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1

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

PubMed

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

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

2005-02-01

2

Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs  

PubMed Central

Summary It remains controversial whether the highly-homologous ribosomal protein (RP) paralogs found in lower eukaryotes have distinct functions and this has not been explored in vertebrates. Here we demonstrate that despite ubiquitous expression, the RP paralogs, Rpl22 and Rpl22-like1 (Rpl22l1) play essential, distinct, and antagonistic roles in hematopoietic development. Knockdown of rpl22 in zebrafish embryos selectively blocks the development of T lineage progenitors after they have seeded the thymus. In contrast, knockdown of the rpl22 paralog, rpl22l1, impairs the emergence of hematopoietic stem cells (HSC) in the aorta-gonad-mesonephros by abrogating Smad1 expression and the consequent induction of essential transcriptional regulator, Runx1. Indeed, despite the ability of both paralogs to bind Smad1 RNA, Rpl22 and Rpl22l1 have opposing effects on Smad1 expression. Accordingly, circumstances that tip the balance of these paralogs in favor of Rpl22 (e.g., Rpl22l1 knockdown or Rpl22 overexpression) result in repression of Smad1 and blockade of HSC emergence. PMID:23449473

Zhang, Yong; Duc, Anne-Cécile E.; Rao, Shuyun; Sun, Xiao-Li; Bilbee, Alison N.; Rhodes, Michele; Li, Qin; Kappes, Dietmar J.; Rhodes, Jennifer; Wiest, David L.

2013-01-01

3

Transcript profiling provides evidence of functional divergence and expression networks among ribosomal protein gene paralogs in Brassica napus.  

PubMed

The plant ribosome is composed of 80 distinct ribosomal (r)-proteins. In Arabidopsis thaliana, each r-protein is encoded by two or more highly similar paralogous genes, although only one copy of each r-protein is incorporated into the ribosome. Brassica napus is especially suited to the comparative study of r-protein gene paralogs due to its documented history of genome duplication as well as the recent availability of large EST data sets. We have identified 996 putative r-protein genes spanning 79 distinct r-proteins in B. napus using EST data from 16 tissue collections. A total of 23,408 tissue-specific r-protein ESTs are associated with this gene set. Comparative analysis of the transcript levels for these unigenes reveals that a large fraction of r-protein genes are differentially expressed and that the number of paralogs expressed for each r-protein varies extensively with tissue type in B. napus. In addition, in many cases the paralogous genes for a specific r-protein are not transcribed in concert and have highly contrasting expression patterns among tissues. Thus, each tissue examined has a novel r-protein transcript population. Furthermore, hierarchical clustering reveals that particular paralogs for nonhomologous r-protein genes cluster together, suggesting that r-protein paralog combinations are associated with specific tissues in B. napus and, thus, may contribute to tissue differentiation and/or specialization. Altogether, the data suggest that duplicated r-protein genes undergo functional divergence into highly specialized paralogs and coexpression networks and that, similar to recent reports for yeast, these are likely actively involved in differentiation, development, and/or tissue-specific processes. PMID:19706795

Whittle, Carrie A; Krochko, Joan E

2009-08-01

4

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

PubMed

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

Lotz, Katrin; Schreiber, Falk; Wünschiers, Röbbe

2012-01-01

5

Identification of Paralogous Life-Cycle Stage Specific Cytoskeletal Proteins in the Parasite Trypanosoma brucei  

PubMed Central

The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule dynamics and associated proteins of the subpellicular microtubule array. Here we employed a gel-based comparative proteomic technique, Difference Gel Electrophoresis, to identify cytoskeletal proteins that are expressed differentially in mammalian infective and insect form trypanosomes. From this analysis we identified a pair of novel, paralogous proteins, one of which is expressed in the procyclic form and the other in the bloodstream form. We show that these proteins, CAP51 and CAP51V, localise to the subpellicular corset of microtubules and are essential for correct organisation of the cytoskeleton and successful cytokinesis in their respective life cycle stages. We demonstrate for the first time redundancy of function between life-cycle stage specific paralogous sets in the cytoskeleton and reveal modification of cytoskeletal components in situ prior to their removal during differentiation from the bloodstream form to the insect form. These specific results emphasise a more generic concept that the trypanosome genome encodes a cohort of cytoskeletal components that are present in at least two forms with life-cycle stage-specific expression. PMID:25180513

Portman, Neil; Gull, Keith

2014-01-01

6

Identification of paralogous life-cycle stage specific cytoskeletal proteins in the parasite Trypanosoma brucei.  

PubMed

The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule dynamics and associated proteins of the subpellicular microtubule array. Here we employed a gel-based comparative proteomic technique, Difference Gel Electrophoresis, to identify cytoskeletal proteins that are expressed differentially in mammalian infective and insect form trypanosomes. From this analysis we identified a pair of novel, paralogous proteins, one of which is expressed in the procyclic form and the other in the bloodstream form. We show that these proteins, CAP51 and CAP51V, localise to the subpellicular corset of microtubules and are essential for correct organisation of the cytoskeleton and successful cytokinesis in their respective life cycle stages. We demonstrate for the first time redundancy of function between life-cycle stage specific paralogous sets in the cytoskeleton and reveal modification of cytoskeletal components in situ prior to their removal during differentiation from the bloodstream form to the insect form. These specific results emphasise a more generic concept that the trypanosome genome encodes a cohort of cytoskeletal components that are present in at least two forms with life-cycle stage-specific expression. PMID:25180513

Portman, Neil; Gull, Keith

2014-01-01

7

Paralogous cAMP receptor proteins in Mycobacterium smegmatis show biochemical and functional divergence.  

PubMed

The cyclic AMP receptor protein (CRP) family of transcription factors consists of global regulators of bacterial gene expression. Here, we identify two paralogous CRPs in the genome of Mycobacterium smegmatis that have 78% identical sequences and characterize them biochemically and functionally. The two proteins (MSMEG_0539 and MSMEG_6189) show differences in cAMP binding affinity, trypsin sensitivity, and binding to a CRP site that we have identified upstream of the msmeg_3781 gene. MSMEG_6189 binds to the CRP site readily in the absence of cAMP, while MSMEG_0539 binds in the presence of cAMP, albeit weakly. msmeg_6189 appears to be an essential gene, while the ?msmeg_0539 strain was readily obtained. Using promoter-reporter constructs, we show that msmeg_3781 is regulated by CRP binding, and its transcription is repressed by MSMEG_6189. Our results are the first to characterize two paralogous and functional CRPs in a single bacterial genome. This gene duplication event has subsequently led to the evolution of two proteins whose biochemical differences translate to differential gene regulation, thus catering to the specific needs of the organism. PMID:25434596

Sharma, Ritu; Zaveri, Anisha; Gopalakrishnapai, Jayashree; Srinath, Thiruneelakantan; Thiruneelakantan, Srinath; Varshney, Umesh; Visweswariah, Sandhya S

2014-12-16

8

RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors.  

PubMed

Ribosomal proteins (RPs) have been shown to be able to impart selectivity on the translating ribosome implicating them in gene expression control. Many ribosomal proteins are highly conserved and recently a number of ribosomal protein paralogs have been described in mammals. We examined the expression pattern of RPs in differentiating mouse Embryonic Stem Cells (ESCs), paying particular attention to the RP paralogs. We find the RP paralog Rpl39l is highly expressed in ESC and its expression strongly correlates with hepatocellular carcinoma tumor (HCC) samples with high tumor grading and alpha-fetoprotein level giving it diagnostic potential. We further screen the expression pattern of all RPs and their paralogs across 22 different tissues. We find that the more recently evolved RP paralogs show a much greater level of tissue-specific expression. We propose that these RP paralogs evolved more recently to provide a greater level of gene expression control to higher eukaryotes. PMID:24452241

Wong, Queenie Wing-Lei; Li, Jia; Ng, Sheng Rong; Lim, Seng Gee; Yang, Henry; Vardy, Leah A

2014-01-01

9

RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors  

PubMed Central

Ribosomal proteins (RPs) have been shown to be able to impart selectivity on the translating ribosome implicating them in gene expression control. Many ribosomal proteins are highly conserved and recently a number of ribosomal protein paralogs have been described in mammals. We examined the expression pattern of RPs in differentiating mouse Embryonic Stem Cells (ESCs), paying particular attention to the RP paralogs. We find the RP paralog Rpl39l is highly expressed in ESC and its expression strongly correlates with hepatocellular carcinoma tumor (HCC) samples with high tumor grading and alpha-fetoprotein level giving it diagnostic potential. We further screen the expression pattern of all RPs and their paralogs across 22 different tissues. We find that the more recently evolved RP paralogs show a much greater level of tissue-specific expression. We propose that these RP paralogs evolved more recently to provide a greater level of gene expression control to higher eukaryotes. PMID:24452241

Wong, Queenie Wing-Lei; Li, Jia; Ng, Sheng Rong; Lim, Seng Gee; Yang, Henry; Vardy, Leah A

2014-01-01

10

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

E-print Network

The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins. We introduce a simple mathematical framework based on a stochastic birth-and-death model that allows one to extract some of this information and apply it to the set of all pairs of paralogous proteins in seven model organisms. It was found that the histogram of sequence identities p generated by an all-to-all alignment of all protein sequences encoded in a genome is well fitted with a power-law form ~p^(-gamma) with the value of the exponent gamma around 4 for the majority of organisms used in this study. This implies that the intra-protein variability of substitution rates is best described by the Gamma-distribution with the exponent alpha ~ 0.33. We separately measure the short-term (``raw'') duplication and deletion rates r*_dup, r*_del which include gene copies that will be removed soon after the duplication event and their dramatically reduced long-term counterparts r_dup, r_del. Systematic trends of each of the four duplication/deletion rates with the total number of genes in the genome were analyzed. All but the deletion rate of recent duplicates r*_del were shown to systematically increase with N_genes. Abnormally flat shapes of sequence identity histograms observed for yeast and human are consistent with lineages leading to these organisms undergoing one or more whole-genome duplications.

Jacob Bock Axelsen; Koon-Kiu Yan; Sergei Maslov

2007-11-05

11

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

PubMed

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

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

2015-05-01

12

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. 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

2014-01-01

13

Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Errors Caused by Confusing Paralogs and Epaktologs  

PubMed Central

In the accompanying paper (Nagy, Szláma, Szarka, Trexler, Bányai, Patthy, Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Gene Prediction Errors) we showed that in the case of UniProtKB/TrEMBL, RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences of Metazoan species the contribution of erroneous (incomplete, abnormal, mispredicted) sequences to domain architecture (DA) differences of orthologous proteins might be greater than those of true gene rearrangements. Based on these findings, we suggest that earlier genome-scale studies based on comparison of predicted (frequently mispredicted) protein sequences may have led to some erroneous conclusions about the evolution of novel domain architectures of multidomain proteins. In this manuscript we examine the impact of confusing paralogous and epaktologous multidomain proteins (i.e., those that are related only through the independent acquisition of the same domain types) on conclusions drawn about DA evolution of multidomain proteins in Metazoa. To estimate the contribution of this type of error we have used as reference UniProtKB/Swiss-Prot sequences from protein families with well-characterized evolutionary histories. We have used two types of paralogy-group construction procedures and monitored the impact of various parameters on the separation of true paralogs from epaktologs on correctly annotated Swiss-Prot entries of multidomain proteins. Our studies have shown that, although public protein family databases are contaminated with epaktologs, analysis of the structure of sequence similarity networks of multidomain proteins provides an efficient means for the separation of epaktologs and paralogs. We have also demonstrated that contamination of protein families with epaktologs increases the apparent rate of DA change and introduces a bias in DA differences in as much as it increases the proportion of terminal over internal DA differences. We have shown that confusing paralogous and epaktologous multidomain proteins significantly increases the apparent rate of DA change in Metazoa and introduces a positional bias in favor of terminal over internal DA changes. Our findings caution that earlier studies based on analysis of datasets of protein families that were contaminated with epaktologs may have led to some erroneous conclusions about the evolution of novel domain architectures of multidomain proteins. A reassessment of the DA evolution of multidomain proteins is presented in an accompanying paper [1]. PMID:24710209

Nagy, Alinda; Bányai, László; Patthy, László

2011-01-01

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. PMID:24040418

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

2013-01-01

15

Genome-Wide Analysis of Human Disease Alleles Reveals That Their Locations Are Correlated in Paralogous Proteins  

PubMed Central

The millions of mutations and polymorphisms that occur in human populations are potential predictors of disease, of our reactions to drugs, of predisposition to microbial infections, and of age-related conditions such as impaired brain and cardiovascular functions. However, predicting the phenotypic consequences and eventual clinical significance of a sequence variant is not an easy task. Computational approaches have found perturbation of conserved amino acids to be a useful criterion for identifying variants likely to have phenotypic consequences. To our knowledge, however, no study to date has explored the potential of variants that occur at homologous positions within paralogous human proteins as a means of identifying polymorphisms with likely phenotypic consequences. In order to investigate the potential of this approach, we have assembled a unique collection of known disease-causing variants from OMIM and the Human Genome Mutation Database (HGMD) and used them to identify and characterize pairs of sequence variants that occur at homologous positions within paralogous human proteins. Our analyses demonstrate that the locations of variants are correlated in paralogous proteins. Moreover, if one member of a variant-pair is disease-causing, its partner is likely to be disease-causing as well. Thus, information about variant-pairs can be used to identify potentially disease-causing variants, extend existing procedures for polymorphism prioritization, and provide a suite of candidates for further diagnostic and therapeutic purposes. PMID:18989397

Yandell, Mark; Moore, Barry; Salas, Fidel; Mungall, Chris; MacBride, Andrew; White, Charles; Reese, Martin G.

2008-01-01

16

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

PubMed Central

Background Fatty acid (FA) binding proteins (FABPs) of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. Methodology/Principal Findings We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15–95% with other related-members. Homology modeling demonstrated a characteristic ?-barrel composed of 10 anti-parallel ?-strands and two ?-helices. TsMFABP2 harbored two additional loops between ?-strands two and three, and ?-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid, dansyl-DL-?-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions of lipids and retinol. Conclusions/Significance The divergent biochemical properties, physiological roles and cellular distributions of the TsMFABPs might be one of the critical mechanisms compensating for inadequate de novo FA synthesis. These proteins might exert harmonized or independent roles on lipid assimilation and intracellular signaling. The specialized distribution of retinol in the canal region further implies that cells in this region might differentiate into diverse cell types during metamorphosis into an adult worm. Identification of bioactive systems pertinent to parasitic homeostasis may provide a valuable target for function-related drug design. PMID:23150743

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

2012-01-01

17

Targeted identification of SUMOylation sites in human proteins using affinity enrichment and paralog-specific reporter ions.  

PubMed

Protein modification by small ubiquitin-like modifier (SUMO) modulates the activities of numerous proteins involved in different cellular functions such as gene transcription, cell cycle, and DNA repair. Comprehensive identification of SUMOylated sites is a prerequisite to determine how SUMOylation regulates protein function. However, mapping SUMOylated Lys residues by mass spectrometry (MS) is challenging because of the dynamic nature of this modification, the existence of three functionally distinct human SUMO paralogs, and the large SUMO chain remnant that remains attached to tryptic peptides. To overcome these problems, we created HEK293 cell lines that stably express functional SUMO paralogs with an N-terminal His6-tag and an Arg residue near the C terminus that leave a short five amino acid SUMO remnant upon tryptic digestion. We determined the fragmentation patterns of our short SUMO remnant peptides by collisional activation and electron transfer dissociation using synthetic peptide libraries. Activation using higher energy collisional dissociation on the LTQ-Orbitrap Elite identified SUMO paralog-specific fragment ions and neutral losses of the SUMO remnant with high mass accuracy (< 5 ppm). We exploited these features to detect SUMO modified tryptic peptides in complex cell extracts by correlating mass measurements of precursor and fragment ions using a data independent acquisition method. We also generated bioinformatics tools to retrieve MS/MS spectra containing characteristic fragment ions to the identification of SUMOylated peptide by conventional Mascot database searches. In HEK293 cell extracts, this MS approach uncovered low abundance SUMOylated peptides and 37 SUMO3-modified Lys residues in target proteins, most of which were previously unknown. Interestingly, we identified mixed SUMO-ubiquitin chains with ubiquitylated SUMO proteins (K20 and K32) and SUMOylated ubiquitin (K63), suggesting a complex crosstalk between these two modifications. PMID:23750026

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

2013-09-01

18

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

PubMed Central

Protein modification by small ubiquitin-like modifier (SUMO) modulates the activities of numerous proteins involved in different cellular functions such as gene transcription, cell cycle, and DNA repair. Comprehensive identification of SUMOylated sites is a prerequisite to determine how SUMOylation regulates protein function. However, mapping SUMOylated Lys residues by mass spectrometry (MS) is challenging because of the dynamic nature of this modification, the existence of three functionally distinct human SUMO paralogs, and the large SUMO chain remnant that remains attached to tryptic peptides. To overcome these problems, we created HEK293 cell lines that stably express functional SUMO paralogs with an N-terminal His6-tag and an Arg residue near the C terminus that leave a short five amino acid SUMO remnant upon tryptic digestion. We determined the fragmentation patterns of our short SUMO remnant peptides by collisional activation and electron transfer dissociation using synthetic peptide libraries. Activation using higher energy collisional dissociation on the LTQ-Orbitrap Elite identified SUMO paralog-specific fragment ions and neutral losses of the SUMO remnant with high mass accuracy (< 5 ppm). We exploited these features to detect SUMO modified tryptic peptides in complex cell extracts by correlating mass measurements of precursor and fragment ions using a data independent acquisition method. We also generated bioinformatics tools to retrieve MS/MS spectra containing characteristic fragment ions to the identification of SUMOylated peptide by conventional Mascot database searches. In HEK293 cell extracts, this MS approach uncovered low abundance SUMOylated peptides and 37 SUMO3-modified Lys residues in target proteins, most of which were previously unknown. Interestingly, we identified mixed SUMO-ubiquitin chains with ubiquitylated SUMO proteins (K20 and K32) and SUMOylated ubiquitin (K63), suggesting a complex crosstalk between these two modifications. PMID:23750026

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

2013-01-01

19

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

PubMed Central

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

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

2014-01-01

20

Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp.  

PubMed

Fragile X syndrome is the most common form of inherited mental retardation and is caused by the absence of expression of the FMR1 gene. The protein encoded by this gene, Fmrp, is an RNA-binding protein that binds a subset of mRNAs and regulates their translation, leading to normal cognitive function. Although the association with RNAs is well established, it is still unknown how Fmrp finds and assembles with its RNA cargoes and how these activities are regulated. We show here that Fmrp is post-translationally methylated, primarily on its arginine-glycine-glycine box. We identify the four arginines that are methylated and show that cellular Fmrp is monomethylated and asymmetrically dimethylated. We also show that the autosomal paralog Fxr1 and the Drosophila ortholog dFmr1 are methylated post-translationally. Recombinant protein arginine methyl transferase 1 (PRMT1) methylates Fmrp on the same arginines in vitro as in cells. In vitro methylation of Fmrp results in reduced binding to the minimal RNA sequence sc1, which encodes a stem loop G-quartet structure. Our data identify an additional mechanism, arginine methylation, for modifying Fmrp function and suggest that methylation occurs to limit or modulate RNA binding by Fmrp. PMID:16319129

Stetler, April; Winograd, Claudia; Sayegh, Joyce; Cheever, Anne; Patton, Erin; Zhang, Xing; Clarke, Steven; Ceman, Stephanie

2006-01-01

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

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

E-print Network

A Novel Function for Fragile X Mental Retardation Protein in Translational Activation Elias G, Universite´ Laval, Que´bec, Canada Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved

Boyer, Edmond

23

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

E-print Network

The Fragile X Mental Retardation Protein in Circadian Rhythmicity and Memory Consolidation Cheryl L. The fragile X mental retardation protein (FMRP), an RNA- binding translational regulator, is a key player causes fragile X syndrome (FraX), the most commonly inherited form of mental retardation and autism

Broadie, Kendal S.

24

Adaptive Mutations that Prevent Crosstalk Enable the Expansion of Paralogous Signaling Protein Families  

E-print Network

Orthologous proteins often harbor numerous substitutions, but whether these differences result from neutral or adaptive processes is usually unclear. To tackle this challenge, we examined the divergent evolution of a model ...

Capra, Emily J.

25

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

E-print Network

In vivo neuronal function of the fragile X mental retardation protein is regulated November 7, 2011 Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene,7). The X-linked neurodevelopmental disorder is caused by the loss of fragile X mental retardation 1 (FMR1

Broadie, Kendal S.

26

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

27

Fragile X mental retardation protein: past, present and future.  

PubMed

We begin by reviewing the first characterization of fragile X syndrome, which ultimately led to cloning of the FMR1 gene. Discovery of the molecular basis of this disorder, including expansion of a trinucleotide repeat, gave insight not only into fragile X syndrome but also into the premutation syndromes. Features of fragile X syndrome are discussed including the patient phenotype down to the neuronal phenotype. The domain features of the fragile X mental retardation protein FMRP are described, as are the mRNAs bound by FMRP and the role of post-translational modifications as regulators of FMRP function. The relatively new role of FMRP in progenitor cells is reviewed, as is FMRP localization in cells and how FMRP is regulated by glutamatergic signaling in the brain. Understanding how metabotropic glutamate receptors impact FMRP has led to novel therapeutic approaches in treating this disorder. PMID:22708486

Kim, Miri; Ceman, Stephanie

2012-06-01

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. PMID:22753055

Dempwolff, Felix; Möller, Heiko M.

2012-01-01

29

A new regulatory function of the region proximal to the RGG box in the fragile X mental retardation protein.  

PubMed

Fragile X mental retardation protein (FMRP) is required for normal cognition. FMRP has two autosomal paralogs, which although similar to FMRP, cannot compensate for the loss of FMRP expression in brain. The arginine- and glycine-rich region of FMRP (the RGG box) is unique; it is the high-affinity RNA-binding motif in FMRP and is encoded by exon 15. Alternative splicing occurs in the 5' end of exon 15, which is predicted to affect the structure of the distally encoded RGG box. Here, we provide evidence that isoform 3, which removes 25 amino acids from the 5' end of exon 15, has an altered conformation that reduces binding of a specific antibody and renders the RGG box unable to efficiently associate with polyribosomes. Isoform 3 is also compromised in its ability to form granules and to associate with a key messenger ribonucleoprotein Yb1 (also known as p50, NSEP1 and YBX1). Significantly, these functions are similarly compromised when the RGG box is absent from FMRP, suggesting an important regulatory role of the N-terminal region encoded by exon 15. PMID:21868366

Blackwell, Ernest; Ceman, Stephanie

2011-09-15

30

A new regulatory function of the region proximal to the RGG box in the Fragile X mental retardation protein  

PubMed Central

Fragile X mental retardation protein (FMRP) is required for normal cognition. FMRP has two autosomal paralogs, which although similar to FMRP, cannot compensate for the loss of FMRP expression in brain. The arginine- and glycine-rich region of FMRP (the RGG box) is unique; it is the high-affinity RNA-binding motif in FMRP and is encoded by exon 15. Alternative splicing occurs in the 5? end of exon 15, which is predicted to affect the structure of the distally encoded RGG box. Here, we provide evidence that isoform 3, which removes 25 amino acids from the 5? end of exon 15, has an altered conformation that reduces binding of a specific antibody and renders the RGG box unable to efficiently associate with polyribosomes. Isoform 3 is also compromised in its ability to form granules and to associate with a key messenger ribonucleoprotein Yb1 (also known as p50, NSEP1 and YBX1). Significantly, these functions are similarly compromised when the RGG box is absent from FMRP, suggesting an important regulatory role of the N-terminal region encoded by exon 15. PMID:21868366

Blackwell, Ernest; Ceman, Stephanie

2011-01-01

31

Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains of Fragile X Mental Retardation Protein  

SciTech Connect

Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence of Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein.

Valverde,R.; Poznyakova, I.; Kajander, T.; Venkatraman, J.; Regan, L.

2007-01-01

32

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

33

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

Microsoft Academic Search

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

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

2001-01-01

34

Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses  

PubMed Central

Fragile X mental retardation is caused by absence of the RNA-binding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1-knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo. This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome. PMID:15548614

Weiler, Ivan Jeanne; Spangler, Chad C.; Klintsova, Anna Y.; Grossman, Aaron W.; Kim, Soong Ho; Bertaina-Anglade, Valerie; Khaliq, Hooma; de Vries, Froukje E.; Lambers, Femke A. E.; Hatia, Fatima; Base, Christine K.; Greenough, William T.

2004-01-01

35

The Role of Fragile X Mental Retardation Protein in Major Mental Disorders  

PubMed Central

Fragile X mental retardation protein (FMRP) is highly enriched in neurons and binds to approximately 4% of mRNAs in mammalian brain. Its loss is a hallmark of fragile X syndrome (FXS), the most common form of mental retardation. In this review we discuss the mutation in the fragile X mental retardation-1 gene (FMR1), that leads to FXS, the role FMRP plays in neuronal cells, experiments from our own laboratory that demonstrate reductions of FMRP in additional psychiatric disorders (autism, schizophrenia, bipolar disorder, and major depressive disorder), and potential therapies to ameliorate the loss of FMRP. PMID:21108954

Fatemi, S. Hossein; Folsom, Timothy D.

2011-01-01

36

Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons  

E-print Network

Fragile X mental retardation protein is required for programmed cell death and clearance Fragile X syndrome (FXS), caused by loss of fragile X mental retardation 1 (FMR1) gene function-trinucleotide repeat expansion in the 5 UTR of the fragile X mental retardation 1 (FMR1) gene (reviewed in Bassell

Broadie, Kendal S.

37

Phylogenomics with paralogs.  

