HSR. Zea mays contains two HSBP paralogs, EMP2 and HSBP2, which exhibit differential accumulation during the HSR and plant development. Embryo-lethal recessive emp2 mutations revealed that EMP2 is required for the down-regulation of hsp transcription during embryogenesis, whereas accumulation of HSBP2 is induced in seedlings following heat shock. Notwithstanding, no interaction has yet been demonstrated between a plant HSBP and a plant HSF. In this report 22 maize HSF isoforms are identified comprising three structural classes: HSF-A, HSF-B and HSF-C. Phylogenetic analysis of Arabidopsis, maize and rice HSFs reveals that at least nine ancestral HSF isoforms were present prior to the separation of monocot and eudicots, followed by differential amplification of HSF members in these lineages. Yeast two-hybrid analyses show that EMP2 and HSBP2 interact non-redundantly with specific HSF-A isoforms. Site-specific mutagenesis of HSBP2 reveals that interactions between hydrophobic residues within the coiled coil are required for HSF::HSBP2 binding; domain swapping demonstrate that the isoform specificity of HSF::HSBP interaction is conferred by residues outside of the coiled coil. These data suggest that the non-redundant functions of the maize HSBPs may be explained, at least in part, by the specificity of HSBP::HSF interactions during plant development. PMID:16331466

Fu, Suneng; Rogowsky, Peter; Nover, Lutz; Scanlon, Michael J

2006-06-01

33

Metabotropic Glutamate Receptors and Fragile X Mental Retardation Protein: Partners in Translational Regulation at the Synapse  

NSDL National Science Digital Library

Fragile X syndrome (FXS) mental retardation is caused by loss-of-function mutations in an RNA-binding protein, fragile X mental retardation protein (FMRP). Previous studies in patients or animal models of FXS have identified alterations in dendritic spine structure, as well as synaptic plasticity induced by metabotropic glutamate receptors (mGluRs). The translation of multiple messenger RNA (mRNA) targets of FMRP is regulated by mGluRs at synapses. Here, we incorporate data from several studies into a working model of how FMRP regulates mGluR-stimulated protein synthesis and, in turn, regulates protein synthesis–dependent synaptic plasticity. Understanding the complex functions of FMRP at the synapse will lead to a better understanding of the neurobiological underpinnings of mental retardation.

Jennifer A. Ronesi (University of Texas Southwestern Medical Center;Department of Neuroscience REV); Kimberly M. Huber (Dallas;Department of Neuroscience, University of Texas Southwestern Medical Center REV)

2008-02-05

34

Fragile X mental retardation protein in learning-related synaptic plasticity  

Microsoft Academic Search

Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP is thought to contribute to synaptic plasticity by regulating plasticity-related protein\\u000a synthesis and other signaling pathways. Previous studies have mostly focused on the roles of FMRP within the hippocampus -

Valentina Mercaldo; Giannina Descalzi; Min Zhuo

2009-01-01

35

Protein Implicated in Nonsyndromic Mental Retardation Regulates Protein Kinase A (PKA) Activity  

PubMed Central

Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been linked to severe autosomal recessive nonsyndromic mental retardation. Using a mouse model that produces a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show that CC2D1A is important for neuronal differentiation and brain development. CC2D1A mutant neurons are hypersensitive to stress and have a reduced capacity to form dendrites and synapses in culture. At the biochemical level, CC2D1A transduces signals to the cyclic adenosine 3?,5?-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell differentiation. PKA activity is compromised, and the translocation of its catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. Consistently, phosphorylation of the PKA target cAMP-responsive element-binding protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA complex to the membrane to facilitate signal transduction. Together, our data show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, which may be the underlying cause for impaired mental function in nonsyndromic mental retardation patients with CC2D1A mutation.

Al-Tawashi, Azza; Jung, Sung Yun; Liu, Dou; Su, Bing; Qin, Jun

2012-01-01

36

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

ERIC Educational Resources Information Center

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

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

2013-01-01

37

The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.  

PubMed Central

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is 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. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo. We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro. This novel protein, FXR2, is very similar to FMR1 (60% identity). FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm. The FXR2 gene is located on human chromosome 17 at 17p13.1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1. Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers. FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome. Images

Zhang, Y; O'Connor, J P; Siomi, M C; Srinivasan, S; Dutra, A; Nussbaum, R L; Dreyfuss, G

1995-01-01

38

Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure  

Microsoft Academic Search

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of expression of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein with high specificity for G-quartet RNA structure. FMRP is involved in several steps of mRNA metabolism: nucleocytoplasmic trafficking, translational control and transport along dendrites in neurons. Fragile X Related Protein

Elias Bechara; Laetitia Davidovic; Mireille Melko; Mounia Bensaid; Sandra Tremblay; Josiane Grosgeorge; Edouard W. Khandjian; Enzo Lalli; Barbara Bardoni

2007-01-01

39

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

PubMed

Fragile X mental retardation is caused by the absence of the FMRP (fragile X mental retardation protein) a RNA-binding protein encoded by the Fmr1 gene. Despite the large number of studies about this syndrome, it is still unclear how the absence of FMRP affects the physiology of the nervous system. It has been reported however that the brain of the Fmr1-KO mouse shows altered membrane protein and lipid oxidation. There is also indirect evidence that FMRP may be involved in a negative feedback mechanism with metabotropic glutamate receptors (mGluRs). In this article, we will discuss several lines of evidences which tend to prove that the lipoxygenase pathway might be the missing link between FMRP and mGluRs. PMID:23313071

Beaulieu, Marc-Alexandre

2013-03-01

40

The Fragile X Mental Retardation Protein in Circadian Rhythmicity and Memory Consolidation  

PubMed Central

The control of new protein synthesis provides a means to locally regulate the availability of synaptic components necessary for dynamic neuronal processes. The Fragile X Mental Retardation Protein (FMRP), an RNA-binding translational regulator, is a key player mediating appropriate synaptic protein synthesis in response to neuronal activity levels. Loss of FMRP causes Fragile X Syndrome (FraX), the most commonly inherited form of mental retardation and autism spectrum disorders. FraX-associated translational dysregulation causes wide-ranging neurological deficits including severe impairments of biological rhythms, learning processes and memory consolidation. Dysfunction in cytoskeletal regulation and synaptic scaffolding disrupts neuronal architecture and functional synaptic connectivity. The understanding of this devastating disease and the implementation of meaningful treatment strategies require a thorough exploration of the temporal and spatial requirements for FMRP in establishing and maintaining neural circuit function.

Gatto, Cheryl L.; Broadie, Kendal

2013-01-01

41

Fragile x mental retardation protein regulates translation by binding directly to the ribosome.  

PubMed

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused by loss of function of the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is involved in the translational regulation of several neuronal mRNAs. However, the precise mechanism of translational inhibition by FMRP is unknown. Here, we show that FMRP inhibits translation by binding directly to the L5 protein on the 80S ribosome. Furthermore, cryoelectron microscopic reconstruction of the 80S ribosome?FMRP complex shows that FMRP binds within the intersubunit space of the ribosome such that it would preclude the binding of tRNA and translation elongation factors on the ribosome. These findings suggest that FMRP inhibits translation by blocking the essential components of the translational machinery from binding to the ribosome. PMID:24746697

Chen, Eileen; Sharma, Manjuli R; Shi, Xinying; Agrawal, Rajendra K; Joseph, Simpson

2014-05-01

42

The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis  

Microsoft Academic Search

Of 11 genes involved in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GTPases, suggesting an important role for Rho signaling in cognitive function. It remains unknown, however, how mutations in Rho-linked genes lead to MRX. Here we report that oligophrenin-1, a Rho-GTPase activating protein that is absent in a family affected with MRX, is

Eve-Ellen Govek; Sarah E Newey; Colin J Akerman; Justin R Cross; Lieven Van der Veken; Linda Van Aelst

2004-01-01

43

Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly  

Microsoft Academic Search

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP

Marie-Cecile Didiot; Murugan Subramanian; Eric Flatter; Jean-Louis Mandel; H. Moine

2009-01-01

44

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

45

Distribution of fragile X mental retardation protein in the human auditory brainstem.  

PubMed

Fragile X mental retardation protein (FMRP) binds select mRNAs, functions in intracellular transport of these mRNAs and represses their translation. FMRP is highly expressed in neurons and lack of FMRP has been shown to result in dendritic dysmorphology and altered synaptic function. FMRP is known to interact with mRNAs for the Kv3.1b potassium channel which is required for neurons to fire action potentials at high rates with remarkable temporal precision. Auditory brainstem neurons are known for remarkably high spike rates and expression of Kv3.1b potassium channels. Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X mental retardation 1 gene (Fmr1) resulting in decreased expression of FMRP and subsequent intellectual disability, seizures, attention deficit and hypersensitivity to auditory and other sensory stimuli. We therefore hypothesize that the auditory difficulties in FXS result, at least in part, from dysfunction of auditory brainstem neurons. To examine this hypothesis, we have studied normal human brainstem tissue with immunohistochemical techniques and confocal microscopy. Our results demonstrate that FMRP is widely expressed in cell bodies and dendritic arbors of neurons in the human cochlear nucleus and superior olivary complex and also that coincidence detector neurons of the medial superior olive colocalization of FMRP and Kv3.1b. We interpret these observations to suggest that the lower auditory brainstem is a potential site of dysfunction in FXS. PMID:24838064

Beebe, K; Wang, Y; Kulesza, R

2014-07-25

46

An archaeal RadA paralog influences presynaptic filament formation  

PubMed Central

Recombinases of the RecA family play vital roles in homologous recombination, a high-fidelity mechanism to repair DNA double-stranded breaks. These proteins catalyze strand invasion and exchange after forming dynamic nucleoprotein filaments on ssDNA. Increasing evidence suggests that stabilization of these dynamic filaments is a highly conserved function across diverse species. Here, we analyze the presynaptic filament formation and DNA binding characteristics of the Sulfolobus solfataricus recombinase SsoRadA in conjunction with the SsoRadA paralog SsoRal1. In addition to constraining SsoRadA ssDNA-dependent ATPase activity, the paralog also enhances SsoRadA ssDNA binding, effectively influencing activities necessary for presynaptic filament formation. These activities result in enhanced SsoRadA-mediated strand invasion in the presence of SsoRal1 and suggest a filament stabilization function for the SsoRal1 protein.

Graham, William J.; Rolfsmeier, Michael L.; Haseltine, Cynthia A.

2014-01-01

47

A Quantitative ELISA Assay for the Fragile X Mental Retardation 1 Protein  

PubMed Central

Non-coding (CGG-repeat) expansions in the fragile X mental retardation 1 (FMR1) gene result in a spectrum of disorders involving altered neurodevelopment (fragile X syndrome), neurodegeneration (late-onset fragile X-associated tremor/ataxia syndrome), or primary ovarian insufficiency. While reliable and quantitative assays for the number of CGG repeats and FMR1 mRNA levels are now available, there has been no scalable, quantitative assay for the FMR1 protein (FMRP) in non-transformed cells. Using a combination of avian and murine antibodies to FMRP, we developed a sensitive and highly specific sandwich enzyme-linked immunosorbent assay (ELISA) for FMRP in peripheral blood lymphocytes. This ELISA method is capable of quantifying FMRP levels throughout the biologically relevant range of protein concentrations and is specific for the intact FMRP protein. Moreover, the ELISA is well-suited for replicate protein determinations across serial dilutions in non-transformed cells and is readily scalable for large sample numbers. The FMRP ELISA is potentially a powerful tool in expanding our understanding of the relationship between FMRP levels and the various FMR1-associated clinical phenotypes.

Iwahashi, Christine; Tassone, Flora; Hagerman, Randi J.; Yasui, Dag; Parrott, George; Nguyen, Danh; Mayeur, Greg; Hagerman, Paul J.

2009-01-01

48

Fragile X Mental Retardation Protein Regulates New Neuron Differentiation in the Adult Olfactory Bulb  

PubMed Central

The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in the Fmr1 knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in the Fmr1 KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutate Fmr1 in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis.

Scotto-Lomassese, Sophie; Nissant, Antoine; Mota, Tatiana; Neant-Fery, Marie; Oostra, Ben A.; Greer, Charles A.; Lledo, Pierre-Marie; Trembleau, Alain; Caille, Isabelle

2013-01-01

49

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

50

Heat Shock Protein 70 Expression is Increased in the Liver of Neonatal Intrauterine Growth Retardation Piglets  

PubMed Central

Intrauterine growth retardation (IUGR) leads to the dysfunction in digestive system, as well as the alteration in the expression of some functional proteins. Heat shock protein 70 (Hsp70) could be induced by various stress factors, but whether Hsp70 expression is changed in neonatal IUGR infants has not been demonstrated. This study was conducted to explore the expression of Hsp70 in the liver by using the IUGR piglet model. Liver and plasma samples were obtained from IUGR and normal birth weight (NBW) piglets at birth. The neonatal IUGR piglets had significantly lower liver weight than their counterparts. The activities of aspartate aminotransferase and alanine aminotransferase in serum were enhanced significantly in IUGR indicating liver dysfunction. The activities of superoxide dismutase (p<0.01), glutathione peroxidase (p<0.01) and catalase (p>0.05) were lower and the level of malondialdehybe was higher (p<0.05) in IUGR liver compared with in NBW. According to the results of histological tests, fatty hepatic infiltrates and cytoplasmic vacuolization were present in the liver of IUGR piglets, but not in NBW liver. The expression of Hsp70 protein was significantly higher (p<0.05) in IUGR piglet liver than in NBW. Similar to where the hepatic injuries were observed, location of Hsp70 was mostly in the midzonal hepatic lobule indicating that oxidative stress might be responsible for the increased expression of Hsp70.

Li, Wei; Zhong, Xiang; Zhang, Lili; Wang, Yuanxiao; Wang, Tian

2012-01-01

51

Nuclear Fragile X Mental Retardation Protein Is localized to Cajal Bodies  

PubMed Central

Fragile X syndrome is caused by loss of function of a single gene encoding the Fragile X Mental Retardation Protein (FMRP). This RNA-binding protein, widely expressed in mammalian tissues, is particularly abundant in neurons and is a component of messenger ribonucleoprotein (mRNP) complexes present within the translational apparatus. The absence of FMRP in neurons is believed to cause translation dysregulation and defects in mRNA transport essential for local protein synthesis and for synaptic development and maturation. A prevalent model posits that FMRP is a nucleocytoplasmic shuttling protein that transports its mRNA targets from the nucleus to the translation machinery. However, it is not known which of the multiple FMRP isoforms, resulting from the numerous alternatively spliced FMR1 transcripts variants, would be involved in such a process. Using a new generation of anti-FMRP antibodies and recombinant expression, we show here that the most commonly expressed human FMRP isoforms (ISO1 and 7) do not localize to the nucleus. Instead, specific FMRP isoforms 6 and 12 (ISO6 and 12), containing a novel C-terminal domain, were the only isoforms that localized to the nuclei in cultured human cells. These isoforms localized to specific p80-coilin and SMN positive structures that were identified as Cajal bodies. The Cajal body localization signal was confined to a 17 amino acid stretch in the C-terminus of human ISO6 and is lacking in a mouse Iso6 variant. As FMRP is an RNA-binding protein, its presence in Cajal bodies suggests additional functions in nuclear post-transcriptional RNA metabolism. Supporting this hypothesis, a missense mutation (I304N), known to alter the KH2-mediated RNA binding properties of FMRP, abolishes the localization of human FMRP ISO6 to Cajal bodies. These findings open unexplored avenues in search for new insights into the pathophysiology of Fragile X Syndrome.

Tremblay, Sandra; Rose, Timothy M.; Cote, Jocelyn; De Koninck, Paul; Khandjian, Edouard W.

2013-01-01

52

Recombinant Bacterial Expression and Purification of Human Fragile X Mental Retardation Protein Isoform 1  

PubMed Central

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 propose 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.

Evans, Timothy L.; Mihailescu, Mihaela-Rita

2010-01-01

53

Structure of the Human Zinc Finger Protein HIVEP3: Molecular Cloning, Expression, Exon–Intron Structure, and Comparison with Paralogous Genes HIVEP1 and HIVEP2  

Microsoft Academic Search

Here we report the cloning and characterization of HIVEP3, the newest member in the human immunodeficiency virus type 1 enhancer-binding protein family that encodes large zinc finger proteins and regulates transcription via the ?B enhancer motif. The largest open reading frame of HIVEP3 contains 2406 aa. and is ?80% identical to the mouse counterpart. The HIVEP3 gene is located in

Mark D. Hicar; Yiling Liu; Carl E. Allen; Lai-Chu Wu

2001-01-01

54

Capillary zone electrophoresis of proteins in semidilute polymer solutions: inter- and intra-polymer predictability of size-dependent retardation.  

PubMed

The retardation of three "spherical" proteins with Stokes' radii of 2.0, 2.4, and 3.0 nm (35-104 kDa) was studied in capillary zone electrophoresis (CZE), using semidilute solutions of polyethylene glycol (PEG), linear polyacrylamide (PA), and polyvinyl alcohol (PVA). The purpose was to test the models predicting that the ratio of particle radius, R, to the mesh size of polymer network (the correlation or screening length of a semidilute polymer solution), xi, directly governs the size-dependent retardation in the form: mu/muo = exp (-R/xi). Here xi = kc-0.75, where c is polymer concentration and the numerical factor kcan be calculated based on polymer molecular weight. In application to polymers in a "good solvent" (PA and PEG in the aqueous buffer) and to proteins of 2.4 and 3.0 nm radius, that relation between relative mobility and R/xi was found to be obeyed for PA, while for PEG the value of k derived from retardation experiments significantly exceeded that which was theoretically calculated. Thus, the retardation appears to be polymer-specific, rather than universal, even for polymers in a "good solvent". It is suggested that, in that case, retardation of proteins of R > 2 nm be quantitatively described in the form mu/muo = exp[-p(R/xi], where p is a parameter depending on monomer type and/or polymer polydispersity. For PVA, the logarithm of mu/muo was found to be linearly related to c (in line with the prediction that the aqueous buffer is a "poor solvent" for this polymer) and to be near-independent of R. PMID:10546824

Stastna, M; Radko, S P; Chrambach, A

1999-10-01

55

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

56

Olfactory discrimination learning in mice lacking the fragile X mental retardation protein  

PubMed Central

An automated training system was used to compare the behavior of knockout (KO) mice lacking the Fragile X Mental Retardation Protein with that of wild-type (WT) mice (C57Bl/6 strain) in the acquisition and retention of olfactory discriminations. KO and WT mice did not differ in the acquisition of a four-stage nose poke shaping procedure. In two separate experiments, mutant mice required substantially more training to acquire a series of novel olfactory discrimination problems than did control mice. The KO mice required significantly more sessions to reach criterion performance, made significantly more errors during training, and more often failed to acquire discriminations. Both KO and WT mice showed similar error patterns when learning novel discriminations and both groups showed evidence of more rapid learning of later discriminations in the problem series. Both groups showed significant long-term memory two or four weeks after training but WT and KO mice did not differ in this regard. A group of well-trained mice were given training on novel odors in sessions limited to 20–80 trials. Memory of these problems at two day delays did not differ between WT and KO mice. Tests using ethyl acetate demonstrated that WT and KO mice had similar odor detection thresholds.

Larson, John; Kim, Daniel; Patel, Roseanne C.; Floreani, Christina

2008-01-01

57

Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila.  

PubMed

Fragile X syndrome (FXS), the most common inherited determinant of intellectual disability and autism spectrum disorders, is caused by loss of the fragile X mental retardation 1 (FMR1) gene product (FMRP), an mRNA-binding translational repressor. A number of conserved FMRP targets have been identified in the well-characterized Drosophila FXS disease model, but FMRP is highly pleiotropic in function and the full spectrum of FMRP targets has yet to be revealed. In this study, screens for upregulated neural proteins in Drosophila fmr1 (dfmr1) null mutants reveal strong elevation of two synaptic heparan sulfate proteoglycans (HSPGs): GPI-anchored glypican Dally-like protein (Dlp) and transmembrane Syndecan (Sdc). Our recent work has shown that Dlp and Sdc act as co-receptors regulating extracellular ligands upstream of intracellular signal transduction in multiple trans-synaptic pathways that drive synaptogenesis. Consistently, dfmr1 null synapses exhibit altered WNT signaling, with changes in both Wingless (Wg) ligand abundance and downstream Frizzled-2 (Fz2) receptor C-terminal nuclear import. Similarly, a parallel anterograde signaling ligand, Jelly belly (Jeb), and downstream ERK phosphorylation (dpERK) are depressed at dfmr1 null synapses. In contrast, the retrograde BMP ligand Glass bottom boat (Gbb) and downstream signaling via phosphorylation of the transcription factor MAD (pMAD) seem not to be affected. To determine whether HSPG upregulation is causative for synaptogenic defects, HSPGs were genetically reduced to control levels in the dfmr1 null background. HSPG correction restored both (1) Wg and Jeb trans-synaptic signaling, and (2) synaptic architecture and transmission strength back to wild-type levels. Taken together, these data suggest that FMRP negatively regulates HSPG co-receptors controlling trans-synaptic signaling during synaptogenesis, and that loss of this regulation causes synaptic structure and function defects characterizing the FXS disease state. PMID:24046358

Friedman, Samuel H; Dani, Neil; Rushton, Emma; Broadie, Kendal

2013-11-01

58

Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila  

PubMed Central

SUMMARY Fragile X syndrome (FXS), the most common inherited determinant of intellectual disability and autism spectrum disorders, is caused by loss of the fragile X mental retardation 1 (FMR1) gene product (FMRP), an mRNA-binding translational repressor. A number of conserved FMRP targets have been identified in the well-characterized Drosophila FXS disease model, but FMRP is highly pleiotropic in function and the full spectrum of FMRP targets has yet to be revealed. In this study, screens for upregulated neural proteins in Drosophila fmr1 (dfmr1) null mutants reveal strong elevation of two synaptic heparan sulfate proteoglycans (HSPGs): GPI-anchored glypican Dally-like protein (Dlp) and transmembrane Syndecan (Sdc). Our recent work has shown that Dlp and Sdc act as co-receptors regulating extracellular ligands upstream of intracellular signal transduction in multiple trans-synaptic pathways that drive synaptogenesis. Consistently, dfmr1 null synapses exhibit altered WNT signaling, with changes in both Wingless (Wg) ligand abundance and downstream Frizzled-2 (Fz2) receptor C-terminal nuclear import. Similarly, a parallel anterograde signaling ligand, Jelly belly (Jeb), and downstream ERK phosphorylation (dpERK) are depressed at dfmr1 null synapses. In contrast, the retrograde BMP ligand Glass bottom boat (Gbb) and downstream signaling via phosphorylation of the transcription factor MAD (pMAD) seem not to be affected. To determine whether HSPG upregulation is causative for synaptogenic defects, HSPGs were genetically reduced to control levels in the dfmr1 null background. HSPG correction restored both (1) Wg and Jeb trans-synaptic signaling, and (2) synaptic architecture and transmission strength back to wild-type levels. Taken together, these data suggest that FMRP negatively regulates HSPG co-receptors controlling trans-synaptic signaling during synaptogenesis, and that loss of this regulation causes synaptic structure and function defects characterizing the FXS disease state.

Friedman, Samuel H.; Dani, Neil; Rushton, Emma; Broadie, Kendal

2013-01-01

59

Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ?2 renders tumor cells dependent on its paralogous gene COPZ1  

PubMed Central

Anticancer drugs are effective against tumors that depend on the molecular target of the drug. Known targets of cytotoxic anticancer drugs are involved in cell proliferation; drugs acting on such targets are ineffective against nonproliferating tumor cells, survival of which leads to eventual therapy failure. Function-based genomic screening identified the coatomer protein complex ?1 (COPZ1) gene as essential for different tumor cell types but not for normal cells. COPZ1 encodes a subunit of coatomer protein complex 1 (COPI) involved in intracellular traffic and autophagy. The knockdown of COPZ1, but not of COPZ2 encoding isoform coatomer protein complex ?2, caused Golgi apparatus collapse, blocked autophagy, and induced apoptosis in both proliferating and nondividing tumor cells. In contrast, inhibition of normal cell growth required simultaneous knockdown of both COPZ1 and COPZ2. COPZ2 (but not COPZ1) was down-regulated in the majority of tumor cell lines and in clinical samples of different cancer types. Reexpression of COPZ2 protected tumor cells from killing by COPZ1 knockdown, indicating that tumor cell dependence on COPZ1 is the result of COPZ2 silencing. COPZ2 displays no tumor-suppressive activities, but it harbors microRNA 152, which is silenced in tumor cells concurrently with COPZ2 and acts as a tumor suppressor in vitro and in vivo. Silencing of microRNA 152 in different cancers and the ensuing down-regulation of its host gene COPZ2 offer a therapeutic opportunity for proliferation-independent selective killing of tumor cells by COPZ1-targeting agents.

Shtutman, Michael; Baig, Mirza; Levina, Elina; Hurteau, Gregory; Lim, Chang-uk; Broude, Eugenia; Nikiforov, Mikhail; Harkins, Timothy T.; Carmack, C. Steven; Ding, Ye; Wieland, Felix; Buttyan, Ralph; Roninson, Igor B.

2011-01-01

60

Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ? 2 renders tumor cells dependent on its paralogous gene COPZ1.  

PubMed

Anticancer drugs are effective against tumors that depend on the molecular target of the drug. Known targets of cytotoxic anticancer drugs are involved in cell proliferation; drugs acting on such targets are ineffective against nonproliferating tumor cells, survival of which leads to eventual therapy failure. Function-based genomic screening identified the coatomer protein complex ?1 (COPZ1) gene as essential for different tumor cell types but not for normal cells. COPZ1 encodes a subunit of coatomer protein complex 1 (COPI) involved in intracellular traffic and autophagy. The knockdown of COPZ1, but not of COPZ2 encoding isoform coatomer protein complex ?2, caused Golgi apparatus collapse, blocked autophagy, and induced apoptosis in both proliferating and nondividing tumor cells. In contrast, inhibition of normal cell growth required simultaneous knockdown of both COPZ1 and COPZ2. COPZ2 (but not COPZ1) was down-regulated in the majority of tumor cell lines and in clinical samples of different cancer types. Reexpression of COPZ2 protected tumor cells from killing by COPZ1 knockdown, indicating that tumor cell dependence on COPZ1 is the result of COPZ2 silencing. COPZ2 displays no tumor-suppressive activities, but it harbors microRNA 152, which is silenced in tumor cells concurrently with COPZ2 and acts as a tumor suppressor in vitro and in vivo. Silencing of microRNA 152 in different cancers and the ensuing down-regulation of its host gene COPZ2 offer a therapeutic opportunity for proliferation-independent selective killing of tumor cells by COPZ1-targeting agents. PMID:21746916

Shtutman, Michael; Baig, Mirza; Levina, Elina; Hurteau, Gregory; Lim, Chang-Uk; Broude, Eugenia; Nikiforov, Mikhail; Harkins, Timothy T; Carmack, C Steven; Ding, Ye; Wieland, Felix; Buttyan, Ralph; Roninson, Igor B

2011-07-26

61

IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor1 and regulates exocytosis  

Microsoft Academic Search

Previously, human genetics-based approaches allowed us to show that mutations in the IL-1 receptor accessory protein-like gene (IL1RAPL) are responsible for a non-specific form of X-linked mental retardation. This gene encodes a predicted protein of 696 amino acids that belongs to a novel class of the IL-1\\/Toll receptor family. In addition to the extracellular portion consisting of three Ig-like domains

Nadia Bahi; Gaelle Friocourt; Alain Carrie ´; Margaret E. Graham; Jamie L. Weiss; Philippe Chafey; Fabien Fauchereau; Robert D. Burgoyne; Jamel Chelly

2003-01-01

62

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

63

Hox11 paralogous genes are essential for metanephric kidney induction  

Microsoft Academic Search

The mammalian Hox complex is divided into four linkage groups containing 13 sets of paralogous genes. These paralogous genes have retained functional redundancy during evolution. For this reason, loss of only one or two Hox genes within a paralogous group often results in incompletely penetrant phenotypes which are difficult to interpret by molecular analysis. For example, mice individually mutant for

Deneen M. Wellik; Patrick J. Hawkes; Mario R. Capecchi

2002-01-01

64

Characterization of paralogous protein families in rice  

Microsoft Academic Search

BACKGROUND: High gene numbers in plant genomes reflect polyploidy and major gene duplication events. Oryza sativa, cultivated rice, is a diploid monocotyledonous species with a ~390 Mb genome that has undergone segmental duplication of a substantial portion of its genome. This, coupled with other genetic events such as tandem duplications, has resulted in a substantial number of its genes, and

Haining Lin; Shu Ouyang; Amy Egan; Kan Nobuta; Brian J Haas; Wei Zhu; Xun Gu; Joana C Silva; Blake C Meyers; C Robin Buell

2008-01-01

65

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

PubMed Central

Abstract 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. Bacillus anthracis harbors two paralogs of the global transcriptional regulator of stress response, SpxA. SpxA1 and SpxA2 contribute to disulfide stress tolerance, but only SpxA1 functions in resistance to peroxide. Transcriptome analysis uncovered potential SpxA1 and SpxA2 regulon members, which include genes activated by both paralogs. However, paralog-specific gene activation was also observed. Genes encoding glutamate racemase, CoA disulfide reductase, and products functioning in bacillithiol biosynthesis, are among the genes activated by the SpxA paralogs.

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

2013-01-01

66

Nuclear Receptors, Nuclear-Receptor Factors, and Nuclear-Receptor-like Orphans Form a Large Paralog Cluster in Homo sapiens  

Microsoft Academic Search

We studied a human protein paralog cluster formed by 38 nonredundant sequences taken from the Swiss-Prot database and its supplement, TrEMBL. These sequences include nuclear receptors, nuclear-receptor factors and nuclear-receptor-like orphans. Working separately with both the central cysteine-rich DNA-binding domain and the carboxy-terminal ligand-binding domain, we performed multialignment analyses that included drawings of paralog trees. Our results show that the

Santiago Garcia-Vallveand; Jaume Palau

67

Characterization of three full-length human nonmuscle myosin II paralogs.  

