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Sample records for family vibrionaceae reveals

  1. Comparative genomics of the family Vibrionaceae reveals the wide distribution of genes encoding virulence-associated proteins

    PubMed Central

    2010-01-01

    Background Species of the family Vibrionaceae are ubiquitous in marine environments. Several of these species are important pathogens of humans and marine species. Evidence indicates that genetic exchange plays an important role in the emergence of new pathogenic strains within this family. Data from the sequenced genomes of strains in this family could show how the genes encoded by all these strains, known as the pangenome, are distributed. Information about the core, accessory and panproteome of this family can show how, for example, genes encoding virulence-associated proteins are distributed and help us understand how virulence emerges. Results We deduced the complete set of orthologs for eleven strains from this family. The core proteome consists of 1,882 orthologous groups, which is 28% of the 6,629 orthologous groups in this family. There were 4,411 accessory orthologous groups (i.e., proteins that occurred in from 2 to 10 proteomes) and 5,584 unique proteins (encoded once on only one of the eleven genomes). Proteins that have been associated with virulence in V. cholerae were widely distributed across the eleven genomes, but the majority was found only on the genomes of the two V. cholerae strains examined. Conclusions The proteomes are reflective of the differing evolutionary trajectories followed by different strains to similar phenotypes. The composition of the proteomes supports the notion that genetic exchange among species of the Vibrionaceae is widespread and that this exchange aids these species in adapting to their environments. PMID:20537180

  2. Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

    PubMed Central

    Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

    2014-01-01

    Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. PMID:25419995

  3. Genomic and Metabolic Profiling of Nonulosonic Acids in Vibrionaceae Reveal Biochemical Phenotypes of Allelic Divergence in Vibrio vulnificus ▿

    PubMed Central

    Lewis, Amanda L.; Lubin, Jean-Bernard; Argade, Shilpa; Naidu, Natasha; Choudhury, Biswa; Boyd, E. Fidelma

    2011-01-01

    Nonulosonic acids (NulOs) encompass a large group of structurally diverse nine-carbon backbone α-keto sugars widely distributed among the three domains of life. Mammals express a specialized version of NulOs called sialic acids, which are displayed in prominent terminal positions of cell surface and secreted glycoconjugates. Within bacteria, the ability to synthesize NulOs has been demonstrated in a number of human pathogens and is phylogenetically widespread. Here we examine the distribution, diversity, evolution, and function of NulO biosynthesis pathways in members of the family Vibrionaceae. Among 27 species of Vibrionaceae examined at the genomic level, 12 species contained nab gene clusters. We document examples of duplication, divergence, horizontal transfer, and recombination of nab gene clusters in different Vibrionaceae lineages. Biochemical analyses, including mass spectrometry, confirmed that many species do, in fact, produce di-N-acetylated NulOs. A library of clinical and environmental isolates of Vibrio vulnificus served as a model for further investigation of nab allele genotypes and levels of NulO expression. The data show that lineage I isolates produce about 20-fold higher levels of NulOs than lineage II isolates. Moreover, nab gene alleles found in a subset of V. vulnificus clinical isolates express 40-fold higher levels of NulOs than nab alleles associated with environmental isolates. Taken together, the data implicate the family Vibrionaceae as a “hot spot” of NulO evolution and suggest that these molecules may have diverse roles in environmental persistence and/or animal virulence. PMID:21724895

  4. Genomic and systems evolution in Vibrionaceae species

    PubMed Central

    Gu, Jianying; Neary, Jennifer; Cai, Hong; Moshfeghian, Audrey; Rodriguez, Stephen A; Lilburn, Timothy G; Wang, Yufeng

    2009-01-01

    pathogenesis mechanisms as well as in the fundamental life cycle of Vibrionaceae species. Conclusion Our results provide evidence of genome plasticity and rapid evolution within the family Vibrionaceae. The comparisons point to sources of genomic variation and candidates for lineage-specific adaptations of each Vibrionaceae pathogen or nonpathogen strain. Such lineage specific expansions could reveal components in bacterial systems that, by their enhanced genetic variability, can be tied to responses to environmental challenges, interesting phenotypes, or adaptive pathogenic responses to host challenges. PMID:19594870

  5. Pathogenicity of members of the vibrionaceae family to cultured juvenile sablefish.

    PubMed

    Arkoosh, Mary R; Dietrich, Joseph P

    2015-06-01

    Sablefish Anoplopoma fimbria are a prized seafood species due to their high oil content and white flaky flesh. Raising these species in culture can help to provide an important source of protein for humans and relief to declining wild fish populations. Understanding the environmental factors that influence the production of Sablefish is important for successful culturing. The significance of host-pathogen interactions in Sablefish culture and the resulting environmental implications are unknown. Pathogens could potentially cause losses of cultured Sablefish stocks due to disease, while Sablefish cultured in net pens may also serve as reservoirs for pathogens and potentially transmit disease to wild fish species. In this initial study, the susceptibility of juvenile Sablefish to three bacterial pathogens from the family Vibrionaceae was examined. Listonella anguillarum, Vibrio ordalii, and V. splendidus can pose serious economic threats to cultured fish and shellfish. Groups of juvenile Sablefish were exposed to five concentrations of each of the pathogens. Sablefish were susceptible to L. anguillarum, but were resistant to V. ordalii and V. splendidus at exposure concentrations of ≤ 1.32 × 10⁷ CFU/mL and ≤ 3.57 × 10⁶ CFU/mL, respectively. The greatest L. anguillarum concentration examined (8.7 × 10⁶ CFU/mL) resulted in 24% mortality in juvenile Sablefish. A 24% loss of Sablefish stock could significantly influence an aquaculture program. As determined by multiple logistic regression, the survival of Sablefish to L. anguillarum exposure was significantly affected by their body mass, and larger fish had a greater probability of survival. Aquaculture operations could employ various strategies to minimize the loss of juvenile Sablefish by accounting for their size and known susceptibilities to pathogens. PMID:25970236

  6. Phylogenetic relationships of marine bacteria, mainly members of the family Vibrionaceae, determined on the basis of 16S rRNA sequences.

    PubMed

    Kita-Tsukamoto, K; Oyaizu, H; Nanba, K; Simidu, U

    1993-01-01

    The phylogenetic relationships of 50 reference strains, mostly marine bacteria which require Na+ for growth, were determined on the basis of 600 16S rRNA nucleotides by using reverse transcriptase sequencing. Strains belonging to 10 genera were included (four genera of the family Vibrionaceae, the genus Aeromonas of the family Aeromonadaceae, and the genera Alteromonas, Marinomonas, Shewanella, Pseudomonas, and Deleya). The sequences were aligned, the similarity values and evolutionary distance values were determined, and a phylogenetic tree was constructed by using the neighbor-joining method. On the basis of our results, the family Vibrionaceae was separated into at least seven groups (genera and families). Vibrio marinus clearly was on a line of descent that was remote from other vibrios. As determined by the similarity and evolutionary distance values, V. marinus is more distantly related to the family Vibrionaceae than the members of the Aeromonadaceae are. Also, Vibrio cholerae strains formed a separate group with Vibrio mimicus at the genus level. Of 30 species of the Vibrionaceae, 17 formed a large phylogenetic cluster. The genus Listonella was found to be a heterogeneous group, and the species were distributed in various subgroups of the Vibrionaceae. The separation of the family Aeromonadaceae from the family Vibrionaceae and the separation of the genera Marinomonas and Shewanella from the genus Alteromonas were confirmed in this phylogenetic study. However, a marine Pseudomonas species, Pseudomonas nautica, was clearly separated from two terrestrial Pseudomonas species. Each group that was separated by the phylogenetic analysis had characteristic 16S rRNA sequence patterns that were common only to species in that group. Therefore, the characteristic sequences described in this paper may be useful for identification purposes. PMID:8427811

  7. Advanced Microbial Taxonomy Combined with Genome-Based-Approaches Reveals that Vibrio astriarenae sp. nov., an Agarolytic Marine Bacterium, Forms a New Clade in Vibrionaceae

    PubMed Central

    Al-saari, Nurhidayu; Gao, Feng; A.K.M. Rohul, Amin; Sato, Kazumichi; Sato, Keisuke; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Ohkuma, Moriya; Meirelles, Pedro M.; Thompson, Fabiano L.; Thompson, Cristiane; A. Filho, Gilberto M.; Gomez-Gil, Bruno; Sawabe, Toko; Sawabe, Tomoo

    2015-01-01

    Advances in genomic microbial taxonomy have opened the way to create a more universal and transparent concept of species but is still in a transitional stage towards becoming a defining robust criteria for describing new microbial species with minimum features obtained using both genome and classical polyphasic taxonomies. Here we performed advanced microbial taxonomies combined with both genome-based and classical approaches for new agarolytic vibrio isolates to describe not only a novel Vibrio species but also a member of a new Vibrio clade. Two novel vibrio strains (Vibrio astriarenae sp. nov. C7T and C20) showing agarolytic, halophilic and fermentative metabolic activity were isolated from a seawater sample collected in a coral reef in Okinawa. Intraspecific similarities of the isolates were identical in both sequences on the 16S rRNA and pyrH genes, but the closest relatives on the molecular phylogenetic trees on the basis of 16S rRNA and pyrH gene sequences were V. hangzhouensis JCM 15146T (97.8% similarity) and V. agarivorans CECT 5085T (97.3% similarity), respectively. Further multilocus sequence analysis (MLSA) on the basis of 8 protein coding genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA, and topA) obtained by the genome sequences clearly showed the V. astriarenae strain C7T and C20 formed a distinct new clade protruded next to V. agarivorans CECT 5085T. The singleton V. agarivorans has never been included in previous MLSA of Vibrionaceae due to the lack of some gene sequences. Now the gene sequences are completed and analysis of 100 taxa in total provided a clear picture describing the association of V. agarivorans into pre-existing concatenated network tree and concluded its relationship to our vibrio strains. Experimental DNA-DNA hybridization (DDH) data showed that the strains C7T and C20 were conspecific but were separated from all of the other Vibrio species related on the basis of both 16S rRNA and pyrH gene phylogenies (e.g., V. agarivorans CECT

  8. Advanced Microbial Taxonomy Combined with Genome-Based-Approaches Reveals that Vibrio astriarenae sp. nov., an Agarolytic Marine Bacterium, Forms a New Clade in Vibrionaceae.

    PubMed

    Al-Saari, Nurhidayu; Gao, Feng; Rohul, Amin A K M; Sato, Kazumichi; Sato, Keisuke; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Ohkuma, Moriya; Meirelles, Pedro M; Thompson, Fabiano L; Thompson, Cristiane; Filho, Gilberto M A; Gomez-Gil, Bruno; Sawabe, Toko; Sawabe, Tomoo

    2015-01-01

    Advances in genomic microbial taxonomy have opened the way to create a more universal and transparent concept of species but is still in a transitional stage towards becoming a defining robust criteria for describing new microbial species with minimum features obtained using both genome and classical polyphasic taxonomies. Here we performed advanced microbial taxonomies combined with both genome-based and classical approaches for new agarolytic vibrio isolates to describe not only a novel Vibrio species but also a member of a new Vibrio clade. Two novel vibrio strains (Vibrio astriarenae sp. nov. C7T and C20) showing agarolytic, halophilic and fermentative metabolic activity were isolated from a seawater sample collected in a coral reef in Okinawa. Intraspecific similarities of the isolates were identical in both sequences on the 16S rRNA and pyrH genes, but the closest relatives on the molecular phylogenetic trees on the basis of 16S rRNA and pyrH gene sequences were V. hangzhouensis JCM 15146T (97.8% similarity) and V. agarivorans CECT 5085T (97.3% similarity), respectively. Further multilocus sequence analysis (MLSA) on the basis of 8 protein coding genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA, and topA) obtained by the genome sequences clearly showed the V. astriarenae strain C7T and C20 formed a distinct new clade protruded next to V. agarivorans CECT 5085T. The singleton V. agarivorans has never been included in previous MLSA of Vibrionaceae due to the lack of some gene sequences. Now the gene sequences are completed and analysis of 100 taxa in total provided a clear picture describing the association of V. agarivorans into pre-existing concatenated network tree and concluded its relationship to our vibrio strains. Experimental DNA-DNA hybridization (DDH) data showed that the strains C7T and C20 were conspecific but were separated from all of the other Vibrio species related on the basis of both 16S rRNA and pyrH gene phylogenies (e.g., V. agarivorans CECT

  9. Microbial experimental evolution as a novel research approach in the Vibrionaceae and squid-Vibrio symbiosis

    PubMed Central

    Soto, William; Nishiguchi, Michele K.

    2014-01-01

    The Vibrionaceae are a genetically and metabolically diverse family living in aquatic habitats with a great propensity toward developing interactions with eukaryotic microbial and multicellular hosts (as either commensals, pathogens, and mutualists). The Vibrionaceae frequently possess a life history cycle where bacteria are attached to a host in one phase and then another where they are free from their host as either part of the bacterioplankton or adhered to solid substrates such as marine sediment, riverbeds, lakebeds, or floating particulate debris. These two stages in their life history exert quite distinct and separate selection pressures. When bound to solid substrates or to host cells, the Vibrionaceae can also exist as complex biofilms. The association between bioluminescent Vibrio spp. and sepiolid squids (Cephalopoda: Sepiolidae) is an experimentally tractable model to study bacteria and animal host interactions, since the symbionts and squid hosts can be maintained in the laboratory independently of one another. The bacteria can be grown in pure culture and the squid hosts raised gnotobiotically with sterile light organs. The partnership between free-living Vibrio symbionts and axenic squid hatchlings emerging from eggs must be renewed every generation of the cephalopod host. Thus, symbiotic bacteria and animal host can each be studied alone and together in union. Despite virtues provided by the Vibrionaceae and sepiolid squid-Vibrio symbiosis, these assets to evolutionary biology have yet to be fully utilized for microbial experimental evolution. Experimental evolution studies already completed are reviewed, along with exploratory topics for future study. PMID:25538686

  10. Reproducibility of Vibrionaceae population structure in coastal bacterioplankton.

    PubMed

    Szabo, Gitta; Preheim, Sarah P; Kauffman, Kathryn M; David, Lawrence A; Shapiro, Jesse; Alm, Eric J; Polz, Martin F

    2013-03-01

    How reproducibly microbial populations assemble in the wild remains poorly understood. Here, we assess evidence for ecological specialization and predictability of fine-scale population structure and habitat association in coastal ocean Vibrionaceae across years. We compare Vibrionaceae lifestyles in the bacterioplankton (combinations of free-living, particle, or zooplankton associations) measured using the same sampling scheme in 2006 and 2009 to assess whether the same groups show the same environmental association year after year. This reveals complex dynamics with populations falling primarily into two categories: (i) nearly equally represented in each of the two samplings and (ii) highly skewed, often to an extent that they appear exclusive to one or the other sampling times. Importantly, populations recovered at the same abundance in both samplings occupied highly similar habitats suggesting predictable and robust environmental association while skewed abundances of some populations may be triggered by shifts in ecological conditions. The latter is supported by difference in the composition of large eukaryotic plankton between years, with samples in 2006 being dominated by copepods, and those in 2009 by diatoms. Overall, the comparison supports highly predictable population-habitat linkage but highlights the fact that complex, and often unmeasured, environmental dynamics in habitat occurrence may have strong effects on population dynamics. PMID:23178668

  11. The fur Gene as a New Phylogenetic Marker for Vibrionaceae Species Identification

    PubMed Central

    Gram, Lone

    2015-01-01

    Microbial taxonomy is essential in all areas of microbial science. The 16S rRNA gene sequence is one of the main phylogenetic species markers; however, it does not provide discrimination in the family Vibrionaceae, where other molecular techniques allow better interspecies resolution. Although multilocus sequence analysis (MLSA) has been used successfully in the identification of Vibrio species, the technique has several limitations. They include the fact that several locus amplifications and sequencing have to be performed, which still sometimes lead to doubtful identifications. Using an in silico approach based on genomes from 103 Vibrionaceae strains, we demonstrate here the high resolution of the fur gene in the identification of Vibrionaceae species and its usefulness as a phylogenetic marker. The fur gene showed within-species similarity higher than 95%, and the relationships inferred from its use were in agreement with those observed for 16S rRNA analysis and MLSA. Furthermore, we developed a fur PCR sequencing-based method that allowed identification of Vibrio species. The discovery of the phylogenetic power of the fur gene and the development of a PCR method that can be used in amplification and sequencing of the gene are of general interest whether for use alone or together with the previously suggested loci in an MLSA. PMID:25662978

  12. Fluorogenic Membrane Overlays to Enumerate Total and Fecal Escherichia coli and Total Vibrionaceae in Shellfish and Seawater.

    PubMed

    Richards, Gary P; Watson, Michael A

    2010-01-01

    Three assays were developed to enumerate total and fecal Escherichia coli and total Vibrionaceae in shellfish, seawater, and other foods and environmental samples. Assays involve membrane overlays of overnight colonies on nonselective agar plates to detect beta-glucuronidase and lysyl aminopeptidase activities for E. coli and Vibrionaceae, respectively. Cellulose membranes containing the substrates 4-methylumbeferyl-beta-D-glucuronide (MUG) produced a bright blue fluorescence when overlaid onto E. coli, while L-lysyl-7-amino-4-trifluoromethylcoumarin produced green fluorescent foci when overlaid onto Vibrionaceae family members. A multiplex assay was also developed for simultaneously enumerating total E. coli and total Vibrionaceae in oysters and seawater. Overall, 65% of overlaid E. coli (non-O157:H7) were MUG-positive, compared with 62% as determined by the most-probable-number-MUG assay. The overlays are rapid, simple, and cost effective for quantification purposes. This research provides practical alternatives for monitoring bacterial indicators and potential pathogens in complex samples, including molluscan shellfish. PMID:20396663

  13. Targeting the Replication Initiator of the Second Vibrio Chromosome: Towards Generation of Vibrionaceae-Specific Antimicrobial Agents

    PubMed Central

    Yamaichi, Yoshiharu; Duigou, Stéphane; Shakhnovich, Elizabeth A.; Waldor, Matthew K.

    2009-01-01

    The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resistance in the normal human flora or in non-vibrio environmental microorganisms. PMID:19936046

  14. Associations and dynamics of Vibrionaceae in the environment, from the genus to the population level

    PubMed Central

    Takemura, Alison F.; Chien, Diana M.; Polz, Martin F.

    2013-01-01

    The Vibrionaceae, which encompasses several potential pathogens, including V. cholerae, the causative agent of cholera, and V. vulnificus, the deadliest seafood-borne pathogen, are a well-studied family of marine bacteria that thrive in diverse habitats. To elucidate the environmental conditions under which vibrios proliferate, numerous studies have examined correlations with bulk environmental variables—e.g., temperature, salinity, nitrogen, and phosphate—and association with potential host organisms. However, how meaningful these environmental associations are remains unclear because data are fragmented across studies with variable sampling and analysis methods. Here, we synthesize findings about Vibrio correlations and physical associations using a framework of increasingly fine environmental and taxonomic scales, to better understand their dynamics in the wild. We first conduct a meta-analysis to determine trends with respect to bulk water environmental variables, and find that while temperature and salinity are generally strongly predictive correlates, other parameters are inconsistent and overall patterns depend on taxonomic resolution. Based on the hypothesis that dynamics may better correlate with more narrowly defined niches, we review evidence for specific association with plants, algae, zooplankton, and animals. We find that Vibrio are attached to many organisms, though evidence for enrichment compared to the water column is often lacking. Additionally, contrary to the notion that they flourish predominantly while attached, Vibrio can have, at least temporarily, a free-living lifestyle and even engage in massive blooms. Fine-scale sampling from the water column has enabled identification of such lifestyle preferences for ecologically cohesive populations, and future efforts will benefit from similar analysis at fine genetic and environmental sampling scales to describe the conditions, habitats, and resources shaping Vibrio dynamics. PMID:24575082

  15. Fluorogenic membrane overlays to enumerate total coliforms, Escherichia coli, and total Vibrionaceae in shellfish and seawater

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three assays were developed to enumerate total coliforms, Escherichia coli, and total Vibrionaceae in shellfish and other foods and in seawater and other environmental samples. Assays involve membrane overlays of overnight colonies on non-selective agar plates to detect ß-glucuronidase and lysyl am...

  16. Water quality parameters and total aerobic bacterial and vibrionaceae loads in eastern oysters (Crassostrea virginica) from oyster gardening sites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oyster gardening is a practice designed to restore habitat for marine life and to improve water quality. This study determined physical and chemical water quality parameters at two oyster gardening sites in the Delaware Inland Bays and compared them with total aerobic bacteria and Vibrionaceae conc...

  17. Phylogenomic analyses reveal novel relationships among snake families.

    PubMed

    Streicher, Jeffrey W; Wiens, John J

    2016-07-01

    Snakes are a diverse and important group of vertebrates. However, relationships among the major groups of snakes have remained highly uncertain, with recent studies hypothesizing very different (and typically weakly supported) relationships. Here, we address family-level snake relationships with new phylogenomic data from 3776 nuclear loci from ultraconserved elements (1.40million aligned base pairs, 52% missing data overall) sampled from 29 snake species that together represent almost all families, a dataset ∼100 times larger than used in previous studies. We found relatively strong support from species-tree analyses (NJst) for most relationships, including three largely novel clades: (1) a clade uniting the boas, pythons and their relatives, (2) a clade placing cylindrophiids and uropeltids with this clade, and (3) a clade uniting bolyeriids (Round Island boas) with pythonids and their relatives (xenopeltids and loxocemids). Relationships among families of advanced snakes (caenophidians) were also strongly supported. The results show the potential for phylogenomic analyses to resolve difficult groups, but also show a surprising sensitivity of the analyses to the inclusion or exclusion of outgroups. PMID:27083862

  18. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.

    PubMed

    Piccolo, Stephen R; Hoffman, Laura M; Conner, Thomas; Shrestha, Gajendra; Cohen, Adam L; Marks, Jeffrey R; Neumayer, Leigh A; Agarwal, Cori A; Beckerle, Mary C; Andrulis, Irene L; Spira, Avrum E; Moos, Philip J; Buys, Saundra S; Johnson, William Evan; Bild, Andrea H

    2016-03-01

    The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development. PMID:26969729

  19. Vibrio galatheae sp. nov., a member of the family Vibrionaceae isolated from a mussel.

    PubMed

    Giubergia, Sonia; Machado, Henrique; Valentina Mateiu, Ramona; Gram, Lone

    2016-01-01

    Based on genetic, chemotaxonomic and phenotypic characteristics, a novel species belonging to the genus Vibrio is described. The facultatively anaerobic strain S2757T was isolated from a mussel collected in the Solomon Sea (Solomon Islands). Phylogenetic analyses based on sequences of 16S rRNA and fur genes indicated affiliation of the strain to a novel species. This observation was supported by a multilocus sequence analysis including sequences of the housekeeping genes 16S rRNA, gyrB, pyrH, recA and topA. In silico DNA-DNA hybridization and average nucleotide identity values comparing the genomic sequence of strain S2757T with those of closely related type strains were lower than 23 and 82 %, respectively. The DNA G+C content of the strain was 45.3 mol%. Phenotypic and chemotaxonomic analyses clearly differentiated the strain from other Vibrio species. Hence, strain S2757T should be considered to represent a novel species of the genus Vibrio, for which the name Vibrio galatheae sp. nov. is proposed. The type strain is S2757T ( = DSM 100497T = LMG 28895T). PMID:26514698

  20. Draft Genome Sequences of Two Vibrionaceae Species, Vibrio ponticus C121 and Photobacterium aphoticum C119, Isolated as Coral Reef Microbiota

    PubMed Central

    Al-saari, Nurhidayu; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Ohkuma, Moriya; Thompson, Fabiano L.; Gomez-Gil, Bruno; Sawabe, Toko

    2014-01-01

    Here, the draft genome sequences of two Vibrionaceae, Vibrio ponticus C121 and Photobacterium aphoticum C119, which were isolated from the coral reef vicinity in Okinawa, Japan, are reported. The genome provides further insight into the genomic plasticity, biocomplexity, and ecophysiology, including pathogenicity and evolution, of these genera. PMID:25359913

  1. Draft Genome Sequences of Two Vibrionaceae Species, Vibrio ponticus C121 and Photobacterium aphoticum C119, Isolated as Coral Reef Microbiota.

    PubMed

    Al-Saari, Nurhidayu; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Ohkuma, Moriya; Thompson, Fabiano L; Gomez-Gil, Bruno; Sawabe, Toko; Sawabe, Tomoo

    2014-01-01

    Here, the draft genome sequences of two Vibrionaceae, Vibrio ponticus C121 and Photobacterium aphoticum C119, which were isolated from the coral reef vicinity in Okinawa, Japan, are reported. The genome provides further insight into the genomic plasticity, biocomplexity, and ecophysiology, including pathogenicity and evolution, of these genera. PMID:25359913

  2. [The family revealing itself as a being of rights during hospitalization of the child].

    PubMed

    Xavier, Daiani Modernel; Gomes, Giovana Calcagno; Barlem, Edison Luiz Devos; Erdmann, Alacoque Lorenzini

    2013-12-01

    This is a descriptive study with a qualitative approach, carried out during the second half of 2011, in a Pediatric Unit in a city in the extreme South of Brazil. The study aimed to understand the situations in which families reveal themselves as beings of rights during the hospitalization of the child. Fifteen family caregivers participated, divided into three sample groups. Data collection was conducted through semi-structured interviews, and the data were analyzed using open, axial and selective analysis. The study had the Grounded Theory as methodological framework. It was found that the family revealed itself as a being of rights, when recognized as such, is called and fights for their rights; suggests improvements for the care and maintains its autonomy, even if it has to submit to the decisions of the team in the child favor. It was concluded that is essential to allow them to be families in the hospital, enabling the exercise of their rights and citizenship. PMID:24488458

  3. Characterization of the Avian Trojan Gene Family Reveals Contrasting Evolutionary Constraints

    PubMed Central

    Petrov, Petar; Syrjänen, Riikka; Smith, Jacqueline; Gutowska, Maria Weronika; Uchida, Tatsuya; Vainio, Olli; Burt, David W

    2015-01-01

    “Trojan” is a leukocyte-specific, cell surface protein originally identified in the chicken. Its molecular function has been hypothesized to be related to anti-apoptosis and the proliferation of immune cells. The Trojan gene has been localized onto the Z sex chromosome. The adjacent two genes also show significant homology to Trojan, suggesting the existence of a novel gene/protein family. Here, we characterize this Trojan family, identify homologues in other species and predict evolutionary constraints on these genes. The two Trojan-related proteins in chicken were predicted as a receptor-type tyrosine phosphatase and a transmembrane protein, bearing a cytoplasmic immuno-receptor tyrosine-based activation motif. We identified the Trojan gene family in ten other bird species and found related genes in three reptiles and a fish species. The phylogenetic analysis of the homologues revealed a gradual diversification among the family members. Evolutionary analyzes of the avian genes predicted that the extracellular regions of the proteins have been subjected to positive selection. Such selection was possibly a response to evolving interacting partners or to pathogen challenges. We also observed an almost complete lack of intracellular positively selected sites, suggesting a conserved signaling mechanism of the molecules. Therefore, the contrasting patterns of selection likely correlate with the interaction and signaling potential of the molecules. PMID:25803627

  4. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

    PubMed Central

    Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Dellon, Evan S.; Demain, Jeffrey G.; Furuta, Glenn T.; Gurian, Larry E.; Harley, John B.; Hopp, Russell J.; Kaul, Ajay; Nadeau, Kari C.; Noel, Richard J.; Putnam, Philip E.; von Tiehl, Karl F.; Rothenberg, Marc E.

    2014-01-01

    Background Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. Objective To quantify risk associated with genes and environment on familial clustering of EoE. Methods Family history was obtained from a hospital-based cohort of 914 EoE probands, (n=2192 first-degree “Nuclear-Family” relatives) and the new international registry of monozygotic and dizygotic twins/triplets (n=63 EoE “Twins” probands). Frequencies, recurrence risk ratios (RRRs), heritability and twin concordance were estimated. Environmental exposures were preliminarily examined. Results Analysis of the Nuclear-Family–based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10–64, depending on the family relationship, and were higher in brothers (64.0; p=0.04), fathers (42.9; p=0.004) and males (50.7; p<0.001) compared to sisters, mothers and females, respectively. Risk of EoE for other siblings was 2.4%. In the Nuclear-Families, combined gene and common environment heritability (hgc2) was 72.0±2.7% (p<0.001). In the Twins cohort, genetic heritability was 14.5±4.0% (p<0.001), and common family environment contributed 81.0±4% (p<0.001) to phenotypic variance. Proband-wise concordance in MZ co-twins was 57.9±9.5% compared to 36.4±9.3% in DZ (p=0.11). Greater birth-weight difference between twins (p=0.01), breastfeeding (p=0.15) and Fall birth season (p=0.02) were associated with twin discordance in disease status. Conclusions EoE recurrence risk ratios are increased 10–64-fold compared with the general population. EoE in relatives is 1.8–2.4%, depending upon relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, Twins cohort analysis revealed a powerful role for common environment (81

  5. Structural and functional analysis of amphioxus HIFα reveals ancient features of the HIFα family.

    PubMed

    Gao, Shan; Lu, Ling; Bai, Yan; Zhang, Peng; Song, Weibo; Duan, Cunming

    2014-04-01

    Hypoxia-inducible factors (HIFs) are master regulators of the transcriptional response to hypoxia. To gain insight into the structural and functional evolution of the HIF family, we characterized the HIFα gene from amphioxus, an invertebrate chordate, and identified several alternatively spliced HIFα isoforms. Whereas HIFα Ia, the full-length isoform, contained a complete oxygen-dependent degradation (ODD) domain, the isoforms Ib, Ic, and Id had 1 or 2 deletions in the ODD domain. When tagged with GFP and tested in mammalian cells, the amphioxus HIFα Ia protein level increased in response to hypoxia or CoCl2 treatment, whereas HIFα Ib, Ic, and Id showed reduced or no hypoxia regulation. Deletion of the ODD sequence in HIFα Ia up-regulated the HIFα Ia levels under normoxia. Gene expression analysis revealed HIFα Ic to be the predominant isoform in embryos and larvae, whereas isoform Ia was the most abundant form in the adult stage. The expression levels of Ib and Id were very low. Hypoxia treatment of adults had no effect on the mRNA levels of these HIFα isoforms. Functional analyses in mammalian cells showed all 4 HIFα isoforms capable of entering the nucleus and activating hypoxia response element-dependent reporter gene expression. The functional nuclear location signal (NLS) mapped to 3 clusters of basic residues. (775)KKARL functioned as the primary NLS, but (737)KRK and (754)KK also contributed to the nuclear localization. All amphioxus HIFα isoforms had 2 functional transactivation domains (TADs). Its C-terminal transactivation (C-TAD) shared high sequence identity with the human HIF-1α and HIF-2α C-TAD. This domain contained a conserved asparagine, and its mutation resulted in an increase in transcriptional activity. These findings reveal many ancient features of the HIFα family and provide novel insights into the evolution of the HIFα family. PMID:24174425

  6. Water-quality parameters and total aerobic bacterial and Vibrionaceae loads in Eastern oysters (Crassostrea virginica) from oyster-gardening sites.

    PubMed

    Fay, Johnna P; Richards, Gary P; Ozbay, Gulnihal

    2012-05-01

    Oyster gardening is a practice designed to restore habitat for marine life and to improve water quality. This study determined physical and chemical water-quality parameters at two oyster gardening sites in the Delaware Inland Bays and compared them with total aerobic bacteria and Vibrionaceae concentrations in Eastern oysters (Crassostrea virginica). One site was located at the end of a man-made canal, whereas the other was located in an open bay. Measured water parameters included temperature, dissolved oxygen (DO), salinity, pH, total nitrogen, nitrate, nitrite, total phosphorus, and total suspended solids. The highest Vibrionaceae levels, as determined by the colony overlay procedure for peptidases, were at the canal site in September (3.5 × 10(5) g(-1)) and at the bay site in August (1.9 × 10(5) g(-1)). Vibrionaceae levels were significantly greater during the duration of the study at the canal site (P = 0.01). This study provides the first baseline levels for total Vibrionaceae in the Delaware Inland Bays. Minimum DO readings at the bay and canal sites were 3.0 and 2.3 mg l(-1), respectively, far less than the state-targeted minimum threshold of 5.0 mg l(-1). Total phosphorus levels exceeded recommendations of ≤0.1 mg l(-1) at the bay and canal sites for all monthly samplings, with mean monthly highs at both sites ≥0.68 mg l(-1) in August. Nitrogen occasionally exceeded the recommended level of 1.0 mg l(-1) at both sites. Overall, waters were highly degraded from high phosphates, nitrogen, and total suspended solids as well as low DO. PMID:22183874

  7. Structure-function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family.

    PubMed

    Yin, DeLu Tyler; Urresti, Saioa; Lafond, Mickael; Johnston, Esther M; Derikvand, Fatemeh; Ciano, Luisa; Berrin, Jean-Guy; Henrissat, Bernard; Walton, Paul H; Davies, Gideon J; Brumer, Harry

    2015-01-01

    Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6-oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure-function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-à-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications. PMID:26680532

  8. Structure–function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family

    PubMed Central

    Yin, DeLu (Tyler); Urresti, Saioa; Lafond, Mickael; Johnston, Esther M.; Derikvand, Fatemeh; Ciano, Luisa; Berrin, Jean-Guy; Henrissat, Bernard; Walton, Paul H.; Davies, Gideon J.; Brumer, Harry

    2015-01-01

    Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6-oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure–function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-à-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications. PMID:26680532

  9. Sequence diversity in haloalkane dehalogenases, as revealed by PCR using family-specific primers.

    PubMed

    Kotik, Michael; Faměrová, Veronika

    2012-02-01

    Haloalkane dehalogenases (HLDs) are hydrolytic enzymes that cleave carbon-halogen bonds in various halogenated compounds. Interest initially grew in HLDs as biocatalysts for bioremediation and later for biotransformation applications; each specific HLD within the HLD family has its own substrate specificity, enantioselectivity and product inhibition characteristics. We developed degenerate oligonucleotide primers for HLD-encoding genes and used these to PCR-amplify large hld gene fragments using genomic DNA from the microbial community of a chlorinated-solvent-contaminated aquifer as a template. An analysis of small subunit ribosomal RNA genes revealed a high complexity in the eubacterial population, dominated by α-, β- and γ-Proteobacteria, and Acidobacteria. Using HLD-family-specific primers, we also retrieved transcribed hld homologues from the microbial consortium of this contaminated site. The DNA-derived hld sequences were phylogenetically broadly distributed over both HLD subclasses I and II. Most hld sequences of the environmental RNA data set clustered in three groups within both HLD subclasses, indicating that a considerable proportion of the microbial consortium carrying hld genes was actively involved in haloalkane dehalogenation. The small sequence variation in hld genes and transcripts within each HLD cluster inferred the presence of a substantial pool of highly related HLD genes. The sequence variability appeared to be unevenly distributed over the HLD genes, however, with no apparent preference for a particular protein segment or domain. PMID:22155739

  10. Transcriptomes of the parasitic plant family Orobanchaceae reveal surprising conservation of chlorophyll synthesis.

    PubMed

    Wickett, Norman J; Honaas, Loren A; Wafula, Eric K; Das, Malay; Huang, Kan; Wu, Biao; Landherr, Lena; Timko, Michael P; Yoder, John; Westwood, James H; dePamphilis, Claude W

    2011-12-20

    Parasitism in flowering plants has evolved at least 11 times [1]. Only one family, Orobanchaceae, comprises all major nutritional types of parasites: facultative, hemiparasitic (partially photosynthetic), and holoparasitic (nonphotosynthetic) [2]. Additionally, the family includes Lindenbergia, a nonparasitic genus sister to all parasitic Orobanchaceae [3-6]. Parasitic Orobanchaceae include species with severe economic impacts: Striga (witchweed), for example, affects over 50 million hectares of crops in sub-Saharan Africa, causing more than $3 billion in damage annually [7]. Although gene losses and increased substitution rates have been characterized for parasitic plant plastid genomes [5, 8-11], the nuclear genome and transcriptome remain largely unexplored. The Parasitic Plant Genome Project (PPGP; http://ppgp.huck.psu.edu/) [2] is leveraging the natural variation in Orobanchaceae to explore the evolution and genomic consequences of parasitism in plants through a massive transcriptome and gene discovery project involving Triphysaria versicolor (facultative hemiparasite), Striga hermonthica (obligate hemiparasite), and Phelipanche aegyptiaca (Orobanche [12]; holoparasite). Here we present the first set of large-scale genomic resources for parasitic plant comparative biology. Transcriptomes of above-ground tissues reveal that, in addition to the predictable loss of photosynthesis-related gene expression in P. aegyptiaca, the nonphotosynthetic parasite retains an intact, expressed, and selectively constrained chlorophyll synthesis pathway. PMID:22169535

  11. Comparative mapping in the Poaceae family reveals translocations in the complex polyploid genome of sugarcane

    PubMed Central

    2014-01-01

    Background The understanding of sugarcane genetics has lagged behind that of other members of the Poaceae family such as wheat, rice, barley and sorghum mainly due to the complexity, size and polyploidization of the genome. We have used the genetic map of a sugarcane cultivar to generate a consensus genetic map to increase genome coverage for comparison to the sorghum genome. We have utilized the recently developed sugarcane DArT array to increase the marker density within the genetic map. The sequence of these DArT markers plus SNP and EST-SSR markers was then used to form a bridge to the sorghum genomic sequence by BLAST alignment to start to unravel the complex genomic architecture of sugarcane. Results Comparative mapping revealed that certain sugarcane chromosomes show greater levels of synteny to sorghum than others. On a macrosyntenic level a good collinearity was observed between sugarcane and sorghum for 4 of the 8 homology groups (HGs). These 4 HGs were syntenic to four sorghum chromosomes with from 98% to 100% of these chromosomes covered by these linked markers. Four major chromosome rearrangements were identified between the other four sugarcane HGs and sorghum, two of which were condensations of chromosomes reducing the basic chromosome number of sugarcane from x = 10 to x = 8. This macro level of synteny was transferred to other members within the Poaceae family such as maize to uncover the important evolutionary relationships that exist between sugarcane and these species. Conclusions Comparative mapping of sugarcane to the sorghum genome has revealed new information on the genome structure of sugarcane which will help guide identification of important genes for use in sugarcane breeding. Furthermore of the four major chromosome rearrangements identified in this study, three were common to maize providing some evidence that chromosome reduction from a common paleo-ancestor of both maize and sugarcane was driven by the same translocation

  12. Homozygosity Mapping and Targeted Sanger Sequencing Reveal Genetic Defects Underlying Inherited Retinal Disease in Families from Pakistan

    PubMed Central

    Waheed, Nadia Khalida; Siddiqui, Sorath Noorani; Mustafa, Bilal; Ayub, Humaira; Ali, Liaqat; Ahmad, Shakeel; Micheal, Shazia; Hussain, Alamdar; Shah, Syed Tahir Abbas; Ali, Syeda Hafiza Benish; Ahmed, Waqas; Khan, Yar Muhammad; den Hollander, Anneke I.; Haer-Wigman, Lonneke; Collin, Rob W. J.; Khan, Muhammad Imran; Qamar, Raheel; Cremers, Frans P. M.

    2015-01-01

    Background Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD). Methods We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families. Results Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. Conclusions Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future. PMID:25775262

  13. Rethinking the roles of CRP, cAMP, and sugar-mediated global regulation in the Vibrionaceae.

    PubMed

    Colton, Deanna M; Stabb, Eric V

    2016-02-01

    Many proteobacteria modulate a suite of catabolic genes using the second messenger cyclic 3', 5'-AMP (cAMP) and the cAMP receptor protein (CRP). Together, the cAMP-CRP complex regulates target promoters, usually by activating transcription. In the canonical model, the phosphotransferase system (PTS), and in particular the EIIA(Glc) component for glucose uptake, provides a mechanistic link that modulates cAMP levels depending on glucose availability, resulting in more cAMP and activation of alternative catabolic pathways when glucose is unavailable. Within the Vibrionaceae, cAMP-CRP appears to play the classical role in modulating metabolic pathways; however, it also controls functions involved in natural competence, bioluminescence, pheromone signaling, and colonization of animal hosts. For this group of marine bacteria, chitin is an ecologically relevant resource, and chitin's monomeric sugar N-acetylglucosamine (NAG) supports robust growth while also triggering regulatory responses. Recent studies with Vibrio fischeri indicate that NAG and glucose uptake share EIIA(Glc), yet the responses of cAMP-CRP to these two carbon sources are starkly different. Moreover, control of cAMP levels appears to be more dominantly controlled by export and degradation. Perhaps more surprisingly, although CRP may require cAMP, its activity can be controlled in response to glucose by a mechanism independent of cAMP levels. Future studies in this area promise to shed new light on the role of cAMP and CRP. PMID:26215147

  14. The Caenorhabditis globin gene family reveals extensive nematode-specific radiation and diversification

    PubMed Central

    2008-01-01

    Background Globin isoforms with variant properties and functions have been found in the pseudocoel, body wall and cuticle of various nematode species and even in the eyespots of the insect-parasite Mermis nigrescens. In fact, much higher levels of complexity exist, as shown by recent whole genome analysis studies. In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles. Results In the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi and EST data from several other nematode species to study the evolutionary history of the nematode globin gene family. We find a high level of conservation of the C. elegans globin complement, with even distantly related nematodes harboring orthologs to many Caenorhabditis globins. Bayesian phylogenetic analysis resolves all nematode globins into two distinct globin classes. Analysis of the globin intron-exon structures suggests extensive loss of ancestral introns and gain of new positions in deep nematode ancestors, and mainly loss in the Caenorhabditis lineage. We also show that the Caenorhabditis globin genes are expressed in distinct, mostly non-overlapping, sets of cells and that they are all under strong purifying selection. Conclusion Our results enable reconstruction of the evolutionary history of the globin gene family in the nematode phylum. A duplication of an ancestral globin gene occurred before the divergence of the Platyhelminthes and the Nematoda and one of the duplicated genes radiated further in the nematode phylum before the split of the Spirurina and Rhabditina and was followed by further radiation in the lineage leading to Caenorhabditis. The resulting globin genes were subject to processes of subfunctionalization and diversification leading to cell-specific expression patterns. Strong purifying

  15. Functional Divergence of the Glutathione S-Transferase Supergene Family in Physcomitrella patens Reveals Complex Patterns of Large Gene Family Evolution in Land Plants1[W][OA

    PubMed Central

    Liu, Yan-Jing; Han, Xue-Min; Ren, Lin-Ling; Yang, Hai-Ling; Zeng, Qing-Yin

    2013-01-01

    Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants. PMID:23188805

  16. Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

    SciTech Connect

    Vanderslice, P.; Ballinger, S.M., Tam, E.K.; Goldstein, S.M.; Craik, C.S.; Caughey, G.H. )

    1990-05-01

    Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the {approx}1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5{prime} regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family.

  17. Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.

    PubMed

    Leppa, Virpi M; Kravitz, Stephanie N; Martin, Christa Lese; Andrieux, Joris; Le Caignec, Cedric; Martin-Coignard, Dominique; DyBuncio, Christina; Sanders, Stephan J; Lowe, Jennifer K; Cantor, Rita M; Geschwind, Daniel H

    2016-09-01

    Rare mutations, including copy-number variants (CNVs), contribute significantly to autism spectrum disorder (ASD) risk. Although their importance has been established in families with only one affected child (simplex families), the contribution of both de novo and inherited CNVs to ASD in families with multiple affected individuals (multiplex families) is less well understood. We analyzed 1,532 families from the Autism Genetic Resource Exchange (AGRE) to assess the impact of de novo and rare CNVs on ASD risk in multiplex families. We observed a higher burden of large, rare CNVs, including inherited events, in individuals with ASD than in their unaffected siblings (odds ratio [OR] = 1.7), but the rate of de novo events was significantly lower than in simplex families. In previously characterized ASD risk loci, we identified 49 CNVs, comprising 24 inherited events, 19 de novo events, and 6 events of unknown inheritance, a significant enrichment in affected versus control individuals (OR = 3.3). In 21 of the 30 families (71%) in whom at least one affected sibling harbored an established ASD major risk CNV, including five families harboring inherited CNVs, the CNV was not shared by all affected siblings, indicating that other risk factors are contributing. We also identified a rare risk locus for ASD and language delay at chromosomal region 2q24 (implicating NR4A2) and another lower-penetrance locus involving inherited deletions and duplications of WWOX. The genetic architecture in multiplex families differs from that in simplex families and is complex, warranting more complete genetic characterization of larger multiplex ASD cohorts. PMID:27569545

  18. Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia.

    PubMed

    Roccaro, Aldo M; Sacco, Antonio; Shi, Jiantao; Chiarini, Marco; Perilla-Glen, Adriana; Manier, Salomon; Glavey, Siobhan; Aljawai, Yosra; Mishima, Yuji; Kawano, Yawara; Moschetta, Michele; Correll, Mick; Improgo, Ma Reina; Brown, Jennifer R; Imberti, Luisa; Rossi, Giuseppe; Castillo, Jorge J; Treon, Steven P; Freedman, Matthew L; Van Allen, Eliezer M; Hide, Winston; Hiller, Elaine; Rainville, Irene; Ghobrial, Irene M

    2016-05-26

    Familial aggregation of Waldenström macroglobulinemia (WM) cases, and the clustering of B-cell lymphoproliferative disorders among first-degree relatives of WM patients, has been reported. Nevertheless, the possible contribution of inherited susceptibility to familial WM remains unrevealed. We performed whole exome sequencing on germ line DNA obtained from 4 family members in which coinheritance for WM was documented in 3 of them, and screened additional independent 246 cases by using gene-specific mutation sequencing. Among the shared germ line variants, LAPTM5(c403t) and HCLS1(g496a) were the most recurrent, being present in 3/3 affected members of the index family, detected in 8% of the unrelated familial cases, and present in 0.5% of the nonfamilial cases and in <0.05 of a control population. LAPTM5 and HCLS1 appeared as relevant WM candidate genes that characterized familial WM individuals and were also functionally relevant to the tumor clone. These findings highlight potentially novel contributors for the genetic predisposition to familial WM and indicate that LAPTM5(c403t) and HCLS1(g496a) may represent predisposition alleles in patients with familial WM. PMID:26903547

  19. Cross-species gene-family fluctuations reveal the dynamics of horizontal transfers

    PubMed Central

    Grilli, Jacopo; Romano, Mariacristina; Bassetti, Federico; Cosentino Lagomarsino, Marco

    2014-01-01

    Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index that captures a family's evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics and horizontal transfer dynamics, which can be used to analyze genome ‘flux’. Groups of families with different values of the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal exchange allowed by natural selection. PMID:24829449

  20. Genes Similar to the Vibrio parahaemolyticus Virulence-Related Genes tdh, tlh, and vscC2 Occur in Other Vibrionaceae Species Isolated from a Pristine Estuary

    PubMed Central

    Klein, Savannah L.; Gutierrez West, Casandra K.; Mejia, Diana M.

    2014-01-01

    Detection of the human pathogen Vibrio parahaemolyticus often relies on molecular biological analysis of species-specific virulence factor genes. These genes have been employed in determinations of V. parahaemolyticus population numbers and the prevalence of pathogenic V. parahaemolyticus strains. Strains of the Vibrionaceae species Photobacterium damselae, Vibrio diabolicus, Vibrio harveyi, and Vibrio natriegens, as well as strains similar to Vibrio tubiashii, were isolated from a pristine salt marsh estuary. These strains were examined for the V. parahaemolyticus hemolysin genes tdh, trh, and tlh and for the V. parahaemolyticus type III secretion system 2α gene vscC2 using established PCR primers and protocols. Virulence-related genes occurred at high frequencies in non-V. parahaemolyticus Vibrionaceae species. V. diabolicus was of particular interest, as several strains were recovered, and the large majority (>83%) contained virulence-related genes. It is clear that detection of these genes does not ensure correct identification of virulent V. parahaemolyticus. Further, the occurrence of V. parahaemolyticus-like virulence factors in other vibrios potentially complicates tracking of outbreaks of V. parahaemolyticus infections. PMID:24212573

  1. Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease.

    PubMed

    Luzón-Toro, Berta; Gui, Hongsheng; Ruiz-Ferrer, Macarena; Sze-Man Tang, Clara; Fernández, Raquel M; Sham, Pak-Chung; Torroglosa, Ana; Kwong-Hang Tam, Paul; Espino-Paisán, Laura; Cherny, Stacey S; Bleda, Marta; Enguix-Riego, María Del Valle; Dopazo, Joaquín; Antiñolo, Guillermo; García-Barceló, María-Mercé; Borrego, Salud

    2015-01-01

    Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR. PMID:26559152

  2. Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease

    PubMed Central

    Luzón-Toro, Berta; Gui, Hongsheng; Ruiz-Ferrer, Macarena; Sze-Man Tang, Clara; Fernández, Raquel M.; Sham, Pak-Chung; Torroglosa, Ana; Kwong-Hang Tam, Paul; Espino-Paisán, Laura; Cherny, Stacey S.; Bleda, Marta; Enguix-Riego, María del Valle; Dopazo, Joaquín; Antiñolo, Guillermo; García-Barceló, María-Mercé; Borrego, Salud

    2015-01-01

    Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR. PMID:26559152

  3. Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family.

    PubMed

    Geertsma, Eric R; Chang, Yung-Ning; Shaik, Farooque R; Neldner, Yvonne; Pardon, Els; Steyaert, Jan; Dutzler, Raimund

    2015-10-01

    The SLC26 family of membrane proteins combines a variety of functions within a conserved molecular scaffold. Its members, besides coupled anion transporters and channels, include the motor protein Prestin, which confers electromotility to cochlear outer hair cells. To gain insight into the architecture of this protein family, we characterized the structure and function of SLC26Dg, a facilitator of proton-coupled fumarate symport, from the bacterium Deinococcus geothermalis. Its modular structure combines a transmembrane unit and a cytoplasmic STAS domain. The membrane-inserted domain consists of two intertwined inverted repeats of seven transmembrane segments each and resembles the fold of the unrelated transporter UraA. It shows an inward-facing, ligand-free conformation with a potential substrate-binding site at the interface between two helix termini at the center of the membrane. This structure defines the common framework for the diverse functional behavior of the SLC26 family. PMID:26367249

  4. Exome sequencing reveals VCP mutations as a cause of familial ALS

    PubMed Central

    Johnson, Janel O.; Mandrioli, Jessica; Benatar, Michael; Abramzon, Yevgeniya; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Gibbs, J Raphael; Brunetti, Maura; Gronka, Susan; Wuu, Joanne; Ding, Jinhui; McCluskey, Leo; Martinez-Lage, Maria; Falcone, Dana; Hernandez, Dena G.; Arepalli, Sampath; Chong, Sean; Schymick, Jennifer C.; Rothstein, Jeffrey; Landi, Francesco; Wang, Michael; Calvo, Andrea; Mora, Gabriele; Sabatelli, Mario; Monsurrò, Maria Rosaria; Battistini, Stefania; Salvi, Fabrizio; Spataro, Rossella; Sola, Patrizia; Borghero, Giuseppe; Galassi, Giuliana; Scholz, Sonja W.; Taylor, J. Paul; Restagno, Gabriella; Chiò, Adriano; Traynor, Bryan J.

    2010-01-01

    Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein (VCP) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget’s disease and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically-proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on TDP-43 protein, a major constituent of ubiquitin inclusions that neuropathologically characterize ALS. Our data broaden the phenotype of IBMPFD to include motor neuron degeneration, suggest that VCP mutations may account for ~1–2% of familial ALS, and represent the first evidence directly implicating defects in the ubiquitination/protein degradation pathway in motor neuron degeneration. PMID:21145000

  5. [Phylogenomic analysis reveals the significant expansion of gene families of Volvariella volvacea ].

    PubMed

    Gong, Ming; Tan, Qi; Chen, Mingjie; Bao, Dapeng; Wang, Hong

    2014-09-01

    [OBJECTIVE] Cryogenic autolysis of Volvariella volvacea is an unusual phenomenon of abnormal metabolism. The aim of this study was to describe this molecular feature of abnormal metabolism at the genome-level. [METHODS] We used 21 fungal species for the phylogenomic analysis and then selected 9 representative species in basidiomycetes for the comparative genomic analysis. [ RESULTS] The phylogenomic analysis shows that V. volvacea was located at the bottom of the cluster consisting of grass-degrading fungi. Phylogenetic tree shows that basidiomycetes and ascomycetes fungi have independent evolutionary trajectories. Therefore, nine representative species in basidiomycetes were chosen for the comparative genomic analysis. The result shows that compared to other grass-degrading fungi, V. volvacea has the tendency of contraction. The comparison of the number of gene families on a different scale shows that there was a significant expansion of 3 large size ( > 200) gene families (faml, fam4 and fam6) in V. volvacea with their total number significantly more than other species, representing that the molecular feature of V. volvacea is correlated with its abnormal metabolism. [ CONCLUSION] The significant expansion of 3 gene families ( > 200) in V. volvacea indicates the enhancement of their function in specific gene families, which is most likely associated with cryogenic autolysis of V. volvacea. PMID:25522588

  6. Molecular and Morphological Analyses Reveal Phylogenetic Relationships of Stingrays Focusing on the Family Dasyatidae (Myliobatiformes)

    PubMed Central

    Lim, Kean Chong; Lim, Phaik-Eem; Chong, Ving Ching; Loh, Kar-Hoe

    2015-01-01

    Elucidating the phylogenetic relationships of the current but problematic Dasyatidae (Order Myliobatiformes) was the first priority of the current study. Here, we studied three molecular gene markers of 43 species (COI gene), 33 species (ND2 gene) and 34 species (RAG1 gene) of stingrays to draft out the phylogenetic tree of the order. Nine character states were identified and used to confirm the molecularly constructed phylogenetic trees. Eight or more clades (at different hierarchical level) were identified for COI, ND2 and RAG1 genes in the Myliobatiformes including four clades containing members of the present Dasyatidae, thus rendering the latter non-monophyletic. The uncorrected p-distance between these four ‘Dasytidae’ clades when compared to the distance between formally known families confirmed that these four clades should be elevated to four separate families. We suggest a revision of the present classification, retaining the Dasyatidae (Dasyatis and Taeniurops species) but adding three new families namely, Neotrygonidae (Neotrygon and Taeniura species), Himanturidae (Himantura species) and Pastinachidae (Pastinachus species). Our result indicated the need to further review the classification of Dasyatis microps. By resolving the non-monophyletic problem, the suite of nine character states enables the natural classification of the Myliobatiformes into at least thirteen families based on morphology. PMID:25867639

  7. Functional specialization among insect chitinase family genes revealed by RNA interference

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological functions of individual members of the large family of chitinase-like proteins from the red flour beetle, Tribolium castaneum, were examined using gene-specific RNA interference (RNAi). One chitinase, TcCHT5, was found to be required for pupal-adult molting only. A lethal phenotype ...

  8. Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders

    PubMed Central

    2014-01-01

    Background Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. Methods To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis Toolkit (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. Results We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the

  9. The Intra-familial Relationships of Pentaphylacaceae s.l. as Revealed by DNA Sequence Analysis.

    PubMed

    Tsou, Chih-Hua; Li, Lu; Vijayan, Kunjupillai

    2016-06-01

    During the past three decades, molecular taxonomy has made considerable changes in the systematic delimitations of several families in the order Ericales which were formed earlier based on morphology. For instance, the Pentaphylacaceae s.l. has been treated differently by both modern and traditional taxonomists. Modern molecular taxonomists constituted this family by combining the traditionally defined Pentaphylacaceae s.s. (Pentaphylax), Sladeniaceae s.s. (Sladenia), the subfamily Ternstroemioideae with 11 genera of Theaceae s.l. and the genus Ficalhoa. There are also treatments placing the genus Pentaphylax with Ternstroemioideae in Pentaphylacaceae and Ficalhoa with Sladenia in Sladeniaceae. Because most of these genera are poorly studied, investigations on all aspects are important to understand the phylogeny to settle the issues surrounding the treatment of the 14 genera in this family. In the present study, DNA sequences of nrITS and trnL-F genes from species of 11 genera from these 14 genera were generated and analyzed together with sequences from other closely related members of Ericales. The results suggested existence of four distinct lineages viz., Sladenia, Pentaphylax, and tribes Frezierieae (9 genera) and Ternstroemieae (2 genera). Further, it demonstrated that within the biggest lineage, Frezierieae, the Visnea remained sister to the clades Adinandra+Cleyera, Euryodendron+Symplococarpon, Freziera, and finally, Eurya. Based on the evidence, it can be concluded that Sladeniaceae and Pentaphylacaceae are very close to each other and the proposal of merging them into a mega family Pentaphylacaceae s.l. with four tribes, i.e., Sladenieae, Pentaphylaceae, Ternstroemieae, and Freziereae should be considered seriously. PMID:26910606

  10. Biochemical characterization of Arabidopsis APYRASE family reveals their roles in regulating endomembrane NDP/NMP homoeostasis.