PubMed

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

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

2015-02-17

38

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)

2008-02-05

39

The MicroRNA Pathway and Fragile X Mental Retardation Protein  

PubMed Central

Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by the functional loss of fragile X mental retardation protein (FMRP). MicroRNAs (miRNAs), a newly discovered class of small noncoding RNAs, have been implicated in multiple biological processes through posttranscriptional gene regulation. Recent evidence supports this view in terms of the biochemical and genetic interaction found between FMRP and the miRNA pathway, providing deeper insight into the molecular pathogenesis of mental retardation. This review briefly summarizes the progress towards an understanding of the role miRNAs play in neurological disorders, with a focus on the mechanism of interaction between FMRP and the miRNA pathway in the context of fragile X syndrome. In addition, we go on to discuss how the miRNA pathway may be involved in mental retardation. PMID:18687414

Li, Yujing; Lin, Li; Jin, Peng

2008-01-01

40

Orthology and paralogy constraints: satisfiability and consistency  

PubMed Central

Background A variety of methods based on sequence similarity, reconciliation, synteny or functional characteristics, can be used to infer orthology and paralogy relations between genes of a given gene family  G. But is a given set  C of orthology/paralogy constraints possible, i.e., can they simultaneously co-exist in an evolutionary history for  G? While previous studies have focused on full sets of constraints, here we consider the general case where  C does not necessarily involve a constraint for each pair of genes. The problem is subdivided in two parts: (1) Is  C satisfiable, i.e. can we find an event-labeled gene tree G inducing  C? (2) Is there such a G which is consistent, i.e., such that all displayed triplet phylogenies are included in a species tree? Results Previous results on the Graph sandwich problem can be used to answer to (1), and we provide polynomial-time algorithms for satisfiability and consistency with a given species tree. We also describe a new polynomial-time algorithm for the case of consistency with an unknown species tree and full knowledge of pairwise orthology/paralogy relationships, as well as a branch-and-bound algorithm in the case when unknown relations are present. We show that our algorithms can be used in combination with ProteinOrtho, a sequence similarity-based orthology detection tool, to extract a set of robust orthology/paralogy relationships. PMID:25572629

2014-01-01

41

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

PubMed Central

Background Nucleoside phosphorylases (NPs) have been extensively investigated in human and bacterial systems for their role in metabolic nucleotide salvaging and links to oncogenesis. In plants, NP-like proteins have not been comprehensively studied, likely because there is no evidence of a metabolic function in nucleoside salvage. However, in the forest trees genus Populus a family of NP-like proteins function as an important ecophysiological adaptation for inter- and intra-seasonal nitrogen storage and cycling. Results We conducted phylogenetic analyses to determine the distribution and evolution of NP-like proteins in plants. These analyses revealed two major clusters of NP-like proteins in plants. Group I proteins were encoded by genes across a wide range of plant taxa while proteins encoded by Group II genes were dominated by species belonging to the order Malpighiales and included the Populus Bark Storage Protein (BSP) and WIN4-like proteins. Additionally, we evaluated the NP-like genes in Populus by examining the transcript abundance of the 13 NP-like genes found in the Populus genome in various tissues of plants exposed to long-day (LD) and short-day (SD) photoperiods. We found that all 13 of the Populus NP-like genes belonging to either Group I or II are expressed in various tissues in both LD and SD conditions. Tests of natural selection and expression evolution analysis of the Populus genes suggests that divergence in gene expression may have occurred recently during the evolution of Populus, which supports the adaptive maintenance models. Lastly, in silico analysis of cis-regulatory elements in the promoters of the 13 NP-like genes in Populus revealed common regulatory elements known to be involved in light regulation, stress/pathogenesis and phytohormone responses. Conclusion In Populus, the evolution of the NP-like protein and gene family has been shaped by duplication events and natural selection. Expression data suggest that previously uncharacterized NP-like proteins may function in nutrient sensing and/or signaling. These proteins are members of Group I NP-like proteins, which are widely distributed in many plant taxa. We conclude that NP-like proteins may function in plants, although this function is undefined. PMID:23957885

2013-01-01

42

Fragile X mental retardation protein and synaptic plasticity  

E-print Network

Loss of the translational repressor FMRP causes Fragile X syndrome. In healthy neurons, FMRP modulates the local translation of numerous synaptic proteins. Synthesis of these proteins is required for the maintenance and ...

Sidorov, Michael Samuel

43

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

44

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

ERIC Educational Resources Information Center

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

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

2004-01-01

45

Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development.  

PubMed

Fragile X syndrome is caused by the lack of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA transport and translation. FMRP is a component of mRNA ribonucleoprotein complexes and it can interact with a range of proteins either directly or indirectly, as demonstrated by two-hybrid selection and co-immunoprecipitation, respectively. Most of FMRP-interacting proteins are RNA-binding proteins such as FXR1P, FXR2P and 82-FIP. Interestingly, FMRP can also interact directly with the cytoplasmic proteins CYFIP1 and CYFIP2, which do not bind RNA and link FMRP to the RhoGTPase pathway. The interaction with these different proteins may modulate the functions of FMRP by influencing its affinity to RNA and by affecting the FMRP ability of cytoskeleton remodeling through Rho/Rac GTPases. To better define the relationship of FMRP with its interacting proteins during brain development, we have analyzed the expression pattern of FMRP and its interacting proteins in the cortex, striatum, hippocampus and cerebellum at different ages in wild type (WT) mice. FMRP and FXR2P were strongly expressed during the first week and gradually decreased thereafter, more rapidly in the cerebellum than in the cortex. FXR1P was also expressed early and showed a reduction at later stages of development with a similar developmental pattern in these two regions. CYFIP1 was expressed at all ages and peaked in the third post-natal week. In contrast, CYFIP2 and 82-FIP (only in forebrain regions) were moderately expressed at P3 and gradually increased after P7. In general, the expression pattern of each protein was similar in the regions examined, except for 82-FIP, which exhibited a strong expression at P3 and low levels at later developmental stages in the cerebellum. Our data indicate that FMRP and its interacting proteins have distinct developmental patterns of expression and suggest that FMRP may be preferentially associated to certain proteins in early and late developmental periods. In particular, the RNA-binding and cytoskeleton remodeling functions of FMRP may be differently modulated during development. PMID:25681562

Bonaccorso, C M; Spatuzza, M; Di Marco, B; Gloria, A; Barrancotto, G; Cupo, A; Musumeci, S A; D'Antoni, S; Bardoni, B; Catania, M V

2015-05-01

46

Deciphering the spatio-temporal expression and stress regulation of Fam107B, the paralog of the resilience-promoting protein DRR1 in the mouse brain.  

PubMed

Understanding the molecular mechanisms that promote stress resilience might open up new therapeutic avenues to prevent stress-related disorders. We recently characterized a stress and glucocorticoid-regulated gene, down-regulated in renal cell carcinoma - DRR1 (Fam107A). DRR1 is expressed in the mouse brain; it is up-regulated by stress and glucocorticoids and modulates neuronal actin dynamics. In the adult mouse, DRR1 was shown to facilitate specific behaviors which might be protective against some of the deleterious consequences of stress exposure: in the hippocampal CA3 region, DRR1 improved cognitive performance whereas in the septum, it specifically increased social behavior. Therefore DRR1 was suggested as a candidate protein promoting stress-resilience. Fam107B (family with sequence similarity 107, member B) is the unique paralog of DRR1, and both share high sequence similarities, predicted glucocorticoid response elements, heat-shock induction and tumor suppressor properties. So far, the role of Fam107B in the central nervous system was not studied. The aim of the present investigation, therefore, was to analyze whether Fam107B and DRR1 display comparable mRNA expression patterns in the brain and whether both are modulated by stress and glucocorticoids. Spatio-temporal mapping of Fam107B mRNA expression in the embryonic and adult mouse brain, by means of in situ hybridization, showed that Fam107B was expressed during embryogenesis and in the adulthood, with particularly high and specific expression in the forming telencephalon suggestive of an involvement in corticogenesis. In the adult mouse, expression was restricted to neurogenic niches, like the dentate gyrus. In contrast to DRR1, Fam107B mRNA expression failed to be modulated by glucocorticoids and social stress in the adult mouse. In summary, Fam107B and DRR1 show different spatio-temporal expression patterns in the central nervous system, suggesting at least partially different functional roles in the brain, and where the glucocorticoid receptor (GR)-induced regulation appears to be a unique property of DRR1. PMID:25637808

Masana, M; Jukic, M M; Kretzschmar, A; Wagner, K V; Westerholz, S; Schmidt, M V; Rein, T; Brodski, C; Müller, M B

2015-04-01

47

Similarities and differences in the structure and function of 4.1G and 4.1R135, two protein 4.1 paralogs expressed in erythroid cells  

PubMed Central

Summary Membrane skeletal protein 4.1R is the prototypical member of a family of four highly paralogous proteins that include 4.1G, 4.1N and 4.1B. Two isoforms of 4.1R (4.1R135 and 4.1R80) as well as 4.1G are expressed in erythroblasts during terminal differentiation, but only 4.1R80 is present in mature erythrocytes. While the function of 4.1R isoforms in erythroid cells has been well characterized, there is little or no information on the function of 4.1G in these cells. In the present study, we performed detailed characterization of the interaction of 4.1G with various erythroid membrane proteins and the regulation of these interactions by calcium-saturated calmodulin. Like both isoforms of 4.1R, 4.1G bound to band 3, glycophorin C, CD44, p55 and calmodulin. While both 4.1G and 4.1R135 interact with similar affinity with CD44 and p55, there are significant differences in the affinity of their interaction with band 3 and glycophorin C. This difference in affinity is related to the non-conserved N-terminal headpiece region of the two proteins that is upstream of the 30kDa membrane binding domain that harbors the binding sites for the various membrane proteins. The headpiece region of 4.1G also contains a high affinity calcium-dependent calmodulin-binding site that plays a key role in modulating its interaction with various membrane proteins. We suggest that expression of the two paralogs of protein 4.1 with different affinities for band 3 and glycophorin C is likely to play a role in assembly of these two membrane proteins during terminal erythroid differentiation. PMID:20812914

Nunomura, Wataru; Kinoshita, Kengo; Parra, Marilyn; Gascard, Philippe; An, Xiuli; Mohandas, Narla; Takakuwa, Yuichi

2015-01-01

48

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

PubMed Central

Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein. FMRP is associated with messenger RiboNucleoParticles (mRNPs) present in polyribosomes and its absence in neurons leads to alteration in synaptic plasticity as a result of translation regulation defects. The molecular mechanisms by which FMRP plays a role in translation regulation remain elusive. Using immunoprecipitation approaches with monoclonal Ab7G1-1 and a new generation of chicken antibodies, we identified Caprin1 as a novel FMRP-cellular partner. In vivo and in vitro evidence show that Caprin1 interacts with FMRP at the level of the translation machinery as well as in trafficking neuronal granules. As an RNA-binding protein, Caprin1 has in common with FMRP at least two RNA targets that have been identified as CaMKII? and Map1b mRNAs. In view of the new concept that FMRP species bind to RNA regardless of known structural motifs, we propose that protein interactors might modulate FMRP functions. PMID:22737234

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

2012-01-01

49

The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers.  

PubMed

Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins. PMID:25799254

Hu, Yufeng; Chen, Zhenhang; Fu, Yanjun; He, Qingzhong; Jiang, Lun; Zheng, Jiangge; Gao, Yina; Mei, Pinchao; Chen, Zhongzhou; Ren, Xueqin

2015-01-01

50

Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells  

PubMed Central

Lack of fragile X mental retardation protein (FMRP) causes fragile X syndrome, a common form of inherited mental retardation. FMRP is an RNA binding protein thought to be involved in translation efficiency and/or trafficking of certain mRNAs. Recently, a subset of mRNAs to which FMRP binds with high affinity has been identified. These FMRP-associated mRNAs contain an intramolecular G-quartet structure. In neurons, dendritic mRNAs are involved in local synthesis of proteins in response to synaptic activity, and this represents a mechanism for synaptic plasticity. To determine the role of FMRP in dendritic mRNA transport, we have generated a stably FMR1-enhanced green fluorescent protein (EGFP)-transfected PC12 cell line with an inducible expression system (Tet-On) for regulated expression of the FMRP-GFP fusion protein. After doxycycline induction, FMRP-GFP was localized in granules in the neurites of PC12 cells. By using time-lapse microscopy, the trafficking of FMRP-GFP granules into the neurites of living PC12 cells was demonstrated. Motile FMRP-GFP granules displayed two types of movements: oscillatory (bidirectional) and unidirectional anterograde. The average velocity of the granules was 0.19 ?m/s with a maximum speed of 0.71 ?m/s. In addition, we showed that the movement of FMRP-GFP labeled granules into the neurites was microtubule dependent. Colocalization studies further showed that the FMRP-GFP labeled granules also contained RNA, ribosomal subunits, kinesin heavy chain, and FXR1P molecules. This report is the first example of trafficking of RNA-containing granules with FMRP as a core constituent in living PC12 cells. PMID:12417734

De Diego Otero, Yolanda; Severijnen, Lies-Anne; van Cappellen, Gert; Schrier, Mariëtte; Oostra, Ben; Willemsen, Rob

2002-01-01

51

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

Microsoft Academic Search

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

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

1996-01-01

52

Paralog-selective Hsp90 inhibitors define tumor-specific regulation of Her2  

PubMed Central

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

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

2014-01-01

53

In Vitro Studies of the Uridylylation of the Three PII Protein Paralogs from Rhodospirillum rubrum: the Transferase Activity of R. rubrum GlnD Is Regulated by ?-Ketoglutarate and Divalent Cations but Not by Glutamine?  

PubMed Central

PII proteins have been shown to be key players in the regulation of nitrogen fixation and ammonia assimilation in bacteria. The mode by which these proteins act as signals is by being in either a form modified by UMP or the unmodified form. The modification, as well as demodification, is catalyzed by a bifunctional enzyme encoded by the glnD gene. The regulation of this enzyme is thus of central importance. In Rhodospirillum rubrum, three PII paralogs have been identified. In this study, we have used purified GlnD and PII proteins from R. rubrum, and we show that for the uridylylation activity of R. rubrum GlnD, ?-ketoglutarate is the main signal, whereas glutamine has no effect. This is in contrast to, e.g., the Escherichia coli system. Furthermore, we show that all three PII proteins are uridylylated, although the efficiency is dependent on the cation present. This difference may be of importance in understanding the effects of the PII proteins on the different target enzymes. Furthermore, we show that the deuridylylation reaction is greatly stimulated by glutamine and that Mn2+ is required. PMID:17337583

Jonsson, Anders; Nordlund, Stefan

2007-01-01

54

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

55

Bidirectional Regulation of Dendritic Voltage-gated Potassium Channels by the Fragile X Mental Retardation Protein  

PubMed Central

Summary How transmitter receptors modulate neuronal signaling by regulating voltage-gated ion channel expression remains an open question. Here we report dendritic localization of mRNA of Kv4.2 voltage-gated potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the most common heritable mental retardation. FMRP suppression of Kv4.2 is revealed by elevation of Kv4.2 in neurons from fmr1 knockout (KO) mice, and in neurons expressing Kv4.2-3?UTR that binds FMRP. Moreover, treating hippocampal slices from fmr1 KO mice with Kv4 channel blocker restores long-term potentiation (LTP) induced by moderate stimuli. Surprisingly, recovery of Kv4.2 after N-methyl-D-aspartate receptor (NMDAR)-induced degradation also requires FMRP, likely due to NMDAR-induced FMRP dephosphorylation, which turns off FMRP suppression of Kv4.2. Our study of FMRP regulation of Kv4.2 reveals a novel aspect of NMDAR signaling and a new FMRP target of potential relevance to FXS. PMID:22099464

Lee, Hye Young; Ge, Woo-Ping; Huang, Wendy; He, Ye; Wang, Gordon X.; Rowson-Baldwin, Ashley; Smith, Stephen J; Jan, Yuh Nung; Jan, Lily Yeh

2012-01-01

56

Fragile X mental retardation protein FMRP binds mRNAs in the nucleus.  

PubMed

The fragile X mental retardation protein FMRP is an RNA binding protein that associates with a large collection of mRNAs. Since FMRP was previously shown to be a nucleocytoplasmic shuttling protein, we examined the hypothesis that FMRP binds its cargo mRNAs in the nucleus. The enhanced green fluorescent protein-tagged FMRP construct (EGFP-FMRP) expressed in Cos-7 cells was efficiently exported from the nucleus in the absence of its nuclear export sequence and in the presence of a strong nuclear localization sequence (the simian virus 40 [SV40] NLS), suggesting an efficient mechanism for nuclear export. We hypothesized that nuclear FMRP exits the nucleus through its bound mRNAs. Using silencing RNAs to the bulk mRNA exporter Tap/NXF1, we observed a significantly increased number of cells containing EGFP-FMRP in the nucleus, which was further augmented by removal of FMRP's nuclear export sequence. Nuclear-retained SV40-FMRP could be released upon treatment with RNase. Further, Tap/NXF1 coimmunoprecipitated with EGFP-FMRP in an RNA-dependent manner and contained the FMR1 mRNA. To determine whether FMRP binds pre-mRNAs cotranscriptionally, we expressed hemagglutinin-SV40 FMRP in amphibian oocytes and found it, as well as endogenous Xenopus FMRP, on the active transcription units of lampbrush chromosomes. Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus. PMID:18936162

Kim, Miri; Bellini, Michel; Ceman, Stephanie

2009-01-01

57

Fragile X Mental Retardation Protein FMRP Binds mRNAs in the Nucleus?  

PubMed Central

The fragile X mental retardation protein FMRP is an RNA binding protein that associates with a large collection of mRNAs. Since FMRP was previously shown to be a nucleocytoplasmic shuttling protein, we examined the hypothesis that FMRP binds its cargo mRNAs in the nucleus. The enhanced green fluorescent protein-tagged FMRP construct (EGFP-FMRP) expressed in Cos-7 cells was efficiently exported from the nucleus in the absence of its nuclear export sequence and in the presence of a strong nuclear localization sequence (the simian virus 40 [SV40] NLS), suggesting an efficient mechanism for nuclear export. We hypothesized that nuclear FMRP exits the nucleus through its bound mRNAs. Using silencing RNAs to the bulk mRNA exporter Tap/NXF1, we observed a significantly increased number of cells containing EGFP-FMRP in the nucleus, which was further augmented by removal of FMRP's nuclear export sequence. Nuclear-retained SV40-FMRP could be released upon treatment with RNase. Further, Tap/NXF1 coimmunoprecipitated with EGFP-FMRP in an RNA-dependent manner and contained the FMR1 mRNA. To determine whether FMRP binds pre-mRNAs cotranscriptionally, we expressed hemagglutinin-SV40 FMRP in amphibian oocytes and found it, as well as endogenous Xenopus FMRP, on the active transcription units of lampbrush chromosomes. Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus. PMID:18936162

Kim, Miri; Bellini, Michel; Ceman, Stephanie

2009-01-01

58

On BC1 RNA and the fragile X mental retardation protein  

PubMed Central

The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1–FMRP model. We report that specific BC1–FMRP interactions could be documented neither in vitro nor in vivo. Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo. The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently. PMID:18184799

Iacoangeli, Anna; Rozhdestvensky, Timofey S.; Dolzhanskaya, Natalia; Tournier, Barthélémy; Schütt, Janin; Brosius, Jürgen; Denman, Robert B.; Khandjian, Edouard W.; Kindler, Stefan; Tiedge, Henri

2008-01-01

59

Identification of mdoD, an mdoG Paralog Which Encodes a Twin-Arginine-Dependent Periplasmic Protein That Controls Osmoregulated Periplasmic Glucan Backbone Structures  

PubMed Central

Osmoregulated periplasmic glucans (OPGs) of Escherichia coli are anionic and highly branched oligosaccharides that accumulate in the periplasmic space in response to low osmolarity of the medium. The glucan length, ranging from 5 to 12 glucose residues, is under strict control. Two genes that form an operon, mdoGH, govern glucose backbone synthesis. The new gene mdoD, which appears to be a paralog of mdoG, was characterized in this study. Cassette inactivation of mdoD resulted in production of OPGs with a higher degree of polymerization, indicating that OpgD, the mdoD product (according to the new nomenclature), controls the glucose backbone structures. OpgD secretion depends on the Tat secretory pathway. Orthologs of the mdoG and mdoD genes are found in various proteobacteria. Most of the OpgD orthologs exhibit a Tat-dependent secretion signal, while most of the OpgG orthologs are Sec dependent. PMID:15175282

Lequette, Yannick; Ödberg-Ferragut, Carmen; Bohin, Jean-Pierre; Lacroix, Jean-Marie

2004-01-01

60

Carbonic adsorbent AST120 retards progression of renal failure by additive effect with ACEI and protein restriction diet  

Microsoft Academic Search

Background. In order to slow the progression of chronic renal failure (CRF), a multimodal approach should be applied if the efficacy is proved. Although compelling evidence of a beneficial effect exists for the use of angiotensin-converting enzyme inhibitors (ACEIs) and low-protein diets, there is little evidence on whether carbon adsorbent has an effect on retardation of the progression of CRF.

Enyu Imai; Masaru Takenaka; Yoshitaka Isaka; Toshiki Moriyama; Yoshitaka Akagi; Jyunji Kakuchi; Takashi Fujii; Takahito Ito; Masatsugu Hori; Masaru Horio; Tatsuya Syoji; Yoshiharu Tsubakihara

2003-01-01

61

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. PMID:25049668

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

2012-01-01

62

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. PMID:23267051

Matsunami, Masatoshi; Saitou, Naruya

2013-01-01

63

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

Microsoft Academic Search

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

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

2004-01-01

64

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets  

PubMed Central

The objective of this study is to investigate the expression and distribution of heat shock protein 70 (Hsp70) in the intestine of intrauterine growth retardation (IUGR) piglets. Samples from the duodenum, prejejunum, distal jejunum, ileum, and colon of IUGR and normal-body-weight (NBW) piglets were collected at birth. The results indicated that the body and intestine weight of IUGR piglets were significantly lower than NBW piglets. The villus height and villus/crypt ratio in jejunum and ileum of IUGR piglets were significantly reduced compared to NBW piglets. These results indicated that IUGR causes abnormal gastrointestinal morphologies and gastrointestinal dysfunction. The mRNA of hsp70 was increased in prejejunum (P?protein levels of Hsp70 in prejejunum (P?

Zhong, Xiang; Zhang, Xuhui; Li, Wei

2009-01-01

65

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. PMID:20541608

Evans, Timothy L.; Mihailescu, Mihaela-Rita

2010-01-01

66

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

PubMed

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

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

2012-02-15

67

Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus  

NASA Astrophysics Data System (ADS)

The ribonucleoprotein (RNP) of the influenza A virus is responsible for the transcription and replication of viral RNA in the nucleus. These processes require interplay between host factors and RNP components. Here, we report that the Fragile X mental retardation protein (FMRP) targets influenza virus RNA synthesis machinery and facilitates virus replication both in cell culture and in mice. We demonstrate that FMRP transiently associates with viral RNP and stimulates viral RNP assembly through RNA-mediated interaction with the nucleoprotein. Furthermore, the KH2 domain of FMRP mediates its association with the nucleoprotein. A point mutation (I304N) in the KH2 domain, identified from a Fragile X syndrome patient, disrupts the FMRP-nucleoprotein association and abolishes the ability of FMRP to participate in viral RNP assembly. We conclude that FMRP is a critical host factor used by influenza viruses to facilitate viral RNP assembly. Our observation reveals a mechanism of influenza virus RNA synthesis and provides insights into FMRP functions.

Zhou, Zhuo; Cao, Mengmeng; Guo, Yang; Zhao, Lili; Wang, Jingfeng; Jia, Xue; Li, Jianguo; Wang, Conghui; Gabriel, Gülsah; Xue, Qinghua; Yi, Yonghong; Cui, Sheng; Jin, Qi; Wang, Jianwei; Deng, Tao

2014-02-01

68

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

69

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. PMID:24046358

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

2013-01-01

70

The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons  

Microsoft Academic Search

The fragile X syndrome, the leading cause of inherited mental retardation, is due to the inactivation of the fragile mental retardation 1 gene (FMR1) and the subsequent absence of its gene product FMRP. This RNA-binding protein is thought to control mRNA translation and its absence in fragile X cells leads to altera- tion in protein synthesis. In neurons, FMRP is

Laetitia Davidovic; Elias Bechara; Maud Gravel; Xavier H. Jaglin; Sandra Tremblay; Attila Sik; Barbara Bardoni; Edouard W. Khandjian

2006-01-01

71

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

SciTech Connect

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

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

2004-07-15

72

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

SciTech Connect

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. 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 {angstrom}, 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. 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.

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

2011-11-23

73

Sequential implication of the mental retardation proteins ARHGEF6 and PAK3 in spine morphogenesis  

Microsoft Academic Search

The biological mechanisms underlying the mental retardation associated with mutation of the ARHGEF6 gene, a Rac1\\/Cdc42 exchange factor, are still unknown, although defects in the plasticity of synaptic networks have been postulated. We have cloned the rat ARHGEF6 gene and investigated, using a transfection approach, its involvement in spine morphogenesis and its relationship to p21-activated kinase 3 (PAK3). We found

R. Node-Langlois; Dominique Muller; Bernadett Boda

2006-01-01

74

Functional diversification of vitamin d receptor paralogs in teleost fish after a whole genome duplication event.  

PubMed

The diversity and success of teleost fishes (Actinopterygii) has been attributed to three successive rounds of whole-genome duplication (WGD). WGDs provide a source of raw genetic material for evolutionary forces to act upon, resulting in the divergence of genes with altered or novel functions. The retention of multiple gene pairs (paralogs) in teleosts provides a unique opportunity to study how genes diversify and evolve after a WGD. This study examines the hypothesis that vitamin D receptor (VDR) paralogs (VDR? and VDR?) from two distantly related teleost orders have undergone functional divergence subsequent to the teleost-specific WGD. VDR? and VDR? paralogs were cloned from the Japanese medaka (Beloniformes) and the zebrafish (Cypriniformes). Initial transactivation studies using 1?, 25-dihydroxyvitamin D3 revealed that although VDR? and VDR? maintain similar ligand potency, the maximum efficacy of VDR? was significantly attenuated compared with VDR? in both species. Subsequent analyses revealed that VDR? and VDR? maintain highly similar ligand affinities; however, VDR? demonstrated preferential DNA binding compared with VDR?. Protein-protein interactions between the VDR paralogs and essential nuclear receptor coactivators were investigated using transactivation and mammalian two-hybrid assays. Our results imply that functional differences between VDR? and VDR? occurred early in teleost evolution because they are conserved between distantly related species. Our results further suggest that the observed differences may be associated with differential protein-protein interactions between the VDR paralogs and coactivators. We speculate that the observed functional differences are due to subtle ligand-induced conformational differences between the two paralogs, leading to divergent downstream functions. PMID:25279795

Kollitz, Erin M; Hawkins, Mary Beth; Whitfield, G Kerr; Kullman, Seth W

2014-12-01

75

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

PubMed

Fragile X syndrome is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein which forms a messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes. Recently, mRNA ligands associated with FMRP have been identified. However, the mechanism by which FMRP regulates the translation of its mRNA ligands remains unclear. MicroRNAs are small noncoding RNAs involved in translational control. Here we show that in vivo mammalian FMRP interacts with microRNAs and the components of the microRNA pathways including Dicer and the mammalian ortholog of Argonaute 1 (AGO1). Using two different Drosophila melanogaster models, we show that AGO1 is critical for FMRP function in neural development and synaptogenesis. Our results suggest that FMRP may regulate neuronal translation via microRNAs and links microRNAs with human disease. PMID:14703574

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

2004-02-01

76

Characterization of paralogous protein families in rice  

E-print Network

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 ...