PubMed

Nonmuscle myosin IIs (NM IIs) are a group of molecular motors involved in a wide variety of cellular processes including cytokinesis, migration, and control of cell morphology. There are three paralogs of the NM II heavy chain in humans (IIA, IIB, and IIC), each encoded by a separate gene. These paralogs are expressed at different levels according to cell type and have different roles and intracellular distributions in vivo. Most previous studies on NM II used tissue-purified protein or expressed fragments of the molecule, which presents potential drawbacks for characterizing individual paralogs of the intact protein in vitro. To circumvent current limitations and approach their native properties, we have successfully expressed and purified the three full-length human NM II proteins with their light chains, using the baculovirus/Sf9 system. The enzymatic and structural properties of the three paralogs were characterized. Although each NM II is capable of forming bipolar filaments, those formed by IIC tend to contain fewer constituent molecules than those of IIA and IIB. All paralogs adopt the compact conformation in the presence of ATP. Phosphorylation of the regulatory light chain leads to assembly into filaments, which bind to actin in the presence of ATP. The nature of interactions with actin filaments is shown with different paralogs exhibiting different actin binding behaviors under equivalent conditions. The data show that although NM IIA and IIB form filaments with similar properties, NM IIC forms filaments that are less well suited to roles such as tension maintenance within the cell. PMID:24072716

Billington, Neil; Wang, Aibing; Mao, Jian; Adelstein, Robert S; Sellers, James R

2013-11-15

68

Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2  

PubMed Central

Background Expansion of the CGG trinucleotide repeat in the 5?-untranslated region of the FMR1, fragile X mental retardation 1, gene results in suppression of protein expression for this gene and is the underlying cause of Fragile X syndrome. In unaffected individuals, the FMRP protein, together with two additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1 and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus that is transported to dendrites and spines of neuronal cells. It is thought that the fragile X family of proteins contributes to the regulation of protein synthesis at sites where mRNAs are locally translated in response to stimuli. Methodology/Principal Findings Here, we report the X-ray crystal structures of the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal paralogues of FMRP, which were determined at 2.50 and 1.92 Å, respectively. The nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures, closely resembling that of UHRF1, which is proposed to bind methylated histone H3K9. Conclusions The FMRP, FXR1 and FXR2 proteins comprise a small family of highly conserved proteins that appear to be important in translational regulation, particularly in neuronal cells. The crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved architecture with that of FMRP. Biochemical analysis of the tandem Tudor doamins reveals their ability to preferentially recognize trimethylated peptides in a sequence-specific manner. Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Adams-Cioaba, Melanie A.; Guo, Yahong; Bian, ChuanBing; Amaya, Maria F.; Lam, Robert; Wasney, Gregory A.; Vedadi, Masoud; Xu, Chao; Min, Jinrong

2010-01-01

69

A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response.  

PubMed

Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protein that functions in the DNA damage response (DDR). Specifically, we show that FMRP binds chromatin through its tandem Tudor (Agenet) domain in vitro and associates with chromatin in vivo. We also demonstrate that FMRP participates in the DDR in a chromatin-binding-dependent manner. The DDR machinery is known to play important roles in developmental processes such as gametogenesis. We show that FMRP occupies meiotic chromosomes and regulates the dynamics of the DDR machinery during mouse spermatogenesis. These findings suggest that nuclear FMRP regulates genomic stability at the chromatin interface and may impact gametogenesis and some developmental aspects of fragile X syndrome. PMID:24813610

Alpatov, Roman; Lesch, Bluma J; Nakamoto-Kinoshita, Mika; Blanco, Andres; Chen, Shuzhen; Stützer, Alexandra; Armache, Karim J; Simon, Matthew D; Xu, Chao; Ali, Muzaffar; Murn, Jernej; Prisic, Sladjana; Kutateladze, Tatiana G; Vakoc, Christopher R; Min, Jinrong; Kingston, Robert E; Fischle, Wolfgang; Warren, Stephen T; Page, David C; Shi, Yang

2014-05-01

70

Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation  

Microsoft Academic Search

Primary or nonspecific X-linked mental retardation (MRX) is a heterogeneous condition in which affected patients do not have any distinctive clinical or biochemical features in common apart from cognitive impairment. Although it is present in approximately 0.15-0.3% of males, most of the genetic defects associated with MRX, which may involve more than ten different genes, remain unknown. Here we report

Pierre Billuart; Thierry Bienvenu; Nathalie Ronce; Vincent Des Portes; Marie Claude Vinet; Ramzi Zemni; Hugues Roest Crollius; Alain Carrié; Fabien Fauchereau; Michele Cherry; Sylvain Briault; Ben Hamel; Jean-Pierre Fryns; Cherif Beldjord; Axel Kahn; Claude Moraine; Jamel Chelly

1998-01-01

71

Phylogenetic Reconstruction of Orthology, Paralogy, and Conserved Synteny for Dog and Human  

Microsoft Academic Search

Accurate predictions of orthology and paralogy relationships are necessary to infer human molecular function from experiments in model organisms. Previous genome-scale approaches to predicting these relationships have been limited by their use of protein similarity and their failure to take into account multiple splicing events and gene prediction errors. We have developed PhyOP, a new phylogenetic orthology prediction pipeline based

Leo Goodstadt; Chris P. Ponting

2006-01-01

72

Orthologs, paralogs and genome comparisons  

NASA Technical Reports Server (NTRS)

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

Gogarten, J. P.; Olendzenski, L.

1999-01-01

73

Growth retardation as well as spleen and thymus involution in latent TGF-beta binding protein (Ltbp)-3 null mice.  

PubMed

The latent TGF-beta binding protein (LTBP)-3 is an extracellular matrix (ECM) protein that binds the small latent complex (SLC) of TGF-beta. Disruption of the Ltbp-3 gene by homologous recombination in mice yields mutant animals that display multiple skeletal abnormalities. In addition, these mice have retarded growth. On an inbred 129 SvEv background, half of the Ltbp-3 mutant mice die between 3 and 4 weeks after birth. These mice show severe involution of the thymus and spleen and a sharp reduction in the numbers of CD4/CD8 double positive T-cells in the thymus. The thymus and spleen defect is caused by elevated corticosterone levels in the serum and can be reversed by injection of aminoglutethimide (AMG), an inhibitor of steroid synthesis. This result indicates that the thymus and spleen defect is a secondary defect due to high corticosterone levels probably induced by stress of unknown etiology. PMID:12811825

Chen, Yan; Dabovic, Branka; Colarossi, Cristina; Santori, Fabio R; Lilic, Mirjana; Vukmanovic, Stanislav; Rifkin, Daniel B

2003-08-01

74

BRCA2 is epistatic to the RAD51 paralogs in response to DNA damage  

PubMed Central

Homologous recombination plays an important role in the high-fidelity repair of DNA double-strand breaks. A central player in this process, RAD51, polymerizes onto single-stranded DNA and searches for homology in a duplex donor DNA molecule, usually the sister chromatid. Homologous recombination is a highly regulated event in mammalian cells: some proteins have direct enzymatic functions, others mediate or overcome rate-limiting steps in the process, and still others signal cell cycle arrest to allow repair to occur. While the human BRCA2 protein has a clear role in delivering and loading RAD51 onto single-stranded DNA generated after resection of the DNA break, the mechanistic functions of the RAD51 paralogs remain unclear. In this study, we sought to determine the genetic interactions between BRCA2 and the RAD51 paralogs during DNA DSB repair. We utilized siRNA-mediated knockdown of these proteins in human cells to assess their impact on the DNA damage response. The results indicate that loss of BRCA2 alone imparts a more severe phenotype than the loss of any individual RAD51 paralog and that BRCA2 is epistatic to each of the four paralogs tested.

Jensen, Ryan B.; Ozes, Ali; Kim, Taeho; Estep, Allison; Kowalczykowski, Stephen C.

2013-01-01

75

The Reduced Expression of the HADH2 Protein Causes X-Linked Mental Retardation, Choreoathetosis, and Abnormal Behavior  

PubMed Central

Recently, we defined a new syndromic form of X-linked mental retardation in a 4-generation family with a unique clinical phenotype characterized by mild mental retardation, choreoathetosis, and abnormal behavior (MRXS10). Linkage analysis in this family revealed a candidate region of 13.4 Mb between markers DXS1201 and DXS991 on Xp11; therefore, mutation analysis was performed by direct sequencing in most of the 135 annotated genes located in the region. The gene (HADH2) encoding l-3-hydroxyacyl-CoA dehydrogenase II displayed a sequence alteration (c.574 C?A; p.R192R) in all patients and carrier females that was absent in unaffected male family members and could not be found in 2,500 control X chromosomes, including in those of 500 healthy males. The silent C?A substitution is located in exon 5 and was shown by western blot to reduce the amount of HADH2 protein by 60%–70% in the patient. Quantitative in vivo and in vitro expression studies revealed a ratio of splicing transcript amounts different from those normally seen in controls. Apparently, the reduced expression of the wild-type fragment, which results in the decreased protein expression, rather than the increased amount of aberrant splicing fragments of the HADH2 gene, is pathogenic. Our data therefore strongly suggest that reduced expression of the HADH2 protein causes MRXS10, a phenotype different from that caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, which is a neurodegenerative disorder caused by missense mutations in this multifunctional protein.

Lenski, Claus; Frank Kooy, R.; Reyniers, Edwin; Loessner, Daniela; Wanders, Ronald J. A.; Winnepenninckx, Birgitta; Hellebrand, Heide; Engert, Stefanie; Schwartz, Charles E.; Meindl, Alfons; Ramser, Juliane

2007-01-01

76

The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior.  

PubMed

Recently, we defined a new syndromic form of X-linked mental retardation in a 4-generation family with a unique clinical phenotype characterized by mild mental retardation, choreoathetosis, and abnormal behavior (MRXS10). Linkage analysis in this family revealed a candidate region of 13.4 Mb between markers DXS1201 and DXS991 on Xp11; therefore, mutation analysis was performed by direct sequencing in most of the 135 annotated genes located in the region. The gene (HADH2) encoding L-3-hydroxyacyl-CoA dehydrogenase II displayed a sequence alteration (c.574 C-->A; p.R192R) in all patients and carrier females that was absent in unaffected male family members and could not be found in 2,500 control X chromosomes, including in those of 500 healthy males. The silent C-->A substitution is located in exon 5 and was shown by western blot to reduce the amount of HADH2 protein by 60%-70% in the patient. Quantitative in vivo and in vitro expression studies revealed a ratio of splicing transcript amounts different from those normally seen in controls. Apparently, the reduced expression of the wild-type fragment, which results in the decreased protein expression, rather than the increased amount of aberrant splicing fragments of the HADH2 gene, is pathogenic. Our data therefore strongly suggest that reduced expression of the HADH2 protein causes MRXS10, a phenotype different from that caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, which is a neurodegenerative disorder caused by missense mutations in this multifunctional protein. PMID:17236142

Lenski, Claus; Kooy, R Frank; Reyniers, Edwin; Loessner, Daniela; Wanders, Ronald J A; Winnepenninckx, Birgitta; Hellebrand, Heide; Engert, Stefanie; Schwartz, Charles E; Meindl, Alfons; Ramser, Juliane

2007-02-01

77

Weak dependence of mobility of membrane protein aggregates on aggregate size supports a viscous model of retardation of diffusion.  

PubMed Central

Proteins in plasma membranes diffuse more slowly than proteins inserted into artificial lipid bilayers. On a long-range scale (>250 nm), submembrane barriers, or skeleton fences that hinder long-range diffusion and create confinement zones, have been described. Even within such confinement zones, however, diffusion of proteins is much slower than predicted by the viscosity of the lipid. The cause of this slowing of diffusion on the micro scale has not been determined and is the focus of this paper. One way to approach this question is to determine the dependence of particle motion on particle size. Some current models predict that the diffusion coefficient of a membrane protein aggregate will depend strongly on its size, while others do not. We have measured the diffusion coefficients of membrane glycoprotein aggregates linked together by concanavalin A molecules bound to beads of various sizes, and also the diffusion coefficients of individual concanavalin A binding proteins. The measurements demonstrate at most a weak dependence of diffusion coefficient on aggregate size. This finding supports retardation by viscous effects, and is not consistent with models involving direct interaction of diffusing proteins with cytoskeletal elements.

Kucik, D F; Elson, E L; Sheetz, M P

1999-01-01

78

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

2008-04-01

79

Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density  

NASA Astrophysics Data System (ADS)

Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

2014-04-01

80

Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density.  

PubMed

Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS. PMID:24709664

Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S; Dolphin, Annette C

2014-01-01

81

Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density  

PubMed Central

Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

2014-01-01

82

Mental retardation-related protease, motopsin (prss12), binds to the BRICHOS domain of the integral membrane protein 2a.  

PubMed

Motopsin (prss12), a mosaic serine protease secreted by neuronal cells, is believed to be important for cognitive function, as the loss of its function causes severe nonsyndromic mental retardation. To understand the molecular role of motopsin, we identified the integral membrane protein 2a (Itm2a) as a motopsin-interacting protein using a yeast two-hybrid system. A pull-down assay showed that the BRICHOS domain of Itm2a was essential for this interaction. Motopsin and Itm2a co-localized in COS cells and in cultured neurons when transiently expressed in these cells. Both proteins were co-immunoprecipitated from lysates of these transfected COS cells. Itm2a was strongly detected in a brain lysate prepared between postnatal day 0 and 10, during which period motopsin protein was also enriched in the brain. Immunohistochemistry detected Itm2a as patchy spots along endothelial cells of brain capillaries (which also expressed myosin II regulatory light chain [RLC]), and on glial fibrillary acidic protein (GFAP)-positive processes in the developing cerebral cortex. The data raise the possibility that secreted motopsin interacts with endothelial cells in the developing brain. PMID:23955961

Mitsui, Shinichi; Osako, Yoji; Yuri, Kazunari

2014-01-01

83

Mutations in C2orf37, Encoding a Nucleolar Protein, Cause Hypogonadism, Alopecia, Diabetes Mellitus, Mental Retardation, and Extrapyramidal Syndrome  

PubMed Central

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 unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.

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

2008-01-01

84

Regulation of Expression of the Paralogous Mlp Family in Borrelia burgdorferi  

PubMed Central

The Mlp (multicopy lipoproteins) family is one of many paralogous protein families in Borrelia burgdorferi. To examine the extent to which the 10 members of the Mlp family in B. burgdorferi strain 297 might be differentially regulated, antibodies specific for each of the Mlps were developed and used to analyze the protein expression profiles of individual Mlps when B. burgdorferi replicated under various cultivation conditions. All of the Mlps were upregulated coordinately when B. burgdorferi was cultivated at either elevated temperature, reduced culture pH, or increased spirochete cell density. Inasmuch as the expression of OspC is influenced by a novel RpoN-RpoS regulatory pathway, similar induction patterns for OspC and the Mlp paralogs prompted an assessment of whether the RpoN-RpoS pathway also was involved in Mlp expression. In contrast to wild-type B. burgdorferi, both RpoN- and RpoS-deficient mutants were unable to upregulate OspC or the Mlp paralogs when grown at lower pH (6.8), indicating that pH-mediated regulation of OspC and Mlp paralogs is dependent on the RpoN-RpoS pathway. However, when RpoN- or RpoS-deficient mutants were shifted from 23°C to 37°C or were cultivated to higher spirochete densities, some induction of the Mlps still occurred, whereas OspC expression was abolished. The combined findings suggest that the Mlp paralogs are coordinately regulated as a family and have an expression profile similar, but not identical, to that of OspC. Although Mlp expression as a family is influenced by the RpoN-RpoS regulatory pathway, there exists at least one additional layer of gene regulation, yet to be elucidated, contributing to Mlp expression in B. burgdorferi.

Yang, Xiaofeng F.; Hubner, Anette; Popova, Taissia G.; Hagman, Kayla E.; Norgard, Michael V.

2003-01-01

85

Retarded protein folding of the human Z-type ??-antitrypsin variant is suppressed by Cpr2p.  

PubMed

The human Z-type ?1-antitrypsin variant has a strong tendency to accumulate folding intermediates due to extremely slow protein folding within the endoplasmic reticulum (ER) of hepatocytes. Human ?1-antitrypsin has 17 peptidyl-prolyl bonds per molecule; thus, the effect of peptidyl-prolyl isomerases on Z-type ?1-antitrypsin protein folding was analyzed in this study. The protein level of Cpr2p, a yeast ER peptidyl-prolyl isomerase, increased more than two-fold in Z-type ?1-antitrypsin-expressing yeast cells compared to that in wild-type ?1-antitrypsin-expressing cells. When CPR2 was deleted from the yeast genome, the cytotoxicity of Z-type ?1-antitrypsin increased significantly. The interaction between Z-type ?1-antitrypsin and Cpr2p was confirmed by co-immunoprecipitation. In vitro folding assays showed that Cpr2p facilitated Z-type ?1-antitrypsin folding into the native state. Furthermore, Cpr2p overexpression significantly increased the extracellular secretion of Z-type ?1-antitrypsin. Our results indicate that ER peptidyl-prolyl isomerases may rescue Z-type ?1-antitrypsin molecules from retarded folding and eventually relieve clinical symptoms caused by this pathological ?1-antitrypsin. PMID:24502947

Jung, Chan-Hun; Kim, Yang-Hee; Lee, Kyunghee; Im, Hana

2014-02-28

86

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

PubMed Central

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.

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

1999-01-01

87

Conservation of adjacency as evidence of paralogous operons  

Microsoft Academic Search

Most of the analyses on the conservation of gene order are limited to orthologous genes. However, the organization of genes into operons might also result in the conservation of gene order of paralogous genes. Thus, we sought computational evidence that conservation of gene order of paralogous genes represents another level of conservation of genes in operons. We found that pairs

Sarath Chandra Jang; Gabriel Moreno-Hagelsieb

2004-01-01

88

Bowman–Birk inhibitors in Lens : identification and characterization of two paralogous gene classes in cultivated lentil and wild relatives  

Microsoft Academic Search

In order to investigate the genetic structure of lentil Bowman–Birk inhibitors (BBIs), primers were designed on pea BBI sequences. The sequences obtained from lentil DNA, using these primers, indicate that lentil possesses at least two paralogous genes. Protein sequences translated in silico from lentil DNA sequences suggest that the two coded proteins are highly similar to Pisum trypsin inhibitor TI1

Gabriella Sonnante; Angelo De Paolis; Domenico Pignone

2005-01-01

89

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

90

Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit.  

PubMed

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

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

2012-01-01

91

Two CDC42 paralogs modulate C. neoformans thermotolerance and morphogenesis under host physiological conditions  

PubMed Central

The precise regulation of morphogenesis is a key mechanism by which cells respond to a variety of stresses, including those encountered by microbial pathogens in the host. The polarity protein Cdc42 regulates cellular morphogenesis throughout eukaryotes, and we explore the role of Cdc42 proteins in the host survival of the human fungal pathogen Cryptococcus neoformans. Uniquely, C. neoformans has two functional Cdc42 paralogs, Cdc42 and Cdc420. Here we investigate the contribution of each paralog to resistance to host stress. In contrast to non-pathogenic model organisms, C. neoformans Cdc42 proteins are not required for viability under non-stress conditions. In the presence of cell stress, strains deleted for either paralog show defects in thermotolerance and morphogenesis, likely as a result of their roles in the organization of actin and septin structures during bud growth and cytokinesis. These proteins act downstream of C. neoformans Ras1 to regulate its morphogenesis subpathway, but not its effects on mating. Cdc42, and not Cdc420, is required for virulence in a murine model of cryptococcosis. The C. neoformans Cdc42 proteins likely perform complementary functions with other Rho-like GTPases to control cell polarity, septin organization, and hyphal transitions that allow survival in the environment and in the host.

Ballou, Elizabeth R.; Nichols, Connie B.; Miglia, Kathleen J; Kozubowski, Lukasz; Alspaugh, J. Andrew

2013-01-01

92

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

93

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

2013-10-01

94

High periconceptional protein intake modifies uterine and embryonic relationships increasing early pregnancy losses and embryo growth retardation in sheep.  

PubMed

The effects of supplemented protein level (PL) during the periconceptional period and their interaction with body condition were evaluated in sheep. Multiparous Rambouillet ewes (n = 12) received two PL of rumen undegradable protein (UIP) during a 30-day pre-mating and 15-day post-mating period: low [LPL, 24% crude protein (CP), 14 g UIP and 36 g/CP animal/day] and high [HPL, 44% CP, 30 g UIP and 50 g/CP animal/day]. While ovulation rate (OR) did not differ between treatments (1.6 +/- 0.5, mean +/- SEM), a lower fertility rate, a decreased embryo number and a reduced uterine pH (UpH) was observed in the HPL group (p < 0.05), irrespective of BC. Luteal tissue weight, volume and progesterone secretion did not differ among treatments. Sheep with lower UpH also had lower conceptus weight (Cwt; p < 0.05, r = 0.65) and conceptuses with lower mass tended to secrete less INF-tau and IGF-1, and the correspondent endometrial explants had a higher basal PGF(2alpha) release. Current study indicates that high protein diets during the periconceptional period in sheep modify uterine and embryonic relationships, increasing early pregnancy losses and inducing embryo growth retardation. Surviving embryos were affected by weight reductions, which could compromise later foetal growth and birth weight. Results evidence the key role of a balanced diet in reproductive success and indicate that the quality and nutrient composition of the maternal diet are essential for an adequate establishment of pregnancy, having paramount effects on the interplay of the embryo and the uterus. PMID:19220796

Meza-Herrera, C A; Ross, T T; Hallford, D M; Hawkins, D E; Gonzalez-Bulnes, A

2010-08-01

95

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

96

Casein Kinase II Phosphorylates the Fragile X Mental Retardation Protein and Modulates Its Biological Properties  

Microsoft Academic Search

Fragile X syndrome is caused by loss of FMR1 protein expression. FMR1 binds RNA and associates with polysomes in the cytoplasm; thus, it has been proposed to function as a regulator of gene expression at the posttranscriptional level. Posttranslational modification of FMR1 had previously been suggested to regulate its activity, but no experimental support for this model has been reported

Mikiko C. Siomi; Kyoko Higashijima; Akira Ishizuka; Haruhiko Siomi

2002-01-01

97

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

Microsoft Academic Search

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

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

2004-01-01

98

Flame retardants  

NASA Technical Reports Server (NTRS)

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

Troitzsch, J.

1988-01-01

99

Loss of the fragile X mental retardation protein decouples metabotropic glutamate receptor dependent priming of long-term potentiation from protein synthesis.  

PubMed

Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). FMRP is a negative regulator of local mRNA translation downstream of group 1 metabotropic glutamate receptor (Gp1 mGluR) activation. In the absence of FMRP there is excessive mGluR-dependent protein synthesis, resulting in exaggerated mGluR-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus. Understanding disease pathophysiology is critical for development of therapies for FXS and the question arises of whether it is more appropriate to target excessive LTD or excessive mGluR-dependent protein synthesis. Priming of long-term potentiation (LTP) is a qualitatively different functional consequence of Gp1 mGluR-stimulated protein synthesis at the same population of CA1 synapses where LTD can be induced. Therefore we determined if LTP priming, like LTD, is also disrupted in the Fmr1 knockout (KO) mouse. We found that mGluR-dependent priming of LTP is of comparable magnitude in wild-type (WT) and Fmr1 KO mice. However, whereas LTP priming requires acute stimulation of protein synthesis in WT mice, it is no longer protein synthesis dependent in the Fmr1 KO. These experiments show that the dysregulation of mGluR-mediated protein synthesis seen in Fmr1 KO mice has multiple consequences on synaptic plasticity, even within the same population of synapses. Furthermore, it suggests that there is a bifurcation in the Gp1 mGluR signaling pathway, with one arm triggering synaptic modifications such as LTP priming and LTD and the other stimulating protein synthesis that is permissive for these modifications. PMID:20554840

Auerbach, Benjamin D; Bear, Mark F

2010-08-01

100

Decreased fragile X mental retardation protein (FMRP) is associated with lower IQ and earlier illness onset in patients with schizophrenia.  

PubMed

The purpose of this study was to investigate Fragile X Syndrome (FXS)-related mechanisms in schizophrenia, including CGG triplet expansion, FMR1 mRNA, and fragile X mental retardation protein (FMRP) levels in lymphocytes. We investigated 36 patients with schizophrenia and 30 healthy controls using Southern blot analysis, mRNA assay, and enzyme-linked immunosorbent assay (ELISA). General intellectual functions were assessed with the Wechsler Adult Intelligence Scale-III, and the clinical symptoms were evaluated with the Positive and Negative Syndrome Scale. Results revealed that, relative to healthy controls, CGG triplet size and FMR1 mRNA were unaltered in patients with schizophrenia. However, the FMRP level was significantly reduced in patients compared with controls. We found an association between lower FMRP levels, reduced IQ, and earlier illness onset in schizophrenia. Chlorpromazine-equivalent antipsychotic dose did not correlate with FMRP levels. These results raise the possibility of impaired translation of FMR1 mRNA, altered epigenetic regulation, or increased degradation of FMRP in schizophrenia, which may play a role in dysfunctional neurodevelopmental processes and impaired neuroplasticity. PMID:23333116

Kovács, Tamás; Kelemen, Oguz; Kéri, Szabolcs

2013-12-30

101

Expression of fragile X mental retardation protein within the vocal control system of developing and adult male zebra finches  

PubMed Central

Individuals with fragile X syndrome (FXS) are cognitively impaired and have marked speech delays and deficits. Our goal was to characterize expression of FMRP, the fragile X mental retardation protein, encoded by the gene FMR1, in an animal model that learns to vocalize, namely the zebra finch Taeniopygia guttata (Tgu). We cloned and sequenced the zebra finch ortholog of FMR1 (TguFmr1) and developed an antibody that recognizes TguFmrp specifically. TguFmrp has structural features similar to its human ortholog FMRP. Because FXS patients exhibit sensorimotor deficits, we examined TguFmrp expression prior to, during, and after sensorimotor song learning in zebra finches. We found that TguFmrp is expressed throughout the brain and in four major song nuclei of the male zebra finch brain, primarily in neurons. Additionally, prior to sensorimotor learning, we observed elevated TguFmrp expression in the RA of post-hatch day 30 males, compared to the surrounding telencephalon, suggesting a preparation for this stage of song learning. Finally, we observed variable TguFmrp expression in the RA of adolescent and adult males: in some males it was elevated and in others it was comparable to the surrounding telencephalon. In summary, we have characterized the zebra finch ortholog of FMRP and found elevated levels in the premotor nucleus RA at a key developmental stage for vocal learning.

Winograd, Claudia; Clayton, David; Ceman, Stephanie

2008-01-01

102

The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses.  

PubMed

Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction in FXS. Matrix Metalloproteinase 9 (MMP-9) is an enzyme involved in activity-dependent reorganization of dendritic spine architecture and was shown to regulate spine morphology in a mouse model of FXS, the Fmr1 knock-out mice. Here we show that MMP-9 mRNA is part of the FMRP complex and colocalizes in dendrites. In the absence of FMRP MMP-9 mRNA translation is increased at synapses, suggesting that this mechanism contributes to the increased metalloproteinase level at synapses of Fmr1 knock-out mice. We propose that such a local effect can contribute to the aberrant dendritic spine morphology observed in the Fmr1 knock-out mice and in patients with FXS. PMID:24227732

Janusz, Aleksandra; Milek, Jacek; Perycz, Malgorzata; Pacini, Laura; Bagni, Claudia; Kaczmarek, Leszek; Dziembowska, Magdalena

2013-11-13

103

Absence of FMR1 protein in two mentally retarded fragile X males without CGG repeat expansion  

SciTech Connect

Fragile X syndrome is characterized by absence of the product of the FMR1 gene due to an expansion and abnormal methylation of a CGG repeat located in exon 1. While the vast majority of fragile X patients demonstrate this common mutation, a small number of non-CGG mutations have been identified among patients exhibiting features of fragile X syndrome. Three patients with large deletions ablating all or a portion of FMR1 have been previously reported. A fourth patient has been described with a point mutation resulting in an Ile367 Asn substitution. While this last individual suggests that FMR1 is directly responsible for fragile X syndrome, the severe phenotype observed suggests a gain of function mutation. Our long-term goal is to understand both the normal function of the FMR1 gene product and the consequences of its absence. Using Western blot analysis of protein extracts prepared from transformed lymphoblastoid cell lines derived from individuals suspected of fragile X syndrome without CGG expansion, we have identified two fragile X males who display no FMR1 protein. In order to facilitate identification of small-scale mutations in these patients, primers have been designed which allow amplification of each exon of the FMR1 gene along with their intron boundaries. Exons 2 through 17 of FMR1 have been analyzed by amplification of patient genomic DNA using these primers. Each patient shows normal length amplification product from each exon as assayed by agarose gel electrophoresis, suggesting the absence of insertions, deletions, or other rearrangements. Sequence analysis of exons 8, 9, 10, 11, and 12 has shown no alteration from the normal FMR1 sequence. Current analysis has focused on the use of mutation detection electrophoresis (MDE) in order to identify candidate exons for mutations. RT-PCR analysis is also under way to determine if FMR1 mRNA is present and to offer an alternative approach to mutation detection.

Lugenbeel, K.A.; Nelson, D.L. [Baylor College of Medicine, Houston, TX (United States); Carson, N.L.; Chudley, A.E. [Univ. of Manitoba, Winnipeg (Canada)

1994-09-01

104

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

2011-10-01

105

Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

106

6-Pyruvoyltetrahydropterin Synthase Paralogs Replace the Folate Synthesis Enzyme Dihydroneopterin Aldolase in Diverse Bacteria? †  

PubMed Central

Dihydroneopterin aldolase (FolB) catalyzes conversion of dihydroneopterin to 6-hydroxymethyldihydropterin (HMDHP) in the classical folate biosynthesis pathway. However, folB genes are missing from the genomes of certain bacteria from the phyla Chloroflexi, Acidobacteria, Firmicutes, Planctomycetes, and Spirochaetes. Almost all of these folB-deficient genomes contain an unusual paralog of the tetrahydrobiopterin synthesis enzyme 6-pyruvoyltetrahydropterin synthase (PTPS) in which a glutamate residue replaces or accompanies the catalytic cysteine. A similar PTPS paralog from the malaria parasite Plasmodium falciparum is known to form HMDHP from dihydroneopterin triphosphate in vitro and has been proposed to provide a bypass to the FolB step in vivo. Bacterial genes encoding PTPS-like proteins with active-site glutamate, cysteine, or both residues were accordingly tested together with the P. falciparum gene for complementation of the Escherichia coli folB mutation. The P. falciparum sequence and bacterial sequences with glutamate or glutamate plus cysteine were active; those with cysteine alone were not. These results demonstrate that PTPS paralogs with an active-site glutamate (designated PTPS-III proteins) can functionally replace FolB in vivo. Recombinant bacterial PTPS-III proteins, like the P. falciparum enzyme, mediated conversion of dihydroneopterin triphosphate to HMDHP, but other PTPS proteins did not. Neither PTPS-III nor other PTPS proteins exhibited significant dihydroneopterin aldolase activity. Phylogenetic analysis indicated that PTPS-III proteins may have arisen independently in various PTPS lineages. Consistent with this possibility, merely introducing a glutamate residue into the active site of a PTPS protein conferred incipient activity in the growth complementation assay, and replacing glutamate with alanine in a PTPS-III protein abolished complementation.