    PubMed

    Chiu, Tsan-Yu; Lao, Jeemeng; Manalansan, Bianca; Loqué, Dominique; Roux, Stanley J; Heazlewood, Joshua L

    2015-11-15

    Plant apyrases are nucleoside triphosphate (NTP) diphosphohydrolases (NTPDases) and have been implicated in an array of functions within the plant including the regulation of extracellular ATP. Arabidopsis encodes a family of seven membrane bound apyrases (AtAPY1-7) that comprise three distinct clades, all of which contain the five conserved apyrase domains. With the exception of AtAPY1 and AtAPY2, the biochemical and the sub-cellular characterization of the other members are currently unavailable. In this research, we have shown all seven Arabidopsis apyrases localize to internal membranes comprising the cis-Golgi, endoplasmic reticulum (ER) and endosome, indicating an endo-apyrase classification for the entire family. In addition, all members, with the exception of AtAPY7, can function as endo-apyrases by complementing a yeast double mutant (Δynd1Δgda1) which lacks apyrase activity. Interestingly, complementation of the mutant yeast using well characterized human apyrases could only be accomplished by using a functional ER endo-apyrase (NTPDase6), but not the ecto-apyrase (NTPDase1). Furthermore, the substrate specificity analysis for the Arabidopsis apyrases AtAPY1-6 indicated that each member has a distinct set of preferred substrates covering various NDPs (nucleoside diphosphates) and NTPs. Combining the biochemical analysis and sub-cellular localization of the Arabidopsis apyrases family, the data suggest their possible roles in regulating endomembrane NDP/NMP (nucleoside monophosphate) homoeostasis. PMID:26338998

  11. Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA

    PubMed Central

    Turner, Tychele N.; Hormozdiari, Fereydoun; Duyzend, Michael H.; McClymont, Sarah A.; Hook, Paul W.; Iossifov, Ivan; Raja, Archana; Baker, Carl; Hoekzema, Kendra; Stessman, Holly A.; Zody, Michael C.; Nelson, Bradley J.; Huddleston, John; Sandstrom, Richard; Smith, Joshua D.; Hanna, David; Swanson, James M.; Faustman, Elaine M.; Bamshad, Michael J.; Stamatoyannopoulos, John; Nickerson, Deborah A.; McCallion, Andrew S.; Darnell, Robert; Eichler, Evan E.

    2016-01-01

    We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism. PMID:26749308

  12. Whole Genome Sequencing Reveals a De Novo SHANK3 Mutation in Familial Autism Spectrum Disorder

    PubMed Central

    Nemirovsky, Sergio I.; Córdoba, Marta; Zaiat, Jonathan J.; Completa, Sabrina P.; Vega, Patricia A.; González-Morón, Dolores; Medina, Nancy M.; Fabbro, Mónica; Romero, Soledad; Brun, Bianca; Revale, Santiago; Ogara, María Florencia; Pecci, Adali; Marti, Marcelo; Vazquez, Martin; Turjanski, Adrián; Kauffman, Marcelo A.

    2015-01-01

    Introduction Clinical genomics promise to be especially suitable for the study of etiologically heterogeneous conditions such as Autism Spectrum Disorder (ASD). Here we present three siblings with ASD where we evaluated the usefulness of Whole Genome Sequencing (WGS) for the diagnostic approach to ASD. Methods We identified a family segregating ASD in three siblings with an unidentified cause. We performed WGS in the three probands and used a state-of-the-art comprehensive bioinformatic analysis pipeline and prioritized the identified variants located in genes likely to be related to ASD. We validated the finding by Sanger sequencing in the probands and their parents. Results Three male siblings presented a syndrome characterized by severe intellectual disability, absence of language, autism spectrum symptoms and epilepsy with negative family history for mental retardation, language disorders, ASD or other psychiatric disorders. We found germline mosaicism for a heterozygous deletion of a cytosine in the exon 21 of the SHANK3 gene, resulting in a missense sequence of 5 codons followed by a premature stop codon (NM_033517:c.3259_3259delC, p.Ser1088Profs*6). Conclusions We reported an infrequent form of familial ASD where WGS proved useful in the clinic. We identified a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder. PMID:25646853

  13. Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.

    PubMed

    Turner, Tychele N; Hormozdiari, Fereydoun; Duyzend, Michael H; McClymont, Sarah A; Hook, Paul W; Iossifov, Ivan; Raja, Archana; Baker, Carl; Hoekzema, Kendra; Stessman, Holly A; Zody, Michael C; Nelson, Bradley J; Huddleston, John; Sandstrom, Richard; Smith, Joshua D; Hanna, David; Swanson, James M; Faustman, Elaine M; Bamshad, Michael J; Stamatoyannopoulos, John; Nickerson, Deborah A; McCallion, Andrew S; Darnell, Robert; Eichler, Evan E

    2016-01-01

    We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism. PMID:26749308

  14. Portrait of the Polana-Eulalia family complex: Surface homogeneity revealed from near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Pinilla-Alonso, Noemí; de León, J.; Walsh, K. J.; Campins, H.; Lorenzi, V.; Delbo, M.; DeMeo, F.; Licandro, J.; Landsman, Z.; Lucas, M. P.; Alí-Lagoa, V.; Burt, B.

    2016-08-01

    The inner asteroid belt is an important source of near-Earth asteroids (NEAs). Dynamical studies of the inner asteroid belt have identified several families overlapping in proper orbital elements, including the Polana and Eulalia families that contain a large fraction of the low-albedo asteroids in this region. We present results from two coordinated observational campaigns to characterize this region through near-infrared (NIR) spectroscopy. These campaigns ran from August 2012 to May 2014 and used the NASA Infrared Telescope Facility and the Telescopio Nazionale Galileo. The observations focused on objects within these families or in the background, with low albedo (pv ≤ 0.1) and low inclination (iP ≤ 7°). We observed 63 asteroids (57 never before observed in the NIR): 61 low-albedo objects and two interlopers, both compatible with S- or E- taxonomical types. We found our sample to be spectrally homogeneous in the NIR. The sample shows a continuum of neutral to moderately-red concave-up spectra, very similar within the uncertainties. Only one object in the sample, asteroid (3429) Chuvaev, has a blue spectrum, with a slope (S‧ = - 1.33 ± 0.21%/1000 Å) significantly different from the average spectrum (S‧ = 0.68 ± 0.68%/1000 Å). This spectral homogeneity is independent of membership in families or the background population. Furthermore, we show that the Eulalia and Polana families cannot be distinguished using NIR data. We also searched for rotational variability on the surface of (495) Eulalia which we do not detect. (495) Eulalia shows a red concave-up spectrum with an average slope S‧ = 0.91 ± 0.60%/1000 Å, very similar to the average slope of our sample. The spectra of two targets of sample-return missions, (101955) Bennu, target of NASA's OSIRIS-Rex and (162173) 1999 JU3 target of the Japanese Space Agency's Hayabusa-2, are very similar to our average spectrum, which would be compatible with an origin in this region of the inner belt.

  15. Exome Sequencing Reveals Novel Rare Variants in the Ryanodine Receptor and Calcium Channel Genes in Malignant Hyperthermia Families

    PubMed Central

    Kim, Jerry H.; Jarvik, Gail P.; Browning, Brian L.; Rajagopalan, Ramakrishnan; Gordon, Adam S.; Rieder, Mark J.; Robertson, Peggy D.; Nickerson, Deborah A.; Fisher, Nickla A.; Hopkins, Philip M.

    2014-01-01

    Background About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, α1S subunit (CACNA1S) gene mutations, leaving many with an unknown cause. We chose to apply a sequencing approach to uncover causal variants in unknown cases. Sequencing the exome, the protein-coding region of the genome, has power at low sample sizes and identified the cause of over a dozen Mendelian disorders. Methods We considered four families with multiple MH cases but in whom no mutations in RYR1 and CACNA1S had been identified by Sanger sequencing of complementary DNA. Exome sequencing of two affecteds per family, chosen for maximum genetic distance, were compared. Variants were ranked by allele frequency, protein change, and measures of conservation among mammals to assess likelihood of causation. Finally, putative pathogenic mutations were genotyped in other family members to verify cosegregation with MH. Results Exome sequencing revealed 1 rare RYR1 nonsynonymous variant in each of 3 families (Asp1056His, Val2627Met, Val4234Leu), and 1 CACNA1S variant (Thr1009Lys) in a 4th family. These were not seen in variant databases or in our control population sample of 5379 exomes. Follow-up sequencing in other family members verified cosegregation of alleles with MH. Conclusions Using both exome sequencing and allele frequency data from large sequencing efforts may aid genetic diagnosis of MH. In our sample, it was more sensitive for variant detection in known genes than Sanger sequencing of complementary DNA, and allows for the possibility of novel gene discovery. PMID:24013571

  16. Subtypes of familial breast tumours revealed by expression and copy number profiling.

    PubMed

    Waddell, Nic; Arnold, Jeremy; Cocciardi, Sibylle; da Silva, Leonard; Marsh, Anna; Riley, Joan; Johnstone, Cameron N; Orloff, Mohammed; Assie, Guillaume; Eng, Charis; Reid, Lynne; Keith, Patricia; Yan, Max; Fox, Stephen; Devilee, Peter; Godwin, Andrew K; Hogervorst, Frans B L; Couch, Fergus; Grimmond, Sean; Flanagan, James M; Khanna, Kumkum; Simpson, Peter T; Lakhani, Sunil R; Chenevix-Trench, Georgia

    2010-10-01

    Extensive expression profiling studies have shown that sporadic breast cancer is composed of five clinically relevant molecular subtypes. However, although BRCA1-related tumours are known to be predominantly basal-like, there are few published data on other classes of familial breast tumours. We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1/2 breast tumours by gene expression profiling and found that 74% BRCA1 tumours were basal-like, 73% of BRCA2 tumours were luminal A or B, and 52% non-BRCA1/2 tumours were luminal A. Thirty-four tumours were also analysed by single nucleotide polymorphism-comparative genomic hybridization (SNP-CGH) arrays. Copy number data could predict whether a tumour was basal-like or luminal with high accuracy, but could not predict its mutation class. Basal-like BRCA1 and basal-like non-BRCA1 tumours were very similar, and contained the highest number of chromosome aberrations. We identified regions of frequent gain containing potential driver genes in the basal (8q and 12p) and luminal A tumours (1q and 17q). Regions of homozygous loss associated with decreased expression of potential tumour suppressor genes were also detected, including in basal tumours (5q and 9p), and basal and luminal tumours (10q). This study highlights the heterogeneity of familial tumours and the clinical consequences for treatment and prognosis. PMID:19960244

  17. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.

    PubMed

    Masters, Seth L; Lagou, Vasiliki; Jéru, Isabelle; Baker, Paul J; Van Eyck, Lien; Parry, David A; Lawless, Dylan; De Nardo, Dominic; Garcia-Perez, Josselyn E; Dagley, Laura F; Holley, Caroline L; Dooley, James; Moghaddas, Fiona; Pasciuto, Emanuela; Jeandel, Pierre-Yves; Sciot, Raf; Lyras, Dena; Webb, Andrew I; Nicholson, Sandra E; De Somer, Lien; van Nieuwenhove, Erika; Ruuth-Praz, Julia; Copin, Bruno; Cochet, Emmanuelle; Medlej-Hashim, Myrna; Megarbane, Andre; Schroder, Kate; Savic, Sinisa; Goris, An; Amselem, Serge; Wouters, Carine; Liston, Adrian

    2016-03-30

    Pyrin responds to pathogen signals and loss of cellular homeostasis by forming an inflammasome complex that drives the cleavage and secretion of interleukin-1β (IL-1β). Mutations in the B30.2/SPRY domain cause pathogen-independent activation of pyrin and are responsible for the autoinflammatory disease familial Mediterranean fever (FMF). We studied a family with a dominantly inherited autoinflammatory disease, distinct from FMF, characterized by childhood-onset recurrent episodes of neutrophilic dermatosis, fever, elevated acute-phase reactants, arthralgia, and myalgia/myositis. The disease was caused by a mutation in MEFV, the gene encoding pyrin (S242R). The mutation results in the loss of a 14-3-3 binding motif at phosphorylated S242, which was not perturbed by FMF mutations in the B30.2/SPRY domain. However, loss of both S242 phosphorylation and 14-3-3 binding was observed for bacterial effectors that activate the pyrin inflammasome, such as Clostridium difficile toxin B (TcdB). The S242R mutation thus recapitulated the effect of pathogen sensing, triggering inflammasome activation and IL-1β production. Successful therapy targeting IL-1β has been initiated in one patient, resolving pyrin-associated autoinflammation with neutrophilic dermatosis. This disease provides evidence that a guard-like mechanism of pyrin regulation, originally identified for Nod-like receptors in plant innate immunity, also exists in humans. PMID:27030597

  18. Transcriptome analysis reveals a diverse family of kinesins essential for spermatogenesis in the fern Marsilea.

    PubMed

    Tomei, Erika J; Wolniak, Stephen M

    2016-03-01

    The male gametophyte of the semi-aquatic fern, Marsilea vestita, produces multiciliated spermatozoids in a rapid developmental sequence that is controlled post-transcriptionally when dry microspores are placed in water. Development can be divided into two phases, mitosis and differentiation. During the mitotic phase, a series of nine successive division cycles produce 7 sterile cells and 32 spermatids in 4.5-5 h. During the next 5-6 h, each spermatid differentiates into a corkscrew-shaped motile spermatozoid with ∼140 cilia. In order to study the mechanisms that regulate spermatogenesis, we used RNAseq to generate a reference transcriptome that allowed us to assess abundance of transcripts at different stages of development. Here, we characterize transcripts present in the kinesin motor family. Over 120 kinesin-like sequences were identified in our transcriptome that represent 56 unique kinesin transcripts. Members of the kinesin-2, -4, -5, -7, -8, -9, -12, -13, and -14 families, in addition to several plant specific and 'orphan' kinesins are present. Most (91%) of these kinesin transcripts change in abundance throughout gametophyte development, with 52% of kinesin mRNAs enriched during the mitotic phase and 39% enriched during differentiation. Functional analyses of six kinesins with different patterns of transcript abundance show that the temporal regulation of these transcripts during gametogenesis correlates directly with kinesin protein function. PMID:26887361

  19. Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies

    PubMed Central

    Saqib, Muhammad Arif Nadeem; Nikopoulos, Konstantinos; Ullah, Ehsan; Sher Khan, Falak; Iqbal, Jamila; Bibi, Rabia; Jarral, Afeefa; Sajid, Sundus; Nishiguchi, Koji M.; Venturini, Giulia; Ansar, Muhammad; Rivolta, Carlo

    2015-01-01

    Inherited retinal dystrophies are phenotypically and genetically heterogeneous. This extensive heterogeneity poses a challenge when performing molecular diagnosis of patients, especially in developing countries. In this study, we applied homozygosity mapping as a tool to reduce the complexity given by genetic heterogeneity and identify disease-causing variants in consanguineous Pakistani pedigrees. DNA samples from eight families with autosomal recessive retinal dystrophies were subjected to genome wide homozygosity mapping (seven by SNP arrays and one by STR markers) and genes comprised within the detected homozygous regions were analyzed by Sanger sequencing. All families displayed consistent autozygous genomic regions. Sequence analysis of candidate genes identified four previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3, and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA splicing of CNGB1 by creating a -1 frameshift leading to a premature termination codon. In addition to better delineating the genetic landscape of inherited retinal dystrophies in Pakistan, our data confirm that combining homozygosity mapping and candidate gene sequencing is a powerful approach for mutation identification in populations where consanguineous unions are common. PMID:25943428

  20. Exome sequencing revealed PMM2 gene mutations in a French-Canadian family with congenital atrophy of the cerebellum.

    PubMed

    Noreau, Anne; Beauchemin, Philippe; Dionne-Laporte, Alexandre; Dion, Patrick A; Rouleau, Guy A; Dupré, Nicolas

    2014-01-01

    Two affected and one unaffected siblings from a French-Canadian family were evaluated in our neurogenetic clinic. The oldest brother had intentional and postural hand tremor while his youngest sister presented mild ataxia, a similar hand tremor and global developmental delay. Brain MRIs of the two affected family members further revealed a significant cerebellar atrophy. For this study we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected brother and sister, alongside DNA prepared from their unaffected mother, and identified two mutations previously reported to cause a rare disorder known as Congenital Disorder of Glycosylation, type Ia (CDG1A) (OMIM #212065). This study emphasizes how the diagnosis of patients presenting a mild tremor phenotype associated with cerebellar atrophy may benefit from WES in establishing genetic defects associated with their conditions. PMID:26331032

  1. rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA.

    PubMed

    Haud, Noémie; Kara, Firat; Diekmann, Simone; Henneke, Marco; Willer, Jason R; Hillwig, Melissa S; Gregg, Ronald G; Macintosh, Gustavo C; Gärtner, Jutta; Alia, A; Hurlstone, Adam F L

    2011-01-18

    T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined for metazoa. RNASET2 mutation in humans is linked with a leukoencephalopathy that arises in infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of RNASET2 within lysosomes. Further, we demonstrate that loss of rnaset2 in mutant zebrafish results in accumulation of undigested rRNA within lysosomes within neurons of the brain. Further, by using high field intensity magnetic resonance microimaging, we reveal white matter lesions in these animals comparable to those observed in RNASET2-deficient infants. This correlates with accumulation of Amyloid precursor protein and astrocytes at sites of neurodegeneration. Thus we conclude that familial cystic leukoencephalopathy is a lysosomal storage disorder in which rRNA is the best candidate for the noxious storage material. PMID:21199949

  2. rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA

    PubMed Central

    Haud, Noémie; Kara, Firat; Diekmann, Simone; Henneke, Marco; Willer, Jason R.; Hillwig, Melissa S.; Gregg, Ronald G.; MacIntosh, Gustavo C.; Gärtner, Jutta; Alia, A.; Hurlstone, Adam F. L.

    2011-01-01

    T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined for metazoa. RNASET2 mutation in humans is linked with a leukoencephalopathy that arises in infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of RNASET2 within lysosomes. Further, we demonstrate that loss of rnaset2 in mutant zebrafish results in accumulation of undigested rRNA within lysosomes within neurons of the brain. Further, by using high field intensity magnetic resonance microimaging, we reveal white matter lesions in these animals comparable to those observed in RNASET2-deficient infants. This correlates with accumulation of Amyloid precursor protein and astrocytes at sites of neurodegeneration. Thus we conclude that familial cystic leukoencephalopathy is a lysosomal storage disorder in which rRNA is the best candidate for the noxious storage material. PMID:21199949

  3. Genetic study in a tunisian family revealed IVS1+1G>A mutation in the CHM gene.

    PubMed

    Ben Charfeddine, Ilhem; Ben Lazreg, Taheni; Ben Rayana, Narjes; Amara, Abdelbasset; Mamaï, Ons; Knani, Leila; Mili, Amira; M'sakni, Ahlem; Saad, Ali; Ben Hadj Hamida, Fafani; Gribaa, Moez

    2015-01-01

    Choroideremia is a rare X-linked recessive, hereditary retinal pigment epithelial dystrophy, characterized by night blindness and progressive constriction of the visual fields leading to blindness in young adulthood. In this study, we reported three cases of choroideremia belonging to a Tunisian family. Patients complained of vision loss and night blindness. Fundus examination revealed diffused chorioretenal atrophy. In all cases, there was a visual field constriction and an undetectable electroretinography. Direct sequencing of the CHM gene detected a guanine to adenine transition (G>A) into the donor splice site of intron 1 leads to aberrantly spliced mRNA producing a premature stop codon and therefore functional loss of the CHM gene product, REP-1. The diagnosis should be considered in patients with a suitable family history and fundus findings. PMID:26411914

  4. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    PubMed Central

    Feitosa, Mary F.; Wojczynski, Mary K.; Straka, Robert; Kammerer, Candace M.; Lee, Joseph H.; Kraja, Aldi T.; Christensen, Kaare; Newman, Anne B.; Province, Michael A.; Borecki, Ingrid B.

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights into biological regulation of HDL metabolism in healthy-longevous subjects. We performed a genome-wide association (GWA) scan on HDL using a mixed model approach to account for family structure using kinship coefficients. A total of 4114 subjects of European descent (480 families) were genotyped at ~2.3 million SNPs and ~38 million SNPs were imputed using the 1000 Genome Cosmopolitan reference panel in MACH. We identified novel variants near-NLRP1 (17p13) associated with an increase of HDL levels at genome-wide significant level (p < 5.0E-08). Additionally, several CETP (16q21) and ZNF259-APOA5-A4-C3-A1 (11q23.3) variants associated with HDL were found, replicating those previously reported in the literature. A possible regulatory variant upstream of NLRP1 that is associated with HDL in these elderly Long Life Family Study (LLFS) subjects may also contribute to their longevity and health. Our NLRP1 intergenic SNPs show a potential regulatory function in Encyclopedia of DNA Elements (ENCODE); however, it is not clear whether they regulate NLRP1 or other more remote gene. NLRP1 plays an important role in the induction of apoptosis, and its inflammasome is critical for mediating innate immune responses. Nlrp1a (a mouse ortholog of human NLRP1) interacts with SREBP-1a (17p11) which has a fundamental role in lipid concentration and composition, and is involved in innate immune response in macrophages. The NLRP1 region is conserved in mammals, but also has evolved adaptively showing signals of positive selection in European populations that might confer an advantage. NLRP1 intergenic SNPs have also been associated with immunity/inflammasome disorders which highlights the biological

  5. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

    PubMed Central

    2011-01-01

    Background Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF), a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) data in mouse and human embryonic stem (ES) cells combined with detection of CTCF-binding motifs. Conclusions The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s) of Ush1g and Otop in developmental pathways. PMID:21261979

  6. Thermodynamic Characterization of a Triheme Cytochrome Family from Geobacter sulfurreducens Reveals Mechanistic and Functional Diversity

    PubMed Central

    Morgado, Leonor; Bruix, Marta; Pessanha, Miguel; Londer, Yuri Y.; Salgueiro, Carlos A.

    2010-01-01

    Abstract A family of five periplasmic triheme cytochromes (PpcA-E) was identified in Geobacter sulfurreducens, where they play a crucial role by driving electron transfer from the cytoplasm to the cell exterior and assisting the reduction of extracellular acceptors. The thermodynamic characterization of PpcA using NMR and visible spectroscopies was previously achieved under experimental conditions identical to those used for the triheme cytochrome c7 from Desulfuromonas acetoxidans. Under such conditions, attempts to obtain NMR data were complicated by the relatively fast intermolecular electron exchange. This work reports the detailed thermodynamic characterization of PpcB, PpcD, and PpcE under optimal experimental conditions. The thermodynamic characterization of PpcA was redone under these new conditions to allow a proper comparison of the redox properties with those of other members of this family. The heme reduction potentials of the four proteins are negative, differ from each other, and cover different functional ranges. These reduction potentials are strongly modulated by heme-heme interactions and by interactions with protonated groups (the redox-Bohr effect) establishing different cooperative networks for each protein, which indicates that they are designed to perform different functions in the cell. PpcA and PpcD appear to be optimized to interact with specific redox partners involving e−/H+ transfer via different mechanisms. Although no evidence of preferential electron transfer pathway or e−/H+ coupling was found for PpcB and PpcE, the difference in their working potential ranges suggests that they may also have different physiological redox partners. This is the first study, to our knowledge, to characterize homologous cytochromes from the same microorganism and provide evidence of their different mechanistic and functional properties. These findings provide an explanation for the coexistence of five periplasmic triheme cytochromes in G

  7. Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response.

    PubMed

    Yuan, Shaochun; Zheng, Tingting; Li, Peiyi; Yang, Rirong; Ruan, Jie; Huang, Shengfeng; Wu, Zhenxin; Xu, Anlong

    2015-12-15

    The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks. PMID:26573836

  8. Conserved evolutionary units in the heme-copper oxidase superfamily revealed by novel homologous protein families

    PubMed Central

    Pei, Jimin; Li, Wenlin; Kinch, Lisa N; Grishin, Nick V

    2014-01-01

    The heme-copper oxidase (HCO) superfamily includes HCOs in aerobic respiratory chains and nitric oxide reductases (NORs) in the denitrification pathway. The HCO/NOR catalytic subunit has a core structure consisting of 12 transmembrane helices (TMHs) arranged in three-fold rotational pseudosymmetry, with six conserved histidines for heme and metal binding. Using sensitive sequence similarity searches, we detected a number of novel HCO/NOR homologs and named them HCO Homology (HCOH) proteins. Several HCOH families possess only four TMHs that exhibit the most pronounced similarity to the last four TMHs (TMHs 9–12) of HCOs/NORs. Encoded by independent genes, four-TMH HCOH proteins represent a single evolutionary unit (EU) that relates to each of the three homologous EUs of HCOs/NORs comprising TMHs 1–4, TMHs 5–8, and TMHs 9–12. Single-EU HCOH proteins could form homotrimers or heterotrimers to maintain the general structure and ligand-binding sites defined by the HCO/NOR catalytic subunit fold. The remaining HCOH families, including NnrS, have 12-TMHs and three EUs. Most three-EU HCOH proteins possess two conserved histidines and could bind a single heme. Limited experimental studies and genomic context analysis suggest that many HCOH proteins could function in the denitrification pathway and in detoxification of reactive molecules such as nitric oxide. HCO/NOR catalytic subunits exhibit remarkable structural similarity to the homotrimers of MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism) proteins. Gene duplication, fusion, and fission likely play important roles in the evolution of HCOs/NORs and HCOH proteins. PMID:24931479

  9. The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation.

    PubMed

    Martinez-Martin, Nadia; Ramani, Sree R; Hackney, Jason A; Tom, Irene; Wranik, Bernd J; Chan, Michelle; Wu, Johnny; Paluch, Maciej T; Takeda, Kentaro; Hass, Philip E; Clark, Hilary; Gonzalez, Lino C

    2016-01-01

    Viruses encode secreted and cell-surface expressed proteins essential to modulate host immune defenses and establish productive infections. However, to date there has been no systematic study of the extracellular interactome of any human virus. Here we utilize the E3 proteins, diverse and rapidly evolving transmembrane-containing proteins encoded by human adenoviruses, as a model system to survey the extracellular immunomodulatory landscape. From a large-scale protein interaction screen against a microarray of more than 1,500 human proteins, we find and validate 51 previously unidentified virus-host interactions. Our results uncover conserved strategies as well as substantial diversity and multifunctionality in host targeting within and between viral species. Prominent modulation of the leukocyte immunoglobulin-like and signalling lymphocyte activation molecule families and a number of inhibitory receptors were identified as hubs for viral perturbation, suggesting unrecognized immunoregulatory strategies. We describe a virus-host extracellular interaction map of unprecedented scale that provides new insights into viral immunomodulation. PMID:27145901

  10. Molecular Phylogenetic Analysis Reveals the New Genus Hemisphaericaspora of the Family Debaryomycetaceae

    PubMed Central

    Hui, Fengli; Ren, Yongcheng; Chen, Liang; Li, Ying; Zhang, Lin; Niu, Qiuhong

    2014-01-01

    Four strains of a novel ascomycetous yeast species were recovered from the frass of wood-boring beetles collected from the Baotianman Nature Reserve and the Laojieling Nature Reserve in Henan Province, China. This species produced unconjugated and deliquescent asci with hemispheroid or helmet-shaped ascospores. Analysis of gene sequences for the D1/D2 domain of the large subunit (LSU) rRNA, as well as analysis of concatenated gene sequences for the nearly complete small subunit (SSU) rRNA and D1/D2 domain of the large subunit (LSU) rRNA placed the novel species in a small clade including only one recognised species, Candida insectamans, in the family Debaryomycetaceae (Saccharomycotina, Ascomycota). DNA sequence analyses demonstrated that the novel species was distinct from all currently recognised teleomorphic yeast genus. The name Hemisphaericaspora nanyangensis gen nov., sp. nov. is proposed to accommodate the novel genus and species. The new genus can be distinguished from closely related teleomorphic genera Lodderomyces and Spathaspora through sequence comparison and ascospore morphology. The ex-type strain of H. nanyangensis is CBS 13020T ( = CICC 33021 = NYNU 13717). Furthermore, based on phenotypic and genotypic characteristics, C. insectamans is transferred to the newly described genus as Hemisphaericaspora insectamans comb. nov., in accordance with the changes in the International Code of Nomenclature for algae, fungi and plants. PMID:25075963

  11. The cloning of Grb10 reveals a new family of SH2 domain proteins.

    PubMed

    Ooi, J; Yajnik, V; Immanuel, D; Gordon, M; Moskow, J J; Buchberg, A M; Margolis, B

    1995-04-20

    SH2 domains function to bind proteins containing phosphotyrosine and are components of proteins that are important signal transducers for tyrosine kinases. We have cloned SH2 domain proteins by screening bacterial expression libraries with the tyrosine phosphorylated carboxyterminus of the epidermal growth factor (EGF) receptor. Here we report the identification of a new SH2 domain protein, Grb10. Grb10 is highly related to Grb7, an SH2 domain protein that we have previously identified. In addition to an SH2 domain, Grb7 and Grb10 have a central domain with similarity to a putative C. elegans gene likely to be involved in neuronal migration. At least three forms of Grb10 exist in fibroblasts apparently due to alternate translational start sites. Grb10 undergoes serine but not tyrosine phosphorylation after EGF treatment resulting in a shift mobility in a large fraction of Grb10 molecules. However Grb10 appears to bind poorly to EGF-Receptor and the true binding partner for the Grb10 SH2 domain is unclear. Grb10 maps to mouse chromosome 11 very close to the EGF-Receptor which is remarkably similar to Grb7 that maps near the EGF-Receptor related HER2 receptor. The finding of multiple family members with evolutionarily conserved domains indicates that these SH2 domain proteins are likely to have an important, although as of yet, unidentified function. PMID:7731717

  12. The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation

    PubMed Central

    Martinez-Martin, Nadia; Ramani, Sree R.; Hackney, Jason A.; Tom, Irene; Wranik, Bernd J.; Chan, Michelle; Wu, Johnny; Paluch, Maciej T.; Takeda, Kentaro; Hass, Philip E.; Clark, Hilary; Gonzalez, Lino C.

    2016-01-01

    Viruses encode secreted and cell-surface expressed proteins essential to modulate host immune defenses and establish productive infections. However, to date there has been no systematic study of the extracellular interactome of any human virus. Here we utilize the E3 proteins, diverse and rapidly evolving transmembrane-containing proteins encoded by human adenoviruses, as a model system to survey the extracellular immunomodulatory landscape. From a large-scale protein interaction screen against a microarray of more than 1,500 human proteins, we find and validate 51 previously unidentified virus–host interactions. Our results uncover conserved strategies as well as substantial diversity and multifunctionality in host targeting within and between viral species. Prominent modulation of the leukocyte immunoglobulin-like and signalling lymphocyte activation molecule families and a number of inhibitory receptors were identified as hubs for viral perturbation, suggesting unrecognized immunoregulatory strategies. We describe a virus–host extracellular interaction map of unprecedented scale that provides new insights into viral immunomodulation. PMID:27145901

  13. Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia

    PubMed Central

    Rafi, Syed K.; Olm-Shipman, Adam J.; Wilson, Nathan R.; Abhyankar, Sunil; Ganter, Brigitte; Furness, L. Mike; Fang, Jianwen; Calado, Rodrigo T.

    2013-01-01

    We recently identified 2 siblings afflicted with idiopathic, autosomal recessive aplastic anemia. Whole-exome sequencing identified a novel homozygous missense mutation in thrombopoietin (THPO, c.112C>T) in both affected siblings. This mutation encodes an arginine to cysteine substitution at residue 38 or residue 17 excluding the 21-amino acid signal peptide of THPO receptor binding domain (RBD). THPO has 4 conserved cysteines in its RBD that form 2 disulfide bonds. Our in silico modeling predicts that introduction of a fifth cysteine may disrupt normal disulfide bonding to cause poor receptor binding. In functional assays, the mutant-THPO–containing media shows two- to threefold reduced ability to sustain UT7-TPO cells, which require THPO for proliferation. Both parents and a sibling with heterozygous R17C change have reduced platelet counts, whereas a sibling with wild-type sequence has normal platelet count. Thus, the R17C partial loss-of-function allele results in aplastic anemia in the homozygous state and mild thrombocytopenia in the heterozygous state in our family. Together with the recent identification of THPO receptor (MPL) mutations and the effects of THPO agonists in aplastic anemia, our results have clinical implications in the diagnosis and treatment of patients with aplastic anemia and highlight a role for the THPO-MPL pathway in hematopoiesis in vivo. PMID:24085763

  14. Structural characterization of Helicobacter pylori dethiobiotin synthetase reveals differences between family members

    SciTech Connect

    Porebski, Przemyslaw J.; Klimecka, Maria; Chruszcz, Maksymilian; Nicholls, Robert A.; Murzyn, Krzysztof; Cuff, Marianne E.; Xu, Xiaohui; Cymborowski, Marcin; Murshudov, Garib N.; Savchenko, Alexei; Edwards, Aled; Minor, Wladek

    2012-07-11

    Dethiobiotin synthetase (DTBS) is involved in the biosynthesis of biotin in bacteria, fungi, and plants. As humans lack this pathway, DTBS is a promising antimicrobial drug target. We determined structures of DTBS from Helicobacter pylori (hpDTBS) bound with cofactors and a substrate analog, and described its unique characteristics relative to other DTBS proteins. Comparison with bacterial DTBS orthologs revealed considerable structural differences in nucleotide recognition. The C-terminal region of DTBS proteins, which contains two nucleotide-recognition motifs, differs greatly among DTBS proteins from different species. The structure of hpDTBS revealed that this protein is unique and does not contain a C-terminal region containing one of the motifs. The single nucleotide-binding motif in hpDTBS is similar to its counterpart in GTPases; however, isothermal titration calorimetry binding studies showed that hpDTBS has a strong preference for ATP. The structural determinants of ATP specificity were assessed with X-ray crystallographic studies of hpDTBS-ATP and hpDTBS-GTP complexes. The unique mode of nucleotide recognition in hpDTBS makes this protein a good target for H. pylori-specific inhibitors of the biotin synthesis pathway.

  15. Ligand-receptor binding revealed by the TNF family member TALL-1.

    SciTech Connect

    Liu, Y. F.; Hong, X.; Kappler, J.; Jiang, L.; Zhang, R. G.; Xu, L. G.; Pan, C.-H.; Martin, W. E.; Murphy, R. C.; Shu, H.-B.; Dai, S. D.; Zhang, G. Y.; Biosciences Division; National Jewish Medical and Research Center; Howard Hughes Medical Inst.; Univ. of Colorado Health Science Center; Peking Univ.

    2003-05-01

    The tumour necrosis factor (TNF) ligand TALL-1 and its cognate receptors, BCMA, TACI and BAFF-R, were recently identified as members of the TNF superfamily, which are essential factors contributing to B-cell maturation. The functional, soluble fragment of TALL-1 (sTALL-1) forms a virus-like assembly for its proper function. Here we determine the crystal structures of sTALL-1 complexed with the extracellular domains of BCMA and BAFF-R at 2.6 and 2.5 {angstrom}, respectively. The single cysteine-rich domain of BCMA and BAFF-R both have saddle-like architectures, which sit on the horseback-like surface formed by four coil regions on each individual sTALL-1 monomer. Three novel structural modules, D2, X2 and N, were revealed from the current structures. Sequence alignments, structural modelling and mutagenesis revealed that one disulphide bridge in BAFF-R is critical for determining the binding specificity of the extracellular domain eBAFF-R to TALL-1 instead of APRIL, a closely related ligand of TALL-1, which was confirmed by binding experiments in vitro.

  16. Targeted Next-generation Sequencing Reveals Novel EYS Mutations in Chinese Families with Autosomal Recessive Retinitis Pigmentosa

    PubMed Central

    Chen, Xue; Liu, Xiaoxing; Sheng, Xunlun; Gao, Xiang; Zhang, Xiumei; Li, Zili; Li, Huiping; Liu, Yani; Rong, Weining; Zhao, Kanxing; Zhao, Chen

    2015-01-01

    EYS mutations demonstrate great genotypic and phenotypic varieties, and are one of the major causes for patients with autosomal recessive retinitis pigmentosa (ARRP). Here, we aim to determine the genetic lesions with phenotypic correlations in two Chinese families with ARRP. Medical histories and ophthalmic documentations were obtained from all participants from the two pedigrees. Targeted next-generation sequencing (NGS) on 189 genes was performed to screen for RP causative mutations in the two families. Two biallelic mutations in EYS, p.[R164*];[C2139Y] and p.[W2640*];[F2954S], were identified in the two families, respectively. EYS p.R164* and p.F2954S are novel alleles associated with RP, while p.C2139Y and p.W2640* are known mutations. Crystal structure modeling on the protein eyes shut homolog encoded by the EYS gene revealed abnormal hydrogen bonds generated by p.C2139Y and p.F2954S, which would likely affect the solubility and cause significant structural changes of the two mutated proteins. In conclusion, our study expands the genotypic spectrums for EYS mutations, and may provide novel insights into the relevant pathogenesis for RP. We also demonstrate targeted NGS approach as a valuable tool for genetic diagnosis. PMID:25753737

  17. The intergenerational correlation in weight: How genetic resemblance reveals the social role of families*

    PubMed Central

    Martin, Molly A.

    2009-01-01

    According to behavioral genetics research, the intergenerational correlation in weight derives solely from shared genetic predispositions, but complete genetic determinism contradicts the scientific consensus that social and behavioral change underlies the modern obesity epidemic. To address this conundrum, this article utilizes sibling data from the National Longitudinal Study of Adolescent Health and extends structural equation sibling models to incorporate siblings’ genetic relationships to explore the role of families’ social characteristics for adolescent weight. The article is the first to demonstrate that the association between parents’ obesity and adolescent weight is both social and genetic. Furthermore, by incorporating genetic information, the shared and social origins of the correlation between inactivity and weight are better revealed. PMID:19569401

  18. Structure of the N-terminal fragment of topoisomerase V reveals a new family of topoisomerases

    SciTech Connect

    Taneja, Bhupesh; Patel, Asmita; Slesarev, Alexei; Mondragon, Alfonso

    2010-09-02

    Topoisomerases are involved in controlling and maintaining the topology of DNA and are present in all kingdoms of life. Unlike all other types of topoisomerases, similar type IB enzymes have only been identified in bacteria and eukarya. The only putative type IB topoisomerase in archaea is represented by Methanopyrus kandleri topoisomerase V. Despite several common functional characteristics, topoisomerase V shows no sequence similarity to other members of the same type. The structure of the 61 kDa N-terminal fragment of topoisomerase V reveals no structural similarity to other topoisomerases. Furthermore, the structure of the active site region is different, suggesting no conservation in the cleavage and religation mechanism. Additionally, the active site is buried, indicating the need of a conformational change for activity. The presence of a topoisomerase in archaea with a unique structure suggests the evolution of a separate mechanism to alter DNA.

  19. Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases.

    PubMed

    Itoh, Takayuki; Tokunaga, Kinya; Matsuda, Yudai; Fujii, Isao; Abe, Ikuro; Ebizuka, Yutaka; Kushiro, Tetsuo

    2010-10-01

    Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities. PMID:20861902

  20. Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases

    NASA Astrophysics Data System (ADS)

    Itoh, Takayuki; Tokunaga, Kinya; Matsuda, Yudai; Fujii, Isao; Abe, Ikuro; Ebizuka, Yutaka; Kushiro, Tetsuo

    2010-10-01

    Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.

  1. Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis

    PubMed Central

    Davies, Kalina T.J.; Bennett, Nigel C.; Tsagkogeorga, Georgia; Rossiter, Stephen J.; Faulkes, Christopher G.

    2015-01-01

    During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein–protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. PMID:26318402

  2. Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons

    PubMed Central

    George, Lynn; Chaverra, Marta; Wolfe, Lindsey; Thorne, Julian; Close-Davis, Mattheson; Eibs, Amy; Riojas, Vickie; Grindeland, Andrea; Orr, Miranda; Carlson, George A.; Lefcort, Frances

    2013-01-01

    Familial dysautonomia (FD) is a devastating developmental and progressive peripheral neuropathy caused by a mutation in the gene inhibitor of kappa B kinase complex-associated protein (IKBKAP). To identify the cellular and molecular mechanisms that cause FD, we generated mice in which Ikbkap expression is ablated in the peripheral nervous system and identify the steps in peripheral nervous system development that are Ikbkap-dependent. We show that Ikbkap is not required for trunk neural crest migration or pathfinding, nor for the formation of dorsal root or sympathetic ganglia, or the adrenal medulla. Instead, Ikbkap is essential for the second wave of neurogenesis during which the majority of tropomyosin-related kinase A (TrkA+) nociceptors and thermoreceptors arise. In its absence, approximately half the normal complement of TrkA+ neurons are lost, which we show is partly due to p53-mediated premature differentiation and death of mitotically-active progenitors that express the paired-box gene Pax3 and give rise to the majority of TrkA+ neurons. By the end of sensory development, the number of TrkC neurons is significantly increased, which may result from an increase in Runx3+ cells. Furthermore, our data demonstrate that TrkA+ (but not TrkC+) sensory and sympathetic neurons undergo exacerbated Caspase 3-mediated programmed cell death in the absence of Ikbkap and that this death is not due to a reduction in nerve growth factor synthesis. In summary, these data suggest that FD does not result from a failure in trunk neural crest migration, but rather from a critical function for Ikbkap in TrkA progenitors and TrkA+ neurons. PMID:24173031

  3. Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

    PubMed

    Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

    2015-12-01

    During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. PMID:26318402

  4. RNA-Seq Analysis Reveals MAPKKK Family Members Related to Drought Tolerance in Maize

    PubMed Central

    Ren, Wen; Yang, Fengling; He, Hang; Zhao, Jiuran

    2015-01-01

    The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction pathway that is involved in plant development and stress responses. As the first component of this phosphorelay cascade, mitogen-activated protein kinase kinase kinases (MAPKKKs) act as adaptors linking upstream signaling steps to the core MAPK cascade to promote the appropriate cellular responses; however, the functions of MAPKKKs in maize are unclear. Here, we identified 71 MAPKKK genes, of which 14 were novel, based on a computational analysis of the maize (Zea mays L.) genome. Using an RNA-seq analysis in the leaf, stem and root of maize under well-watered and drought-stress conditions, we identified 5,866 differentially expressed genes (DEGs), including 8 MAPKKK genes responsive to drought stress. Many of the DEGs were enriched in processes such as drought stress, abiotic stimulus, oxidation-reduction, and metabolic processes. The other way round, DEGs involved in processes such as oxidation, photosynthesis, and starch, proline, ethylene, and salicylic acid metabolism were clearly co-expressed with the MAPKKK genes. Furthermore, a quantitative real-time PCR (qRT-PCR) analysis was performed to assess the relative expression levels of MAPKKKs. Correlation analysis revealed that there was a significant correlation between expression levels of two MAPKKKs and relative biomass responsive to drought in 8 inbred lines. Our results indicate that MAPKKKs may have important regulatory functions in drought tolerance in maize. PMID:26599013

  5. RNA-Seq Analysis Reveals MAPKKK Family Members Related to Drought Tolerance in Maize.

    PubMed

    Liu, Ya; Zhou, Miaoyi; Gao, Zhaoxu; Ren, Wen; Yang, Fengling; He, Hang; Zhao, Jiuran

    2015-01-01

    The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction pathway that is involved in plant development and stress responses. As the first component of this phosphorelay cascade, mitogen-activated protein kinase kinase kinases (MAPKKKs) act as adaptors linking upstream signaling steps to the core MAPK cascade to promote the appropriate cellular responses; however, the functions of MAPKKKs in maize are unclear. Here, we identified 71 MAPKKK genes, of which 14 were novel, based on a computational analysis of the maize (Zea mays L.) genome. Using an RNA-seq analysis in the leaf, stem and root of maize under well-watered and drought-stress conditions, we identified 5,866 differentially expressed genes (DEGs), including 8 MAPKKK genes responsive to drought stress. Many of the DEGs were enriched in processes such as drought stress, abiotic stimulus, oxidation-reduction, and metabolic processes. The other way round, DEGs involved in processes such as oxidation, photosynthesis, and starch, proline, ethylene, and salicylic acid metabolism were clearly co-expressed with the MAPKKK genes. Furthermore, a quantitative real-time PCR (qRT-PCR) analysis was performed to assess the relative expression levels of MAPKKKs. Correlation analysis revealed that there was a significant correlation between expression levels of two MAPKKKs and relative biomass responsive to drought in 8 inbred lines. Our results indicate that MAPKKKs may have important regulatory functions in drought tolerance in maize. PMID:26599013

  6. PHYLOGENETIC ANALYSIS OF PSEUDOCHLORODESMIS STRAINS REVEALS CRYPTIC DIVERSITY ABOVE THE FAMILY LEVEL IN THE SIPHONOUS GREEN ALGAE (BRYOPSIDALES, CHLOROPHYTA)(1).

    PubMed

    Verbruggen, Heroen; Vlaeminck, Caroline; Sauvage, Thomas; Sherwood, Alison R; Leliaert, Frederik; De Clerck, Olivier

    2009-06-01

    The genus Pseudochlorodesmis (Bryopsidales) is composed of diminutive siphons of extreme morphological simplicity. The discovery of Pseudochlorodesmis-like juveniles in more complex Bryopsidales (e.g., the Halimeda microthallus stage) jeopardized the recognition of this genus. Confronted with this uncertainty, taxonomists transferred many simple siphons into a new genus, Siphonogramen. In this study, we used a multimarker approach to clarify the phylogenetic and taxonomic affinities of the Pseudochlorodesmis-Siphonogramen (PS) complex within the more morphologically complex bryopsidalean taxa. Our analyses reveal a new layer of diversity largely distinct from the lineages containing the structurally complex genera. The PS complex shows profound cryptic diversity exceeding the family level. We discuss a potential link between thallus complexity and the prevalence and profundity of cryptic diversity. For taxonomic simplicity and as a first step toward clarifying the taxonomy of these simple siphons, we propose to maintain Pseudochlorodesmis as a form genus and subsume Siphonogramen and Botryodesmis therein. PMID:27034048

  7. Characterization of a fibrillar collagen gene in sponges reveals the early evolutionary appearance of two collagen gene families.

    PubMed Central

    Exposito, J Y; Garrone, R

    1990-01-01

    We have characterized cDNA and genomic clones coding for a sponge collagen. The partial cDNA has an open reading frame encoding 547 amino acid residues. The conceptual translation product contains a probably incomplete triple-helical domain (307 amino acids) with one Gly-Xaa-Yaa-Zaa imperfection in the otherwise perfect Gly-Xaa-Yaa repeats and a carboxyl propeptide (240 amino acids) that includes 7 cysteine residues. Amino acid sequence comparisons indicate that this sponge collagen is homologous to vertebrate and sea urchin fibrillar collagens. Partial characterization of the corresponding gene reveals an intron-exon organization clearly related to the fibrillar collagen gene family. The exons coding for the triple-helical domain are 54 base pairs (bp) or multiples thereof, except for a 57-bp exon containing the Gly-Xaa-Yaa-Zaa coding sequence and for two unusual exons of 126 and 18 bp, respectively. This latter 18-bp exon marks the end of the triple-helical domain, contrary to the other known fibrillar collagen genes that contain exons coding for the junction between the triple-helical domain and the carboxyl propeptide. Compared to other fibrillar collagen genes, the introns are remarkably small. Hybridization to blotted RNAs established that the gene transcript is 4.9 kilobases. Together with previous results that showed the existence of a nonfibrillar collagen in the same species, these data demonstrate that at least two collagen gene families are represented in the most primitive metazoa. PMID:2395869

  8. Crystal structures of a family 8 polysaccharide lyase reveal open and highly occluded substrate-binding cleft conformations.

    PubMed

    Elmabrouk, Zainab H; Vincent, Florence; Zhang, Meng; Smith, Nicola L; Turkenburg, Johan P; Charnock, Simon J; Black, Gary W; Taylor, Edward J

    2011-03-01

    Bacterial enzymatic degradation of glycosaminoglycans such as hyaluronan and chondroitin is facilitated by polysaccharide lyases. Family 8 polysaccharide lyase (PL8) enzymes contain at least two domains: one predominantly composed of α-helices, the α-domain, and another predominantly composed of β-sheets, the β-domain. Simulation flexibility analyses indicate that processive exolytic cleavage of hyaluronan, by PL8 hyaluronate lyases, is likely to involve an interdomain shift, resulting in the opening/closing of the substrate-binding cleft between the α- and β-domains, facilitating substrate translocation. Here, the Streptomyces coelicolor A3(2) PL8 enzyme was recombinantly expressed in and purified from Escherichia coli and biochemically characterized as a hyaluronate lyase. By using X-ray crystallography its structure was solved in complex with hyaluronan and chondroitin disaccharides. These findings show key catalytic interactions made by the different substrates, and on comparison with all other PL8 structures reveals that the substrate-binding cleft of the S. coelicolor enzyme is highly occluded. A third structure of the enzyme, harboring a mutation of the catalytic tyrosine, created via site-directed mutagenesis, interestingly revealed an interdomain shift that resulted in the opening of the substrate-binding cleft. These results add further support to the proposed processive mechanism of action of PL8 hyaluronate lyases and may indicate that the mechanism of action is likely to be universally used by PL8 hyaluronate lyases. PMID:21287626

  9. Gene family analysis of the Arabidopsis pollen transcriptome reveals biological implications for cell growth, division control, and gene expression regulation.

    PubMed

    Pina, Cristina; Pinto, Francisco; Feijó, José A; Becker, Jörg D

    2005-06-01

    Upon germination, pollen forms a tube that elongates dramatically through female tissues to reach and fertilize ovules. While essential for the life cycle of higher plants, the genetic basis underlying most of the process is not well understood. We previously used a combination of flow cytometry sorting of viable hydrated pollen grains and GeneChip array analysis of one-third of the Arabidopsis (Arabidopsis thaliana) genome to define a first overview of the pollen transcriptome. We now extend that study to approximately 80% of the genome of Arabidopsis by using Affymetrix Arabidopsis ATH1 arrays and perform comparative analysis of gene family and gene ontology representation in the transcriptome of pollen and vegetative tissues. Pollen grains have a smaller and overall unique transcriptome (6,587 genes expressed) with greater proportions of selectively expressed (11%) and enriched (26%) genes than any vegetative tissue. Relative gene ontology category representations in pollen and vegetative tissues reveal a functional skew of the pollen transcriptome toward signaling, vesicle transport, and the cytoskeleton, suggestive of a commitment to germination and tube growth. Cell cycle analysis reveals an accumulation of G2/M-associated factors that may play a role in the first mitotic division of the zygote. Despite the relative underrepresentation of transcription-associated transcripts, nonclassical MADS box genes emerge as a class with putative unique roles in pollen. The singularity of gene expression control in mature pollen grains is further highlighted by the apparent absence of small RNA pathway components. PMID:15908605

  10. Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

    PubMed Central

    Motta, Maria Cristina Machado; Martins, Allan Cezar de Azevedo; de Souza, Silvana Sant’Anna; Catta-Preta, Carolina Moura Costa; Silva, Rosane; Klein, Cecilia Coimbra; de Almeida, Luiz Gonzaga Paula; de Lima Cunha, Oberdan; Ciapina, Luciane Prioli; Brocchi, Marcelo; Colabardini, Ana Cristina; de Araujo Lima, Bruna; Machado, Carlos Renato; de Almeida Soares, Célia Maria; Probst, Christian Macagnan; de Menezes, Claudia Beatriz Afonso; Thompson, Claudia Elizabeth; Bartholomeu, Daniella Castanheira; Gradia, Daniela Fiori; Pavoni, Daniela Parada; Grisard, Edmundo C.; Fantinatti-Garboggini, Fabiana; Marchini, Fabricio Klerynton; Rodrigues-Luiz, Gabriela Flávia; Wagner, Glauber; Goldman, Gustavo Henrique; Fietto, Juliana Lopes Rangel; Elias, Maria Carolina; Goldman, Maria Helena S.; Sagot, Marie-France; Pereira, Maristela; Stoco, Patrícia H.; de Mendonça-Neto, Rondon Pessoa; Teixeira, Santuza Maria Ribeiro; Maciel, Talles Eduardo Ferreira; de Oliveira Mendes, Tiago Antônio; Ürményi, Turán P.; de Souza, Wanderley; Schenkman, Sergio; de Vasconcelos, Ana Tereza Ribeiro

    2013-01-01

    Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. In an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. The monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. The assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism

  11. A Genome-Wide Analysis Reveals Stress and Hormone Responsive Patterns of TIFY Family Genes in Brassica rapa

    PubMed Central

    Saha, Gopal; Park, Jong-In; Kayum, Md. Abdul; Nou, Ill-Sup

    2016-01-01

    The TIFY family is a plant-specific group of proteins with a diversity of functions and includes four subfamilies, viz. ZML, TIFY, PPD, and JASMONATE ZIM-domain (JAZ) proteins. TIFY family members, particularly JAZ subfamily proteins, play roles in biological processes such as development and stress and hormone responses in Arabidopsis, rice, chickpea, and grape. However, there is no information about this family in any Brassica crop. This study identifies 36 TIFY genes in Brassica rapa, an economically important crop species in the Brassicaceae. An extensive in silico analysis of phylogenetic grouping, protein motif organization and intron-exon distribution confirmed that there are four subfamilies of BrTIFY proteins. Out of 36 BrTIFY genes, we identified 21 in the JAZ subfamily, seven in the TIFY subfamily, six in ZML and two in PPD. Extensive expression profiling of 21 BrTIFY JAZs in various tissues, especially in floral organs and at different flower growth stages revealed constitutive expression patterns, which suggest that BrTIFY JAZ genes are important during growth and development of B. rapa flowers. A protein interaction network analysis also pointed to association of these proteins with fertility and defense processes of B. rapa. Using a low temperature-treated whole-genome microarray data set, most of the JAZ genes were found to have variable transcript abundance between the contrasting inbred lines Chiifu and Kenshin of B. rapa. Subsequently, the expression of all 21 BrTIFY JAZs in response to cold stress was characterized in the same two lines via qPCR, demonstrating that nine genes were up-regulated. Importantly, the BrTIFY JAZs showed strong and differential expression upon JA treatment, pointing to their probable involvement in JA-mediated growth regulatory functions, especially during flower development and stress responses. Additionally, BrTIFY JAZs were induced in response to salt, drought, Fusarium, ABA, and SA treatments, and six genes (BrTIFY3

  12. A Genome-Wide Analysis Reveals Stress and Hormone Responsive Patterns of TIFY Family Genes in Brassica rapa.

    PubMed

    Saha, Gopal; Park, Jong-In; Kayum, Md Abdul; Nou, Ill-Sup

    2016-01-01

    The TIFY family is a plant-specific group of proteins with a diversity of functions and includes four subfamilies, viz. ZML, TIFY, PPD, and JASMONATE ZIM-domain (JAZ) proteins. TIFY family members, particularly JAZ subfamily proteins, play roles in biological processes such as development and stress and hormone responses in Arabidopsis, rice, chickpea, and grape. However, there is no information about this family in any Brassica crop. This study identifies 36 TIFY genes in Brassica rapa, an economically important crop species in the Brassicaceae. An extensive in silico analysis of phylogenetic grouping, protein motif organization and intron-exon distribution confirmed that there are four subfamilies of BrTIFY proteins. Out of 36 BrTIFY genes, we identified 21 in the JAZ subfamily, seven in the TIFY subfamily, six in ZML and two in PPD. Extensive expression profiling of 21 BrTIFY JAZs in various tissues, especially in floral organs and at different flower growth stages revealed constitutive expression patterns, which suggest that BrTIFY JAZ genes are important during growth and development of B. rapa flowers. A protein interaction network analysis also pointed to association of these proteins with fertility and defense processes of B. rapa. Using a low temperature-treated whole-genome microarray data set, most of the JAZ genes were found to have variable transcript abundance between the contrasting inbred lines Chiifu and Kenshin of B. rapa. Subsequently, the expression of all 21 BrTIFY JAZs in response to cold stress was characterized in the same two lines via qPCR, demonstrating that nine genes were up-regulated. Importantly, the BrTIFY JAZs showed strong and differential expression upon JA treatment, pointing to their probable involvement in JA-mediated growth regulatory functions, especially during flower development and stress responses. Additionally, BrTIFY JAZs were induced in response to salt, drought, Fusarium, ABA, and SA treatments, and six genes (BrTIFY3

  13. Gourds afloat: a dated phylogeny reveals an Asian origin of the gourd family (Cucurbitaceae) and numerous oversea dispersal events

    PubMed Central

    Schaefer, Hanno; Heibl, Christoph; Renner, Susanne S.