Lin, Haining

77

Characterization of dFMR1, a Drosophila melanogaster Homolog of the Fragile X Mental Retardation Protein  

PubMed Central

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by loss of FMR1 gene activity due to either lack of expression or expression of a mutant form of the protein. In mammals, FMR1 is a member of a small protein family that consists of FMR1, FXR1, and FXR2. All three members bind RNA and contain sequence motifs that are commonly found in RNA-binding proteins, including two KH domains and an RGG box. The FMR1/FXR proteins also contain a 60S ribosomal subunit interaction domain and a protein-protein interaction domain which mediates homomer and heteromer formation with each family member. Nevertheless, the specific molecular functions of FMR1/FXR proteins are unknown. Here we report the cloning and characterization of a Drosophila melanogaster homolog of the mammalian FMR1/FXR gene family. This first invertebrate homolog, termed dfmr1, has a high degree of amino acid sequence identity/similarity with the defined functional domains of the FMR1/FXR proteins. The dfmr1 product binds RNA and is similar in subcellular localization and embryonic expression pattern to the mammalian FMR1/FXR proteins. Overexpression of dfmr1 driven by the UAS-GAL4 system leads to apoptotic cell loss in all adult Drosophila tissues examined. This phenotype is dependent on the activity of the KH domains. The ability to induce a dominant phenotype by overexpressing dfmr1 opens the possibility of using genetic approaches in Drosophila to identify the pathways in which the FMR1/FXR proteins function. PMID:11046149

Wan, Lili; Dockendorff, Thomas C.; Jongens, Thomas A.; Dreyfuss, Gideon

2000-01-01

78

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

PubMed Central

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

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

2010-01-01

79

Release Retardation of Model Protein on Polyelectrolyte-Coated PLGA Nano- and Microparticles  

PubMed Central

PEM capsules have been proposed for vehicles of drug microencapsulation, with the release triggered by pH, salt, magnetic field, or light. When built on another carrier encapsulating drugs, such as nanoparticles, it could provide additional release barrier to the releasing drug, providing further control to drug release. Although liposomes have received considerable attention with PEM coating for sustained drug release, similar results employing PEM built on poly(lactic-co-lycolic acid) (PLGA) particles is scant. In this work, we demonstrate that the build-up pH and polyelectrolyte pairs of PEM affect the release retardation of BSA from PLGA particles. PAH/PSS pair, the most commonly used polyelectrolyte pair, was used in comparison with PLL/DES. In addition, we also demonstrate that the release retardation effect of PEM-coated PLGA particles diminishes as the particle size increases. We attribute this to the diminishing relative thickness of the PEM coating with respect to the size of the particle as the particle size increases, reducing the diffusional resistance of the PEM. PMID:24647768

Nugraha, Chandra; Bora, Meghali; Venkatraman, Subbu S.

2014-01-01

80

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

81

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

PubMed

Individuals with fragile X syndrome (FXS) are cognitively impaired and have marked speech delays and deficits. Our goal was to characterize expression of fragile X mental retardation protein (FMRP), encoded by Fmr1 fragile X mental retardation 1 gene or transcript (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 robust nucleus of the arcopallium (RA) of post-hatch day 30 males, compared with 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. PMID:18835331

Winograd, C; Clayton, D; Ceman, S

2008-11-11

82

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. PMID:24709664

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

2014-01-01

83

Gene conversion yields novel gene combinations in paralogs of GOT1 in the copepod Tigriopus californicus  

PubMed Central

Background Gene conversion of duplicated genes can slow the divergence of paralogous copies over time but can also result in other interesting evolutionary patterns. Islands of genetic divergence that persist in the face of gene conversion can point to gene regions undergoing selection for new functions. Novel combinations of genetic variation that differ greatly from the original sequence can result from the transfer of genetic variation between paralogous genes by rare gene conversion events. Genetically divergent populations of the copepod Tigriopus californicus provide an excellent model to look at the patterns of divergence among paralogs across multiple independent evolutionary lineages. Results In this study the evolution of a set of paralogous genes encoding putative aspartate transaminase proteins (called GOT1 here) are examined in populations of the copepod T. californicus. One pair of duplicated genes, GOT1p1 and GOT1p2, has regions of high divergence between the copies in the face of apparent on-going gene conversion. The GOT1p2 gene also has unique haplotypes in two populations that appear to have resulted from a transfer of genetic variation via inter-paralog gene conversion. A second pair of duplicated genes GOT1Sr and GOT1Sd also shows evidence of gene conversion, but this gene conversion does not appear to have maintained each as a functional copy in all populations. Conclusions The patterns of conservation and sequence divergence across this set of paralogous genes among populations of T. californicus suggest that some interesting evolutionary patterns are occurring at these loci. The results for the GOT1p1/GOT1p2 paralogs illustrate how gene conversion can factor in the creation of a mosaic pattern of regions of high divergence and low divergence. When coupled with rare gene conversion events of divergent regions, this pattern can result in the formation of novel proteins differing substantially from either original protein. The evolutionary patterns across these paralogs show how gene conversion can both constrain and facilitate diversification of genetic sequences. PMID:23845062

2013-01-01

84

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

ERIC Educational Resources Information Center

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

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

2014-01-01

85

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

86

Dynamic Association of the Fragile X Mental Retardation Protein as a Messenger Ribonucleoprotein between Microtubules and Polyribosomes  

PubMed Central

The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein that regulates translation and plays essential roles in synaptic function. FMRP is bound to specific mRNA ligands, actively transported into neuronal processes in a microtubule-dependent manner, and associated with polyribosomes engaged in translation elongation. However, the biochemical relationship between FMRP–microtubule association and FMRP–polyribosome association remains elusive. Here, we report that although the majority of FMRP is incorporated into elongating polyribosomes in the soluble cytoplasm, microtubule-associated FMRP is predominantly retained in translationally dormant, polyribosome-free messenger ribonucleoprotein (mRNP) complexes. Interestingly, FMRP–microtubule association is increased when mRNPs are dynamically released from polyribosomes as a result of inhibiting translation initiation. Furthermore, the I304N mutant FMRP that fails to be incorporated into polyribosomes is associated with microtubules in mRNP particles and transported into neuronal dendrites in a microtubule-dependent, 3,5-dihydroxyphenylglycine-stimulated manner with similar kinetics to that of wild-type FMRP. Hence, polyribosome-free FMRP–mRNP complexes travel on microtubules and wait for activity-dependent translational derepression at the site of function. The dual participation of FMRP in dormant mRNPs and polyribosomes suggests distinct roles of FMRP in dendritic transport and translational regulation, two distinct phases that control local protein production to accommodate synaptic plasticity. PMID:17978095

Wang, Houping; Dictenberg, Jason B.; Ku, Li; Li, Wen; Bassell, Gary J.

2008-01-01

87

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. PMID:17589592

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

2007-01-01

88

Expression of fragile X mental retardation protein in neurons and glia of the developing and adult mouse brain.  

PubMed

Fragile X syndrome is the most common inherited form of mental retardation and autism. It is caused by a reduction or elimination of the expression of fragile X mental retardation protein (FMRP). Because fragile X syndrome is a neurodevelopmental disorder, it is important to fully document the cell type expression in the developing CNS to provide a better understanding of the molecular function of FMRP, and the pathogenesis of the syndrome. We investigated FMRP expression in the brain using double-labeling immunocytochemistry and cell type markers for neurons (NeuN), astrocytes (S100?), microglia (Iba-1), and oligodendrocyte precursor cells (NG2). The hippocampus, striatum, cingulate cortex, retrosplenial cortex, corpus callosum and cerebellum were assessed in wild-type C57/BL6 mice at postnatal days 0, 10, 20, and adult. Our results demonstrate that FMRP is ubiquitously expressed in neurons at all times and brain regions studied, except for corpus callosum where FMRP was predominantly present in astrocytes at all ages. FMRP expression in Iba-1 and NG2-positive cells was detected at postnatal day 0 and 10 and gradually decreased to very low or undetectable levels in postnatal day 20 and adult mice. Our results reveal that in addition to continuous and extensive expression in neurons in the immature and mature brain, FMRP is also present in astrocytes, oligodendrocyte precursor cells, and microglia during the early and mid-postnatal developmental stages of brain maturation. Prominent expression of FMRP in glia during these crucial stages of brain development suggests an important contribution to normal brain function, and in its absence, to the fragile X phenotype. PMID:25446451

Gholizadeh, Shervin; Halder, Sebok Kumar; Hampson, David R

2015-01-30

89

Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells.  

PubMed

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

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

2014-12-01

90

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

SciTech Connect

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

Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan)] [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan); Ogawa, Atsushi [Department of Biological Production, Akita Prefectural University, Shimosinjyou-nakano 241-438, Akita 010-0195 (Japan)] [Department of Biological Production, Akita Prefectural University, Shimosinjyou-nakano 241-438, Akita 010-0195 (Japan); Suzuki, Shunji, E-mail: suzukis@yamanashi.ac.jp [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan)] [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan)

2011-02-18

91

Fragile X mental retardation protein expression in Alzheimer’s disease  

PubMed Central

The FMR1 protein product, FMRP, is an mRNA binding protein associated with translational inhibition of target transcripts. One FMRP target is the amyloid precursor protein (APP) mRNA, and APP levels are elevated in Fmr1 KO mice. Given that elevated APP protein expression can elicit Alzheimer’s disease (AD) in patients and model systems, we evaluated whether FMRP expression might be altered in Alzheimer’s autopsy brain samples and mouse models compared to controls. In a double transgenic mouse model of AD (APP/PS1), we found no difference in FMRP expression in aged AD model mice compared to littermate controls. FMRP expression was also similar in AD and control patient frontal cortex and cerebellum samples. Fragile X-associated tremor/ataxia syndrome (FXTAS) is an age-related neurodegenerative disorder caused by expanded CGG repeats in the 5? untranslated region of the FMR1 gene. Patients experience cognitive impairment and dementia in addition to motor symptoms. In parallel studies, we measured FMRP expression in cortex and cerebellum from three FXTAS patients and found reduced expression compared to both controls and Alzheimer’s patient brains, consistent with animal models. We also find increased APP levels in cerebellar, but not cortical, samples of FXTAS patients compared to controls. Taken together, these data suggest that a decrease in FMRP expression is unlikely to be a primary contributor to Alzheimer’s disease pathogenesis. PMID:25452762

Renoux, Abigail J.; Carducci, Nicholas M.; Ahmady, Arya A.; Todd, Peter K.

2014-01-01

92

Picosecond primary structural transition of the heme is retarded after nitric oxide binding to heme proteins  

PubMed Central

We investigated the ultrafast structural transitions of the heme induced by nitric oxide (NO) binding for several heme proteins by subpicosecond time-resolved resonance Raman and femtosecond transient absorption spectroscopy. We probed the heme iron motion by the evolution of the iron-histidine Raman band intensity after NO photolysis. Unexpectedly, we found that the heme response and iron motion do not follow the kinetics of NO rebinding. Whereas NO dissociation induces quasi-instantaneous iron motion and heme doming (< 0.6 ps), the reverse process results in a much slower picosecond movement of the iron toward the planar heme configuration after NO binding. The time constant for this primary domed-to-planar heme transition varies among proteins (?30 ps for myoglobin and its H64V mutant, ?15 ps for hemoglobin, ?7 ps for dehaloperoxidase, and ?6 ps for cytochrome c) and depends upon constraints exerted by the protein structure on the heme cofactor. This observed phenomenon constitutes the primary structural transition in heme proteins induced by NO binding. PMID:20643970

Kruglik, Sergei G.; Yoo, Byung-Kuk; Franzen, Stefan; Vos, Marten H.; Martin, Jean-Louis; Negrerie, Michel

2010-01-01

93

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

94

A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P  

PubMed Central

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP–CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts. PMID:11438699

Schenck, Annette; Bardoni, Barbara; Moro, Annamaria; Bagni, Claudia; Mandel, Jean-Louis

2001-01-01

95

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. PMID:18835331

Winograd, Claudia; Clayton, David; Ceman, Stephanie

2008-01-01

96

Hypothesis: A Role for Fragile X Mental Retardation Protein in Mediating and Relieving MicroRNA-Guided Translational Repression?  

PubMed Central

MicroRNA (miRNA)-guided messenger RNA (mRNA) translational repression is believed to be mediated by effector miRNA-containing ribonucleoprotein (miRNP) complexes harboring fragile X mental retardation protein (FMRP). Recent studies documented the nucleic acid chaperone properties of FMRP and characterized its role and importance in RNA silencing in mammalian cells. We propose a model in which FMRP could facilitate miRNA assembly on target mRNAs in a process involving recognition of G quartet structures. Functioning within a duplex miRNP, FMRP may also mediate mRNA targeting through a strand exchange mechanism, in which the miRNA* of the duplex is swapped for the mRNA. Furthermore, FMRP may contribute to the relief of miRNA-guided mRNA repression through a reverse strand exchange reaction, possibly initiated by a specific cellular signal, that would liberate the mRNA for translation. Suboptimal utilization of miRNAs may thus account for some of the molecular defects in patients with the fragile X syndrome. PMID:17057359

Plante, Isabelle; Provost, Patrick

2006-01-01

97

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

PubMed

Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment. PMID:25253649

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

2014-09-25

98

Contrasted patterns of selective pressure in three recent paralogous gene pairs in the Medicago genus (L.)  

PubMed Central

Background Gene duplications are a molecular mechanism potentially mediating generation of functional novelty. However, the probabilities of maintenance and functional divergence of duplicated genes are shaped by selective pressures acting on gene copies immediately after the duplication event. The ratio of non-synonymous to synonymous substitution rates in protein-coding sequences provides a means to investigate selective pressures based on genic sequences. Three molecular signatures can reveal early stages of functional divergence between gene copies: change in the level of purifying selection between paralogous genes, occurrence of positive selection, and transient relaxed purifying selection following gene duplication. We studied three pairs of genes that are known to be involved in an interaction with symbiotic bacteria and were recently duplicated in the history of the Medicago genus (Fabaceae). We sequenced two pairs of polygalacturonase genes (Pg11-Pg3 and Pg11a-Pg11c) and one pair of auxine transporter-like genes (Lax2-Lax4) in 17 species belonging to the Medicago genus, and sought for molecular signatures of differentiation between copies. Results Selective histories revealed by these three signatures of molecular differentiation were found to be markedly different between each pair of paralogs. We found sites under positive selection in the Pg11 paralogs while Pg3 has mainly evolved under purifying selection. The most recent paralogs examined Pg11a and Pg11c, are both undergoing positive selection and might be acquiring new functions. Lax2 and Lax4 paralogs are both under strong purifying selection, but still underwent a temporary relaxation of purifying selection immediately after duplication. Conclusions This study illustrates the variety of selective pressures undergone by duplicated genes and the effect of age of the duplication. We found that relaxation of selective constraints immediately after duplication might promote adaptive divergence. PMID:23025552

2012-01-01

99

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

PubMed Central

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

Gatto, Cheryl L.; Broadie, Kendal

2011-01-01

100

Paralog, a Control Mutant in DROSOPHILA MELANOGASTER  

PubMed Central

The genetic properties of a pleiotropic mutant mapping at 1.4 ± 0.1 in band 3B3 or its adjacent interbands on the X chromosome are described. The mutation is expressed autonomously in germ line cells, where it is recessive and has antimorphic properties. At 29°, the mutation blocks oocyte differentiation, causing female sterility. At lower temperatures, it disturbs the maternal information in the egg; as a result, the progeny lack germ line cells (grandchildless phenotype) and exhibit defects of the cuticular pattern. The mutation is also expressed in somatic cells through zygotic interactions with neighboring regions, including 3A2, 3A3 (zeste), 3C1–2, 3C4 and 3C6–8 (Notch). We interpret the data by postulating that the expression of sets of dispersed genes might be controlled by the local topology of the chromosome, itself constrained by pairing of dispersed repeated elements. We call the mutation paralog. PMID:6809528

Thierry-Mieg, Danielle

1982-01-01

101

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

PubMed

VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation. PMID:21277284

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

2011-02-18

102

Evolutionary Acquisition of Cysteines Determines FOXO Paralog-Specific Redox Signaling  

PubMed Central

Abstract Reduction–oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor. Aims: In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs. Results: We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8. Innovation and Conclusion: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling. Antioxid. Redox Signal. 22, 15–28. PMID:25069953

Putker, Marrit; Vos, Harmjan R.; van Dorenmalen, Kim; de Ruiter, Hesther; Duran, Ana G.; Snel, Berend; Burgering, Boudewijn M.T.; Vermeulen, Michiel

2015-01-01

103

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

104

Evolution of MIR168 paralogs in Brassicaceae  

PubMed Central

Background In plants, expression of ARGONAUTE1 (AGO1), the catalytic subunit of the RNA-Induced Silencing Complex responsible for post-transcriptional gene silencing, is controlled through a feedback loop involving the miR168 microRNA. This complex auto-regulatory loop, composed of miR168-guided AGO1-catalyzed cleavage of AGO1 mRNA and AGO1-mediated stabilization of miR168, was shown to ensure the maintenance of AGO1 homeostasis that is pivotal for the correct functioning of the miRNA pathway. Results We applied different approaches to studying the genomic organization and the structural and functional evolution of MIR168 homologs in Brassicaeae. A whole genome comparison of Arabidopsis and poplar, phylogenetic footprinting and phylogenetic reconstruction were used to date the duplication events originating MIR168 homologs in these genomes. While orthology was lacking between Arabidopsis and poplar MIR168 genes, we successfully isolated orthologs of both loci present in Arabidopsis (MIR168a and MIR168b) from all the Brassicaceae species analyzed, including the basal species Aethionema grandiflora, thus indicating that (1) independent duplication events took place in Arabidopsis and poplar lineages and (2) the origin of MIR168 paralogs predates both the Brassicaceae radiation and the Arabidopsis alpha polyploidization. Different phylogenetic footprints, corresponding to known functionally relevant regions (transcription starting site and double-stranded structures responsible for microRNA biogenesis and function) or for which functions could be proposed, were found to be highly conserved among MIR168 homologs. Comparative predictions of the identified microRNAs also indicate extreme conservation of secondary structure and thermodynamic stability. Conclusion We used a comparative phylogenetic footprinting approach to identify the structural and functional constraints that shaped MIR168 evolution in Brassicaceae. Although their duplication happened at least 40 million years ago, we found evidence that both MIR168 paralogs have been maintained throughout the evolution of Brassicaceae, most likely functionally as indicated by the extremely high conservation of functionally relevant regions, predicted secondary structure and thermodynamic profile. Interestingly, the expression patterns observed in Arabidopsis indicate that MIR168b underwent partial subfunctionalization as determined by the experimental characterization of its expression pattern provided in this study. We found further evolutionary evidence that pre-miR168 lower stem (the RNA-duplex structure adjacent to the miR-miR* stem) is significantly longer than animal lower stems and probably plays a relevant role in multi-step miR168 biogenesis. PMID:19309501

Gazzani, Silvia; Li, Mingai; Maistri, Silvia; Scarponi, Eliana; Graziola, Michele; Barbaro, Enrico; Wunder, Jörg; Furini, Antonella; Saedler, Heinz; Varotto, Claudio

2009-01-01

105

Functional specialization of chordate CDK1 paralogs during oogenic meiosis.  

PubMed

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

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

2015-03-19

106

Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major  

PubMed Central

Background Leishmania major, a protozoan parasite, is the causative agent of cutaneous leishmaniasis. Due to the development of resistance against the currently available anti-leishmanial drugs, there is a growing need for specific inhibitors and novel drug targets. In this regards, aminoacyl tRNA synthetases, the linchpins of protein synthesis, have received recent attention among the kinetoplastid research community. This is the first comprehensive survey of the aminoacyl tRNA synthetases, their paralogs and other associated proteins from L. major. Results A total of 26 aminoacyl tRNA synthetases were identified using various computational and bioinformatics tools. Phylogenetic analysis and domain architectures of the L. major aminoacyl tRNA synthetases suggest a probable archaeal/eukaryotic origin. Presence of additional domains or N- or C-terminal extensions in 11 aminoacyl tRNA synthetases from L. major suggests possibilities such as additional tRNA binding or oligomerization or editing activity. Five freestanding editing domains were identified in L. major. Domain assignment revealed a novel asparagine tRNA synthetase paralog, asparagine synthetase A which has been so far reported from prokaryotes and archaea. Conclusions A comprehensive bioinformatic analysis revealed 26 aminoacyl tRNA synthetases and five freestanding editing domains in L. major. Identification of two EMAP (endothelial monocyte-activating polypeptide) II-like proteins similar to human EMAP II-like proteins suggests their participation in multisynthetase complex formation. While the phylogeny of tRNA synthetases suggests a probable archaeal/eukaryotic origin, phylogeny of asparagine synthetase A strongly suggests a bacterial origin. The unique features identified in this work provide rationale for designing inhibitors against parasite aminoacyl tRNA synthetases and their paralogs. PMID:23151081

2012-01-01

107

Optical retarder system with programmable spectral retardance.  

PubMed

An optical system that works as a retarder waveplate with programmable spectral retardance is proposed. The system is based on a pixelated liquid crystal on silicon (LCoS) spatial light modulator (SLM). The input light beam is spectrally dispersed and different spectral components are projected onto different pixels of the LCoS-SLM. A different retardance is then addressed for each pixel, adapted to the incoming wavelength. Light reflected from the SLM is then recombined by the same setup. In this way a programmable polarization spectrum can be encoded. We illustrate the broadband characterization that is required for proper use of the system. Then several examples are shown, including spectral compensation to yield retarders with constant retardance, retarders with abrupt changes in the spectral retardance function, or bandpass variable retarder filters. The system is also demonstrated to provide programmable light spectrum generation. PMID:25360908

Moreno, Ignacio; Carrión, José V; Martínez, José Luis; García-Martínez, Pascuala; Sánchez-López, María M; Campos, Juan

2014-10-01

108

In Vitro Studies of the Uridylylation of the Three PII Protein Paralogs from Rhodospirillum rubrum: the Transferase Activity of R. rubrum GlnD Is Regulated by  Ketoglutarate and Divalent Cations but Not by Glutamine  

Microsoft Academic Search

PII proteins have been shown to be key players in the regulation of nitrogen fixation and ammonia assimilation in bacteria. The mode by which these proteins act as signals is by being in either a form modified by UMP or the unmodified form. The modification, as well as demodification, is catalyzed by a bifunctional enzyme encoded by the glnD gene.

Anders Jonsson; Stefan Nordlund

2007-01-01

109

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

PubMed Central

Background Fragile X syndrome is caused by loss of function of the fragile X mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. Methods In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and ?-aminobutyric acid (GABA) A receptor ?3 (GABR?3), as well as glial fibrillary acidic protein (GFAP). Results We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABR?3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. Conclusion These changes may be responsible for cognitive deficits and seizure disorder in people with autism. PMID:21548960

2011-01-01

110

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

PubMed Central

Although cyanobacteria produce a wide range of natural toxins that impact aquatic organisms, food webs and water quality, the mechanisms of toxicity are still insufficiently understood. Here, we implemented a whole-genome expression microarray to identify pathways, gene networks and paralogous gene families responsive to Microcystis stress in Daphnia pulex. Therefore, neonates of a sensitive isolate were given a diet contaminated with Microcystis to contrast with those given a control diet for sixteen days. The microarray revealed 2247 differentially expressed (DE) genes (7.6% of the array) in response to Microcystis, of which 17% are lineage specific( i.e., these genes have no detectable homology to any other gene in currently available databases) and 49% are gene duplicates (paralogs). We identified four pathways/gene networks and eight paralogous gene families affected by Microcystis. Differential regulation of the ribosome, including 3 paralogous gene families encoding 40S, 60S and mitochondrial ribosomal proteins, suggests an impact of Microcystis on protein synthesis of D. pulex. In addition, differential regulation of the oxidative phosphorylation pathway (including the NADH ubquinone oxidoreductase gene family) and the trypsin paralogous gene family (a major component of the digestive system in D. pulex) could explain why fitness is reduced based on energy budget considerations. PMID:22799445

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

2013-01-01

111

Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings.  

PubMed

Protein-loaded (bovine serum albumin (BSA) or luciferase) poly(vinyl alcohol) (PVA) nanofibers were obtained by electrospinning. Poly(p-xylylene) (PPX, also coined as parylene) coated PVA/BSA nanofibers were prepared by chemical vapor deposition (CVD). The release of BSA from PVA nanofibers under physiological conditions was monitored by absorption spectroscopy. Burst release of BSA was noted with uncoated PVA nanofibers. In contrast, PPX-coated nanofibers exhibited a significantly retarded release of BSA depending on the coating thickness of PPX (ranging from 40 to 300 nm). Luciferase was used here as model enzyme, which after electrospinning retained its enzyme activity. This preservation of enzyme activity and the continuous release of the intact enzyme from the immersed fibers meets a fundamental prerequisite for the application of enzymes or other sensitive agents released from electrospun nanofibers under physiological conditions. PMID:15877368

Zeng, Jun; Aigner, Achim; Czubayko, Frank; Kissel, Thomas; Wendorff, Joachim H; Greiner, Andreas

2005-01-01

112

The role of two LEAFY paralogs from Idahoa scapigera (Brassicaceae) in the evolution of a derived plant architecture.  

PubMed

Idahoa scapigera produces solitary flowers in the axils of rosette leaves without elongation of the shoot axis, a rosette-flowering architecture. Previous work with one of the two I. scapigera LFY paralogs, IscLFY1, showed that this gene caused aerial flowering rosettes in Arabidopsis thaliana. In this paper, we report that after three generations IscLFY1 transgenic lines are phenotypically indistinguishable from wild-type Arabidopsis, indicating that IscLFY1 protein is able to replace normal LFY function. Additionally, we found that ectopic LFY expression late in development can phenocopy aspects of the aerial rosette phenotype, suggesting that shoot compression caused by IscLFY1 could be caused by localized overexpression of a functional IscLFY protein. We also characterized the expression and function of the second I. scapigera LFY paralog, IscLFY2, in A. thaliana. In contrast to IscLFY1, this paralog was expressed in floral meristems and the shoot apical meristem (SAM). In I. scapigera, LFY-specific antibodies detected high protein levels in developing flowers but not in the apex, suggesting trans-regulatory differences between I. scapigera and A. thaliana. Most IscLFY2 transgenic A. thaliana plants were indistinguishable from wild type, but in a minority of lines the SAM was converted to a terminal flower as would be expected from the reporter-expression pattern. Taken together these results show that both I. scapigera paralogs have conserved LFY function, both proteins can rescue lfy and both can modify inflorescence architecture in an A. thaliana background: either by affecting internode elongation (IscLFY1) or by causing homeotic conversion of shoots into flowers (IscLFY2). PMID:17559504

Sliwinski, Marek K; Bosch, Justin A; Yoon, Ho-Sung; Balthazar, Maria von; Baum, David A

2007-07-01

113

Ancestral paralogs and pseudoparalogs and their role in the emergence of the eukaryotic cell  

Microsoft Academic Search

Gene duplication is a crucial mechanism of evolu- tionary innovation. A substantial fraction of euka- ryotic genomes consists of paralogous gene families. We assess the extent of ancestral paralogy, which dates back to the last common ancestor of all eukaryotes, and examine the origins of the ancestral paralogs and their potential roles in the emergence of the eukaryotic cell complexity.

Kira S. Makarova; Yuri I. Wolf; Sergey L. Mekhedov; Boris G. Mirkin; Eugene V. Koonin

2005-01-01

114

Paralogous stellate and Su(Ste) repeats: evolution and ability to silence a reporter gene.  