Pribat, Anne; Jeanguenin, Linda; Lara-Nunez, Aurora; Ziemak, Michael J.; Hyde, John E.; de Crecy-Lagard, Valerie; Hanson, Andrew D.

2009-01-01

107

Two Paralogous Families of a Two-Gene Subtilisin Operon Are Widely Distributed in Oral Treponemes  

PubMed Central

Certain oral treponemes express a highly proteolytic phenotype and have been associated with periodontal diseases. The periodontal pathogen Treponema denticola produces dentilisin, a serine protease of the subtilisin family. The two-gene operon prcA-prtP is required for expression of active dentilisin (PrtP), a putative lipoprotein attached to the treponeme's outer membrane or sheath. The purpose of this study was to examine the diversity and structure of treponemal subtilisin-like proteases in order to better understand their distribution and function. The complete sequences of five prcA-prtP operons were determined for Treponema lecithinolyticum, “Treponema vincentii,” and two canine species. Partial operon sequences were obtained for T. socranskii subsp. 04 as well as 450- to 1,000-base fragments of prtP genes from four additional treponeme strains. Phylogenetic analysis demonstrated that the sequences fall into two paralogous families. The first family includes the sequence from T. denticola. Treponemes possessing this operon family express chymotrypsin-like protease activity and can cleave the substrate N-succinyl-alanyl-alanyl-prolyl-phenylalanine-p-nitroanilide (SAAPFNA). Treponemes possessing the second paralog family do not possess chymotrypsin-like activity or cleave SAAPFNA. Despite examination of a range of protein and peptide substrates, the specificity of the second protease family remains unknown. Each of the fully sequenced prcA and prtP genes contains a 5? hydrophobic leader sequence with a treponeme lipobox. The two paralogous families of treponeme subtilisins represent a new subgroup within the subtilisin family of proteases and are the only subtilisin lipoprotein family. The present study demonstrated that the subtilisin paralogs comprising a two-gene operon are widely distributed among treponemes.

Correia, Frederick F.; Plummer, Alvin R.; Ellen, Richard P.; Wyss, Chris; Boches, Susan K.; Galvin, Jamie L.; Paster, Bruce J.; Dewhirst, Floyd E.

2003-01-01

108

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

PubMed

Mental retardation (MR) and autism are highly heterogeneous neurodevelopmental disorders. IL-1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic MR and is associated with autism. Thus, the elucidation of the functional role of IL1RAPL1 will contribute to our understanding of the pathogenesis of these mental disorders. Here, we showed that knockdown of endogenous IL1RAPL1 in cultured cortical neurons suppressed the accumulation of punctate staining signals for active zone protein Bassoon and decreased the number of dendritic protrusions. Consistently, the expression of IL1RAPL1 in cultured neurons stimulated the accumulation of Bassoon and spinogenesis. The extracellular domain (ECD) of IL1RAPL1 was required and sufficient for the presynaptic differentiation-inducing activity, while both the ECD and cytoplasmic domain were essential for the spinogenic activity. Notably, the synaptogenic activity of IL1RAPL1 was specific for excitatory synapses. Furthermore, we identified presynaptic protein tyrosine phosphatase (PTP) ? as a major IL1RAPL1-ECD interacting protein by affinity chromatography. IL1RAPL1 interacted selectively with certain forms of PTP? splice variants carrying mini-exon peptides in Ig-like domains. The synaptogenic activity of IL1RAPL1 was abolished in primary neurons from PTP? knock-out mice. IL1RAPL1 showed robust synaptogenic activity in vivo when transfected into the cortical neurons of wild-type mice but not in PTP? knock-out mice. These results suggest that IL1RAPL1 mediates synapse formation through trans-synaptic interaction with PTP?. Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of MR and autism as a common pathogenic pathway shared by these mental disorders. PMID:21940441

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

2011-09-21

109

The paralogous SPX3 and SPX5 genes redundantly modulate Pi homeostasis in rice.  

PubMed

The importance of SPX-domain-containing proteins to phosphate (Pi) homeostasis and signalling transduction has been established in plants. In this study, phylogenetic analysis revealed that OsSPX3 and OsSPX5 (SPX3/5) are paralogous SPX genes ( SYG1/Pho81/XPR1) in cereal crops. SPX3/5 are specifically responsive to Pi starvation at both the transcriptional and post-transcriptional levels. Similar tissue expression patterns of the two genes and proteins were identified by in situ hybridization and the transgenic plants harbouring SPX3pro-SPX3-GUS or SPX5pro-SPX5-GUS fusions, respectively. Both SPX3/5 are localized in the nucleus and cytoplasm in rice protoplasts and plants. SPX3/5 negatively regulate root-to-shoot Pi translocation with redundant function. The data showed that the Pi-starvation-accumulated SPX3/5 proteins are players in restoring phosphate balance following phosphate starvation. In vitro and in vivo protein-protein interaction analyses indicated that these two proteins can form homodimers and heterodimers, also implying their functional redundancy. Genetic interaction analysis indicated that SPX3/5 are functional repressors of OsPHR2 (PHR2), the rice orthologue of the central regulator AtPHR1 for Pi homeostasis and Pi signalling. These results suggest that the evolution of the additional redundant paralogous SPX genes is beneficial to plants recovering Pi homeostasis after Pi starvation by PHR2 pathway. PMID:24368504

Shi, Jing; Hu, Han; Zhang, Keming; Zhang, Wei; Yu, Yanan; Wu, Zhongchang; Wu, Ping

2014-03-01

110

Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy.  

PubMed

Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ?1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes. PMID:22791636

Mickiewicz, M; Zabielski, R; Grenier, B; Le Normand, L; Savary, G; Holst, J J; Oswald, I P; Metges, C C; Guilloteau, P

2012-06-01

111

Resolving the Ortholog Conjecture: Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs  

PubMed Central

The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the “ortholog conjecture”, or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentally supported functional annotations among homologs from 13 genomes mostly supports this model. We show that to analyze GO annotation effectively, several confounding factors need to be controlled: authorship bias, variation of GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias. After controlling for these biases, we observe that orthologs have generally more similar functional annotations than paralogs. This is especially strong for sub-cellular localization. We observe only a weak decrease in functional similarity with increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organisms such as E. coli, yeast or mouse have conserved function with human proteins.

Altenhoff, Adrian M.; Studer, Romain A.; Robinson-Rechavi, Marc; Dessimoz, Christophe

2012-01-01

112

Derangements of Hippocampal Calcium\\/Calmodulin Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome  

Microsoft Academic Search

Angelman syndrome (AS) is a disorder of human cognition characterized by severe mental retardation and epilepsy. Recently, a mouse model for AS (Ube3a maternal null mutation) was developed that displays deficits in both context-dependent learning and hippocampal long-term potentiation (LTP). In the present studies, we examined the molecular basis for these LTP and learning deficits. Mutant animals exhibited a significant

Edwin J. Weeber; Yong-Hui Jiang; Ype Elgersma; Andrew W. Varga; Yarimar Carrasquillo; Sarah E. Brown; Jill M. Christian; Banefsheh Mirnikjoo; Alcino Silva; Arthur L. Beaudet; J. David Sweatt

2003-01-01

113

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

114

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

115

Analysis of the Cellular Localization of Bdr Paralogs in Borrelia burgdorferi, a Causative Agent of Lyme Disease: Evidence for Functional Diversity  

PubMed Central

The bdr (Borrelia direct repeat) gene family of the genus Borrelia encodes a polymorphic group of proteins that carry a central repeat motif region containing putative phosphorylation sites and a hydrophobic carboxyl-terminal domain. It has been postulated that the Bdr proteins may anchor to the inner membrane via the C-terminal domain. In this study, we used cellular fractionation methodologies, salt and detergent treatments, and immunoblot analyses to assess the association of the Bdr proteins with the cellular infrastructure in both Borrelia burgdorferi (a Lyme disease spirochete) and B. turicatae (a relapsing fever spirochete). Triton X-114 extraction and partitioning experiments demonstrated that most Bdr paralogs are associated with the inner membrane-peptidoglycan complex. Analyses of cells treated with the highly chaotropic bile salt detergent deoxycholic acid demonstrated that some Bdr paralogs may also interact with the peptidoglycan, as evidenced by their tight association with the insoluble cellular matrix. In addition, immunoprecipitation (IP) experiments revealed an enhanced IP of all Bdr paralogs when the cell lysates were boiled prior to addition of the precipitating antibody. Furthermore, some Bdr paralogs were accessible to antibody in the IP experiments only in the boiled cell lysates. These observations suggest that different Bdr paralogs may carry out different structural-functional roles. Demonstration of the inner membrane localization of the Bdr proteins and of the differences in nature of the interaction of individual Bdr paralogs with the cell infrastructure is an important step toward defining the functional role of this unique protein family in the genus Borrelia.

Roberts, David M.; Theisen, Michael; Marconi, Richard T.

2000-01-01

116

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

2012-03-01

117

Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells.  

PubMed

The Polycomb group (PcG) protein BMI1 is a key factor in regulating hematopoietic stem cell (HSC) and leukemic stem cell self-renewal and functions in the context of the Polycomb repressive complex 1 (PRC1). In humans, each of the 5 subunits of PRC1 has paralog family members of which many reside in PRC1 complexes, likely in a mutually exclusive manner, pointing toward a previously unanticipated complexity of Polycomb-mediated silencing. We used an RNA interference screening approach to test the functionality of these paralogs in human hematopoiesis. Our data demonstrate a lack of redundancy between various paralog family members, suggestive of functional diversification between PcG proteins. By using an in vivo biotinylation tagging approach followed by liquid chromatography-tandem mass spectrometry to identify PcG interaction partners, we confirmed the existence of multiple specific PRC1 complexes. We find that CBX2 is a nonredundant CBX paralog vital for HSC and progenitor function that directly regulates the expression of the cyclin-dependent kinase inhibitor p21, independently of BMI1 that dominantly controls expression of the INK4A/ARF locus. Taken together, our data show that different PRC1 paralog family members have nonredundant and locus-specific gene regulatory activities that are essential for human hematopoiesis. PMID:23349393

van den Boom, Vincent; Rozenveld-Geugien, Marjan; Bonardi, Francesco; Malanga, Donatella; van Gosliga, Djoke; Heijink, Anne Margriet; Viglietto, Giuseppe; Morrone, Giovanni; Fusetti, Fabrizia; Vellenga, Edo; Schuringa, Jan Jacob

2013-03-28

118

Meiotic Recombination Between Paralogous RBCSB Genes on Sister Chromatids of Arabidopsis thaliana  

Microsoft Academic Search

Paralogous genes organized as a gene cluster can rapidly evolve by recombination between misaligned paralogs during meiosis, leading to duplications, deletions, and novel chimeric genes. To model unequal recombination within a specific gene cluster, we utilized a synthetic RBCSB gene cluster to isolate recombi- nant chimeric genes resulting from meiotic recombination between paralogous genes on sister chromatids. Several F1 populations

John G. Jelesko; Kristy Carter; Whitney Thompson; Yuki Kinoshita; Wilhelm Gruissem

2004-01-01

119

Mismatch Repair Gene PMS2: Disease-Causing Germline Mutations Are Frequent in Patients Whose Tumors Stain Negative for PMS2 Protein, but Paralogous Genes Obscure Mutation Detection and Interpretation  

Microsoft Academic Search

The MutL heterodimer formed by mismatch repair (MMR) proteins MLH1 and PMS2 is a major component of the MMR complex, yet mutations in the PMS2 gene are rare in the etiology of hereditary non- polyposis colorectal cancer. Evidence from five published cases suggested that contrary to the Knudson principle, PMS2 mutations cause hereditary nonpolyposis colorectal cancer or Turcot syndrome only

Hidewaki Nakagawa; Janet C. Lockman; Wendy L. Frankel; Heather Hampel; Kelle Steenblock; Lawrence J. Burgart; Stephen N. Thibodeau; Albert de la Chapelle

2004-01-01

120

Combined haploinsufficiency and purifying selection drive retention of RPL36a paralogs in Arabidopsis.  

PubMed

Whole-genome duplication events have driven to a large degree the evolution of angiosperm genomes. Although the majority of redundant gene copies after a genome duplication are lost, subfunctionalization or gene balance account for the retention of gene copies. The Arabidopsis 80S ribosome represents an excellent model to test the gene balance hypothesis as it consists of 80 ribosomal proteins, all of them encoded by genes belonging to small gene families. Here, we present the isolation of mutant alleles of the APICULATA2 (API2) and RPL36aA paralogous genes, which encode identical ribosomal proteins but share a similarity of 89% in their coding sequences. RPL36aA was found expressed at a higher level than API2 in the wild type. The loss-of-function api2 and rpl36aa mutations are recessive and affect leaf development in a similar way. Their double mutant combinations with asymmetric leaves2-1 (as2-1) caused leaf polarity defects that were stronger in rpl36aa as2-1 than in api2 as2-1. Our results highlight the role of combined haploinsufficiency and purifying selection in the retention of these paralogous genes in the Arabidopsis genome. PMID:24535089

Casanova-Sáez, Rubén; Candela, Héctor; Micol, José Luis

2014-01-01

121

Treatment With a Fusion Protein of the Extracellular Domains of NKG2D to IL-15 Retards Colon Cancer Growth in Mice.  

PubMed

Tumor-targeted cytokines are a new class of pharmaceutical anticancer agents often considered superior to the corresponding unconjugated cytokines for therapeutic purposes. We generated a new fusion protein, dsNKG2D-IL-15, in which double NKG2D extracellular domains were fused to IL-15, in Escherichia coli. This fusion protein promoted the activation, proliferation, and cytotoxicity of NK cells, and bound to NKG2D ligand-positive tumor cells. These tumor cells were also more susceptible to NK-cell attack when decorated with dsNKG2D-IL-15. The administration of mouse dsNKG2D-IL-15 protein in vivo significantly retarded the growth of transplanted colon cancers and prolonged the survival of tumor-bearing mice. Treatment with dsNKG2D-IL-15 increased the frequencies of NK and CD8 T cells in spleen and tumor tissues. The antitumor effect mediated by dsNKG2D-IL-15 was significantly decreased with in vivo depletion of NK cells or CD8 T cells. Recombinant dsNKG2D-IL-15 thus inhibited NKG2D ligand-positive tumor growth effectively by activating lymphocytes. This new biological fusion protein could potentially be used to elicit immunity in tumor-targeting treatments. PMID:24810637

Xia, Yan; Chen, Bei; Shao, Xiaoqing; Xiao, Weiming; Qian, Li; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

2014-06-01

122

Evolution of teleostean hatching enzyme genes and their paralogous genes  

Microsoft Academic Search

We isolated genes for hatching enzymes and their paralogs having two cysteine residues at their N-terminal regions in addition to four cysteines conserved in all the astacin family proteases. Genes for such six-cysteine-containing astacin proteases (C6AST) were searched out in the medaka genome database. Five genes for MC6AST1 to 5 were found in addition to embryo-specific hatching enzyme genes. RT-PCR

Mari Kawaguchi; Shigeki Yasumasu; Junya Hiroi; Kiyoshi Naruse; Masayuki Inoue; Ichiro Iuchi

2006-01-01

123

Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.  

PubMed

A current hypothesis proposes that fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, acts downstream of glutamatergic transmission, via metabotropic glutamate receptor (mGluR) G(q)-dependent signaling, to modulate protein synthesis critical for trafficking ionotropic glutamate receptors (iGluRs) at synapses. However, direct evidence linking FMRP and mGluR function with iGluR synaptic expression is limited. In this study, we use the Drosophila fragile X model to test this hypothesis at the well characterized glutamatergic neuromuscular junction (NMJ). Two iGluR classes reside at this synapse, each containing common GluRIIC (III), IID and IIE subunits, and variable GluRIIA (A-class) or GluRIIB (B-class) subunits. In Drosophila fragile X mental retardation 1 (dfmr1) null mutants, A-class GluRs accumulate and B-class GluRs are lost, whereas total GluR levels do not change, resulting in a striking change in GluR subclass ratio at individual synapses. The sole Drosophila mGluR, DmGluRA, is also expressed at the NMJ. In dmGluRA null mutants, both iGluR classes increase, resulting in an increase in total synaptic GluR content at individual synapses. Targeted postsynaptic dmGluRA overexpression causes the exact opposite GluR phenotype to the dfmr1 null, confirming postsynaptic GluR subtype-specific regulation. In dfmr1; dmGluRA double null mutants, there is an additive increase in A-class GluRs, and a similar additive impact on B-class GluRs, toward normal levels in the double mutants. These results show that both dFMRP and DmGluRA differentially regulate the abundance of different GluR subclasses in a convergent mechanism within individual postsynaptic domains. PMID:17989302

Pan, Luyuan; Broadie, Kendal S

2007-11-01

124

Rad51 paralogs Rad55-Rad57 balance the anti-recombinase Srs2 in Rad51 filament formation  

PubMed Central

Homologous recombination is a high-fidelity DNA repair pathway. Besides a critical role in accurate chromosome segregation during meiosis, recombination functions in DNA repair and in the recovery of stalled or broken replication forks to ensure genomic stability. In contrast, inappropriate recombination contributes to genomic instability, leading to loss of heterozygosity, chromosome rearrangements, and cell death. The RecA/UvsX/RadA/Rad51 family of proteins catalyzes the signature reactions of recombination, homology search and DNA strand invasion 1,2. Eukaryotes also possess Rad51 paralogs, whose exact role in recombination remains to be defined 3. Here we show that the budding yeast Rad51 paralogs, the Rad55-Rad57 heterodimer, counteract the anti-recombination activity of the Srs2 helicase. Rad55-Rad57 associate with the Rad51-ssDNA filament, rendering it more stable than a nucleoprotein filament containing Rad51 alone. The Rad51/Rad55-Rad57 co-filament resists disruption by the Srs2 anti-recombinase by blocking Srs2 translocation involving a direct protein interaction between Rad55-Rad57 and Srs2. Our results demonstrate an unexpected role of the Rad51 paralogs in stabilizing the Rad51 filament against a biologically important antagonist, the Srs2 anti-recombination helicase. The biological significance of this mechanism is indicated by a complete suppression of the ionizing radiation sensitivity of rad55 or rad57 mutants by concomitant deletion of SRS2, as expected for biological antagonists. We propose that the Rad51 presynaptic filament is a meta-stable reversible intermediate, whose assembly and disassembly is governed by the balance between Rad55-Rad57 and Srs2, providing a key regulatory mechanism controlling the initiation of homologous recombination. These data provide a paradigm for the potential function of the human RAD51 paralogs, which are known to be involved in cancer predisposition and human disease.

Liu, Jie; Renault, Ludovic; Veaute, Xavier; Fabre, Francis; Stahlberg, Henning; Heyer, Wolf-Dietrich

2011-01-01

125

NADPH-Cytochrome P450 Reductase: Molecular Cloning and Functional Characterization of Two Paralogs from Withania somnifera (L.) Dunal  

PubMed Central

Withania somnifera (L.) Dunal, a highly reputed medicinal plant, synthesizes a large array of steroidal lactone triterpenoids called withanolides. Although its chemical profile and pharmacological activities have been studied extensively during the last two decades, limited attempts have been made to decipher the biosynthetic route and identification of key regulatory genes involved in withanolide biosynthesis. Cytochrome P450 reductase is the most imperative redox partner of multiple P450s involved in primary and secondary metabolite biosynthesis. We describe here the cloning and characterization of two paralogs of cytochrome P450 reductase from W. somnifera. The full length paralogs of WsCPR1 and WsCPR2 have open reading frames of 2058 and 2142 bp encoding 685 and 713 amino acid residues, respectively. Phylogenetic analysis demonstrated that grouping of dual CPRs was in accordance with class I and class II of eudicotyledon CPRs. The corresponding coding sequences were expressed in Escherichia coli as glutathione-S-transferase fusion proteins, purified and characterized. Recombinant proteins of both the paralogs were purified with their intact membrane anchor regions and it is hitherto unreported for other CPRs which have been purified from microsomal fraction. Southern blot analysis suggested that two divergent isoforms of CPR exist independently in Withania genome. Quantitative real-time PCR analysis indicated that both genes were widely expressed in leaves, stalks, roots, flowers and berries with higher expression level of WsCPR2 in comparison to WsCPR1. Similar to CPRs of other plant species, WsCPR1 was un-inducible while WsCPR2 transcript level increased in a time-dependent manner after elicitor treatments. High performance liquid chromatography of withanolides extracted from elicitor-treated samples showed a significant increase in two of the key withanolides, withanolide A and withaferin A, possibly indicating the role of WsCPR2 in withanolide biosynthesis. Present investigation so far is the only report of characterization of CPR paralogs from W. somnifera.

Rana, Satiander; Lattoo, Surrinder K.; Dhar, Niha; Razdan, Sumeer; Bhat, Wajid Waheed; Dhar, Rekha S.; Vishwakarma, Ram

2013-01-01

126

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

PubMed Central

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 the inclusion membrane. Results Comparative analysis of this gene family within the published genome sequences provided evidence that multiple levels of genetic variation are evident within this single collection of paralogous genes. Frameshift mutations are found that result in both truncated gene products and pseudogenes that vary among isolates. Several genes in this family contain polycytosine (polyC) tracts either upstream or within the terminal 5' end of the predicted coding sequence. The length of the polyC stretch varies between paralogous genes and within single genes in the three genomes. Sequence analysis of genomic DNA from a collection of 12 C. pneumoniae clinical isolates was used to determine the extent of the variation in the Cpn 1054 gene family. Conclusions These studies demonstrate that sequence variability is present both among strains and within strains at several of the loci. In particular, changes in the length of the polyC tract associated with the different Cpn 1054 gene family members are common within each tested C. pneumoniae isolate. The variability identified within this newly described gene family may modulate either phase or antigenic variation and subsequent physiologic diversity within a C. pneumoniae population.

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

2002-01-01

127

Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent ?-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*  

PubMed Central

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of ?-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

Wang, Hansen; Kim, Susan S.; Zhuo, Min

2010-01-01

128

SUSTAINABLE FLAME RETARDANT NANOCOMPOSITES  

Microsoft Academic Search

This paper examines the current state of research into sustainable flame retardants with the work on nanocomposites highlighted. The motivations to move away from halogen-based flame retardants are discussed and a number of life -cycle-assessments are mentioned which set the stage for a similar LCA study of nanocomposite flame retardant products. Additives, such as hydrotalcite and cellulose nanofibrils, are proposed

Jeffrey W. Gilman

129

Assessment of radionuclide retardation  

Microsoft Academic Search

Radionuclide migration in the unsaturated and saturated rock zones composing the Yucca Mountain site may be retarded compared with groundwater movement. Predicting the potential for retardation by processes that include sorption, dispersion, and diffusion requires a thorough geologic characterization of this candidate site for the disposal of radioactive waste, augmented by geochemical laboratory experiments and modeling. The retardation phenomenon is

R. J. Herbst; J. A. Canepa

1988-01-01

130

Targeted mutagenesis of multiple and paralogous genes in Xenopus laevis using two pairs of transcription activator-like effector nucleases.  

PubMed

Transcription activator-like effector nucleases (TALENs) have been extensively used in genome editing in various organisms. In some cases, however, it is difficult to efficiently disrupt both paralogous genes using a single pair of TALENs in Xenopus laevis because of its polyploidy. Here, we report targeted mutagenesis of multiple and paralogous genes using two pairs of TALENs in X. laevis. First, we show simultaneous targeted mutagenesis of three genes, tyrosinase paralogues (tyra and tyrb) and enhanced green fluorescent protein (egfp) by injection of two TALENs pairs in transgenic embryos carrying egfp. Consistent with the high frequency of both severe phenotypic traits, albinism and loss of GFP fluorescence, frameshift mutation rates of tyr paralogues and egfp reached 40-80%. Next, we show early introduction of TALEN-mediated mutagenesis of these target loci during embryogenesis. Finally, we also demonstrate that two different pairs of TALENs can simultaneously introduce mutations to both paralogues encoding histone chaperone with high efficiency. Our results suggest that targeted mutagenesis of multiple genes using TALENs can be applied to analyze the functions of paralogous genes with redundancy in X. laevis. PMID:24329851

Sakane, Yuto; Sakuma, Tetsushi; Kashiwagi, Keiko; Kashiwagi, Akihiko; Yamamoto, Takashi; Suzuki, Ken-Ichi T

2014-01-01

131

Nutrient Requirements and Interactions Dietary Soybean Protein Compared with Casein Retards Senescence in the Senescence Accelerated Mouse1'2  

Microsoft Academic Search

The effects of replacing dietary casein with soybean protein on mean life span, mean life span of the last one-tenth of a group, grading scores of senes cence and deposition of senile amyloid were investigated in senescence accelerated mice (SAM-P\\/1) compared with a control strain (SAM-R\\/1). SAM-R\\/1 mice fed the soybean protein-containing diet had mean life spans of 618 ±

MASANORI HOSOKAWA; SHINTARO ISHIKAWA; KAORI KITAGAWA; ANDTOSHIO TAKEDA

132

The X-linked Mental Retardation Protein OPHN1 Interacts with Homer1b/c to Control Spine Endocytic Zone Positioning and Expression of Synaptic Potentiation.  

PubMed

At glutamatergic synapses, local endocytic recycling of AMPA receptors (AMPARs) is important for the supply of a mobile pool of AMPARs required for synaptic potentiation. This local recycling of AMPARs critically relies on the presence of an endocytic zone (EZ) near the postsynaptic density (PSD). The precise mechanisms that couple the EZ to the PSD still remain largely elusive, with the large GTPase Dynamin-3 and the multimeric PSD adaptor protein Homer1 as the two main players identified. Here, we demonstrate that a physical interaction between the X-linked mental retardation protein oligophrenin-1 (OPHN1) and Homer1b/c is crucial for the positioning of the EZ adjacent to the PSD, and present evidence that this interaction is important for OPHN1's role in controlling activity-dependent strengthening of excitatory synapses in the rat hippocampus. Disruption of the OPHN1-Homer1b/c interaction causes a displacement of EZs from the PSD, along with impaired AMPAR recycling and reduced AMPAR accumulation at synapses, in both basal conditions and conditions that can induce synaptic potentiation. Together, our findings unveil a novel role for OPHN1 as an interaction partner of Homer1b/c in spine EZ positioning, and provide new mechanistic insight into how genetic deficits in OPHN1 can lead to impaired synapse maturation and plasticity. PMID:24966368

Nakano-Kobayashi, Akiko; Tai, Yilin; Nadif Kasri, Nael; Van Aelst, Linda

2014-06-25

133

Intense and specialized dendritic localization of the fragile X mental retardation protein in binaural brainstem neurons: A comparative study in the alligator, chicken, gerbil, and human.  

PubMed

Neuronal dendrites are structurally and functionally dynamic in response to changes in afferent activity. The fragile X mental retardation protein (FMRP) is an mRNA binding protein that regulates activity-dependent protein synthesis and morphological dynamics of dendrites. Loss and abnormal expression of FMRP occur in fragile X syndrome (FXS) and some forms of autism spectrum disorders. To provide further understanding of how FMRP signaling regulates dendritic dynamics, we examined dendritic expression and localization of FMRP in the reptilian and avian nucleus laminaris (NL) and its mammalian analogue, the medial superior olive (MSO), in rodents and humans. NL/MSO neurons are specialized for temporal processing of low-frequency sounds for binaural hearing, which is impaired in FXS. Protein BLAST analyses first demonstrate that the FMRP amino acid sequences in the alligator and chicken are highly similar to human FMRP with identical mRNA-binding and phosphorylation sites, suggesting that FMRP functions similarly across vertebrates. Immunocytochemistry further reveals that NL/MSO neurons have very high levels of dendritic FMRP in low-frequency hearing vertebrates including alligator, chicken, gerbil, and human. Remarkably, dendritic FMRP in NL/MSO neurons often accumulates at branch points and enlarged distal tips, loci known to be critical for branch-specific dendritic arbor dynamics. These observations support an important role for FMRP in regulating dendritic properties of binaural neurons that are essential for low-frequency sound localization and auditory scene segregation, and support the relevance of studying this regulation in nonhuman vertebrates that use low frequencies in order to further understand human auditory processing disorders. J. Comp. Neurol. 522:2107-2128, 2014. © 2013 Wiley Periodicals, Inc. PMID:24318628

Wang, Yuan; Sakano, Hitomi; Beebe, Karisa; Brown, Maile R; de Laat, Rian; Bothwell, Mark; Kulesza, Randy J; Rubel, Edwin W

2014-06-15

134

Internal and External Paralogy in the Evolution of Tropomyosin Genes in Metazoans  

PubMed Central

Nature contains a tremendous diversity of forms both at the organismal and genomic levels. This diversity motivates the twin central questions of molecular evolution: what are the molecular mechanisms of adaptation, and what are the functional consequences of genomic diversity. We report a 22-species comparative analysis of tropomyosin (PPM) genes, which exist in a variety of forms and are implicated in the emergence of a wealth of cellular functions, including the novel muscle functions integral to the functional diversification of bilateral animals. TPM genes encode either or both of long-form [284 amino acid (aa)] and short-form (approximately 248 aa) proteins. Consistent with a role of TPM diversification in the origins and radiation of bilaterians, we find evidence that the muscle-specific long-form protein arose in proximal bilaterian ancestors (the bilaterian ‘stem’). Duplication of the 5? end of the gene led to alternative promoters encoding long- and short-form transcripts with distinct functions. This dual-function gene then underwent strikingly parallel evolution in different bilaterian lineages. In each case, recurrent tandem exon duplication and mutually exclusive alternative splicing of the duplicates, with further association between these alternatively spliced exons along the gene, led to long- and short-form–specific exons, allowing for gradual emergence of alternative “internal paralogs” within the same gene. We term these Mutually exclusively Alternatively spliced Tandemly duplicated Exon sets “MATEs”. This emergence of internal paralogs in various bilaterians has employed every single TPM exon in at least one lineage and reaches striking levels of divergence with up to 77% of long- and short-form transcripts being transcribed from different genomic regions. Interestingly, in some lineages, these internal alternatively spliced paralogs have subsequently been “externalized” by full gene duplication and reciprocal retention/loss of the two transcript isoforms, a particularly clear case of evolution by subfunctionalization. This parallel evolution of TPM genes in diverse metazoans attests to common selective forces driving divergence of different gene transcripts and represents a striking case of emergence of evolutionary novelty by alternative splicing.