    2008-01-01

    Knowing the geographical origin of economically important plants is important for genetic improvement and conservation, but has been slowed by uneven geographical sampling where relatives occur in remote areas of difficult access. Less biased species sampling can be achieved when herbarium collections are included as DNA sources. Here, we address the history of Cucurbitaceae, one of the most economically important families of plants, using a multigene phylogeny for 114 of the 115 genera and 25 per cent of the 960 species. Worldwide sampling was achieved by using specimens from 30 herbaria. Results reveal an Asian origin of Cucurbitaceae in the Late Cretaceous, followed by the repeated spread of lineages into the African, American and Australian continents via transoceanic long-distance dispersal (LDD). North American cucurbits stem from at least seven range expansions of Central and South American lineages; Madagascar was colonized 13 times, always from Africa; Australia was reached 12 times, apparently always from Southeast Asia. Overall, Cucurbitaceae underwent at least 43 successful LDD events over the past 60 Myr, which would translate into an average of seven LDDs every 10 Myr. These and similar findings from other angiosperms stress the need for an increased tapping of museum collections to achieve extensive geographical sampling in plant phylogenetics. PMID:19033142

  14. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

    PubMed Central

    Suleiman, Suleiman H.; Koko, Mahmoud E.; Nasir, Wafaa H.; Elfateh, Ommnyiah; Elgizouli, Ubai K.; Abdallah, Mohammed O. E.; Alfarouk, Khalid O.; Hussain, Ayman; Faisal, Shima; Ibrahim, Fathelrahamn M. A.; Romano, Maurizio; Sultan, Ali; Banks, Lawrence; Newport, Melanie; Baralle, Francesco; Elhassan, Ahmed M.; Mohamed, Hiba S.; Ibrahim, Muntaser E.

    2015-01-01

    The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions–deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions–deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins. PMID:26442106

  15. Structural Enzymology of Cellvibrio japonicus Agd31B Protein Reveals α-Transglucosylase Activity in Glycoside Hydrolase Family 31*

    PubMed Central

    Larsbrink, Johan; Izumi, Atsushi; Hemsworth, Glyn R.; Davies, Gideon J.; Brumer, Harry

    2012-01-01

    The metabolism of the storage polysaccharides glycogen and starch is of vital importance to organisms from all domains of life. In bacteria, utilization of these α-glucans requires the concerted action of a variety of enzymes, including glycoside hydrolases, glycoside phosphorylases, and transglycosylases. In particular, transglycosylases from glycoside hydrolase family 13 (GH13) and GH77 play well established roles in α-glucan side chain (de)branching, regulation of oligo- and polysaccharide chain length, and formation of cyclic dextrans. Here, we present the biochemical and tertiary structural characterization of a new type of bacterial 1,4-α-glucan 4-α-glucosyltransferase from GH31. Distinct from 1,4-α-glucan 6-α-glucosyltransferases (EC 2.4.1.24) and 4-α-glucanotransferases (EC 2.4.1.25), this enzyme strictly transferred one glucosyl residue from α(1→4)-glucans in disproportionation reactions. Substrate hydrolysis was undetectable for a series of malto-oligosaccharides except maltose for which transglycosylation nonetheless dominated across a range of substrate concentrations. Crystallographic analysis of the enzyme in free, acarbose-complexed, and trapped 5-fluoro-β-glucosyl-enzyme intermediate forms revealed extended substrate interactions across one negative and up to three positive subsites, thus providing structural rationalization for the unique, single monosaccharide transferase activity of the enzyme. PMID:23132856

  16. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis.

    PubMed

    Fossdal, R; Böthvarsson, M; Asmundsson, P; Ragnarsson, J; Peters, D; Breuning, M H; Jensson, O

    1993-07-01

    We have mainly used 3 highly polymorphic DNA markers, 3'HVR (D16S85), 16AC2.5 (D16S291) and SM7 (D16S283), flanking the PKD1 region on chromosome 16p13.3 to establish linkage status in seven Icelandic families with autosomal dominant polycystic kidney disease (ADPKD). In four families, the disease locus is in the PKD1 region, and three families are "unlinked" to chromosome 16p13.3. In one of the "unlinked" families, the disease locus is excluded from a part of the long arm of chromosome 2, and we support a theory of more than 2 loci being responsible for ADPKD. Our data confirm the location of the locus YNH24 (D2S44) to chromosome 2q13-q24. PMID:8340115

  17. Reversal to air-driven sound production revealed by a molecular phylogeny of tongueless frogs, family Pipidae

    PubMed Central

    2011-01-01

    Background Evolutionary novelties often appear by conferring completely new functions to pre-existing structures or by innovating the mechanism through which a particular function is performed. Sound production plays a central role in the behavior of frogs, which use their calls to delimit territories and attract mates. Therefore, frogs have evolved complex vocal structures capable of producing a wide variety of advertising sounds. It is generally acknowledged that most frogs call by moving an air column from the lungs through the glottis with the remarkable exception of the family Pipidae, whose members share a highly specialized sound production mechanism independent of air movement. Results Here, we performed behavioral observations in the poorly known African pipid genus Pseudhymenochirus and document that the sound production in this aquatic frog is almost certainly air-driven. However, morphological comparisons revealed an indisputable pipid nature of Pseudhymenochirus larynx. To place this paradoxical pattern into an evolutionary framework, we reconstructed robust molecular phylogenies of pipids based on complete mitochondrial genomes and nine nuclear protein-coding genes that coincided in placing Pseudhymenochirus nested among other pipids. Conclusions We conclude that although Pseudhymenochirus probably has evolved a reversal to the ancestral non-pipid condition of air-driven sound production, the mechanism through which it occurs is an evolutionary innovation based on the derived larynx of pipids. This strengthens the idea that evolutionary solutions to functional problems often emerge based on previous structures, and for this reason, innovations largely depend on possibilities and constraints predefined by the particular history of each lineage. PMID:21524293

  18. Mutational and Haplotype Analyses of Families with Familial Partial Lipodystrophy (Dunnigan Variety) Reveal Recurrent Missense Mutations in the Globular C-Terminal Domain of Lamin A/C

    PubMed Central

    Speckman, Rebecca A.; Garg, Abhimanyu; Du, Fenghe; Bennett, Lynda; Veile, Rose; Arioglu, Elif; Taylor, Simeon I.; Lovett, Michael; Bowcock, Anne M.

    2000-01-01

    Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missense mutation (R482Q) in five Canadian probands. This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease. We examined 15 families with FPLD for mutations in lamin A/C. Five families harbored the R482Q alteration that segregated with the disease phenotype. Seven families harbored an R482W alteration, and one family harbored a G465D alteration. All these mutations lie within exon 8 of the lamin A/C gene—an exon that has also been shown to harbor different missense mutations that are responsible for EDMD-AD. Mutations could not be detected in lamin A/C in one FPLD family in which there was linkage to chromosome 1q21-q23. One family with atypical FPLD harbored an R582H alteration in exon 11 of lamin A. This exon does not comprise part of the lamin C coding region. All mutations in FPLD affect the globular C-terminal domain of the lamin A/C protein. In contrast, mutations responsible for dilated cardiomyopathy and conduction-system disease are observed in the rod domain of the protein. The FPLD mutations R482Q and R482W occurred on different haplotypes, indicating that they are likely to have arisen more than once. PMID:10739751

  19. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness.

    PubMed

    Bigdeli, Tim B; Ripke, Stephan; Bacanu, Silviu-Alin; Lee, Sang Hong; Wray, Naomi R; Gejman, Pablo V; Rietschel, Marcella; Cichon, Sven; St Clair, David; Corvin, Aiden; Kirov, George; McQuillin, Andrew; Gurling, Hugh; Rujescu, Dan; Andreassen, Ole A; Werge, Thomas; Blackwood, Douglas H R; Pato, Carlos N; Pato, Michele T; Malhotra, Anil K; O'Donovan, Michael C; Kendler, Kenneth S; Fanous, Ayman H

    2016-03-01

    Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R(2 ) = 0.0021; P = 0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant

  20. Complete mtDNA genomes reveal similar penetrances of maternally inherited type 2 diabetes in two Chinese families.

    PubMed

    Yang, Ying; Zhou, Taicheng; Peng, Minsheng; Liu, Yongying; Li, Yiping; Wang, Huawei; Irwin, David M; Zhang, Yaping

    2016-05-01

    Previous work suggests that mitochondrial DNA (mtDNA) derived from the maternal genome has a close affinity with type 2 diabetes. This would support a familial pattern for type 2 diabetes. Thereby, we analyzed complete mtDNA genomes from two families, A and B, from Southwest China that demonstrated maternally inherited type 2 diabetes. Our data support that mtDNA lineages from families A and B belong to haplogroups A4 and D4h1, respectively. This suggests that maternally inherited type 2 diabetes with similar penetrances can arise in Chinese individuals with strikingly different maternal genetic backgrounds. Two private coding region mutations (G13759A in MT-ND5 and G15930A in tRNA-Thr) were identified in family B. Further evolutionary and phylogenetic analyses suggest that both these mutations have multiple origins and are unlikely to be disease causing. PMID:25469813

  1. Ligand-binding specificity and promiscuity of the main lignocellulolytic enzyme families as revealed by active-site architecture analysis.

    PubMed

    Tian, Li; Liu, Shijia; Wang, Shuai; Wang, Lushan

    2016-01-01

    Biomass can be converted into sugars by a series of lignocellulolytic enzymes, which belong to the glycoside hydrolase (GH) families summarized in CAZy databases. Here, using a structural bioinformatics method, we analyzed the active site architecture of the main lignocellulolytic enzyme families. The aromatic amino acids Trp/Tyr and polar amino acids Glu/Asp/Asn/Gln/Arg occurred at higher frequencies in the active site architecture than in the whole enzyme structure. And the number of potential subsites was significantly different among different families. In the cellulase and xylanase families, the conserved amino acids in the active site architecture were mostly found at the -2 to +1 subsites, while in β-glucosidase they were mainly concentrated at the -1 subsite. Families with more conserved binding amino acid residues displayed strong selectivity for their ligands, while those with fewer conserved binding amino acid residues often exhibited promiscuity when recognizing ligands. Enzymes with different activities also tended to bind different hydroxyl oxygen atoms on the ligand. These results may help us to better understand the common and unique structural bases of enzyme-ligand recognition from different families and provide a theoretical basis for the functional evolution and rational design of major lignocellulolytic enzymes. PMID:27009476

  2. Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy

    PubMed Central

    Zhao, Yue; Feng, Yue; Zhang, Yun-Mei; Ding, Xiao-Xue; Song, Yu-Zhu; Zhang, A-Mei; Liu, Li; Zhang, Hong; Ding, Jia-Huan; Xia, Xue-Shan

    2015-01-01

    As a common cardiac disease mainly caused by gene mutations in sarcomeric cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription factor genes, inherited cardiomyopathy is becoming one of the major etiological factors of sudden cardiac death (SCD) and heart failure (HF). This disease is characterized by remarkable genetic heterogeneity, which makes it difficult to screen for pathogenic mutations using Sanger sequencing. In the present study, three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with familial dilated cardiomyopathy (FDCM), were recruited together with their respective family members. Using next-generation sequencing technology (NGS), 24 genes frequently known to be related to inherited cardiomyopathy were screened. Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA-p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be highly correlated with familial cardiomyopathy. FDCM patients with doubly heterozygous mutations show a notably severe phenotype as we could confirm in our study; this indicates that the double mutations had a dose effect. In addition, it is proposed that genetic testing using NGS technology can be used as a cost-effective screening tool and help guide the treatment of patients with familial cardiomyopathy particularly regarding the risk of family members who are clinically asymptomatic. PMID:26199943

  3. Ligand-binding specificity and promiscuity of the main lignocellulolytic enzyme families as revealed by active-site architecture analysis

    PubMed Central

    Tian, Li; Liu, Shijia; Wang, Shuai; Wang, Lushan

    2016-01-01

    Biomass can be converted into sugars by a series of lignocellulolytic enzymes, which belong to the glycoside hydrolase (GH) families summarized in CAZy databases. Here, using a structural bioinformatics method, we analyzed the active site architecture of the main lignocellulolytic enzyme families. The aromatic amino acids Trp/Tyr and polar amino acids Glu/Asp/Asn/Gln/Arg occurred at higher frequencies in the active site architecture than in the whole enzyme structure. And the number of potential subsites was significantly different among different families. In the cellulase and xylanase families, the conserved amino acids in the active site architecture were mostly found at the −2 to +1 subsites, while in β-glucosidase they were mainly concentrated at the −1 subsite. Families with more conserved binding amino acid residues displayed strong selectivity for their ligands, while those with fewer conserved binding amino acid residues often exhibited promiscuity when recognizing ligands. Enzymes with different activities also tended to bind different hydroxyl oxygen atoms on the ligand. These results may help us to better understand the common and unique structural bases of enzyme-ligand recognition from different families and provide a theoretical basis for the functional evolution and rational design of major lignocellulolytic enzymes. PMID:27009476

  4. A combined morphological, ultrastructural, molecular, and biochemical study of the peculiar family Gomontiellaceae (Oscillatoriales) reveals a new cylindrospermopsin-producing clade of cyanobacteria.

    PubMed

    Bohunická, Markéta; Mareš, Jan; Hrouzek, Pavel; Urajová, Petra; Lukeš, Martin; Šmarda, Jan; Komárek, Jiří; Gaysina, Lira A; Strunecký, Otakar

    2015-12-01

    Members of the morphologically unusual cyanobacterial family Gomontiellaceae were studied using a polyphasic approach. Cultured strains of Hormoscilla pringsheimii, Starria zimbabweënsis, Crinalium magnum, and Crinalium epipsammum were thoroughly examined, and the type specimen of the family, Gomontiella subtubulosa, was investigated. The results of morphological observations using both light microscopy and transmission electron microscopy were consistent with previous reports and provided evidence for the unique morphological and ultrastructural traits of this family. Analysis of the 16S rRNA gene confirmed the monophyletic origin of non-marine repre-sentatives of genera traditionally classified into this family. The family was phylogenetically placed among other groups of filamentous cyanobacterial taxa. The presence of cellulose in the cell wall was analyzed and confirmed in all cultured Gomontiellaceae members using Fourier transform infrared spectroscopy and fluorescence microscopy. Evaluation of toxins produced by the studied strains revealed the hepatotoxin cylindrospermopsin (CYN) in available strains of the genus Hormoscilla. Production of this compound in both Hormoscilla strains was detected using high-performance liquid chromatography in tandem with high resolution mass spectrometry and confirmed by positive PCR amplification of the cyrJ gene from the CYN biosynthetic cluster. To our knowledge, this is the first report of CYN production by soil cyanobacteria, establishing a previously unreported CYN-producing lineage. This study indicates that cyanobacteria of the family Gomontiellaceae form a separate but coherent cluster defined by numerous intriguing morphological, ultrastructural, and biochemical features, and exhibiting a toxic potential worthy of further investigation. PMID:26987000

  5. Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies

    PubMed Central

    Beryozkin, Avigail; Shevah, Elia; Kimchi, Adva; Mizrahi-Meissonnier, Liliana; Khateb, Samer; Ratnapriya, Rinki; Lazar, Csilla H.; Blumenfeld, Anat; Ben-Yosef, Tamar; Hemo, Yitzhak; Pe’er, Jacob; Averbuch, Eduard; Sagi, Michal; Boleda, Alexis; Gieser, Linn; Zlotogorski, Abraham; Falik-Zaccai, Tzipora; Alimi-Kasem, Ola; Jacobson, Samuel G.; Chowers, Itay; Swaroop, Anand; Banin, Eyal; Sharon, Dror

    2015-01-01

    Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed. Sanger sequencing was used to validate potential pathogenic variants that were also subjected to segregation analysis in families. Thirty-three causative mutations (19 novel and 14 known) in 25 genes were identified in 33 of the 68 families. The vast majority of mutations (30 out of 33) have not been reported in the Israeli and the Palestinian populations. Nine out of the 33 mutations were detected in additional families from the same ethnic population, suggesting a founder effect. In two families, identified phenotypes were different from the previously reported clinical findings associated with the causative gene. This is the largest genetic analysis of IRDs in the Israeli and Palestinian populations to date. We also demonstrate that WES is a powerful tool for rapid analysis of known disease genes in large patient cohorts. PMID:26306921

  6. An insight into the sialome of Anopheles funestus reveals an emerging pattern in anopheline salivary protein families.

    PubMed

    Calvo, Eric; Dao, Adama; Pham, Van M; Ribeiro, José M C

    2007-02-01

    Anopheles funestus, together with Anopheles gambiae, is responsible for most malaria transmission in sub-Saharan Africa, but little is known about molecular aspects of its biology. To investigate the salivary repertoire of this mosquito, we randomly sequenced 916 clones from a salivary-gland cDNA library from adult female F1 offspring of field-caught An. funestus. Thirty-three protein sequences, mostly full-length transcripts, are predicted to be secreted salivary proteins. We additionally describe 25 full-length housekeeping-associated transcripts. In accumulating mosquito sialotranscriptome information--which includes An. gambiae, Anopheles stephensi, Anopheles darlingi, Aedes aegypti, Aedes albopictus, Culex pipiens quinquefasciatus, and now An. funestus--a pattern is emerging. First, ubiquitous protein families are recruited for a salivary role, such as members of the antigen-5 family and enzymes of nucleotide and carbohydrate catabolism. Second, a group of protein families exclusive to blood-feeding Nematocera includes the abundantly expressed D7 proteins also found in sand flies and Culicoides. A third group of proteins, only found in Culicidae, includes the 30 kDa allergen family and several mucins. Finally, 10 protein and peptide families, five of them multigenic, are exclusive to anophelines. Among these proteins may reside good epidemiological markers to measure human exposure to anopheline species such as An. funestus and An. gambiae. PMID:17244545

  7. Microsynteny and phylogenetic analysis of tandemly organised miRNA families across five members of Brassicaceae reveals complex retention and loss history.

    PubMed

    Rathore, Priyanka; Geeta, R; Das, Sandip

    2016-06-01

    Plant genomes are characterized by the presence of large miRNA gene families which are few in number. The expansion of miRNA families is thought to be driven by gene and genome duplication. Some members of these miRNA gene families are tandemly arranged and their analysis is of interest because such organisation may indicate origin through tandem duplication and also to investigate whether some such tandem clusters have similar expression patterns, and whether these are regulated through a common set of cis-regulatory elements (eg. promoters and enhancers). As a first step, we undertake a comprehensive study using micro-synteny analyses of tandemly organised miRNA families across the Brassicaceae spanning an evolutionary time scale of ca. 45 million years, among Arabidopsis, Capsella, Brassica and Thellungiella species, to address the following questions: Are most miRNA gene families present as tandem clusters? To what extent are these tandem patterns retained? To what extent can family sizes be ascribed to genome duplication? Our analysis of thirteen tandemly organised miRNA families revealed that synteny is largely conserved among Arabidopsis thaliana, A. lyrata and Capsella rubella, which form a clade spanning approximately between 6.2-9.8 my (Acarkan et al., 2000) [1]. On the other hand, comparison of sequences from these species with Brassica rapa, B. oleracea and Thellungiella halophila, which form a separate clade spanning 31 my (Franzke et al., 2011)[2] reveals many differences. The latter clade reveals several paralogous duplications that probably resulted from whole genome duplication, as well as disrupted synteny. Phylogenetic analyses of precursor sequences generally support the history inferred from synteny analysis. Synteny and phylogenetic analysis of six members of the tandemly organised miR169 family suggest that the Brassicaceae ancestral state consisted of a "dimer as a unit" which may have undergone direct local duplication to retain the

  8. Pre-steady-state Kinetic Analysis of a Family D DNA Polymerase from Thermococcus sp. 9°N Reveals Mechanisms for Archaeal Genomic Replication and Maintenance*

    PubMed Central

    Schermerhorn, Kelly M.; Gardner, Andrew F.

    2015-01-01

    Family D DNA polymerases (polDs) have been implicated as the major replicative polymerase in archaea, excluding the Crenarchaeota branch, and bear little sequence homology to other DNA polymerase families. Here we report a detailed kinetic analysis of nucleotide incorporation and exonuclease activity for a Family D DNA polymerase from Thermococcus sp. 9°N. Pre-steady-state single-turnover nucleotide incorporation assays were performed to obtain the kinetic parameters, kpol and Kd, for correct nucleotide incorporation, incorrect nucleotide incorporation, and ribonucleotide incorporation by exonuclease-deficient polD. Correct nucleotide incorporation kinetics revealed a relatively slow maximal rate of polymerization (kpol ∼2.5 s−1) and especially tight nucleotide binding (Kd(dNTP) ∼1.7 μm), compared with DNA polymerases from Families A, B, C, X, and Y. Furthermore, pre-steady-state nucleotide incorporation assays revealed that polD prevents the incorporation of incorrect nucleotides and ribonucleotides primarily through reduced nucleotide binding affinity. Pre-steady-state single-turnover assays on wild-type 9°N polD were used to examine 3′-5′ exonuclease hydrolysis activity in the presence of Mg2+ and Mn2+. Interestingly, substituting Mn2+ for Mg2+ accelerated hydrolysis rates >40-fold (kexo ≥110 s−1 versus ≥2.5 s−1). Preference for Mn2+ over Mg2+ in exonuclease hydrolysis activity is a property unique to the polD family. The kinetic assays performed in this work provide critical insight into the mechanisms that polD employs to accurately and efficiently replicate the archaeal genome. Furthermore, despite the unique properties of polD, this work suggests that a conserved polymerase kinetic pathway is present in all known DNA polymerase families. PMID:26160179

  9. Transcriptome analyses of the Dof-like gene family in grapevine reveal its involvement in berry, flower and seed development

    PubMed Central

    da Silva, Danielle Costenaro; da Silveira Falavigna, Vítor; Fasoli, Marianna; Buffon, Vanessa; Porto, Diogo Denardi; Pappas, Georgios Joannis; Pezzotti, Mario; Pasquali, Giancarlo; Revers, Luís Fernando

    2016-01-01

    The Dof (DNA-binding with one finger) protein family spans a group of plant transcription factors involved in the regulation of several functions, such as plant responses to stress, hormones and light, phytochrome signaling and seed germination. Here we describe the Dof-like gene family in grapevine (Vitis vinifera L.), which consists of 25 genes coding for Dof. An extensive in silico characterization of the VviDofL gene family was performed. Additionally, the expression of the entire gene family was assessed in 54 grapevine tissues and organs using an integrated approach with microarray (cv Corvina) and real-time PCR (cv Pinot Noir) analyses. The phylogenetic analysis comparing grapevine sequences with those of Arabidopsis, tomato, poplar and already described Dof genes in other species allowed us to identify several duplicated genes. The diversification of grapevine DofL genes during evolution likely resulted in a broader range of biological roles. Furthermore, distinct expression patterns were identified between samples analyzed, corroborating such hypothesis. Our expression results indicate that several VviDofL genes perform their functional roles mainly during flower, berry and seed development, highlighting their importance for grapevine growth and production. The identification of similar expression profiles between both approaches strongly suggests that these genes have important regulatory roles that are evolutionally conserved between grapevine cvs Corvina and Pinot Noir. PMID:27610237

  10. Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution

    PubMed Central

    Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

    2016-01-01

    AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening. PMID:26733055

  11. Transcriptome analyses of the Dof-like gene family in grapevine reveal its involvement in berry, flower and seed development.

    PubMed

    da Silva, Danielle Costenaro; da Silveira Falavigna, Vítor; Fasoli, Marianna; Buffon, Vanessa; Porto, Diogo Denardi; Pappas, Georgios Joannis; Pezzotti, Mario; Pasquali, Giancarlo; Revers, Luís Fernando

    2016-01-01

    The Dof (DNA-binding with one finger) protein family spans a group of plant transcription factors involved in the regulation of several functions, such as plant responses to stress, hormones and light, phytochrome signaling and seed germination. Here we describe the Dof-like gene family in grapevine (Vitis vinifera L.), which consists of 25 genes coding for Dof. An extensive in silico characterization of the VviDofL gene family was performed. Additionally, the expression of the entire gene family was assessed in 54 grapevine tissues and organs using an integrated approach with microarray (cv Corvina) and real-time PCR (cv Pinot Noir) analyses. The phylogenetic analysis comparing grapevine sequences with those of Arabidopsis, tomato, poplar and already described Dof genes in other species allowed us to identify several duplicated genes. The diversification of grapevine DofL genes during evolution likely resulted in a broader range of biological roles. Furthermore, distinct expression patterns were identified between samples analyzed, corroborating such hypothesis. Our expression results indicate that several VviDofL genes perform their functional roles mainly during flower, berry and seed development, highlighting their importance for grapevine growth and production. The identification of similar expression profiles between both approaches strongly suggests that these genes have important regulatory roles that are evolutionally conserved between grapevine cvs Corvina and Pinot Noir. PMID:27610237

  12. Systematic Analysis of the Maize PHD-Finger Gene Family Reveals a Subfamily Involved in Abiotic Stress Response

    PubMed Central

    Wang, Qianqian; Liu, Jinyang; Wang, Yu; Zhao, Yang; Jiang, Haiyang; Cheng, Beijiu

    2015-01-01

    Plant homeodomain (PHD)-finger proteins were found universally in eukaryotes and known as key players in regulating transcription and chromatin structure. Many PHD-finger proteins have been well studied on structure and function in animals. Whereas, only a few of plant PHD-finger factors had been characterized, and majority of PHD-finger proteins were functionally unclear. In this study, a complete comprehensive analysis of maize PHD family is presented. Sixty-seven PHD-finger genes in maize were identified and further divided into ten groups according to phylogenetic analysis that was supported by motif and intron/exon analysis. These genes were unevenly distributed on ten chromosomes and contained 12 segmental duplication events, suggesting that segmental duplications were the major contributors in expansion of the maize PHD family. The paralogous genes mainly experienced purifying selection with restrictive functional divergence after the duplication events on the basis of the Ka/Ks ratio. Gene digital expression analysis showed that the PHD family had a wide expression profile in maize development. In addition, 15 potential stress response genes were detected by promoter cis-element and expression analysis. Two proteins ZmPHD14 and ZmPHD19 were located in the nucleus. These results provided a solid base for future functional genome study of the PHD-finger family in maize and afforded important clues for characterizing and cloning potentially important candidates in response to abiotic stresses. PMID:26437398

  13. Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution.

    PubMed

    Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

    2016-01-01

    AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening. PMID:26733055

  14. Molecular evolution analysis of WUSCHEL-related homeobox transcription factor family reveals functional divergence among clades in the homeobox region.

    PubMed

    Segatto, Ana Lúcia A; Thompson, Claudia E; Freitas, Loreta B

    2016-07-01

    Gene families have been shown to play important roles in plant evolution and are associated with diversification and speciation. Genes of WUSCHEL-related homeobox family of transcription factors have important functions in plant development and are correlated with the appearance of evolutionary novelties. There are several published studies related to this family, but little is known about the relationships among the main clades in the phylogeny and the molecular evolution of the family. In this study, we obtained a well-resolved Bayesian phylogenetic tree establishing the relationships among the main clades and determining the position of Selaginella moellendorffii WOX genes. Moreover, a correlation was identified between the number of genes in the genomes and the events of whole-genome duplications. The intron-exon structure is more consistent across the modern clade, which appeared more recently in the WOX evolutionary history, and coincides with the development of higher complexity in plant species. No positive selection was detected among sites through the branches in the tree. However, with regard to the main clades, functional divergence among certain amino acids in the homeodomain region was found. Relaxed purifying selection could be the main driving force in the evolution of these genes and in agreement with some genes have been demonstrated to be functionally redundant. PMID:27150824

  15. Multi-species protein similarity clustering reveals novel expanded immune gene families in the eastern oyster Crassostrea virginica.

    PubMed

    McDowell, Ian C; Modak, Tejashree H; Lane, Chris E; Gomez-Chiarri, Marta

    2016-06-01

    Comparative genomics research in non-model species has highlighted how invertebrate hosts possess complex diversified repertoires of immune molecules. The levels of diversification in particular immune gene families appear to differ between invertebrate lineages and even between species within lineages, reflecting differences not only in evolutionary histories, but also in life histories, environmental niches, and pathogen exposures. The goal of this research was to identify immune-related gene families experiencing high levels of diversification in eastern oysters, Crassostrea virginica. Families containing 1) transcripts differentially expressed in eastern oysters in response to bacterial challenge and 2) a larger number of transcripts compared to other species included those coding for the C1q and C-type lectin domain containing proteins (C1qDC and CTLDC), GTPase of the immune-associated proteins (GIMAP), scavenger receptors (SR), fibrinogen-C domain containing proteins (also known as FREPs), dopamine beta-hydrolase (DBH), interferon-inducible 44 (IFI44), serine protease inhibitors, apextrin, and dermatopontin. Phylogenetic analysis of two of the families significantly expanded in bivalves, IFI44 and GIMAP, showed a patchy distribution within both protostomes and deuterostomes, suggesting multiple independent losses and lineage-specific expansions. Increased availability of genomic information for a broader range of non-model species broadly distributed through vertebrate and invertebrate phyla will likely lead to improved knowledge on mechanisms of immune-gene diversification. PMID:27033806

  16. Genome-wide analysis of tandem repeats in Tribolium castaneum genome reveals abundant and highly dynamic tandem repeat families with satellite DNA features in euchromatic chromosomal arms

    PubMed Central

    Pavlek, Martina; Gelfand, Yevgeniy; Plohl, Miroslav; Meštrović, Nevenka

    2015-01-01

    Although satellite DNAs are well-explored components of heterochromatin and centromeres, little is known about emergence, dispersal and possible impact of comparably structured tandem repeats (TRs) on the genome-wide scale. Our bioinformatics analysis of assembled Tribolium castaneum genome disclosed significant contribution of TRs in euchromatic chromosomal arms and clear predominance of satellite DNA-typical 170 bp monomers in arrays of ≥5 repeats. By applying different experimental approaches, we revealed that the nine most prominent TR families Cast1–Cast9 extracted from the assembly comprise ∼4.3% of the entire genome and reside almost exclusively in euchromatic regions. Among them, seven families that build ∼3.9% of the genome are based on ∼170 and ∼340 bp long monomers. Results of phylogenetic analyses of 2500 monomers originating from these families show high-sequence dynamics, evident by extensive exchanges between arrays on non-homologous chromosomes. In addition, our analysis shows that concerted evolution acts more efficiently on longer than on shorter arrays. Efficient genome-wide distribution of nine TR families implies the role of transposition only in expansion of the most dispersed family, and involvement of other mechanisms is anticipated. Despite similarities in sequence features, FISH experiments indicate high-level compartmentalization of centromeric and euchromatic tandem repeats. PMID:26428853

  17. Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins.

    PubMed

    Cheng, Xiaofang; Wang, Yingli; Gong, Yukang; Li, Faxiang; Guo, Yujiao; Hu, Shichen; Liu, Jianping; Pan, Lifeng

    2016-08-01

    FYCO1 (FYVE and coiled-coil domain containing 1) functions as an autophagy adaptor in directly linking autophagosomes with the microtubule-based kinesin motor, and plays an essential role in the microtubule plus end-directed transport of autophagic vesicles. The specific association of FYCO1 with autophagosomes is mediated by its interaction with Atg8-family proteins decorated on the outer surface of autophagosome. However, the mechanistic basis governing the interaction between FYCO1 and Atg8-family proteins is largely unknown. Here, using biochemical and structural analyses, we demonstrated that FYCO1 contains a unique LC3-interacting region (LIR), which discriminately binds to mammalian Atg8 orthologs and preferentially binds to the MAP1LC3A and MAP1LC3B. In addition to uncovering the detailed molecular mechanism underlying the FYCO1 LIR and MAP1LC3A interaction, the determined FYCO1-LIR-MAP1LC3A complex structure also reveals a unique LIR binding mode for Atg8-family proteins, and demonstrates, first, the functional relevance of adjacent sequences C-terminal to the LIR core motif for binding to Atg8-family proteins. Taken together, our findings not only provide new mechanistic insight into FYCO1-mediated transport of autophagosomes, but also expand our understanding of the interaction modes between LIR motifs and Atg8-family proteins in general. PMID:27246247

  18. Genetic and morphological evidence reveals the existence of a new family, genus and species of Echinorhynchida (Acanthocephala).

    PubMed

    Braicovich, Paola E; Lanfranchi, Ana L; Farber, Marisa D; Marvaldi, Adriana E; Luque, José L; Timi, Juan T

    2014-08-01

    Gymnorhadinorhynchus gen. n. is proposed to accommodate its type species, G. decapteri sp. n., a parasite of the marine fish Decapterus punctatus (Cuvier), caught from the coastal waters of Brazil. Gymnorhadinorhynchus decapteri sp. n. was morphologically most similar to species of two echinorhynchid families, the Rhadinorhynchidae and the Cavisomidae, particularly in the structure of the proboscis and the absence of somatic spines, respectively. This combination of morphological features made it difficult to assign our specimen to an extant family of the Acanthocephala. Therefore, in order to clarify the systematic placement of G. decapteri, a molecular phylogenetic analysis was performed based on the SSU and LSU rDNA and the mitochondrial cox1 gene sequences obtained for the new taxon and other 26 acanthocephalan species. The results of parsimony and maximum likelihood analyses, using individual, combined and concatenated sequence data, consistently indicate that the specimens do not belong to any known family of the Echinorhynchida. Rather, G. decapteri represents a distinct lineage that is closely related to the Transvenidae, but distantly related to both the Rhadinorhynchidae and the Cavisomidae. Gymnorhadinorhynchidae fam. n. is therefore erected. This newly described family can be distinguished from other families of Echinorhynchida by the combination of the following morphological characters: a proboscis cylindrical with 10 rows of 22-26 hooks, dorsoventral differences in proboscis hooks, basal hooks forming a ring and being abruptly larger than anterior hooks, absence of trunk spines and presence of four tubular cement glands. This combination, in addition to several molecular autapomorphies, justifies the erection of a new genus, Gymnorhadinorhynchus gen. n., in order to accommodate this new species. PMID:25185409

  19. MicroRNA expression profiling reveals miRNA families regulating specific biological pathways in mouse frontal cortex and hippocampus.

    PubMed

    Juhila, Juuso; Sipilä, Tessa; Icay, Katherine; Nicorici, Daniel; Ellonen, Pekka; Kallio, Aleksi; Korpelainen, Eija; Greco, Dario; Hovatta, Iiris

    2011-01-01

    MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNAs from FCx and 408 from HP using miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-Seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, several miRNAs from the same family/cluster were predicted to regulate specific biological pathways. We have developed a miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. PMID:21731767

  20. MicroRNA Expression Profiling Reveals MiRNA Families Regulating Specific Biological Pathways in Mouse Frontal Cortex and Hippocampus

    PubMed Central

    Juhila, Juuso; Sipilä, Tessa; Icay, Katherine; Nicorici, Daniel; Ellonen, Pekka; Kallio, Aleksi; Korpelainen, Eija; Greco, Dario; Hovatta, Iiris

    2011-01-01

    MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNAs from FCx and 408 from HP using miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-Seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, several miRNAs from the same family/cluster were predicted to regulate specific biological pathways. We have developed a miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. PMID:21731767

  1. Genome-wide identification of BURP domain-containing genes in rice reveals a gene family with diverse structures and responses to abiotic stresses.

    PubMed

    Ding, Xipeng; Hou, Xin; Xie, Kabin; Xiong, Lizhong

    2009-06-01

    Increasing evidence suggests that a gene family encoding proteins containing BURP domains have diverse functions in plants, but systematic characterization of this gene family have not been reported. In this study, 17 BURP family genes (OsBURP01-17) were identified and analyzed in rice (Oryza sativa L.). These genes have diverse exon-intron structures and distinct organization of putative motifs. Based on the phylogenetic analysis of BURP protein sequences from rice and other plant species, the BURP family was classified into seven subfamilies, including two subfamilies (BURP V and BURP VI) with members from rice only and one subfamily (BURP VII) with members from monocotyledons only. Two BURP gene clusters, belonging to BURP V and BURP VI, were located in the duplicated region on chromosome 5 and 6 of rice, respectively. Transcript level analysis of BURP genes of rice in various tissues and organs revealed different tempo-spatial expression patterns, suggesting that these genes may function at different stages of plant growth and development. Interestingly, all the genes of the BURP VII subfamily were predominantly expressed in flower organs. We also investigated the expression patterns of BURP genes of rice under different stress conditions. The results suggested that, except for two genes (OsBURP01 and OsBURP13), all other members were induced by at least one of the stresses including drought, salt, cold, and abscisic acid treatment. Two genes (OsBURP05 and OsBURP16) were responsive to all the stress treatments and most of the OsBURP genes were responsive to salt stress. Promoter sequence analysis revealed an over-abundance of stress-related cis-elements in the stress-responsive genes. The data presented here provide important clues for elucidating the functions of genes of this family. PMID:19363683

  2. Whole Exome Sequencing Reveals Homozygous Mutations in RAI1, OTOF, and SLC26A4 Genes Associated with Nonsyndromic Hearing Loss in Altaian Families (South Siberia)

    PubMed Central

    Karafet, Tatiana M.; Morozov, Igor V.; Mikhalskaia, Valeriia Yu.; Zytsar, Marina V.; Bondar, Alexander A.

    2016-01-01

    Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies. PMID:27082237

  3. Plastid and nuclear DNA markers reveal intricate relationships at subfamilial and tribal levels in the soapberry family (Sapindaceae).

    PubMed

    Buerki, Sven; Forest, Félix; Acevedo-Rodríguez, Pedro; Callmander, Martin W; Nylander, Johan A A; Harrington, Mark; Sanmartín, Isabel; Küpfer, Philippe; Alvarez, Nadir

    2009-05-01

    The economically important soapberry family (Sapindaceae) comprises about 1900 species mainly found in the tropical regions of the world, with only a few genera being restricted to temperate areas. The infrafamilial classification of the Sapindaceae and its relationships to the closely related Aceraceae and Hippocastanaceae - which have now been included in an expanded definition of Sapindaceae (i.e., subfamily Hippocastanoideae) - have been debated for decades. Here we present a phylogenetic analysis of Sapindaceae based on eight DNA sequence regions from the plastid and nuclear genomes and including 85 of the 141 genera defined within the family. Our study comprises 997 new sequences of Sapindaceae from 152 specimens. Despite presenting 18.6% of missing data our complete data set produced a topology fully congruent with the one obtained from a subset without missing data, but including fewer markers. The use of additional information therefore led to a consistent result in the relative position of clades and allowed the definition of a new phylogenetic hypothesis. Our results confirm a high level of paraphyly and polyphyly at the subfamilial and tribal levels and even contest the monophyletic status of several genera. Our study confirms that the Chinese monotypic genus Xanthoceras is sister to the rest of the family, in which subfamily Hippocastanoideae is sister to a clade comprising subfamilies Dodonaeoideae and Sapindoideae. On the basis of the strong support demonstrated in Sapindoideae, Dodonaeoideae and Hippocastanoideae as well as in 14 subclades, we propose and discuss informal groupings as basis for a new classification of Sapindaceae. PMID:19405193

  4. High-Resolution Survey in Familial Parkinson Disease Genes Reveals Multiple Independent Copy Number Variation Events in PARK2

    PubMed Central

    Wang, Liyong; Nuytemans, Karen; Bademci, Guney; Jauregui, Cherylyn; Martin, Eden R.; Scott, William K.; Vance, Jeffery M.; Zuchner, Stephan

    2015-01-01

    A high density comparative genomic hybridization array was designed to evaluate CNVs in the genomic region of six familial PD genes in 181 PD cases and 67 controls. No CNV was found in PARK7, ATP13A2, PINK1, and LRRK2. Intronic-only CNVs were found in SNCA and PARK2 but were not associated with PD risk. A whole-gene duplication of SNCA was found in one case. The allele frequency of PARK2 exonic CNV is significantly higher in cases than in controls (P = 0.02), higher in early-onset (AAO ≤ 40) than in late-onset cases (P = 0.001), and higher in familial than in sporadic cases (P = 0.005). Except for single exon 2 duplications, all PARK2 exonic CNVs have different breakpoints, even when the same exon(s) were involved. In conclusion, except for SNCA and PARK2, CNVs are not a major contributing mechanism for the familial PD genes examined. The majority of PARK2 exonic CNVs are not recurrent. PMID:23616242

  5. Evolutionary genomics of mycovirus-related dsRNA viruses reveals cross-family horizontal gene transfer and evolution of diverse viral lineages

    PubMed Central

    2012-01-01

    Background Double-stranded (ds) RNA fungal viruses are typically isometric single-shelled particles that are classified into three families, Totiviridae, Partitiviridae and Chrysoviridae, the members of which possess monopartite, bipartite and quadripartite genomes, respectively. Recent findings revealed that mycovirus-related dsRNA viruses are more diverse than previously recognized. Although an increasing number of viral complete genomic sequences have become available, the evolution of these diverse dsRNA viruses remains to be clarified. This is particularly so since there is little evidence for horizontal gene transfer (HGT) among dsRNA viruses. Results In this study, we report the molecular properties of two novel dsRNA mycoviruses that were isolated from a field strain of Sclerotinia sclerotiorum, Sunf-M: one is a large monopartite virus representing a distinct evolutionary lineage of dsRNA viruses; the other is a new member of the family Partitiviridae. Comprehensive phylogenetic analysis and genome comparison revealed that there are at least ten monopartite, three bipartite, one tripartite and three quadripartite lineages in the known dsRNA mycoviruses and that the multipartite lineages have possibly evolved from different monopartite dsRNA viruses. Moreover, we found that homologs of the S7 Domain, characteristic of members of the genus phytoreovirus in family Reoviridae are widely distributed in diverse dsRNA viral lineages, including chrysoviruses, endornaviruses and some unclassified dsRNA mycoviruses. We further provided evidence that multiple HGT events may have occurred among these dsRNA viruses from different families. Conclusions Our study provides an insight into the phylogeny and evolution of mycovirus-related dsRNA viruses and reveals that the occurrence of HGT between different virus species and the development of multipartite genomes during evolution are important macroevolutionary mechanisms in dsRNA viruses. PMID:22716092

  6. A Novel Mutation of LAMB2 in a Multi-Generational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome

    PubMed Central

    Mohney, Brian G.; Pulido, Jose S.; Lindor, Noralane M.; Hogan, Marie C.; Consugar, Mark B.; Peters, Justin; Pankratz, V. Shane; Nasr, Samih H.; Smith, Stephen J.; Gloor, James; Kubly, Vickie; Spencer, Dorothy; Nielson, Rebecca; Puffenberger, Erik G.; Strauss, Kevin A.; Morton, D. Holmes; Eldahdah, Lama; Harris, Peter C.

    2011-01-01

    Purpose To describe a novel laminin beta-2 (LAMB2) mutation associated with nephritic syndrome and severe retinal disease without microcoria in a large, multi-generational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both less than 10 years of age, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array and 2 using GeneChip 10K mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chrioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c. 440A>G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin beta-2 chain. PMID:21236492

  7. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon—results of a cross-sectional study

    PubMed Central

    Farhat, F.; Othman, A.; el Baba, G.; Kattan, J.

    2015-01-01

    Background Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Methods Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Results Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. Conclusions The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite

  8. Crystal Structure of Cytomegalovirus IE1 Protein Reveals Targeting of TRIM Family Member PML via Coiled-Coil Interactions

    PubMed Central

    Sevvana, Madhumati; Otto, Victoria; Schilling, Eva-Maria; Stump, Joachim D.; Müller, Regina; Reuter, Nina; Sticht, Heinrich; Muller, Yves A.; Stamminger, Thomas

    2014-01-01

    PML nuclear bodies (PML-NBs) are enigmatic structures of the cell nucleus that act as key mediators of intrinsic immunity against viral pathogens. PML itself is a member of the E3-ligase TRIM family of proteins that regulates a variety of innate immune signaling pathways. Consequently, viruses have evolved effector proteins to modify PML-NBs; however, little is known concerning structure-function relationships of viral antagonists. The herpesvirus human cytomegalovirus (HCMV) expresses the abundant immediate-early protein IE1 that colocalizes with PML-NBs and induces their dispersal, which correlates with the antagonization of NB-mediated intrinsic immunity. Here, we delineate the molecular basis for this antagonization by presenting the first crystal structure for the evolutionary conserved primate cytomegalovirus IE1 proteins. We show that IE1 consists of a globular core (IE1CORE) flanked by intrinsically disordered regions. The 2.3 Å crystal structure of IE1CORE displays an all α-helical, femur-shaped fold, which lacks overall fold similarity with known protein structures, but shares secondary structure features recently observed in the coiled-coil domain of TRIM proteins. Yeast two-hybrid and coimmunoprecipitation experiments demonstrate that IE1CORE binds efficiently to the TRIM family member PML, and is able to induce PML deSUMOylation. Intriguingly, this results in the release of NB-associated proteins into the nucleoplasm, but not of PML itself. Importantly, we show that PML deSUMOylation by IE1CORE is sufficient to antagonize PML-NB-instituted intrinsic immunity. Moreover, co-immunoprecipitation experiments demonstrate that IE1CORE binds via the coiled-coil domain to PML and also interacts with TRIM5α We propose that IE1CORE sequesters PML and possibly other TRIM family members via structural mimicry using an extended binding surface formed by the coiled-coil region. This mode of interaction might render the antagonizing activity less susceptible to

  9. Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis.

    PubMed

    Sayyab, Shumaila; Viluma, Agnese; Bergvall, Kerstin; Brunberg, Emma; Jagannathan, Vidhya; Leeb, Tosso; Andersson, Göran; Bergström, Tomas F

    2016-03-01

    Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G > C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs. PMID:26747202

  10. Reassessing Breeding Investment in Birds: Class-Wide Analysis of Clutch Volume Reveals a Single Outlying Family

    PubMed Central

    Watson, David M.; Anderson, Susan E.; Olson, Valerie

    2015-01-01

    Reproductive investment is typically considered in terms of size and number of propagules produced. Compared with a thorough understanding of the overall patterns and ecological correlates of avian clutch size, egg size has received less attention and the total effort invested in laying a clutch of eggs is rarely considered. We used clutch volume as an alternative estimate of reproductive investment and present the first class-level analysis of clutch volume in birds using 1,364 randomly-selected species in 204 families. The relationship between body mass and egg volume was very strong (r2 = 0.946), validating previous studies identifying four families (Apterygidae, Pelecanoidiididae, Sternidae and Dromadidiae) with disproportionately large eggs. Clutch volume was also closely related to body mass (r2 = 0.909) and all but one of the taxa with disproportionately large eggs conformed to the overall relationship, their greater egg dimensions compensated by diminished clutch size. The only family which departed significantly from the relationship between body mass and clutch volume was the mound builders (Megapodiidae)—the only group of birds that do not rely on body heat for incubation. Although previously known for laying large clutches of large eggs containing disproportionately large yolks, the remarkable investment of megapodes in reproduction (more than seven times greater than other birds of comparable mass) has been hitherto overlooked. We consider the evolutionary basis and ecological implications of this finding, suggesting that energetic costs associated with incubation act as an upper limit on reproductive output of other birds. We recommend clutch volume as a sensitive, fine-grained measure of reproductive effort for research at a wide range of scales and advocate further analysis of ecological correlates of clutch volume in birds and amniotes generally. PMID:25633998

  11. Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis

    PubMed Central

    Sayyab, Shumaila; Viluma, Agnese; Bergvall, Kerstin; Brunberg, Emma; Jagannathan, Vidhya; Leeb, Tosso; Andersson, Göran; Bergström, Tomas F.

    2016-01-01

    Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10–20 cases and 10–20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G > C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs. PMID:26747202

  12. Diversifying selection in the wheat stem rust fungus acts predominantly on pathogen-associated gene families and reveals candidate effectors.

    PubMed

    Sperschneider, Jana; Ying, Hua; Dodds, Peter N; Gardiner, Donald M; Upadhyaya, Narayana M; Singh, Karam B; Manners, John M; Taylor, Jennifer M

    2014-01-01

    Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defense proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialized gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control. PMID:25225496

  13. Biochemical and structural characterization of a novel ubiquitin-conjugating enzyme E2 from Agrocybe aegeria reveals Ube2w family-specific properties

    PubMed Central

    Qi, Chao; Li, De-Feng; Feng, Lei; Hou, Yanjie; Sun, Hui; Wang, Da-Cheng; Liu, Wei

    2015-01-01

    Ubiquitination is a post-translational modification that is involved in myriad cellar regulation and disease pathways. The ubiquitin-conjugating enzyme (E2) is an important player in the ubiquitin transfer pathway. Although many E2 structures are available, not all E2 families have known structures, and three-dimensional structures from fungal organisms other than yeast are lacking. We report here the crystal structure of UbcA1, which is a novel ubiquitin-conjugating enzyme identified from the edible and medicinal mushroom Agrocybe aegerita and displays potential antitumor properties. The protein belongs to the Ube2w family and shows similar biochemical characteristics to human Ube2w, including monomer-dimer equilibrium in solution, α-NH2 ubiquitin-transfer activity and a mechanism to recognize backbone atoms of intrinsically disordered N-termini in substrates. Its structure displays a unique C-terminal conformation with an orientation of helix α3 that is completely different from the reported E2 structures but similar to a recently reported NMR ensemble of Ube2w. A mutagenesis study on this novel enzyme revealed that an intact C-terminus is significant for protein dimerization and enzymatic activity. As the first crystallized full-length protein of this family, UbcA1 may supersede the truncated X-ray structure of Ube2w (PDB entry 2A7L) as the representative structure of the Ube2w family. PMID:26525192

  14. Cello-oligosaccharide oxidation reveals differences between two lytic polysaccharide monooxygenases (family GH61) from Podospora anserina.

    PubMed

    Bey, Mathieu; Zhou, Simeng; Poidevin, Laetitia; Henrissat, Bernard; Coutinho, Pedro M; Berrin, Jean-Guy; Sigoillot, Jean-Claude

    2013-01-01

    The genome of the coprophilic ascomycete Podospora anserina encodes 33 different genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P. anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1 carbohydrate binding module, were successfully produced in Pichia pastoris. Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the formation of oxidized and nonoxidized cello-oligosaccharides. A striking difference between PaGH61A and PaGH61B was observed through the identification of the products, among which were doubly and triply oxidized cellodextrins, which were released only by the combination of PaGH61B with CDH. The mass spectrometry fragmentation patterns of these oxidized products could be consistent with oxidation at the C-6 position with a geminal diol group. The different properties of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed in regard to the proposed in vivo function of the CDH/GH61 enzyme system in oxidative cellulose hydrolysis. PMID:23124232

  15. Structure-Guided Functional Characterization of DUF1460 Reveals a New, Highly Specific NlpC/P60 Amidase Family

    PubMed Central

    Xu, Qingping; Mengin-Lecreulx, Dominique; Patin, Delphine; Grant, Joanna C.; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Knuth, Mark W.; Godzik, Adam; Lesley, Scott A.; Elsliger, Marc-André; Deacon, Ashley M.; Wilson, Ian A.

    2014-01-01

    SUMMARY GlcNAc-1,6-anhydro-MurNAc-tetrapeptide is a major peptidoglycan degradation intermediate and a cytotoxin. It is generated by lytic transglycosylases and further degraded and recycled by various enzymes. We have identified and characterized a novel, highly specific N-acetylmuramoyl-L-alanine amidase (AmiA) from Bacteroides uniformis, a member of the DUF1460 protein family, that hydrolyzes GlcNAc-1,6-anhydro-MurNAc-peptide into disaccharide and stem peptide. The high-resolution apo-structure at 1.15 Å resolution shows that AmiA is related to NlpC/P60 γ-D-Glu-meso-diaminopimelic acid amidases and shares a common catalytic core and cysteine peptidase-like active site. AmiA has evolved structural adaptations that reconfigure the substrate recognition site. The preferred substrates for AmiA were predicted in silico based on structural and bioinformatics data, and were subsequently characterized experimentally. Further crystal structures of AmiA in complexes with GlcNAc-1,6-anhydro-MurNAc and GlcNAc have enabled us to elucidate substrate recognition and specificity. DUF1460 is highly conserved in structure and defines a new amidase family. PMID:25465128

  16. Complete nucleotide sequence of plasmid pNA6 reveals the high plasticity of IncU family plasmids.

    PubMed

    Dang, Bingjun; Xu, Yan; Mao, Daqing; Luo, Yi

    2016-10-10

    Antibiotic resistance is a serious problem in health care and is of widespread public concern. Conjugative plasmids are the most important vectors in the dissemination of antibiotic resistance genes. In this study, we determined the complete sequence of plasmid pNA6, a plasmid which was isolated from the sediments of Haihe River. This plasmid confers reduced susceptibility to ampicillin, erythromycin and sulfamethoxazole. The complete sequence of plasmid pNA6 was 52,210bp in length with an average G+C content of 52.70%. Plasmid pNA6 belongs to the IncU group by sequence queries against the GenBank database. This plasmid has a typical IncU backbone and shows the highest similarities with plasmid RA3 and plasmid pFBAOT6. Plasmid pNA6 carries a class 1 integron consisting of aacA4, ereA and dfrA1 genes. Moreover, plasmid pNA6 also harbors a blaTEM-1-containing complex structure which inserted into the replication region and maintenance region. This insertion site has never been found on other IncU plasmids. The sequencing of plasmid pNA6 will add new sequence information to IncU family plasmids and enhance our understanding of the plasticity of IncU family plasmids. PMID:27374151

  17. Cello-Oligosaccharide Oxidation Reveals Differences between Two Lytic Polysaccharide Monooxygenases (Family GH61) from Podospora anserina

    PubMed Central

    Bey, Mathieu; Zhou, Simeng; Poidevin, Laetitia; Henrissat, Bernard; Coutinho, Pedro M.; Sigoillot, Jean-Claude

    2013-01-01

    The genome of the coprophilic ascomycete Podospora anserina encodes 33 different genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P. anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1 carbohydrate binding module, were successfully produced in Pichia pastoris. Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the formation of oxidized and nonoxidized cello-oligosaccharides. A striking difference between PaGH61A and PaGH61B was observed through the identification of the products, among which were doubly and triply oxidized cellodextrins, which were released only by the combination of PaGH61B with CDH. The mass spectrometry fragmentation patterns of these oxidized products could be consistent with oxidation at the C-6 position with a geminal diol group. The different properties of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed in regard to the proposed in vivo function of the CDH/GH61 enzyme system in oxidative cellulose hydrolysis. PMID:23124232

  18. The structure of the first representative of Pfam family PF09836 reveals a two-domain organization and suggests involvement in transcriptional regulation

    PubMed Central

    Das, Debanu; Grishin, Nick V.; Kumar, Abhinav; Carlton, Dennis; Bakolitsa, Constantina; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grzechnik, Anna; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; van den Bedem, Henry; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (∼40–99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention. PMID:20944208

  19. Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion

    PubMed Central

    Quétier, Ivan; Marshall, Jacqueline J.T.; Spencer-Dene, Bradley; Lachmann, Sylvie; Casamassima, Adele; Franco, Claudio; Escuin, Sarah; Worrall, Joseph T.; Baskaran, Priththivika; Rajeeve, Vinothini; Howell, Michael; Copp, Andrew J.; Stamp, Gordon; Rosewell, Ian; Cutillas, Pedro; Gerhardt, Holger; Parker, Peter J.; Cameron, Angus J.M.