PubMed

The X-linked Stellate repeats, encoding a putative regulatory subunit of protein kinase CK2, are expressed in XO male testes. The Y-linked, testes-expressed paralogous Su(Ste) repeats are thought to be suppressors of Stellate transcription. The unique, testis-expressed euchromatic gene was suggested to be an ancestor of the both types of amplified paralogous repeats. A Su(Ste)-like orphon was localized on a Y chromosome, outside of the Su(Ste) cluster. Several diagnostic molecular markers peculiar for the both types of diverged Stellate and Su(Ste) units were detected in the orphon sequence. The orphon was suggested to be a close relative of the immediate ancestor of both types of paralogous repeats which initiated evolution on the Y chromosome. Selection pressure on the level of translation was shown as a driving force in the evolution of Su(Ste) repeats, which are considered as more ancient derivatives of the ancestor euchromatic gene than Stellate repeats. In a vicinity of 12E Stellate cluster the undamaged, recently originated euchromatic Stellate orphon was found at 12D, providing the poly(A) signal for the bendless gene. P-element mediated transformations reveal that the fragments of cloned Stellate and Su(Ste) clusters are able to induce variegation of a reporter mini-white gene. The observed variegation phenomenon has peculiar features: a significant increase of trans-activation of a reporter mini-white gene in homozygous state; absence of effects of several conventional modifiers of position effect variegation (PEV) and independence of a severity of variegation on a distance between insertion and centromere region. PMID:11293788

Gvozdev, V A; Kogan, G L; Tulin, A A; Aravin, A A; Naumova, N M; Shevelyov, Y Y

2000-01-01

115

Mildly Retarded Adults: Their Attitudes Toward Retardation  

ERIC Educational Resources Information Center

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

Gan, Jennifer; And Others

1977-01-01

116

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

PubMed

The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the FMR1 gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain and nonneuronal cells. During brain development, FMRP controls the expression of key molecules involved in receptor signaling, cytoskeleton remodeling, protein synthesis and, ultimately, spine morphology. Symptoms associated with FXS include neurodevelopmental delay, cognitive impairment, anxiety, hyperactivity, and autistic-like behavior. Twenty years ago the first Fmr1 KO mouse to study FXS was generated, and several years later other key models including the mutant Drosophila melanogaster, dFmr1, have further helped the understanding of the cellular and molecular causes behind this complex syndrome. Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities. PMID:25227249

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

2014-10-01

117

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. 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

118

Fragile X Mental Retardation Protein is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b  

PubMed Central

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

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

2012-01-01

119

NADPH-cytochrome P450 reductase: molecular cloning and functional characterization of two paralogs from Withania somnifera (L.) dunal.  

PubMed

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. PMID:23437311

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

2013-01-01

120

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. PMID:23437311

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

2013-01-01

121

Introduction to Mental Retardation  

ERIC Educational Resources Information Center

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

Arc of the United States, 2004

2004-01-01

122

Reconstructing the Evolutionary History of Paralogous APETALA1/FRUITFULL-Like Genes in Grasses (Poaceae)  

PubMed Central

Gene duplication is an important mechanism for the generation of evolutionary novelty. Paralogous genes that are not silenced may evolve new functions (neofunctionalization) that will alter the developmental outcome of preexisting genetic pathways, partition ancestral functions (subfunctionalization) into divergent developmental modules, or function redundantly. Functional divergence can occur by changes in the spatio-temporal patterns of gene expression and/or by changes in the activities of their protein products. We reconstructed the evolutionary history of two paralogous monocot MADS-box transcription factors, FUL1 and FUL2, and determined the evolution of sequence and gene expression in grass AP1/FUL-like genes. Monocot AP1/FUL-like genes duplicated at the base of Poaceae and codon substitutions occurred under relaxed selection mostly along the branch leading to FUL2. Following the duplication, FUL1 was apparently lost from early diverging taxa, a pattern consistent with major changes in grass floral morphology. Overlapping gene expression patterns in leaves and spikelets indicate that FUL1 and FUL2 probably share some redundant functions, but that FUL2 may have become temporally restricted under partial subfunctionalization to particular stages of floret development. These data have allowed us to reconstruct the history of AP1/FUL-like genes in Poaceae and to hypothesize a role for this gene duplication in the evolution of the grass spikelet. PMID:16816429

Preston, Jill C.; Kellogg, Elizabeth A.

2006-01-01

123

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

PubMed Central

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

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

2013-01-01

124

Unique gene structure and paralogy define the 7D-cadherin family.  

PubMed

Cadherins are Ca2+-dependent transmembrane glycoproteins crucial for cell-cell adhesion in vertebrates and invertebrates. Classification of this superfamily due to their phylogenetic relationship is currently restricted to three major subfamilies: classical, desmosomal and protocadherins. Here we report evidence for a common phylogenetic origin of the kidney-specific Ksp- (Cdh16) and the intestine-specific LI-cadherin (Cdh17). Both genes consist of 18 exons and the positions of their exon-intron boundaries as well as their intron phases are perfectly conserved. We found an extensive paralogy of more than 40 megabases in mammals as well as teleost fish species encompassing the Ksp- and LI-cadherin genes. A comparable paralogy was not detected for other cadherin gene loci. These findings suggest that the Ksp- and LI-cadherin genes originated by chromosomal duplication early during vertebrate evolution and support our assumption that both proteins are paralogues within a separate cadherin family that we have termed 7D-cadherins. PMID:16791429

Wendeler, M W; Jung, R; Himmelbauer, H; Gessner, R

2006-07-01

125

Mental Retardation and Developmental Disabilities  

E-print Network

Mental Retardation and Developmental Disabilities (MRDD) Branch NICHD Report to the NACHHD ..................................................................................................................... 15 OTHER MENTAL RETARDATION CONDITIONS

Rau, Don C.

126

S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade*S?  

PubMed Central

Fragile X syndrome is a common form of cognitive deficit caused by the functional absence of fragile X mental retardation protein (FMRP), a dendritic RNA-binding protein that represses translation of specific messages. Although FMRP is phosphorylated in a group I metabotropic glutamate receptor (mGluR) activity-dependent manner following brief protein phosphatase 2A (PP2A)-mediated dephosphorylation, the kinase regulating FMRP function in neuronal protein synthesis is unclear. Here we identify ribosomal protein S6 kinase (S6K1) as a major FMRP kinase in the mouse hippocampus, finding that activity-dependent phosphorylation of FMRP by S6K1 requires signaling inputs from mammalian target of rapamycin (mTOR), ERK1/2, and PP2A. Further, the loss of hippocampal S6K1 and the subsequent absence of phospho-FMRP mimic FMRP loss in the increased expression of SAPAP3, a synapse-associated FMRP target mRNA. Together these data reveal a S6K1-PP2A signaling module regulating FMRP function and place FMRP phosphorylation in the mGluR-triggered signaling cascade required for protein-synthesis-dependent synaptic plasticity. PMID:18474609

Narayanan, Usha; Nalavadi, Vijayalaxmi; Nakamoto, Mika; Thomas, George; Ceman, Stephanie; Bassell, Gary J.; Warren, Stephen T.

2008-01-01

127

S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade.  

PubMed

Fragile X syndrome is a common form of cognitive deficit caused by the functional absence of fragile X mental retardation protein (FMRP), a dendritic RNA-binding protein that represses translation of specific messages. Although FMRP is phosphorylated in a group I metabotropic glutamate receptor (mGluR) activity-dependent manner following brief protein phosphatase 2A (PP2A)-mediated dephosphorylation, the kinase regulating FMRP function in neuronal protein synthesis is unclear. Here we identify ribosomal protein S6 kinase (S6K1) as a major FMRP kinase in the mouse hippocampus, finding that activity-dependent phosphorylation of FMRP by S6K1 requires signaling inputs from mammalian target of rapamycin (mTOR), ERK1/2, and PP2A. Further, the loss of hippocampal S6K1 and the subsequent absence of phospho-FMRP mimic FMRP loss in the increased expression of SAPAP3, a synapse-associated FMRP target mRNA. Together these data reveal a S6K1-PP2A signaling module regulating FMRP function and place FMRP phosphorylation in the mGluR-triggered signaling cascade required for protein-synthesis-dependent synaptic plasticity. PMID:18474609

Narayanan, Usha; Nalavadi, Vijayalaxmi; Nakamoto, Mika; Thomas, George; Ceman, Stephanie; Bassell, Gary J; Warren, Stephen T

2008-07-01

128

Effect of nitrogen and zinc fertilization and plant growth retardants on cottonseed, protein, oil yields, and oil properties  

Microsoft Academic Search

The increase in the population in Egypt makes it imperative to explore promising approaches to increase food supply, including\\u000a protein and oil, to meet the needs of the Egyptian people. Cotton is the principal crop of Egyptian agriculture. It is grown\\u000a mainly for its fiber, but cottonseed products are also of economic importance. Cottonseed is presently the main source of

Zakaria M. Sawan; Saeb A. Hafez; Ahmed E. Basyony

2001-01-01

129

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

PubMed Central

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

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

2014-01-01

130

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

131

Gene conversion homogenizes the CMT1A paralogous repeats  

E-print Network

pathogenic microdeletions (caus- ing Smith-Magenis Syndrome) and microduplications [6]. Inverted paralogous repeats are responsible for the in- version of a portion of the factor VIII gene that causes he- mophilia [7]. Published: 11 December 2001 BMC Genomics... reciprocal of the Smith- Magenis microdeletion. Nat. Genet 2000, 24:84-87 7. Lakich D, Kazazian HH, Antonarakis SE, Gitschier J: Inversions Dis- rupting the Factor-VIII Gene Are a Common-Cause of Se- vere Hemophilia-A. Nature Genetics 1993, 5:236-241 8...

Hurles, Matthew E

2001-12-11

132

THE MENTALLY RETARDED CHILD.  

ERIC Educational Resources Information Center

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

LEVINSON, ABRAHAM

133

Brominated Flame Retardants  

EPA Science Inventory

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

134

Therapeutic implications of the mGluR theory of fragile X mental retardation  

E-print Network

Review Therapeutic implications of the mGluR theory of fragile X mental retardation M. F. Bear mGluR) activ- ation are exaggerated in the absence of the fragile X mental retardation protein. The fragile X mental retardation protein (FMRP) has attracted considerable interest as a potential regulator

Bear, Mark

135

Recessive cancer genes engage in negative genetic interactions with their functional paralogs.  

PubMed

Cancer genetic heterogeneity offers a wide repertoire of molecular determinants to be screened as therapeutic targets. Here, we identify potential anticancer targets by exploiting negative genetic interactions between genes with driver loss-of-function mutations (recessive cancer genes) and their functionally redundant paralogs. We identify recessive genes with additional copies and experimentally test our predictions on three paralogous pairs. We confirm digenic negative interactions between two cancer genes (SMARCA4 and CDH1) and their corresponding paralogs (SMARCA2 and CDH3). Furthermore, we identify a trigenic negative interaction between the cancer gene DNMT3A, its functional paralog DNMT3B, and a third gene, DNMT1, which encodes the only other human DNA-methylase domain. Although our study does not exclude other causes of synthetic lethality, it suggests that functionally redundant paralogs of cancer genes could be targets in anticancer therapy. PMID:24360954

D'Antonio, Matteo; Guerra, Rosalinda F; Cereda, Matteo; Marchesi, Stefano; Montani, Francesca; Nicassio, Francesco; Di Fiore, Pier Paolo; Ciccarelli, Francesca D

2013-12-26

136

Litter-Spinning Retarders  

NASA Technical Reports Server (NTRS)

Aerodynamic plates stop litter from spinning during hoisting by helicopter. Features of proposed litter-spinning retarders include convenience of deployment and independence from ground restraint. Retarder plate(s) folded flat against bottom of litter during storage or while litter is loaded. Plate(s) held in storage position by latch that releases manually or automatically as litter is hoisted. Upon release, springs move plates into deployed position.

Wilson, John C.

1995-01-01

137

Characterization of paralogous and orthologous members of the superoxide dismutase gene family from genera of the halophilic archaebacteria.  

PubMed

Four species representing three genera of halophilic archaebacteria were examined for the presence of genomic sequences that encode proteins of the superoxide dismutase family. Three species, Halobacterium cutirubrum, Halobacterium sp. strain GRB, and Haloferax volcanii, contain duplicated (paralogous) genes of the sod family; a fourth species, Haloarcula marismortui, contains only a single gene. These seven genes were cloned and sequenced, and their transcripts were characterized by Northern (RNA) hybridization, S1 nuclease protection, and primer extension. The expression of one of the two genes in H. cutirubrum, Halobacterium sp. strain GRB, and Haloferax volcanii was shown to be elevated in the presence of paraquat, a generator of superoxide radicals. The other genes, including the single gene from Haloarcula marismortui, exhibited no elevated expression in the presence of paraquat. The 5' and 3' flanking regions of all the genes contain recognizable promoter and terminator elements that are appropriately positioned relative to the 5' and 3' transcript end sites. Between genera, the orthologous paraquat-responsive genes exhibit no sequence similarity in either their 5' or 3' flanking regions, whereas the orthologous nonresponsive genes exhibit limited sequence similarity but only in the 5' flanking region. Within the coding region, the two paralogous genes of Haloferax volcanii are virtually identical (99.5%) despite the absence of similarity in the flanking regions. In contrast, the paralogous genes of H. cutirubrum and Halobacterium sp. strain GRB are only about 87% identical. In the alignment of all seven sequences, there are nine codon positions where both the TCN and AGY serine codons are utilized; some or all of these may well be examples of convergent evolution. PMID:8449865

Joshi, P; Dennis, P P

1993-03-01

138

Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs  

PubMed Central

Background Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. Results We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs’ substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. Conclusions Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles. Reviewers This article has been reviewed by Dr. Jia Zeng (nominated by Dr. I. King Jordan), Dr. Fyodor Kondrashov and Dr. Yuri Wolf. PMID:24438455

2014-01-01

139

Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation  

E-print Network

Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation Mei mental retardation protein (FMRP) gives rise to fragile X syndrome, the most common form of inherited mental retardation. A fragile X knockout (fmr1 KO) mouse has been described that has some

Smith, Carolyn Beebe

140

The mGluR theory of fragile X mental retardation  

E-print Network

The mGluR theory of fragile X mental retardation Mark F. Bear1 , Kimberly M. Huber2 and Stephen T-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP frequent inherited cause of mental retardation and an identified cause of autism. Fragile X is the most

Bear, Mark

141

Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice  

E-print Network

with 3p-syndrome mental retardation who are haploinsuf- ficient for WRP MEGAP, a component of the WAVE-1-syndrome mental retardation (19). Although WASp WAVE scaffolding proteins share a conserved modular structureLoss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice Scott H

Scott, John D.

142

Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains  

E-print Network

Structure Article Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains of Fragile X Mental Retardation Protein Roberto Valverde,1 Irina Pozdnyakova,1 Tommi Kajander,1,3 Janani.06.022 SUMMARY Fragile X syndrome is the most common form of inherited mental retardation in humans

Regan, Lynne

143

Altered synaptic plasticity in a mouse model of fragile X mental retardation  

E-print Network

Altered synaptic plasticity in a mouse model of fragile X mental retardation Kimberly M. Huber syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochem- ical evidence indicates

Bear, Mark

144

Diversification of transcription factor paralogs via noncanonical modularity in C2H2 zinc finger DNA binding.  

PubMed

A major challenge in obtaining a full molecular description of evolutionary adaptation is to characterize how transcription factor (TF) DNA-binding specificity can change. To identify mechanisms of TF diversification, we performed detailed comparisons of yeast C2H2 ZF proteins with identical canonical recognition residues that are expected to bind the same DNA sequences. Unexpectedly, we found that ZF proteins can adapt to recognize new binding sites in a modular fashion whereby binding to common core sites remains unaffected. We identified two distinct mechanisms, conserved across multiple Ascomycota species, by which this molecular adaptation occurred. Our results suggest a route for TF evolution that alleviates negative pleiotropic effects by modularly gaining new binding sites. These findings expand our current understanding of ZF DNA binding and provide evidence for paralogous ZFs utilizing alternate modes of DNA binding to recognize unique sets of noncanonical binding sites. PMID:25042805

Siggers, Trevor; Reddy, Jessica; Barron, Brian; Bulyk, Martha L

2014-08-21

145

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. PMID:23915312

2013-01-01

146

Monkey Retardate Learning Analysis  

ERIC Educational Resources Information Center

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

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

1978-01-01

147

Epidemiology of Mental Retardation.  

ERIC Educational Resources Information Center

Prevalence data on mental retardation is presented including international estimates on general prevalence, age directions, geographical variations within the United States, racial and ethnic variations, economic class distributions, family variations, and population distribution in institutions. Statistics are also provided in areas of specific…

Heber, Rick

148

DEATH AND MENTALLY RETARDED PERSONS  

E-print Network

Special images associated with the concept ofdeath are applied to people who are mentally retarded. The images reflect, and are reflected in, social attitudes which often lead to alienating expertences for retarded persons. These experiences...

Evans, Daryl

1981-01-01

149

Assessment of complement C4 gene copy number using the paralog ratio test.  

PubMed

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 throughput 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. PMID:20506482

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

2010-07-01

150

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. PMID:20506482

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

151

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

152

The paralogous pairs of genes involved in clavulanic acid and clavam metabolite biosynthesis are differently regulated in Streptomyces clavuligerus.  

PubMed

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

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

2004-09-01

153

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

PubMed

Phylogenomic studies based on hundreds of genes derived from expressed sequence tags libraries are increasingly used to reveal the phylogeny of taxa. A prerequisite for these studies is the assignment of genes into clusters of orthologous sequences. Sophisticated methods of orthology prediction are used in such analyses, but it is rarely assessed whether paralogous sequences have been erroneously grouped together as orthologous sequences after the prediction, and whether this had an impact on the phylogenetic reconstruction using a super-matrix approach. Herein, I tested the impact of paralogous sequences on the reconstruction of annelid relationships based on phylogenomic datasets. Using single-partition analyses, screening for bootstrap support, blast searches and pruning of sequences in the supermatrix, wrongly assigned paralogous sequences were found in eight partitions and the placement of five taxa (the annelids Owenia, Scoloplos, Sthenelais and Eurythoe and the nemertean Cerebratulus) including the robust bootstrap support could be attributed to the presence of paralogous sequences in two partitions. Excluding these sequences resulted in a different, weaker supported placement for these taxa. Moreover, the analyses revealed that paralogous sequences impacted the reconstruction when only a single taxon represented a previously supported higher taxon such as a polychaete family. One possibility of a priori detection of wrongly assigned paralogous sequences could combine 1) a screening of single-partition analyses based on criteria such as nodal support or internal branch length with 2) blast searches of suspicious cases as presented herein. Also possible are a posteriori approaches in which support for specific clades is investigated by comparing alternative hypotheses based on differences in per-site likelihoods. Increasing the sizes of EST libraries will also decrease the likelihood of wrongly assigned paralogous sequences, and in the case of orthology prediction methods like HaMStR it is likewise decreased by using more than one reference taxon. PMID:23667537

Struck, Torsten H

2013-01-01

154

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. PMID:23667537

Struck, Torsten H.

2013-01-01

155

glucosylphosphatidylinositol (GPI)-anchored protein expressed  

E-print Network

, the paralogs of LORELEI, SETH1 and SETH2, encode GPI-anchored proteins in pollen vegetative cells., Grossniklaus, U., and Twell, D. (2004). SETH1 and SETH2, two components of the glycosylphosphatidylinositol

156

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.

157

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

158

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

PubMed Central

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

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

2014-01-01

159

Identical substitutions in magnesium chelatase paralogs result in chlorophyll-deficient soybean mutants.  

PubMed

The soybean [Glycine max (L.) Merr.] chlorophyll-deficient line MinnGold is a spontaneous mutant characterized by yellow foliage. Map-based cloning and transgenic complementation revealed that the mutant phenotype is caused by a nonsynonymous nucleotide substitution in the third exon of a Mg-chelatase subunit gene (ChlI1a) on chromosome 13. This gene was selected as a candidate for a different yellow foliage mutant, T219H (Y11y11), that had been previously mapped to chromosome 13. Although the phenotypes of MinnGold and T219H are clearly distinct, sequencing of ChlI1a in T219H identified a different nonsynonymous mutation in the third exon, only six base pairs from the MinnGold mutation. This information, along with previously published allelic tests, were used to identify and clone a third yellow foliage mutation, CD-5, which was previously mapped to chromosome 15. This mutation was identified in the ChlI1b gene, a paralog of ChlI1a. Sequencing of the ChlI1b allele in CD-5 identified a nonsynonymous substitution in the third exon that confers an identical amino acid change as the T219H substitution at ChlI1a. Protein sequence alignments of the two Mg-chelatase subunits indicated that the sites of amino acid modification in MinnGold, T219H, and CD-5 are highly conserved among photosynthetic species. These results suggest that amino acid alterations in this critical domain may create competitive inhibitory interactions between the mutant and wild-type ChlI1a and ChlI1b proteins. PMID:25452420

Campbell, Benjamin W; Mani, Dhananjay; Curtin, Shaun J; Slattery, Rebecca A; Michno, Jean-Michel; Ort, Donald R; Schaus, Philip J; Palmer, Reid G; Orf, James H; Stupar, Robert M

2014-01-01

160

Identical Substitutions in Magnesium Chelatase Paralogs Result in Chlorophyll-Deficient Soybean Mutants  

PubMed Central

The soybean [Glycine max (L.) Merr.] chlorophyll-deficient line MinnGold is a spontaneous mutant characterized by yellow foliage. Map-based cloning and transgenic complementation revealed that the mutant phenotype is caused by a nonsynonymous nucleotide substitution in the third exon of a Mg-chelatase subunit gene (ChlI1a) on chromosome 13. This gene was selected as a candidate for a different yellow foliage mutant, T219H (Y11y11), that had been previously mapped to chromosome 13. Although the phenotypes of MinnGold and T219H are clearly distinct, sequencing of ChlI1a in T219H identified a different nonsynonymous mutation in the third exon, only six base pairs from the MinnGold mutation. This information, along with previously published allelic tests, were used to identify and clone a third yellow foliage mutation, CD-5, which was previously mapped to chromosome 15. This mutation was identified in the ChlI1b gene, a paralog of ChlI1a. Sequencing of the ChlI1b allele in CD-5 identified a nonsynonymous substitution in the third exon that confers an identical amino acid change as the T219H substitution at ChlI1a. Protein sequence alignments of the two Mg-chelatase subunits indicated that the sites of amino acid modification in MinnGold, T219H, and CD-5 are highly conserved among photosynthetic species. These results suggest that amino acid alterations in this critical domain may create competitive inhibitory interactions between the mutant and wild-type ChlI1a and ChlI1b proteins. PMID:25452420

Campbell, Benjamin W.; Mani, Dhananjay; Curtin, Shaun J.; Slattery, Rebecca A.; Michno, Jean-Michel; Ort, Donald R.; Schaus, Philip J.; Palmer, Reid G.; Orf, James H.; Stupar, Robert M.

2014-01-01

161

Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation  

PubMed Central

Background The SCN8A gene on chromosome 12q13 encodes the voltage gated sodium channel Nav1.6, which is widely expressed in neurons of the CNS and PNS. Mutations in the mouse ortholog of SCN8A result in ataxia and other movement disorders. Methods We screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia. Results A 2?bp deletion in exon 24 was identified in a 9?year old boy with mental retardation, pancerebellar atrophy, and ataxia. This mutation, Pro1719ArgfsX6, introduces a translation termination codon into the pore loop of domain 4, resulting in removal of the C?terminal cytoplasmic domain and predicted loss of channel function. Three additional heterozygotes in the family exhibit milder cognitive and behavioural deficits including attention deficit hyperactivity disorder (ADHD). No additional occurrences of this mutation were observed in 625 unrelated DNA samples (1250 chromosomes). Conclusions The phenotypes of the heterozygous individuals suggest that mutations in SCN8A may result in motor and cognitive deficits of variable expressivity, but the study was limited by lack of segregation in the small pedigree and incomplete information about family members. Identification of additional families will be required to confirm the contribution of the SCN8A mutation to the clinical features in ataxia, cognition and behaviour disorders. PMID:16236810

Trudeau, M M; Dalton, J C; Day, J W; Ranum, L P W; Meisler, M H

2006-01-01

162

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. PMID:24732281

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

2014-01-01

163

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

164

Fire-retardant materials  

Microsoft Academic Search

Conventional materials (natural and man-made fibres, plastics, wood, paper etc.) used in everyday life are, in different degrees,\\u000a liable to ignition. This fact has impelled the development of new materials which are inherently resistant to flame and heat\\u000a or to modify these materials by using flame-retardant additives\\/treatments to meet the stringent regulations set for fire\\u000a protection.\\u000a \\u000a This paper gives an

Pushpa Bajaj

1992-01-01

165

Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1  

E-print Network

Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators Aft1 and Aft2, 13). The yeast Saccharomyces cerevisiae has two paralogous iron-responsive transcription activators

Boyer, Edmond

166

The Mentally Retarded in Sweden.  

ERIC Educational Resources Information Center

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

Grunewald, Karl

167

China's Approach to Mental Retardation.  

ERIC Educational Resources Information Center

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

Hittman, Stephan

168

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

169

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.

170

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

Ben C. J. Hamel; H.-Hilger Ropers

2005-01-01

171

Meiotic recombination between paralogous RBCSB genes on sister chromatids of Arabidopsis thaliana.  