Irimia, Manuel; Maeso, Ignacio; Gunning, Peter W.; Garcia-Fernandez, Jordi; Roy, Scott William

2010-01-01

135

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

SciTech Connect

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

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

2013-10-15

136

Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase  

PubMed Central

Background Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN. Methods The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats. Results The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1?. RSV reduced IL-1? but increased TNF-? and IL-6 levels in the diabetic kidneys. Conclusions Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.

2011-01-01

137

Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission.  

PubMed

Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak-scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS. PMID:24646437

Wang, Xiao-Sheng; Peng, Chun-Zi; Cai, Wei-Jun; Xia, Jian; Jin, Daozhong; Dai, Yuqiao; Luo, Xue-Gang; Klyachko, Vitaly A; Deng, Pan-Yue

2014-05-01

138

Forest Fire Retardant Research: A Status Report.  

National Technical Information Service (NTIS)

Forest fire retardant research was divided into five different study areas: (1) retardant effectiveness; (2) retardant physical properties; (3) retardant delivery systems; (4) retardant-caused corrosion; and (5) retardant environmental impact. Past resear...

C. W. George A. D. Blakely G. M. Johnson

1976-01-01

139

On the Incidence of Intron Loss and Gain in Paralogous Gene Families  

Microsoft Academic Search

Understanding gene duplication and gene structure evolution are fundamental goals of molecular evolutionary biology. A previous study by Babenko et al. (2004. Prevalence of intron gain over intron loss in the evolution of paralogous gene families. Nucleic Acids Res. 32:3724-3733) employed Dollo parsimony to infer spliceosomal intron losses and gains in paralogous gene families and concluded that there was a

Scott William Roy; David Penny

2007-01-01

140

Nuclear receptors, nuclear-receptor factors, and nuclear-receptor-like orphans form a large paralog cluster in Homo sapiens.  

PubMed

We studied a human protein paralog cluster formed by 38 nonredundant sequences taken from the Swiss-Prot database and its supplement, TrEMBL. These sequences include nuclear receptors, nuclear-receptor factors and nuclear-receptor-like orphans. Working separately with both the central cysteine-rich DNA-binding domain and the carboxy-terminal ligand-binding domain, we performed multialignment analyses that included drawings of paralog trees. Our results show that the cluster is highly multibranched, with considerable differences in the amino acid sequence in the ligand-binding domain (LBD), and 17 proximal subbranches which are identifiable and fully coincident when independent trees from both domains are compared. We identified the six recently proposed subfamilies as groups of neighboring clusters in the LBD paralog tree. We found similarities of 80%-100% for the N-terminal transactivation domain among mammalian ortholog receptors, as well as some paralog resemblances within diverse subbranches. Our studies suggest that during the evolutionary process, the three domains were assembled in a modular fashion with a nonshuffled modular fusion of the LBD. We used the EMBL server PredictProtein to make secondary-structure predictions for all 38 LBD subsequences. Amino acid residues in the multialigned homologous domains--taking the beginning of helix H3 of the human retinoic acid receptor-gamma as the initial point of reference--were substituted with H or E, which identify residues predicted to be helical or extended, respectively. The result was a secondary structure multialignment with the surprising feature that the prediction follows a canonical pattern of alignable alpha-helices with some short extended elements in between, despite the fact that a number of subsequences resemble each other by less than 25% in terms of the similarity index. We also identified the presence of a binary patterning in all of the predicted helices that were conserved throughout the 38-sequence sample. Our results fit well with a recently proposed evolutionary model that combines protein secondary structure and amino acid replacement. We propose a new hypothesis for molecular evolution, in which chaperones--acting as an endogenous cellular device for selection--play a crucial role in preserving protein secondary structure. PMID:9615448

Garcia-Vallvé, S; Palau, J

1998-06-01

141

Identification of mutations in TRAPPC9, which encodes the NIK- and IKK-beta-binding protein, in nonsyndromic autosomal-recessive mental retardation.  

PubMed

Mental retardation/intellectual disability is a devastating neurodevelopmental disorder with serious impact on affected individuals and their families, as well as on health and social services. It occurs with a prevalence of approximately 2%, is an etiologically heterogeneous condition, and is frequently the result of genetic aberrations. Autosomal-recessive forms of nonsyndromic MR (NS-ARMR) are believed to be common, yet only five genes have been identified. We have used homozygosity mapping to search for the gene responsible for NS-ARMR in a large Pakistani pedigree. Using Affymetrix 5.0 single nucleotide polymorphism (SNP) microarrays, we identified a 3.2 Mb region on 8q24 with a continuous run of 606 homozygous SNPs shared among all affected members of the family. Additional genotype data from microsatellite markers verified this, allowing us to calculate a two-point LOD score of 5.18. Within this region, we identified a truncating homozygous mutation, R475X, in exon 7 of the gene TRAPPC9. In a second large NS-ARMR/ID family, previously linked to 8q24 in a study of Iranian families, we identified a 4 bp deletion within exon 14 of TRAPPC9, also segregating with the phenotype and truncating the protein. This gene encodes NIK- and IKK-beta-binding protein (NIBP), which is involved in the NF-kappaB signaling pathway and directly interacts with IKK-beta and MAP3K14. Brain magnetic resonance imaging of affected individuals indicates the presence of mild cerebral white matter hypoplasia. Microcephaly is present in some but not all affected individuals. Thus, to our knowledge, this is the sixth gene for NS-ARMR to be discovered. PMID:20004765

Mir, Asif; Kaufman, Liana; Noor, Abdul; Motazacker, Mahdi M; Jamil, Talal; Azam, Matloob; Kahrizi, Kimia; Rafiq, Muhammad Arshad; Weksberg, Rosanna; Nasr, Tanveer; Naeem, Farooq; Tzschach, Andreas; Kuss, Andreas W; Ishak, Gisele E; Doherty, Dan; Ropers, H Hilger; Barkovich, A James; Najmabadi, Hossein; Ayub, Muhammad; Vincent, John B

2009-12-01

142

Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality.  

PubMed

Leucine-rich repeat-containing, G protein-coupled receptors (LGRs) belong to the largest mammalian superfamily of proteins with seven-transmembrane domains. LGRs can be divided into three subgroups based on their unique domain arrangement. Although two subgroups have been found to be receptors for glycoprotein hormones and relaxin-related ligands, respectively, the third LGR subgroup, consisting of LGR4-6, are orphan receptors with unknown physiological roles. To elucidate the functions of this subgroup of LGRs, LGR4 null mice were generated using a secretory trap approach to delete the majority of the LGR4 gene after the insertion of a beta-galactosidase reporter gene immediately after exon 1. Tissues expressing LGR4 were analyzed based on histochemical staining of the transgene driven by the endogenous LGR4 promoter. LGR4 was widely expressed in kidney, adrenal gland, stomach, intestine, heart, bone/cartilage, and other tissues. The expression of LGR4 in these tissues was further confirmed by immunohistochemical studies in wild-type animals. Analysis of the viability of 250 newborn animals suggested a skewed inheritance pattern, indicating that only 40% of the expected LGR4 null mice were born. For the LGR4 null mice viable at birth, most of them died within 2 d. Furthermore, the LGR4 null mice showed intrauterine growth retardation as reflected by a 14% decrease in body weight at birth, together with 30% and 40% decreases in kidney and liver weights, respectively. The present findings demonstrate the widespread expression of LGR4, and an essential role of LGR4 for embryonic growth, as well as kidney and liver development. The observed pre- and postnatal lethality of LGR4 null mice illustrates the importance of the LGR4 signaling system for the survival and growth of animals during the perinatal stage. PMID:15192078

Mazerbourg, Sabine; Bouley, Donna M; Sudo, Satoko; Klein, Cynthia A; Zhang, Jian V; Kawamura, Kazuhiro; Goodrich, Lisa V; Rayburn, Helen; Tessier-Lavigne, Marc; Hsueh, Aaron J W

2004-09-01

143

Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D).  

PubMed

Bloom's syndrome (BS) is a genetic disorder associated with short stature, fertility defects, and a predisposition to the development of cancer. BS cells are characterized by genomic instability; in particular, a high rate of reciprocal exchanges between sister-chromatids and homologous chromosomes. The BS gene product, BLM, is a helicase belonging to the highly conserved RecQ family. BLM is known to form a complex with the RAD51 recombinase, and to act upon DNA intermediates that form during homologous recombination, including D-loops and Holliday junctions. Here, we show that BLM also makes a direct physical association with the RAD51L3 protein (also known as RAD51D), a so-called RAD51 paralog that shows limited sequence similarity to RAD51 itself. This interaction is mediated through the N-terminal domain of BLM. To analyze functional interactions between BLM and RAD51L3, we have purified a heteromeric complex comprising RAD51L3 and a second RAD51 paralog, XRCC2. We show that the RAD51L3-XRCC2 complex stimulates BLM to disrupt synthetic 4-way junctions that model the Holliday junction. We also show that a truncated form of BLM, which retains helicase activity but is unable to bind RAD51L3, is not stimulated by the RAD51L3-XRCC2 complex. Our data indicate that the activity of BLM is modulated through an interaction with the RAD51L3-XRCC2 complex, and that this stimulatory effect on BLM is dependent upon a direct physical association between the BLM and RAD51L3 proteins. We propose that BLM co-operates with RAD51 paralogs during the late stages of homologous recombination processes that serve to restore productive DNA replication at sites of damaged or stalled replication forks. PMID:12975363

Braybrooke, Jeremy P; Li, Ji-Liang; Wu, Leonard; Caple, Fiona; Benson, Fiona E; Hickson, Ian D

2003-11-28

144

Fire-Retardant, Decorative Inks  

NASA Technical Reports Server (NTRS)

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

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

1987-01-01

145

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

Microsoft Academic Search

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

Mar??a R Gómez-Garc??a; Aurelio Serrano

2002-01-01

146

A Tandem Gene Duplication Followed by Recruitment of a Retrotransposon Created the Paralogous Bucentaur Gene (bcntp97) in the Ancestral Ruminant  

Microsoft Academic Search

Retrotransposable element-1 (RTE-1) is a class of long interspersed nucleotide elements that contain in its open reading frame an apurinic\\/apyrimidinic endonuclease domain (AP-END) and a reverse transcriptase domain. Ruminants have a clade-specific RTE-1 (BovB\\/RTE). The bovine bcnt gene (bucentaur or craniofacial developmental protein 1) has a du- plicated paralog (bcntp97) in tandem that recruited an AP-END of BovB\\/RTE as a

Shintaro Iwashita; Sadao Ueno; Kentaro Nakashima; Si-Young Song; Kenshiro Ohshima; Kazuaki Tanaka; Hideki Endo; Junpei Kimura; Masamichi Kurohmaru; Katsuhiro Fukuta; Lior David; Naoki Osada

2006-01-01

147

The evolutionarily conserved single-copy gene for murine Tpr encodes one prevalent isoform in somatic cells and lacks paralogs in higher eukaryotes  

Microsoft Academic Search

Vertebrate Tpr and its probable homologs in insects and yeast are heptad repeat-dominated nuclear proteins of Mr 195,000 to Mr 267,000 the functions of which are still largely unknown. Whereas two homologs exist in Saccharomyces cerevisiae, it has remained uncertain whether metazoans possess different paralogs or isoforms of Tpr that might explain controversial reports on the subcellular localization of this

Nikolai V. Kuznetsov; Linda Sandblad; Manuela E. Hase; Andreas Hunziker; Michaela Hergt; Volker C. Cordes

2002-01-01

148

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

PubMed Central

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

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

2013-01-01

149

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

PubMed

Arabidopsis thaliana became the model organism for plant studies because of its small diploid genome, rapid lifecycle and short adult size. Its genome was the first among plants to be sequenced, becoming the reference in plant genomics. However, the Arabidopsis genome is characterized by an inherently complex organization, since it has undergone ancient whole genome duplications, followed by gene reduction, diploidization events and extended rearrangements, which relocated and split up the retained portions. These events, together with probable chromosome reductions, dramatically increased the genome complexity, limiting its role as a reference. The identification of paralogs and single copy genes within a highly duplicated genome is a prerequisite to understand its organization and evolution and to improve its exploitation in comparative genomics. This is still controversial, even in the widely studied Arabidopsis genome. This is also due to the lack of a reference bioinformatics pipeline that could exhaustively identify paralogs and singleton genes. We describe here a complete computational strategy to detect both duplicated and single copy genes in a genome, discussing all the methodological issues that may strongly affect the results, their quality and their reliability. This approach was used to analyze the organization of Arabidopsis nuclear protein coding genes, and besides classifying computationally defined paralogs into networks and single copy genes into different classes, it unraveled further intriguing aspects concerning the genome annotation and the gene relationships in this reference plant species. Since our results may be useful for comparative genomics and genome functional analyses, we organized a dedicated web interface to make them accessible to the scientific community. PMID:24833233

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

2013-01-01

150

Effects of the brominated flame retardant tetrabromobisphenol-A (TBBPA) on cell signaling and function of Mytilus hemocytes: involvement of MAP kinases and protein kinase C.  

PubMed

Brominated flame retardants (BFRs) are a large group of compounds added to or applied as a treatment to polymeric materials to prevent fires. Tetrabisphenol A (TBBPA) is the most important individual BFR used in industry. Although TBBPA and its derivatives can be found in environmental samples, data are very limited on the presence of this compound in biota. Research on mammals indicates that TBBPA has low toxicity in vivo; however, in vitro TBBPA can act as a cytotoxicant, neurotoxicant, immunotoxicant, thyroid hormone agonist and has a weak estrogenic activity; in particular, the effects of TBBPA have been recently ascribed to its interactions with cellular signaling pathways, in particular with mitogen activated protein kinases (MAPKs). TBBPA has high acute toxicity to aquatic organisms, such as algae, molluscs, crustaceans and fish; however, little is known on the mechanisms of action of this compound in the cells of aquatic species. In this work, we investigated the possible effects and mechanisms of action of TBBPA on the immune cells, the hemocytes, of the marine mussel Mytilus galloprovincialis. The results demonstrate that TBBPA in the low micromolar range induces hemocyte lysosomal membrane destabilization. The effect was reduced or prevented by hemocyte pre-treatment by specific inhibitors of MAPKs and of protein kinase C (PKC). TBBPA stimulated phosphorylation of MAPK members and PKC, as evaluated by electrophoresis and Western blotting with anti-phospho-antibodies, although to a different extent and with distinct time-courses. A rapid (from 5 min) and transient increase in phosphoryation of the stress-activated JNK MAPKs and of PKC was observed, followed by a later increase (at 30-60 min) in phosphorylation of extracellularly regulated MAPKs (ERK2 MAPK) and of the stress-activated p38 MAPK. TBBPA significantly stimulated the hemocyte microbicidal activity towards E. coli, lysosomal enzyme release, phagocytic activity and extracellular superoxide (O2-) production. The results demonstrate that TBBPA in vitro activates the immune function of mussel hemocytes through kinase-mediated cell signaling and that common transduction pathways are involved in mediating the effects of this BFR in mammalian and aquatic invertebrate cells. PMID:16198432

Canesi, Laura; Lorusso, Lucia Cecilia; Ciacci, Caterina; Betti, Michele; Gallo, Gabriella

2005-11-10

151

Mental Retardation in TSC  

MedlinePLUS

... benefit on cognition, improved seizure control or seizure freedom. Other Therapies Finally, many people with mental retardation ... Outreach Connect With Others Ways to Give Your Impact Volunteer Sign-Up Form Special Events TSC Connect ...

152

Flame Retardant Elastomeric Compositions.  

National Technical Information Service (NTIS)

A patent application for an invention related to novel flame retardant compositions was presented. These elastomeric compositions are comprised of either spandex type polyurethane having incorporated into the polymer chain halogen containing polyols conve...

J. T. Howarth A. A. Massucco K. R. Sidman S. G. Sheth

1976-01-01

153

Fire retardant polyisocyanurate foam  

NASA Technical Reports Server (NTRS)

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

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

1972-01-01

154

Large-Scale Analysis of Orthologs and Paralogs under Covarion-Like and Constant-but-Different Models of Amino Acid Evolution  

PubMed Central

Functional divergence between homologous proteins is expected to affect amino acid sequences in two main ways, which can be considered as proxies of biochemical divergence: a “covarion-like” pattern of correlated changes in evolutionary rates, and switches in conserved residues (“conserved but different”). Although these patterns have been used in case studies, a large-scale analysis is needed to estimate their frequency and distribution. We use a phylogenomic framework of animal genes to answer three questions: 1) What is the prevalence of such patterns? 2) Can we link such patterns at the amino acid level with selection inferred at the codon level? 3) Are patterns different between paralogs and orthologs? We find that covarion-like patterns are more frequently detected than “constant but different,” but that only the latter are correlated with signal for positive selection. Finally, there is no obvious difference in patterns between orthologs and paralogs.

Studer, Romain A.; Robinson-Rechavi, Marc

2010-01-01

155

Effects of the Labels "Mentally Retarded" and "Retarded" on the Social Acceptability of Mentally Retarded Children.  

ERIC Educational Resources Information Center

Effects of the labels "mentally retarded" and "retarded" on 136 fifth- and sixth-grade children's attitudes toward peers were studied. Results indicated that children's attitudes were more positive toward the target child labeled "mentally retarded" than labeled "retarded." Reactions to the two labels were, in part, a function of the physical…

Siperstein, Gary N.; And Others

1980-01-01

156

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

157

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

PubMed Central

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

2013-01-01

158

HELQ promotes RAD51 paralog-dependent repair to avert germ cell attrition and tumourigenesis  

PubMed Central

Repair of interstrand crosslinks (ICLs) requires the coordinate action of the intra-S phase checkpoint and the Fanconi Anemia (FA) pathway, which promote ICL incision, translesion synthesis, and homologous recombination (reviewed in 1,2). Previous studies have implicated the 3?-5? superfamily 2 helicase HELQ/Hel308 in ICL repair in D. melanogaster (known as Mus301 or Spn-C3) and C. elegans (known as Helq-1 or Hel-3084). While in vitro analysis suggests that HELQ preferentially unwinds synthetic replication fork substrates with 3? ssDNA overhangs and also disrupts protein/DNA interactions while translocating along DNA5,6, little is known regarding its functions in mammalian organisms. Here we report that HELQ helicase-deficient mice exhibit subfertility, germ cell attrition, ICL sensitivity and tumour predisposition, with HelQ heterozygous mice exhibiting a similar, albeit less severe, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralog complex, BCDX2, and functions in parallel to the FA pathway to promote efficient HR at damaged replication forks. Thus, our results reveal a critical role for HELQ in replication-coupled DNA repair, germ cell maintenance and tumour suppression in mammals.

Adelman, Carrie A.; Lolo, Rafal L.; Birkbak, Nicolai J.; Murina, Olga; Matsuzaki, Kenichiro; Horejsi, Zuzana; Parmar, Kalindi; Borel, Valerie; Skehel, J. Mark; Stamp, Gordon; D'Andrea, Alan; Sartori, Alessandro A.; Swanton, Charles; Boulton, Simon J.

2013-01-01

159

Assessment of Complement C4 Gene Copy Number Using the Paralog Ratio Test  

PubMed Central

The complement C4 locus is in the class III region of the MHC, and exhibits copy number variation. Complement C4 null alleles have shown association with a number of diseases including systemic lupus erythematosus (SLE). However, most studies to date have used protein immunophenotyping and not direct interrogation of the genome to determine C4 null allele status. Moreover, a lack of accurate C4 gene copy number (GCN) estimation and tight linkage disequilibrium across the disease-associated MHC haplotypes has confounded attempts to establish whether or not these associations are causal. We have therefore developed a high through-put paralog ratio test (PRT) in association with two restriction enzyme digest variant ratio tests (REDVRs) to determine total C4 GCN, C4A GCN, and C4B GCN. In the densely genotyped CEU cohort we show that this method is accurate and reproducible when compared to gold standard Southern blot copy number estimation with a discrepancy rate of 9%. We find a broad range of C4 GCNs in the CEU and the 1958 British Birth Cohort populations under study. In addition, SNP-C4 CNV analyses show only moderate levels of correlation and therefore do not support the use of SNP genotypes as proxies for complement C4 GCN.

Fernando, Michelle M.A.; Boteva, Lora; Morris, David L.; Zhou, Bi; Wu, Yee Ling; Lokki, Marja-Liisa; Yu, Chack Yung; Rioux, John D.; Hollox, Edward J.; Vyse, Timothy J.

2013-01-01

160

Mutations in the FTSJ1 Gene Coding for a Novel S-Adenosylmethionine–Binding Protein Cause Nonsyndromic X-Linked Mental Retardation  

Microsoft Academic Search

Nonsyndromic X-linked mental retardation (NSXLMR) is a very heterogeneous condition, and most of the underlying gene defects are still unknown. Recently, we have shown that approximately 30% of these genes cluster on the proximal Xp, which prompted us to perform systematic mutation screening in brain-expressed genes from this region. Here, we report on a novel NSXLMR gene, FTSJ1, which harbors

Kristine Freude; Kirsten Hoffmann; Lars-Riff Jensen; Martin B. Delatycki; Vincent des Portes; Bettina Moser; B. C. J. Hamel; Hans van Bokhoven; Claude Moraine; Jean-Pierre Fryns; Jamel Chelly; Jozef Gécz; Steffen Lenzner; Vera M. Kalscheuer; Hans-Hilger Ropers

2004-01-01

161

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

162

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

2013-09-25

163

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

164

Flame retardant spandex type polyurethanes  

NASA Technical Reports Server (NTRS)

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

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

1978-01-01

165

Mental Retardation, Selected Conference Papers.  

ERIC Educational Resources Information Center

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

Scheerenberger, R.C., Ed.

166

Systematic Variation in the Pattern of Gene Paralog Retention between the Teleost Superorders Ostariophysi and Acanthopterygii  

PubMed Central

Teleost fish underwent whole-genome duplication around 450 Ma followed by diploidization and loss of 80–85% of the duplicated genes. To identify a deep signature of this teleost-specific whole-genome duplication (TSGD), we searched for duplicated genes that were systematically and uniquely retained in one or other of the superorders Ostariophysi and Acanthopterygii. TSGD paralogs comprised 17–21% of total gene content. Some 2.6% (510) of TSGD paralogs were present as pairs in the Ostariophysi genomes of Danio rerio (Cypriniformes) and Astyanax mexicanus (Characiformes) but not in species from four orders of Acanthopterygii (Gasterosteiformes, Gasterosteus aculeatus; Tetraodontiformes, Tetraodon nigroviridis; Perciformes, Oreochromis niloticus; and Beloniformes, Oryzias latipes) where a single copy was identified. Similarly, 1.3% (418) of total gene number represented cases where TSGD paralogs pairs were systematically retained in the Acanthopterygian but conserved as a single copy in Ostariophysi genomes. We confirmed the generality of these results by phylogenetic and synteny analysis of 40 randomly selected linage-specific paralogs (LSPs) from each superorder and completed with the transcriptomes of three additional Ostariophysi species (Ictalurus punctatus [Siluriformes], Sinocyclocheilus species [Cypriniformes], and Piaractus mesopotamicus [Characiformes]). No chromosome bias was detected in TSGD paralog retention. Gene ontology (GO) analysis revealed significant enrichment of GO terms relative to the human GO SLIM database for “growth,” “Cell differentiation,” and “Embryo development” in Ostariophysi and for “Transport,” “Signal Transduction,” and “Vesicle mediated transport” in Acanthopterygii. The observed patterns of paralog retention are consistent with different diploidization outcomes having contributed to the evolution/diversification of each superorder.

Garcia de la serrana, Daniel; Mareco, Edson A.; Johnston, Ian A.

2014-01-01

167

Systematic variation in the pattern of gene paralog retention between the teleost superorders Ostariophysi and Acanthopterygii.  

PubMed

Teleost fish underwent whole-genome duplication around 450 Ma followed by diploidization and loss of 80-85% of the duplicated genes. To identify a deep signature of this teleost-specific whole-genome duplication (TSGD), we searched for duplicated genes that were systematically and uniquely retained in one or other of the superorders Ostariophysi and Acanthopterygii. TSGD paralogs comprised 17-21% of total gene content. Some 2.6% (510) of TSGD paralogs were present as pairs in the Ostariophysi genomes of Danio rerio (Cypriniformes) and Astyanax mexicanus (Characiformes) but not in species from four orders of Acanthopterygii (Gasterosteiformes, Gasterosteus aculeatus; Tetraodontiformes, Tetraodon nigroviridis; Perciformes, Oreochromis niloticus; and Beloniformes, Oryzias latipes) where a single copy was identified. Similarly, 1.3% (418) of total gene number represented cases where TSGD paralogs pairs were systematically retained in the Acanthopterygian but conserved as a single copy in Ostariophysi genomes. We confirmed the generality of these results by phylogenetic and synteny analysis of 40 randomly selected linage-specific paralogs (LSPs) from each superorder and completed with the transcriptomes of three additional Ostariophysi species (Ictalurus punctatus [Siluriformes], Sinocyclocheilus species [Cypriniformes], and Piaractus mesopotamicus [Characiformes]). No chromosome bias was detected in TSGD paralog retention. Gene ontology (GO) analysis revealed significant enrichment of GO terms relative to the human GO SLIM database for "growth," "Cell differentiation," and "Embryo development" in Ostariophysi and for "Transport," "Signal Transduction," and "Vesicle mediated transport" in Acanthopterygii. The observed patterns of paralog retention are consistent with different diploidization outcomes having contributed to the evolution/diversification of each superorder. PMID:24732281

Garcia de la Serrana, Daniel; Mareco, Edson A; Johnston, Ian A

2014-04-01

168

Flame Retardant Epoxy Resins  

NASA Technical Reports Server (NTRS)

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

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

2004-01-01

169

Fire and smoke retardants  

NASA Astrophysics Data System (ADS)

Despite a reduction in Federal regulatory activity, research concerned with flame retardancy and smoke suppression in the private sector appears to be increasing. This trend seem related to the increased utilization of plastics for end uses which traditionally have employed metal or wood products. As a result, new markets have appeared for thermally stable and fire resistance thermoplastic materials, and this in turn has spurred research and development activity. In addition, public awareness of the dangers associated with fire has increased as a result of several highly publicized hotel and restaurant fires within the past two years. The consumers recognition of flammability characteristics as important materials property considerations has increased. The current status of fire and smoke retardant chemistry and research are summarized.

Drews, M. J.

170

Characterisation of a novel paralog of scavenger receptor class B member I (SCARB1) in Atlantic salmon (Salmo salar)  

PubMed Central

Background Red flesh colour is a unique trait found in some salmonid genera. Carotenoid pigments are not synthesized de novo in the fish, but are provided by dietary uptake. A better understanding of the molecular mechanisms underlying the cellular uptake and deposition of carotenoids could potentially be used to improve the low muscle deposition rate that is typically found in farmed Atlantic salmon. In addition, from an evolutionary point of view, the establishment and maintenance of this trait is still poorly understood. It has been demonstrated in several species that scavenger receptor class B, member 1 (SCARB1) is involved in intestinal absorption of carotenoids, which makes this gene a possible source of genetic variation in salmonid flesh pigmentation. Results In this study, a novel paralog of SCARB1 (SCARB1-2) was detected through screening for genetic variation in Atlantic salmon SCARB1. Full length SCARB1-2 encodes a protein with 89% identity to Atlantic salmon SCARB1, except for the C-terminal cytoplasmic tail that shows only 12% identity. The most prominent site of SCARB1 mRNA expression was in the mid gut, while a five-fold lower level was detected in Atlantic salmon skeletal muscle and liver. The SCARB1-2 mRNA was equally expressed in liver, muscle and mid gut, and at a lower level than SCARB1 mRNA. A total of seven different SCARB1-2 alleles comprising repetitive enhancer of zeste motifs (EZH2) were identified in the founding parents of a resource Atlantic salmon population. We mapped the SCARB1-2 paralog to a region on Atlantic salmon chromosome 1, containing a putative QTL for flesh colour. Addition of the SCARB1-2 marker increased the significance of this QTL, however the large confidence interval surrounding the QTL precludes confirmation of SCARB1-2 as a causative gene underlying variation in this trait. Conclusion We have characterised a novel paralog of SCARB1 (SCARB1-2), have mapped it to Atlantic salmon chromosome 1 and have described its expression in various tissues. Mapping with SCARB1-2 alleles added further evidence for a QTL affecting flesh colour on this chromosome, however further studies are needed to confirm a functional role for this gene in flesh colour pigmentation.

2011-01-01

171

Structural biasing elements for in-cell histone deacetylase paralog selectivity.  

PubMed

We use the structural dissection of two 1,3-dioxanes with in-cell histone deacetylase (HDAC) paralog selectivity to identify key elements for selective HDAC inhibitors. We demonstrate that o-aminoanilides are inactive toward HDAC6 while apparently inhibiting deacetylases that act upon histone substrates. This finding has important clinical implications for the development of HDAC inhibitor-based treatments that do not interfere with microtubule dynamics associated with HDAC6. We also show that suberoylanilide hydroxamic acid (SAHA) alone is a nonparalog-selective HDAC inhibitor and that the 1,3-dioxane diversity appended to SAHA is essential for HDAC6 paralog selectivity. PMID:12733869

Wong, Jason C; Hong, Roger; Schreiber, Stuart L

2003-05-14

172

Control of Copper Resistance and Inorganic Sulfur Metabolism by Paralogous Regulators in Staphylococcus aureus*  

PubMed Central

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

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

2011-01-01

173

Mice Lacking Zfhx1b, the Gene That Codes for Smad-Interacting Protein-1, Reveal a Role for Multiple Neural Crest Cell Defects in the Etiology of Hirschsprung Disease-Mental Retardation Syndrome  

PubMed Central

Recently, mutations in ZFHX1B, the gene that encodes Smad-interacting protein-1 (SIP1), were found to be implicated in the etiology of a dominant form of Hirschsprung disease–mental retardation syndrome in humans. To clarify the molecular mechanisms underlying the clinical features of SIP1 deficiency, we generated mice that bear a mutation comparable to those found in several human patients. Here, we show that Zfhx1b-knockout mice do not develop postotic vagal neural crest cells, the precursors of the enteric nervous system that is affected in patients with Hirschsprung disease, and they display a delamination arrest of cranial neural crest cells, which form the skeletomuscular elements of the vertebrate head. This suggests that Sip1 is essential for the development of vagal neural crest precursors and the migratory behavior of cranial neural crest in the mouse. Furthermore, we show that Sip1 is involved in the specification of neuroepithelium.