    2016-01-01

    Summary In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality. PMID:26774483

  20. Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion.

    PubMed

    Quétier, Ivan; Marshall, Jacqueline J T; Spencer-Dene, Bradley; Lachmann, Sylvie; Casamassima, Adele; Franco, Claudio; Escuin, Sarah; Worrall, Joseph T; Baskaran, Priththivika; Rajeeve, Vinothini; Howell, Michael; Copp, Andrew J; Stamp, Gordon; Rosewell, Ian; Cutillas, Pedro; Gerhardt, Holger; Parker, Peter J; Cameron, Angus J M

    2016-01-26

    In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality. PMID:26774483

  1. Revealing rate-limiting steps in complex disease biology: The crucial importance of studying rare, extreme-phenotype families.

    PubMed

    Chakravarti, Aravinda; Turner, Tychele N

    2016-06-01

    The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate-limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of each GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate-limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. PMID:27062178

  2. Identification and functional analysis of olfactory receptor family reveal unusual characteristics of the olfactory system in the migratory locust.

    PubMed

    Wang, Zhifeng; Yang, Pengcheng; Chen, Dafeng; Jiang, Feng; Li, Yan; Wang, Xianhui; Kang, Le

    2015-11-01

    Locusts represent the excellent model of insect olfaction because the animals are equipped with an unusual olfactory system and display remarkable density-dependent olfactory plasticity. However, information regarding receptor molecules involved in the olfactory perception of locusts is very limited. On the basis of genome sequence and antennal transcriptome of the migratory locust, we conduct the identification and functional analysis of two olfactory receptor families: odorant receptors (ORs) and ionotropic receptors (IRs). In the migratory locust, there is an expansion of OR family (142 ORs) while distinctly lower number of IR genes (32 IRs) compared to the repertoires of other insects. The number of the locust OR genes is much less than that of glomeruli in antennal lobe, challenging the general principle of the "one glomerulus-one receptor" observed in other insects. Most OR genes are found in tandem arrays, forming two large lineage-specific subfamilies in the phylogenetic tree. The "divergent IR" subfamily displays a significant contraction, and most of the IRs belong to the "antennal IR" subfamily in the locust. Most ORs/IRs have olfactory-specific expression while some broadly- or internal-expressed members are also found. Differing from holometabolous insects, the migratory locust contains very similar expression profiles of ORs/IRs between nymph and adult stages. RNA interference and behavioral assays indicate that an OR-based signaling pathway, not IR-based, mediates the attraction of locusts to aggregation pheromones. These discoveries provide insights into the unusual olfactory system of locusts and enhance our understanding of the evolution of insect olfaction. PMID:26265180

  3. Sequence Comparisons of Odorant Receptors among Tortricid Moths Reveal Different Rates of Molecular Evolution among Family Members

    PubMed Central

    Carraher, Colm; Authier, Astrid; Steinwender, Bernd; Newcomb, Richard D.

    2012-01-01

    In insects, odorant receptors detect volatile cues involved in behaviours such as mate recognition, food location and oviposition. We have investigated the evolution of three odorant receptors from five species within the moth genera Ctenopseustis and Planotrotrix, family Tortricidae, which fall into distinct clades within the odorant receptor multigene family. One receptor is the orthologue of the co-receptor Or83b, now known as Orco (OR2), and encodes the obligate ion channel subunit of the receptor complex. In comparison, the other two receptors, OR1 and OR3, are ligand-binding receptor subunits, activated by volatile compounds produced by plants - methyl salicylate and citral, respectively. Rates of sequence evolution at non-synonymous sites were significantly higher in OR1 compared with OR2 and OR3. Within the dataset OR1 contains 109 variable amino acid positions that are distributed evenly across the entire protein including transmembrane helices, loop regions and termini, while OR2 and OR3 contain 18 and 16 variable sites, respectively. OR2 shows a high level of amino acid conservation as expected due to its essential role in odour detection; however we found unexpected differences in the rate of evolution between two ligand-binding odorant receptors, OR1 and OR3. OR3 shows high sequence conservation suggestive of a conserved role in odour reception, whereas the higher rate of evolution observed in OR1, particularly at non-synonymous sites, may be suggestive of relaxed constraint, perhaps associated with the loss of an ancestral role in sex pheromone reception. PMID:22701634

  4. Structural analyses of the CRISPR protein Csc2 reveal the RNA-binding interface of the type I-D Cas7 family.

    PubMed

    Hrle, Ajla; Maier, Lisa-Katharina; Sharma, Kundan; Ebert, Judith; Basquin, Claire; Urlaub, Henning; Marchfelder, Anita; Conti, Elena

    2014-01-01

    Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions. These range from the insertion of the foreign genetic elements into the host genome to the activation of the interference machinery as well as target degradation upon attack. Cas7 family proteins are central to the type I and type III interference machineries as they constitute the backbone of the large interference complexes. Here we report the crystal structure of Thermofilum pendens Csc2, a Cas7 family protein of type I-D. We found that Csc2 forms a core RRM-like domain, flanked by three peripheral insertion domains: a lid domain, a Zinc-binding domain and a helical domain. Comparison with other Cas7 family proteins reveals a set of similar structural features both in the core and in the peripheral domains, despite the absence of significant sequence similarity. T. pendens Csc2 binds single-stranded RNA in vitro in a sequence-independent manner. Using a crosslinking - mass-spectrometry approach, we mapped the RNA-binding surface to a positively charged surface patch on T. pendens Csc2. Thus our analysis of the key structural and functional features of T. pendens Csc2 highlights recurring themes and evolutionary relationships in type I and type III Cas proteins. PMID:25483036

  5. Unconventional Superconductivity in La7Ir3 Revealed by Muon Spin Relaxation: Introducing a New Family of Noncentrosymmetric Superconductor That Breaks Time-Reversal Symmetry

    NASA Astrophysics Data System (ADS)

    Barker, J. A. T.; Singh, D.; Thamizhavel, A.; Hillier, A. D.; Lees, M. R.; Balakrishnan, G.; Paul, D. McK.; Singh, R. P.

    2015-12-01

    The superconductivity of the noncentrosymmetric compound La7 Ir3 is investigated using muon spin rotation and relaxation. Zero-field measurements reveal the presence of spontaneous static or quasistatic magnetic fields below the superconducting transition temperature Tc=2.25 K —a clear indication that the superconducting state breaks time-reversal symmetry. Furthermore, transverse-field rotation measurements suggest that the superconducting gap is isotropic and that the pairing symmetry of the superconducting electrons is predominantly s wave with an enhanced binding strength. The results indicate that the superconductivity in La7 Ir3 may be unconventional and paves the way for further studies of this family of materials.

  6. Mitogenomics reveals phylogeny and repeated motifs in control regions of the deep-sea family Siboglinidae (Annelida).

    PubMed

    Li, Yuanning; Kocot, Kevin M; Schander, Christoffer; Santos, Scott R; Thornhill, Daniel J; Halanych, Kenneth M

    2015-04-01

    Deep-sea tubeworms in the annelid family Siboglinidae have drawn considerable interest regarding their ecology and evolutionary biology. As adults, they lack a digestive tract and rely on endosymbionts for nutrition. Moreover, they are important members of chemosynthetic environments including hydrothermal vents, cold seeps, muddy sediments, and whale bones. Evolution and diversification of siboglinids has been associated with host-symbiont relationships and reducing habitats. Despite their importance, the taxonomy and phylogenetics of this clade are debated due to conflicting results. In this study, 10 complete and 2 partial mitochondrial genomes and one transcriptome were sequenced and analyzed to address siboglinid evolution. Notably, repeated nucleotide motifs were found in control regions of these mt genomes, which may explain previous challenges of sequencing siboglinid mt genomes. Phylogenetic analyses of amino acid and nucleotide datasets were conducted in order to infer evolutionary history. Both analyses generally had strong nodal support and suggest Osedax is most closely related to the Vestimentifera+Sclerolinum clade, rather than Frenulata, as recently reported. These results imply Osedax, the only siboglinid lineage with heterotrophic endosymbionts, evolved from a lineage utilizing chemoautotrophic symbionts. PMID:25721539

  7. A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level.

    PubMed

    Erapaneedi, Raghu; Belousov, Vsevolod V; Schäfers, Michael; Kiefer, Friedemann

    2016-01-01

    Hypoxia is an intensively investigated condition with profound effects on cell metabolism, migration, and angiogenesis during development and disease. Physiologically, hypoxia is linked to tissue homeostasis and maintenance of pluripotency. Hypoxia also contributes to pathologies including cardiovascular diseases and cancer. Despite its importance, microscopic visualization of hypoxia is largely restricted to the detection of reductively activated probes by immunostaining. Here, we describe a novel family of genetically encoded fluorescent sensors that detect the activation of HIF transcription factors reported by the oxygen-independent fluorescent protein UnaG. It comprises sensors with different switching and memory behavior and combination sensors that allow the distinction of hypoxic and reoxygenated cells. We tested these sensors on orthotopically transplanted glioma cell lines. Using a cranial window, we could visualize hypoxia intravitally at cellular resolution. In tissue samples, sensor activity was detected in regions, which were largely devoid of blood vessels, correlated with HIF-1α stabilization, and were highly heterogeneous at a cellular level. Frequently, we detected recently reoxygenated cells outside hypoxic areas in the proximity of blood vessels, suggestive of hypoxia-promoted cell migration. PMID:26598532

  8. Avirulence gene mapping in the Hessian fly (Mayetiola destructor) reveals a protein phosphatase 2C effector gene family.

    PubMed

    Zhao, Chaoyang; Shukle, Richard; Navarro-Escalante, Lucio; Chen, Mingshun; Richards, Stephen; Stuart, Jeffrey J

    2016-01-01

    The genetic tractability of the Hessian fly (HF, Mayetiola destructor) provides an opportunity to investigate the mechanisms insects use to induce plant gall formation. Here we demonstrate that capacity using the newly sequenced HF genome by identifying the gene (vH24) that elicits effector-triggered immunity in wheat (Triticum spp.) seedlings carrying HF resistance gene H24. vH24 was mapped within a 230-kb genomic fragment near the telomere of HF chromosome X1. That fragment contains only 21 putative genes. The best candidate vH24 gene in this region encodes a protein containing a secretion signal and a type-2 serine/threonine protein phosphatase (PP2C) domain. This gene has an H24-virulence associated insertion in its promoter that appears to silence transcription of the gene in H24-virulent larvae. Candidate vH24 is a member of a small family of genes that encode secretion signals and PP2C domains. It belongs to the fraction of genes in the HF genome previously predicted to encode effector proteins. Because PP2C proteins are not normally secreted, our results suggest that these are PP2C effectors that HF larvae inject into wheat cells to redirect, or interfere, with wheat signal transduction pathways. PMID:26439791

  9. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family

    PubMed Central

    Pathak, Anand; Seipel, Katja; Pemov, Alexander; Dewan, Ramita; Brown, Christina; Ravichandran, Sarangan; Luke, Brian T.; Malasky, Michael; Suman, Shalabh; Yeager, Meredith; Gatti, Richard A.; Caporaso, Neil E.; Mulvihill, John J.; Goldin, Lynn R.; Pabst, Thomas; McMaster, Mary L.; Stewart, Douglas R.

    2016-01-01

    Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia. PMID:26721895

  10. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family.

    PubMed

    Pathak, Anand; Seipel, Katja; Pemov, Alexander; Dewan, Ramita; Brown, Christina; Ravichandran, Sarangan; Luke, Brian T; Malasky, Michael; Suman, Shalabh; Yeager, Meredith; Gatti, Richard A; Caporaso, Neil E; Mulvihill, John J; Goldin, Lynn R; Pabst, Thomas; McMaster, Mary L; Stewart, Douglas R

    2016-07-01

    Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia. PMID:26721895

  11. Structure of Natural Killer Receptor 2B4 Bound to CD48 Reveals Basis for Heterophilic Recognition in Signaling Lymphocyte Activation Molecule Family

    SciTech Connect

    Velikovsky,C.; Deng, L.; Chlewicki, L.; Fernandez, M.; Kumar, V.; Mariuzza, R.

    2007-01-01

    Natural killer (NK) cells eliminate virally infected and tumor cells. Among the receptors regulating NK cell function is 2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM) family that binds CD48. 2B4 is the only heterophilic receptor of the SLAM family, whose other members, e.g., NK-T-B-antigen (NTB-A), are self-ligands. We determined the structure of the complex between the N-terminal domains of mouse 2B4 and CD48, as well as the structures of unbound 2B4 and CD48. The complex displayed an association mode related to, yet distinct from, that of the NTB-A dimer. Binding was accompanied by the rigidification of flexible 2B4 regions containing most of the polymorphic residues across different species and receptor isoforms. We propose a model for 2B4-CD48 interactions that permits the intermixing of SLAM receptors with major histocompatibility complex-specific receptors in the NK cell immune synapse. This analysis revealed the basis for heterophilic recognition within the SLAM family.

  12. Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.

    PubMed

    Wang, Xue; Xin, Qian; Li, Lin; Li, Jiangxia; Zhang, Changwu; Qiu, Rongfang; Qian, Chenmin; Zhao, Hailing; Liu, Yongchao; Shan, Shan; Dang, Jie; Bian, Xianli; Shao, Changshun; Gong, Yaoqin; Liu, Qiji

    2014-09-01

    Split-hand/foot malformation (SHFM) is a congenital limb deformity due to the absence or dysplasia of central rays of the autopod. Six SHFM loci have already been identified. Here we describe a Chinese family with autosomal-dominant SHFM1 that has previously been mapped to 7q21.2-21.3. The two affected family members, mother and son, showed deep median clefts between toes, ectrodactyly and syndactyly; the mother also showed triphalangeal thumbs. Exome sequencing and variant screening of candidate genes in the six loci known to be responsible for SHFM revealed a novel heterozygous mutation, c.558G>T (p.(Gln186His)), in distal-less homeobox 5 (DLX5). As DLX5 encodes a transcription factor capable of transactivating MYC, we also tested whether the mutation could affect DLX5 transcription acitivity. Results from luciferase reporter assay revealed that a mutation in DLX5 compromised its transcriptional activity. This is the first report of a mutation in DLX5 leading to autosomal-dominant SHFM1. PMID:24496061

  13. Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of Glycoside Hydrolase

    PubMed Central

    2014-01-01

    Background Gut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain. Results Genomic context and domain architecture analyses support a role for the GxGYxYP domain in carbohydrate metabolism. Sparse occurrences in eukaryotes are the result of lateral gene transfer. The structure of the GxGYxYP domain-containing protein encoded by the BT2193 locus reveals two structural domains, the first composed of three divergent repeats with no recognisable homology to previously solved structures, the second a more familiar seven-stranded β/α barrel. Structure-based analyses including conservation mapping localise a presumed functional site to a cleft between the two domains of BT2193. Matching to a catalytic site template from a GH9 cellulase and other analyses point to a putative catalytic triad composed of Glu272, Asp331 and Asp333. Conclusions We suggest that GxGYxYP-containing proteins constitute a novel glycoside hydrolase family of as yet unknown specificity. PMID:24938123

  14. Structural and Biochemical Analyses of Glycoside Hydrolase Families 5 and 26 β-(1,4)-Mannanases from Podospora anserina Reveal Differences upon Manno-oligosaccharide Catalysis*

    PubMed Central

    Couturier, Marie; Roussel, Alain; Rosengren, Anna; Leone, Philippe; Stålbrand, Henrik; Berrin, Jean-Guy

    2013-01-01

    The microbial deconstruction of the plant cell wall is a key biological process that is of increasing importance with the development of a sustainable biofuel industry. The glycoside hydrolase families GH5 (PaMan5A) and GH26 (PaMan26A) endo-β-1,4-mannanases from the coprophilic ascomycete Podospora anserina contribute to the enzymatic degradation of lignocellulosic biomass. In this study, P. anserina mannanases were further subjected to detailed comparative analysis of their substrate specificities, active site organization, and transglycosylation capacity. Although PaMan5A displays a classical mode of action, PaMan26A revealed an atypical hydrolysis pattern with the release of mannotetraose and mannose from mannopentaose resulting from a predominant binding mode involving the −4 subsite. The crystal structures of PaMan5A and PaMan26A were solved at 1.4 and 2.85 Å resolution, respectively. Analysis of the PaMan26A structure supported strong interaction with substrate at the −4 subsite mediated by two aromatic residues Trp-244 and Trp-245. The PaMan26A structure appended to its family 35 carbohydrate binding module revealed a short and proline-rich rigid linker that anchored together the catalytic and the binding modules. PMID:23558681

  15. Genomic analyses of cherry rusty mottle group and cherry twisted leaf-associated viruses reveal a possible new genus within the family betaflexiviridae.

    PubMed

    Villamor, D E V; Susaimuthu, J; Eastwell, K C

    2015-03-01

    It is demonstrated that closely related viruses within the family Betaflexiviridae are associated with a number of diseases that affect sweet cherry (Prunus avium) and other Prunus spp. Cherry rusty mottle-associated virus (CRMaV) is correlated with the appearance of cherry rusty mottle disease (CRMD), and Cherry twisted leaf-associated virus (CTLaV) is linked to cherry twisted leaf disease (CTLD) and apricot ringpox disease (ARPD). Comprehensive analysis of previously reported full genomic sequences plus those determined in this study representing isolates of CTLaV, CRMaV, Cherry green ring mottle virus, and Cherry necrotic rusty mottle virus revealed segregation of sequences into four clades corresponding to distinct virus species. High-throughput sequencing of RNA from representative source trees for CRMD, CTLD, and ARPD did not reveal additional unique virus sequences that might be associated with these diseases, thereby further substantiating the association of CRMaV and CTLaV with CRMD and CTLD or ARPD, respectively. Based on comparison of the nucleotide and amino acid sequence identity values, phylogenetic relationships with other triple-gene block-coding viruses within the family Betaflexiviridae, genome organization, and natural host range, a new genus (Robigovirus) is suggested. PMID:25496302

  16. Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity

    PubMed Central

    2011-01-01

    Background Acyl-acyl carrier protein thioesterases (acyl-ACP TEs) catalyze the hydrolysis of the thioester bond that links the acyl chain to the sulfhydryl group of the phosphopantetheine prosthetic group of ACP. This reaction terminates acyl chain elongation of fatty acid biosynthesis, and in plant seeds it is the biochemical determinant of the fatty acid compositions of storage lipids. Results To explore acyl-ACP TE diversity and to identify novel acyl ACP-TEs, 31 acyl-ACP TEs from wide-ranging phylogenetic sources were characterized to ascertain their in vivo activities and substrate specificities. These acyl-ACP TEs were chosen by two different approaches: 1) 24 TEs were selected from public databases on the basis of phylogenetic analysis and fatty acid profile knowledge of their source organisms; and 2) seven TEs were molecularly cloned from oil palm (Elaeis guineensis), coconut (Cocos nucifera) and Cuphea viscosissima, organisms that produce medium-chain and short-chain fatty acids in their seeds. The in vivo substrate specificities of the acyl-ACP TEs were determined in E. coli. Based on their specificities, these enzymes were clustered into three classes: 1) Class I acyl-ACP TEs act primarily on 14- and 16-carbon acyl-ACP substrates; 2) Class II acyl-ACP TEs have broad substrate specificities, with major activities toward 8- and 14-carbon acyl-ACP substrates; and 3) Class III acyl-ACP TEs act predominantly on 8-carbon acyl-ACPs. Several novel acyl-ACP TEs act on short-chain and unsaturated acyl-ACP or 3-ketoacyl-ACP substrates, indicating the diversity of enzymatic specificity in this enzyme family. Conclusion These acyl-ACP TEs can potentially be used to diversify the fatty acid biosynthesis pathway to produce novel fatty acids. PMID:21831316

  17. IDENTIFICATION OF NICOTINAMIDE MONONUCLEOTIDE DEAMIDASE OF THE BACTERIAL PYRIDINE NUCLEOTIDE CYCLE REVEALS A NOVEL BROADLY CONSERVED AMIDOHYDROLASE FAMILY

    SciTech Connect

    Galeazzi, Luca; Bocci, Paolo; Amici, Adolfo; Brunetti, Lucia; Ruggieri, Silverio; Romine, Margaret F.; Reed, Samantha B.; Osterman, Andrei; Rodionov, Dmitry A.; Sorci, Leonardo; Raffaelli, Nadia

    2011-09-27

    The pyridine nucleotide cycle (PNC) is a network of salvage and recycling routes maintaining homeostasis of NAD(P) cofactor pool in the cell. Nicotinamide mononucleotide (NMN) deamidase (EC 3.5.1.42), one of the key enzymes of the bacterial PNC was originally described in Enterobacteria, but the corresponding gene eluded identification for over 30 years. A genomics-based reconstruction of NAD metabolism across hundreds bacterial species suggested that NMN deamidase reaction is the only possible way of nicotinamide salvage in the marine bacterium Shewanella oneidensis. This prediction was verified via purification of native NMN deamidase from S. oneidensis followed by the identification of the respective gene, termed pncC. Enzymatic characterization of the PncC protein, as well as phenotype analysis of deletion mutants, confirmed its proposed biochemical and physiological function in S. oneidensis. Of the three PncC homologs present in E. coli, NMN deamidase activity was confirmed only for the recombinant purified product of the ygaD gene. A comparative analysis at the level of sequence and three dimensional structure, which is available for one of the PncC family member, shows no homology with any previously described amidohydrolases. Multiple alignment analysis of functional and non functional PncC homologs, together with NMN docking experiments, allowed us to tentatively identify the active site area and conserved residues therein. An observed broad phylogenomic distribution of predicted functional PncCs in bacterial kingdom is consistent with a possible role in detoxification of NMN, resulting from NAD utilization by DNA ligase.

  18. Conserved synteny at the protein family level reveals genes underlying Shewanella species cold tolerance and predicts their novel phenotypes

    SciTech Connect

    Karpinets, Tatiana V.; Obraztsova, Anna; Wang, Yanbing; Schmoyer, Denise D.; Kora, Guruprasad; Park, Byung H.; Serres, Margrethe H.; Romine, Margaret F.; Land, Miriam L.; Kothe, Terence B.; Fredrickson, Jim K.; Nealson, Kenneth H.; Uberbacher, Edward

    2010-03-01

    Bacteria of the genus Shewanella can thrive in different environments and demonstrate significant variability in their metabolic and ecophysiological capabilities including cold and salt tolerance. Genomic characteristics underlying this variability across species are largely unknown. In this study we address the problem by a comparison of the physiological, metabolic and genomic characteristics of 19 sequenced Shewanella species. We have employed two novel approaches based on association of a phenotypic trait with the number of the trait-specific protein families (Pfam domains) and on the conservation of synteny (order in the genome) of the trait-related genes. Our first approach is top-down and involves experimental evaluation and quantification of the species’ cold tolerance followed by identification of the correlated Pfam domains and genes with a conserved synteny. The second, a bottom-up approach, predicts novel phenotypes of the species by calculating profiles of each Pfam domain among their genomes and following pair-wise correlation of the profiles and their network clustering. Using the first approach we find a link between cold and salt tolerance of the species and the presence in the genome of a Na+/H+ antiporter gene cluster. Other cold tolerance related genes includes peptidases, chemotaxis sensory transducer proteins, a cysteine exporter, and helicases. Using the bottom-up approach we found several novel phenotypes in the newly sequenced Shewanella species, including degradation of aromatic compounds by an aerobic hybrid pathway in S. woodyi, degradation of ethanolamine by S. benthica, and propanediol degradation by S. putrefaciens CN32 and S. sp. W3-18-1.

  19. Functional genomics reveals that a compact terpene synthase gene family can account for terpene volatile production in apple.

    PubMed

    Nieuwenhuizen, Niels J; Green, Sol A; Chen, Xiuyin; Bailleul, Estelle J D; Matich, Adam J; Wang, Mindy Y; Atkinson, Ross G

    2013-02-01

    Terpenes are specialized plant metabolites that act as attractants to pollinators and as defensive compounds against pathogens and herbivores, but they also play an important role in determining the quality of horticultural food products. We show that the genome of cultivated apple (Malus domestica) contains 55 putative terpene synthase (TPS) genes, of which only 10 are predicted to be functional. This low number of predicted functional TPS genes compared with other plant species was supported by the identification of only eight potentially functional TPS enzymes in apple 'Royal Gala' expressed sequence tag databases, including the previously characterized apple (E,E)-α-farnesene synthase. In planta functional characterization of these TPS enzymes showed that they could account for the majority of terpene volatiles produced in cv Royal Gala, including the sesquiterpenes germacrene-D and (E)-β-caryophyllene, the monoterpenes linalool and α-pinene, and the homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene. Relative expression analysis of the TPS genes indicated that floral and vegetative tissues were the primary sites of terpene production in cv Royal Gala. However, production of cv Royal Gala floral-specific terpenes and TPS genes was observed in the fruit of some heritage apple cultivars. Our results suggest that the apple TPS gene family has been shaped by a combination of ancestral and more recent genome-wide duplication events. The relatively small number of functional enzymes suggests that the remaining terpenes produced in floral and vegetative and fruit tissues are maintained under a positive selective pressure, while the small number of terpenes found in the fruit of modern cultivars may be related to commercial breeding strategies. PMID:23256150

  20. Functional Genomics Reveals That a Compact Terpene Synthase Gene Family Can Account for Terpene Volatile Production in Apple1[W

    PubMed Central

    Nieuwenhuizen, Niels J.; Green, Sol A.; Chen, Xiuyin; Bailleul, Estelle J.D.; Matich, Adam J.; Wang, Mindy Y.; Atkinson, Ross G.

    2013-01-01

    Terpenes are specialized plant metabolites that act as attractants to pollinators and as defensive compounds against pathogens and herbivores, but they also play an important role in determining the quality of horticultural food products. We show that the genome of cultivated apple (Malus domestica) contains 55 putative terpene synthase (TPS) genes, of which only 10 are predicted to be functional. This low number of predicted functional TPS genes compared with other plant species was supported by the identification of only eight potentially functional TPS enzymes in apple ‘Royal Gala’ expressed sequence tag databases, including the previously characterized apple (E,E)-α-farnesene synthase. In planta functional characterization of these TPS enzymes showed that they could account for the majority of terpene volatiles produced in cv Royal Gala, including the sesquiterpenes germacrene-D and (E)-β-caryophyllene, the monoterpenes linalool and α-pinene, and the homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene. Relative expression analysis of the TPS genes indicated that floral and vegetative tissues were the primary sites of terpene production in cv Royal Gala. However, production of cv Royal Gala floral-specific terpenes and TPS genes was observed in the fruit of some heritage apple cultivars. Our results suggest that the apple TPS gene family has been shaped by a combination of ancestral and more recent genome-wide duplication events. The relatively small number of functional enzymes suggests that the remaining terpenes produced in floral and vegetative and fruit tissues are maintained under a positive selective pressure, while the small number of terpenes found in the fruit of modern cultivars may be related to commercial breeding strategies. PMID:23256150

  1. Phylogeographic analyses of submesophotic snappers Etelis coruscans and Etelis "marshi" (family Lutjanidae) reveal concordant genetic structure across the Hawaiian Archipelago.

    PubMed

    Andrews, Kimberly R; Moriwake, Virginia N; Wilcox, Christie; Grau, E Gordon; Kelley, Christopher; Pyle, Richard L; Bowen, Brian W

    2014-01-01

    The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m) in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200-360 m) in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787) and E. "marshi" (formerly E. carbunculus; N = 770) with 436-490 bp of mtDNA cytochrome b and 10-11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals) had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper (Hyporthodus quernus). Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management plans. PMID

  2. Knock-down of transcript abundance of a family of Kunitz proteinase inhibitor genes in white clover (Trifolium repens) reveals a redundancy and diversity of gene function.

    PubMed

    Islam, Afsana; Leung, Susanna; Burgess, Elisabeth P J; Laing, William A; Richardson, Kim A; Hofmann, Rainer W; Dijkwel, Paul P; McManus, Michael T

    2015-12-01

    The transcriptional regulation of four phylogenetically distinct members of a family of Kunitz proteinase inhibitor (KPI) genes isolated from white clover (Trifolium repens; designated Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5) has been investigated to determine their wider functional role. The four genes displayed differential transcription during seed germination, and in different tissues of the mature plant, and transcription was also ontogenetically regulated. Heterologous over-expression of Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5 in Nicotiana tabacum retarded larval growth of the herbivore Spodoptera litura, and an increase in the transcription of the pathogenesis-related genes PR1 and PR4 was observed in the Tr-KPI1 and Tr-KPI4 over-expressing lines. RNA interference (RNAi) knock-down lines in white clover displayed significantly altered vegetative growth phenotypes with inhibition of shoot growth and a stimulation of root growth, while knock-down of Tr-KPI1, Tr-KPI2 and Tr-KPI5 transcript abundance also retarded larval growth of S. litura. Examination of these RNAi lines revealed constitutive stress-associated phenotypes as well as altered transcription of cellular signalling genes. These results reveal a functional redundancy across members of the KPI gene family. Further, the regulation of transcription of at least one member of the family, Tr-KPI2, may occupy a central role in the maintenance of a cellular homeostasis. PMID:26377591

  3. Molecular Characterization of the 14-3-3 Gene Family in Brachypodium distachyon L. Reveals High Evolutionary Conservation and Diverse Responses to Abiotic Stresses

    PubMed Central

    Cao, Hui; Xu, Yuxing; Yuan, Linlin; Bian, Yanwei; Wang, Lihui; Zhen, Shoumin; Hu, Yingkao; Yan, Yueming

    2016-01-01

    The 14-3-3 gene family identified in all eukaryotic organisms is involved in a wide range of biological processes, particularly in resistance to various abiotic stresses. Here, we performed the first comprehensive study on the molecular characterization, phylogenetics, and responses to various abiotic stresses of the 14-3-3 gene family in Brachypodium distachyon L. A total of seven 14-3-3 genes from B. distachyon and 120 from five main lineages among 12 species were identified, which were divided into five well-conserved subfamilies. The molecular structure analysis showed that the plant 14-3-3 gene family is highly evolutionarily conserved, although certain divergence had occurred in different subfamilies. The duplication event investigation revealed that segmental duplication seemed to be the predominant form by which the 14-3-3 gene family had expanded. Moreover, seven critical amino acids were detected, which may contribute to functional divergence. Expression profiling analysis showed that BdGF14 genes were abundantly expressed in the roots, but showed low expression in the meristems. All seven BdGF14 genes showed significant expression changes under various abiotic stresses, including heavy metal, phytohormone, osmotic, and temperature stresses, which might play important roles in responses to multiple abiotic stresses mainly through participating in ABA-dependent signaling and reactive oxygen species-mediated MAPK cascade signaling pathways. In particular, BdGF14 genes generally showed upregulated expression in response to multiple stresses of high temperature, heavy metal, abscisic acid (ABA), and salicylic acid (SA), but downregulated expression under H2O2, NaCl, and polyethylene glycol (PEG) stresses. Meanwhile, dynamic transcriptional expression analysis of BdGF14 genes under longer treatments with heavy metals (Cd2+, Cr3+, Cu2+, and Zn2+) and phytohormone (ABA) and recovery revealed two main expression trends in both roots and leaves: up-down and up

  4. Analyses of Sox-B and Sox-E Family Genes in the Cephalopod Sepia officinalis: Revealing the Conserved and the Unusual

    PubMed Central

    Focareta, Laura; Cole, Alison G.

    2016-01-01

    Cephalopods provide an unprecedented opportunity for comparative studies of the developmental genetics of organ systems that are convergent with analogous vertebrate structures. The Sox-family of transcription factors is an important class of DNA-binding proteins that are known to be involved in many aspects of differentiation, but have been largely unstudied in lophotrochozoan systems. Using a degenerate primer strategy we have isolated coding sequence for three members of the Sox family of transcription factors from a cephalopod mollusk, the European cuttlefish Sepia officinalis: Sof-SoxE, Sof-SoxB1, and Sof-SoxB2. Analyses of their expression patterns during organogenesis reveals distinct spatial and temporal expression domains. Sof-SoxB1 shows early ectodermal expression throughout the developing epithelium, which is gradually restricted to presumptive sensory epithelia. Expression within the nervous system appears by mid-embryogenesis. Sof-SoxB2 expression is similar to Sof-SoxB1 within the developing epithelia in early embryogenesis, however appears in largely non-overlapping expression domains within the central nervous system and is not expressed in the maturing sensory epithelium. In contrast, Sof-SoxE is expressed throughout the presumptive mesodermal territories at the onset of organogenesis. As development proceeds, Sof-SoxE expression is elevated throughout the developing peripheral circulatory system. This expression disappears as the circulatory system matures, but expression is maintained within undifferentiated connective tissues throughout the animal, and appears within the nervous system near the end of embryogenesis. SoxB proteins are widely known for their role in neural specification in numerous phylogenetic lineages. Our data suggests that Sof-SoxB genes play similar roles in cephalopods. In contrast, Sof-SoxE appears to be involved in the early stages of vasculogenesis of the cephalopod closed circulatory system, a novel role for a member of

  5. Analyses of Sox-B and Sox-E Family Genes in the Cephalopod Sepia officinalis: Revealing the Conserved and the Unusual.

    PubMed

    Focareta, Laura; Cole, Alison G

    2016-01-01

    Cephalopods provide an unprecedented opportunity for comparative studies of the developmental genetics of organ systems that are convergent with analogous vertebrate structures. The Sox-family of transcription factors is an important class of DNA-binding proteins that are known to be involved in many aspects of differentiation, but have been largely unstudied in lophotrochozoan systems. Using a degenerate primer strategy we have isolated coding sequence for three members of the Sox family of transcription factors from a cephalopod mollusk, the European cuttlefish Sepia officinalis: Sof-SoxE, Sof-SoxB1, and Sof-SoxB2. Analyses of their expression patterns during organogenesis reveals distinct spatial and temporal expression domains. Sof-SoxB1 shows early ectodermal expression throughout the developing epithelium, which is gradually restricted to presumptive sensory epithelia. Expression within the nervous system appears by mid-embryogenesis. Sof-SoxB2 expression is similar to Sof-SoxB1 within the developing epithelia in early embryogenesis, however appears in largely non-overlapping expression domains within the central nervous system and is not expressed in the maturing sensory epithelium. In contrast, Sof-SoxE is expressed throughout the presumptive mesodermal territories at the onset of organogenesis. As development proceeds, Sof-SoxE expression is elevated throughout the developing peripheral circulatory system. This expression disappears as the circulatory system matures, but expression is maintained within undifferentiated connective tissues throughout the animal, and appears within the nervous system near the end of embryogenesis. SoxB proteins are widely known for their role in neural specification in numerous phylogenetic lineages. Our data suggests that Sof-SoxB genes play similar roles in cephalopods. In contrast, Sof-SoxE appears to be involved in the early stages of vasculogenesis of the cephalopod closed circulatory system, a novel role for a member of

  6. Unconventional Superconductivity in La(7)Ir(3) Revealed by Muon Spin Relaxation: Introducing a New Family of Noncentrosymmetric Superconductor That Breaks Time-Reversal Symmetry.

    PubMed

    Barker, J A T; Singh, D; Thamizhavel, A; Hillier, A D; Lees, M R; Balakrishnan, G; Paul, D McK; Singh, R P

    2015-12-31

    The superconductivity of the noncentrosymmetric compound La(7)Ir(3) is investigated using muon spin rotation and relaxation. Zero-field measurements reveal the presence of spontaneous static or quasistatic magnetic fields below the superconducting transition temperature T(c)=2.25  K-a clear indication that the superconducting state breaks time-reversal symmetry. Furthermore, transverse-field rotation measurements suggest that the superconducting gap is isotropic and that the pairing symmetry of the superconducting electrons is predominantly s wave with an enhanced binding strength. The results indicate that the superconductivity in La(7)Ir(3) may be unconventional and paves the way for further studies of this family of materials. PMID:26765016

  7. Genome-Wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide-Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants

    PubMed Central

    Seo, Eunyoung; Kim, Seungill; Yeom, Seon-In; Choi, Doil

    2016-01-01

    Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors are known play critical roles in effector-triggered immunity (ETI) plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267, 443, and 755 NLR-encoding genes in tomato, potato, and pepper genomes, respectively. Phylogenetic analysis and classification of Solanaceae NLRs revealed that the majority of NLR super family members fell into 14 subgroups, including a TIR-NLR (TNL) subgroup and 13 non-TNL subgroups. Specific subgroups have expanded in each genome, with the expansion in pepper showing subgroup-specific physical clusters. Comparative analysis of duplications showed distinct duplication patterns within pepper and among Solanaceae plants suggesting subgroup- or species-specific gene duplication events after speciation, resulting in divergent evolution. Taken together, genome-wide analysis of NLR family members provide insights into their evolutionary history in Solanaceae. These findings also provide important foundational knowledge for understanding NLR evolution and will empower broader characterization of disease resistance genes to be used for crop breeding. PMID:27559340

  8. Genome-Wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide-Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants.

    PubMed

    Seo, Eunyoung; Kim, Seungill; Yeom, Seon-In; Choi, Doil

    2016-01-01

    Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors are known play critical roles in effector-triggered immunity (ETI) plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267, 443, and 755 NLR-encoding genes in tomato, potato, and pepper genomes, respectively. Phylogenetic analysis and classification of Solanaceae NLRs revealed that the majority of NLR super family members fell into 14 subgroups, including a TIR-NLR (TNL) subgroup and 13 non-TNL subgroups. Specific subgroups have expanded in each genome, with the expansion in pepper showing subgroup-specific physical clusters. Comparative analysis of duplications showed distinct duplication patterns within pepper and among Solanaceae plants suggesting subgroup- or species-specific gene duplication events after speciation, resulting in divergent evolution. Taken together, genome-wide analysis of NLR family members provide insights into their evolutionary history in Solanaceae. These findings also provide important foundational knowledge for understanding NLR evolution and will empower broader characterization of disease resistance genes to be used for crop breeding. PMID:27559340

  9. The structure of mouse cytomegalovirus m04 protein determined from sparse NMR data reveals a new fold of the m02-m06 family of viral immune modulators

    PubMed Central

    Sgourakis, Nikolaos G.; Natarajan, Kannan; Ying, Jinfa; Vogeli, Beat; Boyd, Lisa F.; Margulies, David H.; Bax, Ad

    2014-01-01

    Summary Immunoevasins are key proteins employed by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions towards the design of vaccines and other antiviral therapies. Mouse cytomegalovirus (MCMV) encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer (NK) cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, due largely to crystallization bottlenecks. Here we implement a new technology employing sparse NMR data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a new β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. PMID:25126960

  10. Topological analysis of the Escherichia coli WcaJ protein reveals a new conserved configuration for the polyisoprenyl-phosphate hexose-1-phosphate transferase family

    PubMed Central

    Furlong, Sarah E.; Ford, Amy; Albarnez-Rodriguez, Lorena; Valvano, Miguel A.

    2015-01-01

    WcaJ is an Escherichia coli membrane enzyme catalysing the biosynthesis of undecaprenyl-diphosphate-glucose, the first step in the assembly of colanic acid exopolysaccharide. WcaJ belongs to a large family of polyisoprenyl-phosphate hexose-1-phosphate transferases (PHPTs) sharing a similar predicted topology consisting of an N-terminal domain containing four transmembrane helices (TMHs), a large central periplasmic loop, and a C-terminal domain containing the fifth TMH (TMH-V) and a cytosolic tail. However, the topology of PHPTs has not been experimentally validated. Here, we investigated the topology of WcaJ using a combination of LacZ/PhoA reporter fusions and sulfhydryl labelling by PEGylation of novel cysteine residues introduced into a cysteine-less WcaJ. The results showed that the large central loop and the C-terminal tail both reside in the cytoplasm and are separated by TMH-V, which does not fully span the membrane, likely forming a "hairpin" structure. Modelling of TMH-V revealed that a highly conserved proline might contribute to a helix-break-helix structure in all PHPT members. Bioinformatic analyses show that all of these features are conserved in PHPT homologues from Gram-negative and Gram-positive bacteria. Our data demonstrate a novel topological configuration for PHPTs, which is proposed as a signature for all members of this enzyme family. PMID:25776537

  11. The Structure of RdDddP from Roseobacter denitrificans Reveals That DMSP Lyases in the DddP-Family Are Metalloenzymes

    PubMed Central

    Hehemann, Jan-Hendrik; Law, Adrienne; Redecke, Lars; Boraston, Alisdair B.

    2014-01-01

    Marine microbes degrade dimethylsulfoniopropionate (DMSP), which is produced in large quantities by marine algae and plants, with DMSP lyases into acrylate and the gas dimethyl sulfide (DMS). Approximately 10% of the DMS vents from the sea into the atmosphere and this emission returns sulfur, which arrives in the sea through rivers and runoff, back to terrestrial systems via clouds and rain. Despite their key role in this sulfur cycle DMSP lyases are poorly understood at the molecular level. Here we report the first X-ray crystal structure of the putative DMSP lyase RdDddP from Roseobacter denitrificans, which belongs to the abundant DddP family. This structure, determined to 2.15 Å resolution, shows that RdDddP is a homodimeric metalloprotein with a binuclear center of two metal ions located 2.7 Å apart in the active site of the enzyme. Consistent with the crystallographic data, inductively coupled plasma mass spectrometry (ICP-MS) and total reflection X-ray fluorescence (TRXF) revealed the bound metal species to be primarily iron. A 3D structure guided analysis of environmental DddP lyase sequences elucidated the critical residues for metal binding are invariant, suggesting all proteins in the DddP family are metalloenzymes. PMID:25054772

  12. Driving south: a multi-gene phylogeny of the brown algal family Fucaceae reveals relationships and recent drivers of a marine radiation

    PubMed Central

    2011-01-01

    Background Understanding the processes driving speciation in marine ecosystems remained a challenge until recently, due to the unclear nature of dispersal boundaries. However, recent evidence for marine adaptive radiations and ecological speciation, as well as previously undetected patterns of cryptic speciation is overturning this view. Here, we use multi-gene phylogenetics to infer the family-level evolutionary history of Fucaceae (intertidal brown algae of the northern Pacific and Atlantic) in order to investigate recent and unique patterns of radiative speciation in the genus Fucus in the Atlantic, in contrast with the mainly monospecific extant genera. Results We developed a set of markers from 13 protein coding genes based on polymorphic cDNA from EST libraries, which provided novel resolution allowing estimation of ancestral character states and a detailed reconstruction of the recent radiative history. Phylogenetic reconstructions yielded similar topologies and revealed four independent trans-Arctic colonization events by Fucaceae lineages, two of which also involved transitions from hermaphroditism to dioecy associated with Atlantic invasions. More recently, reversion of dioecious ancestral lineages towards hermaphroditism has occurred in the genus Fucus, particularly coinciding with colonization of more extreme habitats. Novel lineages in the genus Fucus were also revealed in association with southern habitats. These most recent speciation events occurred during the Pleistocene glaciations and coincided with a shift towards selfing mating systems, generally southward shifts in distribution, and invasion of novel habitats. Conclusions Diversification of the family occurred in the Late-Mid Miocene, with at least four independent trans-Artic lineage crossings coincident with two reproductive mode transitions. The genus Fucus arose in the Pliocene but radiated within a relatively short time frame about 2.5 million years ago. Current species distributions of

  13. Spitzer Reveals Stellar 'Family Tree'

    NASA Technical Reports Server (NTRS)

    2008-01-01

    [figure removed for brevity, see original site] High resolution poster version

    Generations of stars can be seen in this new infrared portrait from NASA's Spitzer Space Telescope. In this wispy star-forming region, called W5, the oldest stars can be seen as blue dots in the centers of the two hollow cavities (other blue dots are background and foreground stars not associated with the region). Younger stars line the rims of the cavities, and some can be seen as pink dots at the tips of the elephant-trunk-like pillars. The white knotty areas are where the youngest stars are forming. Red shows heated dust that pervades the region's cavities, while green highlights dense clouds.

    W5 spans an area of sky equivalent to four full moons and is about 6,500 light-years away in the constellation Cassiopeia. The Spitzer picture was taken over a period of 24 hours.

    Like other massive star-forming regions, such as Orion and Carina, W5 contains large cavities that were carved out by radiation and winds from the region's most massive stars. According to the theory of triggered star-formation, the carving out of these cavities pushes gas together, causing it to ignite into successive generations of new stars.

    This image contains some of the best evidence yet for the triggered star-formation theory. Scientists analyzing the photo have been able to show that the ages of the stars become progressively and systematically younger with distance from the center of the cavities.

    This is a three-color composite showing infrared observations from two Spitzer instruments. Blue represents 3.6-micron light and green shows light of 8 microns, both captured by Spitzer's infrared array camera. Red is 24-micron light detected by Spitzer's multiband imaging photometer.

  14. Spitzer Reveals Stellar 'Family Tree'

    NASA Technical Reports Server (NTRS)

    2008-01-01

    [figure removed for brevity, see original site] High resolution poster version

    Generations of stars can be seen in this new infrared portrait from NASA's Spitzer Space Telescope. In this wispy star-forming region, called W5, the oldest stars can be seen as blue dots in the centers of the two hollow cavities (other blue dots are background and foreground stars not associated with the region). Younger stars line the rims of the cavities, and some can be seen as dots at the tips of the elephant-trunk-like pillars. The white knotty areas are where the youngest stars are forming.

    W5 spans an area of sky equivalent to four full moons and is about 6,500 light-years away in the constellation Cassiopeia. The Spitzer picture was taken over a period of 24 hours.

    Like other massive star-forming regions, such as Orion and Carina, W5 contains large cavities that were carved out by radiation and winds from the region's most massive stars. According to the theory of triggered star-formation, the carving out of these cavities pushes gas together, causing it to ignite into successive generations of new stars.

    This image contains some of the best evidence yet for the triggered star-formation theory. Scientists analyzing the photo have been able to show that the ages of the stars become progressively and systematically younger with distance from the center of the cavities.

    This picture was taken with Spitzer's infrared array camera. It is a four-color composite, in which light with a wavelength of 3.6 microns is blue; 4.5-micron light is green; 5.8-micron light is orange; and 8-micron light is red.

  15. Identification and characterization of fructose 1,6-bisphosphate aldolase genes in Arabidopsis reveal a gene family with diverse responses to abiotic stresses.

    PubMed

    Lu, Wei; Tang, Xiaoli; Huo, Yanqing; Xu, Rui; Qi, Shengdong; Huang, Jinguang; Zheng, Chengchao; Wu, Chang-ai

    2012-07-15

    Fructose 1,6-biphosphate aldolase (FBA) is a key enzyme in plants, which is involved not only in glycolysis and gluconeogenesis in the cytoplasm, but also in the Calvin cycle in plastids. Research on FBAs in various organisms has been reported, but there is none on FBAs in Arabidopsis at the molecular level. In the current study, eight FBA family genes (AtFBA1-8) were identified and analyzed in Arabidopsis thaliana. These genes have a highly conserved aldolase-type TIM barrel domain and a C-terminal peptide, but variable N-terminal peptides. Based on the phylogenetic analysis of FBA protein sequences from Arabidopsis and other plant species, AtFBA family was classified into two subfamilies, including three members (AtFBA1-3) with high similarities to FBAs occurring at plastid, and five (AtFBA4-8) with high similarities to FBAs localized in the cytoplasm. By confocal microscopy analysis with GFP fusion protein, AtFBA3 and AtFBA4 as well as AtFBA6 were observed to be localized in the plastid and cytoplasm, respectively. At least two duplicated gene pairs of AtFBA1 and AtFBA2, as well as AtFBA4 and AtFBA8 were found. Transcript level analysis of AtFBA genes in various tissues revealed the unique and overlapping expression patterns of plastid and cytosol AtFBA genes, suggesting that these genes may function at different stages of plant growth and development. Interestingly, AtFBA1, AtFBA2, AtFBA5 and AtFBA7 showed undetectable expression in roots. The expression patterns of AtFBA genes under different stress conditions suggested that all the members showed different expression patterns in response to stresses, including ABA, NaCl, Cd, abnormal temperature and drought, and, except for AtFBA3, most of the AtFBA genes were significantly responsive to drought stress in roots. Moreover, AtFBA1, AtFBA2, AtFBA5, AtFBA7 and AtFBA8 were induced by at least one of three sugars (sucrose, glucose and fructose) after 24h of treatment. Further functional analyses indicated important

  16. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    SciTech Connect

    Lee, Dong-Hwa; Ha, Ji-Hyang; Kim, Yul; Bae, Kwang-Hee; Park, Jae-Yong; Choi, Wan Sung; Yoon, Ho Sup; Park, Sung Goo; Park, Byoung Chul; Yi, Gwan-Su; Chi, Seung-Wook

    2011-05-20

    Highlights: {yields} Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. {yields} The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. {yields} A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-X{sub L}. {yields} The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-X{sub L.} {yields} Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. A structural model of the Bcl-X{sub L}/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X{sub L}/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X{sub L}. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  17. Systematic Identification, Evolution and Expression Analysis of the Zea mays PHT1 Gene Family Reveals Several New Members Involved in Root Colonization by Arbuscular Mycorrhizal Fungi.

    PubMed

    Liu, Fang; Xu, Yunjian; Jiang, Huanhuan; Jiang, Chaosheng; Du, Yibin; Gong, Cheng; Wang, Wei; Zhu, Suwen; Han, Guomin; Cheng, Beijiu

    2016-01-01

    The Phosphate Transporter1 (PHT1) family of genes plays pivotal roles in the uptake of inorganic phosphate from soils. However, there is no comprehensive report on the PHT1 family in Zea mays based on the whole genome. In the present study, a total of 13 putative PHT1 genes (ZmPHT1;1 to 13) were identified in the inbred line B73 genome by bioinformatics methods. Then, their function was investigated by a yeast PHO84 mutant complementary experiment and qRT-PCR. Thirteen ZmPHT1 genes distributed on six chromosomes (1, 2, 5, 7, 8 and 10) were divided into two paralogues (Class A and Class B). ZmPHT1;1/ZmPHT1;9 and ZmPHT1;9/ZmPHT1;13 are produced from recent segmental duplication events. ZmPHT1;1/ZmPHT1;13 and ZmPHT1;8/ZmPHT1;10 are produced from early segmental duplication events. All 13 putative ZmPHT1s can completely or partly complement the yeast Pi-uptake mutant, and they were obviously induced in maize under low Pi conditions, except for ZmPHT1;1 (p < 0.01), indicating that the overwhelming majority of ZmPHT1 genes can respond to a low Pi condition. ZmPHT1;2, ZmPHT1;4, ZmPHT1;6, ZmPHT1;7, ZmPHT1;9 and ZmPHT1;11 were up-regulated by arbuscular mycorrhizal fungi (AMF), implying that these genes might participate in mediating Pi absorption and/or transport. Analysis of the promoters revealed that the MYCS and P1BS element are widely distributed on the region of different AMF-inducible ZmPHT1 promoters. In light of the above results, five of 13 ZmPHT1 genes were newly-identified AMF-inducible high-affinity phosphate transporters in the maize genome. Our results will lay a foundation for better understanding the PHT1 family evolution and the molecular mechanisms of inorganic phosphate transport under AMF inoculation. PMID:27304955

  18. Systematic Identification, Evolution and Expression Analysis of the Zea mays PHT1 Gene Family Reveals Several New Members Involved in Root Colonization by Arbuscular Mycorrhizal Fungi

    PubMed Central

    Liu, Fang; Xu, Yunjian; Jiang, Huanhuan; Jiang, Chaosheng; Du, Yibin; Gong, Cheng; Wang, Wei; Zhu, Suwen; Han, Guomin; Cheng, Beijiu

    2016-01-01

    The Phosphate Transporter1 (PHT1) family of genes plays pivotal roles in the uptake of inorganic phosphate from soils. However, there is no comprehensive report on the PHT1 family in Zea mays based on the whole genome. In the present study, a total of 13 putative PHT1 genes (ZmPHT1;1 to 13) were identified in the inbred line B73 genome by bioinformatics methods. Then, their function was investigated by a yeast PHO84 mutant complementary experiment and qRT-PCR. Thirteen ZmPHT1 genes distributed on six chromosomes (1, 2, 5, 7, 8 and 10) were divided into two paralogues (Class A and Class B). ZmPHT1;1/ZmPHT1;9 and ZmPHT1;9/ZmPHT1;13 are produced from recent segmental duplication events. ZmPHT1;1/ZmPHT1;13 and ZmPHT1;8/ZmPHT1;10 are produced from early segmental duplication events. All 13 putative ZmPHT1s can completely or partly complement the yeast Pi-uptake mutant, and they were obviously induced in maize under low Pi conditions, except for ZmPHT1;1 (p < 0.01), indicating that the overwhelming majority of ZmPHT1 genes can respond to a low Pi condition. ZmPHT1;2, ZmPHT1;4, ZmPHT1;6, ZmPHT1;7, ZmPHT1;9 and ZmPHT1;11 were up-regulated by arbuscular mycorrhizal fungi (AMF), implying that these genes might participate in mediating Pi absorption and/or transport. Analysis of the promoters revealed that the MYCS and P1BS element are widely distributed on the region of different AMF-inducible ZmPHT1 promoters. In light of the above results, five of 13 ZmPHT1 genes were newly-identified AMF-inducible high-affinity phosphate transporters in the maize genome. Our results will lay a foundation for better understanding the PHT1 family evolution and the molecular mechanisms of inorganic phosphate transport under AMF inoculation. PMID:27304955

  19. Molecular characterization of the reniform nematode C-type lectin gene family reveals a likely role in mitigating environmental stresses during plant parasitism.

    PubMed

    Ganji, Satish; Jenkins, Johnie N; Wubben, Martin J

    2014-03-10

    The reniform nematode, Rotylenchulus reniformis, is a damaging semi-endoparasitic pathogen of more than 300 plant species. Transcriptome sequencing of R. reniformis parasitic females revealed an enrichment for sequences homologous to C-type lectins (CTLs), an evolutionarily ancient family of Ca(+2)-dependent carbohydrate-binding proteins that are involved in the innate immune response. To gain further insight as to the potential role of CTLs in facilitating plant parasitism by R. reniformis, we performed a comprehensive assessment of the CTL gene family. 5'- and 3'-RACE experiments identified a total of 11 R. reniformis CTL transcripts (Rr-ctl-1 through Rr-ctl-11) that ranged in length from 1083 to 1,194 bp and showed 93-99% identity with one another. An alignment of cDNA and genomic sequences revealed three introns with the first intron residing within the 5'-untranslated region. BLAST analyses showed the closest homologs belonging to the parasitic nematodes Heligmosomoides polygyrus and Heterodera glycines. Rr-ctl-1, -2, and -3 were expressed throughout the R. reniformis life cycle; whereas, the remaining Rr-ctl genes showed life stage-specific expression. Quantitative real time RT-PCR determined that Rr-ctl transcripts were 839-fold higher in sedentary female nematodes than the next most abundant life stage. Predicted Rr-CTL peptides ranged from 301 to 338 amino acids long, possessed an N-terminal signal peptide for secretion, and contained a conserved CLECT domain, including the mannose-binding motifs EPN and EPD and the conserved WND motif that is required for binding Ca(+2). In addition, Rr-CTL peptides harbored repeats of a novel 17-mer motif within their C-terminus that showed similarity to motifs associated with bacterial ice nucleation proteins. In situ hybridization of Rr-ctl transcripts within sedentary females showed specific accumulation within the hypodermis of the body regions exposed to the soil environment; those structures embedded within the

  20. Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae) and Worm Lizards (Amphisbaenia)

    PubMed Central

    Szirovicza, Leonóra; López, Pilar; Kopena, Renáta; Benkő, Mária; Martín, José; Pénzes, Judit J.