PubMed Central

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 recombinant chimeric genes resulting from meiotic recombination between paralogous genes on sister chromatids. Several F1 populations hemizygous for the synthRBCSB1 gene cluster gave rise to Luc+ F2 plants at frequencies ranging from 1 to 3 x 10(-6). A nonuniform distribution of recombination resolution sites resulted in the biased formation of recombinant RBCS3B/1B::LUC genes with nonchimeric exons. The positioning of approximately half of the mapped resolution sites was effectively modeled by the fractional length of identical DNA sequences. In contrast, the other mapped resolution sites fit an alternative model in which recombination resolution was stimulated by an abrupt transition from a region of relatively high sequence similarity to a region of low sequence similarity. Thus, unequal recombination between paralogous RBCSB genes on sister chromatids created an allelic series of novel chimeric genes that effectively resulted in the diversification rather than the homogenization of the synthRBCSB1 gene cluster. PMID:15020479

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

2004-01-01

172

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

173

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

174

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

ERIC Educational Resources Information Center

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

Bonnefon, Jean-Francois

2009-01-01

175

Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons  

E-print Network

Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit, 4 CNRS UMR8542, Ecole Normale Supe´rieure, Paris, France The pontine neurons (PN) represent a major, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using

176

Novel male-biased expression in paralogs of the aphid slimfast nutrient amino acid transporter expansion  

PubMed Central

Background A major goal of molecular evolutionary biology is to understand the fate and consequences of duplicated genes. In this context, aphids are intriguing because the newly sequenced pea aphid genome harbors an extraordinary number of lineage-specific gene duplications relative to other insect genomes. Though many of their duplicated genes may be involved in their complex life cycle, duplications in nutrient amino acid transporters appear to be associated rather with their essential amino acid poor diet and the intracellular symbiosis aphids rely on to compensate for dietary deficits. Past work has shown that some duplicated amino acid transporters are highly expressed in the specialized cells housing the symbionts, including a paralog of an aphid-specific expansion homologous to the Drosophila gene slimfast. Previous data provide evidence that these bacteriocyte-expressed transporters mediate amino acid exchange between aphids and their symbionts. Results We report that some nutrient amino acid transporters show male-biased expression. Male-biased expression characterizes three paralogs in the aphid-specific slimfast expansion, and the male-biased expression is conserved across two aphid species for at least two paralogs. One of the male-biased paralogs has additionally experienced an accelerated rate of non-synonymous substitutions. Conclusions This is the first study to document male-biased slimfast expression. Our data suggest that the male-biased aphid slimfast paralogs diverged from their ancestral function to fill a functional role in males. Furthermore, our results provide evidence that members of the slimfast expansion are maintained in the aphid genome not only for the previously hypothesized role in mediating amino acid exchange between the symbiotic partners, but also for sex-specific roles. PMID:21917168

2011-01-01

177

Characterization of the Drosophila Group Ortholog to the Amino-Terminus of the Alpha-Thalassemia and Mental Retardation X-Linked (ATRX) Vertebrate Protein  

PubMed Central

The human ATRX gene encodes hATRX, a chromatin-remodeling protein harboring an helicase/ATPase and ADD domains. The ADD domain has two zinc fingers that bind to histone tails and mediate hATRX binding to chromatin. dAtrx, the putative ATRX homolog in Drosophila melanogaster, has a conserved helicase/ATPase domain but lacks the ADD domain. A bioinformatic search of the Drosophila genome using the human ADD sequence allowed us to identify the CG8290 annotated gene, which encodes three ADD harboring- isoforms generated by alternative splicing. This Drosophila ADD domain is highly similar in structure and in the amino acids which mediate the histone tail contacts to the ADD domain of hATRX as shown by 3D modeling. Very recently the CG8290 annotated gene has been named dadd1. We show through pull-down and CoIP assays that the products of the dadd1 gene interact physically with dAtrxL and HP1a and all of them mainly co-localize in the chromocenter, although euchromatic localization can also be observed through the chromosome arms. We confirm through ChIP analyses that these proteins are present in vivo in the same heterochromatic regions. The three isoforms are expressed throughout development. Flies carrying transheterozygous combinations of the dadd1 and atrx alleles are semi-viable and have different phenotypes including the appearance of melanotic masses. Interestingly, the dAdd1-b and c isoforms have extra domains, such as MADF, which suggest newly acquired functions of these proteins. These results strongly support that, in Drosophila, the atrx gene diverged and that the dadd1-encoded proteins participate with dAtrx in some cellular functions such as heterochromatin maintenance. PMID:25437195

Hernández-Rodríguez, Benjamín; Campos, Adam; Montero, Daniel; Rudiño, Enrique; Vázquez, Martha; Zurita, Mario; Valadez-Graham, Viviana

2014-01-01

178

Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD  

PubMed Central

SUMMARY 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 Ca2+/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.

2009-01-01

179

INTRODUCTION TO BROMINATED FLAME RETARDANTS  

EPA Science Inventory

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

180

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...

181

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

182

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

PubMed

Salicylic acid (SA) is necessary for plant defence against some pathogens, whereas NPR1 is necessary for SA perception. Plant defence can be induced to an extreme by several applications of benzothiadiazole (BTH), an analogue of SA. Thus, plants that do not perceive BTH grow unaffected, whereas wild-type plants grow stunted. This feature allows us to screen for mutants in Arabidopsis thaliana that show insensitivity to BTH in a high-throughput fashion. Most of the mutants are npr1 alleles, with similar phenotypes in plant weight and pathogen growth. The mutations are clustered in the carboxyl-terminal part of the protein, and no obvious null alleles were recovered. These facts have prompted a search for knockouts in the NPR1 gene. Two of these KO alleles identified are null and have an intermediate phenotype. All the evidence presented lead us to propose a redundancy in SA perception, with the paralogs of NPR1 taking part in this signalling. We show that the mutations recovered in the screening genetically interact with the paralogs preventing their function in SA signalling. PMID:20561252

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

2010-11-01

183

DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.  

PubMed

XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery. PMID:25574025

Ochi, Takashi; Blackford, Andrew N; Coates, Julia; Jhujh, Satpal; Mehmood, Shahid; Tamura, Naoka; Travers, Jon; Wu, Qian; Draviam, Viji M; Robinson, Carol V; Blundell, Tom L; Jackson, Stephen P

2015-01-01

184

ß-tubulin Paralogs Provide a Qualitative Test for a Phylogeny of Cyst Nematodes  

PubMed Central

Evolutionary relationships among cyst nematodes based on predicted ß-tubulin amino acid and DNA sequence data were compared with phylogenies inferred from ribosomal DNA (ITS1, 5.8S gene, ITS2). The ß-tubulin amino acid data were highly conserved and not useful for phylogenetic inference at the taxonomic level of genus and species. Phylogenetic trees based on ß-tubulin DNA sequence data were better resolved, but the relationships at lower taxonomic levels could not be inferred with confidence. Sequences from single species often appeared in more than one monophyletic clade, indicating the presence of ß-tubulin paralogs (confirmed by Southern blot analysis). For a subset of taxa, good congruence between the two data sets was revealed by the presence of the same putative ß-tubulin gene paralogs in monophyletic groups on the rDNA tree, corroborating the taxon relationships inferred from ribosomal DNA data. PMID:19262824

Sabo, A.; Ferris, V. R.

2004-01-01

185

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. PMID:23555707

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

2013-01-01

186

Mutational analysis of three bchH paralogs in (bacterio-)chlorophyll biosynthesis in Chlorobaculum tepidum  

Microsoft Academic Search

The first committed step in the biosynthesis of (bacterio-)chlorophyll is the insertion of Mg2+ into protoporphyrin IX by Mg-chelatase. In all known (B)Chl-synthesizing organisms, Mg-chelatase is encoded by three genes\\u000a that are homologous to bchH, bchD, and bchI of Rhodobacter spp. The genomes of all sequenced strains of green sulfur bacteria (Chlorobi) encode multiple bchH paralogs, and in the genome

Aline Gomez Maqueo Chew; Niels-Ulrik Frigaard; Donald A. Bryant

2009-01-01

187

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

PubMed

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

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

2013-05-24

188

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

PubMed Central

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

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

2013-01-01

189

Allosteric Activation of Trypanosomatid Deoxyhypusine Synthase by a Catalytically Dead Paralog*?  

PubMed Central

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

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

2013-01-01

190

Roles of Rad51 paralogs for promoting homologous recombination in Leishmania infantum  

PubMed Central

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

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

2015-01-01

191

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

192

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

193

Biochemical properties of nematode O-acetylserine(thiol)lyase paralogs imply their distinct roles in hydrogen sulfide homeostasis.  

PubMed

O-Acetylserine(thiol)lyases (OAS-TLs) play a pivotal role in a sulfur assimilation pathway incorporating sulfide into amino acids in microorganisms and plants, however, these enzymes have not been found in the animal kingdom. Interestingly, the genome of the roundworm Caenorhabditis elegans contains three expressed genes predicted to encode OAS-TL orthologs (cysl-1-cysl-3), and a related pseudogene (cysl-4); these genes play different roles in resistance to hypoxia, hydrogen sulfide and cyanide. To get an insight into the underlying molecular mechanisms we purified the three recombinant worm OAS-TL proteins, and we determined their enzymatic activities, substrate binding affinities, quaternary structures and the conformations of their active site shapes. We show that the nematode OAS-TL orthologs can bind O-acetylserine and catalyze the canonical reaction although this ligand may more likely serve as a competitive inhibitor to natural substrates instead of being a substrate for sulfur assimilation. In addition, we propose that S-sulfocysteine may be a novel endogenous substrate for these proteins. However, we observed that the three OAS-TL proteins are conformationally different and exhibit distinct substrate specificity. Based on the available evidences we propose the following model: CYSL-1 interacts with EGL-9 and activates HIF-1 that upregulates expression of genes detoxifying sulfide and cyanide, the CYSL-2 acts as a cyanoalanine synthase in the cyanide detoxification pathway and simultaneously produces hydrogen sulfide, while the role of CYSL-3 remains unclear although it exhibits sulfhydrylase activity in vitro. All these data indicate that C. elegans OAS-TL paralogs have distinct cellular functions and may play different roles in maintaining hydrogen sulfide homeostasis. PMID:24100226

Vozdek, Roman; Hnízda, Aleš; Krijt, Jakub; Será, Leona; Kožich, Viktor

2013-12-01

194

Auto cannibalism in mental retardation.  

PubMed

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

Verma, Rohit; Mina, Shaily; Sachdeva, Ankur

2014-01-01

195

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. PMID:24891909

Verma, Rohit; Mina, Shaily; Sachdeva, Ankur

2014-01-01

196

[Hyperlipoproteinemia in mentally retarded children].  

PubMed

Screening revealed a significantly higher incidence of hyperlipoproteinaemia in mentally retarded children in an Institute for Social Welfare than in the healthy child population (P 1%). In the aetiology participate most markedly secondary influences ensuing in particular from complications of the basic diagnosis of oligophrenia. It is mainly a question of the action of antiepileptics, neuroleptics, the influence of viral hepatic infections and other endogenous and exogenous factors. Early diagnosis of hyperlipoproteinaemia is possible so far only by biochemical methods. It is essential for genetic counselling, for prevention of deterioration as regards mental retardation, restriction of pharmacotherapy and later for a reduced risk of development of cardiovascular disease. PMID:8403035

Höllge, J; Vymlátil, J; Kostiuk, P; Böswart, J

1993-08-01

197

Dichotic Stimulation and Mental Retardation.  

ERIC Educational Resources Information Center

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

Mosley, James L.; Virbancic, Mirna I.

1990-01-01

198

MEDICAL ASPECTS OF MENTAL RETARDATION.  

ERIC Educational Resources Information Center

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

CARTER, CHARLES H., COMP.

199

Fire-retardant epoxy polymers  

NASA Technical Reports Server (NTRS)

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

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

1978-01-01

200

The Mentally Retarded in Sweden.  

ERIC Educational Resources Information Center

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

Grunewald, Karl

201

Avian Atherosclerosis: Retardation by Pectin  

Microsoft Academic Search

A highly significant retardation of spontaneous atherosclerosis was observed in 2-year-old cockerels fed on a standard diet supplemented with 5 percent pectin for 18 months. The pectin-fed birds excreted three times as much lipid extract and almost twice as much cholesterol as did the control cockerels fed the standard diet supplemented with 5 percent nonnutritive fiber.

H. Fisher; P. Griminger; H. S. Weiss; W. G. Siller

1964-01-01

202

[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

203

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.

204

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

205

Consanguinity and familial mental retardation  

Microsoft Academic Search

Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for

B S Sridhara Rama Rao; H S Narayanan

1976-01-01

206

Detection of Malingered Mental Retardation  

ERIC Educational Resources Information Center

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

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

2010-01-01

207

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.

208

Social Facilitation of Retardate Performance.  

ERIC Educational Resources Information Center

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

Zucker, Stanley H.

209

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

210

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

PubMed Central

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

211

An enhanced method for sequence walking and paralog mining: TOPO® Vector-Ligation PCR  

PubMed Central

Background Although technological advances allow for the economical acquisition of whole genome sequences, many organisms' genomes remain unsequenced, and fully sequenced genomes may contain gaps. Researchers reliant upon partial genomic or heterologous sequence information require methods for obtaining unknown sequences from loci of interest. Various PCR based techniques are available for sequence walking - i.e., the acquisition of unknown DNA sequence adjacent to known sequence. Many such methods require rigid, elaborate protocols and/or impose narrowly confined options in the choice of restriction enzymes for necessary genomic digests. We describe a new method, TOPO® Vector-Ligation PCR (or TVL-PCR) that innovatively integrates available tools and familiar concepts to offer advantages as a means of both targeted sequence walking and paralog mining. Findings TVL-PCR exploits the ligation efficiency of the pCR®4-TOPO® (Invitrogen, Carlsbad, California) vector system to capture fragments of unknown sequence by creating chimeric molecules containing defined priming sites at both ends. Initially, restriction enzyme-digested genomic DNA is end-repaired to create 3' adenosine overhangs and is then ligated to pCR4-TOPO vectors. The ligation product pool is used directly as a template for nested PCR, using specific primers to target orthologous sequences, or degenerate primers to enable capture of paralogous gene family members. We demonstrated the efficacy of this method by capturing entire coding and partial promoter sequences of several strawberry Superman-like genes. Conclusions TVL-PCR is a convenient and efficient method for DNA sequence walking and paralog mining that is applicable to any organism for which relevant DNA sequence is available as a basis for primer design. PMID:20202219

2010-01-01

212

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

213

Mental Retardation: Prevention Strategies That Work.  

ERIC Educational Resources Information Center

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

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

214

Low Elevated Lead Levels and Mental Retardation.  

ERIC Educational Resources Information Center

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

Marlowe, Mike; And Others

215

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

2014-07-01

216

Functional divergence of type 2 deiodinase paralogs in the atlantic salmon.  

PubMed

Thyroid hormone (TH) is an ancestral signal linked to seasonal life history transitions throughout vertebrates. TH action depends upon tissue-localized regulation of levels of active TH (triiodothyronine, T3), through spatiotemporal expression of thyroid hormone deiodinase (dio) genes. We investigated the dio gene family in juvenile Atlantic salmon (Salmo salar) parr, which prepare for seaward migration in the spring (smoltification) through TH-dependent changes in physiology. We identified two type 2 deiodinase paralogs, dio2a and dio2b, responsible for conversion of thyroxine (T4) to T3. During smoltification, dio2b was induced in the brain and gills in zones of cell proliferation following increasing day length. Contrastingly, dio2a expression was induced in the gills by transfer to salt water (SW), with the magnitude of the response proportional to the plasma chloride level. This response reflected a selective enrichment for osmotic response elements (OREs) in the dio2a promoter region. Transcriptomic profiling of gill tissue from fish transferred to SW plus or minus the deiodinase inhibitor, iopanoic acid, revealed SW-induced increases in cellular respiration as the principal consequence of gill dio2 activity. Divergent evolution of dio2 paralogs supports organ-specific timing of the TH-dependent events governing the phenotypic plasticity required for migration to sea. PMID:25802152

Lorgen, Marlene; Casadei, Elisa; Król, El?bieta; Douglas, Alex; Birnie, Mike J; Ebbesson, Lars O E; Nilsen, Tom O; Jordan, William C; Jørgensen, Even H; Dardente, Hugues; Hazlerigg, David G; Martin, Samuel A M

2015-03-30

217

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

PubMed Central

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

218

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

PubMed

Despite a significant increase in genomic data, our knowledge of gene functions and their transcriptional responses to environmental stimuli remains limited. Here, we use the model keystone species Daphnia pulex to study environmental responses of genes in the context of their gene family history to better understand the relationship between genome structure and gene function in response to environmental stimuli. Daphnia were exposed to five different treatments, each consisting of a diet supplemented with one of five cyanobacterial species, and a control treatment consisting of a diet of only green algae. Differential gene expression profiles of Daphnia exposed to each of these five cyanobacterial species showed that genes with known functions are more likely to be shared by different expression profiles, whereas genes specific to the lineage of Daphnia are more likely to be unique to a given expression profile. Furthermore, while only a small number of nonlineage-specific genes were conserved across treatment type, there was a high degree of overlap in expression profiles at the functional level. The conservation of functional responses across the different cyanobacterial treatments can be attributed to the treatment-specific expression of different paralogous genes within the same gene family. Comparison with available gene expression data in the literature suggests differences in nutritional composition in diets with cyanobacterial species compared to diets of green algae as a primary driver for cyanobacterial effects on Daphnia. We conclude that conserved functional responses in Daphnia across different cyanobacterial treatments are mediated through alternate regulation of paralogous gene families. PMID:25754071

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

2015-04-01

219

Consanguinity and familial mental retardation.  

PubMed Central

Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for studies in the general population in order to understand the biological significance of consanguinity. PMID:1271423

Sridhara Rama Rao, B S; Narayanan, H S

1976-01-01

220

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

221

[Neuroleptics in mentally retarded children].  

PubMed

Long-term administration of neuroleptic drugs to 149 severely mentally retarded children led to a significantly higher number of somatic complications and respiratory morbidity, as compared with a control group (p < or = 5%). Precise differentiation of the influence of neuroleptics from other drugs, complications of the basic diagnosis of oligophrenia and others is not possible so far. Therefore it is essential to consider carefully the indication for administration of neuroleptics and to reduce thus their undesirable effects to a minimum. PMID:7902782

Höllge, J

1993-09-01

222

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

223

The Effect of a Brominated Flame Retardant, Tetrabromobisphenol-A, on Free Radical Formation in Human Neutrophil Granulocytes: The Involvement of the MAP Kinase Pathway and Protein Kinase C  

Microsoft Academic Search

This study investigates the effects of one of the most frequently used brominated flame-retardants (BFR), tetrabromobisphenol-A (TBBPA), on formation of reactive oxygen species (ROS) and calciumlevelsinhumanneutrophilgranulocytes.TBBPAenhanced ROS production in a concentration-depended manner (1-12 mM), measured as 2,7-dichlorofluorescein diacetate amplified (DCF) fluorescence. The results on ROS production by TBBPA was con- firmed by lucigenin-amplified chemiluminescence. The TBBPA induced formation of ROS

Trine Reistad; Espen Mariussen; Frode Fonnum

2004-01-01

224

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

225

Experimental method to characterize the retardance function of optical variable retarders  

NASA Astrophysics Data System (ADS)

In this work, we present an experimental method to characterize variable optical retarders, which can have linear or non-linear behavior of the retardance variation. A theoretical analysis of such is presented using a combination of Stokes vectors and Mueller matrixes for three different optical retarders. A straightforward method for phase unwrapping, or reconstructing the original phase from the measured retardance, is proposed that yields high-accuracy results. This work can be used in an undergraduate optics lab to help students understand the concepts of retardance and its control and also how variable retardance devices work.

López-Téllez, Juan M.; Bruce, Neil C.; Delgado-Aguillón, Jesús; Garduño-Mejía, Jesús; Avendaño-Alejo, Maximino

2015-02-01

226

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

Microsoft Academic Search

Gene constellations on several human chromosomes are interpreted as indications of large regional duplications that took place during evolution of the vertebrate genome. Four groups of paralogous chromosomal regions in man and the house mouse are suggested and are believed to be conserved remnants of the two or three rounds of tetraploidization that are likely to have occurred during evolution

L Lundin

1993-01-01

227

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. PMID:17083971

Fekete, Éva M.; Zorrilla, Eric P.

2007-01-01

228

A review of flame retardant polypropylene fibres  

Microsoft Academic Search

Flame retardants for polypropylene (PP) and their potential suitability for use in fibre applications are reviewed. Five principal types of generic flame retardant systems for inclusion in polypropylene fibres have been identified as phosphorus-containing, halogen-containing, silicon-containing, metal hydrate and oxide and the more recently developed nanocomposite flame retardant formulations.The most effective to date comprise halogen–antimony and phosphorus–bromine combinations, which while

Sheng Zhang; A. Richard Horrocks

2003-01-01

229

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

PubMed

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

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

2015-03-01

230

Alpha thalassaemia-mental retardation, X linked  

PubMed Central

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s. PMID:16722615

Gibbons, Richard

2006-01-01

231

GORDITA (AGL63) is a young paralog of the Arabidopsis thaliana B(sister) MADS box gene ABS (TT16) that has undergone neofunctionalization.  

PubMed

MIKC-type MADS domain proteins are key regulators of flower development in angiosperms. B(sister) genes constitute a clade with a close relationship to class B floral homeotic genes, and have been conserved for more than 300 million years. The loss-of-function phenotype of the A. thaliana B(sister) gene ABS is mild: mutants show reduced seed coloration and defects in endothelium development. This study focuses on GORDITA (GOA, formerly known as AGL63), the most closely related paralog of ABS in A. thaliana, which is thought to act redundantly with ABS. Phylogenetic trees reveal that the duplication leading to ABS and GOA occurred during diversification of the Brassicaceae, and further analyses show that GOA has evolved under relaxed selection pressure. The knockdown phenotype of GOA suggests a role for this gene in fruit longitudinal growth, while over-expression of GOA results in disorganized floral structure and addition of carpel-like features to sepals. Given the phylogeny and function of other B(sister) genes, our data suggest that GOA has evolved a new function as compared to ABS. Protein analysis reveals that the GOA-specific 'deviant' domain is required for protein dimerization, in contrast to other MIKC-type proteins that require the K domain for dimerization. Moreover, no shared protein interaction partners for ABS and GOA could be identified. Our experiments indicate that modification of a protein domain and a shift in expression pattern can lead to a novel gene function in a relatively short time, and highlight the molecular mechanism by which neofunctionalization following gene duplication can be achieved. PMID:20598091

Erdmann, Robert; Gramzow, Lydia; Melzer, Rainer; Theissen, Günter; Becker, Annette

2010-09-01

232

A RT I C L E S Protein complexes containing CYFIP/Sra/PIR121  

E-print Network

CYFIP (cytoplasmic fragile-X mental retardation interacting protein; Sra, PIR121), a clathrin heavy chain binding protein associated with mental retardation. The Rac1 GTPase and its exchange factor -PIX-X mental retardation protein21 . This protein complex regulates Rac1-dependent WAVE2 function at cellular

Kirchhausen, Tomas

233

314 American Association on Mental Retardation American Journal on Mental Retardation, 2001, Vol. 106, No. 4, 314326  

E-print Network

314 American Association on Mental Retardation American Journal on Mental Retardation, 2001, Vol. 106, No. 4, 314­326 Enhancing Free-Recall Rates of Individuals With Mental Retardation Michael T retardation (Soraci et al., 1994, 1999). The present extension to individuals with mental retardation involved

Dennis, Nancy

234

Do flame retardants threaten ocean life?  

Microsoft Academic Search

Brominated flame retardants are important in modern life. They are used at relatively high concentrations in electronic equipment such as computers and television sets, in textiles, cars and in many other applications. Here we show that two groups of these flame retardants, polybrominated biphenyls (PBBs) and polybrominated diphenyl ethers (PBDEs), are present in sperm whales, which normally stay and feed

Jacob de Boer; Peter G. Wester; Hans J. C. Klamer; Wilma E. Lewis; Jan P. Boon

1998-01-01

235

Interaction between Family Violence and Mental Retardation.  

ERIC Educational Resources Information Center

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

Strickler, Heidi

2001-01-01

236

Political Philosophy and the Mentally Retarded.  

ERIC Educational Resources Information Center

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

Stanovich, Keith E.

237

Problems of Psychology of Mentally Retarded Children.  

ERIC Educational Resources Information Center

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

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

238

Arm Tremor, Tardive Dyskinesia, and Mental Retardation.  

ERIC Educational Resources Information Center

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

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

1993-01-01

239

Body Awareness in Children with Mental Retardation  

ERIC Educational Resources Information Center

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

Simons, Johan; Dedroog, Inge

2009-01-01

240

Assessment of Terms to Describe Mental Retardation  

ERIC Educational Resources Information Center

There is currently debate among professionals in the area of mental retardation/developmental disabilities regarding the use of, and a possible replacement for, the term mental retardation. Using the semantic differential technique, 284 participants drawn from various Midwestern populations completed assessments of several terms used to describe…

Panek, Paul E.; Smith, Jessi L.

2005-01-01

241

Long Term Memory in Normals and Retardates.  

ERIC Educational Resources Information Center

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

McLaughlin, John A.; Stephens, Will Beth

242

Identifying Depression in Students with Mental Retardation.  

ERIC Educational Resources Information Center

Offers guidelines to teachers for identifying depression in students with mental retardation. Discusses prevalence and symptoms of depression, causes of depression, difficulty of diagnosis in students with mental retardation, detecting symptoms in the classroom, treatment of depression, and psychological services. Inserts list ideas for helping…

Stough, Laura M.; Baker, Lynn

1999-01-01

243

EFFECTIVE EDUCATION FOR THE MENTALLY RETARDED CHILD.  

ERIC Educational Resources Information Center

DRAWING ON 40 YEARS OF EXPERIENCE IN TEACHING AND LIVING WITH RETARDED CHILDREN AND ADULTS, THE AUTHOR PRESENTS A SPECIAL EDUCATIONAL SYSTEM AND SOME OF THE METHODS WHICH HE HAS FOUND MOST USEFUL. METHODS AND PRINCIPLES ARE TREATED IN A PRACTICAL AND SPECIFIC MANNER. DEFINITIONS AND THE NATURE OF MENTAL RETARDATION ARE CONSIDERED. THE FOLLOWING…

KOLBURNE, LUMA LOUIS

244

Flame retardant cotton based highloft nonwovens  

Technology Transfer Automated Retrieval System (TEKTRAN)

Flame retardancy has been a serious bottleneck to develop cotton blended very high specific volume bulky High loft fabrics. Alternately, newer approach to produce flame retardant cotton blended High loft fabrics must be employed that retain soft feel characteristics desirable of furnishings. Hence, ...

245

Parental attitudes of retarded young mothers  

Microsoft Academic Search

Thirty-two retarded young mothers were found to have significantly more protective, controlling, and punitive attitudes toward their children than a control group of mothers who had completed two or more years of college work. The retarded mothers regarded their own mothers as even more controlling, protective, and punitive than they themselves were. These findings are compatible with the hypothesis that

Lillian H. Robinson

1978-01-01

246

MR 76. Mental Retardation: Past and Present.  

ERIC Educational Resources Information Center

The tenth annual report of the President's Committee on Mental Retardation reviews the history of America's services for the retarded from the 1850's to the present. Traced is governmental involvement through conferences on children and youth, and reviewed is the role of parents and volunteers in securing appropriate services. Among agencies…

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

247

Reasoning by trainable mentally retarded and young non-retarded individuals.  

PubMed

Three groups of trainable retarded children, and three groups of non-retarded children matched for mental age, were presented with two problem-solving tasks. The tasks required the problem-solver to combine relevant parts of the problem and independently arrive at a solution from their combination. The data was analysed to determine: (1) whether the ability to reason in trainable retarded children showed developmental changes, and (2) to compare the development of reasoning behaviour in trainable retarded children with that of comparable MA non-retarded children. Implications were made from the findings for classroom teaching. PMID:7381934

Zetlin, A G; Bilsky, L H

1980-03-01

248

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. PMID:23527128

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

2013-01-01

249

Care Of The Mentally Retarded  

PubMed Central

Mental retardation is a clinical syndrome, not an intellectual defect or brain disease per se. As such, physicians should not participate in the downgrading labelling of moron, idiot and imbecile. Such labelled people are difficult to relate to and this results in the concept of 'nil expectations' in which the whole of society participates. Maladaptation in this syndrome is more related to poor environmental input than to basic organic defect, and is a family problem. The family doctor is in an ideal situation to help the family handle the problems of anger, shame, guilt, rejection. If aware of his own feelings, he should also be the coordinator of the physical needs of the child and the alternatives available for maximal input. Imagesp1344-a PMID:21297810

Jacobs, J.

1979-01-01

250

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

251

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Mental retardation and personality disorders. 4.127...Ratings Mental Disorders § 4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are...

2013-07-01

252

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Mental retardation and personality disorders. 4.127...Ratings Mental Disorders § 4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are...

2012-07-01

253

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Mental retardation and personality disorders. 4.127...Ratings Mental Disorders § 4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are...

2011-07-01

254

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 2014-07-01 false Mental retardation and personality disorders. 4.127...Ratings Mental Disorders § 4.127 Mental retardation and personality disorders. Mental retardation and personality disorders are...