Van de Putte, Tom; Maruhashi, Mitsuji; Francis, Annick; Nelles, Luc; Kondoh, Hisato; Huylebroeck, Danny; Higashi, Yujiro

2003-01-01

174

Correlated changes between regulatory cis elements and condition-specific expression in paralogous gene families  

Microsoft Academic Search

Gene duplication is integral to evolution, providing novel opportunities for organisms to diversify in function. One fundamental pathway of functional diversification among initially redundant gene copies, or paralogs, is via alterations in their expres- sion patterns. Although the mechanisms underlying expression divergence are not completely under- stood, transcription factor binding sites and nucleosome occupancy are known to play a signifi-

Larry N. Singh; Sridhar Hannenhalli

2010-01-01

175

Prevalence of intron gain over intron loss in the evolution of paralogous gene families  

Microsoft Academic Search

The mechanisms and evolutionary dynamics of intron insertion and loss in eukaryotic genes remain poorly understood. Reconstruction of parsimonious scen- arios of gene structure evolution in paralogous gene families in animals and plants revealed numer- ous gains and losses of introns. In all analyzed lineages, the number of acquired new introns was substantially greater than the number of lost ancestral

Vladimir N. Babenko; Igor B. Rogozin; Sergei L. Mekhedov; Eugene V. Koonin

2004-01-01

176

Why Do Paralogs Persist? Molecular Evolution of CYCLOIDEA and Related Floral Symmetry Genes in Antirrhineae (Veronicaceae)  

Microsoft Academic Search

CYCLOIDEA (CYC) and DICHOTOMA (DICH) are paralogous genes that determine adaxial (dorsal) flower identity in the bilaterally symmetric flowers of Antirrhinum majus (snapdragon). We show here that the duplication leading to the existence of both CYC and DICH in Antirrhinum occurred before the radiation of the Antirrhineae (the tribe to which snapdragon belongs). We find no additional gene duplications within

Lena C. Hileman; David A. Baum

2003-01-01

177

Evolution of Paralogous Genes: Reconstruction of Genome Rearrangements Through Comparison of Multiple Genomes Within Staphylococcus aureus  

Microsoft Academic Search

Analysis of evolution of paralogous genes in a genome is central to our understanding of genome evolution. Comparison of closely related bacterial genomes, which has provided clues as to how genome sequences evolve under natural conditions, would help in such an analysis. With species Staphylococcus aureus, whole-genome sequences have been decoded for seven strains. We compared their DNA sequences to

Takeshi Tsuru; Mikihiko Kawai; Yoko Mizutani-Ui; Ikuo Uchiyama; Ichizo Kobayashi

2006-01-01

178

Extensive concerted evolution of rice paralogs and the road to regaining independence.  

PubMed

Many genes duplicated by whole-genome duplications (WGDs) are more similar to one another than expected. We investigated whether concerted evolution through conversion and crossing over, well-known to affect tandem gene clusters, also affects dispersed paralogs. Genome sequences for two Oryza subspecies reveal appreciable gene conversion in the approximately 0.4 MY since their divergence, with a gradual progression toward independent evolution of older paralogs. Since divergence from subspecies indica, approximately 8% of japonica paralogs produced 5-7 MYA on chromosomes 11 and 12 have been affected by gene conversion and several reciprocal exchanges of chromosomal segments, while approximately 70-MY-old "paleologs" resulting from a genome duplication (GD) show much less conversion. Sequence similarity analysis in proximal gene clusters also suggests more conversion between younger paralogs. About 8% of paleologs may have been converted since rice-sorghum divergence approximately 41 MYA. Domain-encoding sequences are more frequently converted than nondomain sequences, suggesting a sort of circularity--that sequences conserved by selection may be further conserved by relatively frequent conversion. The higher level of concerted evolution in the 5-7 MY-old segmental duplication may reflect the behavior of many genomes within the first few million years after duplication or polyploidization. PMID:18039882

Wang, Xiyin; Tang, Haibao; Bowers, John E; Feltus, Frank A; Paterson, Andrew H

2007-11-01

179

Functional specificity among ribosomal proteins regulates gene expression  

PubMed Central

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.

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

2008-01-01

180

Mental retardation, 1990: an overview.  

PubMed

This paper presents some of the major advances that have occurred in the field of mental retardation over the past 30 years. Included in this list are the developments of cytogenetics, etiology of cerebral palsy, progress in prevention as in Tay-Sachs disease and phenylketonuria, the fragile X syndrome, and the influence of certain aspects of diet on the developing fetus. Also included is a discussion of some of the areas of management of persons with mental retardation which remain as challenging problems for the future. These include persons who are both mentally retarded and emotionally ill, persons who are in penal institutions, and persons who have familial mental retardation. PMID:2290107

Kugel, R B

1990-10-01

181

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

182

Mental Retardation Is Dead: Long Live Mental Retardation!  

ERIC Educational Resources Information Center

This commentary discusses whether the American Association on Mental Retardation should change its name. The history of the term "mental retardation" is reviewed and it is argued that any new term will take on similar risks. The need to involve self-advocates in any terminology change is stressed. (Contains 5 references.) (CR)

Goode, David

2002-01-01

183

[X-linked mental retardation].  

PubMed

X-linked mental retardation (XLMR) affects 1.8 per thousand male births and is usually categorized as "syndromic" (MRXS) or "non-specific" (MRX) forms according to the presence or absence of specific signs in addition to the MR. Up to 60 genes have been implicated in XLMR and certain mutations can alternatively lead to MRXS or MRX. Indeed the extreme phenotypic and allelic heterogeneity of XLMR makes the classification of most genes difficult. Therefore, following identification of new genes, accurate retrospective clinical evaluation of patients and their families is necessary to aid the molecular diagnosis and the classification of this heterogeneous group of disorders. Analyses of the protein products corresponding to XLMR genes show a great diversity of cellular pathways involved in MR. Common mechanisms are beginning to emerge : a first group of proteins belongs to the Rho and Rab GTPase signaling pathways involved in neuronal differentiation and synaptic plasticity and a second group is related to the regulation of gene expression. In this review, we illustrate the complexity of XLMR conditions and present recent data about the FMR1, ARX and Oligophrenin 1 genes. PMID:16274646

Billuart, Pierre; Chelly, Jamel; Gilgenkrantz, Simone

2005-11-01

184

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

185

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.

186

Emotion in Mentally Retarded People.  

ERIC Educational Resources Information Center

The nature of emotion in mentally retarded people is considered. Recent research and theory suggest that two approaches are applicable to the study of mental retardation: the behavioral tradition, particularly conditioned emotional responding as well as emotional expression and recognition; and recent investigations of emotional development in…

Strongman, K. T.

1985-01-01

187

Hypoparathyroidism-retardation-dysmorphism syndrome  

PubMed Central

Congenital hypoparathyroidism, growth retardation and facial dysmorphism is a rare autosomal recessive disorder seen among children born to consanguineous couple of Arab ethnicity. This syndrome is commonly known as Sanjad-Sakati or hypoparathyroidism-retardation-dysmorphism syndrome (HRD). We report 13-year-old Hindu boy with hypoparathyroidism, tetany, facial dysmorphism and developmental delay, compatible with HRD syndrome.

Kumar, Kalenahalli Jagadish; Kumar, Halasahalli Chowdegowda Krishna; Manjunath, Vadambal Gopalakrishna; Mamatha, Sangaraju

2013-01-01

188

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.

189

Nanocomposite fire retardants ? a review  

Microsoft Academic Search

Most 5re retardant nanocomposites are made from layered silicates and organic polymers, a variety of methods are used in their synthesis. The mechanism for the 5re retardancy of these composites is generally considered to be due to the structure of the char formed during combustion, which enables the char to thermally insulate the polymer and inhibit the formation and escape

D. Porter; E. Metcalfe; M. J. K. Thomas

2000-01-01

190

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

191

Fire-Retardant Epoxy Adhesives  

NASA Technical Reports Server (NTRS)

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

Bilow, N.; Giants, T. W.

1982-01-01

192

Modeling amino acid substitution patterns in orthologous and paralogous genes  

Microsoft Academic Search

We study to what degree patterns of amino acid substitution vary between genes using two models of protein-coding gene evolution. The first divides the amino acids into groups, with one substitution rate for pairs of residues in the same group and a second for those in differing groups. Unlike previous applications of this model, the groups themselves are estimated from

Gavin C. Conant; Günter P. Wagner; Peter F. Stadler

2007-01-01

193

Sibling rivalry among paralogs promotes evolution of the human brain.  

PubMed

Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. PMID:22579279

Tyler-Smith, Chris; Xue, Yali

2012-05-11

194

Determining Fire Retardant Quality in the Field.  

National Technical Information Service (NTIS)

Onsite fire retardant effectiveness is dependent on a retardant's physical (rheological( and chemical (active fire-inhibiting salt) properties. Quality control at each retardant base is necessary to assure cost-effectiveness is achieved. Using relatively ...

C. W. George C. W. Johnson

1986-01-01

195

MICU2, a Paralog of MICU1, Resides within the Mitochondrial Uniporter Complex to Regulate Calcium Handling  

PubMed Central

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.

Plovanich, Molly; Bogorad, Roman L.; Sancak, Yasemin; Kamer, Kimberli J.; Strittmatter, Laura; Li, Andrew A.; Girgis, Hany S.; Kuchimanchi, Satya; De Groot, Jack; Speciner, Lauren; Taneja, Nathan; OShea, Jonathan; Koteliansky, Victor; Mootha, Vamsi K.

2013-01-01

196

MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling.  

PubMed

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel. PMID:23409044

Plovanich, Molly; Bogorad, Roman L; Sancak, Yasemin; Kamer, Kimberli J; Strittmatter, Laura; Li, Andrew A; Girgis, Hany S; Kuchimanchi, Satya; De Groot, Jack; Speciner, Lauren; Taneja, Nathan; Oshea, Jonathan; Koteliansky, Victor; Mootha, Vamsi K

2013-01-01

197

Impact of intrauterine growth retardation and early protein intake on growth, adipose tissue, and the insulin-like growth factor system in piglets.  

PubMed

Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity. PMID:18703996

Morise, Anne; Sève, Bernard; Macé, Katherine; Magliola, Corinne; Le Huërou-luron, Isabelle; Louveau, Isabelle

2009-01-01

198

Paralogous cyp51 genes in Fusarium graminearum mediate differential sensitivity to sterol demethylation inhibitors  

Microsoft Academic Search

Analysis of the genome sequence of Fusarium graminearum revealed three paralogous cyp51 genes (designated cyp51A, -B, and -C) encoding 14-? demethylases in this fungus. Targeted gene disruption showed that the cyp51A, -B or -C disruption mutants were morphologically indistinguishable from the parent isolate on potato dextrose agar medium, which indicates that none of these genes is essential for mycelial growth.

Xin Liu; Fangwei Yu; Guido Schnabel; Jianbing Wu; Zhengyi Wang; Zhonghua Ma

2011-01-01

199

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

200

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

201

Expression patterns of Hox10 paralogous genes during lumbar spinal cord development  

Microsoft Academic Search

We have examined the expression of three paralogous Hox genes from E11.5 through E15.5 in the mouse spinal cord. These ages coincide with major phases of spinal cord neurogenesis, neuronal differentiation, cell migration, gliogenesis, and motor neuron cell death. The three genes, Hoxa10, Hoxc10, and Hoxd10, are all expressed in the lumbar spinal cord and have distinct expression patterns. Mutations

Andrea Choe; Huy Q. Phun; David D. Tieu; Yan Hong Hu; Ellen M. Carpenter

2006-01-01

202

Comparative analysis of Hox paralog group 2 gene expression during Nile tilapia ( Oreochromis niloticus ) embryonic development  

Microsoft Academic Search

The hindbrain and pharyngeal arch-derived structures of vertebrates are determined, at least in part, by Hox paralog group 2 genes. In sarcopterygians, the Hoxa2 gene alone appears to specify structures derived from the second pharyngeal arch (PA2), while in zebrafish (Danio rerio), either of the two Hox PG2 genes, hoxa2b or hoxb2a, can specify PA2-derived structures. We previously reported three

Pierre Le Pabic; Edmund J. Stellwag; Shelby N. Brothers; Jean-Luc Scemama

2007-01-01

203

Robustness of Helicobacter pylori Infection Conferred by Context-Variable Redundancy among Cysteine-Rich Paralogs  

PubMed Central

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.

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

2013-01-01

204

Heterogeneous Conservation of Dlx Paralog Co-Expression in Jawed Vertebrates  

PubMed Central

Background The Dlx gene family encodes transcription factors involved in the development of a wide variety of morphological innovations that first evolved at the origins of vertebrates or of the jawed vertebrates. This gene family expanded with the two rounds of genome duplications that occurred before jawed vertebrates diversified. It includes at least three bigene pairs sharing conserved regulatory sequences in tetrapods and teleost fish, but has been only partially characterized in chondrichthyans, the third major group of jawed vertebrates. Here we take advantage of developmental and molecular tools applied to the shark Scyliorhinus canicula to fill in the gap and provide an overview of the evolution of the Dlx family in the jawed vertebrates. These results are analyzed in the theoretical framework of the DDC (Duplication-Degeneration-Complementation) model. Results The genomic organisation of the catshark Dlx genes is similar to that previously described for tetrapods. Conserved non-coding elements identified in bony fish were also identified in catshark Dlx clusters and showed regulatory activity in transgenic zebrafish. Gene expression patterns in the catshark showed that there are some expression sites with high conservation of the expressed paralog(s) and other expression sites with events of paralog sub-functionalization during jawed vertebrate diversification, resulting in a wide variety of evolutionary scenarios within this gene family. Conclusion Dlx gene expression patterns in the catshark show that there has been little neo-functionalization in Dlx genes over gnathostome evolution. In most cases, one tandem duplication and two rounds of vertebrate genome duplication have led to at least six Dlx coding sequences with redundant expression patterns followed by some instances of paralog sub-functionalization. Regulatory constraints such as shared enhancers, and functional constraints including gene pleiotropy, may have contributed to the evolutionary inertia leading to high redundancy between gene expression patterns.

Debiais-Thibaud, Melanie; Metcalfe, Cushla J.; Pollack, Jacob; Germon, Isabelle; Ekker, Marc; Depew, Michael; Laurenti, Patrick

2013-01-01

205

Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance  

SciTech Connect

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

Bozdag, Gonensin Ozan; Uluisik, Irem; Gulculer, Gulce Sila; Karakaya, Huseyin C. [Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir (Turkey)] [Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir (Turkey); Koc, Ahmet, E-mail: ahmetkoc@iyte.edu.tr [Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir (Turkey)] [Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir (Turkey)

2011-06-17

206

Phase retarders for optical communications  

NASA Astrophysics Data System (ADS)

This paper presents the design of quarter-wave retarders for the Dense Wave Division Multiplexing using parallel mirrors coated with a single layer. The output light from the device is parallel to the input light and displaced by a distance d. The quarter-wave retarder total reflection is in the range of 83%. Error analysis on the design is also presented. The error analysis shows how changes on the angle of incident light and the thin film thicknesses affect the design of the retarders.

Habli, Mohamad A.

2009-08-01

207

Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD.  

PubMed

Group I metabotropic glutamate receptors (mGluR) induce long-term depression (LTD) that requires protein synthesis. Here, we demonstrate that Arc/Arg3.1 is translationally induced within 5 min of mGluR activation, and this response is essential for mGluR-dependent LTD. The increase in Arc/Arg3.1 translation requires eEF2K, a Ca(2+)/calmodulin-dependent kinase that binds mGluR and dissociates upon mGluR activation, whereupon it phosphorylates eEF2. Phospho-eEF2 acts to slow the elongation step of translation and inhibits general protein synthesis but simultaneously increases Arc/Arg3.1 translation. Genetic deletion of eEF2K results in a selective deficit of rapid mGluR-dependent Arc/Arg3.1 translation and mGluR-LTD. This rapid translational mechanism is disrupted in the fragile X disease mouse (Fmr1 KO) in which mGluR-LTD does not require de novo protein synthesis but does require Arc/Arg3.1. We propose a model in which eEF2K-eEF2 and FMRP coordinately control the dynamic translation of Arc/Arg3.1 mRNA in dendrites that is critical for synapse-specific LTD. PMID:18614030

Park, Sungjin; Park, Joo Min; Kim, Sangmok; Kim, Jin-Ah; Shepherd, Jason D; Smith-Hicks, Constance L; Chowdhury, Shoaib; Kaufmann, Walter; Kuhl, Dietmar; Ryazanov, Alexey G; Huganir, Richard L; Linden, David J; Worley, Paul F

2008-07-10

208

Can earthworms survive fire retardants?  

USGS Publications Warehouse

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

Beyer, W.N.; Olson, A.

1996-01-01

209

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...

210

Intumescent coatings as fire retardants  

NASA Technical Reports Server (NTRS)

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

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

1970-01-01

211

Adenovirus regulates sumoylation of Mre11-Rad50-Nbs1 components through a paralog-specific mechanism.  

PubMed

The Mre11-Rad50-Nbs1 (MRN) complex plays a key role in the DNA damage response, presenting challenges for DNA viruses and retroviruses. To inactivate this complex, adenovirus (Ad) makes use of the E1B-55K and E4-open reading frame 6 (ORF6) proteins for ubiquitin (Ub)-mediated, proteasome-dependent degradation of MRN and the E4-ORF3 protein for relocalization and sequestration of MRN within infected-cell nuclei. Here, we report that Mre11 is modified by the Ub-related modifier SUMO-2 and Nbs1 is modified by both SUMO-1 and SUMO-2. We found that Mre11 and Nbs1 are sumoylated during Ad5 infection and that the E4-ORF3 protein is necessary and sufficient to induce SUMO conjugation. Relocalization of Mre11 and Nbs1 into E4-ORF3 nuclear tracks is required for this modification to occur. E4-ORF3-mediated SUMO-1 conjugation to Nbs1 and SUMO-2 conjugation to Mre11 and Nbs1 are transient during wild-type Ad type 5 (Ad5) infection. In contrast, SUMO-1 conjugation to Nbs1 is stable in cells infected with E1B-55K or E4-ORF6 mutant viruses, suggesting that Ad regulates paralog-specific desumoylation of Nbs1. Inhibition of viral DNA replication blocks deconjugation of SUMO-2 from Mre11 and Nbs1, indicating that a late-phase process is involved in Mre11 and Nbs1 desumoylation. Our results provide direct evidence of Mre11 and Nbs1 sumoylation induced by the Ad5 E4-ORF3 protein and an important example showing that modification of a single substrate by both SUMO-1 and SUMO-2 is regulated through distinct mechanisms. Our findings suggest how E4-ORF3-mediated relocalization of the MRN complex influences the cellular DNA damage response. PMID:22740413

Sohn, Sook-Young; Hearing, Patrick

2012-09-01

212

Adenovirus Regulates Sumoylation of Mre11-Rad50-Nbs1 Components through a Paralog-Specific Mechanism  

PubMed Central

The Mre11-Rad50-Nbs1 (MRN) complex plays a key role in the DNA damage response, presenting challenges for DNA viruses and retroviruses. To inactivate this complex, adenovirus (Ad) makes use of the E1B-55K and E4-open reading frame 6 (ORF6) proteins for ubiquitin (Ub)-mediated, proteasome-dependent degradation of MRN and the E4-ORF3 protein for relocalization and sequestration of MRN within infected-cell nuclei. Here, we report that Mre11 is modified by the Ub-related modifier SUMO-2 and Nbs1 is modified by both SUMO-1 and SUMO-2. We found that Mre11 and Nbs1 are sumoylated during Ad5 infection and that the E4-ORF3 protein is necessary and sufficient to induce SUMO conjugation. Relocalization of Mre11 and Nbs1 into E4-ORF3 nuclear tracks is required for this modification to occur. E4-ORF3-mediated SUMO-1 conjugation to Nbs1 and SUMO-2 conjugation to Mre11 and Nbs1 are transient during wild-type Ad type 5 (Ad5) infection. In contrast, SUMO-1 conjugation to Nbs1 is stable in cells infected with E1B-55K or E4-ORF6 mutant viruses, suggesting that Ad regulates paralog-specific desumoylation of Nbs1. Inhibition of viral DNA replication blocks deconjugation of SUMO-2 from Mre11 and Nbs1, indicating that a late-phase process is involved in Mre11 and Nbs1 desumoylation. Our results provide direct evidence of Mre11 and Nbs1 sumoylation induced by the Ad5 E4-ORF3 protein and an important example showing that modification of a single substrate by both SUMO-1 and SUMO-2 is regulated through distinct mechanisms. Our findings suggest how E4-ORF3-mediated relocalization of the MRN complex influences the cellular DNA damage response.

Sohn, Sook-Young

2012-01-01

213

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

214

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

215

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

216

Development of novel fire retardants  

NASA Astrophysics Data System (ADS)

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

Sigdel Regmi, Bhawani

217

Independent Evolutionary Origin of fem Paralogous Genes and Complementary Sex Determination in Hymenopteran Insects.  

PubMed

The primary signal of sex determination in the honeybee, the complementary sex determiner (csd) gene, evolved from a gene duplication event from an ancestral copy of the fem gene. Recently, other paralogs of the fem gene have been identified in several ant and bumblebee genomes. This discovery and the close phylogenetic relationship of the paralogous gene sequences led to the hypothesis of a single ancestry of the csd genetic system of complementary sex determination in the Hymenopteran insects, in which the fem and csd gene copies evolved as a unit in concert with the mutual transfers of sequences (concerted evolution). Here, we show that the paralogous gene copies evolved repeatedly through independent gene duplication events in the honeybee, bumblebee, and ant lineage. We detected no sequence tracts that would indicate a DNA transfer between the fem and the fem1/csd genes between different ant and bee species. Instead, we found tracts of duplication events in other genomic locations, suggesting that gene duplication was a frequent event in the evolution of these genes. These and other evidences suggest that the fem1/csd gene originated repeatedly through gene duplications in the bumblebee, honeybee, and ant lineages in the last 100 million years. Signatures of concerted evolution were not detectable, implicating that the gene tree based on neutral synonymous sites represents the phylogenetic relationships and origins of the fem and fem1/csd genes. Our results further imply that the fem1 and csd gene in bumblebees, honeybees, and ants are not orthologs, because they originated independently from the fem gene. Hence, the widely shared and conserved complementary sex determination mechanism in Hymenopteran insects is controlled by different genes and molecular processes. These findings highlight the limits of comparative genomics and emphasize the requirement to study gene functions in different species and major hymenopteran lineages. PMID:24743790

Koch, Vasco; Nissen, Inga; Schmitt, Björn D; Beye, Martin

2014-01-01

218

Convergent synthesis and discovery of a natural product-inspired paralog-selective Hsp90 inhibitor.  

PubMed

A convergent synthesis of benzoquinone ansamycin analogs is described that proceeds by a sequence of metallacycle-mediated alkyne-alkyne coupling, followed by site- and stereoselective dihydroxylation and global carbamate formation. These studies have led to (1) validation of alkyne-alkyne coupling to produce geldanamycin analogs that lack the problematic quinone, (2) the discovery that C6-C7 bis-carbamate functionality is compatible with Hsp90 inhibition, and (3) the identification of 1 as a nonquinone geldanamycin-inspired paralog-selective Hsp90 inhibitor. PMID:21866939

Jeso, Valer; Cherry, Lisa; Macklin, Todd K; Pan, Subhas Chandra; LoGrasso, Philip V; Micalizio, Glenn C

2011-10-01

219

Auto cannibalism in mental retardation  

PubMed Central

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

Verma, Rohit; Mina, Shaily; Sachdeva, Ankur

2014-01-01

220

Extensive Local Gene Duplication and Functional Divergence among Paralogs in Atlantic Salmon.  

PubMed

Many organisms can generate alternative phenotypes from the same genome, enabling individuals to exploit diverse and variable environments. A prevailing hypothesis is that such adaptation has been favored by gene duplication events, which generate redundant genomic material that may evolve divergent functions. Vertebrate examples of recent whole-genome duplications are sparse although one example is the salmonids, which have undergone a whole-genome duplication event within the last 100 Myr. The life-cycle of the Atlantic salmon, Salmo salar, depends on the ability to produce alternating phenotypes from the same genome, to facilitate migration and maintain its anadromous life history. Here, we investigate the hypothesis that genome-wide and local gene duplication events have contributed to the salmonid adaptation. We used high-throughput sequencing to characterize the transcriptomes of three key organs involved in regulating migration in S. salar: Brain, pituitary, and olfactory epithelium. We identified over 10,000 undescribed S. salar sequences and designed an analytic workflow to distinguish between paralogs originating from local gene duplication events or from whole-genome duplication events. These data reveal that substantial local gene duplications took place shortly after the whole-genome duplication event. Many of the identified paralog pairs have either diverged in function or become noncoding. Future functional genomics studies will reveal to what extent this rich source of divergence in genetic sequence is likely to have facilitated the evolution of extreme phenotypic plasticity required for an anadromous life-cycle. PMID:24951567

Warren, Ian A; Ciborowski, Kate L; Casadei, Elisa; Hazlerigg, David G; Martin, Sam; Jordan, William C; Sumner, Seirian

2014-01-01

221

Human DNA helicase HELQ participates in DNA interstrand crosslink tolerance with ATR and RAD51 paralogs  

PubMed Central

Mammalian HELQ is a 3?–5? DNA helicase with strand displacement activity. Here we show that HELQ participates in a pathway of resistance to DNA interstrand crosslinks (ICLs). Genetic disruption of HELQ in human cells enhances cellular sensitivity and chromosome radial formation by the ICL-inducing agent mitomycin C (MMC). A significant fraction of MMC sensitivity is independent of the Fanconi anaemia pathway. Sister chromatid exchange frequency and sensitivity to UV radiation or topoisomerase inhibitors is unaltered. Proteomic analysis reveals that HELQ is associated with the RAD51 paralogs RAD51B/C/D and XRCC2, and with the DNA damage-responsive kinase ATR. After treatment with MMC, reduced phosphorylation of the ATR substrate CHK1 occurs in HELQ-knockout cells, and accumulation of G2/M cells is reduced. The results indicate that HELQ operates in an arm of DNA repair and signalling in response to ICL. Further, the association with RAD51 paralogs suggests HELQ as a candidate ovarian cancer gene.

Takata, Kei-ichi; Reh, Shelley; Tomida, Junya; Person, Maria D.; Wood, Richard D.

2013-01-01

222

foxl2 and foxl3 are two ancient paralogs that remain fully functional in teleosts.  

PubMed

FOXL2 is a forkhead transcription factor involved in mammalian development and regulation of reproduction. Two foxl2 paralogs, foxl2a and foxl2b, have been described in various teleost species and were considered as fish-specific duplicates. Here, we report the isolation and characterization of foxl2a (foxl2) and foxl2b (foxl3) in European sea bass (Dicentrarchus labrax), together with the identification of these two genes in non-teleost genomes. Phylogenetic and synteny analyses indicate that these paralogs originated from an ancient genome duplication event that happened long before the teleost specific duplication. While foxl2/foxl2a has been maintained in most vertebrate lineages, foxl2b, which we propose to rename as foxl3, was repeatedly lost in tetrapods. Gonadal expression patterns of the sea bass genes point to a strong sexual dimorphism, and the mRNA levels of foxl2 in ovary and foxl3 in testis vary significantly during the reproductive cycle. When overexpressed in cultured ovarian follicular cells, foxl2 and foxl3 produced functional transcription factors able to control the expression of reproduction-related genes. Taken together, these data suggest that Foxl2 may play a conserved role in ovarian maturation, while Foxl3 could be involved in testis physiology. PMID:24045113

Crespo, Berta; Lan-Chow-Wing, Olivier; Rocha, Ana; Zanuy, Silvia; Gómez, Ana

2013-12-01

223

[MR imaging in mental retardation].  

PubMed

Mental retardation is considered idiopathic or not otherwise specified when no etiological diagnosis can be identified in spite of comprehensive history, physical examination and metabolic or genetic investigations. In such cases, brain MRI is indicated for patients with abnormal head size or shape, craniofacial malformation, somatic anomalies, neurocutaneous findings, seizures, focal neurological findings or behavioral and/or developmental problems. Brain anomalies are now considered a main category for the etiology of mental retardation. MRI evaluation should include axial images of the entire brain, sagittal images through the midline structures, and coronal images of the posterior fossa or entire brain. MRI allows detection of major and or minor cerebral anomalies or malformations, sometimes multiple. In the literature, the most frequently involved structures include: 1/ corpus callosum (hypoplasia, short corpus callosum and verticalized splenium), 2/ septum pellucidum (cavum septum pellucidum or cavum vergae), 3/ ventricles (ventriculomegaly), 4/ cerebral cortex (cortical dysplasia), 5/ cerebellum (hypoplasia), and 6/ extra-axial CSF spaces (enlargement). In our patient population, dysplasia involving the cerebellum and vermis have been identified, a finding that has not yet been described in the literature. MRI allows detection of multiple minor morphological anomalies. Most have classically been considered as normal variants but they may in fact be markers of cerebral dysgenesis and are currently the only anomaly detected in the work-up of patients with mental retardation. Their role in the pathogenesis of mental retardation is under evaluation. PMID:16237361

Soto-Ares, G; Joyes, B; Delmaire, C; Vallee, L; Pruvo, J P

2005-09-01

224

Fine motor retardation and depression  

Microsoft Academic Search

New computerized techniques allow the precise measurement of psychomotor retardation in patients with a major depressive episode (MDE). One such technique is the analysis of writing and drawing behaviour during figure copying tasks. In the present study, 22 inpatients with an MDE were compared to 22 normal controls. Three tasks were used: the drawing of lines and simple figures, the

Bernard Sabbe; Wouter Hulstijn; Jacques Van Hoof; Frans Zitman

1996-01-01

225

Activity Centers for Retarded Adults.  

ERIC Educational Resources Information Center

Reported were the results of a national study designed to identify and locate activity programs for retarded adults in the United States, to study comprehensively identified programs, to examine national, regional, state, and area standards, and to complete a monograph on activity programs. Findings of a 1964 report were compared with findings in…

Cortazzo, Arnold

226

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.

227

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.

228

Idiots Savants: Retarded and Gifted.  

ERIC Educational Resources Information Center

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

Yewchuk, Carolyn

229

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

230

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

PubMed Central

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

2013-01-01

231

Mental Retardation Deinstitutionalization Planning and Service Improvement.  