    2016-01-01

    Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs) in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni), nine Iberian worm lizards (Blanus cinereus), and two Iberian green lizards (Lacerta schreiberi), respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses. PMID:27399970

  1. Genome-wide analyses of the bZIP family reveal their involvement in the development, ripening and abiotic stress response in banana.

    PubMed

    Hu, Wei; Wang, Lianzhe; Tie, Weiwei; Yan, Yan; Ding, Zehong; Liu, Juhua; Li, Meiying; Peng, Ming; Xu, Biyu; Jin, Zhiqiang

    2016-01-01

    The leucine zipper (bZIP) transcription factors play important roles in multiple biological processes. However, less information is available regarding the bZIP family in the important fruit crop banana. In this study, 121 bZIP transcription factor genes were identified in the banana genome. Phylogenetic analysis showed that MabZIPs were classified into 11 subfamilies. The majority of MabZIP genes in the same subfamily shared similar gene structures and conserved motifs. The comprehensive transcriptome analysis of two banana genotypes revealed the differential expression patterns of MabZIP genes in different organs, in various stages of fruit development and ripening, and in responses to abiotic stresses, including drought, cold, and salt. Interaction networks and co-expression assays showed that group A MabZIP-mediated networks participated in various stress signaling, which was strongly activated in Musa ABB Pisang Awak. This study provided new insights into the complicated transcriptional control of MabZIP genes and provided robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MabZIP genes for potential applications in the genetic improvement of banana cultivars. PMID:27445085

  2. NMR spectroscopic analysis reveals extensive binding interactions of complex xyloglucan oligosaccharides with the Cellvibrio japonicus glycoside hydrolase family 31 α-xylosidase.

    PubMed

    Silipo, Alba; Larsbrink, Johan; Marchetti, Roberta; Lanzetta, Rosa; Brumer, Harry; Molinaro, Antonio

    2012-10-15

    The study of the interaction of glycoside hydrolases with their substrates is fundamental to diverse applications in medicine, food and feed production, and biomass-resource utilization. Recent molecular modeling of the α-xylosidase CjXyl31A from the soil saprophyte Cellvibrio japonicus, together with protein crystallography and enzyme-kinetic analysis, has suggested that an appended PA14 protein domain, unique among glycoside hydrolase family 31 members, may confer specificity for large oligosaccharide fragments of the ubiquitous plant polysaccharide xyloglucan (J. Larsbrink, A. Izumi, F.M. Ibatullin, A. Nakhai, H.J. Gilbert, G.J. Davies, H. Brumer, Biochem. J. 2011, 436, 567-580). In the present study, a combination of NMR spectroscopic techniques, including saturation transfer difference (STD) and transfer NOE (TR-NOE) spectroscopy, was used to reveal extensive interactions between CjXyl31A active-site variants and xyloglucan hexa- and heptasaccharides. The data specifically indicate that the enzyme recognizes the entire cello-tetraosyl backbone of the substrate and product in positive enzyme subsites and makes further significant interactions with internal pendant α-(1→6)-linked xylosyl units. As such, the present analysis provides an important rationalization of previous kinetic data on CjXyl31A and unique insight into the role of the PA14 domain, which was not otherwise obtainable by protein crystallography. PMID:22961810

  3. Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae) and Worm Lizards (Amphisbaenia).

    PubMed

    Szirovicza, Leonóra; López, Pilar; Kopena, Renáta; Benkő, Mária; Martín, José; Pénzes, Judit J

    2016-01-01

    Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs) in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni), nine Iberian worm lizards (Blanus cinereus), and two Iberian green lizards (Lacerta schreiberi), respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses. PMID:27399970

  4. Genome-wide analyses of the bZIP family reveal their involvement in the development, ripening and abiotic stress response in banana

    PubMed Central

    Hu, Wei; Wang, Lianzhe; Tie, Weiwei; Yan, Yan; Ding, Zehong; Liu, Juhua; Li, Meiying; Peng, Ming; Xu, Biyu; Jin, Zhiqiang

    2016-01-01

    The leucine zipper (bZIP) transcription factors play important roles in multiple biological processes. However, less information is available regarding the bZIP family in the important fruit crop banana. In this study, 121 bZIP transcription factor genes were identified in the banana genome. Phylogenetic analysis showed that MabZIPs were classified into 11 subfamilies. The majority of MabZIP genes in the same subfamily shared similar gene structures and conserved motifs. The comprehensive transcriptome analysis of two banana genotypes revealed the differential expression patterns of MabZIP genes in different organs, in various stages of fruit development and ripening, and in responses to abiotic stresses, including drought, cold, and salt. Interaction networks and co-expression assays showed that group A MabZIP-mediated networks participated in various stress signaling, which was strongly activated in Musa ABB Pisang Awak. This study provided new insights into the complicated transcriptional control of MabZIP genes and provided robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MabZIP genes for potential applications in the genetic improvement of banana cultivars. PMID:27445085

  5. Genome-Wide Analysis Reveals Diverged Patterns of Codon Bias, Gene Expression, and Rates of Sequence Evolution in Picea Gene Families

    PubMed Central

    De La Torre, Amanda R.; Lin, Yao-Cheng; Van de Peer, Yves; Ingvarsson, Pär K.

    2015-01-01

    The recent sequencing of several gymnosperm genomes has greatly facilitated studying the evolution of their genes and gene families. In this study, we examine the evidence for expression-mediated selection in the first two fully sequenced representatives of the gymnosperm plant clade (Picea abies and Picea glauca). We use genome-wide estimates of gene expression (>50,000 expressed genes) to study the relationship between gene expression, codon bias, rates of sequence divergence, protein length, and gene duplication. We found that gene expression is correlated with rates of sequence divergence and codon bias, suggesting that natural selection is acting on Picea protein-coding genes for translational efficiency. Gene expression, rates of sequence divergence, and codon bias are correlated with the size of gene families, with large multicopy gene families having, on average, a lower expression level and breadth, lower codon bias, and higher rates of sequence divergence than single-copy gene families. Tissue-specific patterns of gene expression were more common in large gene families with large gene expression divergence than in single-copy families. Recent family expansions combined with large gene expression variation in paralogs and increased rates of sequence evolution suggest that some Picea gene families are rapidly evolving to cope with biotic and abiotic stress. Our study highlights the importance of gene expression and natural selection in shaping the evolution of protein-coding genes in Picea species, and sets the ground for further studies investigating the evolution of individual gene families in gymnosperms. PMID:25747252

  6. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion

    PubMed Central

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-01-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright’s Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but

  7. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion.

    PubMed

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-04-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but it

  8. Sequence-Based Screening for Rare Enzymes: New Insights into the World of AMDases Reveal a Conserved Motif and 58 Novel Enzymes Clustering in Eight Distinct Families

    PubMed Central

    Maimanakos, Janine; Chow, Jennifer; Gaßmeyer, Sarah K.; Güllert, Simon; Busch, Florian; Kourist, Robert; Streit, Wolfgang R.

    2016-01-01

    Arylmalonate Decarboxylases (AMDases, EC 4.1.1.76) are very rare and mostly underexplored enzymes. Currently only four known and biochemically characterized representatives exist. However, their ability to decarboxylate α-disubstituted malonic acid derivatives to optically pure products without cofactors makes them attractive and promising candidates for the use as biocatalysts in industrial processes. Until now, AMDases could not be separated from other members of the aspartate/glutamate racemase superfamily based on their gene sequences. Within this work, a search algorithm was developed that enables a reliable prediction of AMDase activity for potential candidates. Based on specific sequence patterns and screening methods 58 novel AMDase candidate genes could be identified in this work. Thereby, AMDases with the conserved sequence pattern of Bordetella bronchiseptica’s prototype appeared to be limited to the classes of Alpha-, Beta-, and Gamma-proteobacteria. Amino acid homologies and comparison of gene surrounding sequences enabled the classification of eight enzyme clusters. Particularly striking is the accumulation of genes coding for different transporters of the tripartite tricarboxylate transporters family, TRAP transporters and ABC transporters as well as genes coding for mandelate racemases/muconate lactonizing enzymes that might be involved in substrate uptake or degradation of AMDase products. Further, three novel AMDases were characterized which showed a high enantiomeric excess (>99%) of the (R)-enantiomer of flurbiprofen. These are the recombinant AmdA and AmdV from Variovorax sp. strains HH01 and HH02, originated from soil, and AmdP from Polymorphum gilvum found by a data base search. Altogether our findings give new insights into the class of AMDases and reveal many previously unknown enzyme candidates with high potential for bioindustrial processes. PMID:27610105

  9. The Vanadium Iodoperoxidase from the Marine Flavobacteriaceae Species Zobellia galactanivorans Reveals Novel Molecular and Evolutionary Features of Halide Specificity in the Vanadium Haloperoxidase Enzyme Family

    PubMed Central

    Fournier, Jean-Baptiste; Rebuffet, Etienne; Delage, Ludovic; Grijol, Romain; Meslet-Cladière, Laurence; Rzonca, Justyna; Potin, Philippe; Michel, Gurvan; Czjzek, Mirjam

    2014-01-01

    Vanadium haloperoxidases (VHPO) are key enzymes that oxidize halides and are involved in the biosynthesis of organo-halogens. Until now, only chloroperoxidases (VCPO) and bromoperoxidases (VBPO) have been characterized structurally, mainly from eukaryotic species. Three putative VHPO genes were predicted in the genome of the flavobacterium Zobellia galactanivorans, a marine bacterium associated with macroalgae. In a phylogenetic analysis, these putative bacterial VHPO were closely related to other VHPO from diverse bacterial phyla but clustered independently from eukaryotic algal VBPO and fungal VCPO. Two of these bacterial VHPO, heterogeneously produced in Escherichia coli, were found to be strictly specific for iodide oxidation. The crystal structure of one of these vanadium-dependent iodoperoxidases, Zg-VIPO1, was solved by multiwavelength anomalous diffraction at 1.8 Å, revealing a monomeric structure mainly folded into α-helices. This three-dimensional structure is relatively similar to those of VCPO of the fungus Curvularia inaequalis and of Streptomyces sp. and is superimposable onto the dimeric structure of algal VBPO. Surprisingly, the vanadate binding site of Zg-VIPO1 is strictly conserved with the fungal VCPO active site. Using site-directed mutagenesis, we showed that specific amino acids and the associated hydrogen bonding network around the vanadate center are essential for the catalytic properties and also the iodide specificity of Zg-VIPO1. Altogether, phylogeny and structure-function data support the finding that iodoperoxidase activities evolved independently in bacterial and algal lineages, and this sheds light on the evolution of the VHPO enzyme family. PMID:25261522

  10. A family of differentially amplified repetitive DNA sequences in the genus Beta reveals genetic variation in Beta vulgaris subspecies and cultivars.

    PubMed

    Kubis, S; Heslop-Harrison, J S; Schmidt, T

    1997-03-01

    Members of a highly abundant restriction satellite family have been isolated from the wild beet species Beta nana. The satellite DNA sequence is characterized by a conserved RsaI restriction site and is present in three of four sections of the genus Beta, namely Nanae, Corollinae, and Beta. It was not detected in species of the evolutionary old section Procumbentes, suggesting its amplification after separation of this section. Sequences of eight monomers were aligned revealing a size variation from 209 to 233 bp and an AT content ranging from 56.5% to 60.5%. The similarity between monomers in B. nana varied from 77.7% to 92.2%. Diverged subfamilies were identified by sequence analysis and Southern hybridization. A comparative study of this repetitive DNA element by fluorescent in situ hybridization and Southern analyses in three representative species was performed showing a variable genomic organization and heterogeneous localizations along metaphase chromosomes both within and between species. In B. nana the copy number of this satellite, with some 30,000 per haploid genome, is more than tenfold higher than in Beta lomatogona and up to 200 times higher than in Beta vulgaris, indicating different levels of sequence amplification during evolution in the genus Beta. In sugar beet (B. vulgaris), the large-scale organization of this tandem repeat was examined by pulsed-field gel electrophoresis. Southern hybridization to genomic DNA digested with DraI demonstrated that satellite arrays are located in AT-rich regions and the tandem repeat is a useful probe for the detection of genetic variation in closely related B. vulgaris cultivars, accessions, and subspecies. PMID:9060397

  11. Sequence-Based Screening for Rare Enzymes: New Insights into the World of AMDases Reveal a Conserved Motif and 58 Novel Enzymes Clustering in Eight Distinct Families.

    PubMed

    Maimanakos, Janine; Chow, Jennifer; Gaßmeyer, Sarah K; Güllert, Simon; Busch, Florian; Kourist, Robert; Streit, Wolfgang R

    2016-01-01

    Arylmalonate Decarboxylases (AMDases, EC 4.1.1.76) are very rare and mostly underexplored enzymes. Currently only four known and biochemically characterized representatives exist. However, their ability to decarboxylate α-disubstituted malonic acid derivatives to optically pure products without cofactors makes them attractive and promising candidates for the use as biocatalysts in industrial processes. Until now, AMDases could not be separated from other members of the aspartate/glutamate racemase superfamily based on their gene sequences. Within this work, a search algorithm was developed that enables a reliable prediction of AMDase activity for potential candidates. Based on specific sequence patterns and screening methods 58 novel AMDase candidate genes could be identified in this work. Thereby, AMDases with the conserved sequence pattern of Bordetella bronchiseptica's prototype appeared to be limited to the classes of Alpha-, Beta-, and Gamma-proteobacteria. Amino acid homologies and comparison of gene surrounding sequences enabled the classification of eight enzyme clusters. Particularly striking is the accumulation of genes coding for different transporters of the tripartite tricarboxylate transporters family, TRAP transporters and ABC transporters as well as genes coding for mandelate racemases/muconate lactonizing enzymes that might be involved in substrate uptake or degradation of AMDase products. Further, three novel AMDases were characterized which showed a high enantiomeric excess (>99%) of the (R)-enantiomer of flurbiprofen. These are the recombinant AmdA and AmdV from Variovorax sp. strains HH01 and HH02, originated from soil, and AmdP from Polymorphum gilvum found by a data base search. Altogether our findings give new insights into the class of AMDases and reveal many previously unknown enzyme candidates with high potential for bioindustrial processes. PMID:27610105

  12. Differential expression and interaction specificity of the heterotrimeric G-protein family in Brassica nigra reveal their developmental- and condition-specific roles.

    PubMed

    Kumar, Roshan; Arya, Gulab C; Bisht, Naveen C

    2014-11-01

    Heterotrimeric G-proteins, comprised of α, β and γ subunits, are important signal transducers across phyla. The G-proteins are well characterized in the model plants Arabidopsis and rice, and their inventories are possible from a few other plant species; however, information about the roles played by G-proteins in regulating various growth and developmental traits particularly from polyploid crops is still awaited. In this study, we have isolated one Gα (BniB.Gα1), three Gβ (BniB.Gβ1-BniB.Gβ3) and four Gγ (BniB.Gγ1-BniB.Gγ4) coding sequences from the paleopolyploid Brassica nigra, a major condiment crop of the Brassicaceae family. Sequence and phylogenetic analysis revealed that whole-genome triplication events in the Brassica lineage had proportionally increased the inventory of the Gβ subunit, but not of the Gα and Gγ subunits in B. nigra. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis showed that members of the G-protein subunit genes have distinct temporal and spatial expression patterns and were differentially altered in response to various stress and phytohormone treatments, thereby suggesting differential transcriptional regulation of G-protein genes in B. nigra. Interestingly, specific members of G-protein subunits were co-expressed across plant developmental stages, and in response to different elicitor treatments. Yeast-based interaction screens further predicted that the B. nigra G-protein subunits interacted in most of the possible combinations, although showing a high degree of interaction specificity between different G-protein subunits. Our data on physical interactions coupled with the co-expression pattern of the multiple G-protein subunit genes suggested that tissue- and condition-specific functional combinations of Gαβγ heterotrimers may exist in paleopolyploid B. nigra, to control diverse growth and development processes. PMID:25231958

  13. The 2.2 Å resolution crystal structure of Bacillus cereus Nif3-family protein YqfO reveals a conserved dimetal-binding motif and a regulatory domain

    PubMed Central

    Godsey, Michael H.; Minasov, George; Shuvalova, Ludmilla; Brunzelle, Joseph S.; Vorontsov, Ivan I.; Collart, Frank R.; Anderson, Wayne F.

    2007-01-01

    YqfO of Bacillus cereus is a member of the widespread Nif3 family of proteins, which has been highlighted as an important target for structural genomics. The N- and C-terminal domains are conserved across the family and contain a dimetal-binding motif in a putative active site. YqfO contains an insert in the middle of the protein, present in a minority of bacterial family members. The structure of YqfO was determined at a resolution of 2.2 Å and reveals conservation of the putative active site. It also reveals the previously unknown structure of the insert, which despite extremely limited sequence conservation, bears great similarity to PII, CutA, and a number of other trimeric regulatory proteins. Our results suggest that this domain acts as a signal sensor to regulate the still-unknown catalytic activity of the more-conserved domains. PMID:17586767

  14. Family Structure and Family Processes in Mexican American Families

    PubMed Central

    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

    2010-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct, CD/ODD and MDD symptoms, and greater parent-child conflict than their counterparts in two parent families. Single parent mothers reported greater economic hardship, depression and family stress. Family stress and parent-child conflict emerged as significant mediators of the association between family structure and early adolescent outcomes, suggesting important processes linking MA single parent families and adolescent adjustment. PMID:21361925

  15. Conserved small RNAs govern replication and incompatibility of a diverse new plasmid family from marine bacteria

    PubMed Central

    Le Roux, Frédérique; Davis, Brigid M.; Waldor, Matthew K.

    2011-01-01

    Plasmids are autonomously replicating extrachromosomal DNA molecules that often impart key phenotypes to their bacterial hosts. Plasmids are abundant in marine bacteria, but there is scant knowledge of the mechanisms that control their replication in these hosts. Here, we identified and characterized the factors governing replication of a new family of plasmids from marine bacteria, typified by the virulence-linked plasmid pB1067 of Vibrio nigripulchritudo. Members of this family are prevalent among, yet restricted to, the Vibrionaceae. Unlike almost all plasmid families characterized to date, the ori regions of these plasmids do not encode a Rep protein to initiate DNA replication; instead, the ori regions encode two partially complementary RNAs. The smaller, termed RNA I, is ∼68-nt long and functions as a negative regulator and the key determinant of plasmid incompatibility. This Marine RNA-based (MRB) plasmid family is the first characterized family of replicons derived from marine bacteria. Only one other plasmid family (the ColE1 family) has previously been reported to rely on RNA-mediated replication initiation. However, since the sequences and structures of MRB RNA I transcripts are not related to those of ColE1 replicons, these two families of RNA-dependent replicons likely arose by convergent evolution. PMID:20923782

  16. Genomic Resources of Three Pulsatilla Species Reveal Evolutionary Hotspots, Species-Specific Sites and Variable Plastid Structure in the Family Ranunculaceae

    PubMed Central

    Szczecińska, Monika; Sawicki, Jakub

    2015-01-01

    Background: The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the continent. Most plants of the genus Pulsatilla are rare and endangered, which is why most research efforts focused on their biology, ecology and hybridization. The objective of this study was to develop genomic resources, including complete plastid genomes and nuclear rRNA clusters, for three sympatric Pulsatilla species that are most commonly found in Central Europe. The results will supply valuable information about genetic variation, which can be used in the process of designing primers for population studies and conservation genetics research. The complete plastid genomes together with the nuclear rRNA cluster can serve as a useful tool in hybridization studies. Methodology/principal findings: Six complete plastid genomes and nuclear rRNA clusters were sequenced from three species of Pulsatilla using the Illumina sequencing technology. Four junctions between single copy regions and inverted repeats and junctions between the identified locally-collinear blocks (LCB) were confirmed by Sanger sequencing. Pulsatilla genomes of 120 unique genes had a total length of approximately 161–162 kb, and 21 were duplicated in the inverted repeats (IR) region. Comparative plastid genomes of newly-sequenced Pulsatilla and the previously-identified plastomes of Aconitum and Ranunculus species belonging to the family Ranunculaceae revealed several variations in the structure of the genome, but the gene content remained constant. The nuclear rRNA cluster (18S-ITS1-5.8S-ITS2-26S) of studied Pulsatilla species is 5795 bp long. Among five analyzed regions of the rRNA cluster, only Internal Transcribed Spacer 2 (ITS2) enabled the molecular delimitation of closely-related Pulsatilla patens and

  17. Clinical and Molecular Studies Reveal a PSEN1 Mutation (L153V) in a Peruvian Family with Early-Onset Alzheimer's Disease

    PubMed Central

    Cornejo-Olivas, Mario R.; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F.; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B.; Bird, Thomas D.

    2014-01-01

    Presenilin 1 (PSEN1) gene mutations are found in 30 to 70% of familial early onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment was completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. PMID:24495933

  18. Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.

    PubMed

    Cornejo-Olivas, Mario R; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B; Bird, Thomas D

    2014-03-20

    Presenilin 1 (PSEN1) gene mutations are found in 30-70% of familial early-onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment were completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. PMID:24495933

  19. Structure of the first representative of Pfam family PF09410 (DUF2006) reveals a structural signature of the calycin superfamily that suggests a role in lipid metabolism

    SciTech Connect

    Chiu, Hsiu-Ju; Bakolitsa, Constantina; Skerra, Arne; Lomize, Andrei; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2015-10-15

    The first structural representative of the domain of unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with domain duplication. The finding of the calycin signature in the N-terminal domain, combined with remote sequence similarity to two other protein families (PF07143 and PF08622) implicated in isoprenoid metabolism and the oxidative stress response, support an involvement in lipid metabolism. Clusters of conserved residues that interact with ligand mimetics suggest that the binding and regulation sites map to the N-terminal domain and to the interdomain interface, respectively.

  20. Structure of the first representative of Pfam family PF09410 (DUF2006) reveals a structural signature of the calycin superfamily that suggests a role in lipid metabolism

    PubMed Central

    Chiu, Hsiu-Ju; Bakolitsa, Constantina; Skerra, Arne; Lomize, Andrei; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The first structural representative of the domain of unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with domain duplication. The finding of the calycin signature in the N-­terminal domain, combined with remote sequence similarity to two other protein families (PF07143 and PF08622) implicated in isoprenoid metabolism and the oxidative stress response, support an involvement in lipid metabolism. Clusters of conserved residues that interact with ligand mimetics suggest that the binding and regulation sites map to the N-terminal domain and to the interdomain interface, respectively. PMID:20944205

  1. Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

    PubMed Central

    Desvignes, Thomas; Pontarotti, Pierre; Bobe, Julien

    2010-01-01

    Background The Nme gene family is involved in multiple physiological and pathological processes such as cellular differentiation, development, metastatic dissemination, and cilia functions. Despite the known importance of Nme genes and their use as clinical markers of tumor aggressiveness, the associated cellular mechanisms remain poorly understood. Over the last 20 years, several non-vertebrate model species have been used to investigate Nme functions. However, the evolutionary history of the family remains poorly understood outside the vertebrate lineage. The aim of the study was thus to elucidate the evolutionary history of the Nme gene family in Metazoans. Methodology/Principal Findings Using a total of 21 eukaryote species including 14 metazoans, the evolutionary history of Nme genes was reconstructed in the metazoan lineage. We demonstrated that the complexity of the Nme gene family, initially thought to be restricted to chordates, was also shared by the metazoan ancestor. We also provide evidence suggesting that the complexity of the family is mainly a eukaryotic innovation, with the exception of Nme8 that is likely to be a choanoflagellate/metazoan innovation. Highly conserved gene structure, genomic linkage, and protein domains were identified among metazoans, some features being also conserved in eukaryotes. When considering the entire Nme family, the starlet sea anemone is the studied metazoan species exhibiting the most conserved gene and protein sequence features with humans. In addition, we were able to show that most of the proteins known to interact with human NME proteins were also found in starlet sea anemone. Conclusion/Significance Together, our observations further support the association of Nme genes with key cellular functions that have been conserved throughout metazoan evolution. Future investigations of evolutionarily conserved Nme gene functions using the starlet sea anemone could shed new light on a wide variety of key developmental and

  2. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

    PubMed

    Li, Jun; Woods, Susan L; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R M; Spurdle, Amanda B; Simpson, Peter T; da Silva, Leonard; Lakhani, Sunil R; Clouston, Andrew D; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F; Wen, Xiaogang; Martin, Hilary C; Neklason, Deborah W; Davis, Sean R; Walker, Robert L; Calzone, Kathleen A; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N; Hulick, Peter J; Weissman, Scott M; Newlin, Anna; Rubinstein, Wendy S; Sampson, Jone E; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K; Huntsman, David G; Foulkes, William D; Carneiro, Fatima; Lindor, Noralane M; Edwards, Stacey L; French, Juliet D; Waddell, Nicola; Meltzer, Paul S; Worthley, Daniel L; Schrader, Kasmintan A; Chenevix-Trench, Georgia

    2016-05-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present. PMID:27087319

  3. Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family

    PubMed Central

    Reiisi, Somayeh; Tabatabaiefar, Mohammad Amin; Sanati, Mohammad Hosein; Chaleshtori, Morteza Hashemzadeh

    2016-01-01

    Objective(s): Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive non-syndromic hearing loss (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide. Materials and Methods: The aim of the present study was to define the role and frequency of MYO15A gene mutation in Iranian families. In this study 30 Iranian families were enrolled with over three deaf children and negative for GJB2. Then linkage analysis was performed by six DFNB3 short tandem repeat markers. Following that, mutation detection accomplished using DNA sequencing. Results: One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A): as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls. Conclusion: Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein.

  4. Indicators of Economic Status and Social Capital in South African Townships: What Do They Reveal about the Material and Social Conditions in Families of Poor Children?

    ERIC Educational Resources Information Center

    Barbarin, Oscar A.; Khomo, Ngokoana

    1997-01-01

    Employed a method for assessing material well-being and social resources using a set of observable indicators such as adequacy of food, quality of housing, financial assets, consumer goods, and social resources. Identified two dimensions, consumption and social/financial capital, which when used to assign SES were predictive of a family's ability…

  5. Chicken interferon consensus sequence-binding protein (ICSBP) and interferon regulatory factor (IRF) 1 genes reveal evolutionary conservation in the IRF gene family.

    PubMed Central

    Jungwirth, C; Rebbert, M; Ozato, K; Degen, H J; Schultz, U; Dawid, I B

    1995-01-01

    Members of the IRF family mediate transcriptional responses to interferons (IFNs) and to virus infection. So far, proteins of this family have been studied only among mammalian species. Here we report the isolation of cDNA clones encoding two members of this family from chicken, interferon consensus sequence-binding protein (ICSBP) and IRF-1. The predicted chicken ICSBP and IRF-1 proteins show high levels of sequence similarity to their corresponding human and mouse counterparts. Sequence identities in the putative DNA-binding domains of chicken and human ICSBP and IRF-1 were 97% and 89%, respectively, whereas the C-terminal regions showed identities of 64% and 51%; sequence relationships with mouse ICSBP and IRF-1 are very similar. Chicken ICSBP was found to be expressed in several embryonic tissues, and both chicken IRF-1 and ICSBP were strongly induced in chicken fibroblasts by IFN treatment, supporting the involvement of these factors in IFN-regulated gene expression. The presence of proteins homologous to mammalian IRF family members, together with earlier observations on the occurrence of functionally homologous IFN-responsive elements in chicken and mammalian genes, highlights the conservation of transcriptional mechanisms in the IFN system, a finding that contrasts with the extensive sequence and functional divergence of the IFNs. Images Fig. 3 Fig. 4 Fig. 5 PMID:7536924

  6. New mutations in DYNC2H1 and WDR60 genes revealed by whole-exome sequencing in two unrelated Sardinian families with Jeune asphyxiating thoracic dystrophy.

    PubMed

    Cossu, Carla; Incani, Federica; Serra, Maria Luisa; Coiana, Alessandra; Crisponi, Giangiorgio; Boccone, Loredana; Rosatelli, Maria Cristina

    2016-04-01

    Jeune asphyxiating thoracic dystrophy (JATD; Jeune syndrome, MIM 208500) is a rare autosomal recessive chondrodysplasia, phenotypically overlapping with short-rib polydactyly syndromes (SRPS). JATD typical hallmarks include skeletal abnormalities such as narrow chest, shortened ribs, limbs shortened bones, extra fingers and toes (polydactyly), as well as extraskeletal manifestations (renal, liver and retinal disease). To date, disease-causing mutations have been found in several genes, highlighting a marked genetic heterogeneity that prevents a molecular diagnosis of the disease in most families. Here, we report the results of whole-exome sequencing (WES) carried out in four JATD cases, belonging to three unrelated families of Sardinian origin. The exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome. PMID:26874042

  7. Newborn brain event-related potentials revealing atypical processing of sound frequency and the subsequent association with later literacy skills in children with familial dyslexia.

    PubMed

    Leppänen, Paavo H T; Hämäläinen, Jarmo A; Salminen, Hanne K; Eklund, Kenneth M; Guttorm, Tomi K; Lohvansuu, Kaisa; Puolakanaho, Anne; Lyytinen, Heikki

    2010-01-01

    The role played by an auditory-processing deficit in dyslexia has been debated for several decades. In a longitudinal study using brain event-related potentials (ERPs) we investigated 1) whether dyslexic children with familial risk background would show atypical pitch processing from birth and 2) how these newborn ERPs later relate to these same children's pre-reading cognitive skills and literacy outcomes. Auditory ERPs were measured at birth for tones varying in pitch and presented in an oddball paradigm (1100 Hz, 12%, and 1000 Hz, 88%). The brain responses of the typically reading control group children (TRC group, N=25) showed clear differentiation between the frequencies, while those of the group of reading disability with familial risk (RDFR, 8 children) and the group of typical readers with familial risk (TRFR, 14 children) did not differentiate between the tones. The ERPs of the latter two groups differed from those of the TRC group. However, the two risk groups also showed a differential hemispheric ERP pattern. Furthermore, newborn ERPs reflecting passive change detection were associated with phonological skills and letter knowledge prior to school age and with phoneme duration perception, reading speed (RS) and spelling accuracy in the 2nd grade of school. The early obligatory response was associated with more general pre-school language skills, as well as with RS and reading accuracy (RA). Results suggest that a proportion of dyslexic readers with familial risk background are affected by atypical auditory processing. This is already present at birth and also relates to pre-reading phonological processing and speech perception. These early differences in auditory processing could later affect phonological representations and reading development. However, atypical auditory processing is unlikely to suffice as a sole explanation for dyslexia but rather as one risk factor, dependent on the genetic profile of the child. PMID:20656284

  8. Combined Analysis of Genome Scans of Dutch and Finnish Families Reveals a Susceptibility Locus for High-Density Lipoprotein Cholesterol on Chromosome 16q

    PubMed Central

    Pajukanta, Päivi; Allayee, Hooman; Krass, Kelly L.; Kuraishy, Ali; Soro, Aino; Lilja, Heidi E.; Mar, Rebecca; Taskinen, Marja-Riitta; Nuotio, Ilpo; Laakso, Markku; Rotter, Jerome I.; de Bruin, Tjerk W. A.; Cantor, Rita M.; Lusis, Aldons J.; Peltonen, Leena

    2003-01-01

    Several genomewide screens have been performed to identify novel loci predisposing to unfavorable serum lipid levels and coronary heart disease (CHD). We hypothesized that the accumulating data of these screens in different study populations could be combined to verify which of the identified loci truly harbor susceptibility genes. The power of this strategy has recently been demonstrated with other complex diseases, such as inflammatory bowel disease and asthma. We assessed the largely unknown genetic background of CHD by investigating the most common dyslipidemia predisposing to CHD, familial combined hyperlipidemia (FCHL), affecting 1%–2% of Western populations and 10%–20% of families with premature CHD. To be able to perform a combined data analysis, we unified the diagnostic criteria for FCHL and its component traits and combined the data from two genomewide scans performed in two populations, the Finns and the Dutch. As a result of our pooled data analysis, we identified three chromosomal regions, on chromosomes 2p25.1, 9p23, and 16q24.1, exceeding the statistical significance level of a LOD score >2.0. The 2p25.1 region was detected for the FCHL trait, and the 9p23 and 16q24.1 regions were detected for the low high-density lipoprotein cholesterol (HDL-C) trait. In addition, the previously recognized 1q21 region also obtained additional support in the other study sample, when the triglyceride trait was used. Analysis of the 16q24.1 region resulted in a statistically significant LOD score of 3.6 when the data from Finnish families with low HDL-C were included in the analysis. To search for the underlying gene in the 16q24.1 region, we investigated a novel functional and positional candidate gene, helix/forkhead transcription factor (FOXC2), by sequencing and by genotyping of two single-nucleotide polymorphisms in the families. PMID:12638083

  9. UPF201 Archaeal Specific Family Members Reveal Structural Similarity to RNA-Binding Proteins but Low Likelyhood for RNA-Binding Function

    SciTech Connect

    Rao, K.; Burley, S; Swaminathan, S

    2008-01-01

    We have determined X-ray crystal structures of four members of an archaeal specific family of proteins of unknown function (UPF0201; Pfam classification: DUF54) to advance our understanding of the genetic repertoire of archaea. Despite low pairwise amino acid sequence identities (10-40%) and the absence of conserved sequence motifs, the three-dimensional structures of these proteins are remarkably similar to one another. Their common polypeptide chain fold, encompassing a five-stranded antiparallel {beta}-sheet and five {alpha}-helices, proved to be quite unexpectedly similar to that of the RRM-type RNA-binding domain of the ribosomal L5 protein, which is responsible for binding the 5S- rRNA. Structure-based sequence alignments enabled construction of a phylogenetic tree relating UPF0201 family members to L5 ribosomal proteins and other structurally similar RNA binding proteins, thereby expanding our understanding of the evolutionary purview of the RRM superfamily. Analyses of the surfaces of these newly determined UPF0201 structures suggest that they probably do not function as RNA binding proteins, and that this domain specific family of proteins has acquired a novel function in archaebacteria, which awaits experimental elucidation.

  10. UPF201 Archaeal Specific Family Members Reveals Structural Similarity to RNA-Binding Proteins but Low Likelihood for RNA-Binding Function

    SciTech Connect

    Rao, K.N.; Swaminathan, S.; Burley, S. K.

    2008-12-11

    We have determined X-ray crystal structures of four members of an archaeal specific family of proteins of unknown function (UPF0201; Pfam classification: DUF54) to advance our understanding of the genetic repertoire of archaea. Despite low pairwise amino acid sequence identities (10-40%) and the absence of conserved sequence motifs, the three-dimensional structures of these proteins are remarkably similar to one another. Their common polypeptide chain fold, encompassing a five-stranded antiparallel {beta}-sheet and five {alpha}-helices, proved to be quite unexpectedly similar to that of the RRM-type RNA-binding domain of the ribosomal L5 protein, which is responsible for binding the 5S- rRNA. Structure-based sequence alignments enabled construction of a phylogenetic tree relating UPF0201 family members to L5 ribosomal proteins and other structurally similar RNA binding proteins, thereby expanding our understanding of the evolutionary purview of the RRM superfamily. Analyses of the surfaces of these newly determined UPF0201 structures suggest that they probably do not function as RNA binding proteins, and that this domain specific family of proteins has acquired a novel function in archaebacteria, which awaits experimental elucidation.

  11. Genome-wide identification and comparative expression analysis reveal a rapid expansion and functional divergence of duplicated genes in the WRKY gene family of cabbage, Brassica oleracea var. capitata.

    PubMed

    Yao, Qiu-Yang; Xia, En-Hua; Liu, Fei-Hu; Gao, Li-Zhi

    2015-02-15

    WRKY transcription factors (TFs), one of the ten largest TF families in higher plants, play important roles in regulating plant development and resistance. To date, little is known about the WRKY TF family in Brassica oleracea. Recently, the completed genome sequence of cabbage (B. oleracea var. capitata) allows us to systematically analyze WRKY genes in this species. A total of 148 WRKY genes were characterized and classified into seven subgroups that belong to three major groups. Phylogenetic and synteny analyses revealed that the repertoire of cabbage WRKY genes was derived from a common ancestor shared with Arabidopsis thaliana. The B. oleracea WRKY genes were found to be preferentially retained after the whole-genome triplication (WGT) event in its recent ancestor, suggesting that the WGT event had largely contributed to a rapid expansion of the WRKY gene family in B. oleracea. The analysis of RNA-Seq data from various tissues (i.e., roots, stems, leaves, buds, flowers and siliques) revealed that most of the identified WRKY genes were positively expressed in cabbage, and a large portion of them exhibited patterns of differential and tissue-specific expression, demonstrating that these gene members might play essential roles in plant developmental processes. Comparative analysis of the expression level among duplicated genes showed that gene expression divergence was evidently presented among cabbage WRKY paralogs, indicating functional divergence of these duplicated WRKY genes. PMID:25481634

  12. Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model

    PubMed Central

    2016-01-01

    The underlying mechanisms that support robustness in neuronal networks are as yet unknown. However, recent studies provide evidence that neuronal networks are robust to natural variations, modulation, and environmental perturbations of parameters, such as maximal conductances of intrinsic membrane and synaptic currents. Here we sought a method for assessing robustness, which might easily be applied to large brute-force databases of model instances. Starting with groups of instances with appropriate activity (e.g., tonic spiking), our method classifies instances into much smaller subgroups, called families, in which all members vary only by the one parameter that defines the family. By analyzing the structures of families, we developed measures of robustness for activity type. Then, we applied these measures to our previously developed model database, HCO-db, of a two-neuron half-center oscillator (HCO), a neuronal microcircuit from the leech heartbeat central pattern generator where the appropriate activity type is alternating bursting. In HCO-db, the maximal conductances of five intrinsic and two synaptic currents were varied over eight values (leak reversal potential also varied, five values). We focused on how variations of particular conductance parameters maintain normal alternating bursting activity while still allowing for functional modulation of period and spike frequency. We explored the trade-off between robustness of activity type and desirable change in activity characteristics when intrinsic conductances are altered and identified the hyperpolarization-activated (h) current as an ideal target for modulation. We also identified ensembles of model instances that closely approximate physiological activity and can be used in future modeling studies. PMID:27595135

  13. Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model.

    PubMed

    Doloc-Mihu, Anca; Calabrese, Ronald L

    2016-01-01

    The underlying mechanisms that support robustness in neuronal networks are as yet unknown. However, recent studies provide evidence that neuronal networks are robust to natural variations, modulation, and environmental perturbations of parameters, such as maximal conductances of intrinsic membrane and synaptic currents. Here we sought a method for assessing robustness, which might easily be applied to large brute-force databases of model instances. Starting with groups of instances with appropriate activity (e.g., tonic spiking), our method classifies instances into much smaller subgroups, called families, in which all members vary only by the one parameter that defines the family. By analyzing the structures of families, we developed measures of robustness for activity type. Then, we applied these measures to our previously developed model database, HCO-db, of a two-neuron half-center oscillator (HCO), a neuronal microcircuit from the leech heartbeat central pattern generator where the appropriate activity type is alternating bursting. In HCO-db, the maximal conductances of five intrinsic and two synaptic currents were varied over eight values (leak reversal potential also varied, five values). We focused on how variations of particular conductance parameters maintain normal alternating bursting activity while still allowing for functional modulation of period and spike frequency. We explored the trade-off between robustness of activity type and desirable change in activity characteristics when intrinsic conductances are altered and identified the hyperpolarization-activated (h) current as an ideal target for modulation. We also identified ensembles of model instances that closely approximate physiological activity and can be used in future modeling studies. PMID:27595135

  14. Characterization of DNA Binding Sites of RokB, a ROK-Family Regulator from Streptomyces coelicolor Reveals the RokB Regulon

    PubMed Central

    Bekiesch, Paulina; Forchhammer, Karl; Apel, Alexander Kristian

    2016-01-01

    ROK-family proteins have been described to act either as sugar kinases or as transcriptional regulators. Few ROK-family regulators have been characterized so far and most of them are involved in carbon catabolite repression. RokB (Sco6115) has originally been identified in a DNA-affinity capturing approach as a possible regulator of the heterologously expressed novobiocin biosynthetic gene cluster in Streptomyces coelicolor M512. Interestingly, both, the rokB deletion mutants as well as its overexpressing mutants showed significantly reduced novobiocin production in the host strain S.coelicolor M512. We identified the DNA-binding site for RokB in the promoter region of the novobiocin biosynthetic genes novH-novW. It overlaps with the novH start codon which may explain the reduction of novobiocin production caused by overexpression of rokB. Bioinformatic screening coupled with surface plasmon resonance based interaction studies resulted in the discovery of five RokB binding sites within the genome of S. coelicolor. Using the genomic binding sites, a consensus motif for RokB was calculated, which differs slightly from previously determined binding motifs for ROK-family regulators. The annotations of the possible members of the so defined RokB regulon gave hints that RokB might be involved in amino acid metabolism and transport. This hypothesis was supported by feeding experiments with casamino acids and L-tyrosine, which could also explain the reduced novobiocin production in the deletion mutants. PMID:27145180

  15. A Ranking-Based Meta-Analysis Reveals Let-7 Family as a Meta-Signature for Grade Classification in Breast Cancer

    PubMed Central

    Oztemur, Yasemin; Bekmez, Tufan; Aydos, Alp; Yulug, Isik G.; Bozkurt, Betul; Dedeoglu, Bala Gur

    2015-01-01

    Breast cancer is one of the most important causes of cancer-related deaths worldwide in women. In addition to gene expression studies, the progressing work in the miRNA area including miRNA microarray studies, brings new aspects to the research on the cancer development and progression. Microarray technology has been widely used to find new biomarkers in research and many transcriptomic microarray studies are available in public databases. In this study, the breast cancer miRNA and mRNA microarray studies were collected according to the availability of their data and clinical information, and combined by a newly developed ranking-based meta-analysis approach to find out candidate miRNA biomarkers (meta-miRNAs) that classify breast cancers according to their grades and explain the relation between miRNAs and mRNAs. This approach provided meta-miRNAs specific to breast cancer grades, pointing out let-7 family members as grade classifiers. The qRT-PCR studies performed with independent breast tumors confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The concordance between the meta-mRNAs and miRNA target genes specific to tumor grade (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis results showed that most of the let-7 family miRNA targets, and also common genes, were significantly taking part in cancer-related pathways. The qRT-PCR studies, together with bioinformatic analyses, confirmed the results of meta-analysis approach, which is dynamic and allows combining datasets from different platforms. PMID:25978727

  16. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci.

    PubMed

    Najmabadi, Hossein; Motazacker, Mohammad Mahdi; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Chen, Wei; Behjati, Farkhondeh; Hadavi, Valeh; Nieh, Sahar Esmaeeli; Abedini, Seyedeh Sedigheh; Vazifehmand, Reza; Firouzabadi, Saghar Ghasemi; Jamali, Payman; Falah, Masoumeh; Seifati, Seyed Morteza; Grüters, Annette; Lenzner, Steffen; Jensen, Lars R; Rüschendorf, Franz; Kuss, Andreas W; Ropers, H Hilger

    2007-03-01

    Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. PMID:17120046

  17. Expression of cellulose synthase-like (Csl) genes in insect cells reveals that CslA family members encode mannan synthases

    PubMed Central

    Liepman, Aaron H.; Wilkerson, Curtis G.; Keegstra, Kenneth

    2005-01-01

    Glucuronoarabinoxylan, xyloglucan, and galactomannan are noncellulosic polysaccharides found in plant cell walls. All consist of β-linked glycan backbones substituted with sugar side chains. Although considerable progress has been made in characterizing the structure of these polysaccharides, little is known about the biosynthetic enzymes that produce them. Cellulose synthase-like (Csl) genes are hypothesized to encode Golgi-localized β-glycan synthases that polymerize the backbones of noncellulosic polysaccharides. To investigate this hypothesis, we used heterologous expression in Drosophila Schneider 2 (S2) cells to systematically analyze the functions of the gene products of a group of Csl genes from Arabidopsis and rice (Oryza sativa L.), including members from five Csl gene families (CslA, CslC, CslD, CslE, and CslH). Our analyses indicate that several members of the CslA gene family encode β-mannan synthases. Recombinant CslA proteins produce β-linked mannan polymers when supplied GDP-mannose. The same proteins can produce β-linked glucomannan heteropolymers when supplied both GDP-mannose and GDP-glucose. One CslA protein also produced β-linked glucan polymers when supplied GDP-glucose alone. Heterologous expression studies of additional candidate glycan synthases in insect cells or other systems may help identify other noncellulosic polysaccharide biosynthetic enzymes. PMID:15647349

  18. Genome-scale analysis of the cotton KCS gene family revealed a binary mode of action for gibberellin A regulated fiber growth.

    PubMed

    Xiao, Guang-Hui; Wang, Kun; Huang, Gai; Zhu, Yu-Xian

    2016-06-01

    Production of β-ketoacyl-CoA, which is catalyzed by 3-ketoacyl-CoA synthase (KCS), is the first step in very long chain fatty acid (VLCFA) biosynthesis. Here we identified 58 KCS genes from Gossypium hirsutum, 31 from G. arboreum and 33 from G. raimondii by searching the assembled cotton genomes. The gene family was divided into the plant-specific FAE1-type and the more general ELO-type. KCS transcripts were widely expressed and 32 of them showed distinct subgenome-specific expressions in one or more cotton tissues/organs studied. Six GhKCS genes rescued the lethality of elo2Δelo3Δ yeast double mutant, indicating that this gene family possesses diversified functions. Most KCS genes with GA-responsive elements (GAREs) in the promoters were significantly upregulated by gibberellin A3 (GA). Exogenous GA3 not only promoted fiber length, but also increased the thickness of cell walls significantly. GAREs present also in the promoters of several cellulose synthase (CesA) genes required for cell wall biosynthesis and they were all induced significantly by GA3 . Because GA treatment resulted in longer cotton fibers with thicker cell walls and higher dry weight per unit cell length, we suggest that it may regulate fiber elongation upstream of the VLCFA-ethylene pathway and also in the downstream steps towards cell wall synthesis. PMID:26399709

  19. Mutation analysis of the gene encoding Bruton`s tyrosine kinase in a family with a sporadic case of X-linked agammaglobulinemia reveals three female carriers

    SciTech Connect

    Hagemann, T.L.; Kwan, Sau-Ping; Assa`ad, A.H.

    1995-11-06

    Bruton`s tyrosine kinase (Btk) has been identified as the protein responsible for the primary immunodeficiency X-linked agammaglobulinemia (XLA). We and others have cloned the gene for Btk and recently reported the genomic organization. Nineteen exons were positioned within the 37 kb gene. With the sequence data derived from our genomic map, we have designed a PCR based assay to directly identify mutations of the Btk gene in germline DNA of patients with XLA. In this report, the assay was used to analyze a family with a sporadic case of XLA to determine if other female relatives carry the disease. A four base-pair deletion was found in the DNA of the affected boy and was further traced through three generations. With the direct identification of the mutations responsible for XLA, we can now diagnose conclusively the disease and identify the immunologically normal female carriers. This same technique can easily be applied to prenatal diagnosis in families where the mutation can be identified. 34 refs., 3 figs.

  20. Characterization of multigene families in the micronuclear genome of Paramecium tetraurelia reveals a germline specific sequence in an intron of a centrin gene.

    PubMed Central

    Vayssié, L; Sperling, L; Madeddu, L

    1997-01-01

    In Paramecium, as in other ciliates, the transcriptionally active macronucleus is derived from the germline micronucleus by programmed DNA rearrangements, which include the precise excision of thousands of germline-specific sequences (internal eliminated sequences, IESs). We report the characterization of micronuclear versions of genes encoding Paramecium secretory granule proteins (trichocyst matrix proteins, TMPs) and Paramecium centrins. TMP and centrin multigene families, previously studied in the macronuclear genome, consist of genes that are co-expressed to provide mixtures of related polypeptides that co-assemble to form respectively the crystalline trichocyst matrix and the infraciliary lattice, a contractile cytoskeletal network. We present evidence that TMP and centrin genes identified in the macronucleus are also present in the micronucleus, ruling out the possibility that these novel multigene families are generated by somatic rearrangements during macronuclear development. No IESs were found in TMP genes, however, four IESs in or near germline centrin genes were characterized. The only intragenic IES is 75 bp in size, interrupts a 29 bp intron and is absent from at least one other closely related centrin gene. This is the first report of an IES in an intron in Paramecium. PMID:9023115

  1. Evolutionary dynamics and biogeography of Musaceae reveal a correlation between the diversification of the banana family and the geological and climatic history of Southeast Asia.

    PubMed

    Janssens, Steven B; Vandelook, Filip; De Langhe, Edmond; Verstraete, Brecht; Smets, Erik; Vandenhouwe, Ines; Swennen, Rony

    2016-06-01

    Tropical Southeast Asia, which harbors most of the Musaceae biodiversity, is one of the most species-rich regions in the world. Its high degree of endemism is shaped by the region's tectonic and climatic history, with large differences between northern Indo-Burma and the Malayan Archipelago. Here, we aim to find a link between the diversification and biogeography of Musaceae and geological history of the Southeast Asian subcontinent. The Musaceae family (including five Ensete, 45 Musa and one Musella species) was dated using a large phylogenetic framework encompassing 163 species from all Zingiberales families. Evolutionary patterns within Musaceae were inferred using ancestral area reconstruction and diversification rate analyses. All three Musaceae genera - Ensete, Musa and Musella - originated in northern Indo-Burma during the early Eocene. Musa species dispersed from 'northwest to southeast' into Southeast Asia with only few back-dispersals towards northern Indo-Burma. Musaceae colonization events of the Malayan Archipelago subcontinent are clearly linked to the geological and climatic history of the region. Musa species were only able to colonize the region east of Wallace's line after the availability of emergent land from the late Miocene onwards. PMID:26832306

  2. Expression of human Cfdp1 gene in Drosophila reveals new insights into the function of the evolutionarily conserved BCNT protein family

    PubMed Central

    Messina, Giovanni; Atterrato, Maria Teresa; Fanti, Laura; Giordano, Ennio; Dimitri, Patrizio

    2016-01-01

    The Bucentaur (BCNT) protein family is widely distributed in eukaryotes and is characterized by a highly conserved C-terminal domain. This family was identified two decades ago in ruminants, but its role(s) remained largely unknown. Investigating cellular functions and mechanism of action of BCNT proteins is challenging, because they have been implicated in human craniofacial development. Recently, we found that YETI, the D. melanogaster BCNT, is a chromatin factor that participates to H2A.V deposition. Here we report the effects of in vivo expression of CFDP1, the human BCNT protein, in Drosophila melanogaster. We show that CFDP1, similarly to YETI, binds to chromatin and its expression results in a wide range of abnormalities highly reminiscent of those observed in Yeti null mutants. This indicates that CFDP1 expressed in flies behaves in a dominant negative fashion disrupting the YETI function. Moreover, GST pull-down provides evidence indicating that 1) both YETI and CFDP1 undergo homodimerization and 2) YETI and CFDP1 physically interact each other by forming inactive heterodimers that would trigger the observed dominant-negative effect. Overall, our findings highlight unanticipated evidences suggesting that homodimerization mediated by the BCNT domain is integral to the chromatin functions of BCNT proteins. PMID:27151176

  3. Whole-exome sequencing reveals a recurrent mutation in the cathepsin C gene that causes Papillon-Lefevre syndrome in a Saudi family.

    PubMed

    Alkhiary, Yaser Mohammad; Jelani, Musharraf; Almramhi, Mona Mohammad; Mohamoud, Hussein Sheikh Ali; Al-Rehaili, Rayan; Al-Zahrani, Hams Saeed; Serafi, Rehab; Yang, Huanming; Al-Aama, Jumana Yousuf

    2016-09-01

    Papillon-Lefevre syndrome (PALS) is a rare, autosomal recessive disorder characterized by periodontitis and hyperkeratosis over the palms and soles. Mutations in the cathepsin C gene (CTSC) have been recognized as the cause of PALS since the late 1990s. More than 75 mutations in CTSC have been identified, and phenotypic variability between different mutations has been described. Next generation sequencing is widely used for efficient molecular diagnostics in various clinical practices. Here we investigated a large consanguineous Saudi family with four affected and four unaffected individuals. All of the affected individuals suffered from hyperkeratosis over the palms and soles and had anomalies of both primary and secondary dentition. For molecular diagnostics, we combined whole-exome sequencing and genome-wide homozygosity mapping procedures, and identified a recurrent homozygous missense mutation (c.899G>A; p.Gly300Asp) in exon 7 of CTSC. Validation of all eight family members by Sanger sequencing confirmed co-segregation of the pathogenic variant (c.899G>A) with the disease phenotype. This is the first report of whole-exome sequencing performed for molecular diagnosis of PALS in Saudi Arabia. Our findings provide further insights into the genotype-phenotype correlation of CTSC pathogenicity in PALS. PMID:27579005

  4. Expression of human Cfdp1 gene in Drosophila reveals new insights into the function of the evolutionarily conserved BCNT protein family.

    PubMed

    Messina, Giovanni; Atterrato, Maria Teresa; Fanti, Laura; Giordano, Ennio; Dimitri, Patrizio

    2016-01-01

    The Bucentaur (BCNT) protein family is widely distributed in eukaryotes and is characterized by a highly conserved C-terminal domain. This family was identified two decades ago in ruminants, but its role(s) remained largely unknown. Investigating cellular functions and mechanism of action of BCNT proteins is challenging, because they have been implicated in human craniofacial development. Recently, we found that YETI, the D. melanogaster BCNT, is a chromatin factor that participates to H2A.V deposition. Here we report the effects of in vivo expression of CFDP1, the human BCNT protein, in Drosophila melanogaster. We show that CFDP1, similarly to YETI, binds to chromatin and its expression results in a wide range of abnormalities highly reminiscent of those observed in Yeti null mutants. This indicates that CFDP1 expressed in flies behaves in a dominant negative fashion disrupting the YETI function. Moreover, GST pull-down provides evidence indicating that 1) both YETI and CFDP1 undergo homodimerization and 2) YETI and CFDP1 physically interact each other by forming inactive heterodimers that would trigger the observed dominant-negative effect. Overall, our findings highlight unanticipated evidences suggesting that homodimerization mediated by the BCNT domain is integral to the chromatin functions of BCNT proteins. PMID:27151176

  5. Family Preservation & Family Functioning.

    ERIC Educational Resources Information Center

    McCroskey, Jacquelyn; Meezan, William

    This book reports a study of the outcomes of home-based family preservation services for abusive and neglectful families in Los Angeles County. Using the Family Assessment Form, the research project evaluated services provided by two voluntary agencies, and focused on changes in family functioning between the opening and closing of services during…

  6. TAC3 and TACR3 Mutations in Familial Hypogonadotropic Hypogonadism Reveal a Key Role for Neurokinin B in the Central Control of Reproduction

    PubMed Central

    Guclu, Metin; Yalin, Ayse Serap; Kotan, L. Damla; Porter, Keith M; Serin, Ayse; Mungan, Neslihan O; Cook, Joshua R; Imamoglu, Sazi; Akalin, N. Sema; Yuksel, Bilgin; O’Rahilly, Stephen; Semple, Robert K

    2015-01-01

    The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the post-pubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonatrophins, LH and FSH. We report four human pedigrees with severe congenital gonadotrophin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin1, a recently identified regulator of gonadotropin-releasing hormone secretion2. These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest novel approaches to the pharmacological control of human reproduction and sex hormone-related diseases. PMID:19079066

  7. Analysis of a four generation family reveals the widespread sequence-dependent maintenance of allelic DNA methylation in somatic and germ cells

    PubMed Central

    Tang, Aifa; Huang, Yi; Li, Zesong; Wan, Shengqing; Mou, Lisha; Yin, Guangliang; Li, Ning; Xie, Jun; Xia, Yudong; Li, Xianxin; Luo, Liya; Zhang, Junwen; Chen, Shen; Wu, Song; Sun, Jihua; Sun, Xiaojuan; Jiang, Zhimao; Chen, Jing; Li, Yingrui; Wang, Jian; Wang, Jun; Cai, Zhiming; Gui, Yaoting

    2016-01-01

    Differential methylation of the homologous chromosomes, a well-known mechanism leading to genomic imprinting and X-chromosome inactivation, is widely reported at the non-imprinted regions on autosomes. To evaluate the transgenerational DNA methylation patterns in human, we analyzed the DNA methylomes of somatic and germ cells in a four-generation family. We found that allelic asymmetry of DNA methylation was pervasive at the non-imprinted loci and was likely regulated by cis-acting genetic variants. We also observed that the allelic methylation patterns for the vast majority of the cis-regulated loci were shared between the somatic and germ cells from the same individual. These results demonstrated the interaction between genetic and epigenetic variations and suggested the possibility of widespread sequence-dependent transmission of DNA methylation during spermatogenesis. PMID:26758766

  8. Profiling of the Early Nitrogen Stress Response in the Diatom Phaeodactylum tricornutum Reveals a Novel Family of RING-Domain Transcription Factors1[OPEN

    PubMed Central

    Matthijs, Michiel; Fabris, Michele; Broos, Stefan; Vyverman, Wim

    2016-01-01

    Diatoms often inhabit highly variable habitats where they are confronted with a wide variety of stresses, frequently including starvation of nutrients such as nitrogen. In this study, the transcriptome of the model diatom Phaeodactylum tricornutum was profiled during the onset of nitrogen starvation by RNA sequencing, and overrepresented motifs were determined in promoters of genes that were early and strongly up-regulated during the nitrogen stress response. One of these motifs could be bound by a nitrogen starvation-inducible RING-domain protein termed RING-GAF-Gln-containing protein (RGQ1), which was shown to act as a transcription factor and belongs to a previously uncharacterized family that is conserved in heterokont algae. PMID:26582725

  9. A Comparative Metagenome Survey of the Fecal Microbiota of a Breast- and a Plant-Fed Asian Elephant Reveals an Unexpectedly High Diversity of Glycoside Hydrolase Family Enzymes

    PubMed Central

    Ilmberger, Nele; Güllert, Simon; Dannenberg, Joana; Rabausch, Ulrich; Torres, Jeremy; Wemheuer, Bernd; Alawi, Malik; Poehlein, Anja; Chow, Jennifer; Turaev, Dimitrij; Rattei, Thomas; Schmeisser, Christel; Salomon, Jesper; Olsen, Peter B.; Daniel, Rolf; Grundhoff, Adam; Borchert, Martin S.; Streit, Wolfgang R.