2014-07-01

255

38 CFR 4.127 - Mental retardation and personality disorders.  

Code of Federal Regulations, 2010 CFR

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

2010-07-01

256

Exploiting genomic patterns to discover new supramolecular protein assemblies  

PubMed Central

Bacterial microcompartments are supramolecular protein assemblies that function as bacterial organelles by compartmentalizing particular enzymes and metabolic intermediates. The outer shells of these microcompartments are assembled from multiple paralogous structural proteins. Because the paralogs are required to assemble together, their genes are often transcribed together from the same operon, giving rise to a distinctive genomic pattern: multiple, typically small, paralogous proteins encoded in close proximity on the bacterial chromosome. To investigate the generality of this pattern in supramolecular assemblies, we employed a comparative genomics approach to search for protein families that show the same kind of genomic pattern as that exhibited by bacterial microcompartments. The results indicate that a variety of large supramolecular assemblies fit the pattern, including bacterial gas vesicles, bacterial pili, and small heat-shock protein complexes. The search also retrieved several widely distributed protein families of presently unknown function. The proteins from one of these families were characterized experimentally and found to show a behavior indicative of supramolecular assembly. We conclude that cotranscribed paralogs are a common feature of diverse supramolecular assemblies, and a useful genomic signature for discovering new kinds of large protein assemblies from genomic data. PMID:19177352

Beeby, Morgan; Bobik, Thomas A; Yeates, Todd O

2009-01-01

257

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

PubMed Central

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

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

2015-01-01

258

Genome-wide analysis of PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) genes in plants reveals the eudicot-wide PDAT gene expansion and altered selective pressures acting on the core eudicot PDAT paralogs.  

PubMed

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

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

2015-03-01

259

Multi-gene silencing in Arabidopsis: a collection of artificial microRNAs targeting groups of paralogs encoding transcription factors.  

PubMed

Functional redundancy often hampers the analysis of gene families. To overcome this difficulty, we constructed Arabidopsis thaliana lines that expressed artificial microRNAs designed to simultaneously target two to six paralogous genes encoding members of transcription factor families. Of the 576 genes that we chose as targets, only 122 had already been functionally studied at some level. As a simple indicator of the inhibitory effects of our amiRNAs on their targets, we examined the amiRNA-expressing transgenic lines for morphological phenotypes at the rosette stage. Of 338 transgenes tested, 21 caused a visible morphological phenotype in leaves, a proportion that is much higher than that expected as a result of insertional mutagenesis. Also, our collection probably represents many other mutant phenotypes, not just those in leaves. This robust, versatile method enables functional examination of redundant transcription factor paralogs, and is particularly useful for genes that occur in tandem. PMID:25040904

Jover-Gil, Sara; Paz-Ares, Javier; Micol, José Luis; Ponce, María Rosa

2014-10-01

260

Nuclear ribosomal its functional paralogs resolve the phylogenetic relationships of a late-miocene radiation cycad cycas (cycadaceae).  

PubMed

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

Xiao, Long-Qian; Möller, Michael

2015-01-01

261

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

PubMed Central

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

Xiao, Long-Qian; Möller, Michael

2015-01-01

262

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. PMID:1175568

Pearce, E M; Liepins, R

1975-01-01

263

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

PubMed

Hox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions and interspersed shared enhancers. Here, we describe the use of a novel recombineering strategy to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10 and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting Hoxa9,10,11 mutant mice displayed dramatic synergistic homeotic transformations of the reproductive tracts, with the uterus anteriorized towards oviduct and the vas deferens anteriorized towards epididymis. The Hoxa9,10,11 mutant mice also provided a genetic setting that allowed the discovery of Hoxd9,10,11 redundant reproductive tract patterning function. Both shared and distinct Hox functions were defined. Hoxd9,10,11 play a crucial role in the regulation of uterine immune function. Non-coding non-polyadenylated RNAs were among the key Hox targets, with dramatic downregulation in mutants. We observed Hox cross-regulation of transcription and splicing. In addition, we observed a surprising anti-dogmatic apparent posteriorization of the uterine epithelium. In caudal regions of the uterus, the normal simple columnar epithelium flanking the lumen was replaced by a pseudostratified transitional epithelium, normally found near the more posterior cervix. These results identify novel molecular functions of Hox genes in the development of the male and female reproductive tracts. PMID:23760953

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

2013-07-01

264

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. PMID:24732957

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

265

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. PMID:15060096

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

266

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

267

Interaction of CD99 with Its Paralog CD99L2 Positively Regulates CD99L2 Trafficking to Cell Surfaces  

PubMed Central

Mouse CD99 and its paralog CD99-like 2 (CD99L2) are surface proteins implicated in cellular adhesion and migration. Although their distributions overlap in a wide variety of cells, their physical/functional relationship is currently unknown. In this study, we show the interaction between the two molecules and its consequence for membrane trafficking of mouse (m)CD99L2. The interaction was analyzed by bimolecular fluorescence complementation, immunoprecipitation, and fluorescence resonance energy transfer assays. When coexpressed, mCD99 formed heterodimers with mCD99L2, as well as homodimers, and the heterodimers were localized more efficiently at the plasma membrane than were the homodimers. Their interaction was cytoplasmic domain–dependent and enhanced mCD99L2 trafficking to the plasma membrane regardless of whether it was transiently overexpressed or endogenously expressed. Surface levels of endogenous mCD99L2 were markedly low on thymocytes, splenic leukocytes, and CTL lines derived from CD99-deficient mice. Importantly, the surface levels of mCD99L2 on mCD99-deficient cells recovered significantly when wild-type mCD99 was exogenously introduced, but they remained low when a cytoplasmic domain mutant of mCD99 was introduced. Our results demonstrate a novel role for mCD99 in membrane trafficking of mCD99L2, providing useful insights into controlling transendothelial migration of leukocytes. PMID:24133166

Nam, Giri; Lee, Young-Kwan; Lee, Hye Yeong; Ma, Min Jung; Araki, Masatake; Araki, Kimi; Lee, Seungbok; Lee, Im-Soon

2013-01-01

268

Rad51/Dmc1 paralogs and mediators oppose DNA helicases to limit hybrid DNA formation and promote crossovers during meiotic recombination  

PubMed Central

During meiosis programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination using the sister chromatid or the homologous chromosome (homolog) as a template. This repair results in crossover (CO) and non-crossover (NCO) recombinants. Only CO formation between homologs provides the physical linkages guiding correct chromosome segregation, which are essential to produce healthy gametes. The factors that determine the CO/NCO decision are still poorly understood. Using Schizosaccharomyces pombe as a model we show that the Rad51/Dmc1-paralog complexes Rad55-Rad57 and Rdl1-Rlp1-Sws1 together with Swi5-Sfr1 play a major role in antagonizing both the FANCM-family DNA helicase/translocase Fml1 and the RecQ-type DNA helicase Rqh1 to limit hybrid DNA formation and promote Mus81-Eme1-dependent COs. A common attribute of these protein complexes is an ability to stabilize the Rad51/Dmc1 nucleoprotein filament, and we propose that it is this property that imposes constraints on which enzymes gain access to the recombination intermediate, thereby controlling the manner in which it is processed and resolved. PMID:25414342

Lorenz, Alexander; Mehats, Alizée; Osman, Fekret; Whitby, Matthew C.

2014-01-01

269

Retardation Measurements of Infrared PVA Wave plate  

NASA Astrophysics Data System (ADS)

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

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

270

Identifying depression in students with mental retardation  

E-print Network

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Identifying depression in students with mental retardation Stough, Laura M;Baker, Lynn Teaching Exceptional Children; Mar/Apr 1999; 31, 4; Pro...

Stough, Laura

1999-01-01

271

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

272

Retarded Children at Camp with Normal Children  

ERIC Educational Resources Information Center

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

Flax, Norman; Peters, Edward N.

1969-01-01

273

Teaching mending skills to mentally retarded adolescents.  

PubMed Central

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

Cronin, K A; Cuvo, A J

1979-01-01

274

Brominated Flame Retardants and Perfluorinated Chemicals  

EPA Science Inventory

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

275

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...

276

PCBs, PBBs and Brominated Flame Retardants  

EPA Science Inventory

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

277

Identifying depression in students with mental retardation  

E-print Network

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Identifying depression in students with mental retardation Stough, Laura M;Baker, Lynn Teaching Exceptional Children; Mar/Apr 1999; 31, 4; Pro...

Stough, Laura

2003-01-01

278

Gitelman's syndrome: Rare presentation with growth retardation.  

PubMed

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. PMID:24574637

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

2014-01-01

279

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

280

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. PMID:24574637

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

2014-01-01

281

Diagnosis and Management of Intrauterine Growth Retardation  

Microsoft Academic Search

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

J. Lepercq; D. Mahieu-Caputo

1998-01-01

282

A Mental Retardation-linked Nonsense Mutation in Cereblon Is Rescued by Proteasome Inhibition*  

PubMed Central

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.

2013-01-01

283

Including Children with Mental Retardation in the Religious Community.  

ERIC Educational Resources Information Center

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

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

2001-01-01

284

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

ERIC Educational Resources Information Center

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

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

285

Species-specific difference in expression and splice-site choice in Inpp5b, an inositol polyphosphate 5-phosphatase paralogous to the enzyme deficient in Lowe Syndrome  

PubMed Central

The oculocerebrorenal syndrome of Lowe (OCRL; MIM #309000) is an X-linked human disorder characterized by congenital cataracts, mental retardation, and renal proximal tubular dysfunction caused by loss-of-function mutations in the OCRL gene that encodes Ocrl, a type II phosphatidylinositol bisphosphate (PtdIns4,5P2) 5-phosphatase. In contrast, mice with complete loss-of-function of the highly homologous ortholog Ocrl have no detectable renal, ophthalmological, or central nervous system abnormalities. We inferred that the disparate phenotype between Ocrl-deficient humans and mice was likely due to differences in how the two species compensate for loss of the Ocrl enzyme. We therefore turned our attention to Inpp5b, another type II PtdIns4,5P2 5-phosphatase encoded by Inpp5b in mice and INPP5B in humans, as potential compensating genes in the two species, because Inpp5b/INPP5B are the most highly conserved paralogs to Ocrl/OCRL in the respective genomes of both species and Inpp5b demonstrates functional overlap with Ocrl in mice in vivo. We used in silico sequence analysis, reverse-transcription PCR, quantitative PCR, and transient transfection assays of promoter function to define splice-site usage and the function of an internal promoter in mouse Inpp5b versus human INPP5B. We found mouse Inpp5b and human INPP5B differ in their transcription, splicing, and primary amino acid sequence. These observations form the foundation for analyzing the functional basis for the difference in how Inpp5b and INPP5B compensate for loss of Ocrl function and, by providing insight into the cellular roles of Ocrl and Inpp5b, aid in the development of a model system in which to study Lowe syndrome. Electronic supplementary material The online version of this article (doi:10.1007/s00335-010-9281-7) contains supplementary material, which is available to authorized users. PMID:20872266

Bothwell, Susan P.; Farber, Leslie W.; Hoagland, Adam

2010-01-01

286

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.

287

Fragile X protein family member FXR1P is regulated by microRNAs.  

PubMed

FXR1P is one of two autosomal paralogs of the fragile X mental retardation protein FMRP. The absence of FMRP causes fragile X syndrome, the leading cause of hereditary mental retardation. FXR1P plays an important role in normal muscle development and has been implicated in facioscapulohumeral muscular dystrophy (FSHD). Its absence also causes cardiac abnormalities in both mice and zebrafish. To examine miRNA-mediated regulation of FMRP and FXR1P, we studied their expression in a conditional Dicer knockdown cell line, DT40. We found that FXR1P, but not FMRP, is significantly increased upon Dicer knockdown and the consequent reduction of miRNAs, suggesting that FXR1P is regulated by miRNAs while FMRP is not in DT40 cells. Expression of a luciferase reporter bearing the 3' untranslated region (3'UTR) of FXR1 was significantly increased in the absence of miRNAs, confirming miRNA-mediated regulation of FXR1P, while a luciferase reporter bearing the FMR1 3'UTR was not. We identified one of the regulatory regions in the 3'UTR of FXR1 by removing a conserved, 8-nucleotide miRNA seed sequence common to miRNAs 25, 32, 92, 363, and 367 and demonstrated loss of miRNA-mediated suppression. Treatment with specific miRNA hairpin inhibitors to each of the miRNAs in the seed sequence showed that miRs 92b, 363, and 367 regulated FXR1P expression. Accordingly, overexpression of the miRNA 367 mimic significantly decreased endogenous FXR1P expression in human cell lines HEK-293T and HeLa. We report for the first time that FXR1P is regulated through miRNA binding, with one site being the miR-25/32/92/363/367 seed sequence. PMID:20519410

Cheever, Anne; Blackwell, Ernest; Ceman, Stephanie

2010-08-01

288

Fragile X protein family member FXR1P is regulated by microRNAs  

PubMed Central

FXR1P is one of two autosomal paralogs of the fragile X mental retardation protein FMRP. The absence of FMRP causes fragile X syndrome, the leading cause of hereditary mental retardation. FXR1P plays an important role in normal muscle development and has been implicated in facioscapulohumeral muscular dystrophy (FSHD). Its absence also causes cardiac abnormalities in both mice and zebrafish. To examine miRNA-mediated regulation of FMRP and FXR1P, we studied their expression in a conditional Dicer knockdown cell line, DT40. We found that FXR1P, but not FMRP, is significantly increased upon Dicer knockdown and the consequent reduction of miRNAs, suggesting that FXR1P is regulated by miRNAs while FMRP is not in DT40 cells. Expression of a luciferase reporter bearing the 3? untranslated region (3?UTR) of FXR1 was significantly increased in the absence of miRNAs, confirming miRNA-mediated regulation of FXR1P, while a luciferase reporter bearing the FMR1 3?UTR was not. We identified one of the regulatory regions in the 3?UTR of FXR1 by removing a conserved, 8-nucleotide miRNA seed sequence common to miRNAs 25, 32, 92, 363, and 367 and demonstrated loss of miRNA-mediated suppression. Treatment with specific miRNA hairpin inhibitors to each of the miRNAs in the seed sequence showed that miRs 92b, 363, and 367 regulated FXR1P expression. Accordingly, overexpression of the miRNA 367 mimic significantly decreased endogenous FXR1P expression in human cell lines HEK-293T and HeLa. We report for the first time that FXR1P is regulated through miRNA binding, with one site being the miR-25/32/92/363/367 seed sequence. PMID:20519410

Cheever, Anne; Blackwell, Ernest; Ceman, Stephanie

2010-01-01

289

American Association on Mental Retardation 237 VOLUME 107, NUMBER 4: 237251 JULY 2002 AMERICAN JOURNAL ON MENTAL RETARDATION  

E-print Network

American Association on Mental Retardation 237 VOLUME 107, NUMBER 4: 237­251 JULY 2002 AMERICAN JOURNAL ON MENTAL RETARDATION Guided Visual Search in Individuals With Mental Retardation Michael T at the University of Massachusetts Medical School Abstract The ability of individuals with mental retardation

Dennis, Nancy

290

The consequence of an additional NADH dehydrogenase paralog on the growth of Gluconobacter oxydans DSM3504.  

PubMed

Acetic acid bacteria such as Gluconobacter oxydans are used in several biotechnological processes due to their ability to perform rapid incomplete regio- and stereo-selective oxidations of a great variety of carbohydrates, alcohols, and related compounds by their membrane-bound dehydrogenases. In order to understand the growth physiology of industrial strains such as G. oxydans ATCC 621H that has high substrate oxidation rates but poor growth yields, we compared its genome sequence to the genome sequence of strain DSM 3504 that reaches an almost three times higher optical density. Although the genome sequences are very similar, DSM 3504 has additional copies of genes that are absent from ATCC 621H. Most importantly, strain DSM 3504 contains an additional type II NADH dehydrogenase (ndh) gene and an additional triosephosphate isomerase (tpi) gene. We deleted these additional paralogs from DSM 3504, overexpressed NADH dehydrogenase in ATCC 621H, and monitored biomass and the concentration of the representative cell components as well as O2 and CO2 transfer rates in growth experiments on mannitol. The data revealed a clear competition of membrane-bound dehydrogenases and NADH dehydrogenase for channeling electrons in the electron transport chain of Gluconobacter and an important role of the additional NADH dehydrogenase for increased growth yields. The less active the NADH dehydrogenase is, the more active is the membrane-bound polyol dehydrogenase. These results were confirmed by introducing additional ndh genes via plasmid pAJ78 in strain ATCC 621H, which leads to a marked increase of the growth rate. PMID:25267158

Kostner, D; Luchterhand, B; Junker, A; Volland, S; Daniel, R; Büchs, J; Liebl, W; Ehrenreich, A

2015-01-01

291

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. PMID:15020472

Inlow, Jennifer K; Restifo, Linda L

2004-01-01

292

Defining Mental Retardation and Ensuring Access to the General Curriculum  

E-print Network

Defining Mental Retardation and Ensuring Access to the General Curriculum Michael L. Wehmeyer University of Kansas Abstract: Release of the most recent edition (2002) of the American Association on Mental Retardation’s terminology and classification... manual provides a point in time to consider ways in which mental retardation is understood and how that understanding contributes to educational practices to promote positive outcomes for students with mental retardation. Since release of the previous...

Wehmeyer, Michael L.

2003-01-01

293

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

294

The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers.  

PubMed

Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile X mental retardation 1 and has not been directly linked to human cancers. Here we demonstrate that FXR1 is a key regulator of tumor progression and its overexpression is critical for nonsmall cell lung cancer (NSCLC) cell growth in vitro and in vivo. We identified the mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms. FXR1 expression is a candidate biomarker predictive of poor survival in multiple solid tumors including NSCLCs. Because FXR1 is overexpressed and associated with poor clinical outcomes in multiple cancers, these results have implications for other solid malignancies. PMID:25733852

Qian, Jun; Hassanein, Mohamed; Hoeksema, Megan D; Harris, Bradford K; Zou, Yong; Chen, Heidi; Lu, Pengcheng; Eisenberg, Rosana; Wang, Jing; Espinosa, Allan; Ji, Xiangming; Harris, Fredrick T; Rahman, S M Jamshedur; Massion, Pierre P

2015-03-17

295

Clusters of Ancestrally Related Genes That Show Paralogy in Whole or in Part Are a Major Feature of the Genomes of Humans and Other Species  

PubMed Central

Arrangements of genes along chromosomes are a product of evolutionary processes, and we can expect that preferable arrangements will prevail over the span of evolutionary time, often being reflected in the non-random clustering of structurally and/or functionally related genes. Such non-random arrangements can arise by two distinct evolutionary processes: duplications of DNA sequences that give rise to clusters of genes sharing both sequence similarity and common sequence features and the migration together of genes related by function, but not by common descent [1], [2], [3]. To provide a background for distinguishing between the two, which is important for future efforts to unravel the evolutionary processes involved, we here provide a description of the extent to which ancestrally related genes are found in proximity. Towards this purpose, we combined information from five genomic datasets, InterPro, SCOP, PANTHER, Ensembl protein families, and Ensembl gene paralogs. The results are provided in publicly available datasets (http://cgd.jax.org/datasets/clustering/paraclustering.shtml) describing the extent to which ancestrally related genes are in proximity beyond what is expected by chance (i.e. form paraclusters) in the human and nine other vertebrate genomes, as well as the D. melanogaster, C. elegans, A. thaliana, and S. cerevisiae genomes. With the exception of Saccharomyces, paraclusters are a common feature of the genomes we examined. In the human genome they are estimated to include at least 22% of all protein coding genes. Paraclusters are far more prevalent among some gene families than others, are highly species or clade specific and can evolve rapidly, sometimes in response to environmental cues. Altogether, they account for a large portion of the functional clustering previously reported in several genomes. PMID:22563380

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

2012-01-01

296

Thermal damping and retardation in karst conduits  

NASA Astrophysics Data System (ADS)

Water temperature is a non-conservative tracer in the environment. Variations in recharge temperature are damped and retarded as water moves through an aquifer due to heat exchange between water and rock. However, within karst aquifers, seasonal and short-term fluctuations in recharge temperature are often transmitted over long distances before they are fully damped. Using analytical solutions and numerical simulations, we develop relationships that describe the effect of flow path properties, flow-through time, recharge characteristics, and water and rock physical properties on the damping and retardation of thermal peaks/troughs in karst conduits. Using these relationships, one can estimate the thermal retardation and damping that would occur under given conditions with a given conduit geometry. Ultimately, these relationships can be used with thermal damping and retardation field data to estimate parameters such as conduit diameter. We also examine sets of numerical experiments where we relax some of the assumptions used to develop these relationships, testing the effects of variable diameter, variable velocity, open channels, and recharge shape on thermal damping and retardation to provide some constraints on uncertainty. Finally, we discuss a tracer experiment that provides field confirmation of our relationships. High temporal resolution water temperature data are required to obtain sufficient constraints on the magnitude and timing of thermal peaks and troughs in order to take full advantage of water temperature as a tracer.

Luhmann, A. J.; Covington, M. D.; Myre, J. M.; Perne, M.; Jones, S. W.; Alexander, E. C., Jr.; Saar, M. O.

2014-08-01

297

Reduced Cortical Thickness in Mental Retardation  

PubMed Central

Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

2011-01-01

298

Thermal damping and retardation in karst conduits  

NASA Astrophysics Data System (ADS)

Water temperature is a non-conservative tracer in the environment. Variations in recharge temperature are damped and retarded as water moves through an aquifer due to heat exchange between water and rock. However, within karst aquifers, seasonal and short-term fluctuations in recharge temperature are often transmitted over long distances before they are fully damped. Using analytical solutions and numerical simulations, we develop relationships that describe the effect of flow path properties, flow-through time, recharge characteristics, and water and rock physical properties on the damping and retardation of thermal peaks/troughs in karst conduits. Using these relationships, one can estimate the thermal retardation and damping that would occur under given conditions with a given conduit geometry. Ultimately, these relationships can be used with thermal damping and retardation field data to estimate parameters such as conduit diameter. We also examine sets of numerical simulations where we relax some of the assumptions used to develop these relationships, testing the effects of variable diameter, variable velocity, open channels, and recharge shape on thermal damping and retardation to provide some constraints on uncertainty. Finally, we discuss a multitracer experiment that provides some field confirmation of our relationships. High temporal resolution water temperature data are required to obtain sufficient constraints on the magnitude and timing of thermal peaks and troughs in order to take full advantage of water temperature as a tracer.

Luhmann, A. J.; Covington, M. D.; Myre, J. M.; Perne, M.; Jones, S. W.; Alexander, E. C., Jr.; Saar, M. O.

2015-01-01

299

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

300

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

301

Retardation effects in the rotating string model  

SciTech Connect

A new method to study the retardation effects in mesons is presented. Inspired from the covariant oscillator quark model, it is applied to the rotating string model in which a nonzero value is allowed for the relative time between the quark and the antiquark. The straight line ansatz is used to describe the string, and the relevance of this approximation is tested. This approach leads to a retardation term which behaves as a perturbation of the meson mass operator. It is shown that this term preserves the Regge trajectories for light mesons. As an illustration, we show that a satisfactory agreement with the experimental data can be obtained if the quark self-energy contribution is added. The consequences of the retardation on the Coulomb interaction and the wave function are also analyzed.

Buisseret, Fabien; Semay, Claude [Groupe de Physique Nucleaire Theorique, Universite de Mons-Hainaut, Academie Universitaire Wallonie-Bruxelles, Place du Parc 20, BE-7000 Mons (Belgium)

2005-12-01

302

"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. PMID:20152051

2010-01-01

303

ORO-DENTAL PATTERN IN MENTALLY RETARDED  

PubMed Central

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

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

1990-01-01

304

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.

Darryl Leja (National Human Genome Research Institute REV)

2005-04-04

305

Neurobiology of Disease Postadolescent Changes in Regional Cerebral Protein  

E-print Network

, Bethesda, Maryland 20892 Methylation-induced transcriptional silencing of the fragile X mental retardation-1 (Fmr1) gene leads to absence of the gene product, fragile X mental retardation protein (FMRPGluRs) is fragile X mental retardation-1 (Fmr1) (Weiler et al., 1997). Silencing of the gene for Fmr1 by a repeat

Baker, Chris I.

306

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.

307

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

308

Novel additives to retard permeable flow  

SciTech Connect

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

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

2008-09-15

309

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.

310

BROMINATED FLAME RETARDANTS: WHY DO WE CARE?  

EPA Science Inventory

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

311

Flame retardant cotton barrier nonwovens for mattresses  

Technology Transfer Automated Retrieval System (TEKTRAN)

According to regulation CPSC 16 CFR 1633, every new residential mattress sold in the United States since July 2007 must resist ignition by open flame. An environmentally benign “green”, inexpensive way to meet this regulation is to use a low-cost flame retardant (FR) barrier fabric. In this study, a...

312

Conservation Tasks with Retarded and Nonretarded Children  

ERIC Educational Resources Information Center

Forty-six nonretarded children in kindergarten through grade 2 were compared with 47 retarded children in primary through prevocational levels to determine the best predictors of behavior, explanation, and scores for conservation of two dimensional space, substance, continuous quantity, and weight. (MC)

Boland, Sandra K.

1973-01-01

313

Aging, Mental Retardation and Physical Fitness.  

ERIC Educational Resources Information Center

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

Rimmer, James H.

314

Thoughts on Changing the Term Mental Retardation.  

ERIC Educational Resources Information Center

This commentary discusses whether the American Association on Mental Retardation should change its name. It offers some ideas on how society might think about elemental change in terminology so a healthy outcome can be achieved without simply rearranging prejudices. The term "cognitive- adaptive disability" is proposed. (Contains three…

Walsh, Kevin K.

2002-01-01

315

Automatic Memory Processes in Mentally Retarded Persons.  

ERIC Educational Resources Information Center

Automatic memory processes were investigated in 10 mild and moderately retarded persons (21 years old) and in 10 chronological age-matched college level and 10 mental age-matched elementary grade control subjects through use of a frequency estimation task. This task required the subjects to view a series of slides, then estimate how many times…

Stein, Debra Kosteski; And Others

316

Mental Retardation: Past, Present and Future  

ERIC Educational Resources Information Center

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

Crissey, Marie Skodak

1975-01-01

317

Puberty in the Girl Who is Retarded.  

ERIC Educational Resources Information Center

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

Pattullo, Ann

318

Preattentive Orienting in Adolescents with Mental Retardation  

ERIC Educational Resources Information Center

Visual attention is preattentively drawn to abrupt onsets of stimuli appearing in a visual array. In this experiment, I examined the speed of attentional capture for persons with and without mental retardation. Participants identified target stimuli that were signaled by a valid location cue (20% of the time), an invalid location cue (60% of the…

Merrill, Edward C.

2005-01-01

319

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

320

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

321

Mental Retardation and Memory for Spatial Locations.  