National Technical Information Service (NTIS)

The Mississippi Inter-agency Commission received funds in 1974 and 1975 to aid community programs and mental retardation institutions upgrade services, to allow mentally retarded individuals to remain in the community or to reintegrate them into the commu...

1975-01-01

232

Deinstitutionalization Services for Mentally Retarded Offenders.  

ERIC Educational Resources Information Center

The North Carolina Department of Correction, Division of Prisons, provides two deinstitutionalization services for mentally retarded, incarcerated offenders. These projects, funded by monies provided by the Council on Developmental Disabilities, serve mentally retarded youthful offenders (age 17-21) and retarded female offenders regardless of age.…

Urbanik, Richard

233

Energy Conservation and Mentally Retarded Citizens.  

ERIC Educational Resources Information Center

Suggested are some principles of developing energy conservation programs where retarded persons might be particularly affected, ways to conserve energy, and pertinent references. It is thought that the retarded, particularly the retarded in institutions, are more likely to suffer from energy conservation measures than members of the larger…

Fogelman, Charles J.; And Others

234

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

235

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

236

Four Approaches to Classification of Mental Retardation.  

ERIC Educational Resources Information Center

Four approaches to the classification of 110 students as mentally retarded were investigated. The frequency of classification of educable mentally retarded (EMR) and trainable mentally retarded (TMR) and nonretarded (NMR) Ss from three racial-ethnic groups (Anglos, Mexican Americans, and Blacks) and two socioeconomic groups (middle and low) was…

Fisher, Alan T.

237

Control of regenerative retarding of a vehicle equipped with a new energy recovery retarder  

Microsoft Academic Search

Control of regenerative retarding of a vehicle equipped with a new energy recovery retarder is investigated in this paper. The handle and pedal operations are designed to satisfy the need of control of vehicle brake under different working conditions. As the dynamics of the retarding process is highly nonlinear and time-variant, the control of regenerative retarding becomes rather complicated. For

Jing Xie; Binggang Cao; Dan Xu; Shuchen Zhang

2009-01-01

238

Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity  

PubMed Central

Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3?-untranslated regions (3? UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing. Compared with STAU1, STAU2 binds ?10-fold more UPF1 and ?two- to fivefold more of those SBS-containing mRNAs that were tested, and it comparably promotes UPF1 helicase activity, which is critical for SMD. STAU1- or STAU2-mediated augmentation of UPF1 helicase activity is not accompanied by enhanced ATP hydrolysis but does depend on ATP binding and a basal level of UPF1 ATPase activity. Studies of STAU2 demonstrate it changes the conformation of RNA-bound UPF1. These findings, and evidence for STAU1?STAU1, STAU2?STAU2, and STAU1?STAU2 formation in vitro and in cells, are consistent with results from tethering assays: the decrease in mRNA abundance brought about by tethering siRNA-resistant STAU2 or STAU1 to an mRNA 3? UTR is inhibited by downregulating the abundance of cellular STAU2, STAU1, or UPF1. It follows that the efficiency of SMD in different cell types reflects the cumulative abundance of STAU1 and STAU2. We propose that STAU paralogs contribute to SMD by “greasing the wheels” of RNA-bound UPF1 so as to enhance its unwinding capacity per molecule of ATP hydrolyzed.

Park, Eonyoung; Gleghorn, Michael L.; Maquat, Lynne E.

2013-01-01

239

New insights into the roles of Xin repeat-containing proteins in cardiac development, function, and disease.  

PubMed

Since the discovery of Xin repeat-containing proteins in 1996, the importance of Xin proteins in muscle development, function, regeneration, and disease has been continuously implicated. Most Xin proteins are localized to myotendinous junctions of the skeletal muscle and also to intercalated discs (ICDs) of the heart. The Xin gene is only found in vertebrates, which are characterized by a true chambered heart. This suggests that the evolutionary origin of the Xin gene may have played a key role in vertebrate origins. Diverse vertebrates including mammals possess two paralogous genes, Xin? (or Xirp1) and Xin? (or Xirp2), and this review focuses on the role of their encoded proteins in cardiac muscles. Complete loss of mouse Xin? (mXin?) results in the failure of forming ICD, severe growth retardation, and early postnatal lethality. Deletion of mouse Xin? (mXin?) leads to late-onset cardiomyopathy with conduction defects. Molecular studies have identified three classes of mXin?-interacting proteins: catenins, actin regulators/modulators, and ion-channel subunits. Thus, mXin? acts as a scaffolding protein modulating the N-cadherin-mediated adhesion and ion-channel surface expression. Xin expression is significantly upregulated in early stages of stressed hearts, whereas Xin expression is downregulated in failing hearts from various human cardiomyopathies. Thus, mutations in these Xin loci may lead to diverse cardiomyopathies and heart failure. PMID:24725425

Wang, Qinchuan; Lin, Jenny Li-Chun; Erives, Albert J; Lin, Cheng-I; Lin, Jim Jung-Ching

2014-01-01

240

Tree pattern matching in phylogenetic trees: automatic search for orthologs or paralogs in homologous gene sequence databases  

Microsoft Academic Search

Motivation: Comparative sequence analysis is widely used to study genome function and evolution. This approach first requires the iden- tification of homologous genes and then the interpretation of their homology relationships (orthology or paralogy). To provide help in this complex task, we developed three databases of homologous genes containing sequences, multiple alignments and phylogenetic trees: HOBACGEN, HOVERGEN and HOGENOM. In

Jean-françois Dufayard; Laurent Duret; Simon Penel; Manolo Gouy; François Rechenmann; Guy Perrière

2005-01-01

241

A novel paralogous gene family involved in phase-variable flagella-mediated motility in Campylobacter jejuni  

Microsoft Academic Search

these genes are hypothetical and are clustered in the regions involved in formation of three major cell surface structures: capsular polysaccharide, lipooligosaccharide and flagella. Among the genes of unknown function, the flagellar biosynthesis and modification region contains seven hypothetical paralogous genes designated as the motility accessory factor (maf) family. Remarkably, two of these genes (maf1 and maf4) were found to

Andrey V. Karlyshev; Dennis Linton; Norman A. Gregson; Brendan W. Wren

242

The Paralogous Hox Genes Hoxa10 and Hoxd10 Interact to Pattern the Mouse Hindlimb Peripheral Nervous System and Skeleton  

Microsoft Academic Search

The most 5? mouse Hoxa and Hoxd genes, which occupy positions 9–13 and which are related to the Drosophila AbdB gene, are all active in patterning developing limbs. Inactivation of individual genes produces alterations in skeletal elements of both forelimb and hindlimb; inactivation of some of these genes also alters hindlimb innervation. Simultaneous inactivation of paralogous or nonparalogous Hoxa and

George M. Wahba; Sirkka Liisa Hostikka; Ellen M. Carpenter

2001-01-01

243

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

244

Blindness in mentally retarded children  

Microsoft Academic Search

A preliminary survey of the causes of blindness in mentally retarded children in Denmark showed that 50% of the children had\\u000a optic atrophy, 12.5% had cataract while tapeto-retinal degenerations. other malformations and retrolental fibroplasia each\\u000a represents 8–9% of the causes of blindness. The survey, was done through written notification and some patients with tapeto-retinal\\u000a degenerations might have been wrongly diagnosed.

Mette Warburg

1975-01-01

245

Blindness in mentally retarded children  

Microsoft Academic Search

A preliminary survey of the causes of blindness in mentally retarded children in Denmark showed that 50% of the children had optic atrophy, 12.5% had cataract while tapeto-retinal degenerations, other malformations and retrolental fibroplasia each represents 8–9% of the causes of blindness. The survey, was done through written notification and some patients with tapeto-retinal degenerations might have been wrongly diagnosed.

Mette Warburg

1975-01-01

246

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

247

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

PubMed

Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast. PMID:21621519

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

2011-06-17

248

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

PubMed Central

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

Fekete, Eva M.; Zorrilla, Eric P.

2007-01-01

249

Characterization of a major outer membrane protein multigene family in Ehrlichia ruminantium.  

PubMed

Ehrlichia ruminantium is a tick-transmitted rickettsial pathogen, which causes heartwater or cowdriosis in wild and domestic ruminants. A dominant antibody response of animals infected with E. ruminantium is directed against the outer membrane protein MAP1 (major antigenic protein 1). Part of the locus containing map1 has been characterized and consists of four map1 paralogs, designated map1-2, map1-1, map1 and map1+1, indicating that map1 is encoded by a multigene family. The purpose of this study was to determine the total number of map1 paralogs and their transcriptional activities. Using genome walking and data from an ongoing E. ruminantium genome sequencing project at the Onderstepoort Veterinary Institute, we found 16 paralogs of the map1 gene tandemly arranged in a 25 kb region of the E. ruminantium genome. The map1 multigene family is downstream of a hypothetical transcriptional regulator gene and upstream of the secA gene. Thirteen paralogs at the 5' end of the 25-kb locus were connected by short intergenic spaces (ranging from 0 to 42 bp) and the remaining three paralogs at the 3' end were connected by longer intergenic spaces (ranging from 375 to 1612 bp). All 16 map1 paralogs were transcriptionally active in E. ruminantium grown in endothelial cells and paralogs with short intergenic spaces were co-transcribed with their adjacent genes. PMID:15087135

van Heerden, Henriette; Collins, Nicola E; Brayton, Kelly A; Rademeyer, Celia; Allsopp, Basil A

2004-04-14

250

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

PubMed Central

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.

Boucherat, Olivier; Montaron, Severine; Berube-Simard, Felix-Antoine; Aubin, Josee; Philippidou, Polyxeni; Wellik, Deneen M.; Dasen, Jeremy S.

2013-01-01

251

Fire-Retardant Polymeric Additives  

NASA Technical Reports Server (NTRS)

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

Williams, Martha K.; Smith, Trent M.

2011-01-01

252

PAK3 mutation in nonsyndromic X-linked mental retardation  

Microsoft Academic Search

Nonsyndromic X-linked mental retardation (MRX) syndromes are clinically homogeneous but genetically heterogeneous disorders, whose genetic bases are largely unknown. Affected individuals in a multiplex pedigree with MRX (MRX30), previously mapped to Xq22, show a point mutation in the PAK3 (p21-activated kinase) gene, which encodes a serine-threonine kinase. PAK proteins are crucial effectors linking Rho GTPases to cytoskeletal reorganization and to

Kristina M. Allen; Joseph G. Gleeson; Shubha Bagrodia; Michael W. Partington; John C. MacMillan; Richard A. Cerione; John C. Mulley; Christopher A. Walsh

1998-01-01

253

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

254

Accelerating set of retarded cement  

SciTech Connect

This patent describes improvement in a method of setting a volume of cement in a well completed in a subterranean formation in which a cement is or may become retarded and is pumped into the well and allowed to set to form a hard cementitious material there within. The improvement comprises contacting the cement with a solution of a compatible organic accelerator comprising a material that will produce formate ions in the cement slurry and selected from the group consisting of the first four carbon esters of formic acid, the esters including methyl formate, ethyl formate, normal-propyl formate, iso-propyl formate, normal-butyl formate, iso-butyl formate, and t-butyl formate. The patent also describes improvement in a method of setting a volume of cement in a well completed in subterranean formation, in which a cement is or may become retarded and is pumped into the well and allowed to set to form hard cementitious material therewithin at liner tops and in wellbore plugs. The improvement comprises contacting downhole the cement with a solution of a compatible organic accelerator comprising a material that will produce formate ions in the cement slurry and selected from the group consisting of formamide, and esters of formic acid, the esters including methyl formate, ethyl formate, normal propyl formate, isopropyl formate, normal butyl formate, iso-butyl formate and t-butyl formate.

Bloys, J.B.; Carpenter, R.B.; Wilson, W.N.

1991-04-09

255

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

256

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

PubMed Central

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

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

2013-01-01

257

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

258

Protective Effects of the Label "Mentally Retarded" on Children's Attitudes toward Mentally Retarded Peers.  

ERIC Educational Resources Information Center

The possible effect of the label "mentally retarded" to help ameliorate negative attitudes of 126 fourth-sixth graders toward mentally retarded peers with poor social behavior was examined. The label had a protective effect when the retarded child was withdrawn but little effect when the child was aggressive. (Author/CL)

Bak, John J.; Siperstein, Gary N.

1986-01-01

259

Improving fire retardancy of fast growing wood by coating with fire retardant and surface densification  

Microsoft Academic Search

Fire retardant fast-growing wood product was developed by coating with fire retardant and densifying the surface of wood. Trimethylol melamineformaldehyde resin mixed with phosphoric acid was coated on the wood surface, preheated and followed by hot pressing. E?ects of the amount of coating, preheating temperature, and densifying ratio on the fire retardancy of sugi (Cryptomeria japonica D. Don) wood, and

Subyakto; Takeshi Kajimoto; Toshimitsu Hata; Shigehisa Ishihara; Shuichi Kawai; Hideo Getto

1998-01-01

260

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)] [Princeton Univ., NJ (United States)

1997-03-01

261

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

262

Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance  

PubMed Central

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

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

2014-01-01

263

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

2013-03-01

264

Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation  

PubMed Central

Structural genomic variations represent a major driving force of evolution and a burst of large segmental gene duplications occurred in the human lineage during its separation from non-human primates. SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications. Here we find that both duplications (SRGAP2B and SRGAP2C) are partial and encode a truncated F-BAR domain. SRGAP2C is expressed in the developing and adult human brain and dimerizes with ancestral SRGAP2 to inhibit its function. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. Expression of SRGAP2C phenocopies SRGAP2 deficiency. It underlies sustained radial migration and leads to the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. These results suggest that inhibition of SRGAP2 function by its human-specific paralogs has contributed to the evolution of the human neocortex and plays an important role during human brain development.

Charrier, Cecile; Joshi, Kaumudi; Coutinho-Budd, Jaeda; Kim, Ji-Eun; Lambert, Nelle; de Marchena, Jacqueline; Jin, Wei-Lin; Vanderhaeghen, Pierre; Ghosh, Anirvan; Sassa, Takayuki; Polleux, Franck

2012-01-01

265

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

2011-08-01

266

MRI in children with mental retardation  

Microsoft Academic Search

Background. In mental retardation (MR) an aetiological diagnosis is not always obtained despite a detailed history, physical examination and metabolic or genetic investigations. In some of these patients, MRI is recommended and may identify subtle abnormal brain findings. Objective. We reviewed the cerebral MRI of children with non-specific mental retardation in an attempt to establish a neuroanatomical picture of this

Gustavo Soto-Ares; Béatrice Joyes; Marie-Pierre Lemaître; Louis Vallée; Jean-Pierre Pruvo

2003-01-01

267

Innovations in Vocational Rehabilitation and Mental Retardation.  

ERIC Educational Resources Information Center

Conference proceedings of the Vocational Rehabilitation Subdivision Meetings held at the American Association on Mental Deficiency contain discussions of innovative aspects of vocational rehabilitation and mental retardation. In the area of training rehabilitation counselors, George Baroff describes the Mental Retardation Training Institute in…

Ayers, George E., Ed.

268

Severe Mental Retardation: From Theory to Practice.  

ERIC Educational Resources Information Center

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

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

269

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.

270

Imaginative Play in Children with Mental Retardation.  

ERIC Educational Resources Information Center

This Dutch study examined the play behavior of 18 kindergarten children without mental retardation and 55 children with retardation, all at a developmental age of 4 to 5 years, as they played individually with a stimulating adult. The study found few differences with regard to activity, types and quality of play, and play content. (DB)

Hellendoorn, Joop; Hoekman, Joop

1992-01-01

271

Assessment of Mental Retardation by School Psychologists  

Microsoft Academic Search

School psychologists play an important role in the assessment and classification of mental retardation. Although the current diagnostic and classification systems contain slight differences in their diagnostic criteria for mental retardation, they contain three essential elements: (a) a presence of significant deficits in cognitive functioning, (b) a concurrent presence of significant limitations in adaptive behavior, and (c) an onset during

Luc Lecavalier; Marc J. Tassé; Stéphanie Lévesque

2002-01-01

272

Discrimination Learning in Profoundly Retarded Children.  

ERIC Educational Resources Information Center

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

Suib, Michael R.; And Others

1980-01-01

273

A BIBLIOGRAPHY ON MENTAL RETARDATION. NUMBER I.  

ERIC Educational Resources Information Center

INCLUDING BOOKS, JOURNAL ARTICLES, THESES, RESEARCH REPORTS, MONOGRAPHS, AND GOVERNMENT PUBLICATIONS, THE BIBLIOGRAPHY LISTS 105 ITEMS ON MENTAL RETARDATION. PUBLICATION DATES RANGE FROM 1931 THROUGH 1966 (IN PRESS). THE ITEMS CITED COVER CONCEPTS OF MENTAL RETARDATION, EDUCATIONAL PERFORMANCE OF THE MENTALLY HANDICAPPED, AND PROGRAMS FOR THEM. A…

GELHART, ROBERT P.

274

Toward a Unitary Concept of Mental Retardation.  

ERIC Educational Resources Information Center

The author reviews the history of the category of educable mental retardation (EMR), asserts that students with this label are more like children with academic or behavioral difficulties than they are like their more retarded peers, and suggests an approach focusing on returning EMR students to the regular school curriculum. (CL)

Lilly, M. Stephen

1982-01-01

275

Manual Skill Training of Retarded Children.  

ERIC Educational Resources Information Center

In an on-going pilot study, training procedures previously found successful with moderately and severely retarded adolescents and adults have been adapted to teaching trainable retarded children (6-, 8-, and 10-years-old) to assemble a 14-piece coaster brake. Modifications in the carefully detailed task analysis approach have included the need for…

Pomerantz, David J.

1975-01-01

276

Mental Retardation: Update 2002. ERIC Digest.  

ERIC Educational Resources Information Center

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

Hourcade, Jack

277

Environmental Implications of Fire-Retardant Chemicals.  

National Technical Information Service (NTIS)

The report ensures the environmental safety of fire-retardant chemicals used to fight forest fires, the U.S. Forest Service requested an investigation to determine the potential for UV-enhanced toxicity and environmental persistence of fire-retardant chem...

E. E. Little R. D. Calfee

2002-01-01

278

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

279

Genomic imbalances in mental retardation  

PubMed Central

Introduction: It has been estimated that cytogenetically visible rearrangements are present in ~1% of newborns. These chromosomal changes can cause a wide range of deleterious developmental effects, including mental retardation (MR). It is assumed that many other cases exist where the cause is a submicroscopic deletion or duplication. To facilitate the detection of such cases, different techniques have been developed, which have differing efficiency as to the number of loci and patients that can be tested. Methods: We implemented multiplex amplifiable probe hybridisation (MAPH) to test areas known to be rearranged in MR patients (for example, subtelomeric/pericentromeric regions and those affected in microdeletion syndromes) and to look for new regions that might be related to MR. Results: In this study, over 30 000 screens for duplications and deletions were carried out; 162 different loci tested in each of 188 developmentally delayed patients. The analysis resulted in the detection of 19 rearrangements, of which ~65% would not have been detected by conventional cytogenetic analysis. A significant fraction (46%) of the rearrangements found were interstitial, despite the fact that only a limited number of these loci have so far been tested. Discussion: Our results strengthen the arguments for whole genome screening within this population, as it can be assumed that many more interstitial rearrangements would be detected. The strengths of MAPH for this analysis are the simplicity, the high throughput potential, and the high resolution of analysis. This combination should help in the future identification of the specific genes that are responsible for MR.

Kriek, M; White, S; Bouma, M; Dauwerse, H; Hansson, K; Nijhuis, J; Bakker, B; van Ommen, G-J B; den Dunnen, J T; Breuning, M

2004-01-01

280

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

281

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

282

Facilitating the Social Mainstreaming of Retarded Children.  

ERIC Educational Resources Information Center

Educable mentally retarded children who are mainstreamed are likely to have social problems due to personological concerns (maladaptive behavior, labeling) and environmental concerns (teacher attitudes and expectancies, peer attitudes). (CL)

Gottlieb, Jay; Leyser, Yona

1981-01-01

283

Flame Retardant Homopolymer and Polymer Blend Composites  

NASA Astrophysics Data System (ADS)

We investigated the flame retardant performance of homopolymer, EVA, PMMA, PP, and PS, and polymer blends, PS/PMMA, PC/SAN, with organoclay and conventional flame retardant agents such as decabromodiphenyl ether (DB) and phosphorus compounds. These materials were characterized by TEM, STXM, LOI and UL 94 V-0. TEM and STXM photographs show that the addition of organoclays into polymer blends drastically slows down the phase separation and accelerates the decompose of bromine compounds during the combustion. Further, UL 94 V-0 results indicate that PS/PMMA blend with DB can not achieve self-extinguishing in the absence of clay. The amounts of flame retardants and clay used were varied to try to achieve the optimal formula to pass UL 94 V-0. The synergism of clay and flame retardant agents were completely studied by various measurements, time dependence burning (TEM, Ion Chromatography), GC-MS, and cone calorimeter.

Rafailovich, Miriam; Si, Mayu; Sokolov, Jonathan; Araki, Tohru; Ade, Harald; Hefter, Daniel; Sokolov, Aryeh

2006-03-01

284

Retardation analytical model to extend service life  

NASA Technical Reports Server (NTRS)

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

Matejczyk, D.

1984-01-01

285

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

286

Simplified Method for Determining Floodwater Retarding Storage.  

National Technical Information Service (NTIS)

This technical release provides an approximation method to determine the minimum required floodwater retarding storage for single stage principal spillway structures. The method is based on the use of mass curves.

1978-01-01

287

Interaction between family violence and mental retardation.  

PubMed

Although family violence and mental retardation are both prevalent in today's society; very little research has been conducted to investigate the relationship between them. Characteristics that make individuals with mental retardation more vulnerable to family violence are discussed in the areas of child, adult, and sexual abuse. Common psychological effects of this trauma are then explored followed by implications for practice. Because family violence and mental retardation are both societal as well as personal issues, intervention and prevention efforts must occur at both a direct service level and a community/macro service level. With such intervention and prevention efforts, persons with mental retardation will receive superior service when dealing with issues related to family violence. PMID:11714383

Strickler, H L

2001-12-01

288

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...

289

Intrauterine Growth Retardation Associated with Uterine Malformations  

PubMed Central

Intrauterine growth retardation is caused by factors that prevent adequate fetal nourishment or by factors that intrinsically affect the fetus. Limited available space due to a congenitally malformed uterus may prevent normal intrauterine development. Two cases are presented here. A review of the available literature confirms the tendency of women with congenital uterine malformations to have smaller offspring. Intrauterine growth retardation should be added to the more commonly known complications associated with a congenitally malformed uterus. ImagesFigure 1Figure 2

Poma, Pedro A.

1982-01-01

290

Gitelman's syndrome: Rare presentation with growth retardation  

PubMed Central

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypokalemia, hypomagnesaemia, hypocalciuria, hyperreninemia and without hypertension. Gitelman's syndrome is caused by mutations of the SLC12A3 gene, which encodes the Na/Cl co-transporter (NCCT) in the distal convoluted tubule. Majority of cases manifest during adolescence or adulthood and growth retardation is not the common feature. We report a rare presentation of Gitelman's syndrome in a four-year-old boy with growth retardation.

Gaur, A.; Ambey, R.; Gaur, B. K.

2014-01-01

291

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

292

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

293

Flame retardants for polypropylene based on lignin  

Microsoft Academic Search

Lignin has been investigated as flame retardant for isotactic polypropylene (PP) by means of thermogravimetric analysis in nitrogen and cone calorimetry with incident heat flux exposure at 25 kW\\/m2. Lignin has been used in synergism with aluminium hydroxide, poly(vinyl alcohol), melamine phosphate, monoammonium phosphate and ammonium polyphosphate. These flame retardants, based on lignin, increase the thermal degradation temperature, the combustion

A De Chirico; M Armanini; P Chini; G Cioccolo; F Provasoli; G Audisio

2003-01-01

294

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

295

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

SciTech Connect

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

Lundin, L.G. (Univ. of Uppsala (Sweden))

1993-04-01

296

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

297

Toward a More Acceptable Terminology in Mental Retardation.  

ERIC Educational Resources Information Center

This reprint (from a 1961 article) and excerpt (from a 1977 paper) recommend definitions of various terms in the field of mental retardation, such as subaverage, organic retardation, and functional retardation and argue that incidence and prevalence estimates of mental retardation vary so remarkably and change so frequently to fit certain…

Blatt, Burton

1994-01-01

298

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

299

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

PubMed

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. PMID:21926414

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

2011-12-15

300

Current researches on fire retardant materials in Japan  

NASA Astrophysics Data System (ADS)

The use of fire retardant materials is a very effective way to decrease human loss in the event of building fires. However, smoke and toxicity in a fire, which is the collateral phenomena due to fire retardant were paid more attention than the fire retardant materials themselves. This is because much damage is brought about by smoke and toxicity in a fire. Research papers on fire retardant materials are largely concerned with pyrolysis and combustion products. Twenty-eight papers are reviewed and classified into the following three categories: flame retarding mechanism and evaluation of flammability, pyrolysis and gaseous products of flame retardant materials, and development of flame retardant materials.

Akita, K.

301

Genetics of autosomal recessive non-syndromic mental retardation: recent advances.  

PubMed

The identification of the genes mutated in autosomal recessive non-syndromic mental retardation (ARNSMR) has been very active recently. This report presents an overview of the current knowledge on clinical data in ARNSMR and progress in research. To date, 12 ARNSMR loci have been mapped, and three genes identified. Mutations in known ARNSMR genes have been detected so far in only a small number of families; their contribution to mental retardation in the general population might be limited. The ARNSMR-causing genes belong to different protein families, including serine proteases, Adenosine 5'-triphosphate-dependent Lon proteases and calcium-regulated transcriptional repressors. All of the mutations in the ARNSMR-causing genes are protein truncating, indicating a putative severe loss-of-function effect. The future objective will be the development of diagnostic kits for molecular diagnosis in mentally retarded individuals in order to offer at-risk families pre-natal diagnosis to detect affected offspring. PMID:17718851

Basel-Vanagaite, L

2007-09-01

302

A mental retardation-linked nonsense mutation in cereblon is rescued by proteasome inhibition.  

PubMed

A nonsense mutation in cereblon (CRBN) causes autosomal recessive nonsyndromic mental retardation. Cereblon is a substrate receptor for the Cullin-RING E3 ligase complex and couples the ubiquitin ligase to specific ubiquitination targets. The CRBN nonsense mutation (R419X) results in a protein lacking 24 amino acids at its C terminus. Although this mutation has been linked to mild mental retardation, the mechanism by which the mutation affects CRBN function is unknown. Here, we used biochemical and mass spectrometric approaches to explore the function of this mutant. We show that the protein retains its ability to assemble into a Cullin-RING E3 ligase complex and catalyzes the ubiquitination of CRBN-target proteins. However, we find that this mutant exhibits markedly increased levels of autoubiquitination and is more readily degraded by the proteasome than the wild type protein. We also show that the level of the mutant protein can be restored by a treatment of cells with a clinically utilized proteasome inhibitor, suggesting that this agent may be useful for the treatment of mental retardation associated with the CRBN R419X mutation. These data demonstrate that enhanced autoubiquitination and degradation account for the defect in CRBN activity that leads to mental retardation. PMID:23983124

Xu, Guoqiang; Jiang, Xiaogang; Jaffrey, Samie R

2013-10-11

303

Molecular and comparative genetics of mental retardation.  

PubMed Central

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

Inlow, Jennifer K; Restifo, Linda L

2004-01-01

304

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

305

Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects  

Microsoft Academic Search

We compared sleep parameters in mentally retarded infantile autism (MRIA) and mentally retarded Down's syndrome (MRDS) by means of polysomnography, evaluating traditional analysis with particular attention to the phasic components in each disorder. Data were compared with those obtained in normal subjects matched for age and sex. Mental age, Intellectual Quotient and the Childhood Autism Rating Scale were performed to

Marina Diomedi; Paolo Curatolo; Anna Scalise; Fabio Placidi; Flavia Caretto; Gian Luigi Gigli

1999-01-01

306

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

307

Fire retardancy of vinyl ester nanocomposites: Synergy with phosphorus-based fire retardants  

Microsoft Academic Search

Vinyl ester (PVE) nanocomposites were prepared using both clay and polyhedral oligosilsesquioxanes (POSS) as the nano-dimensional material. From cone calorimetric data, it was shown that both POSS and clay affect the flammability of the nanocomposites to the same extent. To improve on the flame retardancy, the nanocomposites were combined with phosphorous-containing fire retardants (FRs) and the result compared to the

Grace Chigwada; Panchatapa Jash; David D. Jiang; Charles A. Wilkie

2005-01-01

308

A novel mutation in JARID1C gene associated with mental retardation.  

PubMed

X-linked mental retardation (XLMR) is an extremely heterogeneous condition that account for 15-25% of all mentally retarded patients. The number of genes newly reported in relation with this condition has been rapidly increased in the past years. One of the latest is called Jumonji AT-rich interactive domain 1C (JARID1C). This gene encodes for a member of a recently discovered protein family that harbours DNA-binding motifs, suggesting a possible role in transcriptional regulation and in the modification of chromatin structure. In this work we describe the results obtained by screening JARID1C gene in 24 mentally retarded males with history of at least two affected males. Remarkably, we have found a novel missense mutation in exon 10 of the gene that results in a Serine-to-arginine change at amino-acid 451 (S451R). This nucleotide change appears to be restricted to mentally retarded patients, since it has not been detected in control samples. Familial analysis has confirmed the segregation of this mutation with mental retardation. Furthermore, sequence alignment analysis with the different members of the human JARID1 family and with homologous proteins of mouse and fruit fly has revealed that the affected amino acid is conserved. Our data highlights the importance of reporting mutations in this gene since it might support the recent findings that implicates JARID1C with XLMR. PMID:16538222

Santos, Cristina; Rodriguez-Revenga, Laia; Madrigal, Irene; Badenas, Celia; Pineda, Merce; Milà, Montserrat

2006-05-01

309

X linked mental retardation: a clinical guide  

PubMed Central

Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non?syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non?syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed.

Raymond, F L

2006-01-01

310

X linked mental retardation: a clinical guide.  