    2014-01-01

    A phylogenetic and metagenomic study of elephant feces samples (derived from a three-weeks-old and a six-years-old Asian elephant) was conducted in order to describe the microbiota inhabiting this large land-living animal. The microbial diversity was examined via 16S rRNA gene analysis. We generated more than 44,000 GS-FLX+454 reads for each animal. For the baby elephant, 380 operational taxonomic units (OTUs) were identified at 97% sequence identity level; in the six-years-old animal, close to 3,000 OTUs were identified, suggesting high microbial diversity in the older animal. In both animals most OTUs belonged to Bacteroidetes and Firmicutes. Additionally, for the baby elephant a high number of Proteobacteria was detected. A metagenomic sequencing approach using Illumina technology resulted in the generation of 1.1 Gbp assembled DNA in contigs with a maximum size of 0.6 Mbp. A KEGG pathway analysis suggested high metabolic diversity regarding the use of polymers and aromatic and non-aromatic compounds. In line with the high phylogenetic diversity, a surprising and not previously described biodiversity of glycoside hydrolase (GH) genes was found. Enzymes of 84 GH families were detected. Polysaccharide utilization loci (PULs), which are found in Bacteroidetes, were highly abundant in the dataset; some of these comprised cellulase genes. Furthermore the highest coverage for GH5 and GH9 family enzymes was detected for Bacteroidetes, suggesting that bacteria of this phylum are mainly responsible for the degradation of cellulose in the Asian elephant. Altogether, this study delivers insight into the biomass conversion by one of the largest plant-fed and land-living animals. PMID:25208077

  10. A proteomic approach reveals transient association of reticulocalbin-3, a novel member of the CREC family, with the precursor of subtilisin-like proprotein convertase, PACE4

    PubMed Central

    Tsuji, Akihiko; Kikuchi, Yayoi; Sato, Yukimi; Koide, Shizuyo; Yuasa, Keizo; Nagahama, Masami; Matsuda, Yoshiko

    2006-01-01

    SPCs (subtilisin-like proprotein convertases) are a family of seven structurally related serine endoproteases that are involved in the proteolytic activation of proproteins. In an effort to examine the substrate protein for PACE4 (paired basic amino-acid-cleaving enzyme-4), an SPC, a potent protein inhibitor of PACE4, an α1-antitrypsin RVRR (Arg-Val-Arg-Arg) variant, was expressed in GH4C1 cells. Ectopic expression of the RVRR variant caused accumulation of the 48 kDa protein in cells. Sequence analysis indicates that the 48 kDa protein is a putative Ca2+-binding protein, RCN-3 (reticulocalbin-3), which had previously been predicted by bioinformatic analysis of cDNA from the human hypothalamus. RCN-3 is a member of the CREC (Cab45/reticulocalbin/ERC45/calumenin) family of multiple EF-hand Ca2+-binding proteins localized to the secretory pathway. The most interesting feature of the RCN-3 sequence is the presence of five Arg-Xaa-Xaa-Arg motifs, which represents the target sequence of SPCs. Biosynthetic studies showed that RCN-3 is transiently associated with proPACE4, but not with mature PACE4. Inhibition of PACE4 maturation by a Ca2+ ionophore resulted in accumulation of the proPACE4–RCN-3 complex in cells. Furthermore, autoactivation and secretion of PACE4 was increased upon co-expression with RCN-3. Our findings suggest that selective and transient association of RCN-3 with the precursor of PACE4 plays an important role in the biosynthesis of PACE4. PMID:16433634

  11. Crystal structure of decameric fructose-6-phosphate aldolase from Escherichia coli reveals inter-subunit helix swapping as a structural basis for assembly differences in the transaldolase family.

    PubMed

    Thorell, Stina; Schürmann, Melanie; Sprenger, Georg A; Schneider, Gunter

    2002-05-24

    Fructose-6-phosphate aldolase from Escherichia coli is a member of a small enzyme subfamily (MipB/TalC family) that belongs to the class I aldolases. The three-dimensional structure of this enzyme has been determined at 1.93 A resolution by single isomorphous replacement and tenfold non-crystallographic symmetry averaging and refined to an R-factor of 19.9% (R(free) 21.3%). The subunit folds into an alpha/beta barrel, with the catalytic lysine residue on barrel strand beta 4. It is very similar in overall structure to that of bacterial and mammalian transaldolases, although more compact due to extensive deletions of additional secondary structural elements. The enzyme forms a decamer of identical subunits with point group symmetry 52. Five subunits are arranged as a pentamer, and two ring-like pentamers pack like a doughnut to form the decamer. A major interaction within the pentamer is through the C-terminal helix from one monomer, which runs across the active site of the neighbouring subunit. In classical transaldolases, this helix folds back and covers the active site of the same subunit and is involved in dimer formation. The inter-subunit helix swapping appears to be a major determinant for the formation of pentamers rather than dimers while at the same time preserving importing interactions of this helix with the active site of the enzyme. The active site lysine residue is covalently modified, by forming a carbinolamine with glyceraldehyde from the crystallisation mixture. The catalytic machinery is very similar to that of transaldolase, which together with the overall structural similarity suggests that enzymes of the MipB/TALC subfamily are evolutionary related to the transaldolase family. PMID:12051943

  12. Regulation of human RNase-L by the miR-29 family reveals a novel oncogenic role in chronic myelogenous leukemia.

    PubMed

    Lee, Teresa Y; Ezelle, Heather J; Venkataraman, Thiagarajan; Lapidus, Rena G; Scheibner, Kara A; Hassel, Bret A

    2013-01-01

    The endoribonuclease RNase-L is the terminal component of an interferon-regulated RNA decay pathway known as the 2'-5'-oligoadenylate (2-5A) system, whose established functions include antimicrobial and tumor suppressive activities. RNase-L activity requires binding of the small molecule 2-5A, leading to RNase-L dimerization and cleavage of single-stranded RNA. RNase-L expression is controlled post-transcriptionally by its 3'-untranslated region (3' UTR), which exerts a strong negative effect on RNase-L levels. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress expression of target genes by binding to regions of complementarity often in the 3' UTR. The miR-29 family acts as a tumor suppressor in several cancers, including acute and chronic myelogenous leukemia (CML), and has many oncogenic targets. We report that the miR-29 family represses RNase-L protein expression across several cell types. Using a luciferase reporter, we showed that miR-29 acts via 4 target sites within the RNASEL 3' UTR. Mutation of all sites is required for abrogation of miR-29 repression. In light of the reported tumor suppressive role of miR-29 in K562 CML cells and miR-29 repression of RNase-L in these cells, we generated K562 cells with stable RNase-L knockdown and demonstrated that loss of RNase-L inhibits proliferation in vitro as well as tumor growth in a xenograft model. Our findings identify a previously unknown miRNA regulator of RNase-L expression and support a novel oncogenic role for RNase-L in CML and potentially other hematopoietic malignancies. PMID:23113544

  13. Crystal Structures of Type-II Inositol Polyphosphate 5-Phosphatase INPP5B with Synthetic Inositol Polyphosphate Surrogates Reveal New Mechanistic Insights for the Inositol 5-Phosphatase Family.

    PubMed

    Mills, Stephen J; Silvander, Camilla; Cozier, Gyles; Trésaugues, Lionel; Nordlund, Pär; Potter, Barry V L

    2016-03-01

    The inositol polyphosphate 5-phosphatase INPP5B hydrolyzes the 5-phosphate group from water- and lipid-soluble signaling messengers. Two synthetic benzene and biphenyl polyphosphates (BzP/BiPhPs), simplified surrogates of inositol phosphates and phospholipid headgroups, were identified by thermodynamic studies as potent INPP5B ligands. The X-ray structure of the complex between INPP5B and biphenyl 3,3',4,4',5,5'-hexakisphosphate [BiPh(3,3',4,4',5,5')P6, IC50 5.5 μM] was determined at 2.89 Å resolution. One inhibitor pole locates in the phospholipid headgroup binding site and the second solvent-exposed ring binds to the His-Tag of another INPP5B molecule, while a molecule of inorganic phosphate is also present in the active site. Benzene 1,2,3-trisphosphate [Bz(1,2,3)P3] [one ring of BiPh(3,3',4,4',5,5')P6] inhibits INPP5B ca. 6-fold less potently. Co-crystallization with benzene 1,2,4,5-tetrakisphosphate [Bz(1,2,4,5)P4, IC50 = 6.3 μM] yielded a structure refined at 2.9 Å resolution. Conserved residues among the 5-phosphatase family mediate interactions with Bz(1,2,4,5)P4 and BiPh(3,3',4,4',5,5')P6 similar to those with the polar groups present in positions 1, 4, 5, and 6 on the inositol ring of the substrate. 5-Phosphatase specificity most likely resides in the variable zone located close to the 2- and 3-positions of the inositol ring, offering insights to inhibitor design. We propose that the inorganic phosphate present in the INPP5B-BiPh(3,3',4,4',5,5')P6 complex mimics the postcleavage substrate 5-phosphate released by INPP5B in the catalytic site, allowing elucidation of two new key features in the catalytic mechanism proposed for the family of phosphoinositide 5-phosphatases: first, the involvement of the conserved Arg-451 in the interaction with the 5-phosphate and second, identification of the water molecule that initiates 5-phosphate hydrolysis. Our model also has implications for the proposed "moving metal" mechanism. PMID:26854536

  14. Crystal Structures of Type-II Inositol Polyphosphate 5-Phosphatase INPP5B with Synthetic Inositol Polyphosphate Surrogates Reveal New Mechanistic Insights for the Inositol 5-Phosphatase Family

    PubMed Central

    2016-01-01

    The inositol polyphosphate 5-phosphatase INPP5B hydrolyzes the 5-phosphate group from water- and lipid-soluble signaling messengers. Two synthetic benzene and biphenyl polyphosphates (BzP/BiPhPs), simplified surrogates of inositol phosphates and phospholipid headgroups, were identified by thermodynamic studies as potent INPP5B ligands. The X-ray structure of the complex between INPP5B and biphenyl 3,3′,4,4′,5,5′-hexakisphosphate [BiPh(3,3′,4,4′,5,5′)P6, IC50 5.5 μM] was determined at 2.89 Å resolution. One inhibitor pole locates in the phospholipid headgroup binding site and the second solvent-exposed ring binds to the His-Tag of another INPP5B molecule, while a molecule of inorganic phosphate is also present in the active site. Benzene 1,2,3-trisphosphate [Bz(1,2,3)P3] [one ring of BiPh(3,3′,4,4′,5,5′)P6] inhibits INPP5B ca. 6-fold less potently. Co-crystallization with benzene 1,2,4,5-tetrakisphosphate [Bz(1,2,4,5)P4, IC50 = 6.3 μM] yielded a structure refined at 2.9 Å resolution. Conserved residues among the 5-phosphatase family mediate interactions with Bz(1,2,4,5)P4 and BiPh(3,3′,4,4′,5,5′)P6 similar to those with the polar groups present in positions 1, 4, 5, and 6 on the inositol ring of the substrate. 5-Phosphatase specificity most likely resides in the variable zone located close to the 2- and 3-positions of the inositol ring, offering insights to inhibitor design. We propose that the inorganic phosphate present in the INPP5B–BiPh(3,3′,4,4′,5,5′)P6 complex mimics the postcleavage substrate 5-phosphate released by INPP5B in the catalytic site, allowing elucidation of two new key features in the catalytic mechanism proposed for the family of phosphoinositide 5-phosphatases: first, the involvement of the conserved Arg-451 in the interaction with the 5-phosphate and second, identification of the water molecule that initiates 5-phosphate hydrolysis. Our model also has implications for the proposed “moving metal” mechanism

  15. Genome-Wide Analysis of the Fasciclin-Like Arabinogalactan Protein Gene Family Reveals Differential Expression Patterns, Localization, and Salt Stress Response in Populus

    PubMed Central

    Zang, Lina; Zheng, Tangchun; Chu, Yanguang; Ding, Changjun; Zhang, Weixi; Huang, Qinjun; Su, Xiaohua

    2015-01-01

    Fasciclin-like arabinogalactan proteins (FLAs) are a subclass of arabinogalactan proteins (AGPs) involved in plant growth, development and response to abiotic stress. Although many studies have been performed to identify molecular functions of individual family members, little information is available on genome-wide identification and characterization of FLAs in the genus Populus. Based on genome-wide analysis, we have identified 35 Populus FLAs which were distributed on 16 chromosomes and phylogenetically clustered into four major groups. Gene structure and motif composition were relatively conserved in each group. All the members contained N-terminal signal peptide, 23 of which included predicted glycosylphosphatidylinositol (GPI) modification sites and were anchored to plasma membranes. Subcellular localization analysis showed that PtrFLA2/20/26 were localized in cell membrane and cytoplasm of protoplasts from Populus stem-differentiating xylem. The Ka/Ks ratios showed that purifying selection has played a leading role in the long-term evolutionary period which greatly maintained the function of this family. The expression profiles showed that 32 PtrFLAs were differentially expressed in four tissues at four seasons based on publicly available microarray data. 18 FLAs were further verified with qRT-PCR in different tissues, which indicated that PtrFLA1/2/3/7/11/12/20/21/22/24/26/30 were significantly expressed in male and female flowers, suggesting close correlations with the reproductive development. In addition, PtrFLA1/9/10/11/17/21/23/24/26/28 were highly expressed in the stems and differentiating xylem, which may be involved in stem development. To determine salt response of FLAs, qRT-PCR was performed to analyze the expression of 18 genes under salinity stress across two time points. Results demonstrated that all the 18 FLAs were expressed in root tissues; especially, PtrFLA2/12/20/21/24/30 were significantly induced at different time points. In summary

  16. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    PubMed Central

    Milano, Teresa

    2016-01-01

    The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH) architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average) that is homologous to fold type-I pyridoxal 5′-phosphate (PLP) dependent enzymes like aspartate aminotransferase (AAT). These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs). Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups. PMID:27446613

  17. Comparative analysis of the Dicer-like gene family reveals loss of miR162 target site in SmDCL1 from Salvia miltiorrhiza

    PubMed Central

    Shao, Fenjuan; Qiu, Deyou; Lu, Shanfa

    2015-01-01

    DCL1, the core component for miRNA biogenesis, is itself regulated by miR162 in Arabidopsis. MiRNA-mediated feedback regulation of AtDCL1 is important to maintain the proper level of DCL1 transcripts. However, it is unknown whether the miRNA-mediated regulation of DCL1 is conserved among plants. We analyzed the SmDCL gene family in Salvia miltiorrhiza, an emerging model plant for Traditional Chinese Medicine (TCM) studies, using a comprehensive approach integrating genome-wide prediction, molecular cloning, gene expression profiling, and posttranscriptional regulation analysis. A total of five SmDCLs were identified. Comparative analysis of SmDCLs and AtDCLs showed an apparent enlargement of SmDCL introns in S. miltiorrhiza. The absence of miR162 in S. miltiorrhiza and the loss of miR162 target site in SmDCL1 were unexpectedly found. Further analysis showed that the miR162 target site was not present in DCL1 from ancient plants and was gained during plant evolution. The gained miR162 target site might be lost in a few modern plants through nucleotide mutations. Our results provide evidence for the gain and loss of miR162 and its target sites in Dicer-like genes during evolution. The data is useful for understanding the evolution of miRNA-mediated feedback regulation of DCLs in plants. PMID:25970825

  18. Familial Dysautonomia (FD) Human Embryonic Stem Cell Derived PNS Neurons Reveal that Synaptic Vesicular and Neuronal Transport Genes Are Directly or Indirectly Affected by IKBKAP Downregulation

    PubMed Central

    Kantor, Gal; Cheishvili, David; Even, Aviel; Birger, Anastasya; Turetsky, Tikva; Gil, Yaniv; Even-Ram, Sharona; Aizenman, Einat; Bashir, Nibal; Maayan, Channa; Razin, Aharon; Reubinoff, Benjamim E.; Weil, Miguel

    2015-01-01

    A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we found new molecular insights for the IKAP role and the impact of the FD mutation in the human PNS lineage by using a novel and unique human embryonic stem cell (hESC) line homozygous to the FD mutation originated by pre implantation genetic diagnosis (PGD) analysis. We found that IKBKAP downregulation during PNS differentiation affects normal migration in FD-hESC derived neural crest cells (NCC) while at later stages the PNS neurons show reduced intracellular colocalization between vesicular proteins and IKAP. Comparative wide transcriptome analysis of FD and WT hESC-derived neurons together with the analysis of human brains from FD and WT 12 weeks old embryos and experimental validation of the results confirmed that synaptic vesicular and neuronal transport genes are directly or indirectly affected by IKBKAP downregulation in FD neurons. Moreover we show that kinetin (a drug that corrects IKBKAP alternative splicing) promotes the recovery of IKAP expression and these IKAP functional associated genes identified in the study. Altogether, these results support the view that IKAP might be a vesicular like protein that might be involved in neuronal transport in hESC derived PNS neurons. This function seems to be mostly affected in FD-hESC derived PNS neurons probably reflecting some PNS neuronal dysfunction observed in FD. PMID:26437462

  19. Analysis of the Fam181 gene family during mouse development reveals distinct strain-specific expression patterns, suggesting a role in nervous system development and function.

    PubMed

    Marks, Matthias; Pennimpede, Tracie; Lange, Lisette; Grote, Phillip; Herrmann, Bernhard G; Wittler, Lars

    2016-01-10

    During somitogenesis differential gene expression can be observed for so-called cyclic genes, which display expression changes with a periodicity of 120min in the mouse. In screens to identify novel cyclic genes in murine embryos, Fam181b was predicted to be an oscillating gene in the presomitic mesoderm (psm). This gene, and its closely related paralog Fam181a, belong to the thus far uncharacterized Fam181 gene family. Here we describe the expression of Fam181b and Fam181a during murine embryonic development. In addition, we confirm oscillation of Fam181b in the psm in-phase with targets of, and regulated by, Notch signaling. Fam181b expression in the psm, as well as in the lateral plate mesoderm, was found to be affected by genetic background. We show that Fam181a and b exhibit partially overlapping mRNA expression patterns, and encode for proteins containing highly-conserved motifs, which predominantly localize to the nucleus. A Fam181b loss-of-function model was generated and found to result in no obvious phenotype. PMID:26407640

  20. Comparative analysis of the Dicer-like gene family reveals loss of miR162 target site in SmDCL1 from Salvia miltiorrhiza.

    PubMed

    Shao, Fenjuan; Qiu, Deyou; Lu, Shanfa

    2015-01-01

    DCL1, the core component for miRNA biogenesis, is itself regulated by miR162 in Arabidopsis. MiRNA-mediated feedback regulation of AtDCL1 is important to maintain the proper level of DCL1 transcripts. However, it is unknown whether the miRNA-mediated regulation of DCL1 is conserved among plants. We analyzed the SmDCL gene family in Salvia miltiorrhiza, an emerging model plant for Traditional Chinese Medicine (TCM) studies, using a comprehensive approach integrating genome-wide prediction, molecular cloning, gene expression profiling, and posttranscriptional regulation analysis. A total of five SmDCLs were identified. Comparative analysis of SmDCLs and AtDCLs showed an apparent enlargement of SmDCL introns in S. miltiorrhiza. The absence of miR162 in S. miltiorrhiza and the loss of miR162 target site in SmDCL1 were unexpectedly found. Further analysis showed that the miR162 target site was not present in DCL1 from ancient plants and was gained during plant evolution. The gained miR162 target site might be lost in a few modern plants through nucleotide mutations. Our results provide evidence for the gain and loss of miR162 and its target sites in Dicer-like genes during evolution. The data is useful for understanding the evolution of miRNA-mediated feedback regulation of DCLs in plants. PMID:25970825

  1. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins.

    PubMed

    Milano, Teresa; Angelaccio, Sebastiana; Tramonti, Angela; Di Salvo, Martino Luigi; Contestabile, Roberto; Pascarella, Stefano

    2016-01-01

    The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH) architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average) that is homologous to fold type-I pyridoxal 5'-phosphate (PLP) dependent enzymes like aspartate aminotransferase (AAT). These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs). Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups. PMID:27446613

  2. Molecular characterization of WFS1 in an Iranian family with Wolfram syndrome reveals a novel frameshift mutation associated with early symptoms.

    PubMed

    Sobhani, Maryam; Tabatabaiefar, Mohammad Amin; Rajab, Asadollah; Kajbafzadeh, Abdol-Mohammad; Noori-Daloii, Mohammad Reza

    2013-10-10

    Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder that represents a likely source of childhood diabetes especially among countries in the consanguinity belt. The main responsible gene is WFS1 for which over one hundred mutations have been reported from different ethnic groups. The aim of this study was to identify the molecular etiology of WS and to perform a possible genotype-phenotype correlation in Iranian kindred. An Iranian family with two patients was clinically studied and WS was suspected. Genetic linkage analysis via 5 STR markers was carried out. For identification of mutations, DNA sequencing of WFS1 including all the exons, exon-intron boundaries and the promoter was performed. Linkage analysis indicated linkage to the WFS1 region. After DNA sequencing of WFS1, one novel pathogenic mutation, which causes frameshift alteration c.2177_2178insTCTTC (or c.2173_2177dupTCTTC) in exon eight, was found. The genotype-phenotype correlation analysis suggests that the presence of the homozygous mutation may be associated with early onset of disease symptoms. This study stresses the necessity of considering the molecular analysis of WFS1 in childhood diabetes with some symptoms of WS. PMID:23845777

  3. Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

    PubMed Central

    Scrivo, R; Conigliaro, P; Riccieri, V; Di Franco, M; Alessandri, C; Spadaro, A; Perricone, R; Valesini, G

    2015-01-01

    Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies. PMID:25178435

  4. Characterization of a Glycoside Hydrolase Family 27 α-Galactosidase from Pontibacter Reveals Its Novel Salt-Protease Tolerance and Transglycosylation Activity.

    PubMed

    Zhou, Junpei; Liu, Yu; Lu, Qian; Zhang, Rui; Wu, Qian; Li, Chunyan; Li, Junjun; Tang, Xianghua; Xu, Bo; Ding, Junmei; Han, Nanyu; Huang, Zunxi

    2016-03-23

    α-Galactosidases are of great interest in various applications. A glycoside hydrolase family 27 α-galactosidase was cloned from Pontibacter sp. harbored in a saline soil and expressed in Escherichia coli. The purified recombinant enzyme (rAgaAHJ8) was little or not affected by 3.5-30.0% (w/v) NaCl, 10.0-100.0 mM Pb(CH3COO)2, 10.0-60.0 mM ZnSO4, or 8.3-100.0 mg mL(-1) trypsin and by most metal ions and chemical reagents at 1.0 and 10.0 mM concentrations. The degree of synergy on enzymatic degradation of locust bean gum and guar gum by an endomannanase and rAgaAHJ8 was 1.22-1.54. In the presence of trypsin, the amount of reducing sugars released from soybean milk treated by rAgaAHJ8 was approximately 3.8-fold compared with that treated by a commercial α-galactosidase. rAgaAHJ8 showed transglycosylation activity when using sucrose, raffinose, and 3-methyl-1-butanol as the acceptors. Furthermore, potential factors for salt adaptation of the enzyme were presumed. PMID:26948050

  5. Identification and characterization of plant-specific NAC gene family in canola (Brassica napus L.) reveal novel members involved in cell death.

    PubMed

    Wang, Boya; Guo, Xiaohua; Wang, Chen; Ma, Jieyu; Niu, Fangfang; Zhang, Hanfeng; Yang, Bo; Liang, Wanwan; Han, Feng; Jiang, Yuan-Qing

    2015-03-01

    NAC transcription factors are plant-specific and play important roles in plant development processes, response to biotic and abiotic cues and hormone signaling. However, to date, little is known about the NAC genes in canola (or oilseed rape, Brassica napus L.). In this study, a total of 60 NAC genes were identified from canola through a systematical analysis and mining of expressed sequence tags. Among these, the cDNA sequences of 41 NAC genes were successfully cloned. The translated protein sequences of canola NAC genes with the NAC genes from representative species were phylogenetically clustered into three major groups and multiple subgroups. The transcriptional activities of these BnaNAC proteins were assayed in yeast. In addition, by quantitative real-time RT-PCR, we further observed that some of these BnaNACs were regulated by different hormone stimuli or abiotic stresses. Interestingly, we successfully identified two novel BnaNACs, BnaNAC19 and BnaNAC82, which could elicit hypersensitive response-like cell death when expressed in Nicotiana benthamiana leaves, which was mediated by accumulation of reactive oxygen species. Overall, our work has laid a solid foundation for further characterization of this important NAC gene family in canola. PMID:25616736

  6. Familial hyperaldosteronism.

    PubMed

    Stowasser, M; Gordon, R D

    2001-09-01

    Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension. PMID:11595502

  7. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma

    PubMed Central

    Cai, Jinquan; Sun, Ying; Wang, Guangzhi; Li, Yongli; Li, Ruiyan; Feng, Yan; Han, Bo; Li, Jianlong; Tian, Yu; Yi, Liye; Jiang, Chuanlu

    2016-01-01

    Background Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. Method The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. Results MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Conclusions Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. PMID:27022952

  8. The crystal structure of ferritin from Chlorobium tepidum reveals a new conformation of the 4-fold channel for this protein family.

    PubMed

    Arenas-Salinas, Mauricio; Townsend, Philip D; Brito, Christian; Marquez, Valeria; Marabolli, Vanessa; Gonzalez-Nilo, Fernando; Matias, Cata; Watt, Richard K; López-Castro, Juan D; Domínguez-Vera, José; Pohl, Ehmke; Yévenes, Alejandro

    2014-11-01

    Ferritins are ubiquitous iron-storage proteins found in all kingdoms of life. They share a common architecture made of 24 subunits of five α-helices. The recombinant Chlorobium tepidum ferritin (rCtFtn) is a structurally interesting protein since sequence alignments with other ferritins show that this protein has a significantly extended C-terminus, which possesses 12 histidine residues as well as several aspartate and glutamic acid residues that are potential metal ion binding residues. We show that the macromolecular assembly of rCtFtn exhibits a cage-like hollow shell consisting of 24 monomers that are related by 4-3-2 symmetry; similar to the assembly of other ferritins. In all ferritins of known structure the short fifth α-helix adopts an acute angle with respect to the four-helix bundle. However, the crystal structure of the rCtFtn presented here shows that this helix adopts a new conformation defining a new assembly of the 4-fold channel of rCtFtn. This conformation allows the arrangement of the C-terminal region into the inner cavity of the protein shell. Furthermore, two Fe(III) ions were found in each ferroxidase center of rCtFtn, with an average FeA-FeB distance of 3 Å; corresponding to a diferric μ-oxo/hydroxo species. This is the first ferritin crystal structure with an isolated di-iron center in an iron-storage ferritin. The crystal structure of rCtFtn and the biochemical results presented here, suggests that rCtFtn presents similar biochemical properties reported for other members of this protein family albeit with distinct structural plasticity. PMID:25079050

  9. Cold Adaptation of Zinc Metalloproteases in the Thermolysin Family from Deep Sea and Arctic Sea Ice Bacteria Revealed by Catalytic and Structural Properties and Molecular Dynamics

    PubMed Central

    Xie, Bin-Bin; Bian, Fei; Chen, Xiu-Lan; He, Hai-Lun; Guo, Jun; Gao, Xiang; Zeng, Yin-Xin; Chen, Bo; Zhou, Bai-Cheng; Zhang, Yu-Zhong

    2009-01-01

    Increased conformational flexibility is the prevailing explanation for the high catalytic efficiency of cold-adapted enzymes at low temperatures. However, less is known about the structural determinants of flexibility. We reported two novel cold-adapted zinc metalloproteases in the thermolysin family, vibriolysin MCP-02 from a deep sea bacterium and vibriolysin E495 from an Arctic sea ice bacterium, and compared them with their mesophilic homolog, pseudolysin from a terrestrial bacterium. Their catalytic efficiencies, kcat/Km (10–40 °C), followed the order pseudolysin < MCP-02 < E495 with a ratio of ∼1:2:4. MCP-02 and E495 have the same optimal temperature (Topt, 57 °C, 5 °C lower than pseudolysin) and apparent melting temperature (Tm = 64 °C, ∼10 °C lower than pseudolysin). Structural analysis showed that the slightly lower stabilities resulted from a decrease in the number of salt bridges. Fluorescence quenching experiments and molecular dynamics simulations showed that the flexibilities of the proteins were pseudolysin < MCP-02 < E495, suggesting that optimization of flexibility is a strategy for cold adaptation. Molecular dynamics results showed that the ordinal increase in flexibility from pseudolysin to MCP-02 and E495, especially the increase from MCP-02 to E495, mainly resulted from the decrease of hydrogen-bond stability in the dynamic structure, which was due to the increase in asparagine, serine, and threonine residues. Finally, a model for the cold adaptation of MCP-02 and E495 was proposed. This is the first report of the optimization of hydrogen-bonding dynamics as a strategy for cold adaptation and provides new insights into the structural basis underlying conformational flexibility. PMID:19181663

  10. Phylogeographic Analyses of Submesophotic Snappers Etelis coruscans and Etelis “marshi” (Family Lutjanidae) Reveal Concordant Genetic Structure across the Hawaiian Archipelago

    PubMed Central

    Andrews, Kimberly R.; Moriwake, Virginia N.; Wilcox, Christie; Grau, E. Gordon; Kelley, Christopher; Pyle, Richard L.; Bowen, Brian W.

    2014-01-01

    The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m) in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200–360 m) in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787) and E. “marshi” (formerly E. carbunculus; N = 770) with 436–490 bp of mtDNA cytochrome b and 10–11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals) had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper (Hyporthodus quernus). Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management plans

  11. Metabolic engineering of raffinose-family oligosaccharides in the phloem reveals alterations in carbon partitioning and enhances resistance to green peach aphid

    PubMed Central

    Cao, Te; Lahiri, Ipsita; Singh, Vijay; Louis, Joe; Shah, Jyoti; Ayre, Brian G.

    2013-01-01

    Many plants employ energized loading strategies to accumulate osmotically-active solutes into the phloem of source organs to accentuate the hydrostatic pressure gradients that drive the flow of water, nutrients and signals from source to sinks. Proton-coupled symport of sugars from the apoplasm into the phloem symplasm is the best studied phloem-loading mechanism. As an alternative, numerous species use a polymer trapping mechanism to load through symplasm: sucrose enters the phloem through specialized plasmodesmata and is converted to raffinose-family oligosaccharides (RFOs) which accumulate because of their larger size. In this study, metabolic engineering was used to generate RFOs at the inception of the translocation stream of Arabidopsis thaliana, which loads from the apoplasm and transports predominantly sucrose, and the fate of the sugars throughout the plant determined. Three genes, GALACTINOL SYNTHASE, RAFFINOSE SYNTHASE and STACHYOSE SYNTHASE, were expressed from promoters specific to the companion cells of minor veins. Two transgenic lines homozygous for all three genes (GRS63 and GRS47) were selected for further analysis. Three-week-old plants of both lines had RFO levels approaching 50% of total soluble sugar. RFOs were also identified in exudates from excised leaves of transgenic plants whereas levels were negligible in exudates from wild type (WT) leaves. Differences in starch accumulation between WT and GRS63 and GRS47 lines were not observed. Similarly, there were no differences in vegetative growth between WT and engineered plants, but the latter flowered slightly earlier. Finally, since the sugar composition of the translocation stream appeared altered, we tested for an impact on green peach aphid (Myzus persicae Sulzer) feeding. When given a choice between WT and transgenic plants, green peach aphids preferred settling on the WT plants. Furthermore, green peach aphid fecundity was lower on the transgenic plants compared to the WT plants. When

  12. Interspecies and Intraspecies Analysis of Trehalose Contents and the Biosynthesis Pathway Gene Family Reveals Crucial Roles of Trehalose in Osmotic-Stress Tolerance in Cassava

    PubMed Central

    Han, Bingying; Fu, Lili; Zhang, Dan; He, Xiuquan; Chen, Qiang; Peng, Ming; Zhang, Jiaming

    2016-01-01

    normal conditions. MeTPS1 was then transformed into tobacco (Nicotiana benthamiana). Results indicated that transgenic tobacco lines accumulated significant level of trehalose and possessed improved drought stress tolerance. In conclusion, cassava accumulated significantly high amount of trehalose under normal conditions due to multiplied trehalose biosynthesis gene families and constant expression of the active MeTPS1 gene. High levels of trehalose subsequently contributed to high drought stress tolerance. PMID:27420056

  13. Interspecies and Intraspecies Analysis of Trehalose Contents and the Biosynthesis Pathway Gene Family Reveals Crucial Roles of Trehalose in Osmotic-Stress Tolerance in Cassava.

    PubMed

    Han, Bingying; Fu, Lili; Zhang, Dan; He, Xiuquan; Chen, Qiang; Peng, Ming; Zhang, Jiaming

    2016-01-01

    conditions. MeTPS1 was then transformed into tobacco (Nicotiana benthamiana). Results indicated that transgenic tobacco lines accumulated significant level of trehalose and possessed improved drought stress tolerance. In conclusion, cassava accumulated significantly high amount of trehalose under normal conditions due to multiplied trehalose biosynthesis gene families and constant expression of the active MeTPS1 gene. High levels of trehalose subsequently contributed to high drought stress tolerance. PMID:27420056

  14. Complete Proteomic-Based Enzyme Reaction and Inhibition Kinetics Reveal How Monolignol Biosynthetic Enzyme Families Affect Metabolic Flux and Lignin in Populus trichocarpa[W

    PubMed Central

    Wang, Jack P.; Naik, Punith P.; Chen, Hsi-Chuan; Shi, Rui; Lin, Chien-Yuan; Liu, Jie; Shuford, Christopher M.; Li, Quanzi; Sun, Ying-Hsuan; Tunlaya-Anukit, Sermsawat; Williams, Cranos M.; Muddiman, David C.; Ducoste, Joel J.; Sederoff, Ronald R.; Chiang, Vincent L.

    2014-01-01

    We established a predictive kinetic metabolic-flux model for the 21 enzymes and 24 metabolites of the monolignol biosynthetic pathway using Populus trichocarpa secondary differentiating xylem. To establish this model, a comprehensive study was performed to obtain the reaction and inhibition kinetic parameters of all 21 enzymes based on functional recombinant proteins. A total of 104 Michaelis-Menten kinetic parameters and 85 inhibition kinetic parameters were derived from these enzymes. Through mass spectrometry, we obtained the absolute quantities of all 21 pathway enzymes in the secondary differentiating xylem. This extensive experimental data set, generated from a single tissue specialized in wood formation, was used to construct the predictive kinetic metabolic-flux model to provide a comprehensive mathematical description of the monolignol biosynthetic pathway. The model was validated using experimental data from transgenic P. trichocarpa plants. The model predicts how pathway enzymes affect lignin content and composition, explains a long-standing paradox regarding the regulation of monolignol subunit ratios in lignin, and reveals novel mechanisms involved in the regulation of lignin biosynthesis. This model provides an explanation of the effects of genetic and transgenic perturbations of the monolignol biosynthetic pathway in flowering plants. PMID:24619611

  15. Activity-Based Profiling of a Physiologic Aglycone Library Reveals Sugar Acceptor Promiscuity of Family 1 UDP-Glucosyltransferases from Grape1[W

    PubMed Central

    Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

    2014-01-01

    Monoterpenols serve various biological functions and accumulate in grape (Vitis vinifera), where a major fraction occurs as nonvolatile glycosides. We have screened the grape genome for sequences with similarity to terpene URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASES (UGTs) from Arabidopsis (Arabidopsis thaliana). A ripening-related expression pattern was shown for three candidates by spatial and temporal expression analyses in five grape cultivars. Transcript accumulation correlated with the production of monoterpenyl β-d-glucosides in grape exocarp during ripening and was low in vegetative tissue. Targeted functional screening of the recombinant UGTs for their biological substrates was performed by activity-based metabolite profiling (ABMP) employing a physiologic library of aglycones built from glycosides isolated from grape. This approach led to the identification of two UDP-glucose:monoterpenol β-d-glucosyltransferases. Whereas VvGT14a glucosylated geraniol, R,S-citronellol, and nerol with similar efficiency, the three allelic forms VvGT15a, VvGT15b, and VvGT15c preferred geraniol over nerol. Kinetic resolution of R,S-citronellol and R,S-linalool was shown for VvGT15a and VvGT14a, respectively. ABMP revealed geraniol as the major biological substrate but also disclosed that these UGTs may add to the production of further glycoconjugates in planta. ABMP of aglycone libraries provides a versatile tool to uncover novel biologically relevant substrates of small-molecule glycosyltransferases that often show broad sugar acceptor promiscuity. PMID:25073706

  16. Genus-Wide Comparative Genome Analyses of Colletotrichum Species Reveal Specific Gene Family Losses and Gains during Adaptation to Specific Infection Lifestyles

    PubMed Central

    Gan, Pamela; Narusaka, Mari; Kumakura, Naoyoshi; Tsushima, Ayako; Takano, Yoshitaka; Narusaka, Yoshihiro; Shirasu, Ken

    2016-01-01

    Members from Colletotrichum genus adopt a diverse range of lifestyles during infection of plants and represent a group of agriculturally devastating pathogens. In this study, we present the draft genome of Colletotrichum incanum from the spaethianum clade of Colletotrichum and the comparative analyses with five other Colletotrichum species from distinct lineages. We show that the C. incanum strain, originally isolated from Japanese daikon radish, is able to infect both eudicot plants, such as certain ecotypes of the eudicot Arabidopsis, and monocot plants, such as lily. Being closely related to Colletotrichum species both in the graminicola clade, whose members are restricted strictly to monocot hosts, and to the destructivum clade, whose members are mostly associated with dicot infections, C. incanum provides an interesting model system for comparative genomics to study how fungal pathogens adapt to monocot and dicot hosts. Genus-wide comparative genome analyses reveal that Colletotrichum species have tailored profiles of their carbohydrate-degrading enzymes according to their infection lifestyles. In addition, we show evidence that positive selection acting on secreted and nuclear localized proteins that are highly conserved may be important in adaptation to specific hosts or ecological niches. PMID:27189990

  17. Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics.

    PubMed

    Lohman, Jeremy R; Huang, Sheng-Xiong; Horsman, Geoffrey P; Dilfer, Paul E; Huang, Tingting; Chen, Yihua; Wendt-Pienkowski, Evelyn; Shen, Ben

    2013-03-01

    Enediyne natural product biosynthesis is characterized by a convergence of multiple pathways, generating unique peripheral moieties that are appended onto the distinctive enediyne core. Kedarcidin (KED) possesses two unique peripheral moieties, a (R)-2-aza-3-chloro-β-tyrosine and an iso-propoxy-bearing 2-naphthonate moiety, as well as two deoxysugars. The appendage pattern of these peripheral moieties to the enediyne core in KED differs from the other enediynes studied to date with respect to stereochemical configuration. To investigate the biosynthesis of these moieties and expand our understanding of enediyne core formation, the biosynthetic gene cluster for KED was cloned from Streptoalloteichus sp. ATCC 53650 and sequenced. Bioinformatics analysis of the ked cluster revealed the presence of the conserved genes encoding for enediyne core biosynthesis, type I and type II polyketide synthase loci likely responsible for 2-aza-l-tyrosine and 3,6,8-trihydroxy-2-naphthonate formation, and enzymes known for deoxysugar biosynthesis. Genes homologous to those responsible for the biosynthesis, activation, and coupling of the l-tyrosine-derived moieties from C-1027 and maduropeptin and of the naphthonate moiety from neocarzinostatin are present in the ked cluster, supporting 2-aza-l-tyrosine and 3,6,8-trihydroxy-2-naphthoic acid as precursors, respectively, for the (R)-2-aza-3-chloro-β-tyrosine and the 2-naphthonate moieties in KED biosynthesis. PMID:23360970

  18. Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics†

    PubMed Central

    Lohman, Jeremy R.; Huang, Sheng-Xiong; Horsman, Geoffrey P.; Dilfer, Paul E.; Huang, Tingting; Chen, Yihua; Wendt-Pienkowski, Evelyn; Shen, Ben

    2013-01-01

    Enediyne natural product biosynthesis is characterized by a convergence of multiple pathways, generating unique peripheral moieties that are appended onto the distinctive enediyne core. Kedarcidin (KED) possesses two unique peripheral moieties, a (R)-2-aza-3-chloro-β-tyrosine and an iso-propoxy-bearing 2-naphthonate moiety, as well as two deoxysugars. The appendage pattern of these peripheral moieties to the enediyne core in KED differs from the other enediynes studied to date with respect to stereochemical configuration. To investigate the biosynthesis of these moieties and expand our understanding of enediyne core formation, the biosynthetic gene cluster for KED was cloned from Streptoalloteichus sp. ATCC 53650 and sequenced. Bioinformatics analysis of the ked cluster revealed the presence of the conserved genes encoding for enediyne core biosynthesis, type I and type II polyketide synthase loci likely responsible for 2-aza-L-tyrosine and 3,6,8-trihydroxy-2-naphthonate formation, and enzymes known for deoxysugar biosynthesis. Genes homologous to those responsible for the biosynthesis, activation, and coupling of the L-tyrosine-derived moieties from C-1027 and maduropeptin and of the naphthonate moiety from neocarzinostatin are present in the ked cluster, supporting 2-aza-L-tyrosine and 3,6,8-trihydroxy-2-naphthoic acid as precursors, respectively, for the (R)-2-aza-3-chloro-β-tyrosine and the 2-naphthonate moieties in KED biosynthesis. PMID:23360970

  19. Genus-Wide Comparative Genome Analyses of Colletotrichum Species Reveal Specific Gene Family Losses and Gains during Adaptation to Specific Infection Lifestyles.

    PubMed

    Gan, Pamela; Narusaka, Mari; Kumakura, Naoyoshi; Tsushima, Ayako; Takano, Yoshitaka; Narusaka, Yoshihiro; Shirasu, Ken

    2016-01-01

    Members from Colletotrichum genus adopt a diverse range of lifestyles during infection of plants and represent a group of agriculturally devastating pathogens. In this study, we present the draft genome of Colletotrichum incanum from the spaethianum clade of Colletotrichum and the comparative analyses with five other Colletotrichum species from distinct lineages. We show that the C. incanum strain, originally isolated from Japanese daikon radish, is able to infect both eudicot plants, such as certain ecotypes of the eudicot Arabidopsis, and monocot plants, such as lily. Being closely related to Colletotrichum species both in the graminicola clade, whose members are restricted strictly to monocot hosts, and to the destructivum clade, whose members are mostly associated with dicot infections, C. incanum provides an interesting model system for comparative genomics to study how fungal pathogens adapt to monocot and dicot hosts. Genus-wide comparative genome analyses reveal that Colletotrichum species have tailored profiles of their carbohydrate-degrading enzymes according to their infection lifestyles. In addition, we show evidence that positive selection acting on secreted and nuclear localized proteins that are highly conserved may be important in adaptation to specific hosts or ecological niches. PMID:27189990

  20. A New Family of Membrane Electron Transporters and Its Substrates, Including a New Cell Envelope Peroxiredoxin, Reveal a Broadened Reductive Capacity of the Oxidative Bacterial Cell Envelope

    PubMed Central

    Cho, Seung-Hyun; Parsonage, Derek; Thurston, Casey; Dutton, Rachel J.; Poole, Leslie B.; Collet, Jean-Francois; Beckwith, Jon

    2012-01-01

    ABSTRACT The Escherichia coli membrane protein DsbD functions as an electron hub that dispatches electrons received from the cytoplasmic thioredoxin system to periplasmic oxidoreductases involved in protein disulfide isomerization, cytochrome c biogenesis, and sulfenic acid reduction. Here, we describe a new class of DsbD proteins, named ScsB, whose members are found in proteobacteria and Chlamydia. ScsB has a domain organization similar to that of DsbD, but its amino-terminal domain differs significantly. In DsbD, this domain directly interacts with substrates to reduce them, which suggests that ScsB acts on a different array of substrates. Using Caulobacter crescentus as a model organism, we searched for the substrates of ScsB. We discovered that ScsB provides electrons to the first peroxide reduction pathway identified in the bacterial cell envelope. The reduction pathway comprises a thioredoxin-like protein, TlpA, and a peroxiredoxin, PprX. We show that PprX is a thiol-dependent peroxidase that efficiently reduces both hydrogen peroxide and organic peroxides. Moreover, we identified two additional proteins that depend on ScsB for reduction, a peroxiredoxin-like protein, PrxL, and a novel protein disulfide isomerase, ScsC. Altogether, our results reveal that the array of proteins involved in reductive pathways in the oxidative cell envelope is significantly broader than was previously thought. Moreover, the identification of a new periplasmic peroxiredoxin indicates that in some bacteria, it is important to directly scavenge peroxides in the cell envelope even before they reach the cytoplasm. PMID:22493033

  1. Family Resilience: Israeli Mothers' Perspectives.

    ERIC Educational Resources Information Center

    Cohen, Orna; Slonim, Iris; Finzi, Ricky; Leichtentritt, Ronit D.

    2002-01-01

    Study reveals components underlying the concept of family resilience based on the perceptions of Israeli women. Five components of family resilience were identified (1) interpersonal relations; (2) ability to share painful feelings; (3) flexibility among family members; (4) connectedness; and (5) family values. Components have practical…

  2. Getting a High-Speed Family Connection: Associations between Family Media Use and Family Connection

    ERIC Educational Resources Information Center

    Padilla-Walker, Laura M.; Coyne, Sarah M.; Fraser, Ashley M.

    2012-01-01

    The way families have used the media has substantially changed over the past decade. Within the framework of family systems theory, this paper examines the relations between family media use and family connection in a sample of 453 adolescents (mean age of child = 14.32 years, SD = 0.98, 52% female) and their parents. Results revealed that cell…

  3. Phylogenomic analysis of 16S rRNA:(guanine-N2) methyltransferases suggests new family members and reveals highly conserved motifs and a domain structure similar to other nucleic acid amino-methyltransferases.

    PubMed

    Bujnicki, J M

    2000-11-01

    The sequences of known Escherichia coli 16S rRNA:m2G1207 methyltransferase (MTase) RsmC and hypothetical 16S rRNA:m2G966 MTase encoded by the ygjo open reading frame were used to carry out a database search of other putative m2G-generating enzymes in finished and unfinished genomic sequences. Sequence comparison and phylogenetic analysis of 21 close homologs of RsmC and YgjO revealed the presence of the third paralogous lineage in E. coli and other gamma-Proteobacteria, which might correspond to the subfamily of MTases specific for G1516 in 16S rRNA. In addition, the comparative sequence analysis supported by sequence/structure threading suggests that rRNA:m2G MTases are very closely related to RNA and DNA:m6A MTases and that these two enzyme families share common architecture of the active site and presumably a similar mechanism of methyl group transfer onto the exocyclic amino group of their target bases. PMID:11053259

  4. Indicators of Familial Alcoholism in Children's Kinetic Family Drawings.

    ERIC Educational Resources Information Center

    Holt, Elizabeth S.; Kaiser, Donna H.

    2001-01-01

    Attempts to delineate indicators in children's depictions of family that suggest the presence of parental alcoholism. Kinetic Family Drawings from two groups of children were collected. Statistical analysis revealed two of six items of the evaluation - depiction of isolation of self and isolation of other family members - were significantly higher…

  5. Family Meals

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  6. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  7. Family Arguments

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  8. Family History

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Family Health History Note: Javascript is disabled or is not supported ... visit this page: About CDC.gov . Family Health History The Basics Family Health History & Chronic Disease Planning ...

  9. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  10. Characterization of the betaherpesviral pUL69 protein family reveals binding of the cellular mRNA export factor UAP56 as a prerequisite for stimulation of nuclear mRNA export and for efficient viral replication.

    PubMed

    Zielke, Barbara; Thomas, Marco; Giede-Jeppe, Antje; Müller, Regina; Stamminger, Thomas

    2011-02-01

    UL69 of human cytomegalovirus (HCMV) encodes a pleiotropic transactivator protein and has a counterpart in every member of the Herpesviridae family thus far sequenced. However, little is known about the conservation of the functions of the nuclear phosphoprotein pUL69 in the homologous proteins of other betaherpesviruses. Therefore, eukaryotic expression vectors were constructed for pC69 of chimpanzee cytomegalovirus, pRh69 of rhesus cytomegalovirus, pM69 of murine cytomegalovirus, pU42 of human herpesvirus 6, and pU42 of elephant endotheliotropic herpesvirus. Indirect immunofluorescence experiments showed that all pUL69 homologs expressed by these vectors were localized to the cell nucleus. Coimmunoprecipitation experiments identified homodimerization as a conserved feature of all homologs, whereas heterodimerization with pUL69 was restricted to its closer relatives. Further analyses demonstrated that pC69 and pRh69 were the only two homologs that functioned, like pUL69, as viral-mRNA export factors. As we had reported recently that nucleocytoplasmic shuttling and interaction with the cellular DExD/H-box helicases UAP56 and URH49 were prerequisites for the nuclear-mRNA export activity of pUL69, the homologs were characterized with regard to these properties. Heterokaryon assays demonstrated nucleocytoplasmic shuttling for all homologs, and coimmunoprecipitation and mRNA export assays revealed that the interaction of UAP56 and/or URH49 with pC69 or pRh69 was required for mRNA export activity. Moreover, characterization of HCMV recombinants harboring mutations within the N-terminal sequence of pUL69 revealed a strong replication defect of viruses expressing pUL69 variants that were deficient in UAP56 binding. In summary, homodimerization and nucleocytoplasmic shuttling activity were identified as conserved features of betaherpesviral pUL69 homologs. UAP56 binding was shown to represent a unique characteristic of members of the genus Cytomegalovirus that is required

  11. The Crystal Structures of Apo and cAMP-Bound GlxR from Corynebacterium glutamicum Reveal Structural and Dynamic Changes upon cAMP Binding in CRP/FNR Family Transcription Factors

    PubMed Central

    Townsend, Philip D.; Jungwirth, Britta; Pojer, Florence; Bußmann, Michael; Money, Victoria A.; Cole, Stewart T.; Pühler, Alfred; Tauch, Andreas; Bott, Michael; Cann, Martin J.; Pohl, Ehmke

    2014-01-01

    The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition. PMID:25469635

  12. Acetone formation in the Vibrio family: a new pathway for bacterial leucine catabolism.

    PubMed

    Nemecek-Marshall, M; Wojciechowski, C; Wagner, W P; Fall, R

    1999-12-01

    There is current interest in biological sources of acetone, a volatile organic compound that impacts atmospheric chemistry. Here, we determined that leucine-dependent acetone formation is widespread in the Vibrionaceae. Sixteen Vibrio isolates, two Listonella species, and two Photobacterium angustum isolates produced acetone in the presence of L-leucine. Shewanella isolates produced much less acetone. Growth of Vibrio splendidus and P. angustum in a fermentor with controlled aeration revealed that acetone was produced after a lag in late logarithmic or stationary phase of growth, depending on the medium, and was not derived from acetoacetate by nonenzymatic decarboxylation in the medium. L-Leucine, but not D-leucine, was converted to acetone with a stoichiometry of approximately 0.61 mol of acetone per mol of L-leucine. Testing various potential leucine catabolites as precursors of acetone showed that only alpha-ketoisocaproate was efficiently converted by whole cells to acetone. Acetone production was blocked by a nitrogen atmosphere but not by electron transport inhibitors, suggesting that an oxygen-dependent reaction is required for leucine catabolism. Metabolic labeling with deuterated (isopropyl-d(7))-L-leucine revealed that the isopropyl carbons give rise to acetone with full retention of deuterium in each methyl group. These results suggest the operation of a new catabolic pathway for leucine in vibrios that is distinct from the 3-hydroxy-3-methylglutaryl-coenzyme A pathway seen in pseudomonads. PMID:10601206

  13. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  14. Cancer, Families, and Family Counselors.

    ERIC Educational Resources Information Center

    Duffy, Maureen; Gillig, Scott

    2003-01-01

    Examines the role of the family counselor in working with cancer patients and their families. Suggests ways in which the family counselor can work proactively with families in the area of cancer prevention and helping them cope more effectively with its impact on their lives. Uses a clinical case example to illustrate intervention with cancer…

  15. Family therapy by family doctors

    PubMed Central

    Neighbour, R.

    1982-01-01

    The experiences of a group of general practitioners learning and attempting family therapy are described. Three principles for working with whole families — facilitation, formulation and focussing — are illustrated by case histories. Family therapy in general practice can be effective for patients and worthwhile for family doctors. PMID:7153974

  16. Crystal structures of Paenibacillus polymyxa beta-glucosidase B complexes reveal the molecular basis of substrate specificity and give new insights into the catalytic machinery of family I glycosidases.