ERIC Educational Resources Information Center

Comparison for memory for spatial location of 30 persons with and 30 persons without mental retardation found the control group recalled more intentionally learned than incidentally learned locations. The experimental group performed better after incidental learning than after intentional learning and scored as highly as controls on incidental…

Jones, Robert S. P.; Vaughan, Francis L.; Roberts, Mary

2002-01-01

322

A de novo paradigm for mental retardation  

Microsoft Academic Search

The per-generation mutation rate in humans is high. De novo mutations may compensate for allele loss due to severely reduced fecundity in common neurodevelopmental and psychiatric diseases, explaining a major paradox in evolutionary genetic theory. Here we used a family based exome sequencing approach to test this de novo mutation hypothesis in ten individuals with unexplained mental retardation. We identified

Lisenka E L M Vissers; Joep de Ligt; Christian Gilissen; Irene Janssen; Marloes Steehouwer; Petra de Vries; Bart van Lier; Peer Arts; Nienke Wieskamp; Marisol del Rosario; Bregje W M van Bon; Alexander Hoischen; Bert B A de Vries; Han G Brunner; Joris A Veltman

2010-01-01

323

Organ transplantation, organ donation and mental retardation  

Microsoft Academic Search

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

Marilee A. Martens; Linda Jones; Steven Reiss

2006-01-01

324

Purdue extension Growth Retardants: A Promising  

E-print Network

of trees into overhead electrical wires, was a costly operation and a chemical alternative was very attractive. Hence, the electric utility industry provided funding in the late 1950s for research on chemical and utility foresters to reduce tree and shrub size. Consequently, chemical growth retardants were developed

325

Brominated flame retardants as food contaminants  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

326

BROMINATED FLAME RETARDANTS: CAUSE FOR CONCERN?  

EPA Science Inventory

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

327

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...

328

Aerobic Fitness for the Moderately Retarded.  

ERIC Educational Resources Information Center

Intended for physical education teachers, the booklet offers ideas for incorporating aerobic conditioning into programs for moderately mentally retarded students. An explanation of aerobic fitness and its benefits is followed by information on initiating a fitness program with evaluation of height, weight, body fat, resting heart rate, and…

Bauer, Dan

1981-01-01

329

Genetics and pathophysiology of mental retardation  

Microsoft Academic Search

Mental retardation (MR) is defined as an overall intelligence quotient lower than 70, associated with functional deficit in adaptive behavior, such as daily-living skills, social skills and communication. Affecting 1–3% of the population and resulting from extraordinary heterogeneous environmental, chromosomal and monogenic causes, MR represents one of the most difficult challenges faced today by clinician and geneticists. Detailed analysis of

Jamel Chelly; Malik Khelfaoui; Fiona Francis; Beldjord Chérif; Thierry Bienvenu

2006-01-01

330

Polybrominated diphenyl ether (PBDE) flame retardants  

Microsoft Academic Search

Polybrominated diphenyl ether, PBDE, flame retardants are now a world-wide pollution problem reaching even remote areas. They have been found to bioaccumulate and there are concerns over the health effects of exposure to PBDEs, they also have potential endocrine disrupting properties. They are lipophilic compounds so are easily removed from the aqueous environment and are predicted to sorb onto sediments

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

2001-01-01

331

Flame retardant effects of magnesium hydroxide  

Microsoft Academic Search

Magnesium hydroxide has all the characteristics required for use as a flame retardant filler. It can be made synthetically with high purity and in a range of useful morphologies, responds well to surface modifiers and decomposes endothermically with release of water at temperatures close to those of polymer degradation and high enough to allow incorporation into most polymer types. Crystal

R. N. Rothon; P. R. Hornsby

1996-01-01

332

READINESS AND READING FOR THE RETARDED CHILD.  

ERIC Educational Resources Information Center

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

BERNSTEIN, BEBE

333

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.

334

Mental Illness in Persons with Mental Retardation  

Microsoft Academic Search

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

Steven Reiss; Ruth Ryan

335

45 CFR 1308.10 - Eligibility criteria: Mental retardation.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 false Eligibility criteria: Mental retardation. 1308.10 Section...DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...1308.10 Eligibility criteria: Mental retardation. (a) A...

2013-10-01

336

45 CFR 1308.10 - Eligibility criteria: Mental retardation.  

Code of Federal Regulations, 2014 CFR

...2014-10-01 false Eligibility criteria: Mental retardation. 1308.10 Section...DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...1308.10 Eligibility criteria: Mental retardation. (a) A...

2014-10-01

337

45 CFR 1308.10 - Eligibility criteria: Mental retardation.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 false Eligibility criteria: Mental retardation. 1308.10 Section...DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...1308.10 Eligibility criteria: Mental retardation. (a) A...

2011-10-01

338

45 CFR 1308.10 - Eligibility criteria: Mental retardation.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 false Eligibility criteria: Mental retardation. 1308.10 Section...DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...1308.10 Eligibility criteria: Mental retardation. (a) A...

2012-10-01

339

Thermal degradation and flame retardancy of epoxy resins containing intumescent flame retardant  

Microsoft Academic Search

Pentaerythritol diphosphonate melamine-urea-formaldehyde resin salt, a novel cheap macromolecular intumescent flame retardants\\u000a (IFR), was synthesized, and its structure was a caged bicyclic macromolecule containing phosphorus characterized by IR. Epoxy\\u000a resins (EP) were modified with IFR to get the flame retardant EP, whose flammability and burning behavior were characterized\\u000a by UL 94 and limiting oxygen index (LOI). 25 mass% of IFR

M. Gao; W. Wu; Y. Yan

2009-01-01

340

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

Microsoft Academic Search

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

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

2007-01-01

341

Recyclable flame retardant nonwoven for sound absorption; RUBA®  

Microsoft Academic Search

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

Kazuhiko Kosuge; Akira Takayasu; Teruo Hori

2005-01-01

342

Set retarded cement compositions and methods for well cementing  

Microsoft Academic Search

This patent describes a retarded cement composition consisting essentially of hydraulic cement, water, a set retarder and a borate compound. It comprises the set retarder, a copolymer consisting of acrylic acid and 2-acrylamido, 2-methylpropane sulfonic acid (AMPS) present in the copolymer in the range of from about 40 to about 60 mole percent, the copolymer having an average molecular weight

L. E. Brothers; D. W. Lindsey; D. T. Terry

1991-01-01

343

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

Microsoft Academic Search

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

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

1989-01-01

344

Characterisation of the dispersion in polymer flame retarded nanocomposites  

Microsoft Academic Search

Flame retardant nanocomposites have attracted many research efforts because they combine the advantages of a conventional flame retardant polymer with that of polymer nanocomposite. However the properties obtained depend on the dispersion of the nanoparticles. In this study, three types of polymer flame retarded nanocomposites based on different matrices (polypropylene (PP), polybutadiene terephtalate (PBT) and polyamide 6 (PA6)) have been

Fabienne Samyn; Serge Bourbigot; Charafeddine Jama; Séverine Bellayer; Shonali Nazare; Richard Hull; Alberto Fina; Andrea Castrovinci; Giovanni Camino

2008-01-01

345

Periventricular heterotopia, mental retardation, and epilepsy associated with  

E-print Network

Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion C features of three unrelated patients with epilepsy, mental retardation, and bilateral PH in the walls), mental retardation, and epilepsy, mapping to chromosome 5q14.3-q15. This observation rein- forces

Cossart, Rosa

346

Generating Models of Mental Retardation from Data with Machine Learning  

E-print Network

Generating Models of Mental Retardation from Data with Machine Learning Subramani Mani 3 Suzanne W domain models of Mental Retardation (MR) from data using Knowledge Discovery and Datamining (KDD) methods selected the domain of Mental Retardation (MR) for our study due to its complex nature and lack of simple

Pazzani, Michael J.

347

Generating Models of Mental Retardation from Data with Machine Learning  

E-print Network

Generating Models of Mental Retardation from Data with Machine Learning Subramani Mani 3 Suzanne W domain models of Mental Retardation (MR) from data using Knowledge Discovery and Datamining (KDD) methods of Medicine, Six Richland Medical Park, Columbia SC 29203. We have selected the domain of Mental Retardation

Pazzani, Michael J.

348

Neuropsychological Profiles of Persons with Mental Retardation and Dementia  

ERIC Educational Resources Information Center

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

Palmer, Glen A.

2006-01-01

349

Evaluation of Community Residential Programs for Mentally Retarded Persons.  

ERIC Educational Resources Information Center

The report evaluates how Minnesota plans, regulates, and finances residential services for mentally retarded persons. The first chapter reviews descriptive findings about the mentally retarded population in the state and notes that despite a decline in the number of state hospital residents, the total number of retarded persons in long-term care…

Minnesota State Office of the Legislative Auditor, St. Paul. Program Evaluation Div.

350

Protein  

MedlinePLUS

... sources, such as fruits, vegetables, grains, nuts and seeds, lack one or more essential amino acids. Vegetarians ... protein came from animal sources. Diabetes Again, protein quality matters more than protein quantity when it comes ...

351

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

PubMed Central

Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under accession nos. AB045357–AB045365.] PMID:11337475

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

2001-01-01

352

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

PubMed

In the present work, seven genes encoding Na(+),K(+)-ATPase (NKA) ?-subunits in the teleost Solea senegalensis are described for the first time. Sequence analysis of the predicted polypeptides revealed a high degree of conservation with those of other vertebrate species and maintenance of important motifs involved in structure and function. Phylogenetic analysis clustered the seven genes into four main clades: ?1 (atp1b1a and atp1b1b), ?2 (atp1b2a and atp1b2b), ?3 (atp1b3a and atp1b3b) and ?4 (atp1b4). In juveniles, all paralogous transcripts were detected in the nine tissues examined albeit with different expression patterns. The most ubiquitous expressed gene was atp1b1a whereas atp1b1b was mainly detected in osmoregulatory organs (gill, kidney and intestine), and atp1b2a, atp1b2b, atp1b3a, atp1b3b and atp1b4 in brain. An expression analysis in three brain regions and pituitary revealed that ?1-type transcripts were more abundant in pituitary than the other ? paralogs with slight differences between brain regions. Quantification of mRNA abundance in gills after a salinity challenge showed an activation of atp1b1a and atp1b1b at high salinity water (60ppt) and atp1b3a and atp1b3b in response to low salinity (5ppt). Transcriptional analysis during larval development showed specific expression patterns for each paralog. Moreover, no differences in the expression profiles between larvae cultivated at 10 and 35ppt were observed except for atp1b4 with higher mRNA levels at 10 than 35ppt at 18days post hatch. Whole-mount in situ hybridization analysis revealed that atp1b1b was mainly localized in gut, pronephric tubule, gill, otic vesicle, and chordacentrum of newly hatched larvae. All these data suggest distinct roles of NKA ? subunits in tissues, during development and osmoregulation with ?1 subunits involved in the adaptation to hyperosmotic conditions and ?3 subunits to hypoosmotic environments. PMID:25483323

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

2015-04-01

353

American Association on Mental Retardation 149 VOLUME 108, NUMBER 3: 149160 MAY 2003 AMERICAN JOURNAL ON MENTAL RETARDATION  

E-print Network

American Association on Mental Retardation 149 VOLUME 108, NUMBER 3: 149­160 MAY 2003 AMERICAN JOURNAL ON MENTAL RETARDATION Receptive Language Skills of Adolescents and Young Adults With Down and fragile X syndrome are the two most common genetic causes of mental retardation (Dykens, Hodapp

Nguyen, Danh

354

American Association on Mental Retardation 445 VOLUME 107, NUMBER 6: 445454 NOVEMBER 2002 AMERICAN JOURNAL ON MENTAL RETARDATION  

E-print Network

American Association on Mental Retardation 445 VOLUME 107, NUMBER 6: 445­454 NOVEMBER 2002 AMERICAN JOURNAL ON MENTAL RETARDATION Guiding Visual Attention During Acquisition of Matching-to-Sample Harry A- formances in young children and individuals with mental retardation was demonstrated here through

Dennis, Nancy

355

American Association on Mental Retardation 181 VOLUME 108, NUMBER 3: 181193 MAY 2003 AMERICAN JOURNAL ON MENTAL RETARDATION  

E-print Network

American Association on Mental Retardation 181 VOLUME 108, NUMBER 3: 181­193 MAY 2003 AMERICAN JOURNAL ON MENTAL RETARDATION Detection of Changes in Naturalistic Scenes: Comparisons of Individuals With and Without Mental Retardation Michael T. Carlin, Sal A. Soraci, and Christina P. Strawbridge Shriver Center

Dennis, Nancy

356

American Association on Mental Retardation 231 VOLUME 109, NUMBER 3: 231236 MAY 2004 AMERICAN JOURNAL ON MENTAL RETARDATION  

E-print Network

American Association on Mental Retardation 231 VOLUME 109, NUMBER 3: 231­236 MAY 2004 AMERICAN JOURNAL ON MENTAL RETARDATION The Relationship Between Age and IQ in Adults With Williams Syndrome Yvonne with autism and no mental retardation show evidence of verbal intellectual skills that improve through

Bellugi, Ursula

357

Breeding Maize for Drought Tolerance: Diversity Characterization and Linkage Disequilibrium of Maize Paralogs ZmLOX4 and ZmLOX5  

E-print Network

diversity to improve drought tolerance and aflatoxin resistance in maize. This study is among the first to investigate genetic diversity at important gene paralogs ZmLOX4 and ZmLOX5 believed to be highly conserved among all Eukaryotes. We show very little...

De La Fuente, Gerald

2012-07-16

358

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

359

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

PubMed Central

Background DNA-dependent RNA polymerase IV and V (Pol IV and V) are multi-subunit enzymes occurring in plants. The origin of Pol V, specific to angiosperms, from Pol IV, which is present in all land plants, is linked to the duplication of the gene encoding the largest subunit and the subsequent subneofunctionalization of the two paralogs (NRPD1 and NRPE1). Additional duplication of the second-largest subunit, NRPD2/NRPE2, has happened independently in at least some eudicot lineages, but its paralogs are often subject to concerted evolution and gene death and little is known about their evolution nor their affinity with Pol IV and Pol V. Results We sequenced a ~1500 bp NRPD2/E2-like fragment from 18 Viola species, mostly paleopolyploids, and 6 non-Viola Violaceae species. Incongruence between the NRPD2/E2-like gene phylogeny and species phylogeny indicates a first duplication of NRPD2 relatively basally in Violaceae, with subsequent sorting of paralogs in the descendants, followed by a second duplication in the common ancestor of Viola and Allexis. In Viola, the mutation pattern suggested (sub-) neofunctionalization of the two NRPD2/E2-like paralogs, NRPD2/E2-a and NRPD2/E2-b. The dN/dS ratios indicated that a 54 bp region exerted strong positive selection for both paralogs immediately following duplication. This 54 bp region encodes a domain that is involved in the binding of the Nrpd2 subunit with other Pol IV/V subunits, and may be important for correct recognition of subunits specific to Pol IV and Pol V. Across all Viola taxa 73 NRPD2/E2-like sequences were obtained, of which 23 (32%) were putative pseudogenes - all occurring in polyploids. The NRPD2 duplication was conserved in all lineages except the diploid MELVIO clade, in which NRPD2/E2-b was lost, and its allopolyploid derivates from hybridization with the CHAM clade, section Viola and section Melanium, in which NRPD2/E2-a occurred in multiple copies while NRPD2/E2-b paralogs were either absent or pseudogenized. Conclusions Following the relatively recent split of Pol IV and Pol V, our data indicate that these two multi-subunit enzymes are still in the process of specialization and each acquiring fully subfunctionalized copies of their subunit genes. Even after specialization, the NRPD2/E2-like paralogs are prone to pseudogenization and gene conversion and NRPD2 and NRPE2 copy number is a highly dynamic process modulated by allopolyploidy and gene death. PMID:20158916

2010-01-01

360

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. PMID:24987398

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

2014-01-01

361

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. PMID:14698924

Birnbaum, Linda S; Staskal, Daniele F

2004-01-01

362

Teaching coin summation to the mentally retarded.  

PubMed Central

A procedure to teach four mild and moderately retarded persons to sum the value of coin combinations was tested. Subjects were first taught to count a single target coin, and then to sum that coin in combination with coins previously trained. Five American coins and various combinations were trained. Modelling, modelling with subject participation, and independent counting by the subject constituted the training sequence. The subjects improved from a mean pretest score of 29% to 92% correct at posttest. A four-week followup score showed a mean of 79% correct. A multiple-baseline design suggested that improvement in coin-counting performance occurred only after the coin was trained. The results indicate that this procedure has potential for teaching the retarded to sum combinations of coinds in 5 to 6 hr of instruction. PMID:1002634

Lowe, M L; Cuvo, A J

1976-01-01

363

The evaluation of reaction time on mentally retarded children.  

PubMed

This study was designed to compare the parameters of reaction time on mentally retarded and healthy children and also to find out the effect of sport on reaction time. The study consisted of 20 non-retarded (group I), 20 non-sporting trainable mentally retarded (group II), and 20 sporting trainable mentally retarded (group III). The avarage age of subjects were determined as 15.35 +/- 0.21 years in group I, 15.00 +/- 0.22 years in group II, and 15.15 +/- 0.21 years in group III. The audiovisual reaction time of both non-retarded and retarded children were measured. It was found that reaction time is lower in trainable mentally retarded children (p < 0.05). It can be concluded that sport is a valid and effective means of training which affects the reaction time positively. PMID:11330846

Un, N; Erbahçeci, F

2001-01-01

364

Chemistry and toxicity of flame retardants for plastics.  

PubMed Central

An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products. PMID:1026419

Liepins, R; Pearce, E M

1976-01-01

365

The Right to Education for the Retarded  

E-print Network

District.69 In another landmark case, Hobson v. Hansen,70 the court ruled that the "tracking" system of educational placement used in Washington, D. C. public schools was illegal. The plaintiffs used the aforementioned argu- ment that the testing...The Right to Education for the Retarded Jan Sheldon James A. Sherman University of Kansas Introduction Today, education is perhaps the most important function of state and local governments. Compulsory school attendance laws and the great...

Sheldon, Jan B.; Sherman, James A.

1974-08-01

366

Diagnostic Genome Profiling in Mental Retardation  

Microsoft Academic Search

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

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

2005-01-01

367

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

368

Unexplained mental retardation: is brain MRI useful?  

Microsoft Academic Search

Background: Mental retardation (MR), defined as an IQ below 70, is a frequent cause of consultation in paediatrics. Objective: To evaluate the yield of brain MRI in the diagnostic work-up of unexplained MR in children. Patients and methods: The MRI features and clinical data of 100 patients (age 1–18 years) affected with non-progressive MR of unknown origin were compared to an

Fabrice Decobert; Sophie Grabar; Valerie Merzoug; Gabriel Kalifa; Gérard Ponsot; Catherine Adamsbaum; Vincent des Portes

2005-01-01

369

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

Microsoft Academic Search

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

Ine Jorgensen; Raphael H. Valdivia

2008-01-01

370

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

PubMed Central

Background The ability to produce physiologically critical LC-PUFA from dietary fatty acids differs greatly among teleost species, and is dependent on the possession and expression of fatty acyl desaturase and elongase genes. Atlantic salmon, as a result of a recently duplicated genome, have more of these enzymes than other fish. Recent phylogenetic studies show that Northern pike represents the closest extant relative of the preduplicated ancestral salmonid. Here we characterise a pike fatty acyl elongase, elovl5, and compare it to Atlantic salmon elovl5a and elovl5b duplicates. Results Phylogenetic analyses show that Atlantic salmon paralogs are evolving symmetrically, and they have been retained in the genome by purifying selection. Heterologous expression in yeast showed that Northern pike Elovl5 activity is indistinguishable from that of the salmon paralogs, efficiently elongating C18 and C20 substrates. However, in contrast to salmon, pike elovl5 was predominantly expressed in brain with negligible expression in liver and intestine. Conclusions We suggest that the predominant expression of Elovl5b in salmon liver and Elovl5a in salmon intestine is an adaptation, enabled by genome duplication, to a diet rich in terrestrial invertebrates which are relatively poor in LC-PUFA. Pike have retained an ancestral expression profile which supports the maintenance of PUFA in the brain but, due to a highly piscivorous LC-PUFA-rich diet, is not required in liver and intestine. Thus, the characterisation of elovl5 in Northern pike provides insights into the evolutionary divergence of duplicated genes, and the ecological adaptations of salmonids which have enabled colonisation of nutrient poor freshwaters. PMID:23597093

2013-01-01

371

Functional Modeling Identifies Paralogous Solanesyl-diphosphate Synthases That Assemble the Side Chain of Plastoquinone-9 in Plastids*  

PubMed Central

It is a little known fact that plastoquinone-9, a vital redox cofactor of photosynthesis, doubles as a precursor for the biosynthesis of a vitamin E analog called plastochromanol-8, the physiological significance of which has remained elusive. Gene network reconstruction, GFP fusion experiments, and targeted metabolite profiling of insertion mutants indicated that Arabidopsis possesses two paralogous solanesyl-diphosphate synthases, AtSPS1 (At1g78510) and AtSPS2 (At1g17050), that assemble the side chain of plastoquinone-9 in plastids. Similar paralogous pairs were detected throughout terrestrial plant lineages but were not distinguished in the literature and genomic databases from mitochondrial homologs involved in the biosynthesis of ubiquinone. The leaves of the atsps2 knock-out were devoid of plastochromanol-8 and displayed severe losses of both non-photoactive and photoactive plastoquinone-9, resulting in near complete photoinhibition at high light intensity. Such a photoinhibition was paralleled by significant damage to photosystem II but not to photosystem I. In contrast, in the atsps1 knock-out, a small loss of plastoquinone-9, restricted to the non-photoactive pool, was sufficient to eliminate half of the plastochromanol-8 content of the leaves. Taken together, these results demonstrate that plastochromanol-8 originates from a subfraction of the non-photoactive pool of plastoquinone-9. In contrast to other plastochromanol-8 biosynthetic mutants, neither the single atsps knock-outs nor the atsps1 atsps2 double knock-out displayed any defects in tocopherols accumulation or germination. PMID:23913686

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

2013-01-01

372

Conservation of Telomere protein complexes: Shuffling through Evolution  

PubMed Central

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

Linger, Benjamin R.; Price, Carolyn M.

2009-01-01

373

Altered synaptic plasticity in a mouse model of fragile X mental retardation  

PubMed Central

Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome. PMID:12032354

Huber, Kimberly M.; Gallagher, Sean M.; Warren, Stephen T.; Bear, Mark F.

2002-01-01

374

Homology Modeling and Domain Interactions in Fetal Serum Protein  

NSDL National Science Digital Library

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

Steve Festin (Hamilton College; )

2003-10-12

375

The mGluR theory of fragile X mental retardation  

Microsoft Academic Search

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

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

2004-01-01

376

Protein  

MedlinePLUS

... meet their protein needs. With some planning, a vegetarian diet can easily meet the recommended protein needs of ... the American Dietetic Association and Dietitians of Canada: Vegetarian diets. JADA , 2003; 103(6) 748 – 765. 2 Source ...

377

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

378

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

379

Nanotechnology finding its way into flame retardancy  

SciTech Connect

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

Schartel, Bernhard, E-mail: bernhard.schartel@bam.de [BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin (Germany)

2014-05-15

380

Optimization of retardance for a complete Stokes polarimeter.  

PubMed

We present two figures of merit based on singular value decomposition, which can be used to assess the noise immunity of a complete Stokes polarimeter. These are used to optimize a polarimeter featuring a rotatable retarder and a fixed polarizer. A retardance of 132 degrees (approximately three-eighths wave) and retarder orientation angles of +/-51.7 degrees and +/-15.1 degrees are found to be optimal when four measurements are used. Use of this retardance affords a factor-of-1.5 improvement in signal-to-noise ratio over systems employing a quarter-wave plate. A geometric means of visualizing the optimization process is discussed, and the advantages of the use of additional measurements are investigated. No advantage of using retarder orientation angles spaced uniformly through 360 degrees is found over repeated measurements made at the four retarder orientation angles. PMID:18064189

Sabatke, D S; Descour, M R; Dereniak, E L; Sweatt, W C; Kemme, S A; Phipps, G S

2000-06-01

381

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

382

?-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome  

PubMed Central

This article describes three rare syndromes in which the presence of ?-thalassemia provided an important clue to the molecular basis of the underlying condition. It exemplifies how rare diseases allied with careful clinical observation can lead to important biological principles. Two of the syndromes, ATR-16 and ATR-X, are characterized by ?-thalassemia in association with multiple developmental abnormalities including mental retardation. The third condition, ATMDS, is an acquired disorder in which ?-thalassemia arises in the context of myelodysplasia. Intriguingly, mutations in the chromatin remodeling factor, ATRX, are common to both ATR-X syndrome and ATMDS. PMID:23028133

Gibbons, Richard J.

2012-01-01

383

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

384

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. PMID:22401293

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

2012-01-01

385

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

386

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. PMID:24600577

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

2014-01-01

387

Bioelectronic measurement of nasality in trainable mentally retarded children.  

PubMed

Fifty trainable mentally retarded children were evaluated with TONAR II, a bioelectronic instrument for detecting and quantitatively measuring voice parameters. Results indicated that one-half of the children tested were hypernasal. The strikingly high prevalence of excessive nasality was contrasted with results obtained from 64 nonretarded children and 50 educable retarded children tested with the same instrument. The study demonstrated the need of retarded persons for improved voice and resonance. PMID:881825

Daly, D A

1977-08-01

388

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. PMID:21927406

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

1989-01-01

389

Evaluation of Still Picture Telephone for Mentally Retarded Persons. Telematics and Mental Retardation.  

ERIC Educational Resources Information Center

This study examined the benefit of using a visual telecommunication system for Sweden's children and adults with mild to moderate mental retardation and speech difficulties. The Panasonic Image Communication Unit connects to standard modular telephones and includes a camera and monitor for the transfer of pictures. Units were placed in eight…

Brodin, Jane; Bjorck-Akesson, Eva

390

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. PMID:24659990

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

2014-01-01

391

High phase retardation by waveguiding in slanted photonic nanostructures.  

PubMed

We report a physical mechanism leading to high phase retardation in slanted photonic nanostructures. The phenomenon is based on the waveguiding of the transverse electric polarization component inside the slanted pillars, while the transverse magnetic component is not guided. Such a mechanism leads to very high phase retardation even with shallow structures that are suitable also for lithographical mass production. We present physical principle, numerical analysis of the phenomenon and designs for half-wave retarders. As an experimental result, a slanted grating producing 177 degrees retardation and 95.5% efficiency is presented. PMID:21263562

Ventola, Kalle; Tervo, Jani; Laakkonen, Pasi; Kuittinen, Markku

2011-01-01

392

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

393

The involvement of epigenetic defects in mental retardation.  

PubMed

Mental retardation is a group of cognitive disorders with a significant worldwide prevalence rate. This high rate, together with the considerable familial and societal burden resulting from these disorders, makes it an important focus for prevention and intervention. While the diseases associated with mental retardation are diverse, a significant number are linked with disruptions in epigenetic mechanisms, mainly due to loss-of-function mutations in genes that are key components of the epigenetic machinery. Additionally, several disorders classed as imprinting syndromes are associated with mental retardation. This review will discuss the epigenetic abnormalities associated with mental retardation, and will highlight their importance for diagnosis, treatment, and prevention of these disorders. PMID:21549207

Franklin, Tamara B; Mansuy, Isabelle M

2011-07-01

394

Differences in neonatal neurotoxicity of brominated flame retardants, PBDE 99 and TBBPA, in mice.  