PubMed

Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non-syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non-syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed. PMID:16118346

Raymond, F L

2006-03-01

311

Uteroplacental insufficiency decreases small intestine growth and alters apoptotic homeostasis in term intrauterine growth retarded rats  

Microsoft Academic Search

Human and animal studies demonstrate that uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) decrease intestinal growth and lead to both an increased incidence of feeding intolerance and necrotizing enterocolitis. Our objective was to determine the effects of uteroplacental insufficiency upon small intestine growth, histology, gene expression of the apoptosis related proteins Bcl-2, Bax and p53, and caspase-3 activity. For

Mariana Baserga; Cristina Bertolotto; Nicole K. Maclennan; Jennifer L. Hsu; Tho Pham; Gizella S. Laksana

2004-01-01

312

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

313

"Idiopathic" mental retardation and new chromosomal abnormalities  

PubMed Central

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

2010-01-01

314

In Vivo Replication of Recombinant Murine Cytomegalovirus Driven by the Paralogous Major Immediate-Early Promoter-Enhancer of Human Cytomegalovirus  

PubMed Central

Transcription of the major immediate-early (MIE) genes of cytomegaloviruses (CMV) is driven by a strong promoter-enhancer (MIEPE) complex. Transactivator proteins encoded by these MIE genes are essential for productive infection. Accordingly, the MIEPE is a crucial control point, and its regulation by activators and repressors is pertinent to virus replication. Since the MIEPE contains multiple regulatory elements, it was reasonable to assume that specific sequence motifs are irreplaceable for specifying the cell-type tropism and replication pattern. Recent work on murine CMV infectivity (A. Angulo, M. Messerle, U. H. Koszinowski, and P. Ghazal, J. Virol. 72:8502–8509, 1998) has documented the proposed enhancing function of the enhancer in that its resection or its replacement by a nonregulatory stuffer sequence resulted in a significant reduction of infectivity, even though replication competence was maintained by a basal activity of the spared authentic MIE promoter. Notably, full capacity for productive in vitro infection of fibroblasts was restored in recombinant viruses by the human CMV enhancer. Using two-color in situ hybridization with MIEPE-specific polynucleotide probes, we demonstrated that a murine CMV recombinant in which the complete murine CMV MIEPE is replaced by the paralogous human CMV core promoter and enhancer (recombinant virus mCMVhMIEPE) retained the potential to replicate in vivo in all tissues relevant to CMV disease. Notably, mCMVhMIEPE was also found to replicate in the liver, a site at which transgenic hCMV MIEPE is silenced. We conclude that productive in vivo infection with murine CMV does not strictly depend on a MIEPE type-specific regulation.

Grzimek, Natascha K. A.; Podlech, Jurgen; Steffens, Hans-Peter; Holtappels, Rafaela; Schmalz, Susanne; Reddehase, Matthias J.

1999-01-01

315

Nrf2b, novel zebrafish paralog of oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2).  

PubMed

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. PMID:22174413

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

2012-02-10

316

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

317

Coordinated diurnal regulation of genes from the Dlk1-Dio3 imprinted domain: implications for regulation of clusters of non-paralogous genes  

Microsoft Academic Search

The functioning of the genome is tightly related to its architecture. Therefore, understanding the relationship between different regulatory mechanisms and the organization of chromosomal domains is essential for understanding genome regulation. The majority of imprinted genes are assembled into clusters, share common regulatory elements, and, hence, represent an attractive model for studies of regulation of clusters of non-paralogous genes. Here,

Stephane Labialle; Lanjian Yang; Xuan Ruan; Aude Villemain; Jennifer V. Schmidt; Arturo Hernandez; Tim Wiltshire; Nicolas Cermakian; Anna K. Naumova

2008-01-01

318

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

2013-01-01

319

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

PubMed Central

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

Matas, Isabel M.; Perez-Martinez, Isabel; Quesada, Jose M.; Rodriguez-Herva, Jose J.; Penyalver, Ramon; Ramos, Cayo

2009-01-01

320

Rad51 Paralog Complexes BCDX2 and CX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous Recombination Pathway  

PubMed Central

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.

Chun, Jarin; Buechelmaier, Erika S.

2013-01-01

321

Kinetics of ferroelectric domain structure: Retardation effects  

Microsoft Academic Search

We review the experimental and theoretical investigations of the kinetics of ferroelectric domain structure in single crystals and thin films. The significant influence of the retardation of screening process on the evolution of the domain structure is pointed out and is demonstrated in various experimental situations.

V. Ya. Shur; E. L. Rumyantsev

1997-01-01

322

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.

323

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

324

Euthanasia and Mental Retardation: Suggesting the Unthinkable.  

ERIC Educational Resources Information Center

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

Hollander, Russell

1989-01-01

325

Chinese Children's Attitudes Toward Mental Retardation  

Microsoft Academic Search

The present study aimed to: (1) examine Chinese children's attitudes toward mental retardation, (2) investigate cross-cultural similarities or differences in these attitudes, and (3) extend the use of Western-attitude questionnaires to Chinese samples. The present study included 489 Chinese children (265 boys and 224 girls), aged from 4 to 15 years. Results showed that Chinese children demonstrated favorable attitudes toward

Catherine So-kum Tang; Cindy Davis; Anize Wu; Christopher Oliver

2000-01-01

326

Trainable Mentally Retarded Staff Deployment Project.  

ERIC Educational Resources Information Center

Reported was a project which revised the staffing pattern at a school for trainable mentally retarded (TMR) students in an attempt to increase the program's cost effectiveness and to maintain the quality of classroom instruction while utilizing personnel without special training in the majority of classroom assignments. Examined were the project's…

Selznick, Harrie M.; And Others

327

International Directory of Mental Retardation Resources.  

ERIC Educational Resources Information Center

The directory lists and describes governmental and voluntary agencies, research, and other resources in the field of mental retardation in foreign countries. The first section, on international organizations, gives names, addresses, names of directors, and one or more paragraphs of description for the United Nations and its specialized agencies,…

Dybwad, Rosemary F., Ed.

328

Assessing Community Attitudes toward Mentally Retarded Persons.  

ERIC Educational Resources Information Center

Responses of residents of 20 neighborhoods who lived immediately beside, across from, or behind a house for sale that might become a group home for mentally handicapped individuals, and residents who lived two or more blocks away from the potential group home were compared to assess attitudes toward mentally retarded people. (Author/PHR)

And Others; Kastner, Laura S.

1979-01-01

329

HEALTH ASPECTS OF BROMINATED FLAME RETARDANTS (BFRS)  

EPA Science Inventory

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

330

Improving Outcomes for Workers with Mental Retardation  

ERIC Educational Resources Information Center

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

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

2008-01-01

331

Counseling the Mentally Retarded: A Behavioral Approach  

ERIC Educational Resources Information Center

The conceptual and methodological aspects of various systems of counseling and psychotherapy are evaluated in relation to characteristics of the mentally retarded. A behavioral approach to modification of problem behaviors is presented as an alternative to the range of counseling and psychotherapy approaches reviewed and considered ineffective and…

Gardner, William I.; Stamm, John M.

1971-01-01

332

MENTAL RETARDATION. CATALOG OF LIBRARY ACCESSIONS.  

ERIC Educational Resources Information Center

LISTING ABOUT 570 ITEMS, THIS BIBLIOGRAPHY REPRESENTS THE MENTAL RETARDATION COLLECTION AT MANTOR LIBRARY, FARMINGTON STATE COLLEGE. ITEMS ARE LISTED BY DEWEY DECIMAL CLASSIFICATION NUMBER OR VERTICAL FILE NUMBER, INCLUDED ARE CURRICULUM AND TEACHER GUIDES, PROGRAM DESCRIPTIONS, PARENT HANDBOOKS, CONFERENCE PROCEEDINGS, DIRECTORIES, RESEARCH…

FEARON, ROSS E.

333

The retarded van der Waals potential: Revisited  

Microsoft Academic Search

The retarded van der Waals potential, as first obtained by Casimir and Polder, is usually computed on the basis of nonrelativistic quantum electrodynamics . The Hamiltonian describes two infinitely heavy nuclei, charge e, separated by a distance R and two spinless electrons, charge -e, nonrelativistically coupled to the quantized radiation field. Casimir and Polder used the dipole approximation and small

Tadahiro Miyao; Herbert Spohn

2009-01-01

334

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.

335

Bibliographic Instruction for Adults with Mental Retardation.  

ERIC Educational Resources Information Center

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

Norlin, Dennis A.

336

Are brominated flame retardants endocrine disruptors?  

Microsoft Academic Search

Brominated flame retardants (BFRs) are a group of compounds that have received much attention recently due to their similarity with “old” classes of organohalogenated compounds such as polychlorinated biphenyls (PCBs), in terms of their fate, stability in the environment and accumulation in humans and wildlife. Toxic effects, including teratogenicity, carcinogenicity and neurotoxicity, have been observed for some BFR congeners, in

Juliette Legler; Abraham Brouwer

2003-01-01

337

Computer Assisted Instruction for the Mentally Retarded.  

ERIC Educational Resources Information Center

Computer Assisted Instruction (CAI) for the mentally retarded is described; the advantages of CAI (which generally follows the pattern of programed instruction) are listed; and the roles of the teacher and the student are summarized. The coursewriter is explained, and its use as an experimental tool discussed. Guidelines are given covering…

Providence Coll., RI.

338

The dielectric modulus: relaxation versus retardation  

Microsoft Academic Search

Experiments which access the quantity ?*(?) are usually termed dielectric relaxation methods, although ?*(?) and ?(t) actually refer to dielectric retardation. The true dielectric relaxation, the modulus M(t), corresponds to the decay of the electric field under the conditions of a constant dielectric displacement. We have measured the polarization in terms of a real dielectric relaxation technique by studying the

Ranko Richert; Hermann Wagner

1998-01-01

339

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

340

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

PubMed Central

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

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

2014-01-01

341

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

PubMed

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

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

2014-01-01

342

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

PubMed

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

Fleurie, Aurore; Manuse, Sylvie; Zhao, Chao; Campo, Nathalie; Cluzel, Caroline; Lavergne, Jean-Pierre; Freton, Céline; Combet, Christophe; Guiral, Sébastien; Soufi, Boumediene; Macek, Boris; Kuru, Erkin; Vannieuwenhze, Michael S; Brun, Yves V; Di Guilmi, Anne-Marie; Claverys, Jean-Pierre; Galinier, Anne; Grangeasse, Christophe

2014-04-01

343

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

344

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

PubMed Central

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

Geraldo, M T; Valente, G T; Braz, A SK; Martins, C

2013-01-01

345

Functional Analysis of BORIS, a Novel DNA Binding Protein.  

National Technical Information Service (NTIS)

BORIS (cT6FL) is a paralog of tbe gene encoding CTCF, a multifunctional DNA binding protein that utilizes different sets of zinc fingers to mediate distinct gene regulatory functions, including those involved in cell growth regulation. Unlike CTCF the exp...

P. Yaswen

2008-01-01

346

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2013 CFR

... 1 2013-07-01 2013-07-01 false Mental retardation and personality disorders. 4.127...FOR RATING DISABILITIES Disability Ratings Mental Disorders § 4.127 Mental retardation and personality disorders....

2013-07-01

347

45 CFR 1308.10 - Eligibility criteria: Mental retardation.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Eligibility criteria: Mental retardation. 1308.10 Section 1308.10 Public Welfare...Performance Standards § 1308.10 Eligibility criteria: Mental retardation. (a) A child is classified as...

2013-10-01

348

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2010 CFR

... 1 2009-07-01 2009-07-01 false Mental retardation and personality disorders. 4.127...FOR RATING DISABILITIES Disability Ratings Mental Disorders § 4.127 Mental retardation and personality disorders....

2009-07-01

349

International Directory of Mental Retardation Resources. Revised Edition.  

ERIC Educational Resources Information Center

The document presents an international directory of mental retardation resources. International organizations pertaining to the mentally retarded are listed and described, including those affiliated with the United Nations, intergovernmental agencies, nongovernmental organizations, international coordinating agencies, and regional nongovernmental…

Dybwad, Rosemary F., Ed.

350

Study on intumescent flame retarded polystyrene composites with improved flame retardancy  

Microsoft Academic Search

The flame retardancy and thermal stability of ammonium polyphosphate\\/tripentaerythritol (APP\\/TPE) intumescent flame retarded polystyrene composites (PS\\/IFR) combined with organically-modified layered inorganic materials (montmorillonite clay and zirconium phosphate), nanofiber (multiwall carbon nanotubs), nanoparticle (Fe2O3) and nickel catalyst were evaluated by cone calorimetry, microscale combustion calorimetry (MCC) and thermogravimetric analysis (TGA). Cone calorimetry revealed that a small substitution of IFR by most

Hongdian Lu; Charles A. Wilkie

2010-01-01

351

Fire retardancy of a reactively extruded intumescent flame retardant polyethylene system enhanced by metal chelates  

Microsoft Academic Search

A reactive extrusion technology was adopted to synthesize a flame retardant (ER), based on the esterification of melamine phosphate and pentaerythritol. The ER imparts good flame retardancy and non-dripping for polyethylene (PE) when combined with ammonium polyphosphate to yield an intumescent polyethylene (PE–IFR). The performance of this intumescent system has been enhanced by the addition of small amounts (0.2%) chelated

De-Yi Wang; Yun Liu; Yu-Zhong Wang; C. Perdomo Artiles; T. Richard Hull; Dennis Price

2007-01-01

352

Characterization of three paralogous members of the Mammalian vaccinia related kinase family.  

PubMed

Members of the novel vaccinia related kinase (VRK) protein family are characterized by notable sequence homology to the vaccinia virus-encoded B1 kinase (vvB1). vvB1 plays an essential role in viral DNA replication, and Boyle and Traktman have demonstrated that VRK1 enzymes complement the replication defect of a temperature-sensitive viral mutant defective in vvB1 (Boyle, K., and Traktman, P. (2004) J. Virol. 78, 1992-2005). This mammalian kinase family comprises three members, VRK1, VRK2, and VRK3. We have annotated the gene structure for the members of this family and have characterized the enzyme activity and subcellular localization for the human and mouse proteins. VRK1 enzymes show robust autophosphorylation activity and will phosphorylate casein; VRK2 enzymes show modest autophosphorylation activity and will also phosphorylate casein. The VRK3 proteins have key amino acid substitutions that disrupt invariant motifs required for catalytic activity, rendering them enzymatically inert. The VRK1 and VRK2 proteins contain COOH-terminal extracatalytic sequences that mediate intracellular localization. VRK1 proteins possess a basic nuclear localization signal and are indeed nuclear; the extreme C termini of the VRK2 proteins are highly hydrophobic, and the proteins are membrane-associated and colocalize with markers of the endoplasmic reticulum. The NH(2)-terminal region of the VRK3s contains a bipartite nuclear localization signal, which directs these proteins to the nucleus. Our findings provide the basis for further studies of the structure and function of this newly discovered family of protein kinases. PMID:14645249

Nichols, R Jeremy; Traktman, Paula

2004-02-27

353

Conjunctive Visual Search in Individuals with and without Mental Retardation  

ERIC Educational Resources Information Center

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

Carlin, Michael; Chrysler, Christina; Sullivan, Kate

2007-01-01

354

Low Elevated Lead Levels and Mild Mental Retardation.  

ERIC Educational Resources Information Center

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

Marlowe, Mike; And Others

355

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

356

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

357

Thermoplastic Polyurethane-Encapsulated Melamine Phosphate Flame Retardant Polyoxymethylene  

Microsoft Academic Search

Due to its “unzipping” degradation mode and poor compatibility with most other flame retardants, polyoxymethylene (POM) is the most difficult flame-retarded polymer among macromolecular materials. In this project, we took advantage of thermoplastic polyurethane (TPU) resin, which possesses good compatibility with POM, serving as an encapsulation layer, and the carrier resin of the nitrogen-phosphorus composite flame retardant melamine phosphate to

Yuan Liu; MeiFang Liu; Daiyi Xie; Qi Wang

2008-01-01

358

Attitudes of High School Students toward Individuals with Mental Retardation.  

ERIC Educational Resources Information Center

The attitudes of 144 high school students toward individuals with mental retardation were examined using the Mental Retardation Attitude Inventory-Revised. Results indicated that gender and frequency of contact both influenced attitudes. Females and students with more frequent contacts with individuals with mental retardation indicated more…

Krajewski, Junean; Flaherty, Thomas

2000-01-01

359

An Aminoacyl-tRNA Synthetase Paralog with a Catalytic Role in Histidine Biosynthesis  

Microsoft Academic Search

In addition to their essential catalytic role in protein biosynthesis, aminoacyl-tRNA synthetases participate in numerous other functions, including regulation of gene expression and amino acid biosynthesis via transamidation pathways. Herein, we describe a class of aminoacyl-tRNA synthetase-like (HisZ) proteins based on the catalytic core of the contemporary class II histidyl-tRNA synthetase whose members lack aminoacylation activity but are instead essential

Marie Sissler; Christine Delorme; Jeff Bond; S. Dusko Ehrlich; Pierre Renault; Christopher Francklyn

1999-01-01

360

Shigella flexneri 2a strain 2457T expresses three members of the H-NS-like protein family: characterization of the Sfh protein  

Microsoft Academic Search

Shigella flexneri 2a is known to express the H-NS nucleoid-structuring protein and the paralogous protein StpA. Using bioinformatic analysis we have now discovered a third member of the H-NS protein family, Sfh (S higellaf lexneriH-NS-like protein), in strain 2457T. This protein is encoded by the sfh gene, which is located on a high-molecular-mass plasmid that is closely related to the

C. Beloin; P. Deighan; M. Doyle; C. J. Dorman

2003-01-01

361

Vegetative growth retardation, improved rooting and viability of olive cuttings in response to application of growth retardants  

Microsoft Academic Search

Spray and soil treatments of paclobutrazol and uniconazole were applied to young and mature olive plants and olive cuttings. Two clear phases, were found in the growth response of olive shoots to growth retardants: an early phase, which retards and even inhibits growth considerably; and a later phase, during which the shoots are released from the retardation and start to

Zeev Wiesman; Shimon Lavee

1994-01-01

362

A novel mutation of the ARX gene in a male with nonsyndromic mental retardation.  

PubMed

ARX (Aristaless-related homeobox gene) is located at Xp22. It contains 5 exons and encodes a 562-amino acid protein. The protein contains 4 polyalanine tracts, 3 of which are encoded in exon 2 and 1 in exon 4. Mutations in the ARX gene have been found in X-linked infantile spasms syndrome, Partington syndrome (mental retardation with dystonic movements of the hands), X-linked lissencephaly with abnormal genitalia, X-linked myoclonus epilepsy with spasticity and intellectual disability, and in nonsyndromic X-linked mental retardation. The most common mutation in ARX (seen in X-linked infantile spasms syndrome, Partington syndrome, and X-linked mental retardation) is a 24-bp duplication in exon 2 resulting in expansion of a polyalanine tract. Truncating mutations (deletions, frameshift, non-sense) have been found in X-linked lissencephaly with abnormal genitalia, as well as homeodomain missense mutations in X-linked myoclonus epilepsy with spasticity and intellectual disability. The authors report a novel 24-bp in-frame deletion within exon 2 of the ARX gene in a male child with X-linked mental retardation and review the spectrum of ARX mutations. This mutation results in a contraction of the second polyalanine repeat. PMID:17641262

Troester, Matthew M; Trachtenberg, Tamara; Narayanan, Vinodh

2007-06-01

363

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

364

High-speed retardation modulation ellipsometer.  

PubMed

Construction and performance of a high-speed retardation modulation ellipsometer are described. An ADP four-crystal electrooptic modulator is used for the retardation modulation and a high-speed digitizer for the simultaneous detection of the transmitted light intensity and the modulation voltage. The ellipsometer can acquire the necessary data for determining a data point (Psi, Delta) in 4 microsec and repeat the data acquisition for fifty data points at intervals of 4 microsec-160 msec. In such conditions, precision represented in terms of an average of root mean squares is 0.05 degrees in Psi and 0.15 degrees in Delta when a BaK1 standard optical glass is used as a sample at the present stage. An example is given of the application to rapid growth of anodic films on a semiconductor GaAs wafer. PMID:18196151

Moritani, A; Okuda, Y; Kubo, H; Nakai, J

1983-08-15

365

Retardation of ice crystallization by short peptides  

NASA Astrophysics Data System (ADS)

The effect of short peptides on the growth of ice crystals is studied using molecular dynamics simulations. The simulations focus on two sequences (Gly-Pro-Ala-Gly and Gly-Gly-Ala-Gly) that are found in collagen hydrolysate, a substance that is known to retard crystal growth. In the absence of peptides, the growth of ice crystal in the solution with the ice/water interface is observed in at a rate comparable to the experimental data. When peptides are present in the liquid phase, the crystal growth is retarded to a significant extent compared to the pure water. It is found that Gly-Pro-Ala-Gly is more effective (crystallization is up to 5 times slower than in its absence) than Gly-Gly-Ala-Gly (up to 3 times slower) implying that the role of the proline residue is important. The mechanism can be understood in the nature of binding of the peptides to the growing crystal.

Kim, Jun Soo; Yethiraj, Arun

2009-03-01

366

Retardation of ice crystallization by short peptides  

Microsoft Academic Search

The effect of short peptides on the growth of ice crystals is studied using molecular dynamics simulations. The simulations focus on two sequences (Gly-Pro-Ala-Gly and Gly-Gly-Ala-Gly) that are found in collagen hydrolysate, a substance that is known to retard crystal growth. In the absence of peptides, the growth of ice crystal in the solution with the ice\\/water interface is observed

Jun Soo Kim; Arun Yethiraj

2009-01-01

367

Retarded thermal oxidation of strained Si substrate  

NASA Astrophysics Data System (ADS)

Strained Si is recognized as a necessary technology booster for modern integrated circuit technology. However, the thermal oxidation behaviors of strained Si substrates are not well understood yet despite their importance. In this study, we for the first time experimentally find that all types of strained Si substrates (uniaxial tensile, uniaxial compressive, biaxial tensile, and biaxial compressive) show smaller thermal oxidation rates than an unstrained Si substrate. The possible mechanisms for these retarded thermal oxidation rates in strained Si substrates are also discussed.

Sun, Jia-Bao; Tang, Xiao-Yu; Yang, Zhou-Wei; Shi, Yi; Zhao, Yi

2014-06-01

368

Epilepsy in People With Mental Retardation  

Microsoft Academic Search

Epilepsy is a tendency of occurrence of transient recurrent abnormal electrical discharges in the brain affecting one or more\\u000a of the following brain functions: motor, sensory, cognitive, speech, behavioral, emotional, and psychological. The lifetime\\u000a prevalence of epilepsy in the general population is between 2 and 3%. The prevalence of epilepsy among people who have mental\\u000a retardation is much higher. Although

Shoumitro Deb

369

Walking Habits of Adults with Mental Retardation  

ERIC Educational Resources Information Center

The walking activity of men and women with mental retardation residing in community settings was described. Participants were 38 women (M age = 0.7, SD = 9.5) and 65 men (M age = 35.9, SD = 11.2). They wore pedometers for 7 days. A 2 ? 2 factorial ANOVA indicated no significant gender differences in total step counts or between participants with…

Stanish, Heidi I.; Draheim, Christopher C.

2005-01-01

370

Combustion toxicity of fire retarded EVA  

Microsoft Academic Search

A Purser furnace has been used to investigate the combustion toxicity of ethylene-vinyl acetate copolymer (EVA) with and without fire retardants, under different fire conditions. Steady state flaming combustion has been studied at equivalence ratios ? varying from 0.5 to 1.5 by driving the materials through the furnace at 750 °C. Yields of CO and CO2 for EVA containing 27% vinyl

T. Richard Hull; Rita E Quinn; Irene G Areri; David A Purser

2002-01-01

371

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

372

Pattern of divergence of amino acid sequences encoded by paralogous genes in human and pufferfish  

Microsoft Academic Search

We used phylogenetic analyses of protein families containing two or more pairs of orthologues in the genomes of human and pufferfish (Takifugu rubripes) to test the hypothesis that these sequences show a strong signal of polyploidization events hypothesized to have occurred early in vertebrate history. In order to test for evidence of two distinct rounds of polyploidization (the 2R hypothesis),

Austin L. Hughes; Robert Friedman

2004-01-01

373

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

374

Characterization of two paralogous muscleblind-like genes from the tiger pufferfish ( Takifugu rubripes)  

Microsoft Academic Search

Muscleblind-like (Mbnl) proteins are required for terminal muscle differentiation in mammals. In this study we have identified two mbnl paralogues from the tiger pufferfish, tmbnl2a and tmbnl3, which are the first examples of non-mammalian mbnl genes. Tmbnl2a and tmbnl3 were found in regions of conserved synteny and had a high degree of global conservation with their mammalian homologues. Phylogenetic analysis

Jorge M. O. Fernandes; James R. Kinghorn; Ian A. Johnston

2007-01-01

375

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

376

Variants in the RAB3A gene are not associated with mental retardation in the Chinese population.  

PubMed

Mental retardation is a common form of cognitive impairment among children. The underlying causes of mental retardation are extremely heterogeneous, and include significant genetic factors. The coexistence of neuropathology and cognitive deficits supports the view that mental retardation is a disorder of brain development and plasticity. Rab3A, a member of the Rab small G protein family, is a key molecule in modulating basal neurotransmission and contributes to synaptic plasticity. The RAB3A gene is located on chromosome 19p13.11, near a region shown by a linkage study to be involved in the etiology of mental retardation. Because of both its function and chromosomal location, RAB3A is a potential candidate susceptibility gene for mental retardation. To investigate the possible genetic contribution of the RAB3A gene, we performed a case-control association study focused on the Han population of northwestern China using four common SNPs in the gene (rs7259012, rs17683539, rs2271882, and rs874628). Pairwise linkage disequilibrium analysis showed that the four SNPs were in linkage disequilibrium. However, there were no significant differences of either allele or genotype frequencies at any of the SNPs nor any significant differences in haplotype distributions between cases and controls. In conclusion, we have found no evidence for RAB3A conferring susceptibility on mental retardation in the Han Chinese population. PMID:16584842

Sun, Yun; Zhang, Fuchang; Gao, Jianjun; Gao, Xiaocai; Guo, Tingwei; Shi, Yongyong; Tang, Wei; Li, Sheng; Zheng, Zijian; Zheng, Yonglan; Li, Xingwang; Feng, Guoyin; He, Lin

2006-06-19

377

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

PubMed

The diverse flowers of Orchidaceae are the result of several major morphological transitions, among them the most studied is the differentiation of the inner median tepal into the labellum, a perianth organ key in pollinator attraction. Type A peloria lacking stamens and with ectopic labella in place of inner lateral tepals are useful for testing models on the genes specifying these organs by comparing their patterns of expression between wild-type and peloric flowers. Previous studies focused on DEFICIENS- and GLOBOSA-like MADS-box genes because of their conserved role in perianth and stamen development. The "orchid code" model summarizes this work and shows in Orchidaceae there are four paralogous lineages of DEFICIENS/AP3-like genes differentially expressed in each floral whorl. Experimental tests of this model showed the conserved, higher expression of genes from two specific DEF-like gene lineages is associated with labellum development. The present study tests whether eight MADS-box candidate SEP-, FUL-, AG-, and STK-like genes have been specifically duplicated in the Orchidaceae and are also differentially expressed in association with the distinct flower organs of Phalaenopsis hyb. "Athens." The gene trees indicate orchid-specific duplications. In a way analogous to what is observed in labellum-specific DEF-like genes, a two-fold increase in the expression of SEP3-like gene PhaMADS7 was measured in the labellum-like inner lateral tepals of peloric flowers. The overlap between SEP3-like and DEF-like genes suggests both are associated with labellum specification and similar positional cues determine their domains of expression. In contrast, the uniform messenger levels of FUL-like genes suggest they are involved in the development of all organs and their expression in the ovary suggests cell differentiation starts before pollination. As previously reported AG-like and STK-like genes are exclusively expressed in gynostemium and ovary, however no evidence for transcriptional divergence was found in the stage investigated. Gene expression suggests a developmental regulatory system based on the combined activity of duplicate MADS-box genes. We discuss its feasibility based on documented protein interactions and patterns of expression. PMID:24659990

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

2014-01-01

378

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

PubMed Central

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

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

2014-01-01

379

Protein  

NSDL National Science Digital Library

Protein structure: Primary protein structure is a sequence of amino acids. Secondary protein structure occurs when the amino acids in the sequence are linked by hydrogen bonds. Tertiary protein structure occurs when certain attractions are present between alpha helices and pleated sheets. Quaternary protein structure is a protein consisting of more than one amino acid chain.

BEGIN:VCARD VERSION:2.1 FN:Darryl Leja N:Leja;Darryl ORG:National Human Genome Research Institute REV:2005-04-04 END:VCARD

2005-04-04

380

Coalescent processes and relaxation of selective constraints leading to contrasting genetic diversity at paralogs AtHVA22d and AtHVA22e in Arabidopsis thaliana  

Microsoft Academic Search

Duplicate loci offer a very powerful system for understanding the complicated genome structure and adaptive evolution of a gene family. In this study, the genetic variation at paralogs AtHVA22d and AtHVA22e, members of an ABA- and stress-inducible gene family, is examined in the selfing Arabidopsis thaliana. Population genetic analysis indicates contrasting levels of nucleotide diversity at overall exon sequence and

Ching-Nen Chen; Yu-Chung Chiang; Tuan-Hua David Ho; Barbara A. Schaal; Tzen-Yuh Chiangb

2004-01-01

381

Discovery of Paralogous Nuclear Gene Sequences Coding for the Second Largest Subunit of RNA Polymerase II (RPB2) and Their Phylogenetic Utility in Gentianales of the Asterids  

Microsoft Academic Search

Paralogous sequences of the RPB2 gene are demonstrated in the angiosperm order Gentianales. Two different copies were found by using different PCR primer pairs targeting a region that corresponds to exons 22-24 in the Arabi- dopsis RPB2 gene. One of the copies (RPB2-d) lacks introns in this region, whereas the other has introns at locations corresponding to those of green

Bengt Oxelman; Birgitta Bremer

382

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

383

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

Microsoft Academic Search

BACKGROUND: DNA-dependent RNA polymerase IV and V (Pol IV and V) are multi-subunit enzymes occurring in plants. The origin of Pol V, specific to angiosperms, from Pol IV, which is present in all land plants, is linked to the duplication of the gene encoding the largest subunit and the subsequent subneofunctionalization of the two paralogs (NRPD1 and NRPE1). Additional duplication

Thomas Marcussen; Bengt Oxelman; Anna Skog; Kjetill S Jakobsen

2010-01-01

384

The complex structure of polyhydroxybutyrate (PHB) granules: four orthologous and paralogous phasins occur in Ralstonia eutropha  

Microsoft Academic Search

Analysis of the genome sequence of the polyhydroxyalkanoate- (PHA) accumulating bacterium Ralstonia eutropha strain H16 revealed three homologues (PhaP2, PhaP3 and PhaP4) of the phasin protein PhaP1. PhaP1 is known to constitute the major component of the layer at the surface of poly(3-hydroxybutyrate), poly(3HB), granules. PhaP2, PhaP3 and PhaP4 exhibited 42, 49 and 45% identity or 61, 62 and 63%

Markus Potter; Helena Muller; Frank Reinecke; Roman Wieczorek; Florian Fricke; Botho Bowien; Barbel Friedrich; Alexander Steinbuchel

2004-01-01

385

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

PubMed

Paralogous genes frequently show differences in patterns and rates of substitution that are typically attributed to different selection regimes, mutation rates, or local recombination rates. Here, two anciently diverged paralogous copies of the histone H3 gene in sea stars, the tandem-repetitive early-stage gene and a newly isolated gene with lower copy number that was termed the "putative late-stage histone H3 gene" were analyzed in 69 species with varying mode of larval development. The two genes showed differences in relative copy number, overall substitution rates, nucleotide composition, and codon usage, but similar patterns of relative nonsynonymous substitution rates, when analyzed by the d(N)/d(S) ratio. Sea stars with a nonpelagic and nonfeeding larval type (i.e., brooding lineages) were observed to have d(N)/d(S) ratios that were larger than for nonbrooders but equal between the two paralogs. This finding suggested that demographic differences between brooding and nonbrooding lineages were responsible for the elevated d(N)/d(S) ratios observed for brooders and refuted a suggestion from a previous analysis of the early-stage gene that the excess nonsynonymous substitutions were due to either (1) gene expression differences at the larval stage between brooders and nonbrooders or (2) the highly repetitive structure of the early-stage histone H3 gene. PMID:20433461

Foltz, David W; Mah, Christopher L

2010-01-01

386

The Arabidopsis RAD51 paralogs RAD51B, RAD51D and XRCC2 play partially redundant roles in somatic DNA repair and gene regulation.  