    PubMed

    Isorna, Pablo; Polaina, Julio; Latorre-García, Lorena; Cañada, Francisco Javier; González, Beatriz; Sanz-Aparicio, Julia

    2007-08-31

    Bacteria species involved in degradation of cellulosic substrates produce a variety of enzymes for processing related compounds along the hydrolytic pathway. Paenibacillus polymyxa encodes two homologous beta-glucosidases, BglA and BglB, presenting different quaternary structures and substrate specificities. We previously reported the 3D-structure of BglA, which is highly specific against cellobiose. Here, we present structural analysis of BglB, a monomeric enzyme that acts as an exo-beta-glucosidase hydrolyzing cellobiose and cellodextrins of higher degree of polymerization. The crystal structure of BglB shows that several polar residues narrow the active site pocket and contour additional subsites. The structure of the BglB-cellotetraose complex confirms these subsites, revealing the substrate-binding mode, and shows the oligosaccharide-enzyme recognition pattern in detail. Comparison between BglA and BglB crystal structures suggests that oligomerization in BglA can assist in fine-tuning the specificity of the active centre by modulating the loops surrounding the cavity. We have solved the crystal structure of BglB with bound thiocellobiose, a competitive inhibitor, which together with the BglB-cellotetraose complex delineate the general features of the aglycon site. The detailed characterization of the atomic interactions at the aglycon site show a recognition pattern common to all bacterial beta-glucosidases, and presents some differences with the aglycon site in plant beta-glycosidases essentially by means of a different orientation of the basal Trp. The crystal structures of of BglB with a covalently bound inhibitor (derived from 2-fluoroglucoside) and glucose (produced by hydrolysis of the substrate in the crystal), provide additional pictures of the binding events and the intermediates formed during the reaction. Altogether, this information can assist in the understanding of subtle differences of the enzyme mechanism and substrate recognition within this

  17. FAMILIAL SUICIDE

    PubMed Central

    Unni, K.E. Sadanaandan

    1996-01-01

    Seven completed suicides in a family of lower socioeconomic status and suburban domicile in Pondicherry are reported. The presence of bipolar affective disorder in the family members and the absence of exogenous factors are illustrated by utilising both family history method and family study method. The details collected formed the basis for the terminology ‘familial suicide’. The management of the index case, one of the only three surviving male members of the family, who presented with suicidal ruminations and depressive features, is described. PMID:21584122

  18. The family and schizophrenia.

    PubMed

    Wuerker, A K

    2000-01-01

    There has been controversy about the role of family in the etiology and course of schizophrenia for almost 70 years. Psychoanalysts and family therapists have proposed theories about the development of schizophrenia that overtly blamed parents, and recently, expressed emotion (EE) research has been criticized as implicating families once again. However, the study of schizophrenia as a brain disorder has resulted in new understandings of the influence of the family. This article reviews recent research revealing a unique vulnerability to stress in persons with schizophrenia and suggesting that communication difficulties may be due to a shared genetic heritage. Advanced practice mental health nurses who have a solid foundation in neurobiology are ideally suited to help the person with schizophrenia and his or her family. Knowledge about the neurobiological basis of schizophrenia has become very sophisticated and complex, but that knowledge is nevertheless essential to understand the otherwise puzzling patterns of behavior shown by persons with schizophrenia. PMID:10839056

  19. Family Support.

    ERIC Educational Resources Information Center

    Wieck, Colleen, Ed.; McBride, Marijo, Ed.

    1990-01-01

    This "Feature Issue" of the quarterly journal "Impact" presents 19 brief articles on family support systems in the United States for persons with developmental disabilities and their families. Emphasis is on provisions of Public Law 99-457. Articles include: "Family Support in the United States: Setting a Course for the 1990s" (James Knoll);…

  20. Family Matters.

    ERIC Educational Resources Information Center

    Mainor, Peggy

    2001-01-01

    Describes a Kellogg Family Collaborative project that involves the University of Montana and four tribal colleges in a family-strengths approach to improving student retention and achievement. States that the project is grounded in social work theory and research that recognize and reinforce family and student resilience through promotion of…

  1. Rural Families.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1992-01-01

    This "special focus" journal issue consists of 13 individual articles on the theme of rural family programs relating to school, health services, church, and other institutions. It includes: (1) "Towards a Rural Family Policy" (Judith K. Chynoweth and Michael D. Campbell); (2) "Montana: Council for Families Collaborates for Prevention (Jean…

  2. Immigrant Family Stability: Some Primary Thoughts.

    ERIC Educational Resources Information Center

    Grant, Geraldine

    1983-01-01

    Suggests that immigration entails redefinition of sex roles and kin obligations in immigrant families; reveals a trend toward increasingly differentiated nuclear families among immigrants; and identifies pressures that may make immigrant families more susceptible to instability than American families, and countervailing forces that may contribute…

  3. Integrating Coping Behavior in Family Stress Theory.

    ERIC Educational Resources Information Center

    McCubbin, Hamilton I.

    1979-01-01

    Reveals the tripartite aspect of coping behavior in the face of family separation: the management of family stability and individual anxiety; the procurement of social support from community, interpersonal relationships, and extended family; and direct attack on the stressor event through individual and collective family efforts. (Author/BEF)

  4. Sibling Ordinal Position and Family Education.

    ERIC Educational Resources Information Center

    McDonough, James J., Jr.

    1978-01-01

    Results for the 30 families as seen as "teaching-demonstration" families suggest that Adler's contention that more "first and youngest" children reveal problems and concerns (as defined by their parents) is correct. (Author)

  5. A novel β-xylosidase structure from Geobacillus thermoglucosidasius: the first crystal structure of a glycoside hydrolase family GH52 enzyme reveals unpredicted similarity to other glycoside hydrolase folds.

    PubMed

    Espina, Giannina; Eley, Kirstin; Pompidor, Guillaume; Schneider, Thomas R; Crennell, Susan J; Danson, Michael J

    2014-05-01

    Geobacillus thermoglucosidasius is a thermophilic bacterium that is able to ferment both C6 and C5 sugars to produce ethanol. During growth on hemicellulose biomass, an intracellular β-xylosidase catalyses the hydrolysis of xylo-oligosaccharides to the monosaccharide xylose, which can then enter the pathways of central metabolism. The gene encoding a G. thermoglucosidasius β-xylosidase belonging to CAZy glycoside hydrolase family GH52 has been cloned and expressed in Escherichia coli. The recombinant enzyme has been characterized and a high-resolution (1.7 Å) crystal structure has been determined, resulting in the first reported structure of a GH52 family member. A lower resolution (2.6 Å) structure of the enzyme-substrate complex shows the positioning of the xylobiose substrate to be consistent with the proposed retaining mechanism of the family; additionally, the deep cleft of the active-site pocket, plus the proximity of the neighbouring subunit, afford an explanation for the lack of catalytic activity towards the polymer xylan. Whilst the fold of the G. thermoglucosidasius β-xylosidase is completely different from xylosidases in other CAZy families, the enzyme surprisingly shares structural similarities with other glycoside hydrolases, despite having no more than 13% sequence identity. PMID:24816105

  6. Revealing Rembrandt

    PubMed Central

    Parker, Andrew J.

    2014-01-01

    The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI). Our results emphasized the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt's portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings. PMID:24795552

  7. Revealing Mercury

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Solomon, S. C.; Head, J. W.; Watters, T. R.; Murchie, S. L.; Robinson, M. S.; Chapman, C. R.; McNutt, R. L.

    2009-04-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, developed under NASA's Discovery Program, launched in August 2004. En route to insertion into orbit about Mercury in 2011, MESSENGER flies by Mercury three times. The first and second of these encounters were accomplished in January and October of 2008. These flybys viewed portions of Mercury's surface that were not observed by Mariner 10 during its reconnaissance of somewhat less than half of the planet in 1974-1975. All MESSENGER instruments operated during each flyby and returned a wealth of new data. Many of the new observations were focused on the planet's geology, including monochrome imaging at resolutions as high as 100 m/pixel, multispectral imaging in 11 filters at resolutions as high as 500 m/pixel, laser altimetry tracks extending over several thousands of kilometers, and high-resolution spectral measurements of several types of terrain. Here we present an overview of the first inferences on the global geology of Mercury from the MESSENGER observations. Whereas evidence for volcanism was equivocal from Mariner 10 data, the new MESSENGER images and altimetry provide compelling evidence that volcanism was widespread and protracted on Mercury. Color imaging reveals three common spectral units on the surface: a higher-reflectance, relatively red material occurring as a distinct class of smooth plains, typically with distinct embayment relationships interpreted to indicate volcanic emplacement; a lower-reflectance, relatively blue material typically excavated by impact craters and therefore inferred to be more common at depth; and a spectrally intermediate terrain that constitutes much of the uppermost crust. Three more minor spectral units are also seen: fresh crater ejecta, reddish material associated with rimless depressions interpreted to be volcanic centers, and high-reflectance deposits seen in some crater floors. Preliminary measurements of crater size

  8. FAMILY LYGISTORRHINIDAE.

    PubMed

    Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-01-01

    The Lygistorrhinidae are a family belonging to the suborder Bibionomorpha, with no previous record from Colombia. This paper refers for the first time to the occurrence of the family in the country, an undetermined species of the genus Lygistorrhina (Probolaeus) Williston. PMID:27395260

  9. Family Potyviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

  10. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  11. Family Empowerment.

    ERIC Educational Resources Information Center

    Sinclair, Mary F., Ed.; And Others

    1992-01-01

    This feature issue of IMPACT focuses on the empowerment of families with a member who has a developmental disability. It presents strategies and models for a collaborative, respectful approach to service provision, and presents the experiences of families in seeking support and assistance. Feature articles include "Two Generations of Disability: A…

  12. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  13. Whole genome sequencing and analysis reveal insights into the genetic structure, diversity and evolutionary relatedness of luxI and luxR homologs in bacteria belonging to the Sphingomonadaceae family

    PubMed Central

    Gan, Han Ming; Gan, Huan You; Ahmad, Nurul H.; Aziz, Nazrin A.; Hudson, André O.; Savka, Michael A.

    2015-01-01

    Here we report the draft genomes and annotation of four N-acyl homoserine lactone (AHL)-producing members from the family Sphingomonadaceae. Comparative genomic analyses of 62 Sphingomonadaceae genomes were performed to gain insights into the distribution of the canonical luxI/R-type quorum sensing (QS) network within this family. Forty genomes contained at least one luxR homolog while the genome of Sphingobium yanoikuyae B1 contained seven Open Reading Frames (ORFs) that have significant homology to that of luxR. Thirty-three genomes contained at least one luxI homolog while the genomes of Sphingobium sp. SYK6, Sphingobium japonicum, and Sphingobium lactosutens contained four luxI. Using phylogenetic analysis, the sphingomonad LuxR homologs formed five distinct clades with two minor clades located near the plant associated bacteria (PAB) LuxR solo clade. This work for the first time shows that 13 Sphingobium and one Sphingomonas genome(s) contain three convergently oriented genes composed of two tandem luxR genes proximal to one luxI (luxR-luxR-luxI). Interestingly, luxI solos were identified in two Sphingobium species and may represent species that contribute to AHL-based QS system by contributing AHL molecules but are unable to perceive AHLs as signals. This work provides the most comprehensive description of the luxI/R circuitry and genome-based taxonomical description of the available sphingomonad genomes to date indicating that the presence of luxR solos and luxI solos are not an uncommon feature in members of the Sphingomonadaceae family. PMID:25621282

  14. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  15. Acculturation gaps in Vietnamese immigrant families: Impact on family relationships

    PubMed Central

    Ho, Joyce; Birman, Dina

    2009-01-01

    Vietnamese immigrants in the United States face acculturation challenges involving the individual, family, and community. Experts suggest that immigrant family members acculturate at different rates resulting in an acculturation gap, which negatively influences family adjustment. In this study we examined the degree and patterns of acculturation differences between 104 first generation immigrant Vietnamese adolescents and their parents, and whether acculturation gap affected family relationships. Operationalizing the “gap” as both absolute value of differences in acculturation and interactions of parent and adolescent acculturation levels, we examined the impact of such gaps in Vietnamese and American language, identity, and behavioral acculturation on family relationships. Results revealed that family cohesion and satisfaction were predicted by gaps in Vietnamese identity acculturation, but not by gaps in other acculturation domains. PMID:20161537

  16. Genetic analysis of familial spontaneous pneumothorax in an Indian family.

    PubMed

    Ray, Anindita; Paul, Suman; Chattopadhyay, Esita; Kundu, Susmita; Roy, Bidyut

    2015-06-01

    Familial spontaneous pneumothorax is one of the phenotypes of Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant condition associated with folliculin (FLCN). We investigated clinical and genetic data of an Indian family having two patients suffering from spontaneous pneumothorax in the absence of skin lesions or renal tumors. HRCT scan of patient's lung revealed paracardiac cysts, and DNA sequencing of all 14 exons of FLCN from patients showed the presence of heterozygous "C allele" deletion in the poly-cytosine (poly-C) tract of exon 11 leading to truncated folliculin. This mutation was also observed in four asymptomatic members of the family. Our results confirmed the presence of deletion mutation in poly-C tract of FLCN in members of BHDS family. This is the first report of genetic insight in a BHDS family from India but in-depth studies with a larger sample set are necessary to understand mechanism of familial pneumothorax. PMID:25827758

  17. Unusual families.

    PubMed

    Golombok, Susan

    2005-03-01

    The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers. PMID:15819999

  18. FAMILY RHAGIONIDAE.

    PubMed

    Santos, Charles Morphy D; Carmo, Daniel D D

    2016-01-01

    The family Rhagionidae is one of the oldest Brachyeran lineages. Its monophyly is still uncertain. There are four rhagionid genera distributed in Neotropical Region but only three species of Chrysopilus are found in Colombia. PMID:27395270

  19. FAMILY BIBIONIDAE.

    PubMed

    Falaschi, Rafaela Lopes; Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-01-01

    The Bibionidae are a family belonging to the suborder Bibionomorpha with four genera and 17 species known from Colombia. This work expands the distribution of these species to other localities in the country. PMID:27395253

  20. Tomorrow's Family

    ERIC Educational Resources Information Center

    Pickett, Robert S.

    1977-01-01

    Author states that "...the traditional form of family which has been the norm in recent times in the West will persist, but will be forced to "move over" to accommodate other forms of domestic life." (Author)

  1. Family Issues

    MedlinePlus

    ... not mean that everyone gets along all the time. Conflicts are a part of family life. Many things can lead to conflict, such as illness, disability, addiction, job loss, school problems, and marital issues. Listening to ...

  2. Family Limitation

    PubMed Central

    Smith, Robert

    1966-01-01

    Dr Robert Smith surveys the history of birth control and sounds a warning for the future of mankind, if the population explosion is allowed to continue unchecked. He stresses the importance of the role of the general practitioner in the limitation of births. Sir Theodore Fox describes the work of the Family Planning Association and stresses that, increasingly, this is a specialist service covering all aspects of fertility. He also feels that the general practitioner has a role in family planning. PMID:5954261

  3. Familial unilateral Brown syndrome

    PubMed Central

    Kenawy, Nihal; Pilz, Daniela T

    2008-01-01

    We present a two-generation family with Brown syndrome. The proband was a six and a half-year-old female who presented with a history of failure of dextro-elevation of her left eye. A full ophthalmic evaluation was consistent with a left Brown syndrome. Family history revealed that her mother was operated on as a child for left Brown syndrome and examination of her four and a half-year-old sibling showed similar affection in the left eye. Autosomal dominant inheritance has been postulated in this condition. To our knowledge this is the first report of three members of a two-generation family with left-sided Brown syndrome. Genetic counseling of Brown syndrome cases is advised; nevertheless, identification of the responsible gene should shed more light on its genetics. PMID:18711279

  4. Genetic recombination at the human RH locus: A family study of the red-cell Evans phenotype reveals a transfer of exons 2-6 from the RHD to the RHCE gene

    SciTech Connect

    Huang, C.H.; Chen, Y.; Reid, M.; Ghosh, S.

    1996-10-01

    The human RH locus appears to consist of two structural genes, D and CE, which map on the short arm p34-36 of chromosome 1 and specify a most complex system of blood-group genetic polymorphisms. Here we describe a family study of the Evans (also known as {open_quotes}D..{open_quotes}) phenotype, a codominant trait associated with both qualitative and quantitative changes in D-antigen expression. A cataract-causing mutation was also inherited in this family and was apparently cotransmitted with Evans, suggesting a chromosomal linkage of these two otherwise unrelated traits. Southern blot analysis and allele-specific PCR showed the linkage of Evans with a SphI RFLP marker and the presence of a hybrid gene in the RH locus. To delineate the pattern of gene expression, the composition and structure of Rh-polypeptide transcripts were characterized by reverse transcriptase-PCR and nucleotide sequencing. This resulted in the identification of a novel Rh transcript expressed only in the Evans-positive erythroid cells. Sequence analysis showed that the transcript maintained a normal open reading frame but occurred as a CE-D-CE composite in which exons 2-6 of the CE gene were replaced by the homologous counterpart of the D gene. This hybrid gene was predicted to encode a CE-D-CE fusion protein whose surface expression correlates with the Evans phenotype. The mode and consequence of such a recombination event suggest the occurrence, in the RH locus, of a segmental DNA transfer via the mechanism of gene conversion. 31 refs., 6 figs., 1 tab.

  5. Family welfare.

    PubMed

    Sinha, N K

    1992-01-01

    Between 1901-1921, India gained 12.9 million people because mortality remained high. The death rate fell between 1921-1951, but birth rates remained the same. Therefore 110 million people were added--2 times the population increase between 1891-1921. Between 1951-1981, the population increased to 324 million. Socioeconomic development was responsible for most of the downward trend in the birth rate during the 20th century. Even though large families were the norm in early India, religious leaders encouraged small family size. The 1st government family planning clinics in the world opened in Mysore and Bangalore in 1930. Right before Independence, the Bhore Committee made recommendations to reduce population growth such as increasing the age of marriage for girls. Since 1951 there has been a change in measures and policies geared towards population growth with each of the 7 5-Year Plans because policy makers applied what they learned from each previous plan. The 1st 5-Year Plan emphasized the need to understand what factors contribute to population growth. It also integrated family planning services into health services of hospitals and health centers. The government was over zealous in its implementation of the sterilization program (2nd 5-Year Plan, 1956-1961), however, which hurt family planning programs for many years. As of early 1992, sterilization, especially tubectomy, remained the most popular family planning method, however. The 7th 5-Year Plan changed its target of reaching a Net Reproductive Rate of 1 by 2001 to 2006-2011. It set a goal of 100% immunization coverage by 1990 but it did not occur. In 1986, the Ministry of Health and Family Welfare planned to make free contraceptives available in urban and rural areas and to involve voluntary organizations. The government needs to instill measures to increase women's status, women's literacy, and age of marriage as well as to eliminate poverty, ensure old age security, and ensure child survival and

  6. Marine bacteria which produce tetrodotoxin.

    PubMed Central

    Simidu, U; Noguchi, T; Hwang, D F; Shida, Y; Hashimoto, K

    1987-01-01

    A number of type strains of marine bacteria, including members of the family Vibrionaceae, were cultured and examined for tetrodotoxin productivity by high-performance liquid chromatography and gas chromatography-mass spectrometry. Most of the Vibrionaceae strains produced tetrodotoxin, anhydrotetrodotoxin, or both. PMID:3310884

  7. Familial Hypercholesterolemia.

    PubMed

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2016-03-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder. PMID:26892994

  8. FAMILY STRATIOMYIDAE.

    PubMed

    Fachin, Diego Aguilar; De Assis-Pujol, Cristiane Vieira

    2016-01-01

    The family Stratiomyidae has more than 2,800 described species, of which 1001 species belongs to the Neotropics. This catalog for Colombia presents 87 species distributed in 32 genera, and ten subfamilies. Merosargus gracilis and the genus Microchrysa, with a single species M. bicolor are recorded for the first time to Colombia. The fauna is very expressive but still poorly known, representing nearly one tenth of the Neotropical diversity of the family in numbers of species, and one fifth of generic diversity. PMID:27395274

  9. Family-Centered Child Care. Families Matter.

    ERIC Educational Resources Information Center

    Lopez, M. Elena; Dorros, Sybilla

    The Families Matter series of papers from the Harvard Family Research Project advances the concept of family-centered child care, advocating an approach to early childhood education that addresses the development of the child and family together. Grounded in family support principles, which build on family strengths and work from a community's…

  10. Cold adaptation of zinc metalloproteases in the thermolysin family from deep sea and arctic sea ice bacteria revealed by catalytic and structural properties and molecular dynamics: new insights into relationship between conformational flexibility and hydrogen bonding.

    PubMed

    Xie, Bin-Bin; Bian, Fei; Chen, Xiu-Lan; He, Hai-Lun; Guo, Jun; Gao, Xiang; Zeng, Yin-Xin; Chen, Bo; Zhou, Bai-Cheng; Zhang, Yu-Zhong

    2009-04-01

    Increased conformational flexibility is the prevailing explanation for the high catalytic efficiency of cold-adapted enzymes at low temperatures. However, less is known about the structural determinants of flexibility. We reported two novel cold-adapted zinc metalloproteases in the thermolysin family, vibriolysin MCP-02 from a deep sea bacterium and vibriolysin E495 from an Arctic sea ice bacterium, and compared them with their mesophilic homolog, pseudolysin from a terrestrial bacterium. Their catalytic efficiencies, k(cat)/K(m) (10-40 degrees C), followed the order pseudolysin < MCP-02 < E495 with a ratio of approximately 1:2:4. MCP-02 and E495 have the same optimal temperature (T(opt), 57 degrees C, 5 degrees C lower than pseudolysin) and apparent melting temperature (T(m) = 64 degrees C, approximately 10 degrees C lower than pseudolysin). Structural analysis showed that the slightly lower stabilities resulted from a decrease in the number of salt bridges. Fluorescence quenching experiments and molecular dynamics simulations showed that the flexibilities of the proteins were pseudolysin < MCP-02 < E495, suggesting that optimization of flexibility is a strategy for cold adaptation. Molecular dynamics results showed that the ordinal increase in flexibility from pseudolysin to MCP-02 and E495, especially the increase from MCP-02 to E495, mainly resulted from the decrease of hydrogen-bond stability in the dynamic structure, which was due to the increase in asparagine, serine, and threonine residues. Finally, a model for the cold adaptation of MCP-02 and E495 was proposed. This is the first report of the optimization of hydrogen-bonding dynamics as a strategy for cold adaptation and provides new insights into the structural basis underlying conformational flexibility. PMID:19181663

  11. Income and Family Events: Family Income, Family Size, and Consumption

    ERIC Educational Resources Information Center

    Cutright, Phillips

    1971-01-01

    This paper considers the structure of family income, examines some factors affecting family size, reviews alternative definitions of an adequate income for families with varying numbers, and presents data on actual consumption, according to family income and family size. A model depicting the causal relations among factors affecting consumption is…

  12. FAMILY SCIARIDAE.

    PubMed

    Carvalho-Fernandes, Sheila Patrícia

    2016-01-01

    Sciaridae are a widely distributed family with high number of species. They are known as black fungus gnats due to their dark color and feeding activity. This catalogue presents 17 species from Colombia distributed in eight genera, and for each species the geographical distribution is provided. PMID:27395255

  13. FAMILY CECIDOMYIIDAE.

    PubMed

    Maia, Valéria Cid

    2016-01-01

    This large family is poorly known in Colombia, where only 44 species have been recorded in 20 genera. All of them are included in Cecidomyiinae, which is the most diverse subfamily of gall midges in number of species and feeding habits, including phytophagous, predaceous and fungivorous species. Most of them are galler. The other subfamilies have never been recorded in this country. PMID:27395254

  14. Familial hyperamylasemia.

    PubMed

    Koda, Yu Kar Ling; Vidolin, Eliana

    2002-01-01

    A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood. PMID:11981589

  15. Family Violence.

    ERIC Educational Resources Information Center

    Sorgen, Carol, Ed.

    1979-01-01

    This quarterly publication, issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), contains articles dealing with family violence and alcohol abuse, children of alcoholic parents, training programs for counselors, and confidentiality of client records. The three articles on alcohol abuse suggest that: (1) there is a clear…

  16. Family Hypnotherapy.

    ERIC Educational Resources Information Center

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

  17. FAMILY TYMOVIRIDAE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

  18. FAMILY ASILIDAE.

    PubMed

    Wolff, Marta; Lamas, Carlos José Einicker

    2016-01-01

    Asilidae is one of the largest Diptera families with more than 7,000 recognized species worldwide. All their species are predators on arthropods, mainly insects. This catalogue presents 71 species distributed in 26 genera, ten tribes or generic groups and four subfamilies. For each species we present the available geographical information and relevant references. PMID:27395278

  19. Serving Families.

    ERIC Educational Resources Information Center

    Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

    Parent Services Project (PSP), the first comprehensive program of resources and mental health activities for parents offered at child care centers in the San Francisco Bay Area (California), has expanded to centers in six states, serving over 19,000 families. This report describes the program's history, aims, and achievements, along with specific…

  20. Family Disruptions

    MedlinePlus

    ... and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family as ... these out-of-town trips. Spend as much time as it takes to explain where you are ... before and during your travels. You need to acknowledge and accept her feelings: " ...

  1. Multigene families in African swine fever virus: family 505.

    PubMed Central

    Rodriguez, J M; Yañez, R J; Pan, R; Rodriguez, J F; Salas, M L; Viñuela, E

    1994-01-01

    Sequencing of restriction fragment EcoRI A-SalI C of African swine fever virus has revealed the existence of a multigene family, designated family 505 because of the average number of amino acids in the proteins, composed of seven homologous and tandemly arranged genes. All the genes of family 505 are expressed during infection. Primer extension analysis showed that transcription is initiated a short distance (3 to 62 nucleotides) from the start codon of the corresponding open reading frame. The proteins of family 505 showed similarity to those of family 360 from African swine fever virus. In particular, a striking conservation of three regions at the amino terminus of the polypeptides was observed. Images PMID:8139051

  2. [Plesiomonas shigelloides, a Vibrionaceae to be taken into account].

    PubMed

    Bravo, L; Cabrera, R; Ramírez, M; Llop, A; Fernández, A; García, B; Morier, L

    2000-01-01

    The antigenic structure and antimicrobial susceptibility were studied in 99 strains isolated from patients with acute diarrhea (6 strains from an outbreak of digestive transmission disease in Santiago de Cuba) and a strain isolated from a patient who died from infections neurological syndrome (INS, meningitis). Four new serotypes (093, 994, 095, 096), which had not been described in the world classification, were identified from the Cuban isolated strains and were included in the International Serotyping Scheme by the International Reference Center located in Prague, Czech Republic. For the first time in Cuba, the circulation of serotypes 017:H11, 011: H2, 023. H1alc, 057: H3 which show cross reaction to Shiguella species was proved. Those strains from the outbreak of digestive disease belonged to serotype 050: H11 and had a thermostable toxin. The first case of infectious neurologic syndrome with Plesionomas shigelloides etiology reported in Cuba was described; the strain corresponded to serotype 050: H11. The worldwide reported pattern of antimicrobial resistance was demonstrated. PMID:11107887

  3. Adolescents’ Perceptions of Family Belonging in Stepfamilies

    PubMed Central

    King, Valarie; Boyd, Lisa M.; Thorsen, Maggie L.

    2015-01-01

    Prior research has established that adolescents’ perceptions of family belonging are associated with a range of well-being indicators and that adolescents in stepfamilies report lower levels of family belonging than adolescents in two-biological-parent families. Yet, we know little regarding what factors are associated with adolescents’ perceptions of family belonging in stepfamilies. Guided by family systems theory, the authors addressed this issue by using nationally representative data (Add Health) to examine the associations between family characteristics and adolescents’ perceptions of family belonging in stepfather families (N = 2,085). Results from structural equation models revealed that both the perceived quality of the stepfather–adolescent relationship, and in particular the perceived quality of the mother–adolescent relationship, were the factors most strongly associated with feelings of family belonging. PMID:26166845

  4. Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries

    PubMed Central

    Moore, Michael J.; Neubig, Kurt M.; Williams, Norris H.; Whitten, W. Mark; Kim, Joo-Hwan

    2015-01-01

    Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability. PMID:26558895

  5. Family Therapy and Disturbed Families.

    ERIC Educational Resources Information Center

    Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

    Presented at a conference at which authors represented major theoretical positions in the field, most of the papers use family therapy as an important source of observations or ideas, or as a means to pinpoint methodological problems. Papers are grouped in sections as follows: four which introduce the reader to the field of specialization, provide…

  6. Functional characterization of two new members of the caffeoyl CoA O-methyltransferase-like gene family from Vanilla planifolia reveals a new class of plastid-localized O-methyltransferases.

    PubMed

    Widiez, Thomas; Hartman, Thomas G; Dudai, Nativ; Yan, Qing; Lawton, Michael; Havkin-Frenkel, Daphna; Belanger, Faith C

    2011-08-01

    Caffeoyl CoA O-methyltransferases (OMTs) have been characterized from numerous plant species and have been demonstrated to be involved in lignin biosynthesis. Higher plant species are known to have additional caffeoyl CoA OMT-like genes, which have not been well characterized. Here, we identified two new caffeoyl CoA OMT-like genes by screening a cDNA library from specialized hair cells of pods of the orchid Vanilla planifolia. Characterization of the corresponding two enzymes, designated Vp-OMT4 and Vp-OMT5, revealed that in vitro both enzymes preferred as a substrate the flavone tricetin, yet their sequences and phylogenetic relationships to other enzymes are distinct from each other. Quantitative analysis of gene expression indicated a dramatic tissue-specific expression pattern for Vp-OMT4, which was highly expressed in the hair cells of the developing pod, the likely location of vanillin biosynthesis. Although Vp-OMT4 had a lower activity with the proposed vanillin precursor, 3,4-dihydroxybenzaldehyde, than with tricetin, the tissue specificity of expression suggests it may be a candidate for an enzyme involved in vanillin biosynthesis. In contrast, the Vp-OMT5 gene was mainly expressed in leaf tissue and only marginally expressed in pod hair cells. Phylogenetic analysis suggests Vp-OMT5 evolved from a cyanobacterial enzyme and it clustered within a clade in which the sequences from eukaryotic species had predicted chloroplast transit peptides. Transient expression of a GFP-fusion in tobacco demonstrated that Vp-OMT5 was localized in the plastids. This is the first flavonoid OMT demonstrated to be targeted to the plastids. PMID:21629984

  7. FAMILY BOMBYLIIDAE.

    PubMed

    Lamas, Carlos José Einicker; Evenhuis, Neal L

    2016-01-01

    Bombyliidae is one of the largest Diptera families with more than 4,500 recognized species worldwide. Their species vary from robust to thin, and may be small to large (2-20mm) and looks like bees or wasps. They also present great variation in color. Adults can often be seen either resting and sunning themselves on trails, rocks or twigs or feeding on flowering plants as they are nectar feeders. All reared bee flies are predators or parasitoids of arthropods. The Colombian fauna of bombyliids comprises at the moment 22 species, and 12 genera, of which, six are endemic species. Nonetheless, this number may be much higher, as Colombia is a megadiverse country and there are not many specimens of this family deposited in collections all over the world. PMID:27395279

  8. Familial Hypercholesterolemia

    PubMed Central

    Pejic, Rade N.

    2014-01-01

    Background Familial hypercholesterolemia (FH) is an autosomal dominant-inherited genetic disorder that leads to elevated blood cholesterol levels. FH may present as severely elevated total cholesterol and low density lipoprotein (LDL) cholesterol levels or as premature coronary heart disease (CHD). Methods This review presents information on the disease and on the effects of drug treatment and lifestyle changes. Results Routine lipid testing should identify most patients with FH. Once an index case is identified, testing should be offered to family members. Early diagnosis and aggressive treatment with therapeutic lifestyle changes and statins can prevent premature CHD and other atherosclerotic sequelae in patients with FH. Conclusion Emerging therapies such as LDL apheresis and novel therapeutic agents may be useful in patients with homozygous FH or treatment-resistant FH. Liver transplantation is the only effective therapy for severe cases of homozygous FH. PMID:25598733

  9. Family Diversity in 50 Years of Storybook Images of Family Life.

    ERIC Educational Resources Information Center

    Rodman, Nancy M.; Hildreth, Gladys J.

    2002-01-01

    Content analysis of a sample of 100 picture storybooks about family life published 1943-1993 reveals no significant differences in the frequency of appearance of different family types or ethnicities over time. Dominant images remained the nuclear (63%) and Caucasian (67%) family. (Contains 37 references.) (SK)

  10. Gender and the Work-Family Interface: Exploring Differences across the Family Life Course

    ERIC Educational Resources Information Center

    Martinengo, Giuseppe; Jacob, Jenet I.; Hill, E. Jeffrey

    2010-01-01

    This study examines gender differences in the work-family interface across six family life stages using a global sample of IBM employees in 79 countries (N = 41,813). Family life stage was constructed using the age of respondent and age of youngest child. Results revealed that having young children at home was the critical catalyst for gender…

  11. The Families of Lesbian and Gay Men: A New Frontier in Family Research.

    ERIC Educational Resources Information Center

    Allen, Katherine R.; Demo, David H.

    1995-01-01

    A review of 8,000 articles in family research journals revealed that research on lesbian and gay families is limited and that studies that do exist have been problematized and their diversity has been overlooked. Challenges the neglect of this population in family studies, and discusses theoretical implications. (JPS)

  12. Family Lessons and Funds of Knowledge: College-Going Paths in Mexican American Families

    ERIC Educational Resources Information Center

    Kiyama, Judy Marquez

    2011-01-01

    Families are crucial in the development of a college-going culture in the home. This qualitative study illustrates that Mexican American families are no exception. Using a multiple case study design, this study explored the funds of knowledge present in Mexican American families. Findings from this study reveal how daily educational practices,…

  13. Familial Hypercholesterolemia

    PubMed Central

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2015-01-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in physicians and patients in order to reduce the burden of this disorder. PMID:25939291

  14. Familial hypercholesterolemia

    PubMed Central

    Turgeon, Ricky D.; Barry, Arden R.; Pearson, Glen J.

    2016-01-01

    Objective To summarize the pathophysiology, epidemiology, screening, diagnosis, and treatment of familial hypercholesterolemia (FH). Quality of evidence A PubMed search was conducted (inception to July 2014) for articles on pathophysiology, screening, diagnosis, and management of FH, supplemented with hand searches of bibliographies of guidelines and reviews. A supporting level of evidence for each recommendation was categorized as level I (randomized controlled trial or systematic review of randomized controlled trials), level II (observational study), or level III (expert opinion). The best available evidence is mostly level II or III. Main message Familial hypercholesterolemia affects 1 in 500 Canadians. Risk of a coronary event is high in these patients and is underestimated by risk calculators (eg, Framingham). Clinicians should screen patients according to guidelines and suspect FH in any patient with a premature cardiovascular event, physical stigmata of hypercholesterolemia, or an elevated plasma lipid level. Physicians should diagnose FH using either the Simon Broome or Dutch Lipid Network criteria. Management of heterozygous FH includes reducing low-density lipoprotein levels by 50% or more from baseline with high-dose statins and other lipid-lowering agents. Clinicians should refer any patient with homozygous FH to a specialized centre. Conclusion Familial hypercholesterolemia represents an important cause of premature cardiovascular disease in Canadians. Early identification and aggressive treatment of individuals with FH reduces cardiovascular morbidity and mortality. PMID:26796832

  15. Family affairs.

    PubMed

    Dupont, M

    1994-06-01

    It's no secret that your job is stressful, forcing you to deal with tragedy and death on a regular basis. You've become good at what you do because you pay attention to details and care about people. Most of the EMS providers I've known dedicate untold hours to their work, usually in addition to the regular jobs they hold. Their communities need them to be ready at a moment's notice when the pager sounds. Someone is in crisis. A life may hang in the balance-a life they may save. But what about the family that's left behind as you run out the door-yet again? How do your spouse/significant other and kids cope with whatever emotional state you're in when you return home? While your stress may be evident, their distress may be overlooked. What price do they pay to live with you? These questions were addressed during several workshops my colleagues and I conducted for EMS providers and their families. Many of the problems and frustrations identified in this article were shared by EMTs' family members who attended. PMID:10134394

  16. Familial Gigantiform Cementoma

    PubMed Central

    Ma, Chunyue; Wang, Hongwei; He, Guang; Qin, Xingjun

    2016-01-01

    Abstract Familial gigantiform cementoma is an exceedingly rare but distinct subtype of cemento-osseous-fibrous lesion. Undocumented radiographic changes and related bone metabolism disorder are herein hypothesized and discussed. We present an adolescent case with recurrent familial gigantiform cementoma who received surgical intervention in our hospital. Apart from typical multiquadrant and expansile abnormalies involving both jaws, he also suffered from several times of fractures in lower extremity. Furthermore, radiographic examinations of calvaria, pelvis, femoris, tibia, and fibula all revealed radiolucent areas signifying diffuse osteopenic bone losses. Some of his consanguineous relatives bore the same burden of fractures during pubertal period. Considering these polyostotic conditions, a correlation of congenital bone metabolism disorder in cases with familial gigantiform cementoma, named “calcium steal disorder,” was thus proposed. Familial gigantiform cementoma is closely associated with “calcium steal disorder.” Whole-body dual-energy absorptiometry should be considered as a routine examination for fracture-related risk prediction. PMID:26945411

  17. Families Speak to Early Childhood Teachers: Impressions and Expectations

    ERIC Educational Resources Information Center

    Thomas, Suzanne B.; Dykes, Frank

    2013-01-01

    Investigators interviewed 54 families of children with disabilities ages seven through nine to examine the expectations that families of young children hold for their child's teacher. Responses themes were examined to determine if a pattern existed between families of different groups of children. Results reveal many families expressed true…

  18. Work, Family and Community Support as Predictors of Work-Family Conflict: A Study of Low-Income Workers

    ERIC Educational Resources Information Center

    Griggs, Tracy Lambert; Casper, Wendy J.; Eby, Lillian T.

    2013-01-01

    This study examines relationships between support from work, family and community domains with time- and strain-based work-family conflict in a sample of low-income workers. Results reveal significant within-domain and cross-domain relationships between support from all three life domains with work--family conflict. With respect to family support,…

  19. FAMILY MYCETOPHILIDAE.

    PubMed

    Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-01-01

    The Mycetophilidae include small fungus-gnats which life cycle is associated with fungi, especially of the larvae. The known diversity of the family in the Neotropical region is 1,145 species, but only some very few papers have been published on the Colombian species of Mycetophilidae, with records for the genera Docosia Winnertz, Paraleia Tonnoir, and Dziedzickia Johannsen. This catalogue gathers the information available on mycetophilids from Colombia, including genera and some species that for the first time are mentioned to occur in the country-as Leiella unicincta Edwards and Leiella zonalis Edwards. PMID:27395261

  20. FAMILY ANISOPODIDAE.

    PubMed

    Amorim, Dalton De Souza; Falaschi, Rafaela Lopes; Oliveira, Sarah Siqueira

    2016-01-01

    This considerably small family is poorly known in Colombia, with only two species reported for the genus Sylvicola Harris (1776) so far. We synonymize Neomesochria Amorim & Tozoni (1994) to Mycetobia Meigen (1818), hence transferring the Dominican amber species Neomesochria antillea (Grimaldi 1991) and N. cryptambra (Grimaldi 1991), and the recent Neotropical species N. limanda (Stone 1966) and N. stonei (Lane & d'Andretta 1958) back to the genus Mycetobia. This paper provides new records for Mycetobia and Olbiogaster Osten-Sacken (1886) for Colombia. PMID:27395252

  1. FAMILY SCIOMYZIDAE.

    PubMed

    Marinoni, Luciane; Murphy, William L

    2016-01-01

    The Sciomyzidae are a family of acalyptrate flies of worldwide distribution, with 543 extant species and 14 described subspecies in 63 genera. Although 274 species in 37 genera are found in the Western Hemisphere, the sciomyzid fauna of Central and South America remains relatively unknown, comprising 103 species in 25 genera, with only seven species in five genera having been recorded from Colombia: Dictya bergi Valley, Perilimnia albifacies Becker, Pherbellia guttata (Coquillett), Sepedomerus bipuncticeps (Malloch), S. macropus (Walker), Sepedonea guianica (Steyskal), and S. isthmi (Steyskal). PMID:27395301

  2. Family Communication Patterns and the Development of Reticence.

    ERIC Educational Resources Information Center

    Kelly, Lynne; Keaten, James A.; Finch, Cynthia; Duarte, Ilze B.; Hoffman, Patrizia; Michels, Margaret M.

    2002-01-01

    Explores the relationship between family communication patterns and reticence. Reveals that reticent individuals reported a significantly lower level of conversation orientation within their families than members of a comparison group. (SG)

  3. Family and family therapy in the Netherlands.

    PubMed

    Wagenaar, Karin; Baars, Jan

    2012-04-01

    This article describes how families are functioning in the Netherlands, and how family therapy is used in mental healthcare. In the open Dutch society, new ideas are easily incorporated, as exemplified by the rapid introduction and growth of family therapy in the 1980s. In recent decades, however, family therapy has lost ground to other treatment models that are more individually orientated, and adhere to stricter protocols. This decline of family therapy has been exacerbated by recent budget cuts in mental healthcare. In regular healthcare institutes family therapy now has a marginal position at best, although family treatment models are used in specific areas such as forensic treatments. In addition, the higher trained family therapists have found their own niches to work with couples and families. We argue that a stronger position of family therapy would be beneficial for patients and for families, in order to counteract the strong individualization of Dutch society. PMID:22515464

  4. Roles within the Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Text Size Email Print Share Roles Within the Family Page Content Article Body Families are not democracies. ...

  5. National Military Family Association

    MedlinePlus

    ... Clinton and Trump Stand Behind the Uniform? Military families have some questions... More Suicide Prevention Awareness Month ... quick fact sheet about this program. Operation Purple Family Retreats Operation Purple Family Retreats provide military families ...

  6. In Support of Families.

    ERIC Educational Resources Information Center

    Murphy, Albert T.

    1979-01-01

    The article discusses support services and sources for the families of handicapped children. Aspects covered include family involvement in early childhood education programs, emotional support, and family mental health. The characteristics of the "ideal" family are also discussed. (DLS)

  7. Multigene families in African swine fever virus: family 360.

    PubMed Central

    González, A; Calvo, V; Almazán, F; Almendral, J M; Ramírez, J C; de la Vega, I; Blasco, R; Viñuela, E

    1990-01-01

    A group of cross-hybridizing DNA segments contained within the restriction fragments RK', RL, RJ, and RD' of African swine fever virus DNA were mapped and sequenced. Analysis of these sequences revealed the presence of a family of homologous open reading frames in regions close to the DNA ends. The whole family is composed of six open reading frames with an average length of 360 coding triplets (multigene family 360), four of which are located in the left part of the genome and two of which are in the right terminal EcoRI fragment. In close proximity to the right terminal inverted repeat, we found an additional small open reading frame which was homologous to the 5'-terminal portion of the other open reading frames, suggesting that most of that open reading frame has been deleted. These repeated sequences account for the previously described inverted internal repetitions (J.M. Sogo, J.M. Almendral, A. Talavera, and E. Viñuela, Virology 133:271-275, 1984). Most of the genes of multigene family 360 are transcribed in African swine fever virus-infected cells. A comparison of the predicted protein sequences of family 360 indicated that several residues are conserved, suggesting that an overall structure is maintained for every member of the family. The transcription direction of each open reading frame, as well as the evolutionary relationships among the genes, suggests that the family originated by gene duplication and translocation of sequences between the DNA ends. Images PMID:2325203

  8. Familial cutaneous leiomyomatosis.

    PubMed

    Thyresson, H N; Su, W P

    1981-04-01

    A 24-year-old Caucasian man was evaluated because of a history of multiple firm, reddish, papulonodular skin lesions occurring over the buttocks, thighs, and lower portions of his back and legs since the age of 17 years. Most lesions had developed within 1 year of onset and had become very painful. The family history revealed that the patient's mother and maternal aunts had similar skin lesions. The mode of inheritance is that of autosomal dominant pattern. The mother and three maternal aunts all had had hysterectomies. Biopsy specimens of skin lesions with hematoxylin-eosin and Masson-trichrome stains showed typical leiomyoma. Bodian's staining method revealed an increased amount of nerve fibers interlacing within muscle fibers and in the surrounding tissue. This finding may explain the painful nature of the cutaneous leiomyomas. Treatments consist of analgesics for control of pain and selective excision of larger painful leiomyomas. PMID:7229147

  9. The olfactory receptor family album

    PubMed Central

    Crasto, Chiquito; Singer, Michael S; Shepherd, Gordon M

    2001-01-01

    Analysis of the human genome draft sequences has revealed a more complete portrait of the olfactory receptor gene repertoire in humans than was available previously. The new information provides a basis for deeper analysis of the functions of the receptors, and promises new insights into the evolutionary history of the family. PMID:11597337

  10. Families Behind the AFDC Stereotype

    ERIC Educational Resources Information Center

    Grindereng, Margaret P.

    1976-01-01

    In an examination of the accuracy of verbal labels generally attributed to AFDC groups, data revealed the majority of AFDC recipients do not fit the public's stereotypes. The AFDC family, in addition to economic stresses, experiences psychological and social stresses. Ways in which Extension can help AFDC groups are suggested. (Author/BP)

  11. The phagosomal nutrient transporter (Pht) family.

    PubMed

    Chen, Derek E; Podell, Sheila; Sauer, John-Demian; Swanson, Michele S; Saier, Milton H

    2008-01-01

    Phagosomal transporters (Phts), required for intracellular growth of Legionella pneumophila, comprise a novel family of multispanning alpha-helical proteins within the major facilitator superfamily (MFS). The members of this family derive exclusively from bacteria. Multiple paralogues are present in a restricted group of Alpha- and Gammaproteobacteria, but single members were also found in Chlamydia and Cyanobacteria. Their protein sequences were aligned, yielding a phylogenetic tree showing the relations of the proteins to each other. Topological analyses revealed a probable 12 alpha-helical transmembrane segment (TMS) topology. Motif identification and statistical analyses provided convincing evidence that these proteins arose from a six TMS precursor by intragenic duplication. The phylogenetic tree revealed some potential orthologous relationships, suggestive of common function. However, several probable examples of lateral transfer of the encoding genetic material between bacteria were identified and analysed. The Pht family most closely resembles a smaller MFS family (the UMF9 family) with no functionally characterized members. However, the UMF9 family occurs in a broader range of prokaryotic organism types, including Archaea. These two families differ in that organisms bearing members of the Pht family often have numerous paralogues, whereas organisms bearing members of the UMF9 family never have more than two. This work serves to characterize two novel families within the MFS and provides compelling evidence for horizontal transfer of some of the family members. PMID:18174124

  12. Transforming Training. Families Matter.

    ERIC Educational Resources Information Center

    Morgan, Gwen

    The Families Matter series of papers from the Harvard Family Research Project advances the concept of family-centered child care, advocating an approach to early childhood education that addresses the development of the child and family together. Grounded in family support principles, which build on family strengths and work from a community's…

  13. Credentialing Caregivers. Families Matter.

    ERIC Educational Resources Information Center

    Dean, Christiana

    The Families Matter series of papers from the Harvard Family Research Project advances the concept of family-centered child care, advocating an approach to early childhood education that addresses the development of the child and family together. Grounded in family support principles, which build on family strengths and work from a community's…

  14. Reclaiming Family Privilege

    ERIC Educational Resources Information Center

    Seita, John

    2012-01-01

    The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

  15. Integrating Family Resilience and Family Stress Theory.

    ERIC Educational Resources Information Center

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  16. Whole Family: Whole Child. Broken Family.

    ERIC Educational Resources Information Center

    DeVaul, Sue; Davis, John U.

    A literature review on the family environments of gifted students found that gifted children are more likely to be living in intact families than in divorced families. Children of single parents were more likely to be low-achieving, tardy, absent, truant, discipline problems, suspended, expelled, and dropouts than students in two-parent families.…

  17. Family Law and Family Studies: Professor's Views

    ERIC Educational Resources Information Center

    Hicks, Mary W.; And Others

    1977-01-01

    The results of a survey of family studies faculty concerning the inclusion of family law topics in family studies courses are discussed. The professor's needs for training and resources in the area of family and the law are identified and recommendations for meeting these needs are suggested. (Author)

  18. The Family Hero in Black Alcoholism Families.

    ERIC Educational Resources Information Center

    Brisbane, Francis L.

    1989-01-01

    Uses data from 20 case studies of Black adult female children of alcoholic parents to discuss Family Hero role often assumed by oldest or only female child in Black alcoholism families. Explains how female-dominated survival role of Family Hero in Black families is significantly more related to racial and cultural factors than numbers alone may…

  19. Family Psychology and Family Therapy in Japan.

    ERIC Educational Resources Information Center

    Kameguchi, Kenji; Murphy-Shigematsu, Stephen

    2001-01-01

    Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family…

  20. The Family Dynamics of Intellectual Development.

    ERIC Educational Resources Information Center

    Zajonc, R. B.

    2001-01-01

    Birth order effects on intellectual performance show both positive and negative results. Considers the intellectual aspects of siblings' changing environments, explaining that birth order and family size effects depend crucially on the age at which children are tested. Within-family data conceal patterns of aggregate effects that are revealed by…

  1. Familial Hypercholesterolaemia

    PubMed Central

    Marais, A David

    2004-01-01

    Familial hypercholesterolaemia (FH), defined as the heritable occurrence of severe hypercholesterolaemia with cholesterol deposits in tendons and premature heart disease, is caused by at least four genes in sterol and lipoprotein pathways and displays varying gene-dose effects. The genes are the low-density lipoprotein (LDL) receptor, apolipoprotein (apo) B, proprotein convertase subtilisin/kexin 9, and the autosomal recessive hypercholesterolaemia (ARH) adaptor protein. All of these disorders have in common defective clearance of LDL within a complex system of lipid and lipoprotein metabolism and regulation. Normal cellular cholesterol and lipoprotein metabolism is reviewed before describing the disorders, their metabolic derangements and their clinical effects. FH is classified as two simplified phenotypes of disease according to the severity of the metabolic derangement. The dominantly inherited heterozygous phenotype comprises defects in the LDL receptor, apoB100, and neural apoptosis regulatory cleavage protein. The homozygous phenotype is co-dominant in defects of the LDL receptor, and occurs also as the ARH of adapter protein mutations. Defective binding of apoB100 does not result in a significant gene dose effect, but enhances the severity of heterozygotes for LDL receptor mutations. The genetic diagnosis of FH has provided greater accuracy in definition and detection of disease and exposes information about migration of populations. All of these disorders pose a high risk of atherosclerosis, especially in the homozygous phenotype. Studies of influences on the phenotype and responses to treatment are also discussed in the context of the metabolic derangements. PMID:18516203

  2. Familial varieties of primary aldosteronism.

    PubMed

    Stowasser, M; Gunasekera, T G; Gordon, R D

    2001-12-01

    1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties. 2. Familial hyperaldosteronism type I (FH-I) is a glucocorticoid-remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)- regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH-I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone "day curve" studies show that the hybrid gene dominates over wild-type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild-type CYP11B2-induced aldosterone production. Control of hypertension in FH-I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended. 3. Familial hyperaldosteronism type II (FH-II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non-familial PAL. Linkage studies in one informative family did not show segregation of FH-II with the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL. PMID:11903322

  3. Revealing a Child's Pathology: Physicians' Experiences

    ERIC Educational Resources Information Center

    Scelles, Regine; Aubert-Godard, Anne; Gargiulo, Marcela; Avant, Monique; Gortais, Jean

    2010-01-01

    In this study, 12 physicians and 12 care-givers were interviewed using semi-structured interviews. We explored physicians' experiences when they revealed a diagnosis. We also tried to understand which family members the physician was thinking of, with whom they identified themselves, and their first choice of the person to whom they prefer to…

  4. Family Reading Night

    ERIC Educational Resources Information Center

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  5. Family Treatment Unit.

    ERIC Educational Resources Information Center

    Sawicki, Donna

    The document describes the Family Treatment Unit, a demonstration program to provide a variety of family treatment services to status offenders (11 to 17 years old) and their families. The goals of the program are: (1) to provide family services to families of status offenders; (2) to maintain status offenders in their natural homes by…

  6. The Changing Family Structure.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1993

    1993-01-01

    This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand: Families of the Garbage Dump";…

  7. Family development: a classic example.

    PubMed

    1979-01-01

    On August 15, 1978, the integrated parasite control/family planning program was launched by the National Family Planning Board in the Tanjong Malim Estate in Kuala Lumpur (the estate is a rubber oil palm plantation) to enhance the health status of the estate workers and their families. Personal hygiene, good toilet habits, and washing fruits and vegetables before eating were emphasized. Pre- and post-surveys of worm infestation of the estate population revealed that treatment with drugs dramatically reduced the rate of intestinal helminthiasis infection among the population. To sustain the prevention or total eradication of the disease, an ongoing educational program was initiated and included the following features: 1) increasing knowledge of the community as to how intestinal helminthiasis is transmitted, and ways of limiting transmission; 2) providing safe and sanitary toilet facilities for young children, and; 3) periodic deworming of susceptible population every 3 months. The estate members are also encouraged to plant vegetables in their backyard. The National Family Planning Board also helped the estate members organize different functional groups, such as Mothers' Group. This multifaceted approach to family planning appears to have an encouraging future, particularly in family development. PMID:12261448

  8. Insights Gained from the Use of Genograms To Analyze Communication Dimensions in Family Systems.

    ERIC Educational Resources Information Center

    Brommel, Bernard J.

    Genograms (a "psychological" family tree) can reveal how the family communicates about its past. The drawing of the family tree becomes an exercise in communication. In a classroom assignment, students can do their own genogram or create one by doing interviews with a family to gain insights into various dimensions of the family's communication.…

  9. The Impact of Family Life Events and Changes on the Health of a Chronically Ill Child.

    ERIC Educational Resources Information Center

    Patterson, Joan M.; McCubbin, Hamilton I.

    1983-01-01

    Examined the relationship between family stress and changes in health of a child with cystic fibrosis. Data from parents (N=100) and clinic records revealed that a decline in pulmonary functioning was associated with family life changes, especially in family development and relationships, family management and decisions, and family finances.…

  10. Shared vision promotes family firm performance

    PubMed Central

    Neff, John E.

    2015-01-01

    A clear picture of the influential drivers of private family firm performance has proven to be an elusive target. The unique characteristics of private family owned firms necessitate a broader, non-financial approach to reveal firm performance drivers. This research study sought to specify and evaluate the themes that distinguish successful family firms from less successful family firms. In addition, this study explored the possibility that these themes collectively form an effective organizational culture that improves longer-term firm performance. At an organizational level of analysis, research findings identified four significant variables: Shared Vision (PNS), Role Clarity (RCL), Confidence in Management (CON), and Professional Networking (OLN) that positively impacted family firm financial performance. Shared Vision exhibited the strongest positive influence among the significant factors. In addition, Family Functionality (APGAR), the functional integrity of the family itself, exhibited a significant supporting role. Taken together, the variables collectively represent an effective family business culture (EFBC) that positively impacted the long-term financial sustainability of family owned firms. The index of effective family business culture also exhibited potential as a predictive non-financial model of family firm performance. PMID:26042075

  11. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  12. Family Reunion Health Guide

    MedlinePlus

    ... Phone (Continued) 1. Send a Kidney Health Message Hi Family, I came across this information and thought ... mails to family members. Before the Reunion 1. Hi family! Taking care of your kidneys is important. ...

  13. Improving Family Communications

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  14. Normal Functioning Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  15. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  16. Developing Strengths in Families

    ERIC Educational Resources Information Center

    Bowman, Ted

    1976-01-01

    There are few descriptions of growth experiences for total families. This paper describes one such model. It expresses the conviction that families need opportunities to come together with other families to identify strengths, sharpen communication skills, and establish goals. (Author)

  17. Living My Family's Story

    PubMed Central

    Underhill, Meghan L.; Lally, Robin M.; Kiviniemi, Marc T.; Murekeyisoni, Christine; Dickerson, Suzanne S.

    2013-01-01

    Background Based on known or suggested genetic risk factors, a growing number of women now live with knowledge of a potential cancer diagnosis that may never occur. Given this, it is important to understand the meaning of living with high risk for hereditary breast cancer. Objective The objective of the study was to explore how women at high risk for hereditary breast cancer (1) form self-identity, (2) apply self-care strategies toward risk, and (3) describe the meaning of care through a high-risk breast program. Methods Interpretive hermeneutic phenomenology guided the qualitative research method. Women at high risk for hereditary breast cancer were recruited from a high-risk breast program. Open-ended interview questions focused on experiences living as women managing high risk for breast cancer. Consistent with hermeneutic methodology, the principal investigator led a team to analyze the interview transcripts. Results Twenty women participated in in-depth interviews. Analysis revealed that women describe their own identity based on their family story and grieve over actual and potential familial loss. This experience influences self-care strategies, including seeking care from hereditary breast cancer risk experts for early detection and prevention, as well as maintaining a connection for early treatment “when” diagnosis occurs. Conclusions Healthy women living with high risk for hereditary breast cancer are living within the context of their family cancer story, which influences how they define themselves and engage in self-care. Implications for Practice Findings present important practical, research, and policy information regarding health promotion, psychosocial assessment, and support for women living with this risk. PMID:22544165

  18. Anticipation in familial leukemia.

    PubMed Central

    Horwitz, M.; Goode, E. L.; Jarvik, G. P.