PubMed

Flame retardants such as polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A are used as flame retardants and detected in the environmental, wildlife species and human tissues. Exposure to PBDEs during the neonatal development of the brain has been shown to affect behavior and learning and memory in adult mice, while neonatal exposure to TBBPA (another brominated flame retardant) did not affect behavioral variables in the adult. In this study, we hypothesized that the effects of these compounds could be reflected by changes in biochemical substrates and cholinergic receptors and have examined the levels of four proteins involved in maturation of the brain, neuronal growth and synaptogenesis and the densities of both muscarinic and nicotinic cholinergic receptors. We measured the levels of radioactivity in the brain after administration of (14)C-labelled TBBPA at different time points and saw that levels of TBBA peaked earlier and decreased faster than the earlier reported levels of PBDE 99. The protein analysis in the neonatal brain showed changes in the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), growth associated protein-43 (GAP-43) and synaptophysin following neonatal exposure to PBDE 99 (21 ?mol/kg body weight), but not following exposure TBBPA. Furthermore, neonatal exposure to PBDE 99 and TBBPA caused a decrease in binding sites of the nicotinic ligand cytisine in frontal cortex. These results confirm earlier reported data that PBDE 99 can act as a developmental neurotoxicant, possibly due to its different uptake and retention in the brain compared to TBBPA. In addition, the changes in protein levels are interesting leads in the search for mechanisms behind the developmental neonatal neurotoxicity of PBDEs in general and PBDE 99 in particular, since also other compounds inducing similar adult behavioral disturbances as PBDE 99, affect these proteins during the period of rapid brain development. PMID:21820030

Viberg, Henrik; Eriksson, Per

2011-10-28

395

Proteins  

NSDL National Science Digital Library

Paul Anderson explains the structure and importance of proteins. He describes how proteins are created from amino acids connected by dehydration synthesis. He shows the importance of chemical properties in the R-groups of individual amino acids in the polypeptide.

Paul Anderson

2013-03-12

396

Proteins  

NSDL National Science Digital Library

Laboratory manual and supplemental resources that were developed for a college laboratory course in protein purification. The enzyme, Beta-galactosidase, is purified in two steps, with analysis and verification of results. Course materials are divided into four units: Why Proteins, Assays, The Purification Process, and Analysis and Verification. Powerpoint lectures and study guides are provided.

Mowery, Jeanette

397

Proteins.  

ERIC Educational Resources Information Center

Examines proteins which give rise to structure and, by virtue of selective binding to other molecules, make genes. Binding sites, amino acids, protein evolution, and molecular paleontology are discussed. Work with encoding segments of deoxyribonucleic acid (exons) and noncoding stretches (introns) provides new information for hypotheses. (DH)

Doolittle, Russell F.

1985-01-01

398

Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers  

PubMed Central

Background Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Results Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Conclusion Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies. PMID:19154605

Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

2009-01-01

399

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

400

Expression, localization, structural, and functional characterization of pFGE, the paralog of the Calpha-formylglycine-generating enzyme.  

PubMed

pFGE is the paralog of the formylglycine-generating enzyme (FGE), which catalyzes the oxidation of a specific cysteine to Calpha-formylglycine, the catalytic residue in the active site of sulfatases. The enzymatic activity of sulfatases depends on this posttranslational modification, and the genetic defect of FGE causes multiple sulfatase deficiency. The structural and functional properties of pFGE were analyzed. The comparison with FGE demonstrates that both share a tissue-specific expression pattern and the localization in the lumen of the endoplasmic reticulum. Both are retained in the endoplasmic reticulum by a saturable mechanism. Limited proteolytic cleavage at similar sites indicates that both also share a similar three-dimensional structure. pFGE, however, is lacking the formylglycine-generating activity of FGE. Although overexpression of FGE stimulates the generation of catalytically active sulfatases, overexpression of pFGE has an inhibitory effect. In vitro pFGE interacts with sulfatase-derived peptides but not with FGE. The inhibitory effect of pFGE on the generation of active sulfatases may therefore be caused by a competition of pFGE and FGE for newly synthesized sulfatase polypeptides. PMID:15708861

Mariappan, Malaiyalam; Preusser-Kunze, Andrea; Balleininger, Martina; Eiselt, Nicole; Schmidt, Bernhard; Gande, Santosh Lakshmi; Wenzel, Dirk; Dierks, Thomas; von Figura, Kurt

2005-04-15

401

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

PubMed

Gene duplication is an important mechanism for the origination of functional novelties in organisms. We performed a comparative genome analysis to systematically estimate recent lineage specific gene duplication events in Arabidopsis thaliana and further investigate whether and how these new duplicate genes (NDGs) play a functional role in the evolution and adaption of A. thaliana. We accomplished this using syntenic relationship among four closely related species, A. thaliana, A. lyrata, Capsella rubella and Brassica rapa. We identified 100 NDGs, showing clear origination patterns, whose parental genes are located in syntenic regions and/or have clear orthologs in at least one of three outgroup species. All 100 NDGs were transcribed and under functional constraints, while 24% of the NDGs have differential expression patterns compared to their parental genes. We explored the underlying evolutionary forces of these paralogous pairs through conducting neutrality tests with sequence divergence and polymorphism data. Evolution of about 15% of NDGs appeared to be driven by natural selection. Moreover, we found that 3 NDGs not only altered their expression patterns when compared with parental genes, but also evolved under positive selection. We investigated the underlying mechanisms driving the differential expression of NDGs and their parents, and found a number of NDGs had different cis-elements and methylation patterns from their parental genes. Overall, we demonstrated that NDGs acquired divergent cis-elements and methylation patterns and may experience sub-functionalization or neo-functionalization influencing the evolution and adaption of A. thaliana. PMID:24009676

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

2013-01-01

402

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

PubMed Central

Identification of genes regulated by the ferric uptake regulator (Fur) protein has provided insights into the diverse mechanisms of adaptation to iron limitation. In the soil bacterium Bacillus subtilis, Fur senses iron sufficiency and represses genes that enable iron uptake, including biosynthetic and transport genes for the siderophore bacillibactin and uptake systems for siderophores produced by other organisms. We here demonstrate that Fur regulates hmoA (formerly yetG), which encodes a haem monooxygenase. HmoA is the first characterized member of a divergent group of putative monooxygenases that cluster separately from the well-characterized IsdG family. B. subtilis also encodes an IsdG family protein designated HmoB (formerly YhgC). Unlike hmoA, hmoB is constitutively expressed and not under Fur control. HmoA and HmoB both bind haemin in vitro with approximately 1?:?1 stoichiometry and degrade haemin in the presence of an electron donor. Mutational and spectroscopic analyses indicate that HmoA and HmoB have distinct active site architectures and interact differently with haem. We further show that B. subtilis can use haem as an iron source, but that this ability is independent of HmoA and HmoB. PMID:21873409

Gaballa, Ahmed

2011-01-01

403

Programs for Preventing the Causes of Mental Retardation.  

ERIC Educational Resources Information Center

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

Oliphant, Peter S.; And Others

404

Novel phosphonates triazine derivative as economic flame retardant for cotton  

Technology Transfer Automated Retrieval System (TEKTRAN)

Phosphorous-containing flame retardants are widely used in standard and engineering plastics, polyurethane foams, thermosets, coatings, and textiles. Organophosphorous flame retardants have been known to be more effective when used in conjunction with nitrogen-containing systems. Their mixture produ...

405

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

ERIC Educational Resources Information Center

Review of the literature on psychopharmacology and mental retardation from 1990-1999 found most studies had major methodological flaws. Also, most drug administrations were not based in science, were not evaluated appropriately, and generally did not follow best practices for treatment of persons with mental retardation. A table lists the studies…

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

2000-01-01

406

Cognitive Representation of Motion in Individuals with Mental Retardation.  

ERIC Educational Resources Information Center

Fifteen adolescents with and 15 without mental retardation were compared on their tendency to show the representational momentum effect when viewing a stimulus array that implied motion. Participants with mental retardation showed the representational momentum effects as did the others, although the magnitude of the memory shift was smaller.…

Conners, Frances A.; Wyatt, Beverly S.; Dulaney, Cynthia L.

1998-01-01

407

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 ...

408

Zinc Stannates as Alternative Synergists in Selected Flame Retardant Systems  

Microsoft Academic Search

Zinc stannates, including zinc hydroxystannate, are used components within synergistic fire retardant systems usually in conjunction with halogenated species in a number of polymers. Their behavior is similar to antimony III oxide (ATO) in that they enhance the effectiveness of the halogenated and, principally brominated retardant (Br-FR), present. Unlike antimony III oxide, they are non-toxic but are specific in their

A. R. Horrocks; G. Smart; D. Price; B. Kandola

2009-01-01

409

Physical Trauma as an Etiological Agent in Mental Retardation.  

ERIC Educational Resources Information Center

The conference on Physical Trauma as a Cause of Mental Retardation dealt with two major areas of etiological concern - postnatal and perinatal trauma. Following two introductory statements on the problem of and issues related to mental retardation (MR) after early trauma to the brain, five papers on the epidemiology of head trauma cover…

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

410

Matt: The Mentally Retarded Child in Your Classroom.  

ERIC Educational Resources Information Center

Intended for regular class teachers, the booklet provides information to aid in mainstreaming the mentally retarded (MR) child. Sections address the following areas: reasons for mainstreaming the MR student; definition of mental retardation; assessment (areas of assessment and suggested evaluation measures, the assessment team); suggested readings…

Gear, Gayle; And Others

411

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

412

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

413

Development of the Fear Survey for Adults with Mental Retardation  

ERIC Educational Resources Information Center

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

Ramirez, Sylvia Z.; Lukenbill, James F.

2007-01-01

414

Family Problem-Solving with Children Who Have Mental Retardation  

ERIC Educational Resources Information Center

Problem-solving discussions were observed within families of children with mental retardation and multiple comparison groups (total N = 162 families). As expected, parents were more persistent and directive with their children who had mental retardation, but they also avoided negative exchanges with these children. These patterns did not spillover…

Floyd, Frank J; Harter, Kristina S. M.; Costigan, Catherine L.

2004-01-01

415

Reflections on a Lifetime in Human Services and Mental Retardation  

ERIC Educational Resources Information Center

The author, a life member of the American Association on Mental Retardation, has reflected on over 30 years of primary engagement in mental retardation and inventoried what he believes are certain changes for the better and for the worse that have occurred since the 1950s as well as certain things that have not changed. Some action implications…

Wolfensberger, Wolf

2011-01-01

416

Community Involvement and Socialization among Individuals with Mental Retardation  

ERIC Educational Resources Information Center

Mental retardation, a condition characterized by significantly lower than average intellectual ability and adaptive behavior deficits, currently affects between 2% and 3% of the population. Individuals with mental retardation experience many difficulties throughout their lives, with one such difficulty being that they have few opportunities for…

Kampert, Amy L.; Goreczny, Anthony J.

2007-01-01

417

Defining Mental Retardation and Ensuring Access to the General Curriculum.  

ERIC Educational Resources Information Center

Discussion of trends in the American Association on Mental Retardation's definition of mental retardation notes a shift toward a support paradigm and a definition stressing the interaction between a person's independent functioning and the various contexts of the person's life. The current definition is seen to promote greater access to the…

Wehmeyer, Michael L.

2003-01-01

418

Adaptive Behavior Malingering in Legal Claims of Mental Retardation  

ERIC Educational Resources Information Center

In 2002, the Supreme Court ruled that it is unconstitutional to put people with mental retardation to death for capital crimes ("Atkins v. Virginia," 2002). Justice Scalia dissented, suggesting that mental retardation is a condition easy to feign. The current study examined whether participants provided with the definition of mental…

Kadlubek, Renee Marie

2012-01-01

419

Defining Mental Retardation: A Matter of Life or Death  

ERIC Educational Resources Information Center

Because persons with mental retardation cannot be executed for murder, the diagnosis becomes a life and death matter. The American Association on Mental Retardation (now the American Association on Intellectual and Developmental Disabilities) and other associations agree that IQ alone is an insufficient criterion and adaptive functioning also…

Lichten, William; Simon, Elliot W.

2007-01-01

420

Promotion of asparagus shoot and root growth by growth retardants  

Microsoft Academic Search

Plantlets regenerated from shoot-tip culture of Asparagus officinalis L. possessed weak shoots and roots. Various combinations of auxins and cytokinins did not improve the plantlets. Incorporation of a number of growth retardants, viz. ancymidol, B-995, phosfon, Amo 1618, cycocel and paclobutrazol, promoted growth of stronger shoots and roots. The effectiveness of the growth retardants varied, with ancymidol being most effective

Alisa Khunachak; Chee-Kok Chin; Trang Le; Tom Gianfagna

1987-01-01

421

Qualitative Differences in the Structure of Intelligence of Retarded Children.  

ERIC Educational Resources Information Center

To examine whether or not retarded individuals have the same structure of intelligence as normal IQ individuals, test scores from the Wechsler Intelligence Scale for Children-Revised (WISC-R), Reitan's Trail Making Test (TMT), and Beery's Developmental Test of Visual Motor Integration (VMI) for both a mildly retarded and normal IQ population of…

Wilson, Sheryl L.; Cleaves, Wallace T.

422

Muscle Fatigue during Intermittent Exercise in Individuals with Mental Retardation  

ERIC Educational Resources Information Center

This study examined fatigue profile during intermittent exercise in 10 men with mild to moderate mental retardation (MR) and 10 men without mental retardation (C). They performed 4 x 30 s maximal knee extensions and flexions with 1-min rest on an isokinetic dynamometer. Peak torque of flexors (PTFL) and extensors (PTEX), total work (TW), and…

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

2010-01-01

423

Further Evidence for Cognitive Inertia of Persons with Mental Retardation.  

ERIC Educational Resources Information Center

Forty young adults with mental retardation (MR) were compared to 40 young adults without mental retardation in tests examining postpractice interference effects in naming colors of Stroop words. The study concluded that practice developed automatized reading suppression responses which held greater cognitive inertia for longer periods among MR…

Ellis, Norman R.; Dulaney, Cynthia L.

1991-01-01

424

Newborn Screening To Prevent Mental Retardation. The Arc Q & A.  

ERIC Educational Resources Information Center

This information fact sheet on screening newborns to prevent mental retardation defines newborn screening and outlines how screening is performed. It discusses the six most common disorders resulting in mental retardation for which states most commonly screen. These include phenylketonuria, congenital hypothyroidism, galactosemia, maple syrup…

Arc, Arlington, TX.

425

Flame retardant properties of triazine phosphonates derivative with cotton fabric  

Technology Transfer Automated Retrieval System (TEKTRAN)

The flame retardant behavior of a cotton fabric treated with phosphorus-nitrogen containing triazine compound was evaluated. It was found that cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) is an excellent starting material for the preparation of phosphonates flame retardants that interacts wel...

426

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

427

Flame retardant antibacterial cotton high-loft nonwoven fabrics  

Technology Transfer Automated Retrieval System (TEKTRAN)

Flame retardant treated gray cotton fibers were blended with antibacterial treated gray cotton fibers and polyester/polyester sheath/core bicomponent fibers to form high-loft fabrics. The high flame retardancy (FR) and antibacterial property of these high lofts were evaluated by limiting oxygen inde...

428

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...

429

Cursorial spiders retard initial aphid population growth at low densities  

E-print Network

Cursorial spiders retard initial aphid population growth at low densities in winter wheat K technique that revealed species-specific aphid consump- tion rates with a factorial field experiment on aphid population growth. Only cursorial spiders retarded aphid population growth in our cage experiment

Illinois at Chicago, University of

430

Emerging Brominated Flame Retardants in the Environment  

Microsoft Academic Search

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

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

431

Teaching coin equivalence to the mentally retarded.  

PubMed Central

A program was designed to teach coin equivalence to mentally retarded adolescents. Coin equivalence was defined as choosing several different combinations of coins to equal specified target values. A pretest-posttest matched-groups design was employed with an experimental group receiving the monetary training, and a no-training control group. A multiple baseline across coin-counting responses was also incorporated in the experimental group. Training was divided into six stages, each teaching one specific method of combining coins to equal 10 target values from 5 cents through 50 cents. A three-component response chain was used, requiring (a) naming, (b) selecting and counting, and (c) depositing target monetary values into a coin machine. Experimental subjects improved significantly in coin equivalence performance and maintained their skill on follow up tests; control subjects did not. PMID:845100

Trace, M W; Cuvo, A J; Criswell, J L

1977-01-01

432

Highly accurate spectral retardance characterization of a liquid crystal retarder including Fabry-Perot interference effects  

SciTech Connect

Multiple-beam Fabry-Perot (FP) interferences occur in liquid crystal retarders (LCR) devoid of an antireflective coating. In this work, a highly accurate method to obtain the spectral retardance of such devices is presented. On the basis of a simple model of the LCR that includes FP effects and by using a voltage transfer function, we show how the FP features in the transmission spectrum can be used to accurately retrieve the ordinary and extraordinary spectral phase delays, and the voltage dependence of the latter. As a consequence, the modulation characteristics of the device are fully determined with high accuracy by means of a few off-state physical parameters which are wavelength-dependent, and a single voltage transfer function that is valid within the spectral range of characterization.

Vargas, Asticio [Departamento de Ciencias Físicas, Universidad de La Frontera, Temuco (Chile); Center for Optics and Photonics, Universidad de Concepción, Casilla 4016, Concepción (Chile); Mar Sánchez-López, María del [Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche (Spain); García-Martínez, Pascuala [Departament d'Òptica, Universitat de València, 45100 Burjassot (Spain); Arias, Julia; Moreno, Ignacio [Departamento de Ciencia de Materiales, Óptica y Tecnología Electrónica, Universidad Miguel Hernández, 03202 Elche (Spain)

2014-01-21

433

16 CFR 1631.33 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2012 CFR

...rugs with fire-retardant treatment. 1631.33 Section 1631...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF SMALL CARPETS...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2012-01-01

434

16 CFR 1630.32 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2010 CFR

...rugs with fire-retardant treatment. 1630.32 Section 1630...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF CARPETS AND...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2010-01-01

435

16 CFR 1630.32 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2011 CFR

...rugs with fire-retardant treatment. 1630.32 Section 1630...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF CARPETS AND...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2011-01-01

436

16 CFR 1630.32 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2013 CFR

...rugs with fire-retardant treatment. 1630.32 Section 1630...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF CARPETS AND...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2013-01-01

437

16 CFR 1630.32 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2014 CFR

...rugs with fire-retardant treatment. 1630.32 Section 1630...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF CARPETS AND...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2014-01-01

438

16 CFR 1630.32 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2012 CFR

...rugs with fire-retardant treatment. 1630.32 Section 1630...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF CARPETS AND...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2012-01-01

439

16 CFR 1631.33 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2011 CFR

...rugs with fire-retardant treatment. 1631.33 Section 1631...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF SMALL CARPETS...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2011-01-01

440

16 CFR 1631.33 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2010 CFR

...rugs with fire-retardant treatment. 1631.33 Section 1631...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF SMALL CARPETS...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2010-01-01

441

16 CFR 1631.33 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2013 CFR

...rugs with fire-retardant treatment. 1631.33 Section 1631...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF SMALL CARPETS...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2013-01-01

442

16 CFR 1631.33 - Carpets and rugs with fire-retardant treatment.  

Code of Federal Regulations, 2014 CFR

...rugs with fire-retardant treatment. 1631.33 Section 1631...REGULATIONS STANDARD FOR THE SURFACE FLAMMABILITY OF SMALL CARPETS...rugs with fire-retardant treatment. (a) For the purposes... (2) Fire-retardant treatment means...

2014-01-01

443

76 FR 66750 - Certain Projectors With Controlled-Angle Optical Retarders, Components Thereof, and Products...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Certain Projectors With Controlled-Angle Optical Retarders, Components Thereof, and Products...Certain Projectors with Controlled-Angle Optical Retarders, Components Thereof, And Products...certain projectors with controlled-angle optical retarders, components thereof, and...

2011-10-27

444

Muscle Specific Fragile X Related Protein 1 Isoforms are Sequestered in the Nucleus of Undifferentiated Myoblast  

Microsoft Academic Search

BACKGROUND: The family of Fragile X Mental Retardation Proteins is composed of three members: Fragile Mental Retardation 1, Fragile X Related 1 and X Related 2 proteins. These proteins are associated with mRNPs within translating ribosomes and have the capacity to shuttle between the nucleus and the cytoplasm. Great attention has been given to FMRP due to its implication in

Marthe Dubé; Marc-Etienne Huot; Edouard W Khandjian

2000-01-01

445

Schizosaccharomyces pombe possesses two paralogous valyl-tRNA synthetase genes of mitochondrial origin.  

PubMed

Previous studies showed that VAS1 of Saccharomyces cerevisiae encodes both cytosolic and mitochondrial forms of valyl-tRNA synthetase (ValRS) through alternative initiation of translation. We show herein that except for Schizosaccharomyces pombe, all yeast species studied contained a single ValRS gene encoding both forms, and all of the mature protein forms deduced from those genes possessed an N-terminal appended domain (Ad) that was absent from their bacterial relatives. In contrast, S. pombe contained two distinct nuclear ValRS genes, one encoding the mitochondrial form and the other its cytosolic counterpart. Although the cytosolic form closely resembles other yeast ValRS sequences (approximately 60% identity), the mitochondrial form exhibits significant divergence from others (approximately 35% identity). Both genes are active and essential for the survival of the yeast. Most conspicuously, the mitochondrial form lacks the characteristic Ad. A phylogenetic analysis further suggested that both forms of S. pombe ValRS are of mitochondrial origin, and the mitochondrial form is ancestral to the cytoplasmic form. PMID:20106903

Chiu, Wen-Chih; Chang, Chia-Pei; Wen, Wei-Ling; Wang, Shao-Win; Wang, Chien-Chia

2010-06-01

446

78 FR 5755 - Change in Terminology: “Mental Retardation” to “Intellectual Disability”  

Federal Register 2010, 2011, 2012, 2013, 2014

...Retardation'' to ``Intellectual Disability'' AGENCY: Social Security...retardation'' with ``intellectual disability'' in our Listing of Impairments...adoption of the term ``intellectual disability'' by Congress,...

2013-01-28

447

78 FR 46499 - Change in Terminology: “Mental Retardation” to “Intellectual Disability”  

Federal Register 2010, 2011, 2012, 2013, 2014

...Retardation'' to ``Intellectual Disability'' AGENCY: Social Security...retardation'' with ``intellectual disability'' in our Listing of Impairments...adoption of the term ``intellectual disability'' by Congress,...

2013-08-01

448

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

Code of Federal Regulations, 2012 CFR

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

2012-07-01

449

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

Code of Federal Regulations, 2010 CFR

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

2010-07-01

450

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

Code of Federal Regulations, 2011 CFR

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

2011-07-01

451

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

Code of Federal Regulations, 2014 CFR

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

2014-07-01

452

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

Code of Federal Regulations, 2013 CFR

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

2013-07-01

453

Flame Retardant Applications in Camping Tents and Potential Exposure  

PubMed Central

Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met CPAI-84 standards by analyzing 11 samples of tent fabrics for chemical flame retardant additives. Furthermore, we investigated potential exposure by collecting paired samples of tent wipes and hand wipes from 27 individuals after tent setup. Of the 11 fabric samples analyzed, 10 contained flame retardant additives, which included tris(1,3-dichloroisopropyl) phosphate (TDCPP), decabromodiphenyl ether (BDE-209), triphenyl phosphate, and tetrabromobisphenol-A. Flame retardant concentrations were discovered to be as high as 37.5 mg/g (3.8% by weight) in the tent fabric samples, and TDCPP and BDE-209 were the most frequently detected in these samples. We also observed a significant association between TDCPP levels in tent wipes and those in paired hand wipes, suggesting that human contact with the tent fabric material leads to the transfer of the flame retardant to the skin surface and human exposure. These results suggest that direct contact with flame retardant-treated textiles may be a source of exposure. Future studies will be needed to better characterize exposure, including via inhalation and dermal sorption from air. PMID:24804279

2015-01-01

454

Flame Retardant Applications in Camping Tents and Potential Exposure.  

PubMed

Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met CPAI-84 standards by analyzing 11 samples of tent fabrics for chemical flame retardant additives. Furthermore, we investigated potential exposure by collecting paired samples of tent wipes and hand wipes from 27 individuals after tent setup. Of the 11 fabric samples analyzed, 10 contained flame retardant additives, which included tris(1,3-dichloroisopropyl) phosphate (TDCPP), decabromodiphenyl ether (BDE-209), triphenyl phosphate, and tetrabromobisphenol-A. Flame retardant concentrations were discovered to be as high as 37.5 mg/g (3.8% by weight) in the tent fabric samples, and TDCPP and BDE-209 were the most frequently detected in these samples. We also observed a significant association between TDCPP levels in tent wipes and those in paired hand wipes, suggesting that human contact with the tent fabric material leads to the transfer of the flame retardant to the skin surface and human exposure. These results suggest that direct contact with flame retardant-treated textiles may be a source of exposure. Future studies will be needed to better characterize exposure, including via inhalation and dermal sorption from air. PMID:24804279

Keller, Alexander S; Raju, Nikhilesh P; Webster, Thomas F; Stapleton, Heather M

2014-02-11

455

Pcgf6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ESCs and functions in iPS reprogramming.  

PubMed

Polycomb group (PcG) proteins comprise evolutionary conserved factors with essential functions for embryonic development and adult stem cells. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene transcription. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (Pcgf) paralogs. So far, six Pcgf paralogs (Pcgf1-6) have been identified as defining components of different PCR1-type complexes. Paralog-specific functions are not well understood. Here, we show that Pcgf6 is the only Pcgf paralog with high expression in undifferentiated embryonic stem cells (ESCs). Upon differentiation Pcgf6 expression declines. Following Pcgf6 kockdown (KD) in ESCs, the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were derepressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities upon differentiation suggesting a function of Pcgf6 in repressing mesodermal-specific lineage genes. Consistant with a role in pluripotency, Pcgf6 replaced Sox2 in the generation of germline-competent induced pluripotent stem (iPS) cells. Furthermore, Pcgf6 KD in mouse embryonic fibroblasts reduced the formation of ESC-like colonies in OSKM-driven reprogramming. Together, these analyses indicate that Pcgf6 is nonredundantly involved in maintaining the pluripotent nature of ESCs and it functions in iPS reprogramming. PMID:25187489

Zdzieblo, D; Li, X; Lin, Q; Zenke, M; Illich, D J; Becker, M; Müller, A M

2014-12-01

456

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 5 days after hatching (dah) in the somatic cells in XX gonads, whereas in XY gonads, both StARs could be detected from 30 dah until adulthood. Intraperitoneal injection of human chorionic gonadotropin experiments showed that expression of StAR1 and 2 was significantly elevated at 8h and persisted until 24h after injection in the testis. Taken together, our data suggested that StAR1 is likely to be required for cortisol production in the head kidney, and StAR2 is probably involved in estrogen production during early sex differentiation in XX gonads. In contrast, both StARs might be required for androgen production in testes. For the first time, our data demonstrated that two fish StARs might be involved 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