PubMed

The eukaryotic RAD51 gene family has seven ancient paralogs conserved between plants and animals. Among these, RAD51, DMC1, RAD51C and XRCC3 are important for homologous recombination and/or DNA repair, whereas single mutants in RAD51B, RAD51D or XRCC2 show normal meiosis, and the lineages they represent diverged from each other evolutionarily later than the other four paralogs, suggesting possible functional redundancy. The function of Arabidopsis RAD51B, RAD51D and XRCC2 genes in mitotic DNA repair and meiosis was analyzed using molecular genetic, cytological and transcriptomic approaches. The relevant double and triple mutants displayed normal vegetative and reproductive growth. However, the triple mutant showed greater sensitivity than single or double mutants to DNA damage by bleomycin. RNA-Seq transcriptome analysis supported the idea that the triple mutant showed DNA damage similar to that caused by bleomycin. On bleomycin treatment, many genes were altered in the wild-type but not in the triple mutant, suggesting that the RAD51 paralogs have roles in the regulation of gene transcription, providing an explanation for the hypersensitive phenotype of the triple mutant to bleomycin. Our results provide strong evidence that Arabidopsis XRCC2, RAD51B and RAD51D have complex functions in somatic DNA repair and gene regulation, arguing for further studies of these ancient genes that have been maintained in both plants and animals during their long evolutionary history. PMID:24102485

Wang, Yingxiang; Xiao, Rong; Wang, Haifeng; Cheng, Zhihao; Li, Wuxing; Zhu, Genfeng; Wang, Ying; Ma, Hong

2014-01-01

387

Interactome Analyses of Mature ?-Secretase Complexes Reveal Distinct Molecular Environments of Presenilin (PS) Paralogs and Preferential Binding of Signal Peptide Peptidase to PS2*  

PubMed Central

?-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.

Jeon, Amy Hye Won; Bohm, 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

2013-01-01

388

Electrode contamination effects of retarding potential analyzer  

NASA Astrophysics Data System (ADS)

The electrode contamination in electrostatic analyzers such as Langmuir probes and retarding potential analyzers (RPA) is a serious problem for space measurements. The contamination layer acts as extra capacitance and resistance and leads to distortion in the measured I-V curve, which leads to erroneous measurement results. There are two main effects of the contamination layer: one is the impedance effect and the other is the charge attachment and accumulation due to the capacitance. The impedance effect can be reduced or eliminated by choosing the proper sweeping frequency. However, for RPA the charge accumulation effect becomes serious because the capacitance of the contamination layer is much larger than that of the Langmuir probe of similar dimension. The charge accumulation on the retarding potential grid causes the effective potential, that ions experience, to be changed from the applied voltage. Then, the number of ions that can pass through the retarding potential grid to reach the collector and, thus, the measured ion current are changed. This effect causes the measured ion drift velocity and ion temperature to be changed from the actual values. The error caused by the RPA electrode contamination is expected to be significant for sounding rocket measurements with low rocket velocity (1-2 km/s) and low ion temperature of 200-300 K in the height range of 100-300 km. In this paper we discuss the effects associated with the RPA contaminated electrodes based on theoretical analysis and experiments performed in a space plasma operation chamber. Finally, the development of a contamination-free RPA for sounding rocket missions is presented.

Fang, H. K.; Oyama, K.-I.; Cheng, C. Z.

2014-01-01

389

Electrode contamination effects of retarding potential analyzer.  

PubMed

The electrode contamination in electrostatic analyzers such as Langmuir probes and retarding potential analyzers (RPA) is a serious problem for space measurements. The contamination layer acts as extra capacitance and resistance and leads to distortion in the measured I-V curve, which leads to erroneous measurement results. There are two main effects of the contamination layer: one is the impedance effect and the other is the charge attachment and accumulation due to the capacitance. The impedance effect can be reduced or eliminated by choosing the proper sweeping frequency. However, for RPA the charge accumulation effect becomes serious because the capacitance of the contamination layer is much larger than that of the Langmuir probe of similar dimension. The charge accumulation on the retarding potential grid causes the effective potential, that ions experience, to be changed from the applied voltage. Then, the number of ions that can pass through the retarding potential grid to reach the collector and, thus, the measured ion current are changed. This effect causes the measured ion drift velocity and ion temperature to be changed from the actual values. The error caused by the RPA electrode contamination is expected to be significant for sounding rocket measurements with low rocket velocity (1-2 km/s) and low ion temperature of 200-300 K in the height range of 100-300 km. In this paper we discuss the effects associated with the RPA contaminated electrodes based on theoretical analysis and experiments performed in a space plasma operation chamber. Finally, the development of a contamination-free RPA for sounding rocket missions is presented. PMID:24517809

Fang, H K; Oyama, K-I; Cheng, C Z

2014-01-01

390

Nanotechnology finding its way into flame retardancy  

NASA Astrophysics Data System (ADS)

Nanotechnology is one of the key technologies of the 21st century. The exploitation of "new" effects that arise from materials structured on the nano-scale has also been proposed successfully for flame retardancy of polymers since the end of the 90s. Of all of the approaches these include, at this time the use of nanocomposites offers the best potential for industrial application, also some other ideas are sketched, such as using electrospun nanofibers mats or layer-by-layer deposits as protection coatings, as well as sub-micrometer multilayer coatings as effective IR-mirrors. The general phenomena, inducing a flow limit in the pyrolysing melt and changing the fire residue, are identified in nanocomposites. Key experiments are performed such as quasi online investigation of the protection layer formation to understand what is going on in detail. The flame retardancy mechanisms are discussed and their impact on fire behaviour quantified. With the latter, the presentation pushes forward the state of the art. For instance, the heat shielding is experimentally quantified for a layered silicate epoxy resin nanocomposite proving that it is the only import mechanism controlling the reduction in peak heat release rate in the investigated system for different irradiations. The flame retardancy performance is assessed comprehensively illuminating not only the strengths but also the weak points of the concepts. Guidelines for materials development are deduced and discussed. Apart from inorganic fillers (layered silicate, boehmite, etc.) not only carbon nanoobjects such as multiwall carbon nanotubes, multilayer graphene and graphene are investigated, but also nanoparticles that are more reactive and harbor the potential for more beneficial interactions with the polymer matrix.

Schartel, Bernhard

2014-05-01

391

A New Neurological Syndrome with Mental Retardation, Choreoathetosis, and Abnormal Behavior Maps to Chromosome Xp11  

PubMed Central

Summary Choreoathetosis is a major clinical feature in only a small number of hereditary neurological disorders. We define a new X-linked syndrome with a unique clinical picture characterized by mild mental retardation, choreoathetosis, and abnormal behavior. We mapped the disease in a four-generation pedigree to chromosome Xp11 by linkage analysis and defined a candidate region containing a number of genes possibly involved in neuronal signaling, including a potassium channel gene and a neuronal G protein–coupled receptor.

Reyniers, Edwin; Van Bogaert, Patrick; Peeters, Nils; Vits, Lieve; Pauly, Fernand; Fransen, Erik; Van Regemorter, Nicole; Kooy, R. Frank

1999-01-01

392

New hybrid halogen-free flame retardants  

NASA Astrophysics Data System (ADS)

The main objective of this work were researches concerning the methods of the in-situ modification of silicate layer-tubular mineral (SL-TM) halloysite, using the salts of melamine, i.e. melamine cyanurate. The modified mineral was used as flame retardant to thermoplastic polymers. In the case of the application of halloysite modified by melamine cyanurate to polyamide 6 (PA6) the highest parameters of vertical and horizontal flammability were achieved. The mechanical properties of filled polyamide 6 have been improved.

Kijowska, Dorota; Jankowski, Piotr

2014-05-01

393

Fire-retardant decorative inks for aircraft interiors  

NASA Technical Reports Server (NTRS)

Commercial and experimental fire retardants were screened as potential fire retardants for acrylic printing inks used on aircraft interior sandwich panels. The fire retardants are selected according to their physical properties and their thermostabilities. A criterion for selecting a more stable fire retardant is established. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are used to determine thermostabilities. Results show that the fire retardant formulations are more thermally stable than the acrylic ink control. It is determined that an ink formulation containing a brominated phenol and carboxy-terminated butadiene acrylonitrile which has been modified with a brominated polymeric additive (BPA), yields the highest limiting oxygen index (LOI) of all the compounds tested. All of the fire-retardant formulations have a higher oxygen index than the baseline acrylic ink.

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

1985-01-01

394

New environmentally conscious flame-retarding plastics for electronics products  

Microsoft Academic Search

Flame-retardant plastics containing no toxic flame-retarding additives such as halogen (bromine) compounds and phosphorus compounds have been developed for electronic products. A polycarbonate (PC) resin containing a silicone derivative as a new safer flame-retarding aromatic has been developed for use in housings. A special silicone with a branched chain structure and with an aromatic group in the chain was found

M. Iji; S. Serizawa; Y. Kiuchi

1999-01-01

395

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

396

ASSESSMENT OF MENTAL RETARDATION : NEED FOR NEWER APPROACHES*  

PubMed Central

SUMMARY Mental retardation is a complex, multifaceted condition. It is not a simple condition based primarily on intellectual capacities. Assessment of a retarded child should not be limited to intellectual functioning alone. It should give an idea of the individual?s strength and weaknesses globally. Unfortunately, in India, assessment of mental retardation is still primarily based on intelligence tests. There is a need to understand the limitations of such an approach.

Nizamie, Alka; Nizamie, S. Haque; James, M.X.; Shukla, T.R.

1989-01-01

397

Growth and sexual maturity pattern of girls with mental retardation  

PubMed Central

Background: Growth of mentally retarded children differs from that of normal children. However, the adolescent growth and development of Indian mentally retarded children has not been studied. Aim: This study was conducted to evaluate the physical growth and sexual development of adolescent mentally retarded girls in North Indian population and to compare it with that of normal girls of same age group. Materials and Methods: One hundred mentally retarded (intelligence quotient (IQ) less than 70) and 100 normal girls between 10 and 20 years of age were categorized into 1-year age groups. Their height was measured and the sexual development was assessed based on breast development (BD) and pubic hair growth (PH) stages 1-5 on the basis of Tanner scale. The data was then compared between the two groups using Student's t-test. The mean age of menarche was calculated by applying Probit analysis. Results: The mean height of mentally retarded girls was significantly retarded as compared to normal girls at all ages; however, the mean height gain during 11-20 years was same in both the groups. The mentally retarded girls also showed significant retardation in PH growth at 15-17 years and in BD at 15-16 years of age. Conclusions: The physical growth and sexual development of adolescent mentally retarded girls was retarded as compared to the normal girls. The physical growth retardation occurred during early childhood (before 11 years), however the retardation in sexual maturity occurred during middle adolescence, between 15-17 years of age.

Baidwan, Sukhinder; Paul, Molly M; Chhatwal, Jugesh; Deswal, RS

2014-01-01

398

Travis County Mental Retardation Services Plan of the Travis County Mental Retardation Planning Council.  

ERIC Educational Resources Information Center

Presented is a county wide (Travis County, Texas) plan developed by 12 human service agencies to provide comprehensive educational, maintenance, and prevention services to the mentally retarded of all ages. Described are three underlying principles: human ecology (which stresses an individual approach to fulfillment), normalization, and community…

Austin - Travis County Mental Health - Mental Retardation Center, TX.

399

Fire-retardant decorative inks for aircraft interiors  

NASA Technical Reports Server (NTRS)

Commercial and experimental fire retardants were screened for possible use wiith acrylic printing inks on aircraft interior sandwich panels. The fire retardants were selected according to their physical properties and thermostabilities. Thermostabilities were determined by thermogravimetric analysis and differential scanning calorimetry. A criterion was then established for selecting the more stable agent. Results show that some of the bromine-containing fire retardants are more thermostable than the acrylic ink, alone, used as a control. Also, the bromine-containing fire retardants yield even better limiting oxygen index values when tested after adding carboxy-terminated butadiene acrylonitrile (CTBN) rubber.

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

1984-01-01

400

Psychomotor retardation in depression: biological underpinnings, measurement, and treatment.  

PubMed

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. PMID:21044654

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

2011-03-30

401

Rotatable broadband retarders for far infrared spectroscopic ellipsometry  

SciTech Connect

Rotatable retarders have been developed for applications in spectroscopic, full Mueller Matrix ellipsometry in the far-IR spectral range. Several materials, such as silicon, KRS-5, and a commercial polymer plastic (TOPAS) have been utilized to achieve a fully adjustable retardation between 0{sup o} and 90{sup o}. Experimental characteristics of the rotatable retarders that utilize three- and four-bounce designs are compared with calculations. We discuss the effect of light focusing on the performance of these rotatable retarders. Broadband optical retarders are required for spectroscopic ellipsometry in its full Mueller matrix (MM) realization. Performance of the MM ellipsometer depends on the capability to produce substantially linearly-independent Stokes vectors for the light incident onto the sample. As has been shown, the errors in the measuredMMof the sample are proportional to the condition number of the 4 x 4 matrix composed of the Stokes vectors of four polarization states incident at the sample. It can be proven that it is impossible to cover the Poincare sphere with linearly-independent Stokes vectors by only changing the linear polarization at the input surface of a stationary retarder. As we will illustrate further in this paper, total coverage of the Poincare sphere is possible by rotating a tandem of a linear polarizer and a retarder with a retardation of 90{sup o}. It is this goal that we are trying to achieve in the retarder designs described in this paper.

Kang, T.D.; Carr, G.; Zhou, T.; Kotelyanskii, M.; Sirenko, A.A.

2010-12-09

402

Structure of the Highly Conserved HERC2 Gene and of Multiple Partially Duplicated Paralogs in Human  

PubMed Central

Recombination between chromosome-specific low-copy repeats (duplicons) is an underlying mechanism for several genetic disorders. Recently, a chromosome 15 duplicon was discovered in the common breakpoint regions of Prader–Willi and Angelman syndrome deletions. We identified previously the large HERC2 transcript as an ancestral gene in this duplicon, with ?11 HERC2-containing duplicons, and demonstrated that recessive mutations in mouse Herc2 lead to a developmental syndrome, juvenile development and fertility 2 (jdf2). We have now constructed and sequenced a genomic contig of HERC2, revealing a total of 93 exons spanning ?250 kb and a CpG island promoter. A processed ribosomal protein L41 pseudogene occurs in intron 2 of HERC2, and putative VNTRs occur in intron 70 (28 copies, ?76-bp repeat) and 3? exon 40 through intron 40 (6 copies, ?62-bp repeat). Sequence comparisons show that HERC2-containing duplicons have undergone several deletion, inversion, and dispersion events to form complex duplicons in 15q11, 15q13, and 16p11. To further understand the developmental role of HERC2, a highly conserved Drosophila ortholog was characterized, with 70% amino acid sequence identity to human HERC2 over the carboxy-terminal 743 residues. Combined, these studies provide significant insights into the structure of complex duplicons and into the evolutionary pathways of formation, dispersal, and genomic instability of duplicons. Our results establish that some genes not only have a protein coding function but can also play a structural role in the genome. [The sequence data described in this paper have been submitted to GenBank under accession nos. AF189221 (Drosophila HERC2 partial cDNA), AC004583 (human HERC2 exons 1–52, genomic); AF224242–AF224257 (human HERC2 exons 54–70, partial genomic sequences); AF225400–AF225409 (human HERC2 exons 71–93, partial genomic sequences). The exon-intron boundaries for exons 53–93 are derived from BACs R-142A11 and 263O22. Additional information is available as a supplementary table at www.genome.org.

Ji, Yonggang; Rebert, Nancy A.; Joslin, John M.; Higgins, Michael J.; Schultz, Roger A.; Nicholls, Robert D.

2000-01-01

403

Functional Analysis of Paralogous Thiol-disulfide Oxidoreductases in Streptococcus gordonii*  

PubMed Central

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.

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

2013-01-01

404

Paralogous antirepressors acting on the master regulator for biofilm formation in Bacillus subtilis.  

PubMed

Matrix production during biofilm formation by Bacillus subtilis is governed by a gene control circuit at the heart of which are three dedicated regulatory proteins, the antirepressor SinI, the repressor SinR and the downstream regulator SlrR. Matrix production is triggered by the synthesis of SinI, which binds to and inactivates SinR, thereby derepressing genes for matrix production as well as the gene for SlrR. Recently, two additional regulators of matrix genes were identified: SlrA, which was reported to be an activator of SlrR, and YwcC, a repressor of SlrA synthesis (Kobayashi, 2008). We present evidence indicating that SlrA, which is a paralogue of SinI, is like SinI, an antirepressor that binds to, and inactivates, SinR. We also show that SlrA does not activate SlrR for expression of matrix genes. Instead, SlrR binds to, and inhibits the activity of, SlrA. Thus, the YwcC-SlrA-SinR-SlrR pathway is a negative feedback loop in which SlrA indirectly stimulates the synthesis of SlrR, and SlrR, in turn, inhibits the activity of SlrA. Finally, we report that under standard laboratory conditions SlrA makes only a small contribution to the expression of genes for matrix production. We propose that in response to an unknown signal recognized by the YwcC repressor, SlrA transiently boosts matrix production. PMID:19788541

Chai, Yunrong; Kolter, Roberto; Losick, Richard

2009-11-01

405

Mental Retardation. Fact Sheet = El Retraso Mental. Hojas Informativas Sobre Discapacidades.  

ERIC Educational Resources Information Center

This fact sheet on mental retardation is written in both English and Spanish. It begins with a vignette of a 15-year-old boy with mental retardation. Mental retardation is briefly explained as are some causes of mental retardation. It notes that a diagnosis of mental retardation looks at two things: first, the ability of a person's brain to learn,…

National Information Center for Children and Youth with Disabilities, Washington, DC.

406

On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report  

PubMed Central

A recent paper (Nehrt et al., PLoS Comput. Biol. 7:e1002073, 2011) has proposed a metric for the “functional similarity” between two genes that uses only the Gene Ontology (GO) annotations directly derived from published experimental results. Applying this metric, the authors concluded that paralogous genes within the mouse genome or the human genome are more functionally similar on average than orthologous genes between these genomes, an unexpected result with broad implications if true. We suggest, based on both theoretical and empirical considerations, that this proposed metric should not be interpreted as a functional similarity, and therefore cannot be used to support any conclusions about the “ortholog conjecture” (or, more properly, the “ortholog functional conservation hypothesis”). First, we reexamine the case studies presented by Nehrt et al. as examples of orthologs with divergent functions, and come to a very different conclusion: they actually exemplify how GO annotations for orthologous genes provide complementary information about conserved biological functions. We then show that there is a global ascertainment bias in the experiment-based GO annotations for human and mouse genes: particular types of experiments tend to be performed in different model organisms. We conclude that the reported statistical differences in annotations between pairs of orthologous genes do not reflect differences in biological function, but rather complementarity in experimental approaches. Our results underscore two general considerations for researchers proposing novel types of analysis based on the GO: 1) that GO annotations are often incomplete, potentially in a biased manner, and subject to an “open world assumption” (absence of an annotation does not imply absence of a function), and 2) that conclusions drawn from a novel, large-scale GO analysis should whenever possible be supported by careful, in-depth examination of examples, to help ensure the conclusions have a justifiable biological basis.

Thomas, Paul D.; Wood, Valerie; Mungall, Christopher J.; Lewis, Suzanna E.; Blake, Judith A.

2012-01-01

407

Characterization of two paralogous StAR genes in a teleost, Nile tilapia (Oreochromis niloticus).  

PubMed

Steroidogenic acute regulatory protein (StAR) transports cholesterol, the substrate for steroid synthesis, to the inner membranes of mitochondria. It is well known that estrogen is essential for female sex determination/differentiation in fish. However, no reports showed that the conventional StAR, which was supposed to be essential for estrogen production, was expressed in female gonads during the critical timing of sex determination/differentiation. In this study, two different StAR isoforms, named as StAR1 and StAR2, were characterized from the gonads of Nile tilapia (Oreochromis niloticus). Phylogenetic and synteny analysis revealed that two StAR genes existed in teleosts, Xenopus and chicken indicating that the duplication event occurred before the divergence of teleosts and tetrapods. Real-time PCR revealed that StAR1 was dominantly expressed in the testis, head kidney and kidney; while StAR2 was expressed exclusively in the gonads. In situ hybridization and immunohistochemistry demonstrated that StAR1 was expressed in the interrenal cells of the head kidney and Leydig cells of the testis; while StAR2 was expressed in the Leydig cells of the testis and the interstitial cells of the ovary. Ontogenic analysis demonstrated that StAR2 was expressed abundantly from 5days after hatching (dah) in the somatic cells in XX gonads, whereas in XY gonads, both StARs could be detected from 30dah until adulthood. Intraperitoneal injection of human chorionic gonadotropin experiments showed that expression of StAR1 and 2 was significantly elevated at 8h and persisted until 24h after injection in the testis. Taken together, our data suggested that StAR1 is likely to be required for cortisol production in the head kidney, and StAR2 is probably involved in estrogen production during early sex differentiation in XX gonads. In contrast, both StARs might be required for androgen production in testes. For the first time, our data demonstrated that two fish StARs might be involved in steroidogenesis in a tissue and developmental stage dependent manner. PMID:24859646

Yu, Xiangguo; Wu, Limin; Xie, Lang; Yang, Shijie; Charkraborty, Tapas; Shi, Hongjuan; Wang, Deshou; Zhou, Linyan

2014-07-01

408

Mental Retardation in the Caribbean: Needs, Resources, Approaches.  

ERIC Educational Resources Information Center

Presented are conference reports including an opening address on the economic benefits of programs for the mentally retarded (MR), and eight papers discussing the problem of mental retardation in the Caribbean. Two papers on preschool age children, respectively, consider the identification and assessment of MR children in the Caribbean and present…

Thorburn, Marigold J., Ed.

409

Implicit Learning in Children and Adolescents with Mental Retardation.  

ERIC Educational Resources Information Center

A study compared the implicit learning of 58 children (ages 7-14) with mental retardation and 53 controls (ages 3-8). Individuals with mental retardation modified their behavior after an implicit training procedure similar to the controls. The effect of implicit learning did not vary as a function of IQ or age. (Contains references.) (Author/CR)

Vinter, Annie; Detable, Christelle

2003-01-01

410

Retardation in depression: assessment by means of simple motor tasks  

Microsoft Academic Search

Background: psychomotor retardation in depression has mostly been assessed with tasks requiring both cognitive and motor processes. This study tested whether retardation could be measured if the cognitive demands of the task were minimal. Methods: 30 inpatients with a major depressive episode were compared one week after the start of antidepressant treatment, to 30 healthy control persons, matched for age,

Bernard Sabbe; Wouter Hulstijn; Jacques van Hoof; H. G Tuynman-Qua; Frans Zitman

1999-01-01

411

WEEE recycling: Pyrolysis of fire retardant model polymers  

Microsoft Academic Search

Pyrolysis treatments of model polymers were made with the aim of studying the recycling of wastes from electronic, electric equipment containing brominated flame retardants. Pyrolysis of flame retarded high impact polystyrene and epoxy resins were made both in flow and closed systems. Products of pyrolysis were analysed with FT–IR spectroscopy and GC–MS and the evolution of bromine was followed with

M. P. Luda; N. Euringer; U. Moratti; M. Zanetti

2005-01-01

412

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

413

Pre-Professional Training in Mental Retardation. Final Report.  

ERIC Educational Resources Information Center

To interest students in mental retardation health services careers, 10 eligible prebaccalaureate students were selected to participate in a 10-week summer training program. The first 2 weeks involved orientation to informational and training aspects of mental retardation and exposure to the health services related disciplines of recreational and…

Lown, Irving C., Jr.

414

Counseling Mentally Retarded Students in the Public School.  

ERIC Educational Resources Information Center

Working with three groups of mildly to severely mentally retarded children in counseling sessions, it was found that the ease with which groups develop and work productively is dependent upon the social-emotional makeup of their members more than upon their mental retardation. Recommendations for public school counseling are presented. (Author/PN)

Janus, Nancy G.; Podolec, Melanie

1982-01-01

415

The Vanderbilt Kennedy Center and the Mental Retardation Research Centers.  

ERIC Educational Resources Information Center

The Kennedy Center at Peabody College of Vanderbilt University is one of 12 Mental Retardation Research Centers (MRRCs) constructed by the federal government. Several major discoveries in mental retardation have come from MRCCs. The Kennedy Center is unique in its focus on education integrated with a university and medical school environment,…

Alexander, Duane

1996-01-01

416

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

417

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 ...

418

Screening of the ARX gene in 682 retarded males  

Microsoft Academic Search

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

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

2004-01-01

419

Vocational Adjustment of Mentally Retarded Persons: Personal-Environmental Variables.  

ERIC Educational Resources Information Center

Analysis of vocational adjustment for 109 male and 89 female mentally retarded workers (ages 16-45) indicated that while no single factor predicted vocational success, work-related personality traits and basic work skills should be emphasized. It is concluded that mental retardation and vocational inadequacy should be considered separately.…

Misawa, Gi-ichi; Obata, Fumiya

1987-01-01

420

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...

421

Estate Planning for Retarded Persons and Their Families.  

ERIC Educational Resources Information Center

Intended for parents and legal guardians of mentally retarded persons, the manual provides guidelines for estate planning. An overview of definitions, causes, and prevalence factors in retardation is followed by reviews of the major financial assistance governmental programs such as Medicare, and Supplemental Security Income, and of legal…

Fruge, Don L.; Green, Karen O.

422

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

423

THE NEW AND MORE OPEN OUTLOOK FOR THE MENTALLY RETARDED.  

ERIC Educational Resources Information Center

THE PROCEEDINGS OF THIS 1965 WORKSHOP ON MENTAL RETARDATION ARE PRESENTED AS A COLLECTION OF NINE PAPERS AND SUMMARIES OF THREE SEMINAR DISCUSSIONS. IN THE INTRODUCTION, MAYNARD C. REYNOLDS DISCUSSES "THE NEW AND MORE OPEN OUTLOOK FOR THE MENTALLY RETARDED." OTHER PAPERS ARE (1) "THE IMPACT OF FEDERAL LEGISLATION ON DEVELOPMENT OF COMPREHENSIVE…

KELLY, ELIZABETH M.

424

Advantages of flame retardants based on nitrogen compounds  

Microsoft Academic Search

Nitrogen compounds are a small but rapidly growing group of flame retardants (FR) which are in the focus of public interest concerning environmentally friendly flame retardants. Today their main applications are melamine for polyurethane flexible foams, melamine cyanurate in nylons, melamine phosphates in polyolefines, melamine and melamine phosphates or dicyandiamide in intumescent paints, guanidine phosphates for textiles and guanidine sulfamate

H. Horacek; R. Grabner

1996-01-01

425

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

426

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

427

Growing Old with Retardation: The Language of Survivors.  

ERIC Educational Resources Information Center

This paper examines general issues in the communicative skills and needs of elderly persons with mental retardation. It then compared 20 elderly and 20 young adults with mild to moderate mental retardation and found that elderly subjects were better able to respond to listener feedback and were more assertive in controlling the conversation. (JDD)

Fujiki, Martin; Brinton, Bonnie

1993-01-01

428

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

429

College Students' Attitudes towards Mental Retardation: A Pilot Study.  

ERIC Educational Resources Information Center

Two studies examined college students' attitudes toward people with mental retardation as a function of experiences with this population. In the first study, college students (N=107), who were enrolled in a course, "Psychology of Mental Retardation," participated in a service learning experience by working in group homes, day treatment programs,…

Curran, Joanne M.

430

New monomers for fire-retardant radiation curable polymers  

SciTech Connect

Novel photosensitive compositions are described which combine excellent UV curability and good flame-retardant properties. These compositions consist of halogenated allyl or methallyl esters, which, in combination with polythiols and photoinitiators and other additives, result in screenable liquids which can be applied to electronic circuit boards and cured with UV light to hard, fire-retardant coatings.

Kang, W.G.; Bush, R.W.; Ketley, A.D.

1983-01-01

431

Flame Retardants Common in Dust at Child Care Centers: Study  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Flame Retardants Common in Dust at Child Care Centers: Study ... Pollution THURSDAY, May 15, 2014 (HealthDay News) -- Hazardous flame retardants are found indoors at U.S. child care centers, ...

432

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

PubMed Central

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.

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

2013-01-01

433

Linking energy production and protein synthesis in hydrogenotrophic methanogens  

PubMed Central

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 tRNAPro 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.

Oza, Javin P.; Sowers, Kevin R.; Perona, John J.

2012-01-01