    1996-01-01

    Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22. PMID:8900225

  19. Spiritual Coping: A Gateway to Enhancing Family Communication During Cancer Treatment.

    PubMed

    Prouty, Anne M; Fischer, Judith; Purdom, Ann; Cobos, Everardo; Helmeke, Karen B

    2016-02-01

    The researchers examined the spiritual coping, family communication, and family functioning of 95 participants in 34 families by an online survey. Multilevel linear regression was used to test whether individuals' and families' higher endorsement of more use of spiritual coping strategies to deal with a member's cancer would be associated with higher scores on family communication and family functioning, and whether better communication would also be associated with higher family functioning scores. Results revealed that spiritual coping was positively associated with family communication, and family communication was positively associated with healthier family functioning. The researchers provide suggestions for further research. PMID:26311053

  20. The Invisible Mirror: In-Home Family Therapy and Supervision.

    ERIC Educational Resources Information Center

    Zarski, John J.; And Others

    1991-01-01

    Discusses home-based family therapy intervention programs, designed as a preventive strategy for multiproblem, at-risk families in mental health agencies. Maintains that a review of the literature reveals little information on clinical supervision, which is a major component of home-based family intervention. Focuses on providing an alternative…

  1. Families and family therapy in Hong Kong.

    PubMed

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families. PMID:22515459

  2. Family Patterns of Gender Role Attitudes

    PubMed Central

    Marks, Jaime; Bun, Lam Chun; McHale, Susan M.

    2012-01-01

    Study goals were to identify family patterns of gender role attitudes, to examine the conditions under which these patterns emerged, and to assess the implications of gender attitude patterns for family conflict. Participants were mothers, fathers, and first- and second-born adolescents from 358 White, working and middle-class US families. Results of cluster analysis revealed three gender role attitude patterns: egalitarian parents and children, traditional parents and children, and a divergent pattern, with parents more traditional and children more egalitarian. Mixed-model ANOVAs indicated that these family patterns were related to socioeconomic status, parents' time spent in gendered household tasks and with children, and the gender constellation of the sibling dyad. The traditional family group reported the most family conflict. PMID:22308059

  3. Genome Sequencing Reveals Unique Mutations in Characteristic Metabolic Pathways and the Transfer of Virulence Genes between V. mimicus and V. cholerae

    PubMed Central

    Zhou, Yanyan; Zhang, Qiuxiang; Zhang, Fanfei; Du, Pengcheng; Wang, Shujing; Chen, Chen; Kan, Biao

    2011-01-01

    Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes. PMID:21731695

  4. Strengthening Family Practices for Latino Families

    PubMed Central

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9–12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto Rican families. PMID:20871785

  5. Scholastic Achievement and Family Marital Structure: Bedouin-Arab Adolescents from Monogamous and Polygamous Families in Israel.

    ERIC Educational Resources Information Center

    Elbedour, Salman; Bart, William M.; Hektner, Joel M.

    2000-01-01

    Examines the scholastic achievement in Arabic, English, Hebrew, and mathematics of 240 Bedouin-Arab adolescents from monogamous and polygamous families in Negev (Israel). Reveals that adolescents from monogamous and polygamous families demonstrate equivalent levels of scholastic achievement, although boys in polygamous families and girls in…

  6. Familial ankyloglossia (tongue-tie).

    PubMed

    Klockars, Tuomas

    2007-08-01

    Ankyloglossia (tongue-tie) is a congenital anomaly with a prevalence of 4-5% and characterized by an abnormally short lingual frenulum. For unknown reasons the abnormality seems to be more common in males. The pathogenesis of ankyloglossia is not known. The author reports a family with isolated ankyloglossia inherited as an autosomal dominant trait. The identification of the defective gene(s) causing ankyloglossia might reveal novel information on the craniofacial embryogenesis and its disorders. PMID:17588677

  7. Testing a model of family stress and coping based on war and non-war stressors, family resources and coping among Lebanese families.

    PubMed

    Farhood, L F

    1999-08-01

    This study was undertaken to describe the objective stressors, perceived stress, coping, and resources of families living in Beirut during the Lebanese war (1975-1991) and to test a model predicting the relationships of these variables to family adaptation. The sample consisted of 438 families chosen at random. Independent variables included objective stressors and perceived stress. The mediating variables were family resources and coping strategies. The dependent variables were health and interactional indicators of family adaptation: physical and psychological health, depression, and interpersonal and marital relationships. Findings provided support for the theoretical framework. Multiple regression analyses revealed that perceived stress, rather than the objective occurrence of events, predicted family adaptation. Family resources, particularly social support, positively impacted family adaptation and was associated with increased use of cognitive coping. The findings provide a theoretical model which, on further testing, can serve as a basis for practice by health professionals when working with traumatized families. PMID:10478497

  8. Systematic review of family functioning in families of children and adolescents with chronic pain

    PubMed Central

    Lewandowski, Amy S.; Palermo, Tonya M.; Stinson, Jennifer; Handley, Susannah; Chambers, Christine T.

    2010-01-01

    Disturbances in family functioning have been identified in youth with chronic pain and are associated with worse child physical and psychological functioning. Assessment measures of family functioning used in research and clinical settings vary. This systematic review summarizes studies investigating relationships among family functioning, pain and pain-related disability in youth with chronic pain. Sixteen articles were reviewed. All studies were cross-sectional, seven utilized between-group comparisons (chronic pain versus healthy/control) and twelve examined within-group associations among family functioning, pain and/or pain-related disability. Studies represented youth with various pain conditions (e.g., headache, abdominal pain, fibromyalgia) aged 6 – 20 years. Findings revealed group differences in family functioning between children with chronic pain and healthy controls in five of seven studies. Significant associations emerged among family variables and pain-related disability in six of nine studies with worse family functioning associated with greater child disability; relationships between family functioning and children’s pain were less consistent. Different patterns of results emerged depending on family functioning measure used. Overall, findings showed that families of children with chronic pain generally have poorer family functioning than healthy populations, and that pain-related disability is more consistently related to family functioning than pain intensity. PMID:21055709

  9. Dual-Income Families.

    ERIC Educational Resources Information Center

    McKitric, Eloise J.

    The impact of economic conditions on two-earner families was examined. Three family types were studied: (1) dual-career family--both the husband and wife are in the labor force but in occupations classified as professional-technical or managerial; (2) dual-earner--both the husband and wife are in the labor force; and (3) traditional family--the…

  10. Building Family Capital

    ERIC Educational Resources Information Center

    Lamb, Penny

    2007-01-01

    The family is centre stage of many current policy agendas and this is an exciting time to expand the understanding of the wider benefits of learning as a family and in a family. This article aims to open up new discussions and debate on using the concept of "family capital". The author states that as the debate on the social value of learning and…

  11. [Teaching about Family Law].

    ERIC Educational Resources Information Center

    Ryan, John Paul, Ed.

    1992-01-01

    This issue of "Focus on Law Studies""contains a special emphasis on teaching about law and the family", in the form of the following three articles: "Teaching Family Law: Growing Pains and All" (Susan Frelich Appleton); "The Family Goes to Court: Including Law in a Sociological Perspective on the Family" (Mary Ann Lamanna); and Michael Grossberg's…

  12. Families in Transition .

    ERIC Educational Resources Information Center

    Bundy, Michael L., Ed.; Gumaer, James, Ed.

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  13. Black Families. Third Edition.

    ERIC Educational Resources Information Center

    McAdoo, Harriette Pipes, Ed.

    The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say 'Amen'" (William Harrison…

  14. Familial colorectal cancer.

    PubMed

    Lung, M S; Trainer, A H; Campbell, I; Lipton, L

    2015-05-01

    Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. PMID:25955461

  15. Exploring the spiritual needs of families with seriously ill children.

    PubMed

    Ferrell, Betty; Wittenberg, Elaine; Battista, Vanessa; Walker, Gay

    2016-08-01

    Although we know that families of seriously ill children experience spiritual distress, especially at the end of the child's life, there is little information on the specific spiritual needs of families. In order to develop further training for nurses in paediatrics and help nurses develop skills for communicating about spirituality, this research examined the spiritual needs of families based on nurses' experiences with families of seriously ill children. Nurses' experiences revealed that families' anger with God, blame/regret, forgiveness, and ritual and cultural traditions are salient spiritual needs requiring effective nurse communication skills to support families of ill children. PMID:27568778

  16. How Are Preferences Revealed?

    PubMed Central

    Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

    2009-01-01

    Revealed preferences are tastes that rationalize an economic agent’s observed actions. Normative preferences represent the agent’s actual interests. It sometimes makes sense to assume that revealed preferences are identical to normative preferences. But there are many cases where this assumption is violated. We identify five factors that increase the likelihood of a disparity between revealed preferences and normative preferences: passive choice, complexity, limited personal experience, third-party marketing, and intertemporal choice. We then discuss six approaches that jointly contribute to the identification of normative preferences: structural estimation, active decisions, asymptotic choice, aggregated revealed preferences, reported preferences, and informed preferences. Each of these approaches uses consumer behavior to infer some property of normative preferences without equating revealed and normative preferences. We illustrate these issues with evidence from savings and investment outcomes. PMID:24761048

  17. Nontraditional family romance.

    PubMed

    Corbett, K

    2001-07-01

    Family stories lie at the heart of psychoanalytic developmental theory and psychoanalytic clinical technique, but whose family? Increasingly, lesbian and gay families, multiparent families, and single-parent families are relying on modern reproductive technologies to form families. The contemplation of these nontraditional families and the vicissitudes of contemporary reproduction lead to an unknowing of what families are, including the ways in which psychoanalysts configure the family within developmental theory. This article focuses on the stories that families tell in order to account for their formation--stories that include narratives about parental union, parental sexuality, and conception. The author addresses three constructs that inform family stories and that require rethinking in light of the category crises posed by and for the nontraditional family: (1) normative logic, (2) family reverie and the construction of a family romance, and (3) the primal scene. These constructs are examined in tandem with detailed clinical material taken from the psychotherapy of a seven-year-old boy and his two mothers. PMID:11491437

  18. Family Therapy for the "Truncated" Nuclear Family.

    ERIC Educational Resources Information Center

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  19. Conceptualising Family Life and Family Policies.

    ERIC Educational Resources Information Center

    Edgar, Don

    The United Nations International Year of the Family 1994 will give policymakers the opportunity to bring together threads of social life that have previously been treated separately. The danger in talking about the concept of "the family" lies both in its abstractness and in its emotional, religious, and political overtones. To avoid this…

  20. Putting the "family" back into family therapy.

    PubMed

    Breunlin, Douglas C; Jacobsen, Elizabeth

    2014-09-01

    In this article, we examine the field of family therapy by drawing a distinction between two forms of practice: Whole Family Therapy (WFT), defined as treating the whole family, and Relational Family Therapy (RFT), defined as working with a subsystem of the family or an individual while retaining a systemic lens. Our thesis is that the practice of WFT has been in decline for some time and steps must be taken to keep it from becoming a defunct practice. We consider the trajectory of WFT and RFT throughout the development of family therapy through reference to the people, the literature, training, and practice patterns associated with family therapy. We remind the reader of the many benefits of WFT and suggest that today WFT is likely to be practiced in conjunction with RFT and individual therapy. Since training of family therapists today is largely located in degree-granting programs, we identify constraints to including WFT in such programs. We conclude by offering suggestions that can enhance a program's ability to train students in WFT. PMID:24948531

  1. Strengthening Family Practices for Latino Families

    ERIC Educational Resources Information Center

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  2. Families and Family Study in International Perspective

    ERIC Educational Resources Information Center

    Adams, Bert N.

    2004-01-01

    Many changes are occurring in the world's families. Some observers feel that the changes are destructive, whereas others see them as leading to new opportunities and understanding. Issues in international family studies include regional limitations and the various aspects of doing research cross-culturally. Knowledge regarding certain categories…

  3. Invest in Family*

    PubMed Central

    Shah, Nilesh; De Sousa, Avinash

    2015-01-01

    The family is an integral part of one's life. It is very essential that every individual employed or unemployed invests time therein. The family is a source of support and growth for an individual, and the lack of family support or loneliness may be a causative factor in the genesis of psychiatric disorders, especially depression. In India, family plays a paramount role when it comes to mental health of the individual. Tips on how one should invest time in one's family along with the role of a family in one's personal and social structure are discussed. PMID:25838732

  4. Assessing interagency collaboration through perceptions of families.

    PubMed

    Ervin, Naomi E

    2004-01-01

    The purpose of the study reported in this article was to describe the perceptions of families about services they received from multiple health and social service agencies. The conceptual framework of the Interagency Collaboration Model was used to guide the descriptive study. Face-to-face interviews were conducted with 12 families who had received services from at least 3 agencies in the year before data collection. Results of the study showed that families had an average of 5.6 services over the year before the interviews were conducted. Family incomes ranged from totally inadequate to mostly adequate. Education of the participants ranged from 6th grade to some college. Most services were health-related. Interviews revealed that agency personnel were aware of other agencies, according to families' reports. Domain similarity did not appear to be a characteristic of the agencies in this study. PMID:14979846

  5. Improving Youth Mental Health through Family-Based Prevention In Family Homeless Shelters.

    PubMed

    Lynn, Cynthia J; Acri, Mary C; Goldstein, Leah; Bannon, William; Beharie, Nisha; McKay, Mary M

    2014-09-01

    This exploratory study examines changes in suicidal ideation among a sample (N = 28) of homeless youth, ages 11-14, residing within family shelters in a large metropolitan area. Changes in suicidal ideation from pretest to posttest are compared across two group approaches to delivering HIV prevention. Youth and their families participating in the HOPE Family Program, incorporating a family strengthening approach, are compared to those receiving a traditional health education-only approach. Multivariate analyses reveal that youth in the HOPE Family Program were 13 times more likely to report a decrease of suicidal ideation. These findings indicate that health education programs integrating a family strengthening approach hold promise for positively impacting mental health outcomes for vulnerable youth. PMID:25157200

  6. Stress on the Job: How Family Literacy Program Directors Perceive Occupational Stress

    ERIC Educational Resources Information Center

    Sandlin, Jennifer A.; Chen, Chia-Yin

    2007-01-01

    Little research has examined stress among family literacy administrators, although studies in other contexts reveal occupational stress can lead to illness, distress, and organizational problems. This article presents findings from a recent study of stress among family literacy program directors in Texas. Findings reveal family literacy program…

  7. The Changing American Family.

    ERIC Educational Resources Information Center

    Joseph, Pamela B.

    1986-01-01

    Reviews recent statistics which demonstrate how different modern families are from the stereotyped model American nuclear family. Provides suggestions for elementary social studies teachers and includes an annotated bibliography of instructional resources. (JDH)

  8. Familial Periodic Paralyses

    MedlinePlus

    ... NINDS NINDS Familial Periodic Paralyses Information Page Synonym(s): Periodic Paralyses Table of Contents (click to jump to sections) What are Familial Periodic Paralyses? Is there any treatment? What is the ...

  9. Familial Pulmonary Fibrosis

    MedlinePlus

    ... are here: Health Information > Condition Information Familial Pulmonary Fibrosis: Overview When two or more members within the ... Associate Professor View full profile More Familial Pulmonary Fibrosis Information Forms Causes Genetic Counseling Print Page Email ...

  10. Family Patterns in Dogmatism

    ERIC Educational Resources Information Center

    Lesser, Harvey; Steininger, Marion

    1975-01-01

    Explored Rokeach's theory that dogmatism develops within the family. Subjects were college students and their parents who took the 40-item Dogmatism Scale. Results indicated that family experiences are one source of children's dogmatism but not the only source. (SDH)

  11. Importance of Family Routines

    MedlinePlus

    ... Listen Español Text Size Email Print Share The Importance of Family Routines Page Content ​Every family needs ... child to sleep. These rituals can include storytelling, reading aloud, conversation, and songs. Try to avoid exciting ...

  12. Familial multiple lipomatosis.

    PubMed

    Dolph, J L; Demuth, R J; Miller, S H

    1980-10-01

    The literature on familial multiple lipomatosis is reviewed, and a striking case is described. The associated family history is outlined. Excisional biopsy is advocated when there is doubt in terms of diagnosis, pain, or functional impairment. PMID:7208678

  13. Strengthening America's Families.

    ERIC Educational Resources Information Center

    Alvarado, Rose; Kumpfer, Karol

    2000-01-01

    Improving parenting practices and the family environment is the most effective, enduring strategy for combating juvenile delinquency. Describes the Office of Juvenile Justice and Delinquency Prevention's Strengthening America's Families Initiative. Highlights several family-focused prevention programs identified as exemplary, explaining how they…

  14. Families in Multicultural Perspective.

    ERIC Educational Resources Information Center

    Ingoldsby, Bron B., Ed.; Smith, Suzanna, Ed.

    Covering contemporary Third World as well as Western families, this teaching text addresses topics essential for developing a multicultural perspective on the family. It is an ideal text for comparative family courses and includes exercises (as well as exercise guidelines for instructors) developed to challenge students' existing viewpoints and…

  15. Single Mothers "Do" Family

    ERIC Educational Resources Information Center

    Nelson, Margaret K.

    2006-01-01

    This paper explores how single mothers both incorporate others into family life (e.g., when they ask others to care for their children) and simultaneously "do families" in a manner that holds out a vision of a "traditional" family structure. Drawing on research with White, rural single mothers, the author explores the manner in which these women…

  16. The Resiliency of Families.

    ERIC Educational Resources Information Center

    Morrison, T. R.

    According to researchers, the family may be changing but it is still one of the central institutions in society. Studies report a shift in more than 20 attitudes and values, most of which relate to the context of family life. Specifically, these include attitudes toward marriage, divorce, childbearing, childrearing, working women, family violence,…

  17. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  18. Rape: A Family Crisis.

    ERIC Educational Resources Information Center

    White, Priscilla N.; Rollins, Judith C.

    1981-01-01

    Rape is a crisis shared by the victim and her family. The family's reaction is influenced by cultural views such as viewing rape as sex rather than violence. Adaptive responses can be supported by open expression, education, and family, as well as individual counseling. (JAC)

  19. Family Violence: An Overview.

    ERIC Educational Resources Information Center

    National Center on Child Abuse and Neglect (DHHS/OHDS), Washington, DC.

    Family violence is a widespread problem; research has shown multiple factors are associated with family violence. Types of family violence include spouse abuse; elder abuse and neglect; child abuse and neglect; parent abuse; and sibling abuse. There are three types of spouse abuse: physical abuse, sexual violence, and psychological/emotional…

  20. Fatherhood and Family Support.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1996-01-01

    On the assumption that fathers have been relatively absent from family support programs, this publication of the Family Resource Coalition addresses the role of fathers in family support programs, examines the impact of fathers on their children, and describes programs involving fathers successfully. Articles include: (1) "What's Behind the…

  1. Families and Assisted Living

    ERIC Educational Resources Information Center

    Gaugler, Joseph E.; Kane, Robert L.

    2007-01-01

    Purpose: Despite growing research on assisted living (AL) as a residential care option for older adults, the social ramifications of residents' transitions to AL are relatively unexplored. This article examines family involvement in AL, including family structures of residents, types of involvement from family members living outside the AL…

  2. Families for All Children.

    ERIC Educational Resources Information Center

    Shoultz, Bonnie, Ed.; Kalyanpur, Maya, Ed.

    This bulletin reflects the commitment of Syracuse University's Center on Human Policy to the idea that children belong with families. The bulletin contains a policy statement which recommends; that all children, regardless of disability, belong with families and need enduring relationships with adults; that families with severely disabled children…

  3. Focus on the Family.

    ERIC Educational Resources Information Center

    Hardy, James M.

    This research attempts to evaluate the YMCA's program in terms of its effect upon the family members it serves. The study was designed to: (1) classify, by descriptive types, the various kinds of YMCA operations which serve the family, identifying their characteristic differences; (2) examine and describe operating practices of family YMCAs…

  4. Doing Better for Families

    ERIC Educational Resources Information Center

    OECD Publishing (NJ3), 2011

    2011-01-01

    All OECD governments want to give parents more choice in their work and family decisions. This book looks at the different ways in which governments support families. It seeks to provide answers to questions like: Is spending on family benefits going up, and how does it vary by the age of the child? Has the crisis affected public support for…

  5. Launching Family Message Journals.

    ERIC Educational Resources Information Center

    Wollman-Bonilla, Julie

    This lesson introduces Family Message Journals, a tool for encouraging family involvement and supporting writing to reflect and learn. First and second graders are led into composing through demonstration, guided writing, and finally independent writing of messages that they will bring home for family to read and write a reply. During the three…

  6. Family Life Education Transparencies.

    ERIC Educational Resources Information Center

    Clemson Univ., SC. Vocational Education Media Center.

    This compilation of thirty-three transparencies, a supplement to the family life education curriculum guide (see related note), is designed for use by secondary education home economics teachers in teaching family life education classes. The transparencies, covering three areas in family life education, each consist of a captioned picture…

  7. Year of the Family.

    ERIC Educational Resources Information Center

    California Agriculture, 1994

    1994-01-01

    This special issue focuses on problems and challenges confronting the California family and on research and extension efforts to provide at least partial answers. Research briefs by staff include "Challenges Confront the California Family" (state trends in poverty, divorce, single-parent families, child abuse, delinquency, teen births, limited…

  8. Family Customs and Traditions.

    ERIC Educational Resources Information Center

    MacGregor, Cynthia

    Recognizing the importance of maintaining open communication with immediate and extended family members, this book provides a compilation of ideas for family traditions and customs that are grounded in compassion and human kindness. The traditions were gathered from families in the United States and Canada who responded to advertisements in…

  9. Parental Substance Use, Family Support and Outcome Following Treatment for Adolescent Psychoactive Substance Use Disorders.

    ERIC Educational Resources Information Center

    Whitney, Stephen D.; Kelly, John F.; Myers, Mark G.; Brown, Sandra A.

    2002-01-01

    Examines family variables that may influence adolescent substance use during the 6 months following inpatient treatment: parental substance use, family aftercare attendance, and adolescent ratings of family helpfulness. Results revealed no relationship between either parental substance use and family aftercare attendance or reports of family…

  10. Family Issues for the Nineties.

    ERIC Educational Resources Information Center

    Mirabelli, Alan

    This presentation reviews the characteristics of the Canadian family at present. Discussion focuses on divorce, family structure, reproductive technology, fertility, family size, family mobility, family support, government role, women's participation in the labor force, daily family routines, television viewing, work and the family, the need for…

  11. Observed sensitivity during family interactions and cumulative risk: A study of multiple dyads per family.

    PubMed

    Browne, Dillon T; Leckie, George; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M

    2016-07-01

    The present study sought to investigate the family, individual, and dyad-specific contributions to observed cognitive sensitivity during family interactions. Moreover, the influence of cumulative risk on sensitivity at the aforementioned levels of the family was examined. Mothers and 2 children per family were observed interacting in a round robin design (i.e., mother-older sibling, mother younger-sibling and sibling-dyad, N = 385 families). Data were dyadic, in that there were 2 directional scores per interaction, and were analyzed using a multilevel formulation of the Social Relations Model. Variance partitioning revealed that cognitive sensitivity is simultaneously a function of families, individuals and dyads, though the importance of these components varies across family roles. Cognitive sensitivity for mothers was primarily attributable to individual differences, whereas cognitive sensitivity for children was predominantly attributable to family and dyadic differences, especially for youngest children. Cumulative risk explained family and individual variance in cognitive sensitivity, particularly when actors were older or in a position of relative competence or authority (i.e., mother to children, older to younger siblings). Overall, this study demonstrates that cognitive sensitivity operates across levels of family organization, and is negatively impacted by psychosocial risk. (PsycINFO Database Record PMID:27337515

  12. [Family policy in Belgium].

    PubMed

    Dumon, W

    1987-01-01

    The development of family policy in Belgium since the end of World War I is described. Three periods are identified. The original objectives were to provide a basic income level for all families and to promote fertility. After World War II, measures were introduced to foster the physical and psychological health of the family, including the protection of women's rights. More recent policy trends have concentrated on family income and providing services at the family rather than the institutional level. (SUMMARY IN ENG AND FRE) PMID:12280764

  13. Family traditions and generations.

    PubMed

    Schneiderman, Gerald; Barrera, Maru

    2009-01-01

    Currently, traditional family values that have been passed down through generations appear to be at risk. This has significant implications for the stability and health of individuals, families, and communities. This article explores selected issues related to intergenerational transmission of family values and cultural beliefs, with particular reference to Western culture and values that are rooted in Jewish and Christian traditions. It also examines family values and parenting styles as they influence the developing perspective of children and the family's adaptation to a changing world. PMID:19752638

  14. Free-Choice Family Learning Experiences at Telescope Observing Events

    NASA Astrophysics Data System (ADS)

    Wenger, M. C.; Carter, K.; Harris, C. J.

    2011-09-01

    This study examines family experiences at nighttime telescope observing events. The goal was to observe family visitors and understand how they negotiate meaning and incorporate these experiences into their family culture. In this case study of one family's telescope observing experience, the participants' motivations and agenda are described as well as ways in which they negotiated identity and family-community membership at the same time as they were involved in the construction of meaning. The analysis revealed evidence of both meaning making and identity negotiation during, and related to, the educational leisure activity of attending a nighttime telescope observing event.

  15. Familial occurrence of adiposis dolorosa.

    PubMed

    Campen, R; Mankin, H; Louis, D N; Hirano, M; Maccollin, M

    2001-01-01

    Adiposis dolorosa is a rare condition characterized by multiple painful lipomas. We describe two typically affected siblings who were found to have at least 5 affected first-degree relatives in two generations. Manifestations were remarkably variable, ranging from complete disability to solitary asymptomatic tumors. Review of histopathologic findings did not reveal any features that might distinguish the tumors from common sporadic lipomas. Mutational analysis excluded the 8344 A to G mitochondrial mutation seen in other patients with multiple lipomas. Adiposis dolorosa may be an extreme manifestation of the more common condition of familial multiple lipomas. Further work is needed to define the genetic basis of these conditions. PMID:11148491

  16. US weapons secrets revealed

    SciTech Connect

    Norris, R.S.; Arkin, W.M.

    1993-03-01

    Extraordinary details have only recently been revealed about the struggle over the control of early U.S. nuclear weapons and their initial deployments abroad. The information comes from a newly declassified top secret report, part of a larger study, The History of the Strategic Arms Competition, 1945-1972, commissioned by Defense Secretary James R. Schlisinger in summer 1974.

  17. A case of functional urinary retention: the use of family play therapy.

    PubMed

    Stoddard, F R; Wilberger, M S; Olafson, E

    1993-09-01

    This case presents a technique for doing family therapy in families with young children. In family play therapy, the entire family plays together, allowing full participation of even the youngest children in the therapeutic process. Standard family therapy interventions in the latter part of each session make use of family interaction patterns and unconscious processes revealed during the earlier play. In the case presented here, the technique was successfully applied to a family with a 3-year-old son who had functional urinary retention. This case also provided an opportunity for interdisciplinary collaboration between the separate Child and Family Services at a major teaching hospital. PMID:8243618

  18. Plant transcriptomes reveal hidden guests.

    PubMed

    Zhu, Jiao; Wang, Guirong; Pelosi, Paolo

    2016-06-01

    With the wide adoption of transcriptome sequencing an ever increasing amount of information is becoming available, together with spurious data originating from contamination. We show that sometimes errors and inaccuracy can turn beneficial, revealing insect and arthropod pests when analysing plant transcriptomes. We have found a large number of soluble olfactory proteins, odorant-binding proteins (OBPs) and chemosensory proteins (CSPs), in plant databases, likely due to contamination by guest insects. In fact, both classes of proteins are only expressed in insects, with few CSPs also present in other arthropods. In addition, we found many sequences of the Niemann-Pick (Npc2) family, proteins dedicated to cholesterol transport in vertebrates and hypothesised to be involved in chemical communication in insects, but absent in plants. In several cases we were able to trace down members of the three classes of proteins to the insect or arthopod species responsible for contamination. Our work suggests that genes found in plants and recognised as contaminants can be turned into useful information to investigate plant-insect relationships or to identify new sequences from insects species not yet investigated. PMID:27130825

  19. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  20. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  1. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  2. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  3. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  4. Family Relationships From Adolescence to Early Adulthood: Changes in the Family System Following Firstborns’ Leaving Home

    PubMed Central

    Whiteman, Shawn D.; McHale, Susan M.; Crouter, Ann C.

    2010-01-01

    This study charted the course of parent-child and sibling relationships from early adolescence to early adulthood and examined how these relationships changed following firstborns’ departure from their parents’ home for the first time. Data were drawn from a 10-year longitudinal study of family relationships. Participants included mothers, fathers, and first- and second-born children from 184, White, working and middle class families. Multilevel models revealed declines in parent-child conflict, acceptance, and sibling negativity, and increases or U-shaped patterns in sibling and parent-child intimacy over time. Birth order X leaving home interactions revealed that firstborns’ leaving home related to changes in family relationship qualities for both first- and second-borns, with relationships improving for firstborns and no changes or declines in relationship quality for second-borns. Overall, the results highlight the inter-relatedness of family subsystems. PMID:21765625

  5. Creating a Family Health History

    MedlinePlus

    ... Health History? Click for more information A Family Tree for Health A family health history is a ... family members grew up. It's like a family tree for health. Click for more information What a ...

  6. Fields of Toil: A Migrant Family's Journey.

    ERIC Educational Resources Information Center

    Valle, Isabel

    Journalist Isabel Valle lived and traveled for 1 year with the family of Raul and Maria Elena Martinez, migrant farmworkers who make their permanent home in south Texas. Her reports appeared every Sunday in the Walla Walla Union-Bulletin's award-winning series "Fields of Toil." This book compiles those weekly reports, which reveal the issues that…

  7. Some Family Antecedents of Severe Shyness.

    ERIC Educational Resources Information Center

    Gilmartin, Brian G.

    1985-01-01

    Comparison of 100 older and 200 younger love-shy men to 200 nonshy men revealed that love-shys were more likely to have grown up without sisters or as only children, and to have come from homes characterized by disharmony, verbal abuse, and isolation from kin family networks. (Author/NRB)

  8. Intractable Tangles in the Bird Family Tree.

    PubMed

    Roberts, Roland G

    2015-08-01

    Rapid sequential speciation events can outpace the fixation of genetic variants, resulting in a family tree that lacks clear branching patterns. A new study of bird genomes reveals such an explosive super-radiation that may coincide with the mass extinction at the end of the Cretaceous period. PMID:26284616

  9. Methadone Maintenance: The Addict's Family Recreated.

    ERIC Educational Resources Information Center

    Schwartzman, John; Bokos, Peter

    1979-01-01

    A study of four methadone clinics, the addicts treated at these clinics, and their families, reveals basic dissonances in treatment ideology and professional-paraprofessional relationships which, combined with the addict's particular mode of functioning, make significant change in his behavior improbable. (Author)

  10. Family Factors in End-of-Life Decision-Making: Family Conflict and Proxy Relationship

    PubMed Central

    Winter, Laraine; Santana, Abbie J.; Parker, Barbara; Diamond, James J.; Rose, Molly; Myers, Ronald E.

    2011-01-01

    Abstract Background Few studies have examined proxy decision-making regarding end-of-life treatment decisions. Proxy accuracy is defined as whether proxy treatment choices are consistent with the expressed wishes of their index elder. The purpose of this study was to examine proxy accuracy in relation to two family factors that may influence proxy accuracy: perceived family conflict and type of elder-proxy relationship. Methods Telephone interviews with 202 community-dwelling elders and their proxy decision makers were conducted including the Life-Support Preferences Questionnaire (LSPQ), and a measure of family conflict, and sociodemographic characteristics, including type of relationship. Results Elder-proxy accuracy was associated with the type of elder-proxy relationship. Adult children demonstrated the lowest elder-proxy accuracy and spousal proxies the highest elder-proxy accuracy. Elder-proxy accuracy was associated with family conflict. Proxies reporting higher family conflict had lower elder-proxy accuracy. No interaction between family conflict and relationship type was revealed. Conclusions Spousal proxies were more accurate in their substituted judgment than adult children, and proxies who perceive higher degree of family conflict tended to be less accurate than those with lower family conflict. Health care providers should be aware of these family factors when discussing advance care planning. PMID:21254816

  11. The tify family previously known as ZIM.

    PubMed

    Vanholme, Bartel; Grunewald, Wim; Bateman, Alex; Kohchi, Takayuki; Gheysen, Godelieve

    2007-06-01

    The ZIM domain was originally identified in the ZIM protein (BAA97679; Zinc-finger protein expressed in Inflorescence Meristem). Since then it has been found in other proteins and the corresponding genes have been grouped into a plant-specific family. However, the family lacks consistency in its classification among different databases. Here, we try to clarify this incongruity by presenting an overview of the Arabidopsis proteins having this domain. The presented genome-wide survey can be seen as a start point to reveal the unknown function of these proteins. Furthermore, because of the confusing ZIM nomenclature being used at present, we propose to rename the domain and family as tify, after the most conserved amino acid motif characterizing the members of this family. PMID:17499004

  12. Advancing family psychology.

    PubMed

    Fiese, Barbara H

    2016-02-01

    To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year. PMID:26845635

  13. Patients and their families.

    PubMed

    Firth, P

    2006-01-01

    The focus of this chapter is on how clinicians can understand and communicate with the families of patients suffering from cancer. Most doctors and nurses do not have training in this area and are uncomfortable when conducting interviews with whole families. The need to extend our skills in the family context reflects the changes in the way care is provided to patients with a serious illness. We recognise the part families play in providing care and the subsequent effects on family life. The influence of systemic thinking and social construction theories has led to the acknowledgement that we are all part of systems which interact with each other and it is no longer appropriate to see the patient in isolation. The chapter will look at ideas from family therapy which can help us assess and intervene when necessary. The patient suffering from a life-threatening illness such as cancer looks to his family and friends for care and support. The management and course of the illness is affected by the involvement of the family and how they manage the stress and the effects of illness on a family member (Wright and Leahey 2000). Duhamel and Dupuis (2003) point out that there are three important factors in the management of the illness: the effects of family stress, the needs of the family as caregivers, and the effects of the role and how the family cope with the way the patient experiences his illness. This presents professionals working in the field with challenges they are often ill-equipped to deal with. Most healthcare workers have inadequate training in understanding family dynamics and even less knowledge about how to communicate effectively with whole families. Consequently, many healthcare professionals avoid couple and family interviews, feeling inadequate and helpless like the families themselves. I will address some of these issues in the chapter, firstly by examining what we now regard as the family and then by using ideas from systemic theory I will look at

  14. The Growth of a Family

    PubMed Central

    Carroll, June C.; Biringer, Anne

    1991-01-01

    Caring for a family during pregnancy and birth is an ideal opportunity for family physicians to assess family functioning and help the family adjust to the birth of a new child. Stress and support systems can influence the course of pregnancy, including obstetric and perinatal outcomes. A family-centered approach can help patients during this critical stage of family development. PMID:21229107

  15. Putting 'family' back in family planning.

    PubMed

    Seifer, David B; Minkoff, Howard; Merhi, Zaher

    2015-01-01

    Family planning visits are designed to help women build families in a manner most compatible with their life goals. Women's knowledge regarding age-related fertility is suboptimal, and first wanted pregnancies are now occurring at older ages. Here we review the issue of diminishing chances of a pregnancy occurring in women over 30 years of age. A debate arises over whether to perform a standard fertility assessment at an age when, for example, oocyte freezing is still practical and feasible, knowing that the proven predictors in subfertile couples may be less informative, or even inappropriate, in women without complaints about fertility. Studies have demonstrated that if women knew that their fertility was diminishing, they might alter life plans, including having children sooner or considering oocyte preservation. Therefore, we argue that physicians need to make an effort to evaluate a woman's childbearing priorities, though not necessarily their fertility, during the initial family planning visit. PMID:25406182

  16. FAMILIES TIPULIDAE AND LIMONIIDAE.

    PubMed

    Ribeiro, Guilherme C; Santos, Daubian

    2016-01-01

    A catalogue of the Colombian crane flies (Tipulomorpha, families Tipulidae and Limoniidae) is provided, based on updated information from the Catalogue of the Crane flies of World, with additional data on the geographical distribution of the species in Colombia taken from the primary literature. A total of 131 valid species are recorded for Colombia, 38 in the family Tipulidae and 93 in the family Limoniidae. PMID:27395262

  17. The family lecture.

    PubMed

    Rose, Nancy E

    2002-10-01

    SUMMARY This paper describes a lecture about my extended family, in which I discuss a variety of configurations consisting of lesbian, gay, and bisexual adults, and our children. It raises an array of issues, including alternative insemination, biological and nonbiological parentage, donors and birthmothers, adoption, co-parenting and blended families, significant others, and gay marriage and domestic partnership. It helps many students obtain both a more expansive sense of family and adeeper understanding of homophobia. PMID:24804601

  18. Dentistry preventing family violence.

    PubMed

    Mouden, L D

    1996-01-01

    Dentistry has a long history of dealing with one form of family violence, child maltreatment. However, a recent national survey shows that dentists are not living up to their legal and ethical obligations to report suspected child victims. Dentistry needs to be equally concerned with adult victims of family violence--the victims of spousal abuse and elder abuse and neglect. Successful child abuse prevention programs need to expand to cover all of family violence. All health care professionals need education and awareness training to help develop the necessary attitudes to deal with all victims of family violence. PMID:9564320

  19. Family troubles - resources

    MedlinePlus

    ... abuse , incest, domestic violence, and family troubles: National Domestic Violence Hotline -- www.thehotline.org Prevent Child Abuse America -- www.preventchildabuse.org National Runaway Safeline -- ...

  20. Focus groups reveal consumer ambivalence.

    PubMed

    1983-01-01

    According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

  1. Familism, Family Environment, and Suicide Attempts among Latina Youth

    ERIC Educational Resources Information Center

    Pena, Juan B.; Kuhlberg, Jill A.; Zayas, Luis H.; Baumann, Ana A.; Gulbas, Lauren; Hausmann-Stabile, Carolina; Nolle, Allyson P.

    2011-01-01

    In this study, we examined the relationship between familism and family environment type as well as the relationship between family environment type and suicide attempts among Latina youth. Latina teen attempters (n = 109) and nonattempters (n = 107) were recruited from the New York City area. Latent class analysis revealed three family…

  2. Presentations of the Elderly in Textbooks on Marriage and Family.

    ERIC Educational Resources Information Center

    Stolley, Kathy Shepherd; Hill, Archie E.

    1996-01-01

    Discovers a very stereotypical representation of the elderly in marriage and family textbooks. Reveals that the aged receive limited amounts of coverage, often are often separated from other family issues and events, and generally are associated with specific "elderly" topics in these texts. (MJP)

  3. Family-Centered Residential Treatment: Knowledge, Research, and Values Converge

    ERIC Educational Resources Information Center

    Walter, Uta M.; Petr, Christopher G.

    2008-01-01

    Although the evidence base for the effectiveness of residential treatment is still very limited, a review of the literature reveals family-centered residential care as an emerging best practice. Synthesizing knowledge from research, families, youth, professionals, as well as values put forth in the standards by accrediting organizations, this…

  4. Results Not Typical: One Latino Family's Experiences in Higher Education

    ERIC Educational Resources Information Center

    Jimenez-Silva, Margarita; Jimenez Hernandez, Norma V.; Luevanos, Ruth; Jimenez, Dulcemonica; Jimenez, Abel, Jr.

    2009-01-01

    In this narrative, five adult siblings bring their voices together to tell the stories of their interwoven college experiences--how they influenced, supported, and relied on one another and other family members. As the stories unfold, they reveal the strengths of the familial ties that provide meaning and purpose to the college experience, the…

  5. Family Environment and Social Development in Gifted Students

    ERIC Educational Resources Information Center

    Olszewski-Kubilius, Paula; Lee, Seon-Young; Thomson, Dana

    2014-01-01

    Involving more than 1,500 academically gifted students and their parents, this study examined relationships between family environment and social competence of gifted students. Results from an online survey revealed that our gifted students rated their families as cohesive and flexible with high levels of satisfaction and communication among…

  6. Strengthening Families: Exploring the Impacts of Family Camp Experiences on Family Functioning and Parenting

    ERIC Educational Resources Information Center

    Garst, Barry A.; Baughman, Sarah; Franz, Nancy K.; Seidel, Richard W.

    2013-01-01

    Research suggests that family camp experiences can enhance family relationships. Families often participate in family camp experiences for a vacation, as part of a therapeutic and/or intervention strategy, or to gain general enrichment or engagement. To better understand the impacts of family camp experiences on family functioning, a mixed-methods…

  7. Revealing power in truth

    PubMed Central

    Lee, Kelley

    2015-01-01

    Jeremy Shiffman’s editorial appropriately calls on making all forms of power more apparent and accountable, notably productive power derived from expertise and claims to moral authority. This commentary argues that relationships based on productive power can be especially difficult to reveal in global health policy because of embedded notions about the nature of power and politics. Yet, it is essential to recognize that global health is shot through with power relationships, that they can take many forms, and that their explicit acknowledgement should be part of, rather than factored out of, any reform of global health governance. PMID:25844390

  8. Bolivia survey reveals disparities.

    PubMed

    1999-01-01

    Findings from the Bolivia Demographic and Health Survey in 1998 indicate that large fertility and reproductive health disparities based on education level and geographic location still persist in the country. Despite substantial improvement in the overall education level of Bolivian women in the past 5 years, urban women are almost 5 times more likely to attend high school than rural women are. Major differences in education level also exist between provinces. Total fertility rate is at 4.2 children per woman, with women without education having more than 3 times the number of children compared to those with higher education. At such rates, rural women will have an average of 6.3 children, which are 2.5 children more than their urban counterparts. Moreover, nearly 80% of women in union know of a modern method of contraception and 45% of them are using some form of family planning. The highest levels of contraceptive use are among women with higher education and women in urban areas. There is also a notable increase in the number of women who receive assistance from a trained medical professional during delivery. Infant and child mortality rates remain among the highest in Latin America although both rates have declined since the 1994 survey findings. Infant mortality rates are still 80% higher in rural areas than urban areas. PMID:12349605

  9. The Universe Revealed

    NASA Astrophysics Data System (ADS)

    Spence, Pam

    1998-10-01

    The Universe is a bewildering place to the uninitiated. The concepts and theories that govern space seem complex and often contradictory. The Universe Revealed provides the keys to unlocking the wonders of the cosmos. Elegantly written and lavishly illustrated, it begins with the Sun and stretches through our solar system into deepest space. Lucid prose, written by many of the people who have shaped our current thinking on space, and spectacular photographs make the physics of the Universe accessible and provide a solid background for understanding the most recent astronomical discoveries. Covering the most intriguing features of the cosmos, the topics discussed range from the Earth and global warming to cosmic collisions and the size of the Universe. Major sections examine the Solar System, stars, galaxies, cosmology, and the observational techniques used by astronomers, both amateur and professional. The Universe Revealed represents the collaboration of internationally renowned experts in astronomy and cosmology, with contributions from authors including David Malin, F. Duccio Macchetto, Iain Nicholson, Neil Bone, Ian Ridpath, Seth Shostak, Mike Lancaster, Steve Miller, Ken Croswell, Geoff McNamara, and Steven Young. This extraordinary blend of astronomy, astrophysics, and cosmology, will appeal to amateur and armchair astronomers alike.

  10. Forgotten Streams in the Family Life Course: Utilization of Qualitative Retrospective Interviews in the Analysis of Lifelong Single Women's Family Careers.

    ERIC Educational Resources Information Center

    Allen, Katherine R.; Pickett, Robert S.

    1987-01-01

    Combined life course perspective with life history interviewing to compare 15 lifelong unmarried, childless women and 15 ever-married mothers from the 1910 birth cohort. Results suggest that linear progression from family of origin to family of procreation reveals one stream in family life course; experiences of lifelong single women revealed…

  11. Family History Resources.

    ERIC Educational Resources Information Center

    Bookmark, 1991

    1991-01-01

    The 12 articles in this issue focus on the theme of family history resources: (1) "Introduction: Family History Resources" (Joseph F. Shubert); (2) "Work, Credentials, and Expectations of a Professional Genealogist" (Coreen P. Hallenbeck and Lewis W. Hallenbeck); (3) "Computers and Genealogy" (Theresa C. Strasser); (4) "Finding Historical Records…

  12. Balancing Work & Family.

    ERIC Educational Resources Information Center

    Hutchinson Community Junior Coll., KS.

    This curriculum is based on what students need to know, to be able to do, and to be like in order to be competent in the work of the family. Each of the 12 units follows a uniform format that includes the following: perennial problem (one faced over and over by successive generations of families); practical problem (the organizing scheme for how…

  13. Uninsured Rural Families

    ERIC Educational Resources Information Center

    Ziller, Erika C.; Coburn, Andrew F.; Anderson, Nathaniel J.; Loux, Stephenie L.

    2008-01-01

    Context: Although research shows higher uninsured rates among rural versus urban individuals, prior studies are limited because they do not examine coverage across entire rural families. Purpose: This study uses the Medical Expenditure Panel Survey (MEPS) to compare rural and urban insurance coverage within families, to inform the design of…

  14. Family Reunification Project.

    ERIC Educational Resources Information Center

    Administration for Children, Youth, and Families (DHHS), Washington, DC.

    Utah's Department of Human Services' Family Reunification Project was initiated to demonstrate that intensive, time-limited, home-based services would enable children in foster care to return to their natural families more rapidly than regular foster care management permits. The following steps were taken in project development: (1) sites were…

  15. Family-Friendly Art

    ERIC Educational Resources Information Center

    Williams, Patterson; Garcia, Maria

    2004-01-01

    In the late 1980s, the Denver Art Museum initiated efforts to make the museum a destination for families. From 1997 to 2001, with a generous grant from The Pew Charitable Trusts, these efforts came to fruition. From the moment they walk through the doors, families' needs are anticipated. For example, they can pick up a welcoming brochure, Free…

  16. Assessment of Troubled Families.

    ERIC Educational Resources Information Center

    Combs-Orme, Terri; Thomas, Katherine H.

    1997-01-01

    Tests the utility of four standardized instruments used in assessing 105 families that sought services in a juvenile corrections setting for their teenage children. Results demonstrate that parents and adolescents can complete standardized assessment instruments and that the information provided can help in understanding distressed families. (RJM)

  17. Alcohol and Family Violence.

    ERIC Educational Resources Information Center

    Cantrell, Leslie A., Comp.

    This document reports on the relationship between alcohol abuse and battering. Several theories, e.g., the disinhibition, disavowal, and learned behavior theories concerning the relationship between alcohol abuse and family violence are discussed. Literature on the relationship between alcohol and family violence is reviewed. Five intervention and…

  18. Patent Family Databases.

    ERIC Educational Resources Information Center

    Simmons, Edlyn S.

    1985-01-01

    Reports on retrieval of patent information online and includes definition of patent family, basic and equivalent patents, "parents and children" applications, designated states, patent family databases--International Patent Documentation Center, World Patents Index, APIPAT (American Petroleum Institute), CLAIMS (IFI/Plenum). A table noting country…

  19. Family Bonding with Universities

    ERIC Educational Resources Information Center

    Meer, Jonathan; Rosen, Harvey S.

    2010-01-01

    One justification offered for legacy admissions policies at universities is that that they bind entire families to the university. Proponents maintain that these policies have a number of benefits, including increased donations from members of these families. We use a rich set of data from an anonymous selective research institution to investigate…

  20. The Family Constellation Scale.

    ERIC Educational Resources Information Center

    Lemire, David

    The Family Constellation Scale (FC Scale) is an instrument that assesses perceived birth order in families. It can be used in counseling to help initiate conversations about various traits and assumptions that tend to characterize first-born, middle-born children, youngest-born, and only children. It provides both counselors and clients insights…

  1. Explaining Family Interactions.

    ERIC Educational Resources Information Center

    Fitzpatrick, Mary Anne, Ed.; Vangelisti, Anita L., Ed.

    A detailed review of current research and state-of-the-art ideas concerning both communication processes and family functioning is presented in this collection of articles. The volume is organized around three sections. Part 1, "The Development of Family Communication Patterns," contains: (1) "Communication in Infancy" (Marguerite Stevenson…

  2. Golden Matrix Families

    ERIC Educational Resources Information Center

    Fontaine, Anne; Hurley, Susan

    2011-01-01

    This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

  3. Family Support and Education

    ERIC Educational Resources Information Center

    Goldstein, Lou Ann

    2013-01-01

    Family involvement is essential to the developmental outcome of infants born into Neonatal Intensive Care Unit (NICU). In this article, evidence has been presented on the parent's perspective of having an infant in the NICU and the context of family. Key points to an educational assessment are also reviewed. Throughout, the parent's concerns and…

  4. Education and the Family.

    ERIC Educational Resources Information Center

    Kaplan, Leonard, Ed.

    This book is the report of the Family Ties Commission, which was established by the Association of Teacher Educators to study the relationship between home and school. Following the preface and two introductory essays, "Education and My Family" (K.B. O'Rourke as told to E. Johnson) and "Preparing for Successful Children" (B. Clawson), the book is…

  5. America's Family Time Famine.

    ERIC Educational Resources Information Center

    Mattox, Jr., William R.

    1990-01-01

    Parents spend increasingly less time with their children because of the pressures of dual careers and single parenthood. Economic pressures and social values have affected sharing of family time. Studies show both parents and children consider spending time together the most important element in improving family life. (BC)

  6. [Focus: Family Communication].

    ERIC Educational Resources Information Center

    Barnes, Richard E., Ed.

    1977-01-01

    This issue of the "Journal of the Wisconsin Communication Association" focuses on family communication and contains the following articles: "Marital Typologies: An Alternative Approach to the Study of Communication in Enduring Relations" by Mary Anne Fitzpatrick, "Intimate Communication and the Family" by Marilyn D. LaCourt, and "A Study in…

  7. Black Families. Interdisciplinary Perspectives.

    ERIC Educational Resources Information Center

    Cheatham, Harold E., Ed.; Stewart, James B., Ed.

    Since the early 1960s, the black family has been characterized as pathological. This six-part collection of 18 research studies presents alternative approaches to understanding the special characteristics of black families. Part I, "Theoretical and Methodological Perspectives," comprises a comparison of the pioneering work of W. E. B. Du Bois and…

  8. The Borromean Family.

    ERIC Educational Resources Information Center

    Bardis, Panos D.

    This paper attempts to contribute an original approach to the study of the "anti-family movement." A more objective approach to this issue is necessary due to the preponderance of value judgements put forth by both the mass media and social scientists. The paper presents discussions on family functions, divorce, sex, and communes. The author then…

  9. Familial multiple lipomatosis.

    PubMed

    Mohar, N

    1980-01-01

    A family genealogy, comprising four cases of familial multiple lipomatosis, making their appearance one after the other in three generations is reported. Two cases with impressive clinical features are presented in detail. This report contributes to the opinion that the disease is transmitted by the autosomal dominant route of inheritance. PMID:6162336

  10. Changing Families, Changing Workplaces

    ERIC Educational Resources Information Center

    Bianchi, Suzanne M.

    2011-01-01

    American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

  11. Firearms and family violence.

    PubMed

    Kellermann, A; Heron, S

    1999-08-01

    Firearms contribute significantly to morbidity and mortality in family violence. This article discusses the debate on gun use for protection and guns in the home. Weapons-related risks in the setting of intimate partner violence are closely reviewed. Recommendations for physicians are discussed in the context of firearms and family violence. PMID:10516848

  12. THE URBAN NEGRO FAMILY.

    ERIC Educational Resources Information Center

    DOUGLASS, JOSEPH H.

    IN TRACING THE MOVEMENT OF THE NEGRO FAMILY TOWARD A MIDDLE-CLASS ORIENTATION AND TOWARD URBANIZATION, THIS ARTICLE NOTES THAT THE PATTERN IS BECOMING SIMILAR TO THAT OF THE GENERAL AMERICAN FAMILY. NEGROES HAVE LEFT THEIR SOUTHERN RURAL FARMS FOR BOTH SOUTHERN AND NORTHERN URBAN AREAS AND HAVE TENDED TO SETTLE IN THE INNER CORE OF THE LARGEST…

  13. Marinating the Family.

    ERIC Educational Resources Information Center

    Hensel, Karen A.

    1982-01-01

    Describes the New York Aquarium's program specifically designed for family learning and teaching. The program's goal is to create an environment where child-parent roles are dropped and where the philosophy that no one of us is as smart as all of us prevails. Strategies for family involvement are outlined. (MH)

  14. Family/Individual Health.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This document contains teacher's materials for a six-unit secondary education vocational home economics course on personal and family health. The units cover: (1) personal health and wellness (including the decisions and other factors that influence health, principles of personal health, and stress management); (2) family health (including coping…

  15. Therapy for Family Systems.

    ERIC Educational Resources Information Center

    Rosmann, Michael R.

    A family therapy model, based on a conceptualization of the family as a behavioral system whose members interact adaptively so that an optimal level of functioning is maintained within the system, is described. The divergent roots of this conceptualization are discussed briefly, as are the treatment approaches based on it. The author's model,…

  16. Reaching Rural Families.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1995

    1995-01-01

    This newsletter issue focuses on programming undertaken to address the health and educational needs of rural families in developing and developed nations. After examining the nature of rural families and rural poverty, the newsletter discusses: (1) the Mon Women's Organization in Thailand; (2) The "Contact With Kids" parent education project in…

  17. Family Perspectives on Prematurity

    ERIC Educational Resources Information Center

    Zero to Three (J), 2003

    2003-01-01

    In this article, seven families describe their experiences giving birth to and raising a premature baby. Their perspectives vary, one from another, and shift over time, depending on each family's circumstances and the baby's developmental course. Experiences discussed include premature labor, medical interventions and the NICU, bringing the baby…

  18. Employers, Families and Education.

    ERIC Educational Resources Information Center

    Partnership for Family Involvement in Education (ED), Washington, DC.

    Family involvement in education is good for business, critical to children's school achievement, and important in creating strong and vibrant communities. This report discusses the role of businesses and employers in helping partners and family members be more involved in children's learning. Throughout the report, programs at specific companies…

  19. India: New family planning program direction outlined.

    PubMed

    1977-01-01

    The focus of the current Family Welfare Program in India is education and active community involvement rather than coercion and compulsion. The government is totally committed to the program and has indicated that it will spare no efforts to motivate people to voluntarily accept family planning. However, there is a need for family planning efforts to include all aspects of family welfare, particularly those designed to promote the health of mothers and children. All family planning methods will be made available, and the family will be free to choose the method they prefer. As part of the program, employees of the Union government, State governments, autonomous and local bodies are expected to set an example and adopt the small family norm. The policy statement made by Mr. Raj Narain, Minister of Health and Family Welfare, revealed the government's decision not to legislate, either at the national or the State level, for compulsory sterilization. Sterilization services will be available free of charge to those who voluntarily choose this method. A plan for training indigenous midwives will be implemented as part of the program in order that maternity services may be available to all expectant mothers. Additionally, in recognition of the direct correlation between illiteracy and fertility and between infant/maternal mortality and age at marriage, the government will introduce legislation to raise the minimum age at marriage to 18 years for girls and to 21 years for boys. The plan is for trade unions, Chambers of Commerce, cooperative societies, women's organizations, teachers' federation, district councils, and other voluntary institutions to be associated intimately with the educational campaign launching the Family Welfare Program. PMID:12260383

  20. Family stroke education.

    PubMed

    Evans, R L; Held, S; Kleinman, L; Halar, E M

    1985-01-01

    To increase families' involvement in rehabilitation, an informational session called Family Stroke Education Class was implemented at a 305 bed medical center serving disabled veterans and their families. After a year, a study of questionnaires completed by family and patients at the meetings showed that anxiety level about their illness had decreased significantly. Twenty-six (86.7 percent) of thirty participants felt more comfortable about approaching team members with questions in the future, and 76.7 percent felt more informed as a result of taking the class. Knowledge scores improved significantly on the post tests. Thus it appears that the educational format is a practical way of including the needs and soliciting participation of families as well as a means for providing basic information to patients on stroke rehabilitation. PMID:23952227